US20100122382A1 - Cell Cycle Genes and Related Methods - Google Patents

Cell Cycle Genes and Related Methods Download PDF

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US20100122382A1
US20100122382A1 US12/555,853 US55585309A US2010122382A1 US 20100122382 A1 US20100122382 A1 US 20100122382A1 US 55585309 A US55585309 A US 55585309A US 2010122382 A1 US2010122382 A1 US 2010122382A1
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plant
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wood
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Richard L. Forster
Marie B. Connett
Sarah Jane Emerson
Murray Robert Grigor
Colleen M. Higgins
Steven Troy Lund
Andreas Magusin
Bob Kodrzycki
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ArborGen LLC
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/415Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from plants
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4738Cell cycle regulated proteins, e.g. cyclin, CDC, INK-CCR
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/82Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
    • C12N15/8241Phenotypically and genetically modified plants via recombinant DNA technology
    • C12N15/8261Phenotypically and genetically modified plants via recombinant DNA technology with agronomic (input) traits, e.g. crop yield
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A40/00Adaptation technologies in agriculture, forestry, livestock or agroalimentary production
    • Y02A40/10Adaptation technologies in agriculture, forestry, livestock or agroalimentary production in agriculture
    • Y02A40/146Genetically Modified [GMO] plants, e.g. transgenic plants

Definitions

  • the present invention relates generally to the field of plant cell cycle genes and polypeptides encoded by such genes, and the use of such polynucleotide and polypeptide sequences for regulating a plant cell cycle.
  • the invention specifically provides cell cycle polynucleotide and polypeptide sequences isolated from Eucalyptus and Pinus and sequences related thereto.
  • Plant development and division are controlled by the temporal expression of different sets of genes, allowing the dividing cell to progress through the different phases of the cell cycle. Continued growth and organogesis in plants requires precise function of the cell cycle machinery. Plant development, which is directly affected by cell division rates and patterns, also is influenced by environmental factors, such as temperature, nutrient availability, light, etc. See Gastal and Nelon, Plant Physiol. 105:191-7 (1994), Ben-Haj-Sahal and Tardieu, Plant Physiol. 109:861-7 (1995), and Sacks et al., Plant Physiol. 114:519-27 (1997). Plant development and phenotype are connected with the cell cycle, and altering expression of the genes involved in the cell cycle can be a useful method of modifying plant development and altering plant phenotype.
  • the ability to alter expression of cell cycle genes is extremely powerful because the cell cycle drives plant development, including growth rates, responses to environmental cues, and resulting plant phenotype.
  • Control of the plant cell cycle and phenotypes associated with alteration of cell cycle gene expression, in the vascular cambium has applications for, inter alia, alteration of wood properties and, in particular, lumber and wood pulp properties.
  • improvements to wood pulp that can be effected by altering cell cycle gene expression include increased or decreased lignin and cellulose content, and altered length, diameter, and lumen diameter of cells.
  • Manipulating the plant cell cycle, and in particular the cambium cell cycle i.e.
  • the rate and angle of cell division can also engineer better lumber having increased dimensional stability, increased tensile strength, increased shear strength, increased compression strength, increased shock resistance, increased stiffness, increased or decreased hardness, decreased spirality, decreased shrinkage, and desirable characteristics with respect to weight, density, and specific gravity.
  • CDKs cyclin-dependent kinases
  • CDK types A the cyclin binding consensus sequence is PSTAIRE.
  • the cyclin binding consensus sequence in CDK types B-1, B-2, and C are PPTTLRE, PPTALRE, and PITAIRE, respectively. Joubes et al, Plant Physiol, 126: 1403-15 (2001).
  • CDK activity is modulated by a number of different cell cycle protein components, such as changes in the abundance of individual cyclins due to changing rates of biosynthesis and proteolysis. Fluctuations in cyclin concentrations result in commensurate fluctuations in CDK activity. Cyclin accumulation is especially important in terminating the G1 phase of the cell cycle because DNA replication is initiated by an increase in CDK activity.
  • CDK-activating kinase Activation of CDK also requires phosphorylation of a threonine residue within the T-loop of CDK by a CDK-activating kinase (CAK).
  • CAK CDK-activating kinase
  • CDK inhibitors are low molecular weight proteins, which are important for cell cycle regulation and development. CKIs bind stoichiometrically to CDK and down-regulate the activity of CDKs.
  • ICK1 is expressed at low levels in many tissue types, and there can be a threshold level of ICK1 that must be overcome before a cell can enter the cell cycle. Wang et al., Plant J. 24: 613-23 (2000).
  • ICK1 is induced by the plant growth regulator abscisic acid (ABA), which inhibits cell division by blocking DNA replication. When the expression of ICK1 increases, there is a corresponding decrease in Cdc2-like H1 histone activity.
  • ICK1 has been shown to bind in vitro with the cyclins C2c2a and CycD3, and deletion experiments have identified different domain regions for these two interactions.
  • CDK regulatory protein or a subunit thereof Altering the expression of CDK regulatory protein or a subunit thereof is known to cause changes in plant phenotype.
  • Overexpression of the Arabidopsis CDK regulatory subunit, CKS1At resulted in a reduction of leaf size, root growth rates and meristem size. Additionally, overexpression of CKS1At resulted in inhibition of cell-cycle progression, with an extension in the duration of the G1 and G2 phases of the cell cycle.
  • Cyclins are positive regulatory subunits of cyclin-dependent kinase (CDK) enzymes and are required for CDK activity. Fowler et al., Mol. Biotech. 10, 123, 126. Cyclins and CDK complexes provide temporal regulation of transition through the cell cycle. Evidence also suggests that cyclins provide spatial regulation of specific CDK activity, differentially targeting the cytoskeleton, spindle, phragmoplast, nuclear envelope, and chromosomes.
  • CDK cyclin-dependent kinase
  • Plant cyclins are classified into five major groups: A, B, C, D, and H. Renaudin et al., Plant Mol. Biol. 32: 1003-18 (1996) and Yamaguchi et al., (supra 2000). Cyclins can be divided into mitotic cyclins (A and B) and G 1 cyclins.
  • the mitotic cyclins possess a consensus sequence (R-x-x-L-x-x-I-x-N) located at the N-terminal region, termed a destruction box, adjacent to a lysine-rich region.
  • the destruction box and lysine-rich region target the mitotic cyclins for ubiquitin-dependent proteolysis during mitosis. Stals, supra at 361, and Fowler, supra at 126.
  • the destruction box in A versus B cyclins differs slightly and this difference is thought to result in slightly different timing of degradation of A versus B cyclins. Fowler, supra at 126.
  • A-type cyclins accumulate during the S, G2, and early M phase of the cell cycle, whereas B-type cyclins accumulate during the late G2 and early M phase.
  • Cyclin A1 cycA1;zm;1 from Zea cans
  • Cyclin A2 is most concentrated during cytokinesis at the microtubule-containing phragmoplast.
  • Expression of cyclin A2 is upregulated by auxins in roots, and by cytokinins in the shoot apex. Abrahams et al., Biochim. Biophys. Acta 28: 1-2 (2001).
  • D-type cyclins of which five subgroups are known, are thought to control the progression through the G1 phase in response to growth factors and nutrients.
  • Riou-Khamlichi et al. Mol. Cell Biol. 20: 4513-21 (2000).
  • the expression of D-type cyclins is upregulated by sucrose as shown by an increase in cycD2 mRNA 30 minutes after sucrose exposure, and an increase in cycD3 four hours after sucrose exposure. This timing corresponds to early G1-phase and late G1-phase, respectively.
  • Cockcroft et al. Nature 405: 575-9 (2000).
  • a D3 cyclin was shown to be upregulated by the brassinosteroid, epi-brassinolide.
  • Cyclin D2 proteins bind with CDKA to produce an active complex, which binds to and phosphorylates retinoblastoma-related protein (Rb). This process is found in actively proliferating tissue, suggesting it plays an important function during late G1- and early S-phase.
  • Rb retinoblastoma-related protein
  • Three different D3-type cyclins are active during tomato fruit development. These proteins all contain a retinoblastoma binding motif and a PEST-destruction motif. There are differences in the spatial and temporal expression of these D3 cyclins, inferring different roles during fruit development.
  • cyclin D Overexpression of cyclin D was shown to increase overall growth rate. Over-expression of cyclin D2 in tobacco increases causes shortening the G1-phase which producing a faster rate of cell cycling.
  • C- and H-type cyclins were characterized in poplar ( Populus tremula ⁇ tremuloides ) and rice ( Oryza sativa ) but their exact function is still unclear. Putative cyclins with a lesser degree of peptide sequence conservation have also been identified. For example, Arabidopsis CycJ18 has only 20% identity with homologues over the cyclin box domain. CycJ18 is expressed predominantly in young seedlings. Arabidopsis F3O9.13 protein also has similarity to the cyclin family.
  • Histone acetyltransferase and histone deacetyltransferase (HAD) control the net level of acetylation of histones.
  • Histone acetylation and deacetylation are thought to exert their regulatory effects on gene expression by altering the accessibility of nucleosomal DNA to DNA-binding transcriptional activators, other chromatin-modifying enzymes or multi-subunit chromatin remodeling complexes capable of displacing nucleosomes. Lusser et al., Nucleic Acids Res. 27: 4427-35 (1999). Therefore, in general, the HDAs are involved in the repression of gene expression, while HAs are correlated with gene activation.
  • HA effects acetylation at the ⁇ -amino group of conserved lysine residues clustered near the amino terminus of core histones which up-regulates gene expression.
  • HDAs remove acetyl groups from the core histones of the nucleosome. There are numerous family members in the HDA group, many of which are conserved throughout evolution. Lechner et al., Biochim Biophys Acta 5:181-8 (1996). HDAs function as part of multi-protein complexes facilitating chromatin condensation.
  • HDAs and HAs recognize highly distinct acetylation patterns on the nucleosome. It is thought that different types of HDAs interact with specific regions of the genome, to influence gene silencing.
  • KRAB-ZFPs Kruppel-associated-box zinc finger proteins
  • PHD plant homeodomain
  • PPIases peptidyl-prolyl cis-trans isomerases
  • Peptidylprolyl isomerases catalyze the interconversion of peptide bonds between the cis and trans conformations at proline residues. Sheldon and Venis, Biochem J. 315: 965-70 (1996). This interconversion is thought to be the rate limiting step of protein folding.
  • PPIases belong to a conserved family of proteins that are present in animals, fungi, bacteria and plants. PPIases are implicated in a number of responses including the response to environmental stress, calcium signals, transcriptional repression, cell cycle control, etc. Viaud, et al., Plant Cell 14: 917-30 (2002).
  • Retinoblastoma (Rb)-related protein putatively regulates progression of the cell cycle through the G1 phase and into S phase.
  • Rb Retinoblastoma
  • Rb is well-characterized in mammalian systems, the role of Rb-related proteins in regulation of G1 phase progression and S phase entry is not well characterized in plants. It is known, however, that RB-related protein functions through its association with various other cellular proteins involved in cell cycle regulation, such as the cyclins, WD40 proteins, Soni et al., Plant. Cell. 7:85-103 (1995); Grafi et al., Proc. Natl. Acad. Sci. U.S.A. 93:8962 (1996); Ach et al., Plant Cell 9:1595-606 (1997); Umen and Goodenough, Genes Dev. 15:1652-61 (2001); Mariconti et al., J. Biol. Chem. 277:9911-9 (2002).
  • WD40 is a common repeating motif involved in many different protein-protein interactions.
  • the WD40 domain is found in proteins having a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly. Goh et al., Eur. J. Biochem. 267: 434-49 (2000).
  • the WD40 domain which is 40 residues long, typically contains a GH dipeptide 11-24 residues from the N-terminus and the WD dipeptide at the C-terminus. Id. Between the GH dipeptide and the WD dipeptide lies a conserved core which serves as a stable platform where proteins can bind either stably or reversibly.
  • the core forms a propeller-like structure with several blades. Each blade is composed of a four-stranded anti-parallel ⁇ -sheet.
  • Each WD40 sequence repeat forms the first three strands of one blade and the last strand in the next blade.
  • the last C-terminal WD40 repeat completes the blade structure of the first WD40 repeat to create the closed ring propeller-structure.
  • the residues on the top and bottom surface of the propeller are proposed to coordinate interactions with other proteins and/or small ligands.
  • Cdc20 which contains the WD40 motif, is required for the proteolysis of mitotic cyclins. This process is mediated by an ubiquitin-protein ligase called anaphase-promoting complex (APC) or cyclosome. Following ubiquitination and proteolysis by the 26S proteasome, the cell can segregate chromosomes, and exit from mitosis. Cdc20 also contains a destruction-box domain.
  • APC anaphase-promoting complex
  • WEE1 controls the activity of cyclin-dependent kinases.
  • WEE1 itself is a serine/threonine kinase. Sorrell et al., Planta 215: 518-22 (2002).
  • the enzymatic activity of these protein kinases is controlled by phosphorylation of specific residues in the activation segment of the catalytic domain, sometimes combined with reversible conformational changes in the C-terminal autoregulatory tail. This process is conserved among eukaryotes, from fungi to animals and plants.
  • WEE1 proteins there is a high degree of homology between WEE1 proteins from various organisms. For example, there is 50% identity between the protein kinase domains of the human and maize WEE1 proteins.
  • WEE1 is shown to occur only in actively dividing tissues and is believed to inhibit cell division by acting as a negative regulator of mitosis. WEE1 is believed to prevent entry from G2 to M by protecting the nucleus from cytoplasmically-activated cyclin B1-complexed CDC2 before the onset of mitosis.
  • AtWEE1 from Arabidopsis
  • ZmWEE1 from Zea cans
  • the multigenic control of plant phenotype presents difficulties in determining the genes responsible for phenotypic determination.
  • One major obstacle to identifying genes and gene expression differences that contribute to phenotype in plants is the difficulty with which the expression of more than a handful of genes can be studied concurrently.
  • Another difficulty in identifying and understanding gene expression and the interrelationship of the genes that contribute to plant phenotype is the high degree of sensitivity to environmental factors that plants demonstrate.
  • Whetten et al. discloses expression profiling of cell wall biosynthetic genes in Pinus taeda L. using cDNA probes. Whetten et al. examined genes which were differentially expressed between differentiating juvenile and mature secondary xylem. Additionally, to determine the effect of certain environmental stimuli on gene expression, gene expression in compression wood was compared to normal wood. 156 of the 2300 elements examined showed differential expression. Whetten, supra at 285. Comparison of juvenile wood to mature wood showed 188 elements as differentially expressed. Id. at 286.
  • microarrays comprising cDNA or EST probes may not be able to distinguish genes of the same family because of sequence similarities among the genes. That is, cDNAs or ESTs, when used as microarray probes, may bind to more than one gene of the same family.
  • Methods of manipulating gene expression to yield a plant with a more desirable phenotype would be facilitated by a better understanding of cell cycle gene expression in various types of plant tissue, at different stages of plant development, and upon stimulation by different environmental cues.
  • the ability to control plant architecture and agronomically important traits would be improved by a better understanding of how cell cycle gene expression effects formation of plant tissues, how cell cycle gene expression causes plant cells to enter or exit cell division, and how plant growth and the cell cycle are connected.
  • the expression of which can change during development of a plant only a fraction are likely to effect phenotypic changes during any given stage of the plant development.
  • the present invention provides an isolated polynucleotide comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof.
  • the present invention provides a DNA construct comprising at least one polynucleotide having the sequence of any one of SEQ ID NOs: 1-237 and conservative variants thereof.
  • Another aspect of the invention is a plant cell transformed with a DNA construct of comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof.
  • a further aspect of the invention is a transgenic plant comprising a plant cell transformed with a DNA construct comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof.
  • Another aspect of the invention is an isolated polynucleotide comprising a sequence encoding the catalytic or substrate-binding domain of a polypeptide selected from of any one of SEQ ID NOs: 261-497, wherein the polynucleotide encodes a polypeptide having the activity of said polypeptide selected from any one of SEQ ID NOs: 261-497.
  • a further aspect of the invention is a method of making a transformed plant comprising transforming a plant cell with a DNA construct comprising at least one polynucleotide having the sequence of any of SEQ ID NOs: 1-237; and culturing the transformed plant cell under conditions that promote growth of a plant.
  • the invention provides a wood obtained from a transgenic tree.
  • the invention provides a wood pulp obtained from a transgenic tree which has been transformed with the DNA construct of the invention.
  • Another aspect of the invention is a method of making wood, comprising transforming a plant with a DNA construct comprising a polynucleotide having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof; culturing the transformed plant under conditions that promote growth of a plant; and obtaining wood from the plant.
  • the invention further provides a method of making wood pulp, comprising transforming a plant with a DNA construct comprising a polynucleotide having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof; culturing the transformed plant under conditions that promote growth of a plant; and obtaining wood pulp from the plant.
  • the invention provides an isolated polypeptide comprising an amino acid sequence encoded by the isolated polynucleotide comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof.
  • the invention also provides, an isolated polypeptide comprising an amino acid sequence selected from the group consisting of 261-497.
  • the invention further provides a method of altering a plant phenotype of a plant, comprising altering expression in the plant of a polypeptide encoded by any one of SEQ ID NOs: 1-237.
  • the invention provides a polynucleotide comprising a nucleic acid selected from the group comprising of SEQ ID NOs: 471-697.
  • An aspect of the invention is a method of correlating gene expression in two different samples, comprising detecting a level of expression of one or more genes encoding a product encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof in a first sample; detecting a level of expression of the one or more genes in a second sample; comparing the level of expression of the one or more genes in the first sample to the level of expression of the one or more genes in the second sample; and correlating a difference in expression level of the one or more genes between the first and second samples.
  • a further aspect of the invention is a method of correlating the possession of a plant phenotype to the level of gene expression in the plant of one or more genes comprising detecting a level of expression of one or more genes encoding a product encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof in a first plant possessing a phenotype; detecting a level of expression of the one or more genes in a second plant lacking the phenotype; comparing the level of expression of the one or more genes in the first plant to the level of expression of the one or more genes in the second plant; and correlating a difference in expression level of the one or more genes between the first and second plants to possession of the phenotype.
  • the invention provides a method of correlating gene expression to a stage of the cell cycle, comprising detecting a level of expression of one or more genes encoding a product encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof in a first plant cell in a first stage of the cell cycle; detecting a level of expression of the one or more genes in a second plant cell in a second, different stage of the cell cycle; comparing the level of the expression of the one or more genes in the first plant cells to the level of expression of the one or more genes in the second plants cells; and correlating a difference in expression level of the one or more genes between the first and second samples to the first or second stage of the cell cycle.
  • An aspect of the invention is a combination for detecting expression of one or more genes, comprising two or more oligonucleotides, wherein each oligonucleotide is capable of hybridizing to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237.
  • Another aspect of the invention is a combination for detecting expression of one or more genes, comprising two or more oligonucleotides, wherein each oligonucleotide is capable of hybridizing to a nucleic acid sequence encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237.
  • the invention further provides a microarray comprising a combination for detecting expression of one or more genes, comprising two or more oligonucleotides, wherein each oligonucleotide is capable of hybridizing to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 or wherein each oligonucleotide is capable of hybridizing to a nucleic acid sequence encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237, wherein each of said two or more oligonucleotides occupies a unique location on said solid support.
  • the invention provides a method for detecting one or more genes in a sample, comprising contacting the sample with two or more oligonucleotides, wherein each oligonucleotide is capable of hybridizing to a gene comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 under standard hybridization conditions; and detecting the one or more genes of interest which are hybridized to the one or more oligonucleotides.
  • the invention also provides a method for detecting one or more nucleic acid sequences encoded by one or more genes in a sample, comprising contacting the sample with two or more oligonucleotides, wherein each oligonucleotide is capable of hybridizing to a nucleic acid sequence encoded by a gene comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 under standard hybridization conditions; and detecting the one or more nucleic acid sequences which are hybridized to the one or more oligonucleotides.
  • the invention further provides a kit for detecting gene expression comprising the microarray of the invention together with one or more buffers or reagents for a nucleotide hybridization reaction.
  • FIG. 1 Exemplary microarray sampling parameters.
  • FIG. 2 Plasmid map for pWVK202.
  • FIG. 3 Plasmid map for pGrowth14.
  • FIG. 4 Plasmid map for pGrowth15.
  • FIG. 5 Plasmid map for pGrowth16.
  • FIG. 6 Plasmid map for pGrowth18.
  • FIG. 7 Plasmid map for pGrowth19.
  • FIG. 8 Plasmid map for pGrowth20.
  • Table 1 shows genes having greater than doubled signal with any one sample as compared to the mean signal of the other three samples.
  • Table 2 identifies plasmid(s), genes, and Genesis ID numbers for constructs described in Example 17.
  • Table 3 Rooting medium for Populus deltoids.
  • Table 4 pGrowth information.
  • Table 5 shows genes having greater than doubled signal with any one sample as compared to the mean signal of the other three samples.
  • Table 8 pGrowth information.
  • Table 9 Eucalyptus grandis cell cycle genes and proteins.
  • Table 10 Pinus radiata cell cycle genes and proteins.
  • Table 11 Annotated peptide sequences of the present invention.
  • Table 12 Eucalyptus in silico data.
  • Table 16 BLAST sequence alignment table.
  • the inventors have discovered novel isolated cell cycle genes and polynucleotides useful for identifying the multigenic factors that contribute to a phenotype and for manipulating gene expression to affect a plant phenotype.
  • These genes which are derived from plants of commercially important forestry genera, pine and eucalyptus, are involved in the plant cell cycle and are, at least in part, responsible for expression of phenotypic characteristics important in commercial wood, such as stiffness, strength, density, fiber dimensions, coarseness, cellulose and lignin content, and extractives content.
  • the genes and polynucleotides encode a protein which can be a cyclin, cyclin dependent kinase, cyclin dependent kinase inhibitor, histone acetyltransferase, histone deacetylase, peptidyl-prolyl cis-trans isomerase, retinoblastoma-related protein, WEE1-like protein, or WD40 repeat protein, or a catalytic domain thereof, or a polypeptide having the same function, and the invention further includes such proteins and polypeptides.
  • the methods of the present invention for selecting cell cycle gene sequences to target for manipulation will permit better design and control of transgenic plants with more highly engineered phenotypes.
  • the ability to control plant architecture and agronomically important traits in commercially important forestry species will be improved by the information obtained from the methods, such as which genes affect which phenotypes, which genes affect entry into which stage of the cell cycle, which genes are active in which stage of plant development, and which genes are expressed in which tissue at a given point in the cell cycle or plant development.
  • plant cell cycle genes refers to genes encoding proteins that function during the plant cell cycle
  • plant cell cycle proteins refers to proteins that function during the plant cell cycle.
  • plant cell cycle proteins There are several known families of plant cell cycle proteins, including cyclin, cyclin dependent kinase, cyclin dependent kinase inhibitor, histone acetyltransferase, histone deacetylase, peptidyl-prolyl cis-trans isomerase, retinoblastoma-related protein, WEE1-like protein, and WD40 repeat protein.
  • the present invention provides novel plant cell cycle genes and polynucleotides and novel cell cycle proteins and polypeptides.
  • the novel plant cell cycle genes are the same as those expressed in a wild-type plant of a species of Pinus or Eucalyptus.
  • Exemplary novel plant cell cycle gene sequences of the invention are set forth in Tables 9 and 10, which depict Eucalyptus grandis sequences and Pinus radiata sequences, respectively.
  • Corresponding gene products, i.e., oligonucleotides and polypeptides are also listed in Tables 14, 15, and 16.
  • the Sequence Listing in APPENDIX 1 provides the sequences of these aspects of the invention.
  • sequences of the invention have cell cycle activity and encode proteins that are active in the cell cycle, such as proteins of the cell cycle families discussed above.
  • manipulation of the expression of the cell cycle genes and polynucleotides, or manipulation of the activity of the encoded proteins and polypeptides can result in a transgenic plant with a desired phenotype that differs from the phenotype of a wild-type plant of the same species.
  • cell cycle gene product is a product encoded by a cell cycle gene, and includes both nucleotide products, such as RNA, and amino acid products, such as proteins and polypeptides.
  • Examples of specific cell cycle genes of the invention include SEQ ID NOs: 1-237.
  • Examples of specific cell cycle gene products of the invention include products encoded by any one of SEQ ID NOs: 1-237.
  • One aspect of the invention is directed to a subset of these cell cycle genes and cell cycle gene products, namely SEQ ID NOs: 1-12, 14-58, 60-62, 64-70, 72-75, 77-83, 85-86, 88-91, 93-119, 121-130, 132-148, 150-156, 158-191, 193-207, 209-218, 220-221, 223-231, 233-237, their respective conservative variants (as that term is defined below), and the nucleotide and amino acid products encoded thereby.
  • Another aspect of the invention is directed to a subset of the cell cycle genes and cell cycle gene products, namely SEQ ID NOs: 1-12, 14, 16-26, 30-37, 40-41, 43-76, 78-103, 106, 108-113, 116-121, 124-125, 128-147, 150-152, 154-155, 161-162, 164-172, 174, 177-183, 185-191, 193-197, 200-204, 208-213, and 215-234 their respective conservative variants, and the nucleotide and amino acid products encoded thereby.
  • a further aspect of the invention is directed to a subset of the cell cycle genes and cell cycle gene products, namely SEQ ID NOs: 1-12, 14, 16-26, 30-37, 40-41, 43-58, 60-62, 64-70, 72-75, 78-83, 85-86, 88-91, 93-103, 106, 108-113, 116-119, 121, 124-125, 128-130, 132-147, 150-152, 154-155, 161-162, 164-172, 174, 177-183, 185-191, 193-197, 200-204, 209-213, 215-218, 220-221, 223-231, and 233-234 their respective conservative variants, and the nucleotide and amino acid products encoded thereby.
  • the present invention also includes sequences that are complements, reverse sequences, or reverse complements to the nucleotide sequences disclosed herein.
  • the present invention also includes conservative variants of the sequences disclosed herein.
  • variant refers to a nucleotide or amino acid sequence that differs in one or more nucleotide bases or amino acid residues from the reference sequence of which it is a variant.
  • the invention includes conservative variant polynucleotides.
  • conservative variant polynucleotide refers to a polynucleotide that hybridizes under stringent conditions to an oligonucleotide probe that, under comparable conditions, binds to the reference gene the conservative variant is a variant of.
  • a conservative variant of SEQ ID NO: 1 hybridizes under stringent conditions to an oligonucleotide probe that, under comparable conditions, binds to SEQ ID NO: 1.
  • One aspect of the invention provides conservative variant polynucleotides that exhibit at least about 75% sequence identity to their respective reference sequences.
  • Sequence identity has an art-recognized meaning and can be calculated using published techniques. See C OMPUTATIONAL M OLECULAR B IOLOGY, Lesk, ed. (Oxford University Press, 1988), B IOCOMPUTING: I NFORMATICS A ND G ENOME P ROJECTS, Smith, ed.
  • Methods commonly employed to determine identity or similarity between two sequences include but are not limited to those disclosed in G UIDE T O H UGE C OMPUTERS, Bishop, ed., (Academic Press, 1994) and Carillo & Lipton, supra. Methods to determine identity and similarity are codified in computer programs. Preferred computer program methods to determine identity and similarity between two sequences include but are not limited to the GCG program package (Devereux et al., Nucleic Acids Research 12: 387 (1984)), BLASTP, BLASTN, FASTA (Atschul et al., J. Mol. Biol. 215: 403 (1990)), and FASTDB (Brutlag et al., Comp. App. Biosci. 6: 237 (1990)).
  • the invention includes conservative variant polynucleotides having a sequence identity that is greater than or equal to 99%, 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, 90%, 89%, 88%, 87%, 86%, 85%, 84%, 83%, 82%, 81%, 80%, 79%, 78%, 77%, 76%, 75%, 74%, 73%, 72%, 71%, 70%, 69%, 68%, 67%, 66%, 65%, 64%, 63%, 62%, 61%, or 60% to any one of SEQ ID NOs: 1 to 237.
  • differences between the variant and the reference sequence can occur at the 5′ or 3′ terminal positions of the reference nucleotide sequence or anywhere between those terminal positions, interspersed either individually among nucleotides in the reference sequence or in one or more contiguous groups within the reference sequence.
  • Additional conservative variant polynucleotides contemplated by and encompassed within the present invention include polynucleotides comprising sequences that differ from the polynucleotide sequences of SEQ ID NO: 1-237, or complements, reverse complements or reverse sequences thereof, as a result of deletions and/or insertions totaling less than 10% of the total sequence length.
  • the invention also includes conservative variant polynucleotides that, in addition to sharing a high degree of similarity in their primary structure (sequence) to SEQ ID NOs: 1 to 237, have at least one of the following features: (i) they contain an open reading frame or partial open reading frame encoding a polypeptide having substantially the same functional properties in the cell cycle as the polypeptide encoded by the reference polynucleotide, or (ii) they have nucleotide domains or encoded protein domains in common.
  • the invention includes conservative variants of SEQ ID NOs: 1-237 that encode proteins having the enzyme or biological activity or binding properties of the protein encoded by the reference polynucleotide. Such conservative variants are functional variants, in that they have the enzymatic or binding activity of the protein encoded by the reference polynucleotide.
  • polynucleotide variants can include a “shuffled gene” such as those described in e.g. U.S. Pat. Nos. 6,500,639, 6,500,617 6,436,675, 6,379,964, 6,352,859 6,335,198 6,326,204, and 6,287,862.
  • a variant of a nucleotide sequence of the present invention also can be a polynucleotide modified as disclosed in U.S. Pat. No. 6,132,970, which is incorporated herein by reference.
  • the invention provides a polynucleotide that encodes a cell cycle protein from one of the following families: cyclin, cyclin dependent kinase, cyclin dependent kinase inhibitor, histone acetyltransferase, histone deacetylase, peptidyl-prolyl cis-trans isomerase, retinoblastoma-related protein, WEE1-like protein, or WD40 repeat protein.
  • SEQ ID NOs: 1-237 provide examples of such polynucleotides.
  • a polynucelotide of the invention encodes the catalytic or protein binding domain of a polypeptide encoded by any of SEQ ID NOs: 1-237 or of a polypeptide comprising any of SEQ ID NOs: 261-497.
  • the catalytic and protein binding domains of the cell cycle proteins of the invention are known in the art. The conserved sequences of these proteins are shown in Entries 1-195 as underlined, bold, and/or italicized text.
  • the invention also encompasses as conservative variants polynucleotides that differ from the sequences discussed above but that, as a consequence of the degeneracy of the genetic code, encode a polypeptide which is the same as that encoded by a polynucleotide of the present invention.
  • the invention also includes as conservative variants polynucleotides comprising sequences that differ from the polynucleotide sequences discussed above as a result of substitutions that do not affect the amino acid sequence of the encoded polypeptide sequence, or that result in conservative substitutions in the encoded polypeptide sequence.
  • the present invention also includes an isolated polypeptide encoded by a polynucleotide comprising any of SEQ ID NOs: 1-237 or any of the conservative variants thereof discussed above.
  • the invention also includes polypeptides comprising SEQ ID NOs: 261-497 and 495-497 and conservative variants of these polypeptides.
  • Another aspect of the invention include polypeptides comprising SEQ ID NOs: 261-272, 274-318, 320-322, 324-330, 332-335, 337-343, 345-346, 348-351, 353-379, 381-390, 392-408, 410-416, 418-451, 453-467, 469-478, 480-481, 483-491, and 493-494 and conservative variants thereof.
  • a further aspect of the invention includes polypeptides comprising SEQ ID NOs: 261-272, 274, 276-286, 289, 290-297, 300-301, 303-345, 347-363, 366, 368-373, 376-381, 384-385, 388-407, 410-412, 414-415, 420-422, 424-432, 434, 437-443, 445-451, 453-457, 460-464, 468-473, and 475-494 and conservative variants thereof.
  • polypeptides comprising SEQ ID NOs: 261-272, 274, 276-286, 290-297, 300-301, 303-318, 320-322, 324-330, 332-335, 337-343, 345, 348-351, 353-363, 366, 368-373, 376-381, 384-385, 388-390, 392-407, 410-412, 414-415, 421-422, 424-432, 434, 437-443, 445-451, 453-457, 460-464, 469-473, 475-478, 480-481, 483-491, and 493-494 and conservative variants thereof.
  • a variant polypeptide or protein refers to an amino acid sequence that is altered by the addition, deletion or substitution of one or more amino acids.
  • the invention includes conservative variant polypeptides.
  • conservative variant polypeptide refers to a polypeptide that has similar structural, chemical or biological properties to the protein it is a conservative variant of.
  • Guidance in determining which amino acid residues can be substituted, inserted, or deleted can be found using computer programs well known in the art such as Vector NTI Suite (InforMax, MD) software.
  • conservative variant polypeptides that exhibit at least about 75% sequence identity to their respective reference sequences.
  • Conservative variant protein includes an “isoform” or “analog” of the polypeptide.
  • Polypeptide isoforms and analogs refers to proteins having the same physical and physiological properties and the same biological function, but whose amino acid sequences differs by one or more amino acids or whose sequence includes a non-natural amino acid.
  • Polypeptides comprising sequences that differ from the polypeptide sequences of SEQ ID NO: 261-497 as a result of amino acid substitutions, insertions, and/or deletions totaling less than 10% of the total sequence length are contemplated by and encompassed within the present invention.
  • the invention provides conservative variant polypeptides that have the same function in the cell cycle as the proteins of which they are variants, as determined by one or more appropriate assays, such as those described below.
  • the invention includes variant polypeptides that function as cell cycle proteins, such as those having the biological activity of cyclin, cyclin dependent kinase, cyclin dependent kinase inhibitor, histone acetyltransferase, histone deacetylase, peptidyl-prolyl cis-trans isomerase, retinoblastoma-related protein, WEE1-like protein, and WD40 repeat protein, and are thus capable of modulating the cell cycle in a plant.
  • the invention includes variant polynucleotides that encode polypeptides that function as cell cycle proteins.
  • cell cycle proteins can be examined using any method known in the art.
  • assay methods are not exhaustive and are included to provide some guidance in examining the activity and distinguishing protein characteristics of cell cycle protein variants.
  • CDK activity can be assessed using roscovitine as described in Yamaguchi et al., Proc. Natl. Acad. Sci. U.S.A. 100:8019 (2003).
  • CDK histone kinase activity can be assayed using autoradiography to detect histone H1 phosphorylation by CDK as described in Joubés et al., Plant Physiol. 121:857 (1999).
  • CKI activity can be assayed using a variation of the method described in Zhou et al., Planta. 6:604 (2003).
  • the modified method can employ co-transformation or subsequent transformations to identify the interaction of CKI and cyclins in vivo.
  • pine tissue can be transformed using the method described in U.S. Patent Application Publication No. 2002/0100083 using geneticin selection to obtain transgenic plants possessing cycD3 and cdc2a homologs.
  • the second transformation can be performed using alpha-methyltryptophan as a selectable marker to obtain transformants having an ICK1 homologue as described in U.S. Provisional Application No. 60/476,189.
  • Tissue capable of growing on both on geneticin and on alpha-methyltryptophan contains the ICK1 homologue and the cycD3 and cdc2a homologues.
  • the CKI activity is determined by comparison of the phenotype of transformants having the cycD3 and cdc2a homologues to the transformants having ICK1 homologue and the cycD3 and cdc2a homologs.
  • Histone deacetylase activity can be assessed by complementation of the Arabidopsis mutants described in Tian et al., Genetics 165:399 (2003).
  • Histone acetyltransferase activity can be assayed using anacardic acid as described in Balasubramanyam et al., J. Biol. Chem. 278:19134 (2003).
  • Histone acetyltransferase also can be assayed using trichostatin A-treated plant lines as is described in Bhat et al., Plant J. 33:455 (2003).
  • Peptidyl-prolyl isomerase can be assayed as described in Edvardsson et al., FEBS Lett. 542:137 (2003).
  • WD40 proteins can be evaluated based on the possession of the WD40 motif as well as their ability to interact with cdc2.
  • WEE-1 can be assayed using any kinase activity assay known in the art.
  • the present invention provides methods of using plant cell cycle genes and conservative variants thereof.
  • the invention includes methods and constructs for altering expression of plant cell cycle genes and/or gene products for purposes including, but not limited to (i) investigating function during the cell cycle and ultimate effect on plant phenotype and (ii) to effect a change in plant phenotype.
  • the invention includes methods and tools for modifying wood quality, fiber development, cell wall polysaccharide content, fruit ripening, and plant growth and yield by altering expression of one or more plant cell cycle genes.
  • the invention comprises methods of altering the expression of any of the cell cycle genes and variants discussed above.
  • the invention comprises altering expression of a cell cycle gene present in the genome of a wild-type plant of a species of Eucalyptus or Pinus.
  • the cell cycle gene comprises a nucleotide sequence selected from SEQ ID NOs: 1-237, from the subset thereof comprising SEQ ID NOs: SEQ ID NOs: 1-12, 14-58, 60-62, 64-70, 72-75, 77-83, 85-86, 88-91, 93-119, 121-130, 132-148, 150-156, 158-191, 193-207, 209-218, 220-221, 223-231, and 233-237, from the subset thereof comprising SEQ ID NOs: 1-12, 14, 16-26, 30-37, 40-41, 43-76, 78-103, 106, 108-113, 116-121, 124-125, 128-147, 150-152, 154-155, 161-162, 164-172, 174, 177-183, 185-191, 193-197, 200-204, 208-213, and 215-234, from the subset thereof comprising SEQ ID NOs: 1-12, 14, 16-26, 30-37
  • Techniques which can be employed in accordance with the present invention to alter gene expression include, but are not limited to: (i) over-expressing a gene product, (ii) disrupting a gene's transcript, such as disrupting a gene's mRNA transcript; (iii) disrupting the function of a polypeptide encoded by a gene, or (iv) disrupting the gene itself
  • Over-expression of a gene product the use of antisense RNAs, ribozymes, and the use of double-stranded RNA interference (dsRNAi) are valuable techniques for discovering the functional effects of a gene and for generating plants with a phenotype that is different from a wild-type plant of the same species.
  • Over-expression of a target gene often is accomplished by cloning the gene or cDNA into an expression vector and introducing the vector into recipient cells.
  • over-expression can be accomplished by introducing exogenous promoters into cells to drive expression of genes residing in the genome. The effect of over-expression of a given gene on cell function, biochemical and/or physiological properties can then be evaluated by comparing plants transformed to over-express the gene to plants that have not been transformed to over-express the gene.
  • Antisense RNA, ribozyme, and dsRNAi technologies typically target RNA transcripts of genes, usually mRNA.
  • Antisense RNA technology involves expressing in, or introducing into, a cell an RNA molecule (or RNA derivative) that is complementary to, or antisense to, sequences found in a particular mRNA in a cell. By associating with the mRNA, the antisense RNA can inhibit translation of the encoded gene product.
  • the use of antisense technology to reduce or inhibit the expression of specific plant genes has been described, for example in European Patent Publication No. 271988, Smith et al., Nature, 334:724-726 (1988); Smith et. al., Plant Mol. Biol., 14:369-379 (1990)).
  • a ribozyme is an RNA that has both a catalytic domain and a sequence that is complementary to a particular mRNA.
  • the ribozyme functions by associating with the mRNA (through the complementary domain of the ribozyme) and then cleaving (degrading) the message using the catalytic domain.
  • RNA interference involves a post-transcriptional gene silencing (PTGS) regulatory process, in which the steady-state level of a specific mRNA is reduced by sequence-specific degradation of the transcribed, usually fully processed mRNA without an alteration in the rate of de novo transcription of the target gene itself.
  • PTGS post-transcriptional gene silencing
  • the RNAi technique is discussed, for example, in Elibashir, et al., Methods Enzymol. 26: 199 (2002); McManus & Sharp, Nature Rev. Genetics 3: 737 (2002); PCT application WO 01/75164; Martinez et al., Cell 110: 563 (2002); Elbashir et al., supra; Lagos-Quintana et al., Curr. Biol.
  • the present invention provides a DNA construct comprising at least one polynucleotide of SEQ ID NOs: 1-235 or conservative variants thereof, such as the conservative variants discussed above. Any method known in the art can be used to generate the DNA constructs of the present invention. See, e.g. Sambrook et al., supra.
  • the invention includes DNA constructs that optionally comprise a promoter.
  • Any suitable promoter known in the art can be used.
  • a promoter is a nucleic acid, preferably DNA, that binds RNA polymerase and/or other transcription regulatory elements.
  • the promoters of the invention facilitate or control the transcription of DNA or RNA to generate an mRNA molecule from a nucleic acid molecule that is operably linked to the promoter.
  • the RNA can encode a protein or polypeptide or can encode an antisense RNA molecule or a molecule useful in RNAi.
  • Promoters useful in the invention include constitutive promoters, inducible promoters, temporally regulated promoters and tissue-preferred promoters.
  • CaMV 35S promoter which confers constitutive, high-level expression in most plant tissues (Odel et al. Nature 313:810(1985)); the nopaline synthase promoter (An et al. Plant Physiol. 88:547 (1988)); and the octopine synthase promoter (Fromm et al., Plant Cell 1: 977 (1989)).
  • CaMV 35S promoter is commonly referred to as a constitutive promoter, some tissue preference can be seen. The use of CaMV 35S is envisioned by the present invention, regardless of any tissue preference which may be exhibited during use in the present invention.
  • Inducible promoters regulate gene expression in response to environmental, hormonal, or chemical signals.
  • hormone inducible promoters include auxin-inducible promoters (Baumann et al. Plant Cell 11:323-334(1999)), cytokinin-inducible promoters (Guevara-Garcia, Plant Mol. Biol. 38:743-753(1998)), and gibberellin-responsive promoters (Shi et al. Plant Mol. Biol. 38:1053-1060(1998)).
  • promoters responsive to heat, light, wounding, pathogen resistance, and chemicals such as methyl jasmonate or salicylic acid, can be used in the DNA constructs and methods of the present invention.
  • Tissue-preferred promoters allow for preferred expression of polynucleotides of the invention in certain plant tissue. Tissue-preferred promoters are also useful for directing the expression of antisense RNA or siRNA in certain plant tissues, which can be useful for inhibiting or completely blocking the expression of targeted genes as discussed above.
  • vascular plant tissue refers to xylem, phloem or vascular cambium tissue. Other preferred tissue includes apical meristem, root, seed, and flower.
  • tissue-preferred promoters of the invention are either “xylem-preferred,” “cambium-preferred” or “phloem-preferred,” and preferentially direct expression of an operably linked nucleic acid sequence in the xylem, cambium or phloem, respectively.
  • the DNA constructs of the invention comprise promoters that are tissue-specific for xylem, cambium or phloem, wherein the promoters are only active in the xylem, cambium or phloem.
  • a vascular-preferred promoter is preferentially active in any of the xylem, phloem or cambium tissues, or in at least two of the three tissue types.
  • a vascular-specific promoter is specifically active in any of the xylem, phloem or cambium, or in at least two of the three. In other words, the promoters are only active in the xylem, cambium or phloem tissue of plants. Note, however, that because of solute transport in plants, a product that is specifically or preferentially expressed in a tissue may be found elsewhere in the plant after expression has occurred.
  • the promoter is under temporal regulation, wherein the ability of the promoter to initiate expression is linked to factors such as the stage of the cell cycle or the stage of plant development.
  • the promoter of a cyclin D2 gene may be expressed only during the G1 and early S-phase, and the promoters of particular cyclin genes may be expressed only within the primary vascular poles of the developing seedling.
  • the promoters of particular cell cycle genes may be expressed only within the cambium in developing secondary vasculature. Within the cambium, particular cell cycle gene promoters may be expressed exclusively in the stem or in the root. Moreover, the cell cycle promoters may be expressed only in the spring (for early wood formation) or only in the summer.
  • a promoter may be operably linked to the polynucleotide.
  • operably linked refers to linking a polynucleotide encoding a structural gene to a promoter such that the promoter controls transcription of the structural gene.
  • the coding region can be operably linked to regulatory elements, such as to a promoter and a terminator, that bring about expression of an associated messenger RNA transcript and/or a protein product encoded by the desired polynucleotide.
  • the polynucleotide is operably linked in the 5′- to 3′-orientation to a promoter and, optionally, a terminator sequence.
  • the invention provides DNA constructs comprising a polynucleotide in an “antisense” orientation, the transcription of which produces nucleic acids that can form secondary structures that affect expression of an endogenous cell cycle gene in the plant cell.
  • the DNA construct may comprise a polynucleotide that yields a double-stranded RNA product upon transcription that initiates RNA interference of a cell cycle gene with which the polynucleotide is associated.
  • a polynucleotide of the present invention can be positioned within a t-DNA, such that the left and right t-DNA border sequences flank or are on either side of the polynucleotide.
  • a construct may comprise a t-DNA comprising one, two, three, four, five, six, seven, eight, nine, ten, or more polynucleotides.
  • the invention also includes DNA constructs comprising a promoter that includes one or more regulatory elements.
  • the invention includes DNA constructs comprising a regulatory element that is separate from a promoter. Regulatory elements confer a number of important characteristics upon a promoter region. Some elements bind transcription factors that enhance the rate of transcription of the operably linked nucleic acid. Other elements bind repressors that inhibit transcription activity. The effect of transcription factors on promoter activity can determine whether the promoter activity is high or low, i.e. whether the promoter is “strong” or “weak.”
  • a DNA construct of the invention can include a nucleotide sequence that serves as a selectable marker useful in identifying and selecting transformed plant cells or plants.
  • markers include, but are not limited to, a neomycin phosphotransferase (nptII) gene (Potrykus et al., Mol. Gen. Genet. 199:183-188 (1985)), which confers kanamycin resistance.
  • Cells expressing the nptII gene can be selected using an appropriate antibiotic such as kanamycin or G418.
  • the present invention also includes vectors comprising the DNA constructs discussed above.
  • the vectors can include an origin of replication (replicons) for a particular host cell.
  • replicons origin of replication
  • Various prokaryotic replicons are known to those skilled in the art, and function to direct autonomous replication and maintenance of a recombinant molecule in a prokaryotic host cell.
  • the present invention utilizes a pWVR8 vector as described in U.S. Application No. 60/476,222, filed Jun. 6, 2003, or pART27 as described in Gleave, Plant Mol. Biol, 20:1203-27 (1992).
  • the invention also provides host cells which are transformed with the DNA constructs of the invention.
  • a host cell refers to the cell in which a polynucleotide of the invention is expressed. Accordingly, a host cell can be an individual cell, a cell culture or cells that are part of an organism. The host cell can also be a portion of an embryo, endosperm, sperm or egg cell, or a fertilized egg. In one embodiment, the host cell is a plant cell.
  • the present invention further provides transgenic plants comprising the DNA constructs of the invention.
  • the invention includes transgenic plants that are angiosperms or gymnosperms.
  • the DNA constructs of the present invention can be used to transform a variety of plants, both monocotyledonous (e.g. grasses, corn, grains, oat, wheat and barley), dicotyledonous (e.g., Arabidopsis, tobacco, legumes, alfalfa, oaks, eucalyptus, maple), and Gymnosperms (e.g., Scots pine; see Aronen, Finnish Forest Res. Papers, Vol. 595, 1996), white spruce (Ellis et al., Biotechnology 11:84-89, 1993), and larch (Huang et al., In Vitro Cell 27:201-207, 1991).
  • monocotyledonous e.g. grasses, corn, grains, oat, wheat and barley
  • the plants also include turfgrass, wheat, maize, rice, sugar beet, potato, tomato, lettuce, carrot, strawberry, cassava, sweet potato, geranium, soybean, and various types of woody plants.
  • Woody plants include trees such as palm oak, pine, maple, fir, apple, fig, plum and acacia. Woody plants also include rose and grape vines.
  • the DNA constructs of the invention are used to transform woody plants, i.e., trees or shrubs whose stems live for a number of years and increase in diameter each year by the addition of woody tissue.
  • the invention includes methods of transforming plants including eucalyptus and pine species of significance in the commercial forestry industry such as plants selected from the group consisting of Eucalyptus grandis and its hybrids, and Pinus taeda, as well as the transformed plants and wood and wood pulp derived therefrom.
  • suitable plants include those selected from the group consisting of Pinus banksiana, Pinus brutia, Pinus caribaea, Pinus clausa, Pinus contorta, Pinus coulteri, Pinus echinata, Pinus eldarica, Pinus ellioti, Pinus jeffreyi, Pinus lambertiana, Pinus massoniana, Pinus monticola, Pinus nigra, Pinus palustris, Pinus pinaster, Pinus ponderosa, Pinus radiata, Pinus resinosa, Pinus rigida, Pinus serotina, Pinus strobus, Pinus sylvestris, Pinus taeda, Pinus virginiana, Abies amabilis, Abies balsamea, Abies concolor, Abies grandis, Abies lasiocarpa, Abies magnifica, Abies procera, Chamaecyparis lawsoniona, Chamaecyparis nootkat
  • the term “plant” also is intended to include the fruit, seeds, flower, strobilus, etc. of the plant.
  • a transformed plant of the current invention can be a direct transfectant, meaning that the DNA construct was introduced directly into the plant, such as through Agrobacterium, or the plant can be the progeny of a transfected plant.
  • the second or subsequent generation plant can be produced by sexual reproduction, i.e., fertilization.
  • the plant can be a gametophyte (haploid stage) or a sporophyte (diploid stage).
  • plant tissue encompasses any portion of a plant, including plant cells.
  • Plant cells include suspension cultures, callus, embryos, meristematic regions, callus tissue, leaves, roots, shoots, gametophytes, sporophytes, pollen, seeds and microspores.
  • Plant tissues can be grown in liquid or solid culture, or in soil or suitable media in pots, greenhouses or fields.
  • plant tissue also refers to a clone of a plant, seed, progeny, or propagule, whether generated sexually or asexually, and descendents of any of these, such as cuttings or seeds.
  • a transgenic plant that has been transformed with a DNA construct of the invention has a phenotype that is different from a plant that has not been transformed with the DNA construct.
  • phenotype refers to a distinguishing feature or characteristic of a plant which can be altered according to the present invention by integrating one or more DNA constructs of the invention into the genome of at least one plant cell of a plant.
  • the DNA construct can confer a change in the phenotype of a transformed plant by modifying any one or more of a number of genetic, molecular, biochemical, physiological, morphological, or agronomic characteristics or properties of the transformed plant cell or plant as a whole.
  • transformation of a plant with a DNA construct of the present invention can yield a phenotype including, but not limited to any one or more of increased drought tolerance, herbicide resistance, reduced or increased height, reduced or increased branching, enhanced cold and frost tolerance, improved vigor, enhanced color, enhanced health and nutritional characteristics, improved storage, enhanced yield, enhanced salt tolerance, enhanced resistance of the wood to decay, enhanced resistance to fungal diseases, altered attractiveness to insect pests, enhanced heavy metal tolerance, increased disease tolerance, increased insect tolerance, increased water-stress tolerance, enhanced sweetness, improved texture, decreased phosphate content, increased germination, increased micronutrient uptake, improved starch composition, improved flower longevity, production of novel resins, and production of novel proteins or peptides.
  • a phenotype including, but not limited to any one or more of increased drought tolerance, herbicide resistance, reduced or increased height, reduced or increased branching, enhanced cold and frost tolerance, improved vigor, enhanced color, enhanced health and nutritional characteristics, improved storage, enhanced yield, enhanced salt tolerance, enhanced resistance of the wood to decay, enhanced
  • the affected phenotype includes one or more of the following traits: propensity to form reaction wood, a reduced period of juvenility, an increased period of juvenility, self-abscising branches, accelerated reproductive development or delayed reproductive development, as compared to a plant of the same species that has not been transformed with the DNA construct.
  • the phenotype that is different in the transgenic plant includes one or more of the following: lignin quality, lignin structure, wood composition, wood appearance, wood density, wood strength, wood stiffness, cellulose polymerization, fiber dimensions, lumen size, other plant components, plant cell division, plant cell development, number of cells per unit area, cell size, cell shape, cell wall composition, rate of wood formation, aesthetic appearance of wood, formation of stem defects, average microfibril angle, width of the S2 cell wall layer, rate of growth, rate of root formation ratio of root to branch vegetative development, leaf area index, and leaf shape.
  • Phenotype can be assessed by any suitable means.
  • the plants can be evaluated based on their general morphology.
  • Transgenic plants can be observed with the naked eye, can be weighed and their height measured.
  • the plant can be examined by isolating individual layers of plant tissue, namely phloem and cambium, which is further sectioned into meristematic cells, early expansion, late expansion, secondary wall formation, and late cell maturation. See, e.g., Hertzberg, supra.
  • the plants also can be assessed using microscopic analysis or chemical analysis.
  • Microscopic analysis includes examining cell types, stage of development, and stain uptake by tissues and cells.
  • Fiber morphology such as fiber wall thickness and microfibril angle of wood pulp fibers can be observed using, for example, microscopic transmission ellipsometry. See Ye and Sundström, Tappi J., 80:181 (1997).
  • Wood strength, density, and grain slope in wet wood and standing trees can be determined by measuring the visible and near infrared spectral data in conjunction with multivariate analysis. See, U.S. Patent Application Publication Nos. 2002/0107644 and 2002/0113212.
  • Lumen size can be measured using scanning electron microscopy. Lignin structure and chemical properties can be observed using nuclear magnetic resonance spectroscopy as described in Marita et al., J. Chem. Soc., Perkin Trans. I 2939 (2001).
  • the biochemical characteristic of lignin, cellulose, carbohydrates and other plant extracts can be evaluated by any standard analytical method known including spectrophotometry, fluorescence spectroscopy, HPLC, mass spectroscopy, and tissue staining methods.
  • transformation refers to a process by which a nucleic acid is inserted into the genome of a plant cell. Such insertion encompasses stable introduction into the plant cell and transmission to progeny. Transformation also refers to transient insertion of a nucleic acid, wherein the resulting transformant transiently expresses the nucleic acid. Transformation can occur under natural or artificial conditions using various methods well known in the art. Transformation can be achieved by any known method for the insertion of nucleic acid sequences into a prokaryotic or eukaryotic host cell, including Agrobacterium -mediated transformation protocols, viral infection, whiskers, electroporation, microinjection, polyethylene glycol-treatment, heat shock, lipofection, and particle bombardment. Transformation can also be accomplished using chloroplast transformation as described in e.g. Svab et al., Proc. Natl Acad. Sci. 87:8526-30 (1990).
  • transformation in Eucalyptus is performed as described in U.S. Patent Application No. 60/476,222 (supra) which is incorporated herein by reference in its entirety.
  • transformation of Pinus is accomplished using the methods described in U.S. Patent Application Publication No. 2002/0100083.
  • Another aspect of the invention provides methods of obtaining wood and/or making wood pulp from a plant transformed with a DNA construct of the invention.
  • Methods of producing a transgenic plant are provided above and are known in the art.
  • a transformed plant can be cultured or grown under any suitable conditions.
  • pine can be cultured and grown as described in U.S. Patent Application Publication No. 2002/0100083.
  • Eucalyptus can be cultured and grown as in, for example, Rydelius, et al., G ROWING E UCALYPTUS FOR P ULP AND E NERGY, presented at the Mechanization in Short Rotation, Intensive Culture Forestry Conference, Mobile, Ala., 1994.
  • Wood and wood pulp can be obtained from the plant by any means known in the art.
  • the wood or wood pulp obtained in accordance with this invention may demonstrate improved characteristics including, but not limited to any one or more of lignin composition, lignin structure, wood composition, cellulose polymerization, fiber dimensions, ratio of fibers to other plant components, plant cell division, plant cell development, number of cells per unit area, cell size, cell shape, cell wall composition, rate of wood formation, aesthetic appearance of wood, formation of stem defects, rate of growth, rate of root formation ratio of root to branch vegetative development, leaf area index, and leaf shape include increased or decreased lignin content, increased accessibility of lignin to chemical treatments, improved reactivity of lignin, increased or decreased cellulose content increased dimensional stability, increased tensile strength, increased shear strength, increased compression strength, increased shock resistance, increased stiffness, increased or decreased hardness, decreased spirality, decreased shrinkage, and differences in weight, density, and specific gravity.
  • the present invention also provides methods and tools for performing expression profiling of cell cycle genes.
  • Expression profiling is useful in determining whether genes are transcribed or translated, comparing transcript levels for particular genes in different tissues, genotyping, estimating DNA copy number, determining identity of descent, measuring mRNA decay rates, identifying protein binding sites, determining subcellular localization of gene products, correlating gene expression to a phenotype or other phenomenon, and determining the effect on other genes of the manipulation of a particular gene.
  • Expression profiling is particularly useful for identifying gene expression in complex, multigenic events. For this reason, expression profiling is useful in correlating gene expression to plant phenotype and formation of plant tissues and the interconnection thereof to the cell cycle.
  • the present invention provides methods and tools for determining, for example, a gene expression profile at a given point in the cell cycle, a gene expression profile at a given point in plant development, and a gene expression profile a given tissue sample.
  • the invention also provides methods and tools for identifying cell cycle genes whose expression can be manipulated to alter plant phenotype or to alter the biological activity of cell cycle gene products. In support of these methods, the invention also provides methods and tools that distinguish expression of different genes of the same family.
  • gene expression refers to the process of transcription of a DNA sequence into an RNA sequence, followed by translation of the RNA into a protein, which may or may not undergo post-translational processing. Thus, the relationship between cell cycle stage and/or developmental stage and gene expression can be observed by detecting, quantitatively or qualitatively, changes in the level of an RNA or a protein.
  • biological activity includes, but is not limited to, the activity of a protein gene product, including enzyme activity.
  • the present invention provides oligonucleotides that are useful in these expression profiling methods.
  • Each oligonucleotide is capable of hybridizing under a given set of conditions to a cell cycle gene or gene product.
  • a plurality of oligonucleotides is provided, wherein each oligonucleotide hybridizes under a given set of conditions to a different cell cycle gene product.
  • Examples of oligonucleotides of the present invention include SEQ ID NOs: 471-697. Each of the oligos of SEQ ID NOs 471-697 hybridizes under standard conditions to a different gene product of one of SEQ ID NOs: 1-237.
  • the oligonucleotides of the invention are useful in determining the expression of one or more cell cycle genes in any of the above-described methods.
  • Samples for use in methods of the present invention may be derived from plant tissue.
  • suitable plant tissues include, but are not limited to, somatic embryos, pollen, leaves, stems, calli, stolons, microtubers, shoots, xylem, male strolbili, pollen cones, vascular tissue, apical meristem, vascular cambium, xylem, root, flower, and seed.
  • Plant tissue is used as described previously herein. Plant tissue can be obtained from any of the plants types or species described supra.
  • samples are obtained from plant tissue at different stages of the cell cycle, from plant tissue at different developmental stages, from plant tissue at various times of the year (e.g. spring versus summer), from plant tissues subject to different environmental conditions (e.g. variations in light and temperature) and/or from different types of plant tissue and cells.
  • plant tissue is obtained during various stages of maturity and during different seasons of the year.
  • plant tissue can be collected from stem dividing cells, differentiating xylem, early developing wood cells, differentiated spring wood cells, and differentiated summer wood cells.
  • gene expression in a sample obtained from a plant with developing wood can be compared to gene expression in a sample obtained from a plant which does not have developing wood.
  • Differentiating xylem includes samples obtained from compression wood, side-wood, and normal vertical xylem. Methods of obtaining samples for expression profiling from pine and eucalyptus are known. See, e.g., Allona et al., Proc. Nat'l Acad. Sci. 95:9693-8 (1998) and Whetton et al., Plant Mol. Biol. 47:275-91, and Kirst et al., I NT'L U NION OF F ORESTRY R ESEARCH O RGANIZATIONS B IENNIAL C ONFERENCE, S6.8 (June 2003, Umea, Sweden).
  • gene expression in one type of tissue is compared to gene expression in a different type of tissue or to gene expression in the same type of tissue in a difference stage of development.
  • Gene expression can also be compared in one type of tissue which is sampled at various times during the year (different seasons). For example, gene expression in juvenile secondary xylem can be compared to gene expression in mature secondary xylem.
  • gene expression in cambium can be compared to gene expression in xylem.
  • gene expression in apical meristems can be compared to gene expression in cambium.
  • differences in gene expression are determined as cells from different tissues advance during the cell cycle.
  • the cells from the different tissues are synchronized and their gene expression is profiled.
  • Methods of synchronizing the stage of cell cycle in a sample include, e.g., cold acclimation, photoperiod, and aphidicoline. See, e.g., Nagata et al., Int. Rev. Cytol. 132:1-30 (1992), Breyne and Zabeau, Curr. Opin. Plant Biol. 4:136-42, 140 (2001).
  • a sample is obtained during a specific stage of the cell cycle and gene expression in that sample is compared to a sample obtained during a different stage of the cell cycle.
  • tissue can be examined in any of the phases of the cell cycle, such as mitosis, G1, G0, S, and G2. In particular, one can examine the changes in gene expression at the G1, G2, and metaphase checkpoints.
  • a sample is obtained from a plant having a specific phenotype and gene expression in that sample is compared to a sample obtained from a plant of the same species that does not have that phenotype.
  • a sample can be obtained from a plant exhibiting a fast rate of growth and gene expression can be compared with that of a sample obtained from a plant exhibiting a normal or slow rate of growth. Differentially expressed genes identified from such a comparison can be correlated with growth rate and, therefore, useful for manipulating growth rate.
  • a sample is obtained from clonally propagated plants.
  • the clonally propagated plants are of the species Pinus or Eucalyptus.
  • Individual ramets from the same genotype can be sacrificed at different times of year.
  • Each of these trees can be divided into juvenile (top) to mature (bottom) samples.
  • tissue samples can be divided into, for example, phloem to xylem, in at least 5 layers of peeling. Each of these samples can be evaluated for phenotype and gene expression. See Entry 196.
  • Gene products including nucleic acid and amino acid gene products, can be isolated from cell fragments or lysates by any method known in the art.
  • Nucleic acids used in accordance with the invention can be prepared by any available method or process, or by other processes as they become known in the art. Conventional techniques for isolating nucleic acids are detailed, for example, in Tijssen, L ABORATORY T ECHNIQUES IN B IOCHEMISTRY AND M OLECULAR B IOLOGY: H YBRIDIZATION W ITH N UCLEIC A CID P ROBES, chapter 3 (Elsevier Press, 1993), Berger and Kimmel, Methods Enzymol. 152:1 (1987), and G IBCO BRL & L IFE T ECHNOLOGIES T RIZOL RNA I SOLATION P ROTOCOL, Form No. 3786 (2000).
  • a suitable nucleic acid sample can contain any type of nucleic acid derived from the transcript of a cell cycle gene, i.e., RNA or a subsequence thereof or a nucleic acid for which an mRNA transcribed from a cell cycle gene served as a template.
  • Suitable nucleic acids include cDNA reverse-transcribed from a transcript, RNA transcribed from that cDNA, DNA amplified from the cDNA, and RNA transcribed from the amplified DNA. Detection of such products or derived products is indicative of the presence and/or abundance of the transcript in the sample.
  • suitable samples include, but are not limited to, transcripts of the gene or genes, cDNA reverse-transcribed from the transcript, cRNA transcribed from the cDNA, DNA amplified from the genes, and RNA transcribed from amplified DNA.
  • transcripts of the gene or genes include, but are not limited to, transcripts of the gene or genes, cDNA reverse-transcribed from the transcript, cRNA transcribed from the cDNA, DNA amplified from the genes, and RNA transcribed from amplified DNA.
  • the category of “transcripts” includes but is not limited to pre-mRNA nascent transcripts, transcript processing intermediates, and mature mRNAs and degradation products thereof.
  • the expression profiling methods of the invention can be conducted by detecting only one type of transcript, such as mature mRNA levels only.
  • a chromosomal DNA or cDNA library (comprising, for example, fluorescently labeled cDNA synthesized from total cell mRNA) is prepared for use in hybridization methods according to recognized methods in the art. See Sambrook et al., supra.
  • mRNA is amplified using, e.g., the MessageAmp kit (Ambion).
  • the mRNA is labeled with a detectable label.
  • mRNA can be labeled with a fluorescent chromophore, such as CyDye (Amersham Biosciences).
  • RNase that often is present in homogenates or lysates, before use in hybridization techniques.
  • Methods of inhibiting or destroying nucleases are well known.
  • cells or tissues are homogenized in the presence of chaotropic agents to inhibit nuclease.
  • RNase is inhibited or destroyed by heat treatment, followed by proteinase treatment.
  • Protein samples can be obtained by any means known in the art. Protein samples useful in the methods of the invention include crude cell lysates and crude tissue homogenates. Alternatively, protein samples can be purified. Various methods of protein purification well known in the art can be found in Marshak et al., S TRATEGIES FOR P ROTEIN P URIFICATION AND C HARACTERIZATION: A L ABORATORY C OURSE M ANUAL (Cold Spring Harbor Laboratory Press 1996).
  • any method for observing gene expression can be used, without limitation. Such methods include traditional nucleic acid hybridization techniques, polymerase chain reaction (PCR) based methods, and protein determination.
  • PCR polymerase chain reaction
  • the invention includes detection methods that use solid support-based assay formats as well as those that use solution-based assay formats.
  • Absolute measurements of the expression levels need not be made, although they can be made.
  • the invention includes methods comprising comparisons of differences in expression levels between samples. Comparison of expression levels can be done visually or manually, or can be automated and done by a machine, using for example optical detection means. Subrahmanyam et al., Blood. 97: 2457 (2001); Prashar et al., Methods Enzymol. 303: 258 (1999). Hardware and software for analyzing differential expression of genes are available, and can be used in practicing the present invention. See, e.g., GenStat Software and GeneExpress® GX ExplorerTM Training Manual, supra; Baxevanis & Francis-Ouellette, supra.
  • nucleic acid hybridization techniques are used to observe gene expression.
  • Exemplary hybridization techniques include Northern blotting, Southern blotting, solution hybridization, and S1 nuclease protection assays.
  • Nucleic acid hybridization typically involves contacting an oligonucleotide probe and a sample comprising nucleic acids under conditions where the probe can form stable hybrid duplexes with its complementary nucleic acid through complementary base pairing.
  • the probe can form stable hybrid duplexes with its complementary nucleic acid through complementary base pairing.
  • the nucleic acids that do not form hybrid duplexes are then washed away leaving the hybridized nucleic acids to be detected, typically through detection of an attached detectable label.
  • the detectable label can be present on the probe, or on the nucleic acid sample.
  • the nucleic acids of the sample are detectably labeled polynucleotides representing the mRNA transcripts present in a plant tissue (e.g., a cDNA library).
  • Detectable labels are commonly radioactive or fluorescent labels, but any label capable of detection can be used. Labels can be incorporated by several approached described, for instance, in WO 99/32660, supra.
  • RNA can be amplified using the MessageAmp kit (Ambion) with the addition of aminoallyl-UTP as well as free UTP. The aminoallyl groups incorporated into the amplified RNA can be reacted with a fluorescent chromophore, such as CyDye (Amersham Biosciences)
  • Duplexes of nucleic acids are destabilized by increasing the temperature or decreasing the salt concentration of the buffer containing the nucleic acids.
  • low stringency conditions e.g., low temperature and/or high salt
  • hybrid duplexes e.g., DNA:DNA, RNA:RNA or RNA:DNA
  • specificity of hybridization is reduced at lower stringency.
  • higher stringency e.g., higher temperature and/or lower salt and/or in the presence of destabilizing reagents
  • hybridization tolerates fewer mismatches.
  • stringent conditions for short probes will be those in which the salt concentration is at least about 0.01 to 1.0 M at pH 7.0 to 8.3 and the temperature is at least about 30° C.
  • Stringent conditions can also be achieved with the addition of destabilizing agents such as formamide.
  • hybridization at conditions of low stringency, e.g., 6 ⁇ SSPE-T (0.9 M NaCl, 60 mM NaH 2 PO 4 , pH 7.6, 6 mM EDTA, 0.005% Triton) at 37° C., to ensure hybridization.
  • Subsequent washes can then be performed at higher stringency (e.g., 1 ⁇ SSPE-T at 37° C.) to eliminate mismatched hybrid duplexes.
  • Successive washes can be performed at increasingly higher stringency (e.g., down to as low as 0.25 ⁇ SSPE-T at 37° C. to 50° C.) until a desired level of hybridization specificity is obtained.
  • hybridized nucleic acids are washed at successively higher stringency conditions and read between each wash. Analysis of the data sets produced in this manner will reveal a wash stringency above which the hybridization pattern is not appreciably altered and which provides adequate signal for the particular oligonucleotide probes of interest.
  • the final wash may be selected as that of the highest stringency that produces consistent results and that provides a signal intensity greater than approximately 10% of the background intensity.
  • Oligonucleotide probes useful in nucleic acid hybridization techniques employed in the present invention are capable of binding to a nucleic acid of complementary sequence through one or more types of chemical bonds, usually through complementary base pairing via hydrogen bond formation.
  • a probe can include natural bases (i.e., A, G, U, C or T) or modified bases (7-deazaguanosine, inosine, etc.).
  • the nucleotide bases in the probes can be joined by a linkage other than a phosphodiester bond, so long as it does not interfere with hybridization.
  • probes can be peptide nucleic acids in which the constituent bases are joined by peptide bonds rather than phosphodiester linkages.
  • Oligonucleotide probes can be prepared by any means known in the art. Probes useful in the present invention are capable of hybridizing to a nucleotide product of cell cycle genes, such as one of SEQ ID NOs: 1-237. Probes useful in the invention can be generated using the nucleotide sequences disclosed in SEQ ID NOs: 1-237.
  • the invention includes oligonucleotide probes having at least a 2, 10,15, 20, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 100 nucleotide fragment of a corresponding contiguous sequence of any one of SEQ ID NOs: 1-237.
  • the invention includes oligonucleotides of less than 2, 1, 0.5, 0.1, or 0.05 kb in length. In one embodiment, the oligonucleotide is 60 nucleotides in length.
  • Oligonucleotide probes can be designed by any means known in the art. See, e.g., Li and Stormo, Bioinformatics 17: 1067-76 (2001). Oligonucleotide probe design can be effected using software. Exemplary software includes ArrayDesigner, GeneScan, and ProbeSelect. Probes complementary to a defined nucleic acid sequence can be synthesized chemically, generated from longer nucleotides using restriction enzymes, or can be obtained using techniques such as polymerase chain reaction (PCR). PCR methods are well known and are described, for example, in Innis et al. eds., PCR P ROTOCOLS: A G UIDE TO M ETHODS AND A PPLICATIONS, Academic Press Inc.
  • PCR polymerase chain reaction
  • the probes can be labeled, for example, with a radioactive, biotinylated, or fluorescent tag. Optimally, the nucleic acids in the sample are labeled and the probes are not labeled. Oligonucleotide probes generated by the above methods can be used in solution or solid support-based methods.
  • the invention includes oligonucleotide probes that hybridize to a product of the coding region or a 3′ untranslated region (3′ UTR) of a cell cycle gene.
  • the oligonucleotide probe hybridizes to the 3′UTR of any one of SEQ ID NOs: 1-237.
  • the 3′ UTR is generally a unique region of the gene, even among members of the same family. Therefore, the probes capable of hybridizing to a product of the 3′ UTR can be useful for differentiating the expression of individual genes within a family where the coding region of the genes likely are highly homologous.
  • oligonucleotide probes to be used as members of a plurality of oligonucleotides, each capable of uniquely binding to a single gene.
  • the oligonucleotide probe comprises any one of SEQ ID NOs: 471-697.
  • the oligonucleotide probe consists of any one of SEQ ID NOs:471-697.
  • One embodiment of the invention employs two or more oligonucleotide probes in combination to detect a level of expression of one or more cell cycle genes, such as the genes of SEQ ID NOs: 1-237.
  • the level of expression of two or more different genes is detected.
  • the two or more genes may be from the same or different cell cycle gene families discussed above.
  • Each of the two or more oligonucleotides may hybridize to a different one of the genes.
  • One embodiment of the invention employs two or more oligonucleotide probes, each of which specifically hybridize to a polynucleotide derived from the transcript of a gene provided by SEQ ID NOs: 1-237. Another embodiment employs two or more oligonucleotide probes, at least one of which comprises a nucleic acid sequence of SEQ ID NOs: 471-697. Another embodiment employs two or more oligonucleotide probes, at least one of which consists of SEQ ID NOs: 471-697.
  • the oligonucleotide probes may comprise from about 5 to about 60, or from about 5 to about 500, nucleotide bases, such as from about 60 to about 100 nucleotide bases, including from about 15 to about 60 nucleotide bases.
  • One embodiment of the invention uses solid support-based oligonucleotide hybridization methods to detect gene expression.
  • Solid support-based methods suitable for practicing the present invention are widely known and are described, for example, in PCT application WO 95/11755; Huber et al., Anal. Biochem. 299: 24 (2001); Meiyanto et al., Biotechniques. 31: 406 (2001); Relogio et al., Nucleic Acids Res. 30:e51 (2002).
  • Any solid surface to which oligonucleotides can be bound, covalently or non-covalently can be used.
  • Such solid supports include filters, polyvinyl chloride dishes, silicon or glass based chips, etc.
  • oligonucleotide arrays i.e. microarrays, which can be used to simultaneously observe the expression of a number of genes or gene products.
  • Oligonucleotide arrays comprise two or more oligonucleotide probes provided on a solid support, wherein each probe occupies a unique location on the support.
  • the location of each probe may be predetermined, such that detection of a detectable signal at a given location is indicative of hybridization to an oligonucleotide probe of a known identity.
  • Each predetermined location can contain more than one molecule of a probe, but each molecule within the predetermined location has an identical sequence. Such predetermined locations are termed features.
  • each oligonucleotide is located at a unique position on an array at least 2, at least 3, at least 4, at least 5, at least 6, or at least 10 times.
  • Oligonucleotide probe arrays for detecting gene expression can be made and used according to conventional techniques described, for example, in Lockhart et al., Nat'l Biotech. 14: 1675 (1996), McGall et al., Proc. Nat'l Acad. Sci. USA 93: 13555 (1996), and Hughes et al., Nature Biotechnol. 19:342 (2001).
  • a variety of oligonucleotide array designs is suitable for the practice of this invention.
  • the one or more oligonucleotides include a plurality of oligonucleotides that each hybridize to a different gene expressed in a particular tissue type.
  • the tissue can be developing wood.
  • a nucleic acid sample obtained from a plant can be amplified and, optionally labeled with a detectable label.
  • Any method of nucleic acid amplification and any detectable label suitable for such purpose can be used.
  • amplification reactions can be performed using, e.g. Ambion's MessageAmp, which creates “antisense” RNA or “aRNA” (complementary in nucleic acid sequence to the RNA extracted from the sample tissue).
  • the RNA can optionally be labeled using CyDye fluorescent labels.
  • CyDye fluorescent labels are coupled to the aaUTPs in a non-enzymatic reaction.
  • labeled amplified antisense RNAs are precipitated and washed with appropriate buffer, and then assayed for purity.
  • purity can be assay using a NanoDrop spectrophotometer.
  • the nucleic acid sample is then contacted with an oligonucleotide array having, attached to a solid substrate (a “microarray slide”), oligonucleotide sample probes capable of hybridizing to nucleic acids of interest which may be present in the sample.
  • the step of contacting is performed under conditions where hybridization can occur between the nucleic acids of interest and the oligonucleotide probes present on the array.
  • the array is then washed to remove non-specifically bound nucleic acids and the signals from the labeled molecules that remain hybridized to oligonucleotide probes on the solid substrate are detected.
  • the step of detection can be accomplished using any method appropriate to the type of label used.
  • the step of detecting can accomplished using a laser scanner and detector.
  • on can use and Axon scanner which optionally uses GenePix Pro software to analyze the position of the signal on the microarray slide.
  • Data from one or more microarray slides can analyzed by any appropriate method known in the art.
  • Oligonucleotide probes used in the methods of the present invention can be generated using PCR.
  • PCR primers used in generating the probes are chosen, for example, based on the sequences of SEQ ID NOs:1-237, to result in amplification of unique fragments of the cell cycle genes (i.e., fragments that hybridize to only one polynucleotide of any one of SEQ ID NOs: 1-237 under standard hybridization conditions).
  • Computer programs are useful in the design of primers with the required specificity and optimal hybridization properties. For example, Li and Stormo, supra at 1075, discuss a method of probe selection using ProbeSelect which selects an optimum oligonucleotide probe based on the entire gene sequence as well as other gene sequences to be probed at the same time.
  • oligonucleotide control probes also are used.
  • Exemplary control probes can fall into at least one of three categories referred to herein as (1) normalization controls, (2) expression level controls and (3) negative controls.
  • one or more of these control probes may be provided on the array with the inventive cell cycle gene-related oligonucleotides.
  • Normalization controls correct for dye biases, tissue biases, dust, slide irregularities, malformed slide spots, etc.
  • Normalization controls are oligonucleotide or other nucleic acid probes that are complementary to labeled reference oligonucleotides or other nucleic acid sequences that are added to the nucleic acid sample to be screened.
  • the signals obtained from the normalization controls, after hybridization provide a control for variations in hybridization conditions, label intensity, reading efficiency and other factors that can cause the signal of a perfect hybridization to vary between arrays.
  • signals e.g., fluorescence intensity or radioactivity
  • read from all other probes used in the method are divided by the signal from the control probes, thereby normalizing the measurements.
  • Virtually any probe can serve as a normalization control. Hybridization efficiency varies, however, with base composition and probe length. Preferred normalization probes are selected to reflect the average length of the other probes being used, but they also can be selected to cover a range of lengths. Further, the normalization control(s) can be selected to reflect the average base composition of the other probes being used. In one embodiment, only one or a few normalization probes are used, and they are selected such that they hybridize well (i.e., without forming secondary structures) and do not match any test probes. In one embodiment, the normalization controls are mammalian genes.
  • Expression level controls probes hybridize specifically with constitutively expressed genes present in the biological sample. Virtually any constitutively expressed gene provides a suitable target for expression level control probes. Typically, expression level control probes have sequences complementary to subsequences of constitutively expressed “housekeeping genes” including, but not limited to certain photosynthesis genes.
  • Negative control probes are not complementary to any of the test oligonucleotides (i.e., the inventive cell cycle gene-related oligonucleotides), normalization controls, or expression controls.
  • the negative control is a mammalian gene which is not complementary to any other sequence in the sample.
  • background and background signal intensity refer to hybridization signals resulting from non-specific binding or other interactions between the labeled target nucleic acids (i.e., mRNA present in the biological sample) and components of the oligonucleotide array. Background signals also can be produced by intrinsic fluorescence of the array components themselves.
  • a single background signal can be calculated for the entire array, or a different background signal can be calculated for each target nucleic acid.
  • background is calculated as the average hybridization signal intensity for the lowest 5 to 10 percent of the oligonucleotide probes being used, or, where a different background signal is calculated for each target gene, for the lowest 5 to 10 percent of the probes for each gene.
  • the oligonucleotide probes corresponding to a particular cell cycle gene hybridize well and, hence, appear to bind specifically to a target sequence, they should not be used in a background signal calculation.
  • background can be calculated as the average hybridization signal intensity produced by hybridization to probes that are not complementary to any sequence found in the sample (e.g., probes directed to nucleic acids of the opposite sense or to genes not found in the sample).
  • background can be calculated as the average signal intensity produced by regions of the array that lack any oligonucleotides probes at all.
  • PCR-based methods are used to detect gene expression. These methods include reverse-transcriptase-mediated polymerase chain reaction (RT-PCR) including real-time and endpoint quantitative reverse-transcriptase-mediated polymerase chain reaction (Q-RTPCR). These methods are well known in the art. For example, methods of quantitative PCR can be carried out using kits and methods that are commercially available from, for example, Applied BioSystems and Stratagene®. See also Kochanowski, Q UANTITATIVE PCR P ROTOCOLS (Humana Press, 1999); Innis et al., supra.; Vandesompele et al., Genome Biol. 3: RESEARCH0034 (2002); Stein, Cell Mol. Life Sci. 59: 1235 (2002).
  • RT-PCR reverse-transcriptase-mediated polymerase chain reaction
  • Q-RTPCR quantitative reverse-transcriptase-mediated polymerase chain reaction
  • Q-RTPCR relies on detection of a fluorescent signal produced proportionally during amplification of a PCR product. See Innis et al., supra.
  • this technique employs PCR oligonucleotide primers, typically 15-30 bases long, that hybridize to opposite strands and regions flanking the DNA region of interest.
  • a probe e.g., TaqMan®, Applied Biosystems
  • TaqMan® Applied Biosystems
  • the probe is labeled at the 5′ end with a reporter fluorophore, such as 6-carboxyfluorescein (6-FAM) and a quencher fluorophore like 6-carboxy-tetramethyl-rhodamine (TAMRA).
  • a reporter fluorophore such as 6-carboxyfluorescein (6-FAM) and a quencher fluorophore like 6-carboxy-tetramethyl-rhodamine (TAMRA).
  • 6-FAM 6-carboxyfluorescein
  • TAMRA 6-carboxy-tetramethyl-rhodamine
  • the forward and reverse amplification primers and internal hybridization probe is designed to hybridize specifically and uniquely with one nucleotide derived from the transcript of a target gene.
  • the selection criteria for primer and probe sequences incorporates constraints regarding nucleotide content and size to accommodate TaqMan® requirements.
  • SYBR Green® can be used as a probe-less Q-RTPCR alternative to the Taqman®-type assay, discussed above.
  • a device measures changes in fluorescence emission intensity during PCR amplification. The measurement is done in “real time,” that is, as the amplification product accumulates in the reaction. Other methods can be used to measure changes in fluorescence resulting from probe digestion. For example, fluorescence polarization can distinguish between large and small molecules based on molecular tumbling (see U.S. Pat. No. 5,593,867).
  • Proteins can be observed by any means known in the art, including immunological methods, enzyme assays and protein array/proteomics techniques.
  • Measurement of the translational state can be performed according to several protein methods.
  • whole genome monitoring of protein the “proteome”
  • binding sites comprise immobilized, preferably monoclonal, antibodies specific to a plurality of proteins having an amino acid sequence of any of SEQ ID NOs: 261-497 or proteins encoded by the genes of SEQ ID NOs:1-237 or conservative variants thereof.
  • Methods for making polyclonal and monoclonal antibodies are well known, as described, for instance, in Harlow & Lane, A NTIBODIES: A L ABORATORY M ANUAL (Cold Spring Harbor Laboratory Press, 1988).
  • proteins can be separated by two-dimensional gel electrophoresis systems.
  • Two-dimensional gel electrophoresis is well-known in the art and typically involves isoelectric focusing along a first dimension followed by SDS-PAGE electrophoresis along a second dimension. See, e.g., Hames et al, G EL E LECTROPHORESIS OF P ROTEINS: A P RACTICAL A PPROACH (IRL Press, 1990).
  • the resulting electropherograms can be analyzed by numerous techniques, including mass spectrometric techniques, western blotting and immunoblot analysis using polyclonal and monoclonal antibodies, and internal and N-terminal micro-sequencing.
  • the invention provides methods and tools to correlate gene expression to plant phenotype.
  • Gene expression may be examined in a plant having a phenotype of interest and compared to a plant that does not have the phenotype or has a different phenotype.
  • Such a phenotype includes, but is not limited to, increased drought tolerance, herbicide resistance, reduced or increased height, reduced or increased branching, enhanced cold and frost tolerance, improved vigor, enhanced color, enhanced health and nutritional characteristics, improved storage, enhanced yield, enhanced salt tolerance, enhanced resistance of the wood to decay, enhanced resistance to fungal diseases, altered attractiveness to insect pests, enhanced heavy metal tolerance, increased disease tolerance, increased insect tolerance, increased water-stress tolerance, enhanced sweetness, improved texture, decreased phosphate content, increased germination, increased micronutrient uptake, improved starch composition, improved flower longevity, production of novel resins, and production of novel proteins or peptides.
  • the phenotype includes one or more of the following traits: propensity to form reaction wood, a reduced period of juvenility, an increased period of juvenility, self-abscising branches, accelerated reproductive development or delayed reproductive development.
  • the phenotype that is differs in the plants compares includes one or more of the following: lignin quality, lignin structure, wood composition, wood appearance, wood density, wood strength, wood stiffness, cellulose polymerization, fiber dimensions, lumen size, other plant components, plant cell division, plant cell development, number of cells per unit area, cell size, cell shape, cell wall composition, rate of wood formation, aesthetic appearance of wood, formation of stem defects, average microfibril angle, width of the S2 cell wall layer, rate of growth, rate of root formation ratio of root to branch vegetative development, leaf area index, and leaf shape.
  • Phenotype can be assessed by any suitable means as discussed above.
  • gene expression can be correlated to a given point in the cell cycle, a given point in plant development, and in a given tissue sample.
  • Plant tissue can be examined at different stages of the cell cycle, from plant tissue at different developmental stages, from plant tissue at various times of the year (e.g. spring versus summer), from plant tissues subject to different environmental conditions (e.g. variations in light and temperature) and/or from different types of plant tissue and cells.
  • plant tissue is obtained during various stages of maturity and during different seasons of the year. For example, plant tissue can be collected from stem dividing cells, differentiating xylem, early developing wood cells, differentiated spring wood cells, differentiated summer wood cells.
  • Example 1 illustrates a procedure for RNA extraction and purification, which is particularly useful for RNA obtained from conifer needle, xylem, cambium, and phloem.
  • Tissue is obtained from conifer needle, xylem, cambium or phloem. The tissue is frozen in liquid nitrogen and ground. The total RNA is extracted using Concert Plant RNA reagent (Invitrogen). The resulting RNA sample is extracted into phenol:chloroform and treated with DNase. The RNA is then incubated at 65° C. for 2 minutes followed by centrifugation at 4° C. for 30 minutes. Following centrifugation, the RNA is extracted into phenol at least 10 times to remove contaminants.
  • RNA is further cleaned using RNeasy columns (Qiagen).
  • the purified RNA is quantified using RiboGreen reagent (Molecular Probes) and purity assessed by gel electrophoresis.
  • RNA is then amplified using MessageAmp (Ambion). Aminoallyl-UTP and free UTP are added to the in vitro transcription of the purified RNA at a ratio of 4:1 aminoallyl-UTP-to-UTP. The aminoallyl-UTP is incorporated into the new RNA strand as it is transcribed. The amino-allyl group is then reacted with Cy dyes to attach the colorimetric label to the resulting amplified RNA using the Amersham procedure modified for use with RNA. Unincorporated dye is removed by ethanol precipitation. The labeled RNA is quantified spectrophotometrically (NanoDrop). The labeled RNA is fragmented by heating to 95° C. as described in Hughes et al., Nature Biotechnol. 19:342 (2001).
  • Example 2 illustrates how cell cycle genes important for wood development in Pinus radiata can be determined and how oligonucleotides which uniquely bind to those genes can be designed and synthesized for use on a microarray.
  • Pine trees of the species Pinus radiata are grown under natural light conditions. Tissue samples are prepared as described in, e.g., Sterky et al., Proc. Nat'l Acad. Sci. 95:13330 (1998). Specifically, tissue samples are collected from woody trees having a height of 5 meters. Tissue samples of the woody trees are prepared by taking tangential sections through the cambial region of the stem. The stems are sectioned horizontally into sections ranging from juvenile (top) to mature (bottom).
  • the stem sections separated by stage of development are further separated into 5 layers by peeling into sections of phloem, differentiating phloem, cambium, differentiating xylem, developing xylem, and mature xylem.
  • Tissue samples, including leaves, buds, shoots, and roots are also prepared from seedlings of the species Pinus radiata.
  • RNA is isolated and ESTs generated as described in Example 1 or Sterky et al., supra.
  • the nucleic acid sequences of ESTs derived from samples containing developing wood are compared with nucleic acid sequences of genes known to be involved in the plant cell cycle.
  • ESTs from samples that do not contain developing wood are also compared with sequences of genes known to be involved in the plant cell cycle.
  • An in silico hybridization analysis is performed using BLAST (NCBI). Sequences from among the known cell cycle genes that show hybridization in silico to ESTs made from samples containing developing wood, but that do not hybridize to ESTs from samples not containing developing wood are selected for further examination.
  • cDNA clones containing sequences that hybridize to the genes showing wood-preferred expression are selected from cDNA libraries using techniques well known in the art of molecular biology.
  • oligonucleotides are designed such that each oligonucleotide is specific for only one cDNA sequence in the library.
  • the oligonucleotide sequences are provided in Table 14. 60-mer oligonucleotide probes are designed using the method of Li and Stormo, supra or using software such as ArrayDesigner, GeneScan, and ProbeSelect.
  • oligonucleotides are then synthesized in situ described in Hughes et al., Nature Biotechnol. 19:324 (2002) or as described in Kane et al., Nucleic Acids Res. 28:4552 (2000) and affixed to an activated glass slide (Sigma-Genosis, The Woodlands, Tex.) using a 5′ amino linker. The position of each oligonucleotide on the slide is known.
  • Example 3 illustrates how cell cycle genes important for wood development in Eucalyptus grandis can be determined and how oligonucleotides which uniquely bind to those genes can be designed and synthesized for use on a microarray.
  • Tissue samples are prepared as described in, e.g., Sterky et al., Proc. Nat'l Acad. Sci. 95:13330 (1998). Specifically, tissue samples are collected from woody trees having a height of 5 meters. Tissue samples of the woody trees are prepared by taking tangential sections through the cambial region of the stem. The stems are sectioned horizontally into sections ranging from juvenile (top) to mature (bottom).
  • the stem sections separated by stage of development are further separated into 5 layers by peeling into sections of phloem, differentiating phloem, cambium, differentiating xylem, developing xylem, and mature xylem.
  • Tissue samples, including leaves, buds, shoots, and roots are also prepared from seedlings of the species Pinus radiata.
  • RNA is isolated and ESTs generated as described in Example 1 or Sterky et al., supra.
  • the nucleic acid sequences of ESTs derived from samples containing developing wood are compared with nucleic acid sequences of genes known to be involved in the plant cell cycle.
  • ESTs from samples that do not contain developing wood are also compared with sequences of genes known to be involved in the plant cell cycle.
  • An in silico hybridization analysis is performed as described in, for example, Audic and Claverie, Genome Res. 7:986 (1997). Sequences from among the known cell cycle genes that show hybridization in silico to ESTs made from samples containing developing wood, but do not hybridize to ESTs from samples not containing developing wood are selected for further examination.
  • cDNA clones containing sequences that hybridize to the genes showing wood-preferred expression are selected from cDNA libraries using techniques well known in the art of molecular biology.
  • oligonucleotides are designed such that each oligonucleotide is specific for only one cDNA sequence in the library.
  • the oligonucleotide sequences are provided in Table 14. 60-mer oligonucleotide probes are designed using the method of Li and Stormo, supra or using software such as ArrayDesigner, GeneScan, and ProbeSelect.
  • oligonucleotides are then synthesized in situ described in Hughes et al., Nature Biotechnol. 19:324 (2002) or as described in Kane et al., Nucleic Acids Res. 28:4552 (2000) and affixed to an activated glass slide (Sigma-Genosus, The Woodlands, Tex.) using a 5′ amino linker. The position of each oligonucleotide on the slide is known.
  • Example 4 illustrates how to detect expression of Pinus radiata cell cycle genes which are important in wood formation using an oligonucleotide microarray prepared as in Example 2.
  • This is an example of a balanced incomplete block designed experiment carried out using aRNA samples prepared from mature-phase phloem (P), cambium (C), expanding xylem found in a layer below the cambium (X1) and differentiating, lignifying xylem cells found deeper in the same growth ring (X2).
  • P mature-phase phloem
  • C cambium
  • X1 expanding xylem found in a layer below the cambium
  • X2 differentiating, lignifying xylem cells found deeper in the same growth ring
  • RNA is subsequently isolated from the frozen tissue samples as described in Example 1. Equal microgram quantities of total RNA are purified from each sample using RNeasy Mini columns (Qiagen, Valencia, Calif.) according to the manufacturers instructions.
  • Amplification reactions are carried out for each of the P, C, X1, and X2 tissue samples.
  • Amplification reactions are performed using Ambion's MessageAmp kit, a T7-based amplification procedure, following the manufacturer's instructions, except that labeled aaUTP is added to the reagent mix during in the amplification step. aaUTP is incorporated into the resulting antisense RNA formed during this step.
  • CyDye fluorescent labels are coupled to the aaUTPs in a non-enzymatic reaction as described in Example 1.
  • Labeled amplified antisense RNAs are precipitated and washed, and then assayed for purity using a NanoDrop spectrophotometer.
  • These labeled antisense RNAs corresponding to the RNA isolated from the P, C, X1, and X2 tissue samples, constitute the sample nucleic acids, which are referred to as the P, C, X1, and X2 samples.
  • Normalization control samples of known nucleic acids are added to each sample in a dilution series of 500, 200, 100, 50, 25 and 10 pg/ ⁇ l for quantitation of the signals.
  • Positive controls corresponding to specific genes showing expression in all tissues of pine, such as housekeeping genes, are also added to the plant sample.
  • Each of four microarray slides is incubated with 125 ⁇ L of a P, C, X1 or X2 sample under a coverslip at 42° C. for 16-18 hours.
  • the arrays are washed in 1 ⁇ SSC, 0.1% SDS for 10 minutes and then in 0.1 ⁇ SSC, 0.1% SDS for 10 minutes and the allowed to dry.
  • Mean signal intensity for each signal at any given position on the microarray slide is determined for each of three of P, C, X1, and X2 sample microarray slides. This mean signal/probe position is compared to the signal at the same position on sample slide which was not used for calculating the mean. For example, a mean signal at a given position is determined for P, C, and X1 and the signal at that position in the X2 microarray slide is compared to the P, C, and X1 mean signal value.
  • Table 1 shows genes having greater than doubled signal with any one sample as compared to the mean signal of the other three samples.
  • WD40 repeat protein A encodes a WD40 repeat protein is less highly expressed in cambium than in developing xylem
  • WD40 repeat protein B encodes a WD40 repeat protein that is more highly expressed in phloem than in the other tissues.
  • Signal data are then verified with RT-PCR to confirm gene expression in the target tissue of the genes corresponding to the unique oligonucleotides in the probe.
  • Example 5 demonstrates how one can correlate cell cycle gene expression with agronomically important wood phenotypes such as density, stiffness, strength, distance between branches, and spiral grain.
  • Mature clonally propagated pine trees are selected from among the progeny of known parent trees for superior growth characteristics and resistance to important fungal diseases.
  • the bark is removed from a tangential section and the trees are examined for average wood density in the fifth annual ring at breast height, stiffness and strength of the wood, and spiral grain.
  • the trees are also characterized by their height, mean distance between major branches, crown size, and forking.
  • trees lacking common parents are chosen for specific crosses on the criterion that they exhibit the widest variation from each other with respect to the density, stiffness, strength, distance between branches, and spiral grain criteria.
  • pollen from a plus tree exhibiting high density, low mean distance between major branches, and high spiral grain is used to pollinate cones from the unrelated plus tree among the selections exhibiting the lowest density, highest mean distance between major branches, and lowest spiral grain.
  • Seeds are collected from these controlled pollinations and grown such that the parental identity is maintained for each seed and used for vegetative propagation such that each genotype is represented by multiple ramets. Vegetative propagation is accomplished using micropropagation, hedging, or fascicle cuttings. Some ramets of each genotype are stored while vegetative propagules of each genotype are grown to sufficient size for establishment of a field planting. The genotypes are arrayed in a replicated design and grown under field conditions where the daily temperature and rainfall are measured and recorded.
  • the trees are measured at various ages to determine the expression and segregation of density, stiffness, strength, distance between branches, spiral grain, and any other observable characteristics that may be linked to any of the genes affecting these characteristics.
  • Samples are harvested for characterization of cellulose content, lignin content, cellulose microfibril angle, density, strength, stiffness, tracheid morphology, ring width, and the like. Samples are also examined for gene expression as described in Example 4. Ramets of each genotype are compared to ramets of the same genotype at different ages to establish age:age correlations for these characteristics.
  • Example 6 demonstrates how the stage of plant development and responses to environmental conditions such as light and season can be correlated to cell cycle gene expression using microarrays prepared as in Example 4. In particular, the changes in gene expression associated with wood density are examined.
  • Trees of three different clonally propagated Eucalyptus grandis hybrid genotypes are grown on a site with a weather station that measures daily temperatures and rainfall. During the spring and subsequent summer, genetically identical ramets of the three different genotypes are first photographed with north-south orientation marks, using photography at sufficient resolution to show bark characteristics of juvenile and mature portions of the plant, and then felled as in Example 4. The age of the trees is determined by planting records and confirmed by a count of the annual rings. In each of these trees, mature wood is defined as the outermost rings of the tree below breast height, and juvenile wood as the innermost rings of the tree above breast height. Each tree is accordingly sectored as follows:
  • Tissue is harvested from the plant trunk as well as from juvenile and mature form leaves. Samples are prepared simultaneously for phenotype analysis, including plant morphology and biochemical characteristics, and gene expression analysis. The height and diameter of the tree at the point from which each sector was taken is recorded, and a soil sample from the base of the tree is taken for chemical assay. Samples prepared for gene expression analysis are weighed and placed into liquid nitrogen for subsequent preparation of RNA samples for use in the microarray experiment. The tissues are denoted as follows:
  • Thin slices in tangential and radial sections from each of the sectors of the trunk are fixed as described in Ruzin, Plant Microtechnique and Microscopy, Oxford University Press, Inc., New York, N.Y. (1999) for anatomical examination and confirmation of wood developmental stage.
  • Microfibril angle is examined at the different developmental stages of the wood, for example juvenile, transition and mature phases of Eucalyptus grandis wood.
  • Other characteristics examined are the ratio of fibers to vessel elements and ray tissue in each sector.
  • the samples are examined for characteristics that change between juvenile and mature wood and between spring wood and summer wood, such as fiber morphology, lumen size, and width of the S2 (thickest) cell wall layer.
  • Samples are further examined for measurements of density in the fifth ring and determination of modulus of elasticity using techniques well known to those skilled in the art of wood assays. See, e.g., Wang, et al., Non - destructive Evaluations of Trees, E XPERIMENTAL T ECHNIQUES, pp. 28-30 (2000).
  • biochemical analysis 50 grams from each of the harvest samples are freeze-dried and analyzed, using biochemical assays well known to those skilled in the art of plant biochemistry for quantities of simple sugars, amino acids, lipids, other extractives, lignin, and cellulose. See, e.g., Pettersen & Schwandt, J. Wood Chem. & Technol. 11:495 (1991).
  • the phenotypes chosen for comparison are high density wood, average density wood, and low density wood.
  • Nucleic acid samples are prepared as described in Example 3, from trees harvested in the spring and summer. Gene expression profiling by hybridization and data analysis is performed as described in Examples 3 and 4.
  • cell cycle gene expression as it is related to other complex wood characteristics such as strength, stiffness and spirality.
  • Example 7 demonstrates the ability of the oligonucleotide probes of the invention to distinguish between highly homologous members of a family of cell cycle genes.
  • Hybridization to a particular oligonucleotide on the array identifies a unique WD40 gene that is expressed more strongly in a genotype having a higher density wood than in observed in other genotypes examined.
  • the WD40 gene is also expressed more strongly in mature wood than in juvenile wood and more strongly in summer wood than in spring wood. This gene is not found to be expressed at high levels either in leaves or buds.
  • the gene expression pattern is confirmed by RT-PCR.
  • This gene the putative “density-related” gene, is used for in situ hybridization of fixed radial sections.
  • the density-related WD40 gene hybridizes most strongly to the vascular cambium in regions of the stem where the xylem is comprised primarily of fibers with few vessel elements and few xylem ray cells.
  • this gene product functions specifically in developing secondary xylem to guide the cell division patterns of fibers, such that higher expression of this gene results in greater fiber production relative to vessel element or ray production.
  • the fiber content is correlated with a principal components analysis (PCA) variable that accounts for at least 10% of the variation in basic density.
  • PCA principal components analysis
  • Example 8 demonstrates how the use of oligonucleotide probes of the invention can be used to identify one wood “density related” WD40 repeat protein gene and its promoter from among the family of homologous genes. Further, this example demonstrates how a promoter sequence identified using this method is used to transform other hardwood species to result in increased diameter growth rates as compared to wild-type plants of the same species.
  • the sequence of the WD40 gene is used to probe a Genome Walker library in order to isolate 5′ flanking sequences comprising a promoter region.
  • the promoter region is then operably linked to a beta-glucuronidase reporter gene and cloned into a binary vector for transformation into Eucalyptus using the method described in U.S. Application Ser. No. 60/476,222.
  • Regenerated transgenic tobacco and Eucalyptus plants are then sectioned and stained using X-gluc, demonstrating that the microarray data results in isolation of a promoter capable of highly cambial-specific expression solely in those portions of the stem that develop more fibers than vessel elements or xylem rays.
  • the promoter is then operably linked to a cell division promoting gene and this construct placed in a binary vector for transformation into hardwood plants such as Sweetgum and Populus, such that the cell division promoting gene is expressed more strongly than normally in the vascular cambium. This results in increased diameter growth rate in the transgenic hardwood plants relative to control hardwood plants.
  • Example 9 demonstrates how a density related polypeptide can be linked to a tissue-preferred promoter and expressed in pine resulting in a plant with increased wood density.
  • a density-related polypeptide which is more highly expressed during the early spring, is identified by the method described in Example 7.
  • a DNA construct having the density-related polypeptide operably linked to a promoter is placed into an appropriate binary vector and transformed into pine using the method of Connett et al. (U.S. patent application Ser. Nos. 09/973,088 and 09/973,089). Pine plants are transformed as described in Connett et al., supra, and the transgenic pine plants are used to establish a forest planting. Increased density even in the spring wood (early wood) is observed in the transgenic pine plants relative to control pine plants which are not transformed with the density related DNA construct.
  • Example 7 Using techniques well known to those skilled in the art of molecular biology, the sequence of the putative density-related gene isolated in Example 7 is analyzed in genomic DNA isolated from alfalfa. This enables the identification of an orthologue in alfalfa whose sequence is then used to create an RNAi knockout construct. This construct is then transformed into alfalfa. See, e.g., Austin et al., Euphytica 85, 381 1995. The regenerated transgenic plants show lower fiber content and increased ray cells content in the xylem. Such properties improved digestability which results in higher growth rates in cattle fed on this alfalfa as compared to wild-type alfalfa of the same species.
  • Example 11 demonstrates how gene expression analysis can be used to find gene variants which are present in mature plants having a desirable phenotype. The presence or absence of such a variant can be used to predict the phenotype of a mature plant, allowing screening of the plants at the seedling stage.
  • this example employs eucalyptus, the method used herein is also useful in breeding programs for pine and other tree species.
  • the sequence of a putative density-related gene is used to probe genomic DNA isolated from Eucalyptus that vary in density as described in previous examples.
  • Non-transgenically produced Eucalyptus hybrids of different wood phenotypes are examined. One hybrid exhibits high wood density and another hybrid exhibits lower wood density.
  • a molecular marker in the 3′ portion of the coding region is found which distinguishes a high-density gene variant from a lower density gene variant.
  • This molecular marker enables tree breeders to assay non-transgenic Eucalyptus hybrids for likely density profiles while the trees are still at seedling stage, whereas in the absence of the marker, tree breeders must wait until the trees have grown for multiple years before density at harvest age can be reliably predicted. This enables selective outplanting of the best trees at seedling stage rather than an expensive culling operation and resultant erosion at thinning age. This molecular marker is further useful in the breeding program to determine which parents will give rise to high density outcross progeny.
  • markers found in the 3′ portion of the coding region of the gene that do not correspond to variants seen more frequently in higher or lower wood density non-transgenic Eucalyptus hybrid trees are also useful. These markers are found to be useful for fingerprinting different genotypes of Eucalyptus, for use in identity-tracking in the breeding program and in plantations.
  • This Example describes microarrays for identifying gene expression differences that contribute to the phenotypic characteristics that are important in commercial wood, namely wood appearance, stiffness, strength, density, fiber dimensions, coarseness, cellulose and lignin content, extractives content and the like.
  • RNA is also isolated from seedlings of the same genera.
  • the longest cDNA clones containing sequences hybridizing to the putative novel genes showing wood-preferred expression are selected from cDNA libraries using techniques well known to those skilled in the art of molecular biology.
  • the cDNAs are sequenced and full-length gene-coding sequences together with untranslated flanking sequences are obtained where possible.
  • Stretches of 45-80 nucleotides (or oligonucleotides) are selected from each of the sequences of putative novel genes showing wood-preferred expression such that each oligonucleotide probe hybridizes at high stringency to only one sequence represented in the ESTs made from RNA isolated from trees or seedlings of the same genus.
  • Oligomers are then chemically synthesized and placed onto a microarray slide as described in Example 3. Each oligomer corresponds to a particular sequence of a putative novel gene showing wood-preferred expression and to no other gene whose sequence is represented among the ESTs made from RNA isolated from trees or seedlings of the same genus.
  • Example 4 Sample preparation and hybridization are carried out as in Example 4.
  • the technique used in this example is more effective than use of a microarray using cDNA probes because the presence of a signal represents significant evidence of the expression of a particular gene, rather than of any of a number of genes that may contain similarities to the cDNA due to conserved functional domains or common evolutionary history.
  • homologous genes such as those in the same family, but which may have different functions in phenotype determination.
  • hybridization data gained using the method of Example 4, enable the user to identify which of the putative novel genes actually has a pattern of coordinate expression with known genes, a pattern of expression consistent with a particular developmental role, and/or a pattern of expression that suggests that the gene has a promoter that drives expression in a valuable way.
  • the hybridization data thus using this method can be used, for example, to identify a putative novel gene that shows an expression pattern particular to the tracheids with the lowest cellulose microfibril angle in developing spring wood (early wood).
  • the promoter of this gene can also be isolated as in Example 8, and operably linked to a gene that has been shown as in Example 9 to be associated with late wood (summer wood).
  • Transgenic pine plants containing this construct are generated using the methods of Example 9, and the early wood of these plants is then shown to display several characteristics of late wood, such as higher microfibril angle, higher density, smaller average lumen size, etc.
  • Example 13 demonstrates the use of a cambium-specific promoter functionally linked to a cell cycle gene for increased plant biomass.
  • Cambium-specific cell cycle transcripts are identified via array analyses of different secondary vasculature layers as described in Example 4.
  • Candidate promoters linked to the genes corresponding to these transcripts are cloned from pine genomic DNA using, e.g., the BD Clontech GenomeWalker kit and tested in transgenic tobacco via a reporter assay(s) for cambium specificity/preference.
  • the cambium-specific promoter overexpressing a cell cycle gene involved in secondary xylem cell division is used to increased wood biomass.
  • a tandem cambium-specific promoter is constructed driving the cell cycle ORF. Boosted transcript levels of the candidate cell cycle gene result in an increased xylem biomass phenotype.
  • Eucalyptus grandis cDNA expression libraries were prepared from mature shoot buds, early wood phloem, floral tissue, leaf tissue (two independent libraries), feeder roots, structural roots, xylem or early wood xylem and were constructed and screened as follows.
  • the resulting cDNAs were packaged using a Gigapack II Packaging Extract (Stratagene) using an aliquot (1-5 ⁇ l) from the 5 ⁇ l ligation reaction dependent upon the library. Mass excision of the library was done using XL1-Blue MRF′ cells and XLOLR cells (Stratagene) with ExAssist helper phage (Stratagene). The excised phagemids were diluted with NZY broth (Gibco BRL, Gaithersburg, Md.) and plated out onto LB-kanamycin agar plates containing X-gal and isopropylthio-beta-galactoside (IPTG).
  • NZY broth Gibco BRL, Gaithersburg, Md.
  • DNA sequence for positive clones was obtained using a Perkin Elmer/Applied Biosystems Division Prism 377 sequencer. cDNA clones were sequenced first from the 5′ end and, in some cases, also from the 3′ end. For some clones, internal sequence was obtained using either Exonuclease III deletion analysis, yielding a library of differentially sized subclones in pBK-CMV, or by direct sequencing using gene-specific primers designed to identified regions of the gene of interest.
  • the determined cDNA sequences were compared with known sequences in the EMBL database using the computer algorithms FASTA and/or BLASTN. Multiple alignments of redundant sequences were used to build reliable consensus sequences. Based on similarity to known sequences from other plant species, the isolated polynucleotide sequences were identified as encoding transcription factors, as detailed herein. The predicted polypeptide sequences corresponding to the polynucleotide sequences are also depicted therein.
  • Pinus radiata cDNA expression libraries prepared from either shoot bud tissue, suspension cultured cells, early wood phloem (two independent libraries), fascicle meristem tissue, male strobilus, root (unknown lineage), feeder roots, structural roots, female strobilus, cone primordia, female receptive cones and xylem (two independent libraries) were constructed and screened as described above in Example 14.
  • DNA sequence for positive clones was obtained using forward and reverse primers on a Perkin Elmer/Applied Biosystems Division Prism 377 sequencer and the determined sequences were compared to known sequences in the database as described above.
  • the isolated polynucleotide sequences were identified as encoding transcription factors, as detailed herein.
  • the predicted polypeptide sequences corresponding to the polynucleotide sequences are also depicted therein.
  • RACE 5′ and 3′ rapid amplification of cDNA ends
  • Gene-specific primers were designed to be used along with adaptor specific primers for both 5′ and 3′ RACE reactions. Using 5′ and 3′ RACE reactions, 5′ and 3′ RACE fragments were obtained, sequenced, and cloned. The process may be repeated until 5′ and 3′ ends of the full-length gene were identified. A full-length cDNA may generated by PCR using primers specific to 5′ and 3′ ends of the gene by end-to-end PCR.
  • a primer was designed 5′ ⁇ 3′ from the opposite strand of the template sequence, and from the region between ⁇ 100-200 bp of the template sequence.
  • a successful amplification should give an overlap of ⁇ 100 bp of DNA sequence between the 5′ end of the template and PCR product.
  • RNA from xylem, phloem, seedling and root was used and the SMART RACE cDNA amplification kit (Clontech Laboratories Inc, Palo Alto, Calif.) was followed according to manufacturer's protocol.
  • RACE PCR the cDNA from the four tissue types was combined.
  • the master mix for PCR was created by combining equal volumes of cDNA from xylem, phloem, root and seedling tissues. PCR reactions were performed in 96 well PCR plates, with 1 ⁇ l of primer from primer dilution plate (10 mM) to corresponding well positions. 49 ⁇ l of master mix is aliquoted into the PCR plate with primers. Thermal cycling commenced on a GeneAmp 9700 (Applied Biosystems, Foster City, Calif.) at the following parameters:
  • cDNA was separated on an agarose gel following standard procedures. Gel fragments were excised and eluted from the gel by using the Qiagen 96-well Gel Elution kit, following the manufacturer's instructions.
  • PCR products were ligated into pGEMTeasy (Promega, Madison, Wis.) in a 96 well plate overnight according to the following specifications: 60-80 ng of DNA, 5 ⁇ l 2 ⁇ rapid ligation buffer, 0.5 ⁇ l pGEMT easy vector, 0.1 ⁇ l DNA ligase, filled to 10 ⁇ l with water, and incubated overnight.
  • Each clone was transformed into E. coli following standard procedures and DNA was extracted from 12 clones picked by following standard protocols. DNA extraction and the DNA quality was verified on an 1% agarose gel. The presence of the correct size insert in each of the clones was determined by restriction digests, using the restriction endonuclease EcoRI, and gel electrophoresis, following standard laboratory procedures.
  • the original transcripts or their DNA counterparts may have features that prevent them from coding for functional proteins. There may be insertions, deletions, base substitutions, or unspliced or improperly spliced introns. If such features exist, it is often possible to identify them so that they can be changed. Similar curation can be performed on any other sequences that have homology to sequences in the public databases.
  • BLAST analysis shows that it is related to an Arabidopsis gene on the publicly available Arabidopsis genome sequence). However, instead of coding for an approximately 240 amino acid polypeptide, the consensus being curated is predicted to code for a product of only 157 amino acid residues, suggesting an error in the DNA sequence. To identify where the genuine coding region might be, the DNA sequence to the end of each EST is translated in each of the three reading frames and the predicted sequences are aligned with the Arabidopsis gene's amino acid sequence. It is found that the DNA segment in one portion of the EST codes for a sequence with similarity to the carboxyl terminus of the Arabidopsis gene. Therefore, it appears that an unspliced intron is present in the EST.
  • Unspliced introns are a relatively minor issue with regard to use of a cloned sequence for overexpression of the gene of interest.
  • the RNA resulting from transcription of the cDNA can be expected to undergo normal processing to remove the intron.
  • Antisense and RNAi constructs are also expected to function to suppress the gene of interest.
  • the sequence in question has a published sequence that is highly similar, it may be possible to find the intron by aligning the two sequences and identifying the locations where the sequence identity falls off, aided by the knowledge that introns start with the sequence GT and end with the sequence AG.
  • DNA oligomers can be synthesized flanking the region where the suspected intron is located.
  • RNA from the source species either Pinus or Eucalyptus
  • the selected primers are then used in a PCR reaction to amplify the correctly spliced DNA segment (predicted size of approximately 350 by smaller than the corresponding segment of the original consensus) from the population of cDNAs.
  • the amplified segment is then subjected to sequence analysis and compared to the consensus sequence to identify the differences.
  • Table 2 identifies plasmid(s), genes, and Genesis ID numbers for constructions described in Example 17.
  • Populus deltoides stock plant cultures were maintained on DKW medium (Driver and Kuniyuki, 1984, McGranahan et al. 1987, available commercially from Sigma/Aldrich) with 2.5 uM zeatin in a growth room with a 16 h photoperiod.
  • DKW medium Driver and Kuniyuki, 1984, McGranahan et al. 1987, available commercially from Sigma/Aldrich
  • petioles were excised aseptically using a sharp scalpel blade from the stock plants, cut into 4-6 mm lengths, placed on DKW medium with 1 ug/ml BAP and 1 ug/ml NAA immediately after harvest, and incubated in a dark growth chamber (28 degrees) for 24 hours.
  • Agrobacterium cultures containing the desired constructs were grown to log phase, indicated by an OD600 between 0.8-1.0 A, then pelleted and resuspended in an equal volume of Agrobacterium Induction Medium (AIM), which contains Woody Plant Medium salts (Lloyd, G., and McCown, B., 1981. Woody plant medium. Proc. Intern. Plant Prop. Soc. 30:421, available commercially from Sigma/Aldrich), 5 g/L glucose and 0.6 g/L MES at pH 5.8, with the addition of 1 ul of a 100 mM stock solution of acetosyringone per ml of AIM. The pellet was resuspended by vortexing. The bacterial cells were incubated for an hour in this medium at 28 degrees C. in an environmental chamber, shaking at 100 rpm.
  • AIM Agrobacterium Induction Medium
  • Populus deltoides explants were exposed to the Agrobacterium mixture for 15 minutes. The explants were then lightly blotted on sterile paper towels, replaced onto the same plant medium and cultured in the dark at 18-20 degrees C. After a three-day co-cultivation period, the explants were transferred to DKW medium in which the NAA concentration was reduced to 0.1 ug/ml and to which was added 400 mg/L timentin to eradicate the Agrobacterium.
  • explants were transferred to small magenta boxes containing the same medium supplemented with timentin (400 mg/L) as well as the selection agent geneticin (50 mg/L). Explants were transferred every two weeks to fresh selection medium. Calli that grow in the presence of selection were isolated and sub-cultured to fresh selection medium every three weeks. Calli were observed for the production of adventitious shoots.
  • BTM-1 Media Components mg/L NH 4 NO 3 412 KNO 3 475 Ca(NO 3 ) 2 •4H 2 O 640 CaCl 2 •2H 2 O 440* MgSO 4 •7H 2 O 370 KH 2 PO 4 170 MnSO 4 •H 2 O 2.3 ZnSO 4 •7H 2 O 8.6 CuSO 4 •5H 2 O 0.25 CoCl 2 •6H 2 O 0.02 KI 0.15 H 3 BO 3 6.2 Na 2 MoO 4 •2H 2 O 0.25 FeSO 4 •7H 2 O 27.8 Na 2 EDTA•2H 2 O 37.3 Myo-inositol 100 Nicotinic acid 0.5 Pyridoxine HCl 0.5 Thiamine HCl 1 Glycine 2 Sucrose 20000 Activated Carbon 5000
  • transgenic plants were propagated in the greenhouse by rooted cutting methods, or in vitro through axillary shoot induction for four weeks on DKW medium containing 11.4 uM zeatin, after which the multiplied shoots were separated and transferred to root induction medium. Rooted plants were transferred to soil for evaluation of growth in glasshouse and field conditions.
  • This example illustrates how polynucleotides important for wood development in P. radiata can be determined and how oligonucleotides which uniquely bind to those genes can be designed and synthesized for use on a microarray.
  • Trees Open pollinated trees of approximately 16 years of age are selected from plantation-grown sites, in the United States for loblolly pine, and in New Zealand for radiata pine. Trees are felled during the spring and summer seasons to compare the expression of genes associated with these different developmental stages of wood formation. Trees are felled individually and trunk sections are removed from the bottom area approximately one to two meters from the base and within one to two meters below the live crown. The section removed from the basal end of the trunk contains mature wood. The section removed from below the live crown contains juvenile wood. Samples collected during the spring season are termed earlywood or springwood, while samples collected during the summer season are considered latewood or summerwood (Larson et al., Gen. Tech. Rep. FPL-GTR-129. Madison, Wis.: U.S. Department of Agriculture, Forest Service, Forest Products Laboratory. p. 42).
  • Tissues are isolated from the trunk sections such that phloem, cambium, developing xylem, and maturing xylem are removed. These tissues are collected only from the current year's growth ring. Upon tissue removal in each case, the material is immediately plunged into liquid nitrogen to preserve the nucleic acids and other components.
  • the bark is peeled from the section and phloem tissue removed from the inner face of the bark by scraping with a razor blade.
  • Cambium tissue is isolated from the outer face of the peeled section by gentle scraping of the surface.
  • Developing xylem and lignifying xylem are isolated by sequentially performing more vigorous scraping of the remaining tissue. Tissues are transferred from liquid nitrogen into containers for long term storage at ⁇ 70 until RNA extraction and subsequent analysis is performed.
  • This example illustrates a procedure for RNA extraction and purification, which is particularly useful for RNA obtained from conifer needle, xylem, cambium, and phloem.
  • Tissue is obtained from conifer needle, xylem, cambium or phloem. The tissue is frozen in liquid nitrogen and ground. The total RNA is extracted using Concert Plant RNA reagent (Invitrogen). The resulting RNA sample is extracted into phenol:chloroform and treated with DNase. The RNA is then incubated at 65° C. for 2 minutes followed by centrifugation at 4° C. for 30 minutes. Following centrifugation, the RNA is extracted into phenol at least 10 times to remove contaminants.
  • RNA is further cleaned using RNeasy columns (Qiagen).
  • the purified RNA is quantified using RiboGreen reagent (Molecular Probes) and purity assessed by gel electrophoresis.
  • RNA is then amplified using MessageAmp (Ambion). Aminoallyl-UTP and free UTP are added to the in vitro transcription of the purified RNA at a ratio of 4:1 aminoallyl-UTP-to-UTP. The aminoallyl-UTP is incorporated into the new RNA strand as it is transcribed. The amino-allyl group is then reacted with Cy dyes to attach the colorimetric label to the resulting amplified RNA using the Amersham procedure modified for use with RNA. Unincorporated dye is removed by ethanol precipitation. The labeled RNA is quantified spectrophotometrically (NanoDrop). The labeled RNA is fragmented by heating to 95° C. as described in Hughes et al., Nature Biotechnol. 19:342 (2001).
  • This Example illustrates how genes important for wood development in P. radiata can be determined and how oligonucleotides which uniquely bind to those genes can be designed and synthesized for use on a microarray.
  • Pine trees of the species P. radiata are grown under natural light conditions. Tissue samples are prepared as described in, e.g., Sterky et al., Proc. Nat'l Acad. Sci. 95:13330 (1998). Specifically, tissue samples are collected from woody trees having a height of 5 meters. Tissue samples of the woody trees are prepared by taking tangential sections through the cambial region of the stem. The stems are sectioned horizontally into sections ranging from juvenile (top) to mature (bottom).
  • the stem sections separated by stage of development are further separated into 5 layers by peeling into sections of phloem, differentiating phloem, cambium, differentiating xylem, developing xylem, and mature xylem.
  • Tissue samples, including leaves, buds, shoots, and roots are also prepared from seedlings of the species P. radiata.
  • RNA is isolated and ESTs generated as described in the Example above or Sterky et al., supra.
  • the nucleic acid sequences of ESTs derived from samples containing developing wood are compared with nucleic acid sequences of genes known to be involved in polysaccharide synthesis.
  • ESTs from samples that do not contain developing wood are also compared with sequences of genes known to be involved in the plant cell cycle.
  • An in silico hybridization analysis is performed using BLAST (NCBI) as follows.
  • In silico gene expression can be used to determine the membership of the consensi EST libraries. For each library, a consensus is determined from the number of ESTs in any tissue class divided by the total number of ESTs in a class multiplied by 1000. These values provide a normalized value that is not biased by the extent of sequencing from a library. Several libraries were sampled for a consensus value, including reproductive, bud reproductive, bud vegetative, fruit, leaf, phloem, cambium, xylem, root, stem, sap vegetative, whole plant libraries.
  • In silico gene expression can be used to determine the membership of the consensi EST libraries. For each library, a consensus is determined from the number of ESTs in any tissue class divided by the total number of ESTs in a class multiplied by 1000. These values provide a normalized value that is not biased by the extent of sequencing from a library. Several libraries were sampled for a consensus value, including needles, phloem, cambium, xylem, root, stem and, whole plant libraries.
  • Sequences that show hybridization in silico to ESTs made from samples containing developing wood, but that do not hybridize to ESTs from samples not containing developing wood are selected for further examination.
  • cDNA clones containing sequences that hybridize to the genes showing wood-preferred expression are selected from cDNA libraries using techniques well known in the art of molecular biology.
  • oligonucleotides are designed such that each oligonucleotide is specific for only one cDNA sequence in the library.
  • the oligonucleotide sequences are provided in Table 14. 60-mer oligonucleotide probes are designed using the method of Li and Stormo, supra or using software such as ArrayDesigner, GeneScan, and ProbeSelect.
  • oligonucleotides are then synthesized in situ described in Hughes et al., Nature Biotechnol. 19:324 (2002) or as described in Kane et al., Nucleic Acids Res. 28:4552 (2000) and affixed to an activated glass slide (Sigma-Genosis, The Woodlands, Tex.) using a 5′ amino linker. The position of each oligonucleotide on the slide is known.
  • This example illustrates how to detect expression of Pinus radiata genes of the instant application which are important in wood formation using an oligonucleotide microarray prepared as described above.
  • This is an example of a balanced incomplete block designed experiment carried out using aRNA samples prepared from mature-phase phloem (P), cambium (C), expanding xylem found in a layer below the cambium (X1) and differentiating, lignifying xylem cells found deeper in the same growth ring (X2).
  • cell cycle gene expression is compared among the four samples, namely P, C, X1, and X2.
  • RNA is subsequently isolated from the frozen tissue samples as described in Example 1. Equal microgram quantities of total RNA are purified from each sample using RNeasy Mini columns (Qiagen, Valencia, Calif.) according to the manufacturers instructions.
  • Amplification reactions are carried out for each of the P, C, X1, and X2 tissue samples.
  • Amplification reactions are performed using Ambion's MessageAmp kit, a T7-based amplification procedure, following the manufacturer's instructions, except that labeled aaUTP is added to the reagent mix during in the amplification step. aaUTP is incorporated into the resulting antisense RNA formed during this step.
  • CyDye fluorescent labels are coupled to the aaUTPs in a non-enzymatic reaction as described in Example 1.
  • Labeled amplified antisense RNAs are precipitated and washed, and then assayed for purity using a NanoDrop spectrophotometer.
  • These labeled antisense RNAs corresponding to the RNA isolated from the P, C, X1, and X2 tissue samples, constitute the sample nucleic acids, which are referred to as the P, C, X1, and X2 samples.
  • Normalization control samples of known nucleic acids are added to each sample in a dilution series of 500, 200, 100, 50, 25 and 10 pg/ ⁇ l for quantitation of the signals.
  • Positive controls corresponding to specific genes showing expression in all tissues of pine, such as housekeeping genes, are also added to the plant sample.
  • Each of four microarray slides is incubated with 125 ⁇ L of a P, C, X1 or X2 sample under a coverslip at 42° C. for 16-18 hours.
  • the arrays are washed in 1 ⁇ SSC, 0.1% SDS for 10 minutes and then in 0.1 ⁇ SSC, 0.1% SDS for 10 minutes and the allowed to dry.
  • Mean signal intensity for each signal at any given position on the microarray slide is determined for each of three of P, C, X1, and X2 sample microarray slides. This mean signal/probe position is compared to the signal at the same position on sample slide which was not used for calculating the mean. For example, a mean signal at a given position is determined for P, C, and X1 and the signal at that position in the X2 microarray slide is compared to the P, C, and X1 mean signal value.
  • Table 5 shows genes having greater than doubled signal with any one sample as compared to the mean signal of the other three samples.
  • WD40 repeat protein A encodes a WD40 repeat protein is less highly expressed in cambium than in developing xylem
  • WD40 repeat protein B encodes a WD40 repeat protein that is more highly expressed in phloem than in the other tissues.
  • Signal data are then verified with RT-PCR to confirm gene expression in the target tissue of the genes corresponding to the unique oligonucleotides in the probe.
  • RNAs of tissues from multiple pine species in this case both P. radiata and loblolly pine P. taeda trees, are selected for analysis of the pattern of gene expression associated with wood development in the juvenile wood and mature wood forming sections of the trees using the microarrays derived from P. radiata cDNA sequences described in Example 4.
  • Trees Open pollinated trees of approximately 16 years of age are selected from plantation-grown sites, in the United States for loblolly pine, and in New Zealand for radiata pine. Trees are felled during the spring and summer seasons to compare the expression of genes associated with these different developmental stages of wood formation. Trees are felled individually and trunk sections are removed from the bottom area approximately one to two meters from the base and within one to two meters below the live crown. The section removed from the basal end of the trunk contains mature wood. The section removed from below the live crown contains juvenile wood. Samples collected during the spring season are termed earlywood or springwood, while samples collected during the summer season are considered latewood or summerwood. Larson et al., Gen. Tech. Rep. FPL-GTR-129. Madison, Wis.: U.S. Department of Agriculture, Forest Service, Forest Products Laboratory. p. 42.
  • Tissues are isolated from the trunk sections such that phloem, cambium, developing xylem, and maturing xylem are removed. These tissues are collected only from the current year's growth ring. Upon tissue removal in each case, the material is immediately plunged into liquid nitrogen to preserve the nucleic acids and other components.
  • the bark is peeled from the section and phloem tissue removed from the inner face of the bark by scraping with a razor blade. Cambium tissue is isolated from the outer face of the peeled section by gentle scraping of the surface.
  • Developing xylem and lignifying xylem are isolated by sequentially performing more vigorous scraping of the remaining tissue. Tissues are transferred from liquid nitrogen into containers for long term storage at ⁇ 70° C. until RNA extraction and subsequent analysis is performed.
  • This example illustrates procedures alternative to those used in the example above for RNA extraction and purification, particularly useful for RNA obtained from a variety of tissues of woody plants, and a procedure for hybridization and data analysis using the arrays described in Example 4.
  • RNA is isolated according to the protocol of Chang et al., Plant Mol. Biol. Rep. 11:113. DNA is removed using DNase I (Invitrogen, Carlsbad, Calif.) according to the manufacturer's recommendations. The integrity of the RNA samples is determined using the Agilent 2100 Bioanalyzer (Agilent Technologies, USA).
  • RNA is extracted and treated as previously described and 100 ng of total RNA is amplified using the OvationTM Nanosample RNA Amplification system from NuGENTM (NuGEN, CA, USA). Similar amplification kits such as those manufactured by Ambion may alternatively be used. The amplified RNA is reverse transcribed into cDNA and labelled as described above.
  • Hybridization and stringency washes are performed using the protocol as described in the US Patent Application for “Methods and Kits for Labeling and Hybridizing cDNA for Microarray Analysis” (supra) at 42 C.
  • the arrays (slides) are scanned using a ScanArray 4000 Microarray Analysis System (GSI Lumonics, Ottawa, ON, Canada).
  • Raw, non-normalized intensity values are generated using QUANTARRAY software (GSI Lumonics, Ottawa, ON, Canada).
  • Y ijkls represents the intensity of the s th spot in the 1 th slide with the k th dye applying the j th treatment for the i th cell line.
  • ⁇ ij , D k , S l , and D Skl represent the mean effect of the jth treatment in the ith cell line, the kth dye effect, the l th slide random effect, and the random interaction effect of the k th dye in the l th slide.
  • ⁇ ijkls is the stochastic error term. represent the similar roles as ⁇ ij , D k , S l , and D Skl except they are specific for the g th gene.
  • R ijkls (g) represents the residual of the g th gene from model (1).
  • ⁇ ij (g) , D k (g) , S l (g) , and DS kl (g) represent the similar roles as ⁇ ij , D k , S l , and DS kl except they are specific for the g th gene.
  • SS ls (g) represent the spot by slide random effect for the g th gene.
  • ⁇ ijkls (g) represent the stochastic error term. All random terms are assumed to be normal distributed and mutually independent within each model.
  • This example demonstrates how one can correlate polysaccharide gene expression with agronomically important wood phenotypes such as density, stiffness, strength, distance between branches, and spiral grain.
  • Mature clonally propagated pine trees are selected from among the progeny of known parent trees for superior growth characteristics and resistance to important fungal diseases.
  • the bark is removed from a tangential section and the trees are examined for average wood density in the fifth annual ring at breast height, stiffness and strength of the wood, and spiral grain.
  • the trees are also characterized by their height, mean distance between major branches, crown size, and forking.
  • trees lacking common parents are chosen for specific crosses on the criterion that they exhibit the widest variation from each other with respect to the density, stiffness, strength, distance between branches, and spiral grain criteria.
  • pollen from a tree exhibiting high density, low mean distance between major branches, and high spiral grain is used to pollinate cones from the unrelated plus tree among the selections exhibiting the lowest density, highest mean distance between major branches, and lowest spiral grain.
  • Seeds are collected from these controlled pollinations and grown such that the parental identity is maintained for each seed and used for vegetative propagation such that each genotype is represented by multiple ramets. Vegetative propagation is accomplished using micropropagation, hedging, or fascicle cuttings. Some ramets of each genotype are stored while vegetative propagules of each genotype are grown to sufficient size for establishment of a field planting. The genotypes are arrayed in a replicated design and grown under field conditions where the daily temperature and rainfall are measured and recorded.
  • the trees are measured at various ages to determine the expression and segregation of density, stiffness, strength, distance between branches, spiral grain, and any other observable characteristics that may be linked to any of the genes affecting these characteristics.
  • Samples are harvested for characterization of cellulose content, lignin content, cellulose microfibril angle, density, strength, stiffness, tracheid morphology, ring width, and the like.
  • RNA is then collected from replicated samples of trees showing divergent stiffness and density, or other characteristics, from genotypes that are otherwise as similar as possible in growth habit, in spring and fall so that early and late wood development is assayed. These samples are examined for gene expression similarly as described in above examples.
  • Ramets of each genotype are compared to ramets of the same genotype at different ages to establish age:age correlations for these characteristics.
  • Example 8 demonstrates how responses to environmental conditions such as light and season alter plant phenotype and can be correlated to polysaccharide synthesis gene expression using microarrays. In particular, the changes in gene expression associated with wood density are examined.
  • Trees of three different clonally propagated E. grandis hybrid genotypes are grown on a site with a weather station that measures daily temperatures and rainfall. During the spring and subsequent summer, genetically identical ramets of the three different genotypes are first photographed with north-south orientation marks, using photography at sufficient resolution to show bark characteristics of juvenile and mature portions of the plant, and then felled. The age of the trees is determined by planting records and confirmed by a count of the annual rings. In each of these trees, mature wood is defined as the outermost rings of the tree below breast height, and juvenile wood as the innermost rings of the tree above breast height. Each tree is accordingly sectored as follows:
  • Tissue is harvested from the plant trunk as well as from juvenile and mature form leaves. Samples are prepared simultaneously for phenotype analysis, including plant morphology and biochemical characteristics, and gene expression analysis. The height and diameter of the tree at the point from which each sector was taken is recorded, and a soil sample from the base of the tree is taken for chemical assay. Samples prepared for gene expression analysis are weighed and placed into liquid nitrogen for subsequent preparation of RNA samples for use in the microarray experiment. The tissues are denoted as follows:
  • Thin slices in tangential and radial sections from each of the sectors of the trunk are fixed as described in Ruzin, P LANT M ICROTECHNIQUE AND M ICROSCOPY, Oxford University Press, Inc., New York, N.Y. (1999) for anatomical examination and confirmation of wood developmental stage.
  • Microfibril angle is examined at the different developmental stages of the wood, for example juvenile, transition and mature phases of Eucalyptus grandis wood. Other characteristics examined are the ratio of fibers to vessel elements and ray tissue in each sector.
  • the samples are examined for characteristics that change between juvenile and mature wood and between spring wood and summer wood, such as fiber morphology, lumen size, and width of the S2 (thickest) cell wall layer.
  • Samples are further examined for measurements of density in the fifth ring and determination of modulus of elasticity using techniques well known to those skilled in the art of wood assays. See, e.g., Wang, et al., Non - destructive Evaluations of Trees, E XPERIMENTAL T ECHNIQUES, pp. 28-30 (2000).
  • biochemical analysis 50 grams from each of the harvest samples are freeze-dried and analyzed, using biochemical assays well known to those skilled in the art of plant biochemistry for quantities of simple sugars, amino acids, lipids, other extractives, lignin, and cellulose. See, e.g., Pettersen & Schwandt, J. Wood Chem. & Technol. 11:495 (1991).
  • the phenotypes chosen for comparison are high density wood, average density wood, and low density wood.
  • Nucleic acid samples are prepared as described in Example 3, from trees harvested in the spring and summer. Gene expression profiling by hybridization and data analysis is performed as described above.
  • polysaccharide gene expression as it is related to other complex wood characteristics such as strength, stiffness and spirality.
  • Example 32 demonstrates the use of a vascular-preferred promoter functionally linked to one of the genes of the instant application.
  • a vascular-preferred promoter is then linked to one of the genes in the instant application and used to transform tree species. Boosted transcript levels of the candidate gene in the xylem of the transformants results in an increased xylem biomass phenotype.
  • vascular-preferred promoter such as any of those in ArborGen's November 2003 patent applications is then linked to an RNAi construct containing sequences from one of the genes in the instant application and used to transform a tree of the genus from which the gene was isolated. Reduced transcript levels of the candidate gene in the xylem of the transformants results in an increased xylem biomass phenotype.
  • the vector pARB476 was developed using the following steps.
  • the Bluescript vector (Stratagene, La Jolla, Calif.) was modified by adding the Superubiquitin 3′UTR and nos 3′terminator sequence at the KpnI and ClaI sites to produce the vector pARB005 (SEQ ID NO. 773).
  • the P. radiata superubiquitin promoter with intron was added.
  • the promoter/intron sequence was first amplified from the P. radiata superubiquitin sequence identified in U.S. Pat. No. 6,380,459 using standard PCR techniques and the primers of SEQ ID NOS 774 and 775.
  • the amplified fragment was then ligated into pARB005 using XbaI and PstI restriction digestion to produce the vector pARB119 (SEQ ID NO. 776).
  • the poplus tremuloises UDB Glucose binding domain gene (patent WO 0071670, ptCelA Genbank number AF072131) was amplified using standard PCR techniques and primers including and ATG and a ClaI site as part of the 5′ primer and a TGA and a ClaI site as part of the 3′ primer. The amplified fragment was then cloned into the ClaI site of pARB119 to produce the vector pARB476 (SEQ ID NO. 777).
  • the NotI cassette containing the P. radiata superubiquitin promoter with intron::UDP Glucose Binding domain::3′UTR: nos terminator from pARB476 was removed and cloned into the NotI site of pART29 to produce the vector pARB483.
  • the binary vector pART29 is a modified pART27 vector (Gleave, Plant Mol. Biol. 20:1203-1207, 1992) that contains the Arabidopsis thaliana ubiquitin 3 (UBQ3) promoter instead of the nos5′ promoter and no lacZ sequences.
  • an acceptor vector (pWVK202) was built by first inserting the NotI-SUBIN::UDPGBD::nos term-NotI cassette from pARB483a into plasmid pWVK147 at NotI. Next, the UDPGBD gene was removed using restriction sites PstI and ClaI. A polylinker containing the restriction sites PstI, NheI, AvrII, ScaI, and ClaI was inserted in place of the UDPGBD gene. Sites AvrII and NheI are both compatible with SpeI, a site found often in the plasmids provided by Genesis.
  • ScaI is blunt, so any fragment can be blunted and then inserted at that position into the acceptor vector.
  • Plasmids were received from Genesis and analyzed to determine which restriction sites would be most suitable for subcloning into the acceptor vector pWVK202. After the ligations were performed, the resulting products were checked by extensive restriction digest analysis to make sure that the desired plasmid had been created.
  • Annotated Peptide Sequence 1 The amino acid sequence of SEQ ID MGDGSLGSGGRGNSGGGGGGGSRPEWLQQ YDLIGKIGEG 261.
  • the conserved eukaryotic TYGLVFLARIKHPSTNRGKYIAIKKFKQSKDGDGVSPTA protein kinase domain is IREIMLLREISHENVVKLVNVHINPVDMSLYLAFDYADH underlined and the DLYEIIRHHRDKVNQAINPYTVKSLLWQLLNGLNYLHSN serine/threonine protein kinases W IIHRDLKPSNILV MGEGEEQGVVKIADFGLARVYQAPL active-site signature is in bold.
  • the conserved eukaryotic EDEGIPSTAIREISLLKQLQHPNIVRLYDVVHTEKKLTL protein kinase domain is VFEFLDQDLKKYLDACGDNGLEPYTVKSFLYQLLQGIAF underlined and the protein kinases CHEHR VLHRDLKPQNLLI NMEGELKLADFGLARAFGIPV ATP-binding region and RNYTHEVVTLWYRAPDVLMGSRKYSTQVDIWSVGCIFAE serine/threonine protein kinases MVNGRPLFPGSSEQDQLLRIFKTLGTPSLKTWPGMAELP active-site signatures are in DFKDNFPKYVVQSFKKICPKKLDKTGLDLLSRMLQYDPA bold.
  • KRISAEQAMGHPYF KDLKLRKPKAAGPGP 3 The amino acid sequence of SEQ ID MDQ YEKIEK IGEGTYGVVYKAIDRSTNKTIALKK IRLEQ 263.
  • the conserved eukaryotic EDEGVPSTAIREISLLKEMQHGNIVKLQDVVHSERRLYL protein kinase domain is VFEYLDLDLKKHMDSCPEFSKDTHTIKMFLYQILRGISY underlined and the protein kinases CHSHRV LHRDLKPQNLLL DRRTNSLKLADFGLARAFGIP ATP-binding region and VRTFTHEVVTLWYRAPEILLGSRHYSTPVDVWSVGCIFA serine/threonine protein kinases
  • EMVNRRPLFPGDSEIDELFKIFRIMGTPNEDSWPGVTSL active-site signatures are in PDFKSTFPKWASQDLKTVTPTVDPAGIDLLSKMLCMDPR bold.
  • RRITAKVALEHEYF KDVGVIP 4 The amino acid sequence of SEQ ID MVMKSKLDK YEKLEK LGEGTYGVVYKAQDKTTKEIYALK 264.
  • the conserved eukaryotic K IRLESEDEGIPSTAIREIALLKELQHPNVVRIHDVIHT protein kinase domain is NKKLILVFEFVDYDLKKFLHNFDKGIDPKIVKSLLYQLV underlined and the protein kinases RGVAHCHQQKV LHRDLKPQNLLV SQEGILKLGDFGLARA ATP-binding region and FGIPVKNYTNEVVTLWYRAPDILLGSKNYSTSVDIWSIG serine/threonine protein kinases CIFVEMLNQKPLFPGSSEQDQLKKIFKIMGTPDATKWPG active-site signatures are in IAELPDWKPENFEKYPGEPLNKVCPKMDPDGLDLLDKML bold.
  • KCNPSERIAAKNAMSHPYF KDIPDNLKKLYN 5 The amino acid sequence of SEQ ID MDQ YEKVEK IGEGTYGVVYKAIDRLTNETIALK KIRLEQ 265.
  • the conserved eukaryotic EDEGVPSTAIREISLLKEMQHGNIVRLQDVVHSENRLYL protein kinase domain is VFEYLDLDLKKHMDSSPDFAKDPRLVKIFLYQILRGIAY underlined and the protein kinases CHSHR VLHRDLKPQNLLI DRRTNALKLADFGLARAFGIP ATP-binding region and VRTFTHEVVTLWYRAPEILLGSRHYSTPVDVWSVGCIFA serine/threonine protein kinases
  • EMVNQRPLFPGDSEIDELFKIFRILGTPNEDTWPGVTAL active-site signatures are in PDFKSAFPKWPAKNLQDMVPGLNSAGIDLLSKMLCLDPS bold.
  • KRITARSALEHEYF KDIGFVP 6 The amino acid sequence of SEQ ID MEK YEKLEK VGEGTYGKVYKAKDKATGQLVALKK TRLEM 266.
  • the conserved eukaryotic DEEGVPPTALREVSLLQLLSQSLYVVRLLSVEHVDGGSK protein kinase domain is RKAAAAAAAEGGGGEAHGGGAVGGGKPMLYLVFEYLDTD underlined and the protein kinases LKKFIDSHRKGPNPRPVPAATVQNFLYQLLKGVAHCHSH ATP-binding region and G VLHRDLKPQNLLV DKEKGILKIADLGLGRAFTVPLKSY serine/threonine protein kinases THEVFAFLAILLWRSEGESAADFDSXFRVSPVQVVTLWY active-site signatures are in RAPEVLLGSAHYSIGVDMWSVGCIFAEMVRRQALFPGDS bold.
  • the conserved eukaryotic IVALK KTRLHEDEEGVPPTTLREISILRMLSRDPHIVRL protein kinase domain is MDVKQGQNKEGKTVLYLVFEYMETDLKKYIRGFRSSGES underlined and the protein kinases IPVNIVKSLMYQLCKGVAFCHGHGV LHRDLKPHNLLM DK ATP-binding region and KTLTLKIADLGLARAFTVPIKKYTHEILTLWYRAPEVLL serine/threonine protein kinases GATHYSTAVDMWSVGCIFAELVTKQALFPGDSELQQLLH active-site signatures are in IFRLLGTPNEKMWPGVSSLMNWHEYPQWKPQSLSTAVPN bold.
  • LDKDGLDLLSQMLHYEPSRRISAKAAMEHPYF DDVNKTCL 8 The amino acid sequence of SEQ ID MGCVLGREVSSGIVTESKGRDSSEVETSKRDDSVAAKVE 268.
  • the conserved eukaryotic GEGKAEEVRTEETQKKEKVEDDQQSREQRRRSKPSTKLG protein kinase domain is NLPKHIRGEQVAAGWPSWLSDICGEALNGWIPRRANT FE underlined and the KIDKIGQGTYSNVYKAKDLLTGKIVALKKVRFDNLEPES serine/threonine protein kinases VRFMAREILILRHLDHPNVVKLEGLVTSRMSCSLYLVFE active-site signature is in bold.
  • the conserved eukaryotic NGFRARDKVGDVSVMLIDKKVNGSARFCDDQIEKKSDRL protein kinase domain is QKQRRERAEAAAAADHPGAGRVPKAVEGEQVAAGWPVWL underlined and the SAVAGEAIKGWLPRRADT FEKLDKIGQGTYSSVYKARDV serine/threonine protein kinase TNNKIVALKRVRFDNLDTESVKFMAREIHILRMLDHPNV active-site signature is in bold.
  • the conserved eukaryotic AAGSEGGESARGAPGKERPEPAPRFVVRSPQGWPPWLVA protein kinase domain is AVGHAIGEFVPRCADS FRKLAKIGEGTYSNVYKARDLVT underlined and the GKTVALKKVRFDNLEAESIKFMAREILVLTRLNHPNVIK serine/threonine protein kinase LEGPVTSRMSSGLYLAFEYMEHDLSGIAARQNGKFTEPQ active-site is in bold VKCFMRQLLSGLEHCHNHD VLHRDIKCSNLLI DNEGNLK IADFGLATFYDPERKQVMTNRVVTLWYRAPELLLGATSY GIGIDLWSAGCILAELLYGKPIMPGRTEVEQLHKIFKLC GSPSEAYWNKFKLPNANIFKPPQPYARCIAETFKDFPPS ALPLLETLLSIDPDERGTATTALNSEFF AAEPHACEPSS LPKYPPSKEMDLKLI
  • the conserved eukaryotic YMAKEKKTGEIVALKK IRMDNEREGFPITAIREIKILKK protein kinase domain is LHHENVIKLKEIVTSPGPEKDEQGRPEGNKYKGGIYMVF underlined and the protein kinases EYMDHDLTGLADRPGMRFSVPQIKCYMRQLLTGLHYCHI ATP-binding region and NQV LHRDIKGSNL LIDNEGNLKLADFGLARSFSNDHNAN serine/threonine protein kinases LTNRVITLWYRPPELLLGATKYGPAVDMWSVGCIFAELL active-site signatures are in HGKPIFPGKDEPEQLNKIFELCGAPDEINWPGVSKIPWY bold.
  • the conserved AVSANGGGNDAADRLISSPHEVENEVEDRKNVDFNEKLS serine/threonine protein kinase KSLQRRATMDVASGGHTQAQLKVGKVGGFPLGERGAQVV domain is underlined, and the AGWPSWLTAVAGEAINGWVPRRADS FEKLEKIGQGTYSS serine/threonine protein kinase VYRARDLETNTIVALKKVRFANMDPESVRFMAREIIIMR active-site signature is in bold.
  • the conserved protein kinase DVYRGRRLSDGLAVALKEVHDYQSAFREIEALQILRGSP family domain is underlined and HVVLLHEYFWREDEDAVLVLEFLRSDLAAVIADASRRPR the serine/threonine protein DGGGGGAAALRAGEVKRWMLQVLEGVDACHRNS IVHRDL kinases active-site signature is KPGNLLI SEEGVLKIADFGQARILLDDGNVAPDYEPESF in bold.
  • the conserved DVYRGRRLSDGLAVALKEVHDYQSAFREIEALQILRGSP serine/threonine protein kinase HVVLLHEYFWREDEDAVLVLEFLRSDLAAVIADASRRPR domain is underlined, and the GGGVAPLRAGEGKRWMLQVLEGVDACHRNS IVHRDLKPG serine/threonine protein kinase NLLI SEEGVLKIADFGQARILLDDGNVAPDYEPESFEER active-site signature is in bold.
  • the conserved cyclin and AAVPSHLAKKRAPLGNLTNLKAGDGNSRSSSAPSTLVAN cyclin C-terminal domains are ATKLAKTRKGSSTSSSIMGLSGSALPRYASTKPSGVLPS underlined and the cyclins VNPSIPRIEIAVDPMSCSMVVSPSRSDMQSVSLDESMST signature is in bold.
  • the conserved cyclin N- and SNINSNIIGAPPYPCAVNKRVLSEKNVNSENDLLNAAHR C-terminal family domains are PITRQFAAQMAYKQQLRPEENKRTTQSVSNPSKSEDCAI underlined and the cyclins LDVDDDKMADDFPVPMFVQHTEAMLEEIDRMEEVEMEDV signature is in bold.
  • AEEPVTDIDSGDKENQLAVVEYID DLYMFYQKAEASSCV PPNYMDRQQDINERM RGILIDWLIEVHYKFELMDETLYL TVNLIDRF LAVQPVVKKKLQLVGVTAMLLACKYEEVSVP VVEDLILISDRAYSRKEVLEMERLMVNTLHFNMSVPTPY VFMRRFLKAAQSDKKLELLSFFIIELSLVEYDMLKFPPS LLAASAIYTALSTITRTKQWSTTCEWHTSYSEEQLLECA RLMVTFHQRAGSGKLTGVHRKYSTSKFGHAARTEPANFL LDFRL 19 The amino acid sequence of SEQ ID MASRPIVPVQARGEAAIGGGAGKAAIGGGAGKQQKKNGA 279.
  • the conserved cyclin and AEGRNRKALGDIGNLVTVRGIEGKVQPHRPITRSFCAQL cyclin C-terminal domains are LANAQAAAAAENNKKQAVVNVNGAPSILDVPGAGKRAEP underlined.
  • the conserved cyclin and LSVINQNLVGDRAYPCHVVNKRGHSKRDAVCGKDQVDPV cyclin C-terminal domains are HRPLTRKFAAQTASTQQHCIEEAKKPRTAVQERNEFGDC underlined and the cyclins IFVDVEDCQPSSENQPVPMFLEIPESRLDDDMEEVEMED signature is in bold.
  • the conserved cyclin and LSVINQNLVGDRAYPCHVVNKRGHSKRDAVCGKDQVDPV cyclin C-terminal domains are HRPLTRKFAAQTASTQQHCIEEAKKPRTAVQERNEFGDC underlined and the cyclins IFVDVEDCQPSSENQPVPMFLEIPESRLDDDMEEVEMED signature is in bold.
  • the conserved cyclin N- and DDGGGGGQVDGIPLFPSQPADRQQDSPWADEDGEEKEEE C-terminal family domains are EAELQSLFSKERGARPELAKDDGGAVAARREAV EWMLMV underlined.
  • the conserved cyclin- EWRAIGVQQSRGWVHYAIHRPEPHIMLFRRPLN YQQQQE dependent kinases regulatory NQAQQNMLAK subunit domain is underlined and the cyclin-dependent kinases regulatory subunits signature 1 is in bold. 26
  • the conserved chromo domain HSNGTAAEPDVATKRRRMSVLPLEVGTRVMCRWRDG KYH is underlined and the MOZ/SAS-like PVKVIERRKLNPGDPNDYEYYVHYTEFNRRLDEWVKLEQ protein domain is in bold/italics.
  • LDLNSVETVVDEKVEDKV TGLKMTRHQKRKIDETHVEGH EELDAASLREHEEFTKVKNIATIELGRYEIETWYFSPFP PEYNDCSKLYFCEFCLNFMKRKEQLQRHMKKCD PKVLDRHLKAAGRG GLEVDVSKLIWTPYREQG 27
  • the conserved histone KPVPARDRDLCRFHADDYVAFLRSITPETQQDQLRQLKR deacetylase family domain is FNVGEDCPVFDGLHSFCQTYAGGSVGGAVKLNHGLCDIA underlined.
  • the conserved histone PHRIRMTHALLAHYGLLQHMQVLKPVPARDRDLCRFHAD deacetylase family domain is DYVAFLRSITPETQQDQLRQLKRFNVGEDCPVFDGLHSF underlined.
  • the conserved histone ELLCQELPERQVILEFEGTRPKPYFSDHNGGENSALGVR deacetylase family domain is ATEDDLNSDVEAEEKQKEMTLEDMYKNDGTLYDDDEDDS underlined and the Zinc finger DWEPVKRQVELMR WFCTNCTMVNVEDVFLCDIC GEHRDS RanBP2-type profile is in bold.
  • GILRHGFYASPFMQDVGAPSVEAEVQESREDHARSSPPS SSTVVGFDEKMLLHSEVEMKSHPHPERADRLQAIAASLA TAGIFPGRCRSLPVREITKEELQMVHSSEHVDAVEMTSH MFSSYFTPDTYANEHSARAARIAAGLCADLASTIISGRS KNGFALVRPPGHHAGIKHAMGFCLHNNAAVAALAAQGAG AKKVLIVDWDVHHGNGTQEIFDGNKSVLYISLHRHEGGN FYPGTGAAHEVGTMGAEGYCVNIPWSRRGVGDNDYVFAF HHIVLPIASAFAPDFTIISAGFDAARGDPLGCCDVTPAG YAQMTHMLSALSGGKLLVILEGGYNLRSISSSAVAVIKV LLG DSPISEIADAVPSKAGLRTVLEVLKIQRSYWPSLES IFWELQSQWGMFLVDNRRKQIRKRRRVLVPIWWKWGRKS VLYHLLNGHLHVKTKR 31
  • the conserved cyclophilin- NNAASVRQFVTRCSSSPSSRGQWQPHQNGEKGRSFSLRE type peptidyl-prolyl cis-trans CAISIALAVGLVTGVPSLDMSTGNAYAASPALPDLSVLI isomerase family domain is SGPPIKDPEALLRYALPINNKAIREVQKPLEDITDSLKV underlined.
  • the conserved FKBP-type KQGLKKKLVKE GDAWETPDNGDEVE VHYTGTLLDGTQFD peptidylprolyl isomerase domains SS RDRGTPFKFTLGQGQ are underlined.
  • the conserved cyclophilin- FVQLCLEGY YDNTIFHRIIKDFLVQGGD PTGSGTGGESI type peptidyl-prolyl cis-trans YGDAFSDEFHSRLRFKHRGLVACANAGSPHSNGSQFFIT isomerase family domain is LDRCDWLDRKNTIFGKITGDSIYNLSGLAEVETDKSDRP underlined and the cyclophilin- LDPPPKIISVEVLW NPFEDIVPRAPVRSLVPTVPDVQNK type peptidyl-prolyl cis-trans EPKKKAVKKLNLLSFGEEAEEEEKALVVVKQKIKSSHDV isomerase signature is in bold.
  • the conserved cyclophilin- QRKYGATCCVARGLTSRSHYASSLAFKQFSKTPSIKYDR type peptidyl-prolyl cis-trans MVEIKAMATDLGLQAKVTN KCFFDVEIGGEPAGRIVIGL isomerase family domain is FGDDVPKTVENFRALCTGEKGFG YKGCSFHRIIKDFMIQ underlined and the cyclophilin- GG DFTRGNGTGGKSIYGSTFEDENFALKHVGPGVLSMAN type peptidyl-prolyl cis-trans AGPSTNGSQFFICTVKTPWLDNRHVVFGQVVDGMDVVQK isomerase signature is in bold.
  • LESQETSRSDVPRQPCRIVNCGELP LDG 37 The amino acid sequence of SEQ ID MAASFTALSNVGSLSSPRNGSEIRRFRPSCNVAASVRPP 303.
  • the conserved cyclophilin- PLKAGLSASSSSSFSGSLRLIPLSSSPQRKSRPCSVRAS type peptidyl-prolyl cis-trans AEAAAAQSKVTN KVYLDISIGNPVGKLVGRIVIGLYGDD isomerase signature is underlined.
  • the FKBP-type ESGSPPTIPPNATLQFDVE peptidyl-prolyl cis-trans LL SWSSVKDICKDGGILKKVLVE GEKWDNPKDLDEVFVK isomerase signature 1 is in bold YEASLEDGTLISKSDGVEFTVGDGYFCAALAKAVKTMKK and the FKBP-type peptidyl-prolyl GEKVLLTVMPQYAFGETGRPASGDEAAVPPDASLQIMLE cis-trans isomerase signature 2 is LV SWKTVSDVTKDKKVLKKTLKE GEGYERPNDGAAVQVR in bold/italics.
  • the TPR repeat LCGKLQDGTVFVKKDDEEPFEFKIDEEQ is in italics.
  • the conserved cyclophilin- CTGEKGIGPHTGAPLH YKGVRFHRVIKGFMVQGG DISAG type peptidyl-prolyl cis-trans DGTGGESIYGLKFEDENFDLKHERKGMLSMANSGPNTNG isomerase family domain is SQFFITTTRTSHLDGKHVVFGRVVKGMGVVRSVEHVTTA underlined and the cyclophilin- AGDCPTVDVVIADCGEIP AGADDGIRNFFKDGDTYPDWP type peptidyl-prolyl cis-trans ADLDESPAELSWWMDAVDSIKAFGNGSYKKQDYKMALRK isomerase signature is in bold.
  • YRKALRYLDICWEKEGIDEVESSSLRKTKSQIFTNSSAC The TPR repeat is in bold/italics.
  • KLKLCDLKGALLDAEFAVRDGENN GIKKELNAAKKKIFERREQ EKRAYRKMFL 48 The amino acid sequence of SEQ ID MTKRKNP LVFLDVSIDGDPVERIVIELFADTVPRTAENF 314.
  • the conserved cyclophilin- RSLCTGEKGVGKTTGKPLHYKGSYFHRIIK GFMAQGG DF type peptidyl-prolyl cis-trans SNGNGTGGESIYGGKFADENFKLAHDGPGLLSMANGGPN isomerase signature is underlined TNGSQFFIIFKRQPHLDGKHVVFGKVMRGMEVVKKIEQV and the cyclophilin-type peptidyl- GSANGKPLQPVKIVDCGETS ETGTQDAVVEEKSKSATLK prolyl cis-trans isomerase AKKKRSARDSSSESRGKRRQRKSRKERTRKRRRYSSSDS signature is in bold.
  • the conserved cyclophilin- CVFHTVQKDFTAQTGDPTGTGTGGDSVYKFLYGDQARFF type peptidyl-prolyl cis-trans MDEIHLDLKHSKTGTVAMASGGENLNASQFYFTLRDDLD isomerase signature is underlined.
  • YLDGKHTVFGEVAEGLETLTRINEAYVDEKGRPYKNIRI The CCHC type zinc finger is in RHTYILD DPFDDPPQLAELIPDASPEGKPKDEVVDDVRL bold and the RNA-binding region EDDWVPLDEQLGPAQLEEAIRAKEAHSRAVVLESIGDIP RNP-1 (RNA recognition motif) is DAEIKPPDNV in bold/italics.
  • the conserved G-protein beta DNGE RLGTYRGHNGAVWCCDVSRDSMRLITGSADTTAKL WD-40 repeat domains are WS VQNGTQLFTFNFDSPARSVDFSIGDKLAVITTDPFME underlined.
  • the conserved G-protein beta DSSPMLRN GET GDWIGTFEGHKGAVWSCCLDTNALRAAS domain is underlined and the WD-40 GSADFSAKLWD ALS GDELHSFEHKHIVRSCAFSEDTHLL repeat domains are in bold LTGGVEKILRIFD LNRP DAPPREVDNSPGSIRTVAWLHS DQTILSSCTDIGGVRLWD VRS GKIVQTLETKSPVTSSEV SQDGRYITTADGSTVKFWD ANHFGLVKSYNMPCNIESAS LEPKLGNKFIAGGEDMWVHIFDFHT GEEIGCNKGHHGPV HCVRFSPGGESYASGSEDGTIRIWQ TGPANNVEGDANPS NGPVTGKAKVGADEVTRKVEDLQIGKEGKDWREG 61
  • the conserved G-protein beta IILWH LTKEEKVYGV PRRRLTGHSHFVQDVVLSSDGQFA1 WD-40 repeat domains are LSGSWDGELRLWD LATGV SARRFVGHTKDVLSVAFSIDN underlined.
  • the conserved G-protein beta IILWHLTKEDKV YGVPRRRLTGHSHFVQDVVLSSDGQFA WD-40 repeat domains are LSGSWDGELRLWD LA TGVSARRFVGHTKDVLSVAFSIDN underlined.
  • the conserved G-protein beta IILWH LTKEDKVY GVPRRRLTGHSHFVQDVVLSSDGQFA WD-40 repeat domains are LSGSWDGELRLWD LAT GVSARRFVGHTKDVLSVAFSIDN underlined and the Trp-Asp (WD) RQ IVSASRDRTIKLWN T LGEC KYTIQEGEAHNDWVSCVR repeats signature is in bold.
  • the conserved G-protein beta FLDDSDIIHEVAVDDEDLPDADDEADEAEEADDS LHIFT WD-40 repeat domains are GHNGEVYSLACSPTDATLVATGAGDDKGFLWR IGHGD WA underlined.
  • PKSGENIH VVKGHPYHAEGLTSMAISSDSGLAITGAK DGSVRIVN ISSGR VVSSLDAHADSVEFVGLALSSPWAAT GSLDQKLIIWD LQHS SPRATCDHEDGVTCLSWVGASRFL
  • the conserved G-protein beta PPPGYKPYR HLKTLTGHVAAVSCVKFSNDGTLLASASLD WD-40 repeat domains are KTLIIWS SAALS LLHRLVGHSEGVSDLAWSSDSHYICSA underlined.
  • the conserved G-protein beta VSNSSGSQ HLASLSGHKGPVWQVAWAHPKFGSILASCSY WD-40 repeat domains are DGQVILWK EGNQNDWA QAHVFNDHKSSVNSIAWAPHELG underlined.
  • the conserved G-protein beta ETVKLWR PDELA LERTNAGHFLGVVSVAAHPSGVIAASA WD-40 repeat domains are SIDSFVRVFD VDTNA TIATLEAPPSEVWQMQFDPKGTTL underlined and the Trp-Asp (WD) AVAGGGSASIKLWD TATWELNATLSIPRPEQPKPSEKGN repeats signature is in bold.
  • the conserved G-protein beta SPEKLLEVRAHGESCRAVRFINDGKAILTGSPDCSILAT WD-40 repeat domains are D VET GSVVARVENAHEAAVNRLVNLTESTIATGDDNGCI underlined and the Trp-Asp (WD) KVWD TRQ RSCCNTFSAHEDFISDMTFASDSMKLVVTSGD repeats signature is in bold.
  • the conserved G-protein beta NRLEITPHKRYLAVAGNPSIRLFD VNSNTPQ PVMSFDSH WD-40 repeat domains are TNNVMAVGFQYDGNWMYSGSEDGTVRIWD LRARG CQREY underlined and the Trp-Asp (WD) ESRGAVNTVVLHPNQTELISGDQNGNIRVWD LTANSCS C repeats signature is in bold.
  • the conserved G-protein beta DEEYDHLDNKITDTSAADARRGKDIQGIPWERLSVTREK domain is underlined and the WD-40 YRRTRIEQYKNYENVPQSGESSEKDCKPTRKGGNYYEFW repeat domains are in bold RNTRSVKSTILHFQLRNLVWSTTKHDVYLMSHFSIIHWS SLTCKKTEVLDVYGHVAPREKHPGSLLEGFTQTQVSTLA VRDKLLIAGGFQGELICKNLDRPGVSYCCRTTYDDNAIT NAVEIYDYPSGAVHFMASNNDCGVRDFDMEKFELSRHFT FPWPVNHTSLSPDGKLLVIVGDNPEGIVVDSQR GKTIRP LQGHLDFSFASAWHPDGHIFATGNQDKTCRIWD IRNL SK SVAVLKGNLGAIRSIRFTSDGRFMAMAEPADFVHVYD VK SGYEKEQEIDFFGEISGVSFSPDTESLFVG
  • the conserved G-protein beta DKKYRLAIASLLDHPAAAAAVPNRVEIVQLDDSTGEIRA WD-40 repeat domains are DPNLSFDHPYPATKAAFVPDKDCQRADLLATSSDFLRIW underlined.
  • RIADDSSRVDLRSFL NGNKNSEFCRPLTSFDWNEAEPKR IGTSSIDTTCTIWD IERET
  • LRDKEHSTIIYESSEPDTPLVRL GWNKQDPRYMATIIMDSAKVVVLDIRYPTMP VVELQRHQ ASVNAIAWAPHSSCHICTAGDDSQALIWD LSSMAQPVEG
  • GLDPILAYTAGAEIEQLQWSSSQPDWVAIAFSLKLQ 73 The amino acid sequence of SEQ ID MRGGGGGGDATGWDEDAYRES VLKEREVQTRTVFRAAFA 339.
  • the conserved G-protein beta PSPSPSPSPDAVVVASSDGSVASYS ISACLSDHRLQSLR WD-40 repeat domains are FADAKSQNVLEAE PACFLQGHDGPAYDVKFYGEGEDSLL underlined.
  • the conserved G-protein beta AGCTDGSCIIWD FETRGVA KELRDKECTAAITSVCWSKY WD-40 repeat domains are GHRILVSASDKSLILWD VLSGEKIAHTTLQHTVLQACLH underlined.
  • the conserved G-protein beta PSASNIFKLLVQREVSPRSKHSSKKLWREASKCQPYPFQ WD-40 repeat domains are QSCEAVRDVRQGLISWVESASLRHL SAKYCPLVPPPRST underlined.
  • the conserved G-protein beta ADLQPHPKNPSRPPPQPAAKKVHAKSHAHGADKDKNKRH WD-40 repeat domains are HPL DLNTLKGHGDSVTGLCFASDGRSLATACADGVVRVF underlined and the Trp-Asp (WD) K LDDASNKSFKFLRINLPAGGHPTAVAFGDGVSSVIVAS repeats signature is in bold.
  • the conserved G-protein beta TTHPLDNLSFSVPSLAFSPSPPHLLAAAHSATVSLFSPH WD-40 repeat domains are RTTISSFSDVVSSLSFRSDGQLLAASDLSGLIQVFD VRS underlined.
  • RTPLRRLRSHARPVRFVRYPVLDKLHLVSGGDDALVKYW D VAG ESVVSELRGHKDYVRCGDCSPADANCFVTGSYDHV VKLWD VRVRD GNRAATEVNHGSPVQDVIFLPSGSLVATA GGNSVKIWD LIGG GRMVYSMESHNKTVTSICVGTMGAQQ SGEEGVQLRILSVGLDGYMKVFD YSRMKVTHSMRFPAPL LSIGFSPDSNVRAIGTSNGILYVGKRKAKENAEGGANGI LGLGSVEEPRRRVLKPSFYRYFHRGQSEKPSEGDYLVMR PKKVKLAEHDKLLKKFQHKNALISVLGGNDPEKVVAVME ELVAR
  • the conserved G-protein beta EENEVHLLRLSSGGTELICEGLFSHPSEIWDLSSCPFDQ WD-40 repeat domains are RIFSTVFSTGESYGAAVWQIPELYGQLNSPQ LEKIASLD underlined.
  • AHSRKISCVLWWPSGRHDKLVSIDEENIFLWGLDCSKKS AQVQSQESAGMLHNLSGGAWDPHDVNTVAATCESSIQFW D LRTMKKANSLESVHARDLDYDMRKKHLLVTSEDESGVR VWDLRMP KAPIQEFPGHTHWTWAVRCNPDYEGLILSAGT DSAVNLWW SSTASSDELISERLIDSPTRKL DPLLHSYND YEDSVYGLAWSSREPWIFASLSYDGRVVVES VKPFLSRK 79 The amino acid sequence of SEQ ID MAEEEGSAELEQQLEEEFAVWKKNTPILYDLLISHALEW 345.
  • the conserved G-protein beta PSLTVHWAPLLPQPSSSAAAAAGDPSLAAHRLVLGTHTS WD-40 repeat domains are DGAPNFLILADALLPSSESDHCGDDAVLPKVEISQKIRV underlined.
  • DGEVNRARFMPQNHNIVGAKTNGCEVYVFDCSKQAAKQH DGGFDPDLRLTGHDGEGYGLSWSPLKENYLLSASHDKKI CLWDISAAAQDKV LGAMHVFEAHEGAVGDASWHSKNDNL FGSAGDDCQLMIWD LRT NKAQQCVKAHEKEVNSVSFNSY NDWILATASSDTTVGLFD MRKL TTPLHVFSSHEGEVLQV EWDPNHEAVLASSSEDRRVMVWD LNRIGDEQQEGDASDG P AELLFSHGGHKAKISDFSWNKNEPWVISSVAEDNSVQV WQ MAESICGDDDDMQAMEGYI 80 The amino acid sequence of SEQ ID MGNYGEEDEDQYFD
  • the conserved G-protein beta DENVLDSLGFEFWTKFPESVRARRNRFLMLTGLGIEANS WD-40 repeat domains are VDKEDAFPPSCNEIEVYTCKVTRDDGAVQRSLDSYNCIS underlined.
  • the conserved G-protein beta TVRLWA PSAGERRKYE VARVLLGHKSFVGPLAWVPPSEE WD-40 repeat domains are LPEGGIVSGGMDTLVMAWD LRNG EAQTLKGHQLQVTGIV underlined.
  • the conserved G-protein beta VVQLFSCLDKISYIEWALDSEYILCGLYKRPMIQAWSLI domain is underlined and the WD-40 QPEWTCKIDEGPAGIAYARWSPDSRHILTTSDFQLRLTV repeat domains are in bold WSLVNTACVHVQWPKHASKGVSFTRDGKFAAICTRHDCK DYINLLSCHNWEIMGVFAVDTLDLADIQWSPDDSAIVIW DSPLEYKVLVYSPDGR CLFKYQAYESGLGVKSVSWSPCG QFLAVGSYDQMLRVLS HLTWKTFAEFTHLSNVRAPCCAA IFKEVDEPLQIDMSELSLSDDYMQGNSGDAPEGHYRVRY DVTEVPITLPCQKPPADRPNPKQGIGLMSWSNDSQYICT RNDSMPTILWIWDMRH LELAAILVQKDPIRAAVWDPTGT RLVLCTGSSHLYMWT PSGAYCVSVPLSQFNITDLKWNS
  • the conserved G-protein beta LVTAGEDDSVRLYD IANARLLKTTFHKKHGTDRVCFTHH WD-40 repeat domains are PNSLICSSTKNLDTGESLRYISMYDNR SLRYFKGHKQRV underlined.
  • VSLCMSPINDSFMSGSLDHSVRMWD LRVNACQGILRLRG RPTVAYDQQGLVFAVAMEGGAIKLFDSRSYDKGPF DAFL VGGDTSEVCDIKFSNDGKSVLLSTTNNNIYVLD AYAGDK QC GFNLEPSPSTPIEASFSPDGQYVVSGSGDGTLHAWN I SRRNEVACWNSHIGVASCLKWAPRRAMFVAASTVLTFWI PNSEPELASAKGEAGVPPEQV 84 The amino acid sequence of SEQ ID MSVAELKERHRAATETVNSLRERLKQKRVQLLDTDVAGY 350.
  • the conserved G-protein beta ARTQGKTPVTFGATDLV CCRTLQGHTGKVYSLDWTPERN WD-40 repeat domains are RIVSVSQDGRFIVWN ALTSQ KTHAIRLPCAWVMTCAFA P underlined and the beta G-protein NGQSVACGGLDSVCSIF N LNSPVDRDGNLP VSRMLSGHK (transducin) is in bold.
  • the conserved G-protein beta LVLR LDIYNKLKGHRGCVNTVGFNLDGDIVISGSDDRHV domain is underlined and the WD-40 KLWD WQ TGKVKLSFDSGHLSNVFQAKIMPYTDDRSIVTC repeat domains are in bold AADGQARHAQ ILEGG QVQTMLLAKHRGRAHKLAIDPGSP HIVYTCGEDGLVQRLD LRSNTAREL FTCREVYGTHVEVV HLNAIAIDPRNPNLFVIGGSDEYARVYD IRNYKWNGSHN FGRSANYF CPSHLIGEAHVGITGLAFSGQSELLVSYNDE SIYLFT QEMGLGPDPLSASTKSVDSNSSEVTSPTAVNVD D NVTPQVYKGHRNCETVKGVGFFGPKCEYVVSGSDCGRI FIWK KKG GQLIRVMAADKHVVNCIEPHPHIPALASSGIE NDIKIWT PKAIERATLPMNVEQ
  • the conserved G-protein beta VNLWA IGK PNSLMSLCGHTNAVESVAFDSAEVLVLAGAS WD-40 repeat domains are SGVIKLWD VEE AKLVRGLTGHRSNCTAMEFHPFGEFFAS underlined and the Trp-Asp (WD) GSTDTNLKIWD IRK KGCIHTYKGHTRGISTIRFSPDGRW repeats signature is in bold.
  • the conserved G-protein beta FLVATSWDNQVRCWE IVRSGTSLGT TPKASISHDQPVLC WD-40 repeat domains are STWKDDGTTVFSGGCDKQVKMWP LSGG QPMTVAMHDAPI underlined.
  • the conserved G-protein beta LQQMVNKLLSNEDKLPYTFYISDQELVVPLESYLQKNKV WD-40 repeat domains are SVEKVLSIVYQPQAIFRIRPVNR CSATIAGHSEAVLSVA underlined and the Trp-Asp (WD) FSPDGKQ LASGSGDTTVRLWD L STQTP MFTCKGHKNWVL repeats signatures are in bold.
  • the conserved G-protein beta NRSAMDFDYAHYMLTEGRKGKENPAVSSPSREAYRKQLA WD-40 repeat domains are ETLNMNRTRILAFKNKPPTPVELIPHELTSAQPAKPTKT underlined.
  • RRYIPQTSERTLDAPDLLDDYYLNLLDWGSSNVLSIALG NTVYLWNASDGSTS ELVTIDDETGPVTSVSWAPDGRHIA VGLNNSDVQLWD SADNRL LRTLRGGHRSRVGSLAWNNHI LTTGGMDGLIVNND
  • VDTGSQVCALLWNKNERELLSSHGFTQNQLTLWKYPSMV KIAELTGHTSRVLFMAQSPDGCTVASAAGDETLRFWN VF GVPEVAKPAPKAN
  • the conserved G-protein beta DQTARVWH IEPHGHG KVKDIELKGHTDSVDQLCWDPKHA WD-40 repeat domains are DL IATASGDKTVRLWD A RSGKCSQQAELSGENINITYKP underlined and the Trp-Asp (WD) DGTHVAVGNRDDELTILDVRKFKPIHKRKFNYEVNEIAW repeats signature is in bold.
  • the conserved G-protein beta LEWPSLTVEWLPDREEPPGKDYSVQKLVLGTHTSENEPN WD-40 repeat domains are YLMLAQVQLPLEDAENDARHYDDDRADVGGFGCANGKVQ underlined.
  • the conserved G-protein beta SSSSGQPTSRRSTGNVFKLLARREVSPRSKHSLKKFWGE WD-40 repeat domains are ASECQLCPFQQSYEAVRDVRRSLISWVEAFSLQHLS AKY underlined.
  • the conserved G-protein beta RTIRLWN PHRGI HIKTYKSHGREVRDVHCTSDNSKLISC WD-40 repeat domains are GGDRQIFYWD VSTGR VIRRFRGHDSEVNAVKFNDYASVV underlined.
  • the conserved G-protein beta SLEIFGLDFQSDDRDLPLIAESPSSERFNRLSWGKNGSG WD-40 repeat domains are SDEFSLGLIAGGLVDGTIGLWNPLSLIRSEAGD KAIVGH underlined LSRHKGPVRGLEFNVIAPNLLASGADDGEICIWD LAAPR EPSHF PPLRGSGSAAQGEISFLSWNSKVQHILASTSYNG TTVVWD LKKQKPVISFSDSVRRRCSVLQWNPDLATQLVV ASDEDSSPTLRLWDMRNI MSPVKEFAGHTRGVIAMSWCP NDSSYLVTCAKDNRTICWD TVT GEIVCELPAGSNWNFDV HWYPKIPGVISASSFDGKIGIYN VEGCSRYGVRENEFGA ATLRAPKWFKRPVGASFGFGGKVVSFHTRSTGGPSVNSS EVFVHDIITEQTLVSRSSEFEAAIQSGDRPSLRALCEKK SQHCESTDDQETWGFLKVLLEDDGTARSKLL
  • the conserved G-protein beta LSCRWGPQLEQATYKNRQRLYLSEQTDGSVPNTLVIANV WD-40 repeat domains are EVVKPRVAAAEHISQFNEEARSPFVKKFKTIIHPGEVNR underlined.
  • the conserved G-protein beta VFNFIDSRYFNVFATVGGNRVTVYQCLEGGVIAVL QSYI WD-40 repeat domains are DEDKDESFYTVSWACNIDRTPFVVAGGINGIIRVID AGN underlined and the Trp-Asp (WD) EK IHRSFVGHGDSINEIRTQPLNPSL IVSASKDESVRLW repeats signature is in bold.
  • VGNSQGPNELPRCLDHELAHLTNLKSRPHEHLIRDFPGR WD-40 repeat domains are RALPVSTVKMLAGRECNYSRRGRFSSADCCHMLSRYVPV underlined.
  • the conserved G-protein beta APAPAPAATRSSTSGSAGGRDRRPQQQHAVDEKYARWKS WD-40 repeat domains are LVPVLYDWLANHNLLWPSLSCRWGPQLEQATYKNRQRLY underlined.
  • the conserved G-protein beta VYNCAKLSLVLVGPQLPKKIRALASYREYTFAAYGSDIG WD-40 repeat domains are IFKRAHQLATWSGHTAKVCLLLLFGEHILSVDVDGNAYI underlined and the Trp-Asp (WD) WAFKGMNYNLSPVGHILLDSNFTPSCIMHPDTYLNKVIL repeats signature is in bold.
  • the GSQEGPLQLWNISTKTKLYEFKGWNSSVSSCVSSPALDV Utp21 specific WD40 associated VAVGCADGKIHVHNIRYD EELVTFSHSMRGSVTALSFST putative domain is in italics.
  • the conserved G-protein beta FDPKSTSLSSSPLVAHVIEEIEGDPLAIAVHPNGEDIVC WD-40 repeat domains are FASSGSCLSFELSGQESNLKLLTK ELPPLRGIGPQKCMA underlined.
  • FSVDGSRFATGGVDGRLRILE WPSLRI ILDEPKAHKSIR DLDFSLDSEFLATTSTDGSARIWK AEDGLPCTTLTRRSD EKIELCRFSKDGTKPFLFCTVQRGDKAVTGVWDISTWNK IG HKRLLRKPAVVMSISLDGKYLAQGSKDGDMCVVE VKK MEVSHWSKRLHLGTSLTSLEFCPIERVVITTSDEWGVLV TKLNVPADWKAWQVYLLLLGLFLASLVAFYIFYENSDSF WGFPLGKDQPARPKIGSVLGDPKSADDQNMWGEFGPLDM 101 The amino acid sequence of SEQ ID MADPVEHQHQQHQQHQLQQRRRGWRIQGGQYLGEISAL
  • the conserved G-protein beta CFLHLPPPPLSLSSSPVLSLSSGLDSESRDRPACSFRFP WD-40 repeat domains are SAGSGSQVSLFDLASGAMVRTFYVFRGIRVHGIVLGCAD underlined.
  • the conserved G-protein beta F RQSPSSFT PASVIRAGSRFVNAIAYLPPTPRAPQGYAV WD-40 repeat domains are VGGQDTVVNVFA LGPGDKEE PEYTLVGHTDNVCALSVNS underlined.
  • the conserved G-protein beta VSSSG SQHLATLIGHQGPVWQISWAHPKFGSLLASCSYD domain is underlined and the WD-40 GRVIIWR EGNPNE WTQAQVFEEHKSSVNSVAWAPHELGL repeat domains are in bold CLACGSSDGNISVFT ARQDGG WDTSRIDQAHPVGVTSVS WAPSTAPGALVGSGMMEPVQKLCSGGCDNTVKVWK LYNR VWK LDCFPVLQMHTDWVRDVAWAPNLGLPKSTIASASQD GRVIIWT LAKEGD QWQGKVLYDFRTPVWRVSWSLTGNIL AVADGNNNVSLWN EAVDGEWIQVSTVEP 104 The amino acid sequence of SEQ ID MSAPMLEIEARDVVKIVLQFCKENSLHQTFQTLQSECQV 370.
  • the conserved G-protein beta SLNTVDSIETFVADINSGRWDAILPQVAQLKLPRNTLED WD-40 repeat domains are LYEQIVLEMIELRELDTARAILRQTQAMGVMKQEQPERY underlined and the Trp-Asp (WD) LRLEHLLVRTYFDPNEAYQDSTKEKRRAQIAQALAAEVT repeats signature is in bold.
  • the conserved G-protein beta DTTLALTVAQTNQTLARPIDPSQHAVAFNPTYDQLWAPI WD-40 repeat domains are CGPAHPYAKDGIAQGMRNHKLGFVEDAAIGSFLFDEQYN underlined.
  • the conserved G-protein beta VALATMTPLNVEAPRNRLLELVAKGLAVEKGELLRGVSH WD-40 repeat domains are AGTNDLGGSIPASYGLVPAPWTAIDFSSLRDTKGMSKSF underlined.
  • TKHETRHLSDHKNVARCARFSTDGRFFATGSADTSIKLF E VSKIKQMMLPDSTDGA
  • IRAVIRTFYDHTHPVNDLDF HP QNTVLISAAKDHTVKFFD YSKAT AKRAFRVIQDTHNVRS
  • VAFHPSGDFLLAGTDHPIPHLYD VN TFQCYLSANVPEFA VNAAINQVRYSSSGGMYVTASKDGTIRFWD GA SANCVRS IAGAHGAAEVTSANFTKDQRYVLSCGKDSTVKLWE VGTG RLVKQYLGATHMQLRCQAVFNNTEEFVLSIDEPSNEIVV WDAM TAEKVARWPSNHNGPPRWIEHSPTEAAFVSCSTDR
  • the conserved G-protein beta IDTPSNRFTDTTADQARRGRDIQGIPWERLSITREKYRR WD-40 repeat domains are TRLEQYKNYENVPQSGEKSGKDCTVTEKGNSFYEFRRNS underlined.
  • the conserved G-protein beta PPILPPVIPPPAVPVVAPVPTIPPVLRPLAPLPIRPPVL WD-40 repeat domains are RPPAPKRDEAGSSDSDSDHDGTAAGSTAEYEITEESRLV underlined and the splicing factor RERHEKAMQDLMMKRRGAALAVP TNDKAVRARLRRLGEP motif is in bold.
  • the conserved G-protein beta KVGVWHVRQGVCTKALAPSASSAAGPSLAVTAIASSPSS WD-40 repeat domains are L IASGYADGSIRIWDF EKGSCETTLNGHKGAVSVLRYGK underlined, and the conserved LGSL LASGSKDNDIILWDV VGETGLYRLRGHRDQVTDLV Dip2/Utp12 domain is in bold.
  • the conserved G-protein beta SSMDFHRASSYLVTASDDESIRLYD VASATCLKTINSKK WD-40 repeat domains are YSVDLVSFTSHPMTVIYSSKNGWDESLRLLSLH DNKYLR underlined. YFKGHHDRVVSLSLCPRNECFISGSLDRTVLLWD QRAEK CQGLLRVQGRPATAYDDPGLVFAIAFGGCVRMFDARKYE K GPFEIFSVGGDVSDANVVKFSNDGRLMLLTTTDGHIHV LD SF RGTLLYTFNVKPTSSKSTLEASFSPEGMFVISGSG DGSVYAWS VRGGKEVASWLSTDTEPPVIKWAPGNLMFAT GSSELSFWIPDLSKLGAYVGRK 111 The amino acid sequence of SEQ ID MAAFGAAPAGNHN PNKSSEVIQPPSDSVSSLCFSPRANH 377.
  • the conserved G-protein beta LVATSWDNQVRCWE LTKNGASV TSVPKASMSHDQPVLCS WD-40 repeat domains are AWKDDGTTVFSGGCDKQAKMWS LMS GGQPVTVAMHDAPI underlined.
  • the conserved G-protein beta VSGEPLTMDDVLPVKMGKIVKPRPLQAASIPGLLSIFQN WD-40 repeat domains are EWDSLMLSNFALEQQLHTARQELSHALYQHDAACRVIAR underlined.
  • LKKERDEARSLLALAERQIPMTASSDIAVNAPAMSNGRK ASLDEEPGYAGKKMRPGISASIIAEITDCNLALSQQRKK RQIPSTLAPVEDLE RYTQLSSYPLHKTGKPGITSLDICH SKDIIATGGIDTSAVLFD RS SGQIMSTLSGHSKKVTSVN FDAQGDMVLTGSADKTVRIWQ GSEDG SYNCRHILKDHTA EVQAITVHATNNYFATASLDNTWCFYE FS TGLCLTQVEG ASGSEGYTSAAFHPDGLILGTGTSNADVKIWD VK TQANV TTFSGHTGAITAISFSENGYFLATAAQDGVKLWD LR KLK NFRTFS
  • the conserved G-protein beta KSVPEVSAALKQRRI LKGHFGKIYALHWSADSRHLVSAS domain is underlined and the WD-40 QDGKLIIWN GFT TNKVHAIPLRSSWVMTCAYSPSGNLVA repeat domains are in bold CGGLDNLCSVYK VPHGGNKESSSA QKTYGELAQHEGYLS CCRFIKDNEIVTSSGDSTCILWD VET KTPKAIFNDHTGD VMSLAVFDDKGVFVSGSCDATAKLWD HRVH KQCVMTFQG HESDINSVQFFPDGDAFGTGSDDSSCRLFD IRAYQ QINK YSSDKILCGITSVAFSKTGKSLFAGYDDYNTYVWD TLS G NQVEVLTGHENRVSCLGVSEDGKALATGSWDTLLKIWA 114 The amino acid sequence of SEQ ID MGGVEDESEPASKRMKLSSRVLRGLANGSSRTEPAAGSS 380.
  • the conserved G-protein beta LDLMARPLPIEGDEEVIGSKGVIKRVEFVRLIAKALYSL WD-40 repeat domains are GYEKSGARLEEESGIPLQSSVVNLFMQQISDGLWDESVV underlined.
  • the conserved G-protein beta SVVILNLD NPLDISVYAEHAYPATVARFSPNGEWVASAD WD-40 repeat domains are SSGAVRIWG AYNDHVLKKEFKVLSGRIDDLQWSPDGLRI underlined.
  • the conserved G-protein beta EYVRALNAAKLDKVFA RPFVGAMDGHVDSVSCMAKNPNY WD-40 repeat domains are LKGIFSGSMDGDIRLWD IAS RRTVCQFPGHQGPVRGLAA underlined and the SOF1 protein STDGQILVSCGIDSTVRLWN VPVATLGESDGTHENLAKP domain is in bold.
  • the conserved G-protein beta PGVDKLEEGEELQCDPSAYNSLHAFHIGWPCLSFDIVRD WD-40 repeat domains are TLGLVRTEFPHQVYFVAGTQAEKPTWNSIGIFKVSNITG underlined.
  • the conserved eukaryotic YIWEECINLREVKSLRKLNHPNIIKLKEVIRENNELFFI protein kinase domain is FEYMECNLYQIMKERSTPFSETAIIKFCYQILQGLSYMH underlined and the protein kinases RNGY FHRDLKPENLLV TSDLIKIADFGLAREVLTSPPYT ATP-binding region and DYVSTRWYRAPEVLLQSPTYTTAIDMWAVGAILAELFTL serine/threonine protein kinases HPLFPGESELDEIYKICGVLGTPDYETWPDGMQLAAFRN active-site signatures are in FIFPQFLPVNLSVLIPHASPEAIDLITRLCSWDPQKRPT bold.
  • the conserved eukaryotic VFLARSKLPNNRGLRIAIKK FKQSKDGDGVSPTAIREIM protein kinase domain is LLREFSHENVVKLVNVHINHVDMSLYLAFDYAEHDLYEI underlined and the protein kinases IRHHREKLNHHNINQYTVKSLLWQLLNGLNYLHSNW IVH ATP-binding region and RDLKPSNI LVMGEGEEHGVVKIADFGLARIYQAPLKPLS serine/threonine protein kinases DNGVVVTIWYRAPELLLGAKHYTSAVDMWAVGCIFAELI active-site signatures are boxed TLKPLFQGVEVKASPNPFQLDQLDKIFKVLGHPTIEKWP in bold.
  • the conserved protein kinase DEEGVPPSSLREISLLQMLSQSIYVVRLLCVEHVTKKGK family domain is underlined.
  • the PLLYLVFEYLDTDLKKFIDYRRSVNAGPLPQNVIQSFMY protein kinases ATP-binding region QLLKGVAHCHSHG VLHRDLKPQNLLV DKSKGLLKVGDLG is in bold and the LGRAFTVPLKCYTHEVVTLWYRAPEVLLGSTHYSTPVDI serine/threonine protein kinases WSVGCIFAEMVRRQPLFPGDCEIQQLLHIFTLLGTPTEE active-site signature is in MWPGVKRLRDWHEYPQWKPENLARAVPNLSPTGLDLISK bold/italics.
  • MLQCDPAKRISAKAAMNHPYF DDLDKSQF 121 The amino acid sequence of SEQ ID MDG YEKMDK VGEGTYGKVYMARDKKTGQLVALK KTRLEN 387.
  • the conserved protein kinase DGEGIPPTALREISLLQMLSQDIYIVRLLDVKHTENKLG family domain is underlined.
  • MLVYEPSKRISAKKALEHPYF DDLDKSQF 122 The amino acid sequence of SEQ ID MDAYEK LEK VGEGTYGKVYKAKDKNTGQLVALK KTRLES 388.
  • the conserved eukaryotic DDEGIPPTALREISLLQMLSQDIHIVRLLDVEHTENKNG protein kinase domain is KPLLYLVFEYMDSDLKKYIDGYRRSHTKVPPNIIKSFMY underlined and the protein kinases QLCQGVAYCHSRG VMHRDLKPHNLLV DKQRGVVKIADLG ATP-binding region and LGRAFTIPIKKYTHEIVTLWYRAPEVLLGATHYSTPVDI serine/threonine protein kinases WSVGCIFAEMVRLQALFIGDSEVQQLFKIFSFLGTPNEE active-site signatures are in IWPGVTKFRDWHIYPQWKPQDISSAVPDLEPSGVDLLSK bold.
  • MLVYEPSKRISAKKALEHPYF DDLDKSQF 123 The amino acid sequence of SEQ ID MDS YEKLEK VGEGTYGKVYKAKDKKTGKLVALK KTRLEN 389.
  • the conserved protein kinase DGEGIPPTALREISLLQMLSQDMNIVRLLDVEHTENKNG family domain is underlined.
  • MLVYEPSKRISAKKALQHPYF DDLDKSQF 124 The amino acid sequence of SEQ ID MEK YEKLEK VGEGTYGKVYKGRDKRTGRLVALK KTPFHQ 390.
  • the conserved eukaryotic EEGIPPTAIREISLLKSLSQCIYIVKLLDVKASFNGKGK protein kinase domain is HVLFMVFEYADSDLKKHIDAHRQCNTKLSPRSIQSYMFQ underlined and the protein kinases LCKGIAYCHSHG VLHRDLKPQNILV DQKIGLLKIADLGL ATP-binding region and GRACTVPIKSYTFEVVTLWYRAPEVLLGAKRYSMALDIW serine/threonine protein kinases SLGCIFAELCNLQALFAGDSQIQQLINIFRLLGTPNEQL active-site signatures are in WPGVTQLSDWHEFPQWRPQDLSKVVFNLDPNGVDLLSKM bold
  • LQYDPAKRISAKEALDHPYF DSLDKSQF 125 The amino acid sequence of SEQ ID MGCVCGKPSARAADYVESPAEKGASSNSRSSSMASRRLV 391.
  • the conserved eukaryotic APAVMDQGIDAENGHEGDYRTKLRGKQSNGADPVSLLSD protein kinase domain is DAEKQRHSRHHQHQQHHPIRPHHLRPQGEFVPNANSNPR underlined and the FGNPPRHIEGEQVAAGWPAWLTAVAGEAIKGWIPRRADS serine/threonine protein kinases FEKLDKIGQGTYSNVYKARDLDTGKIVALKKVRFDNLEP active-site signatures are in ESVRFMAREIQVLRRLDHPNVVKLEGLVTSRMSCSLYLV bold.
  • the conserved eukaryotic PQHSDSGILHHQHYYHPRDESDEAKLKESNYGGSKRRTR protein kinase domain is QGRDPADLDMGIFVRTPSSQSEAELVAAGWPAWMAAFAG underlined and serine/threonine EAIHGWIPRRAES FEKLYKIGQGTYSNVYKARDLDNGKI protein kinases active-site VALKKVRFDSLDAESVRFMAREILVLRKLDHPNIVKLEG signatures is in bold.
  • the conserved protein kinase YMAKEIETGEIVALK KIRMDNEREGFPITAIREIKLLKK family domain is underlined.
  • the LQHENVIKLKEIVTSPGPEKDEQGKSDGNKYNGSIYMVF protein kinases ATP-binding region EYMDHDLTGLAERPGMRFSVPQIKCYMKQLLIGLHYCHI is in bold and the NQ DNNGILKLADFGLARSFCSDQNGN serine/threonine protein kinases LTNRVITLWYRPPELLLGSTKYGPAVDMWSVGCIFAELL active-site signature is in YGKPILPGKNEPEQLTKIFELCGSPDESNWPGVSKLPWY bold/italics.
  • the conserved eukaryotic RGRRKADGLIVALKEVHDYQSSWREIEALQRLCGCPNVV protein kinase domain is RLYEWFWRENEDAVLVLEFLPSDLYSVIKSGKNKGENGI underlined and the PEAEVKAWMIQILQGLADCHANW VIHRDLKPSNLLI SAD serine/threonine protein kinases GILKLADFGQARILEEPEAIYEVEYELPQEDIVADAPGE active-site signature is in bold.
  • the conserved eukaryotic KPLDPSER YRKGIT LGQGTYGIVYKAFDTVTNKTVAVKK protein kinase domain is IHLGKAKEGVNVTALREIKLLKELSHPNIIQLIDAYPHK underlined and the protein kinases QNLHIVFEFMETDLEAVIKDRNLVFSPADIKSYLQMTLK ATP-binding region and GLAVCHKKW VLHRDMKPNNLLI AADGQLKLGDFGLARLF serine/threonine protein kinases GSPDRKFTHQVFAVWYRAPELLFGAKQYGPAVDIWATGC active-site signatures are in IFAELLLRKPFLQGVSDLDQIGKIFAAFGTPRQSQWPDV bold.
  • ASLPDFVEFQFVPAPSLRSLFPMASEDALDLLSKMFTLD PKNRITAQQALEHRYF SSVPAPTRPDLLPKPSKVDSSRP PKHASPDGPVVLSPSKARRVMLFPNNLAGILPKQVSQST TGGTPIEFDMPTQKLREVCPRSRITESGKKHLKRKTMDM SAALDECAREQEGQEGKTILDPDHQRSAKKEKHM 130
  • SEQ ID MAGGQENCVRITRARAACVSKASAPVIQSQVDEKKSRKR 396 The amino acid sequence of SEQ ID MAGGQENCVRITRARAACVSKASAPVIQSQVDEKKSRKR 396.
  • the conserved cyclin N- and APKRAAVDDLAANASGSQPKRRAVLGDVTNLHAAATDCL C-terminal family domains are STAEDQVDAPNPSIKGRARNKKKEARTSTKVVKDEIHPE underlined.
  • the conserved cyclin and AATESNISGFSVAAEPLKRRAVLSDVSNICKEAAAVDCL cyclin C-terminal domains are KKPKAVKVVSQNANAKGRGRGIPRNNKKITQEAEIKKET underlined and the cyclins SPAICNVDDASAGNAIGDDKQNNNVNPLKEVQDNPKELN signature is in bold.
  • the conserved cyclin and ARKRAFGDIGNLVEDLDAKCTISKYWVRKRPRTNFGVNA cyclin C-terminal domains are NKGASSSTQGQGIVVRGEQKAWDRIVWGNKQSCAIKMNA underlined and the cyclins QHVTATQRGTAISISDIIDSSVQDGGIKAPSQLKARKQT signature is in bold.
  • the conserved cyclin N- and RALGDIGNIVADVGGKCNVTKDGVNGKPLAQVSRPITRS C-terminal family domains are FGAQLLAQAAANKGISAANNQTQVPVVIPKADVRGNKQR underlined.
  • the conserved cyclin and PVSMLVQRETHYMLPEDYLQRLRNRTLDVNVRREAVGWI cyclin C-terminal domains are LKVHSFYNFSAPTAYLAVNYLDRFLSRHRMPQGVKAWMI underlined QLMAVACLSLAAKMEETQVPLPSDLQREDARFIFDARTI QRMELLILSTLQWGMR S ITPFSFIDYFAYRAVQGHGHGH DATPKAVMSRAIELILSTTEEIDFMEYRPSAIAAAALLC AAEEVVPLQAVHYKRALSSSITDVDKDKMFGCYNLIQET IIEGGCYWTPMSLQSTEKTPVGVLDAAACLSNTPTSS YS VKPYASVTAAKRRKLNEICSALLVSQAHPC 135 The amino acid sequence of SEQ ID MAANFWTSSHCKELLDAEKVGIVHPLDKDQGLTQEDVKI 401.
  • the conserved GCN5-related N- EARVKAIAEIVGAMVEGCRKGEDVDLNALKAAACRRYGL acetyltransferase family domain is SRAPKLVEMIAALPDGERAAVLPKLKAKPVRTASGIAVV underlined and the radical SAM AV MSKPHRCPHIATTGNICVYCPGGPDSDFEYSTQSYTG family domain is in bold.
  • the conserved chromo domain VEKENKAPNSVDKMGMGSADESGRFSTSNGQFMNMNNGV is underlined and the MOZ/SAS-like VKEEWKGGVPVVPSAPTTVPVITNVKLETPSSPDHDMAR protein domain is in bold.
  • the conserved GCN5-related N- QKRKRNEVEHAGVASNSTGMFAVPPSHIYSHLHPMSMSM acetyltransferase family domain is PMPMHNSHPSSLSESRDGALTSNDDDDNLTGGNQSQLDS underlined and the bromodomain is MSAGNTDGREDFDDEDDDDDDEEDDDEVEGDEEDQDHDP in bold.
  • the conserved histone PHRIRMAHSLIVHYALDEKMEVCRPNLLQSRELRVFHAD deacetylase family domain is DYISFLQSVTPETQHEQLRQLKRFNVGEDCPVFDGLYNF underlined.
  • the conserved histone KPHRIRMTHALLVQYGLHKEMQILKPYPARDRDLCRFHA deacetylase family domain is DDYVAFLRGITPETIQDQVKALKRFNVGDDCPVFDGLYQ underlined.
  • the conserved histone SYELHKKMEIYRPHKAYPVELAQFHSADYVEFLHRITPD deacetylase family domain is TQHLFTKELVKYNMGEDCPVFENLFEFCQIYAGGTIDAA underlined.
  • the conserved histone EVLEKHPENADRVRNMLSILRKGPIAPYTEWHTGRAAYL deacetylase family domain is SELYSFHRPDYVDMLAKTSTAGGKTLCHGTRLNPGSWEA underlined.
  • the conserved histone PHRMRMAHNLIVHYGLHQRMEVCRPHLAQSKDIRAFHTD deacetylase family domain is DYIHFLSSVAPDTQQEQLRQLKRFNVGEDCPVFDGLFNF underlined.
  • CQSSAGGSIGAALKLNRKDADIAINWAGGLHHAKKCEAS GFCYVNDIVLGILELLKVHQRVLYIDIDIHHGDGVEEAF YTTDRVMTVSFHKFGDYFPGTGHIKDVGYGKGKYYALNV PLNDGIDDESYKHLFRPIIQKVMEVYQPEAVVLQCGADS LSGDRLGCFNLSVKGHADCVRFVRSFNIPLMLVGGGGYT IRNVARCWCYETAVAVG VEPQDKLPYNEYYEYFGPDYTL YVAPSNMENLNTEKDLEKMRNVLLEQLSKIQHTPSVPFQ ERPPDTEFNDEEEEDMEKRSKCRIWDGEYVGSEPEEDGK LPRFD
  • the FKBP-type ILKRIISD GEKYERPKDPDEVTVKYEAKLEDGMLVAKSP peptidyl-prolyl cis-trans EEGVEFYVNDGNFCPAIVKAVKTMKKGENVTLTIKPAYA isomerase signatures 1 and 2 are FGEQGKDAEEGFAAIPPNATITINLQLV SFKAVKEVTED in bold.
  • the TPR repeat is in KKVIKKILKE ADGYDKPSDGTVVQIRYTAKLQDGTIFEK bold/italics.
  • the conserved cyclophilin- CTGEKGNGRSGKPLH FKGSSFHRVIPGFMCQGG DFTRGN type peptidyl-prolyl cis-trans GTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGS isomerase signature is underlined QFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGS and The cyclophilin-type peptidyl- GRTSKPVVIADSGQLA prolyl cis-trans isomerase signature 2 is in bold. 158 The amino acid sequence of SEQ ID MPNP KVFFDMQVGGAPAGRIVMELYADVVPKTAENFRAL 426.
  • the conserved cyclophilin- CTGEKGTGRSGKPLH FKGSSFHRVIPGFMCQGG DFTRGN type peptidyl-prolyl cis-trans GTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGS isomerase signature is underlined QFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGS and The cyclophilin-type peptidyl- GRTSKPVVIADSGQLA prolyl cis-trans isomerase signature 2 is in bold. 159 The amino acid sequence of SEQ ID MPNP KVFFDMQVGGAPAGRIVMELYADVVPKTAENFRAL 427.
  • the conserved cyclophilin- CTGEKGTGRSGKPLH FKGSSFHRVIPGFMCQGG DFTRGN type peptidyl-prolyl cis-trans GTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGS isomerase signature is underlined QFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGS and The cyclophilin-type peptidyl- GRTSKPVVIADSGQLA prolyl cis-trans isomerase signature 2 is in bold. 160 The amino acid sequence of SEQ ID MADDFELPESAGMMENEDFGDTVFKVGEEKEIGKQGLKK 428.
  • the conserved FKBP-type LLVKE GGSWETPETGDEVE VHYTGTLLDGTKFDS SRDRG peptidyl-prolyl cis-trans TPFKFKLGQGQVIKGWDQGIATMKKGENAVFTIPPDLAY isomerase signature is underlined GESGSQPTIPPNATLKFDVELL SWASVKDICKDGGIFKK and the FKBP-type peptidyl-prolyl IIKE GEKWEHPKEADEVLVKYEARLEDGTVVSKSEEGVE cis-trans isomerase signature 1 is FYVKDGYFCPAFAIAVKTMKKGEKVLLTVKPQYGFGHQG in bold and underlined.
  • the TPR REAIGNDVARSTNATLLVDLELV SWKVVDEVTDDKKVLK repeat is in bold/italics.
  • KILKQ GEGYERPNDGAVVKVKYTGKLEDGTIFEEKGSDE EPFEFMAGEEQVVDGLDRAVMTMKKGEVALVSVAAEYGY QTEIKTDLAVVPPKSTLIYEVELV SFVKEKESWDMNTAE KIEAAGKKKEEGNALFKVGKYFRASKKYEKATKYIEYDT SFSEEEKKQSKPLK RDVKLEYRALKEKQKEYNKKEAKFYGNMFARMSKL EELESRKSGSQKVETANKEEGSDAMAVDGESA 161 The amino acid sequence of SEQ ID MAASLTPLGAGLAYATIYDQAKVRKLEPTKRSLIALCQH 429.
  • the conserved FKBP-type SDSQHRRFITRKYHVNVQILNRRDAIRLIGLAAGLCIDL peptidylprolyl isomerase domain is SLMYDARGAGLPPQENAKLCDTTCEKELENAPMITTESG underlined.
  • the conserved FKBP-type KCPPHTLRKMRFSAQDLQSKNFYSGFTPFKSVFISTSKR peptidylprolyl isomerase domain is SWQAGSARAMSQDAAFQSKVTT KCFLDIEIGGDPAGRIV underlined and the Cyclophilin- LGLFGEDVPKTAENFRALCTGEKGFG YKGSSFHRIIKDF type peptidyl-prolyl cis-trans MLQGG DFDRGDGTGGKSIYGRTFEDENFKLAHVGPGVLS isomerase signature is in bold.
  • the conserved FKBP-type WSTKDPGQKPFTFTIGQGR VIKGWDEGVLDMQLGEIFKL peptidylprolyl isomerase domain is RCSPDYGYG SNGFPAWGIRPNSVLVFEIEVL SVN underlined and the Cyclophilin- type peptidyl-prolyl cis-trans isomerase signature is in bold. 169 The amino acid sequence of SEQ ID MPNP RCYLDITIGEELEGRILVELYSDVVPKTAENFRAL 438.
  • the conserved cyclophilin- CTGEKGIGPHTGVPLH YKGLPFHRVIKGFMIQGG DISAQ type peptidyl-prolyl cis-trans NGTGGESIYGLKFDDENFQLKHERRGMLSMANSGPNTNG isomerase family domain is SQFFITTTRTSHLDGKHVVFGKVIKGMGVVRGIEHTPTE underlined and the cyclophilin- SNDRPSLDVVISDCGEIP EGSDDGIANFFKDGDLYPDWP type peptidyl-prolyl cis-trans ADLDEKSAEISWWMNAVDSAKCFGNENYKKGDYKMALRK isomerase signature is in bold.
  • the conserved FKBP-type EGTLADTGEVFDTTREDNTLFSFELGKGT VIKAWDIAVK peptidylprolyl isomerase domain is TMKVGEVARITCKPEYAYG SAGSPPDIPENATLIFEVEL underlined and the Cyclophilin- V ACKPRKGSTFGSVSDEKARLEELKKQREIAAASKEEEK type peptidyl-prolyl cis-trans KRREEAKATAAARVQAKLEAKKGQGRGKGKSKGK isomerase signature is in bold. 171 The amino acid sequence of SEQ ID MGLGLKIASASFLPIFNIMATRSLCILLVCFIPVLAHVL 440.
  • the conserved FKBP-type DVSELQIGVKHKP KSCDIQAHKGDRIK VHYRGSLTDGTV peptidylprolyl isomerase domain is FDSS FERGDPIEFELGSGQ VIKGWDQGLLGMCVGEKRKL underlined and the Cyclophilin- RIPSKLGYG AQGSPPKIPGGATLIFDTELV AVNGKGISN type peptidyl-prolyl cis-trans DGDSDL isomerase signatures are in bold. 173 The amino acid sequence of SEQ ID MSGAPAERP ISYFDITIGGKPIGRIVFSLYADLVPKTAE 442.
  • the conserved FKBP-type NFRALCTGEKGIGKSGKPLC YAGSGFHRVIKGFMCQGG D peptidylprolyl isomerase domain is FTAGNGTGGESIYGEKFEDEAFPVKHTKPFLLSMANAGK underlined and the Cyclophilin- DTNGSQFFITVSQTPHLDDKHVVFGEVIKGKSIVRAIEN type peptidyl-prolyl cis-trans YPTASGDVPTSPIIISACGVLS PDDPSLAASEETIGDSY isomerase signatures are in bold.
  • the conserved G-protein beta PQPPDQRSQRIRIACKVRAEYEVVKNLPTLPQREVGSSV WD-40 repeat domains are SNSNVGETHSSLTTNQAQGFPTDTSGDLSKDEGKEITSI underlined and the Trp-Asp (WD) AVHLQPQTGLIDGKAGAIAGTSTAISSVGSSDRYQPSAA repeats signature is in bold.
  • the conserved G-protein beta HNGE RLGTYRGHNGAVWCCDVSRDSTRLITSSADQTAKL WD-40 repeat domains are WN VETGAQLFSFNFESPARAVDLAIGDKLVVITTDPFME underlined.
  • LPSAIHIKRIEKDLSKQTAD SVLTITGIKGRINRAVWGP LNSTIISGGEDSVVRIWD SETGKLLR ESDKETGHQKPIT SLCKSADGSHFLTGSLDKSARLWD IRTLTLIKTYVTERP VNAVAISPLLDHVVIGGGQEASHVTTTDREAGKFEAKFF HKILEE EIGGVKGHFGPINSLAFNPDGRSFASGGEDGYV RLHH FDPDYFHIKM 178
  • SEQ ID M RPILMKGHERPLTFLKYNRDGDLLFSCAKDHTPTVWY G 447.
  • the conserved G-protein beta HNGE RLGTYRGHNGAVWCCDVSRDSTRLITSSADQTAKL WD-40 repeat domains are WN VETGNQLFSFNFESPARAVDLAIGDKLVVITTDPFME underlined.
  • LPSAIHIKRIEKDLSKQTAD SVLTITGIKGRINRAVWGP LNSTIISGGEDSVVRIWD SETGKLLR ESDKETGHQKAIT SLCKSADGSHFLTGSLDKSARLWD IRTLTLIKTYVTERP VNAVAISPLLDHVVIGGGQEASHVTTTDRRAGKFEAKFF HKILEE EIGGVKGHFGPINSLAFNPDGRSFASGGEDGYV RLHH FDPDYFHIKM 179
  • the conserved G-protein beta SRQIAGVTCINFCPEPPHDFAVTSSTRVHIYD GKSCE LK WD-40 repeat domains are KTITKFKDVAYSGVFRSDGQIIAAGGETGVIQVFN AKSQ underlined.
  • the conserved C-x8-C-x5-C-x3- LHVDEPGSVKRGGATNGFAPKRSYNGSDERDTLAAGPPG H type zinc finger is underlined GSRRNISARWGRGRGGIFISDERQKI RNKV NYWLAGN and in italics and the conserved QRGEE KYL SF VMGS DVKFLTQLSGHVKAIRGIAFPSD Cys and His residues in bold,
  • the SGKLYSGGQDKKVIVWD CQTGQGTDIPLNDEVGCLMSEG conserved G-protein beta WD-40 PWIFVGLPNAVKAWN ILTSTELSLVGPRGQVHALAVGNG repeat domains are underlined and MLFAGTHDGSILAW KFSPAS NTFEPAASLVGHTQAVVSL the Trp-Asp (WD) repeats signature VSGADRLY SGSMDKTIRVW DL GTFQCLQTLRDHTSVVMS is in bold (non-italics).
  • the conserved G-protein beta EYVRALNAAKLDKIF AKPFLAAMSGHIDGISAMAKSPRH WD-40 repeat domains are LKSIFSGSVDGDIRLWD IA ARRTVQQFPGHRGAVRGLTV underlined.
  • the conserved G-protein beta SENDFDLNNKSPDTTALQAKRGKDIQGIPWNRLNFTREK WD-40 repeat domains are YRETRLQQYKNYENLPRPRRSRNLDKECTNFERGSSFYD underlined.
  • the conserved G-protein beta ILLWN L TKEPEK YGVPRRRLTGHSHFVQDVVISSDGQFA WD-40 repeat domains are LSGSWDSELRLWD LN TGLTTRRFVGHTKDVLSVAFSIDN underlined and the Trp-Asp (WD) RQ IVSASRDRTIKLWN T LGECKYTIQPDAEGHSNWISCV repeats signatures are in bold.
  • the conserved G-protein beta AWNCTGTKLASGSVDQTARVWN IEPHGH SKTKDLELKGH WD-40 repeat domains are ADSVDQLCWDPKHSEL LATASGDRTVRLWD A R SGKCSQQ underlined and the Trp-Asp (WD) VELSGENINITFKPDGTHIAVGNRDDELTIID VR KFKPL repeats signature is in bold.
  • the conserved G-protein beta WDRKVRLYD AS ANSLKGQFVHGGPVLDCCFHDDASGFSG WD-40 repeat domains are SADNTVRRYD F STRKEDILGRHEAPVRCVEYSYAAGQVI underlined.
  • the conserved G-protein beta KKQAPLESIHSATKRPEDPRPRRQLGPPRPPPSILAEQE WD-40 repeat domains are DSDRFVGPPRPPQFVRDDNDDGEAEIMIGPPRPPAQYSD underlined and the Trp-Asp (WD) DHDNEETIGPPKPSYLEKGEETDQMVGPSKRGSDDETSG repeats signature is in bold.
  • the conserved G-protein beta PSLSCRWGPQMHQATYKNSQRLYLSEQTDGTVPNTLVIA WD-40 repeat domains are TCEVVKPRVAAAEHISQFNEEARSPFVKKFKTIIHPGEV underlined.
  • the conserved G-protein beta YFDEKAQAGEWDEVERYLSGFTKVDDNRYSMKIFFEIRK WD-40 repeat domains are QKYLEALDRQDRAK AVDILVKDLKVFSTFNEELYKEITQ underlined.
  • the Lissencephaly LLTLDNFRENEQLSKYGDTKSARTIMMSELKKLIEANPL type-1-like homology motif is in FREKLIYPNLKASRLRTLINQSLNWQHQLCKNPRPNPDI bold and the CTLH, C-terminal to KTLFTDHACGPPNGARTPTQPTASLGVLPKATTFTPIGP LisH motif is in italics.
  • the conserved G-protein beta LEWPSLTVQWLPDREEPPGKDYSVQKMILGTHTSDNEPN WD-40 repeat domains are YLMLAQVQLPLEDAENDARQYDDERGEIGGFGCANGKVQ underlined.
  • the conserved G-protein beta RTIKLFG LNASD TPSLLASLTGHEGPVWQVAWAHPKFGS WD-40 repeat domains are MLASCSYDGRVIIWR EGQQEN EWSQVQVFKEHEASVNSI underlined.
  • the conserved G-protein beta RTIKLFG MNTSDT PTLLASLTGHEGPVWQVAWAHPKFGS WD-40 repeat domains are MLASCSYDRRVIIWR EGQQENE WSQVQVFKEHEASVNSI underlined.
  • the conserved G-protein beta ANYLVATSWDNQVRCWE VLQTG ASMPKAAMSHDQPVLCS WD-40 repeat domains are TWKDDGTAVFSAGCDKQAKMWP LLT GGQPVTVAMHDAPI underlined.
  • the conserved G-protein beta ADVEGEDVQEDNKRSEPDENSSSLDDAIHTFEGHEDTLF WD-40 repeat domains are AVACSPVDATWVASGGGDDKAFMWRIGH ATPFFELKGHT underlined.
  • ADL GKCLS VYTGHCESVTCGDFTPDGKAICTGSADGSLRVWN
  • PQTQE S KLTVKGYPYHTEGLTCLSISSDSTLVVSGSTDGSVHVV N IKN GKVVASLVGHSGSIECVRFSPSLTWVATGGMDKKL MIWE LQ SSSLRCTCQHEEGVMRLSWSLSSQHIITSSLDG IVRLWD SRS GVCERVFEGHNDSIQDMVVTVDQRFILTGS DDTTAKVFE IGAF 197
  • the conserved G-protein beta HVLELTPNGIVEVCAFDSSDGLYDCTWSEANENL VVSAS WD-40 repeat domains are GDGSVKIWD I ALPPV ANPIRSLEEHAREVYSVDWNLVRK underlined and the Trp-Asp (WD) DCFLSASWDDTIRLWT IDR PQSMRLFKEHTYCIYAAVWN repeats signature is in bold.
  • the conserved G-protein beta STPSPSRTTTYSDRFIPSRTGSRLNGFALIDKQPQPLPS WD-40 repeat domains are PTRSAAEGRDDASSSSASAYSTLLRNELFGEDVVGPATP underlined.
  • the conserveed G-protein beta DSSTMLRN GE TGDWIGTFEGHKGAVWSCCLDNRALRAAS WD-40 repeat domains are GSADFSAKIWD AL TGDELHCFVHKHIVRACAFSESTSLL underlined.
  • the conserveed G-protein beta IGSFLEEYNNRVEIIELDEESGEFKSDPRLAFDHPYPTT WD-40 repeat domains are KIMFVPDKECQRPDLLATTGDYLRIWQVCEDRVE PKSLL underlined.
  • the conserved G-protein beta APSMLASCSGDKTVRIWE NTHTLNSTSP SWACKAVLEET WD-40 repeat domains are HTRTVRSCAWSPNGKLLATASFDATTAIWE NVGG EFECI underlined.
  • the conserved G-protein beta NMWA IGK PNAILSLSGHSSAVESVTFDSAEALVVAGAAS WD-40 repeat domains are GTIKLWD LE EAKIVRTLTGHRSNCISVDFHPFGEFFASG underlined and the Trp-Asp (WD) SLDTNLKIWD IR RKGCIHTYKGHTRGVNSIRFSPDGRWV repeats signature is in bold.
  • the conserved G-protein beta NTVDSLETFVADINSGRWDVILPQVAQLKLPRKKLEDLY WD-40 repeat domains are EQIVLEMIELRELDTARAILRQTQAMGFMKQEQPERYLR underlined and the Trp-Asp (WD) LEHLLVRTYFDPREAYHESSKEKRRSQIAQALASEVTVV repeats signature is in bold.
  • the conserved G-protein beta S EPERLWTVTAHTESCRAARFINAGSSVLTASPDCSILA WD-40 repeat domains are TN VE TGQPVARLDNAHGAAINCLTNLTESTIASGDENGI underlined.
  • the conserved G-protein beta SPPSITYSDRFIPSRKASNFEEFALPDKTSPSPNSAGGQ WD-40 repeat domains are SSSTNGEGRDDACAAYSALLRTELFPATPDKTEGCRRPV underlined.
  • the conserved G-protein beta INSLDFHRTNNYLVTASDDEAIRLFD TASATWQKTSYSK WD-40 repeat domains are KYGVDLICFTNHQTSVLYSSKNGWDESLRHLSLM DNKYL underlined. RYFKGHHDRVVSLCMSPKGECFMSGSLDRTVLLWD LRID KCQGLIRVRGRPAVAYDEQGLVFAISNEGGLIKMFDARL YDK GPFDTFVVEGDKSEASGIKFSNDGKLILLSTMDSNI HVLD AY QGTTVHSFSVEAVPNGGEAVPNGGTLEASFSPD GKFVISGSGNGNIHAWS VNSGKEVACWTTEGVIPAVVKW APRRLMFASGSSVLSLWVPDLSKLASLTGSNSNSAY 207 The amino acid sequence of SEQ ID MHRVGSTGNTSNSSRPRR EKRLTYVLNDANDSRHCSGIN 476.
  • the conserved G-protein beta DNTILIHS YPSSS SSKPITLRHHKNAVTALAINSNVRSL WD-40 repeat domains are ASGSVDHSVKLYS YP GGEFQSNVTRFTLPIRSLAFNKSG underlined.
  • the conserved G-protein beta DEEGGNSSNIEDDIIYSSSEEDPVVSSDYEEDEDAESDA WD-40 repeat domains are EGVTAEQELEGDIDNALQNYMGTLTVLSNFHGENLKNAE underlined.
  • the conserved G-protein beta PIMLLTGHHAAIYTMKFNPTGTVIASGSHEREIFLWN VH WD-40 repeat domains are GD CKNFMVLKGHKNAVLDLHWTTDGCQIISASPDKTLRA underlined.
  • the conserved G-protein beta VVQLYSCMDKISNIEWALDSEYILCGLYKRAMVQAWS LS WD-40 repeat domains are QPEWTCKIDEGPAGIAHARWSPDSRHIITTSDFQLRLTV underlined.
  • WS LVNTACIHIQWPKHASKGVSETQDSKfAAIATRRDCK DYVNLLSCHTWEVMGTFTVDTIDLADLEWSPNDSAIVVW DSPLEYKVLIYSP
  • DGRCLFKYQAYDSWLGVKTVAWSPCS QFLAVGSYDQTLRTLN HLTWKPFAEFVHVSTVRGPASAV VFKEVEEPWNLDVSGLHLNDDNAHDIQDGKPAEGHSRVR YKVVEFPVNVSSQKHPVDKPNPKQGIGLLAWSRDSQYLF TRNDNMPTALWIWDIC
  • RLELAALLIQKEPIRAAAWDPVY PRVALCTGSSHLYMWT PSGACCVNIPLPQ
  • the conserved G-protein beta IMRNLD NPLEASVYGEHSYPATVARFSPNGEWVASGDTS WD-40 repeat domains are GTVRIWG RGS DHTLKYEYKALAGRIDDLEWSADGQRIVV underlined.
  • VNSN NPQPVISYDSHT WD-40 repeat domains are NNVTAVGFQCDGKWMYSGSEDGTVKIWD LR APGFQREYE underlined and the Trp-Asp (WD) SRAAVNTVVLHPNQTELISGDQNGNIRVWD LN ANSCSCE repeats signature is in bold.
  • the conserved G-protein beta M GTLIDKFDEHDGPVRGVHFHKTQPLFVSGGDDYKIKVW WD-40 repeat domains are N YKM RQCLFTFVGHLDYIRTVHFHNEYPWIVSASDDQTI underlined and the Trp-Asp (WD) RLWN WQS RVCISVLTGHNHYVMSASFHPKEDL VVSASLD repeats signature is in bold.
  • the QTVRVWD I SGLRKKTVSPADDLSRLAQMNTDLFGGGD VV coatomer WD associated region is VKYVLEGHDRGVNWAAFHTSLPLIVSGADDRQVKLWR MN in bold/italics.
  • the conserved G-protein beta TSSSPDSSPLRLALPAKSCAPDVDETLMALGVPGSEKKN WD-40 repeat domains are NHNKPIDPTQHSVTFNPSYDQLWAPLYGPAHPYAKDGIA underlined.
  • the conserved G-protein beta IAFNFIDARYHNIFATAGGTRVTIYQCLEGGAISVLQAY WD-40 repeat domains are VDDD KDESFYTLSWACDVNGSPLLVAGGHNGIIRVLD VA underlined and the Trp-Asp (WD) NEKVHKSFVGHGDSVNEIRTQALKPSL ILSASKDESVRL repeats signature is in bold.
  • the conserved G-protein beta APVPSSNPNTVSKWELDKDFLCPICMQTMKDAFLTACGH WD-40 repeat domains are SFCYMCIMTHLNNKSNCPCCSLYLTNNQLFPNFLLNKLL underlined and the Trp-Asp (WD) KKTSACQMASTASPVENLCLSLQQGAEVSVKELDFLLTL repeats signature is in bold.
  • the conserved G-protein beta NDEVKVVDLAT GSVKNTLEGDSELIVALALTPDNKYLFS WD-40 repeat domains are ASRSTQIKFWD LSS ATCKRTWKAHNGPVADMACDASGGL underlined.
  • the conserved G-protein beta PARGSIDLDVARFMVTQKQKDNNDIHALSPSPSPSKKAY WD-40 repeat domains are QKEMADTLLKNAGAADNNCRILSFNGKSSTVSQGSQENV underlined.
  • the conserved G-protein beta QWLPDRHQSPTKDYSLQKMIVGTHTSGDEPNYLMIAEVQ WD-40 repeat domains are MPLQYSEDGNVGGFESTEAKVHIIQQINHEGEVNRAQYM underlined.
  • the conserved G-protein beta ALEWPSLTVQWLPPSCKQQQDIIKDDDIDHPNTQMVILG WD-40 repeat domains are THTSDNEPNYLILAEVQLHDGTEDEDGDGDVKRPQDKMK underlined.
  • the conserved G-protein beta SLTVQWLPDRHQSSTADYSLQKMIVGTHTSEDEPNYLMI WD-40 repeat domains are AEVQIPLQNSEDNIIGGFESTEA KVQIIQKINHEGEVNK underlined.
  • the conserved G-protein beta IYNCAKLIPVLVGPQMDKKIRALACWRDFTFAATGHDIA WD-40 repeat domains are VFRRAHQVATWSGHKAKVTLLLSFGQHVLSVDLEGCLFI underlined and the Trp-Asp (WD) WAVAEVNQN KPPIGQIQLGEKFSPSCIMHPDTYLNKVLI repeats signature is in bold.
  • the conserved G-protein beta SDDNEDSDEESEEMDTETDKNTDAVAKALAAANALGSQS WD-40 repeat domains are SDFQRQHKVDDIANGLKELDMDHYDDEDEGIDIFGSGSL underlined and the Trp-Asp (WD) GNCYYPANDMDPYLVEQDDDDEDEIEDMTIKPSDLIILS repeats signature is in bold.
  • the conserved eukaryotic AGEFTVTGNEEVVAIAEDDVNTGILSQDLFSSQDYCTPS protein kinase domain is QPQDSTDLDSKDKAPCPLSPVKSTIQRKRCRPELLSNPP underlined.
  • the conserved G-protein beta PPDPESKKMRISYKLNFEYGGGSGSEDQVPKRKESGAAQ WD-40 repeat domains are NQGQQAAGASNALALPGPEGSKIPPMEKSQNALTVGPSL underlined and the Trp-Asp (WD) RPQGLNDVGLHGKGTAIISASGSSDRNLSTSAIMERLPS repeats signature is in bold.
  • the conserved G-protein beta PPPPPPPQQQAAPAPAPAATRSSTSGSAGGRDRRPQQQH WD-40 repeat domains are AVDEKYARWKSLVPVLYDWLANHNLLWPSLSCRWGPQLE underlined.
  • the conserved G-protein beta LEWPSLTVQWLPDREEPPGKDYSVQKMILGTHTSDNEPN WD-40 repeat domains are YLMLAQVQLPLEDAENDARQYDDERGEIGGFGCANGKVQ underlined.
  • the conserved histone NESSIDDEEENLSDNVATNNMGTTPQGQACMAVTVEGIE deacetylase family domain is HANSVGCGRNGREGSEEVTAAEDMGHVSIENIREQGRNR underlined KSSEQLLALYEQEGLLEDDEDDDDVDWEPFEGVTVQMKW YCTNCTMANSDDSVHCDSCGEHRNSDILRQGFLASPYLP AESPSSSDVPDERLEESKCVMTTLTPSISPMIGVCCSSL QSE RRTVVGFDERMLLHSEIQMETYPHPERPDRLRAIAA SLRAAGLFPGKCFSIPAREATCEELQTIHSLEHVNAVES TSCGMLSHLSPDTYANEHSSLAARLAAGLCADLAKAIMT GQAQNGFALVRPPGHHAGVKDSMGFCLHNNAAIAVSASR VVGAKKVLIVDWDVHHGNGTQEIFEADQSVLYISLHRHG EGFYPGSGAVTEVGSSKGEGYSVNIPWKCGGVGDNDYIF AF
  • the conserved cyclophilin- KMELFADIVPRTAENFRQFCTGEYRKAGIPIG YKGCHFH type peptidyl-prolyl cis-trans RVIKDFMIQAG DFVKGDGSGCISIYGSKFEDENFIAKHT isomerase family domain is GPGLLSMANSGPNTNGCQFFLTCAKCDWLDNKHVVFGRV underlined and the cyclophilin- LGEGLLVLRKIENVQTGQHNRPKLPCVIAECGEM type peptidyl-prolyl cis-trans isomerase signature is in bold.
  • the conserved G-protein beta DARSKYEIWKRAPSSIQERRQRFLVRMGLANPSELGNQV WD-40 repeat domains are NSTSAESTCSTETANIPNGIERLRENSGAVLRTAGSSGR underlined.
  • the conserved G-protein beta LTRYGLSDIVNTLLGNDKPQPFDFLVESELVRTSLEKLL WD-40 repeat domains are LIKGISAEKILNIEYILAVVPPKQEEPSLHDDWVSVVDG underlined.
  • SYPNFIFSGSFDSIGRIWKGEGLCTHVLEGHRDAITSAA FIMPSDSSDSFIN LATASKDRTLRLWQF KPNEHMTNGKM VRPYKLLKGHTSSVQTVSACPRRNLICSGSWDCSIKIWQ TAGEMDIESNAGSVKKRKLEDSTEQIISQIEASRTLEGH
  • SQCVSSVVWLEKDT IYSASWDHSVRSWDV ETGVNSLTVG CRKALHCLSIGGEGSALIAAGGADSVLRIWDPRMPGTFT PILQLSSHKSWITACKWHPKSRHH LISASHDGTLKLWDV RSKVPLTTLEAHKDKVLCADWWKEDCVISGGADSTLQIF SNLNLT 237 The amino acid sequence
  • the conserved G-protein beta PQISTPGINQPGLTIPVPPEAAPLTASLVAASAGMPPAV WD-40 repeat domains are VPSFVRPAIVAHPSVMPPPSMPLAALPMPVASAVPVAAP underlined and the splicing factor HFPPSTPNDNSITPSMPVPTPIVASSSVPPSVTIPGIAP motif is in bold.
  • the conserved G-protein beta NMWA IGK PNAILSLSGHSSAVESVTFDSAEALVVAGAAS WD-40 repeat domains are GTIKLWD LEE AKIVRTLTGHRSNCISVDFHPFGEFFASG underlined and the Trp-Asp (WD) SLDTNLKIWD IRR KGCIHTYKGHTRGVNSIRFSPDGRWV repeats signature is in bold.
  • the conserved cyclin N- and SNINSNIIGAPPYPCAVNKRVLSEKNVNSENDLLNAAHR C-terminal family domains are PITRQFAAQMAYKQQLRPEENKRTTQSVSNPSKSEDCAI underlined.
  • the conserved GCN5-related N- KLSAANASAASAAAAAAAAAAAADDHAPPFPPSSISADT acetyltransferase family domain is RDGALTSNDDLESISARGGGAGDDSDDDSDDEEEDDGDN underlined and the bromodomain is DGGSSLRTFTAARLENVGPAAARNRKIKAESNATVKVEK in bold.
  • the conserved G-protein beta SGDSDGEEDDENMDAVASEKADEVSTALSAADALGRISK WD-40 repeat domains are VTKAGSGFEDIADGLRELDMDNYDEEDEDVKLFSTGLGD underlined.
  • EFRNI LASASADRQVKIWDV AAGKCNITMEHHTDKVQAV AWNHHAPQVLLSGSFDHSVVMKDGRIPSHSGYRWSVTAD
  • the conserved G-protein beta AAAAASLPFKKNYRSSQALQQFYAGGPFAVSSDGSFIAC WD-40 repeat domains are NCGDSIKIVDSSNASLRPSIDCGSDTITALSLSPDGKLL underlined.
  • ERGILRIWKSEGSVCLFKQEHSDVTVISDEDDSRSGFTA AVMLPLDQGLLCVTADQQQFLFYYPEKHPEGIFSLTLCRR LVGYNEEIVDMKFLGEEENFLAVATNLEQVRVYELASMS CSYVLAGHTETVLC
  • the conserved G-protein beta NLTSPSKSSSISDRFIPCRSSSRLHTFGLVERGSPVKEG WD-40 repeat domains are GNEAYSRLLKAELFGSDFGSLSPAGQGSPMSPSKNMLRF underlined.
  • KTESSGPNSPFSPSILRQDSGFSSEASTPPKPPRKVPKT PHKVLDAPSLQDDFYLNLVDWSSQNTLAVGLGTCVYLWS
  • the conserved G-protein beta GPAPAPAPASSSSLPSTTSPSAAGGAGKSSGLPSLSSSS WD-40 repeat domains are TAWLEGLRAGNPRAGREAGIGSRGGDGEDGGRAMIGPPR underlined.
  • Patent Patent Protein ORF SEQ ID Target Patent PEPTIDE Sequence start stop 261 CDK type A MGDGSLGSGGRGNSGGGGGGGSRPEWLQQYDLIGKIGEGTYGLVFLARIKHPST 387 1820 NRGKYIAIKKFKQSKDGDGVSPTAIREIMLLREISHENVVKLVNVHINPVDMSL YLAFDYADHDLYEIIRHHRDKVNQAINPYTVKSLLWQLLNGLNYLHSNWIIHRD LKPSNILVMGEGEEQGVVKIADFGLARVYQAPLKPLSDNGVVVTIWYRAPELLL GAKHYTSAVDMWAVGCIFAELLTLKPLFQGQEVKANPNPFQLDQLDKIFKVLGH PTQEKWPMLVNLPHWQSDVQHIQRHKYDDNALGNVVRLSSKNATFDLLSKMLEY DPQKRITAAQALEHEYFRMEPLPGRNALVPSSPGDKV
  • Cyclin B eucalyptusSpp_041006 Q40337 B-like e ⁇ 158 300 439 cyclin 22 Cyclin D eucalyptusSpp_006643 Q9SXN7 NtcycD3-1 1E ⁇ 73 177 404 protein 23 Cyclin D eucalyptusSpp_045338 Q8LK74 Cyclin D3.1 e ⁇ 101 190 332 protein.
  • SPTREMBL 37 Histone eucalyptusSpp_037831 Q9FML2 Histone 0 356 464 deacetylase deacetylase.
  • SPTREMBL 38 MAT1 CDK- eucalyptusSpp_034958 Q8LES8 Hypothetical 4E ⁇ 47 101 190 activating protein kinase assembly factor 39
  • Peptidylprolyl 0 329 392 isomerase cis- trans isomerase, chloroplast precursor 40 Peptidylprolyl 010310EGXD012820HT Q9FJL3 PEPTIDYLPROLYL 0 453 579 isomerase ISOMERASE 41 Peptidylprolyl 010310EGXD013036HT O82646 HYPOTHETICAL 0 302 521 isomerase 57.1 KDA PROTEIN (EC 5.2.1.8
  • WD40 repeat eucalyptusSpp_007518 Q93ZN5 AT4G00090/F6N15_8 0 311 436 protein 83 WD40 repeat eucalyptusSpp_007717 O82266 At2g47990 e ⁇ 180 327 528 protein protein (Hypothetical 58.9 kDa protein) 84 WD40 repeat eucalyptusSpp_007718 Q8RWD8 Hypothetical e ⁇ 173 278 350 protein protein.

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Abstract

Novel plant polysaccharide synthesis genes and polypeptides encoded by such genes are provided. These genes and polynucleotide sequences are useful regulating polysaccharide synthesis and plant phenotype. Moreover, these genes are useful for expression profiling of plant polysaccharide synthesis genes. The invention specifically provides cell cycle polynucleotide and polypeptide sequences isolated from Eucalyptus and Pinus.

Description

    CROSS REFERENCE TO RELATED APPLICATION
  • This application claims priority to U.S. provisional application Ser. No. 60/533,036, filed on Dec. 30, 2003, which is specifically incorporated in its entirety herein by reference.
  • FIELD OF THE INVENTION
  • The present invention relates generally to the field of plant cell cycle genes and polypeptides encoded by such genes, and the use of such polynucleotide and polypeptide sequences for regulating a plant cell cycle. The invention specifically provides cell cycle polynucleotide and polypeptide sequences isolated from Eucalyptus and Pinus and sequences related thereto.
  • BACKGROUND OF THE INVENTION
  • Cell growth and division are controlled by the temporal expression of different sets of genes, allowing the dividing cell to progress through the different phases of the cell cycle. Continued growth and organogesis in plants requires precise function of the cell cycle machinery. Plant development, which is directly affected by cell division rates and patterns, also is influenced by environmental factors, such as temperature, nutrient availability, light, etc. See Gastal and Nelon, Plant Physiol. 105:191-7 (1994), Ben-Haj-Sahal and Tardieu, Plant Physiol. 109:861-7 (1995), and Sacks et al., Plant Physiol. 114:519-27 (1997). Plant development and phenotype are connected with the cell cycle, and altering expression of the genes involved in the cell cycle can be a useful method of modifying plant development and altering plant phenotype.
  • The ability to alter expression of cell cycle genes is extremely powerful because the cell cycle drives plant development, including growth rates, responses to environmental cues, and resulting plant phenotype. Control of the plant cell cycle and phenotypes associated with alteration of cell cycle gene expression, in the vascular cambium, in particular, has applications for, inter alia, alteration of wood properties and, in particular, lumber and wood pulp properties. For example, improvements to wood pulp that can be effected by altering cell cycle gene expression include increased or decreased lignin and cellulose content, and altered length, diameter, and lumen diameter of cells. Manipulating the plant cell cycle, and in particular the cambium cell cycle (i.e. the rate and angle of cell division), can also engineer better lumber having increased dimensional stability, increased tensile strength, increased shear strength, increased compression strength, increased shock resistance, increased stiffness, increased or decreased hardness, decreased spirality, decreased shrinkage, and desirable characteristics with respect to weight, density, and specific gravity.
  • A. Cell Cycle Genes and Proteins
  • 1. Cyclin Dependent Protein Kinase
  • Progression through the cell cycle is regulated primarily by cyclin-dependent kinases (CDKs). CDKs are a conserved family of eukaryotic serine/threonine protein kinases, which require heterodimer formation with a cyclin subunit for activity. For review see, e.g. Joubes et al., Plant Mol. Biol. 43: 607-20 (2000), Stals and Inze, Trends Plant Sci. 6:359-64 (2001), and John et al., Protoplasma 216: 119-42 (2001).
  • The are five subclasses of CDK's, each having a different cyclin binding consensus sequence. In CDK type A the cyclin binding consensus sequence is PSTAIRE. Id. The cyclin binding consensus sequence in CDK types B-1, B-2, and C are PPTTLRE, PPTALRE, and PITAIRE, respectively. Joubes et al, Plant Physiol, 126: 1403-15 (2001).
  • Cell cycle progression is directed, in part, by changes in CDK activity. CDK activity is modulated by a number of different cell cycle protein components, such as changes in the abundance of individual cyclins due to changing rates of biosynthesis and proteolysis. Fluctuations in cyclin concentrations result in commensurate fluctuations in CDK activity. Cyclin accumulation is especially important in terminating the G1 phase of the cell cycle because DNA replication is initiated by an increase in CDK activity.
  • Activation of CDK also requires phosphorylation of a threonine residue within the T-loop of CDK by a CDK-activating kinase (CAK). Umeda et al., Proc. Nat'l Acad. Sci. U.S.A. 97: 13396-400 (2000). It was suggested by Yamaguchi et al., Plant J. 24: 11-20 (2000), that cyclin H is a regulatory subunit of CAK. CDK activity is further regulated by interaction with a CDK regulatory subunit, a small (70-100 AA) protein involved in cell cycle regulation.
  • A cell must exit the cell cycle in order to commit to differentiation, senescence or apoptosis. This process involves the down-regulation of CDK activities. CDK inhibitors (CKI) are low molecular weight proteins, which are important for cell cycle regulation and development. CKIs bind stoichiometrically to CDK and down-regulate the activity of CDKs.
  • Many biochemical properties of ICK1, the first plant CKI to be identified from Arabidopsis thaliana, are known. Wang et al., Nature 386:451-2 (1997) Wang et al., Plant J. 24: 613-23 (2000). ICK1 is expressed at low levels in many tissue types, and there can be a threshold level of ICK1 that must be overcome before a cell can enter the cell cycle. Wang et al., Plant J. 24: 613-23 (2000). ICK1 is induced by the plant growth regulator abscisic acid (ABA), which inhibits cell division by blocking DNA replication. When the expression of ICK1 increases, there is a corresponding decrease in Cdc2-like H1 histone activity. ICK1 has been shown to bind in vitro with the cyclins C2c2a and CycD3, and deletion experiments have identified different domain regions for these two interactions.
  • Altering the expression of CDK regulatory protein or a subunit thereof is known to cause changes in plant phenotype. Overexpression of the Arabidopsis CDK regulatory subunit, CKS1At, resulted in a reduction of leaf size, root growth rates and meristem size. Additionally, overexpression of CKS1At resulted in inhibition of cell-cycle progression, with an extension in the duration of the G1 and G2 phases of the cell cycle.
  • 2. Cyclins
  • Cyclins are positive regulatory subunits of cyclin-dependent kinase (CDK) enzymes and are required for CDK activity. Fowler et al., Mol. Biotech. 10, 123, 126. Cyclins and CDK complexes provide temporal regulation of transition through the cell cycle. Evidence also suggests that cyclins provide spatial regulation of specific CDK activity, differentially targeting the cytoskeleton, spindle, phragmoplast, nuclear envelope, and chromosomes.
  • Plant cyclins are classified into five major groups: A, B, C, D, and H. Renaudin et al., Plant Mol. Biol. 32: 1003-18 (1996) and Yamaguchi et al., (supra 2000). Cyclins can be divided into mitotic cyclins (A and B) and G1 cyclins.
  • The mitotic cyclins possess a consensus sequence (R-x-x-L-x-x-I-x-N) located at the N-terminal region, termed a destruction box, adjacent to a lysine-rich region. The destruction box and lysine-rich region target the mitotic cyclins for ubiquitin-dependent proteolysis during mitosis. Stals, supra at 361, and Fowler, supra at 126. The destruction box in A versus B cyclins differs slightly and this difference is thought to result in slightly different timing of degradation of A versus B cyclins. Fowler, supra at 126. A-type cyclins accumulate during the S, G2, and early M phase of the cell cycle, whereas B-type cyclins accumulate during the late G2 and early M phase. Mironov et al., Plant Cell 11: 509-22 (1999). Three subgroups of A-type cyclins are known in plants, but only one is known in animals. Cyclin A1 (cycA1;zm;1 from Zea cans) is most concentrated during cytokinesis at the microtubule-containing phragmoplast. Expression of cyclin A2 is upregulated by auxins in roots, and by cytokinins in the shoot apex. Abrahams et al., Biochim. Biophys. Acta 28: 1-2 (2001).
  • D-type cyclins, of which five subgroups are known, are thought to control the progression through the G1 phase in response to growth factors and nutrients. Riou-Khamlichi et al., Mol. Cell Biol. 20: 4513-21 (2000). For example, the expression of D-type cyclins is upregulated by sucrose as shown by an increase in cycD2 mRNA 30 minutes after sucrose exposure, and an increase in cycD3 four hours after sucrose exposure. This timing corresponds to early G1-phase and late G1-phase, respectively. Cockcroft et al., Nature 405: 575-9 (2000). Furthermore, in Arabidopsis, a D3 cyclin was shown to be upregulated by the brassinosteroid, epi-brassinolide.
  • Cyclin D2 proteins bind with CDKA to produce an active complex, which binds to and phosphorylates retinoblastoma-related protein (Rb). This process is found in actively proliferating tissue, suggesting it plays an important function during late G1- and early S-phase. Three different D3-type cyclins are active during tomato fruit development. These proteins all contain a retinoblastoma binding motif and a PEST-destruction motif. There are differences in the spatial and temporal expression of these D3 cyclins, inferring different roles during fruit development.
  • Overexpression of cyclin D was shown to increase overall growth rate. Over-expression of cyclin D2 in tobacco increases causes shortening the G1-phase which producing a faster rate of cell cycling.
  • C- and H-type cyclins were characterized in poplar (Populus tremula×tremuloides) and rice (Oryza sativa) but their exact function is still unclear. Putative cyclins with a lesser degree of peptide sequence conservation have also been identified. For example, Arabidopsis CycJ18 has only 20% identity with homologues over the cyclin box domain. CycJ18 is expressed predominantly in young seedlings. Arabidopsis F3O9.13 protein also has similarity to the cyclin family.
  • 3. Histone Acetyltransferase/Deacetyltransferase
  • Histone acetyltransferase (HA) and histone deacetyltransferase (HAD) control the net level of acetylation of histones. Histone acetylation and deacetylation are thought to exert their regulatory effects on gene expression by altering the accessibility of nucleosomal DNA to DNA-binding transcriptional activators, other chromatin-modifying enzymes or multi-subunit chromatin remodeling complexes capable of displacing nucleosomes. Lusser et al., Nucleic Acids Res. 27: 4427-35 (1999). Therefore, in general, the HDAs are involved in the repression of gene expression, while HAs are correlated with gene activation.
  • HA effects acetylation at the ε-amino group of conserved lysine residues clustered near the amino terminus of core histones which up-regulates gene expression.
  • HDAs remove acetyl groups from the core histones of the nucleosome. There are numerous family members in the HDA group, many of which are conserved throughout evolution. Lechner et al., Biochim Biophys Acta 5:181-8 (1996). HDAs function as part of multi-protein complexes facilitating chromatin condensation.
  • HDAs and HAs recognize highly distinct acetylation patterns on the nucleosome. It is thought that different types of HDAs interact with specific regions of the genome, to influence gene silencing.
  • Schultz et al., Genes Dev. 15: 428-43 (2001), demonstrated that the superfamily of Kruppel-associated-box zinc finger proteins (KRAB-ZFPs) are linked to the nucleosome remodeling and histone deacetylation complex via the PHD (plant homeodomain) and bromodomains of co-repressor KAP-1, to form a cooperative unit that is required for transcriptional repression. A maize HDAC (HD2) has been identified that has no sequence homology to other eukaryotic HDACs, but instead contains sequence similarity to peptidyl-prolyl cis-trans isomerases (PPIases).
  • The effects of interfering with histone deacetylation are discussed in e.g. Tian and Chen, Proc. Nat'l Acad. Sci. USA 98: 200-5 (2001).
  • 4. Peptidyl Prolyl Cis-Trans Isomerase
  • Peptidylprolyl isomerases (e.g., peptidylprolyl cis-trans isomerase, peptidyl-prolyl cis-trans isomerase, PPIase, rotamase, cyclophilin) catalyze the interconversion of peptide bonds between the cis and trans conformations at proline residues. Sheldon and Venis, Biochem J. 315: 965-70 (1996). This interconversion is thought to be the rate limiting step of protein folding. PPIases belong to a conserved family of proteins that are present in animals, fungi, bacteria and plants. PPIases are implicated in a number of responses including the response to environmental stress, calcium signals, transcriptional repression, cell cycle control, etc. Viaud, et al., Plant Cell 14: 917-30 (2002).
  • 5. Retinoblastoma-Related Protein
  • Retinoblastoma (Rb)-related protein putatively regulates progression of the cell cycle through the G1 phase and into S phase. Xie et al., EMBO J. 15: 4900-8 (1996) and Ach et al., Mol. Cell Biol. 17: 5077-86 (1997).
  • Although Rb is well-characterized in mammalian systems, the role of Rb-related proteins in regulation of G1 phase progression and S phase entry is not well characterized in plants. It is known, however, that RB-related protein functions through its association with various other cellular proteins involved in cell cycle regulation, such as the cyclins, WD40 proteins, Soni et al., Plant. Cell. 7:85-103 (1995); Grafi et al., Proc. Natl. Acad. Sci. U.S.A. 93:8962 (1996); Ach et al., Plant Cell 9:1595-606 (1997); Umen and Goodenough, Genes Dev. 15:1652-61 (2001); Mariconti et al., J. Biol. Chem. 277:9911-9 (2002).
  • 6. WD40 Repeat Protein
  • WD40 is a common repeating motif involved in many different protein-protein interactions. The WD40 domain is found in proteins having a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly. Goh et al., Eur. J. Biochem. 267: 434-49 (2000).
  • The WD40 domain, which is 40 residues long, typically contains a GH dipeptide 11-24 residues from the N-terminus and the WD dipeptide at the C-terminus. Id. Between the GH dipeptide and the WD dipeptide lies a conserved core which serves as a stable platform where proteins can bind either stably or reversibly. The core forms a propeller-like structure with several blades. Each blade is composed of a four-stranded anti-parallel β-sheet. Each WD40 sequence repeat forms the first three strands of one blade and the last strand in the next blade. The last C-terminal WD40 repeat completes the blade structure of the first WD40 repeat to create the closed ring propeller-structure. The residues on the top and bottom surface of the propeller are proposed to coordinate interactions with other proteins and/or small ligands.
  • Studies in yeast demonstrated that Cdc20, which contains the WD40 motif, is required for the proteolysis of mitotic cyclins. This process is mediated by an ubiquitin-protein ligase called anaphase-promoting complex (APC) or cyclosome. Following ubiquitination and proteolysis by the 26S proteasome, the cell can segregate chromosomes, and exit from mitosis. Cdc20 also contains a destruction-box domain.
  • 7. WEE1-Like Protein
  • WEE1 controls the activity of cyclin-dependent kinases. WEE1 itself is a serine/threonine kinase. Sorrell et al., Planta 215: 518-22 (2002). The enzymatic activity of these protein kinases is controlled by phosphorylation of specific residues in the activation segment of the catalytic domain, sometimes combined with reversible conformational changes in the C-terminal autoregulatory tail. This process is conserved among eukaryotes, from fungi to animals and plants. Similarly, there is a high degree of homology between WEE1 proteins from various organisms. For example, there is 50% identity between the protein kinase domains of the human and maize WEE1 proteins.
  • Expression of WEE1 is shown to occur only in actively dividing tissues and is believed to inhibit cell division by acting as a negative regulator of mitosis. WEE1 is believed to prevent entry from G2 to M by protecting the nucleus from cytoplasmically-activated cyclin B1-complexed CDC2 before the onset of mitosis. For example, over-expression of AtWEE1 (from Arabidopsis) and ZmWEE1 (from Zea cans) in fission yeast inhibits cell division which results in elongated cells. Sun et al., Proc. Nat'l Acad. Sci. USA 96: 4180-5 (1999).
  • B. Expression Profiling and Microarray Analysis in Plant Development
  • The multigenic control of plant phenotype presents difficulties in determining the genes responsible for phenotypic determination. One major obstacle to identifying genes and gene expression differences that contribute to phenotype in plants is the difficulty with which the expression of more than a handful of genes can be studied concurrently. Another difficulty in identifying and understanding gene expression and the interrelationship of the genes that contribute to plant phenotype is the high degree of sensitivity to environmental factors that plants demonstrate.
  • There have been recent advances using genome-wide expression profiling. In particular, the use of DNA microarrays has been useful to examine the expression of a large number of genes in a single experiment. Several studies of plant gene responses to developmental and environmental stimuli have been conducted using expression profiling. For example, microarray analysis was employed to study gene expression during fruit ripening in strawberry, Aharoni et al., Plant Physiol. 129:1019-1031 (2002), wound response in Arabodopsis, Cheong et al., Plant Physiol. 129:661-7 (2002), pathogen response in Arabodopsis, Schenk et al., Proc. Nat'l Acad. Sci. 97:11655-60 (2000), and auxin response in soybean, Thibaud-Nissen et al., Plant Physiol. 132:118. Whetten et al., Plant Mol. Biol. 47:275-91 (2001) discloses expression profiling of cell wall biosynthetic genes in Pinus taeda L. using cDNA probes. Whetten et al. examined genes which were differentially expressed between differentiating juvenile and mature secondary xylem. Additionally, to determine the effect of certain environmental stimuli on gene expression, gene expression in compression wood was compared to normal wood. 156 of the 2300 elements examined showed differential expression. Whetten, supra at 285. Comparison of juvenile wood to mature wood showed 188 elements as differentially expressed. Id. at 286.
  • Although expression profiling and, in particular, DNA microarrays provide a convenient tool for genome-wide expression analysis, their use has been limited to organisms for which the complete genome sequence or a large cDNA collection is available. See Hertzberg et al., Proc. Nat'l Acad. Sci. 98:14732-7 (2001a), Hertzberg et al., Plant J., 25:585 (2001b). For example, Whetten, supra, states, “A more complete analysis of this interesting question awaits the completion of a larger set of both pine and poplar ESTs.” Whetten et al. at 286. Furthermore, microarrays comprising cDNA or EST probes may not be able to distinguish genes of the same family because of sequence similarities among the genes. That is, cDNAs or ESTs, when used as microarray probes, may bind to more than one gene of the same family.
  • Methods of manipulating gene expression to yield a plant with a more desirable phenotype would be facilitated by a better understanding of cell cycle gene expression in various types of plant tissue, at different stages of plant development, and upon stimulation by different environmental cues. The ability to control plant architecture and agronomically important traits would be improved by a better understanding of how cell cycle gene expression effects formation of plant tissues, how cell cycle gene expression causes plant cells to enter or exit cell division, and how plant growth and the cell cycle are connected. Among the large number of genes, the expression of which can change during development of a plant, only a fraction are likely to effect phenotypic changes during any given stage of the plant development.
  • SUMMARY
  • Accordingly, there is a need for tools and methods useful in determining the changes in the expression of cell cycle genes that occur during the plant cell cycle. There is also a need for polynucleotides useful in such methods. There is a further need for methods which can correlate changes in cell cycle gene expression to phenotype or stage of plant development. There is a further need for methods of identifying cell cycle genes and gene products that impact plant phenotype, and that can be manipulated to obtain a desired phenotype.
  • In one aspect, the present invention provides an isolated polynucleotide comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof.
  • In another aspect, the present invention provides a DNA construct comprising at least one polynucleotide having the sequence of any one of SEQ ID NOs: 1-237 and conservative variants thereof.
  • Another aspect of the invention is a plant cell transformed with a DNA construct of comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof.
  • A further aspect of the invention is a transgenic plant comprising a plant cell transformed with a DNA construct comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof.
  • Another aspect of the invention is an isolated polynucleotide comprising a sequence encoding the catalytic or substrate-binding domain of a polypeptide selected from of any one of SEQ ID NOs: 261-497, wherein the polynucleotide encodes a polypeptide having the activity of said polypeptide selected from any one of SEQ ID NOs: 261-497.
  • A further aspect of the invention is a method of making a transformed plant comprising transforming a plant cell with a DNA construct comprising at least one polynucleotide having the sequence of any of SEQ ID NOs: 1-237; and culturing the transformed plant cell under conditions that promote growth of a plant.
  • In another aspect, the invention provides a wood obtained from a transgenic tree.
  • In a further aspect, the invention provides a wood pulp obtained from a transgenic tree which has been transformed with the DNA construct of the invention.
  • Another aspect of the invention is a method of making wood, comprising transforming a plant with a DNA construct comprising a polynucleotide having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof; culturing the transformed plant under conditions that promote growth of a plant; and obtaining wood from the plant.
  • The invention further provides a method of making wood pulp, comprising transforming a plant with a DNA construct comprising a polynucleotide having a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof; culturing the transformed plant under conditions that promote growth of a plant; and obtaining wood pulp from the plant.
  • In another aspect, the invention provides an isolated polypeptide comprising an amino acid sequence encoded by the isolated polynucleotide comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof.
  • The invention also provides, an isolated polypeptide comprising an amino acid sequence selected from the group consisting of 261-497.
  • The invention further provides a method of altering a plant phenotype of a plant, comprising altering expression in the plant of a polypeptide encoded by any one of SEQ ID NOs: 1-237.
  • In another aspect, the invention provides a polynucleotide comprising a nucleic acid selected from the group comprising of SEQ ID NOs: 471-697.
  • An aspect of the invention is a method of correlating gene expression in two different samples, comprising detecting a level of expression of one or more genes encoding a product encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof in a first sample; detecting a level of expression of the one or more genes in a second sample; comparing the level of expression of the one or more genes in the first sample to the level of expression of the one or more genes in the second sample; and correlating a difference in expression level of the one or more genes between the first and second samples.
  • A further aspect of the invention is a method of correlating the possession of a plant phenotype to the level of gene expression in the plant of one or more genes comprising detecting a level of expression of one or more genes encoding a product encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof in a first plant possessing a phenotype; detecting a level of expression of the one or more genes in a second plant lacking the phenotype; comparing the level of expression of the one or more genes in the first plant to the level of expression of the one or more genes in the second plant; and correlating a difference in expression level of the one or more genes between the first and second plants to possession of the phenotype.
  • In a further aspect, the invention provides a method of correlating gene expression to a stage of the cell cycle, comprising detecting a level of expression of one or more genes encoding a product encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 and conservative variants thereof in a first plant cell in a first stage of the cell cycle; detecting a level of expression of the one or more genes in a second plant cell in a second, different stage of the cell cycle; comparing the level of the expression of the one or more genes in the first plant cells to the level of expression of the one or more genes in the second plants cells; and correlating a difference in expression level of the one or more genes between the first and second samples to the first or second stage of the cell cycle.
  • An aspect of the invention is a combination for detecting expression of one or more genes, comprising two or more oligonucleotides, wherein each oligonucleotide is capable of hybridizing to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237.
  • Another aspect of the invention is a combination for detecting expression of one or more genes, comprising two or more oligonucleotides, wherein each oligonucleotide is capable of hybridizing to a nucleic acid sequence encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237.
  • The invention further provides a microarray comprising a combination for detecting expression of one or more genes, comprising two or more oligonucleotides, wherein each oligonucleotide is capable of hybridizing to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 or wherein each oligonucleotide is capable of hybridizing to a nucleic acid sequence encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237, wherein each of said two or more oligonucleotides occupies a unique location on said solid support.
  • In another aspect, the invention provides a method for detecting one or more genes in a sample, comprising contacting the sample with two or more oligonucleotides, wherein each oligonucleotide is capable of hybridizing to a gene comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 under standard hybridization conditions; and detecting the one or more genes of interest which are hybridized to the one or more oligonucleotides.
  • The invention also provides a method for detecting one or more nucleic acid sequences encoded by one or more genes in a sample, comprising contacting the sample with two or more oligonucleotides, wherein each oligonucleotide is capable of hybridizing to a nucleic acid sequence encoded by a gene comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-237 under standard hybridization conditions; and detecting the one or more nucleic acid sequences which are hybridized to the one or more oligonucleotides.
  • The invention further provides a kit for detecting gene expression comprising the microarray of the invention together with one or more buffers or reagents for a nucleotide hybridization reaction.
  • Other features, objects, and advantages of the present invention are apparent from the detailed description that follows. It should be understood, however, that the detailed description, while indicating preferred embodiments of the invention, are given by way of illustration only, not limitation. Various changes and modifications within the spirit and scope of the invention will be apparent to those skilled in the art from the detailed description.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1: Exemplary microarray sampling parameters.
  • FIG. 2: Plasmid map for pWVK202.
  • FIG. 3: Plasmid map for pGrowth14.
  • FIG. 4: Plasmid map for pGrowth15.
  • FIG. 5: Plasmid map for pGrowth16.
  • FIG. 6: Plasmid map for pGrowth18.
  • FIG. 7: Plasmid map for pGrowth19.
  • FIG. 8: Plasmid map for pGrowth20.
  • LIST OF TABLES
  • Table 1: shows genes having greater than doubled signal with any one sample as compared to the mean signal of the other three samples.
  • Table 2: identifies plasmid(s), genes, and Genesis ID numbers for constructs described in Example 17.
  • Table 3: Rooting medium for Populus deltoids.
  • Table 4: pGrowth information.
  • Table 5: shows genes having greater than doubled signal with any one sample as compared to the mean signal of the other three samples.
  • Table 6: Differentially expressed cDNAs.
  • Table 7: Consensus ID information.
  • Table 8: pGrowth information.
  • Table 9: Eucalyptus grandis cell cycle genes and proteins.
  • Table 10: Pinus radiata cell cycle genes and proteins.
  • Table 11: Annotated peptide sequences of the present invention.
  • Table 12: Eucalyptus in silico data.
  • Table 13: Pine in silico data.
  • Table 14: Oligo table.
  • Table 15: Peptide table.
  • Table 16: BLAST sequence alignment table.
  • DETAILED DESCRIPTION
  • The inventors have discovered novel isolated cell cycle genes and polynucleotides useful for identifying the multigenic factors that contribute to a phenotype and for manipulating gene expression to affect a plant phenotype. These genes, which are derived from plants of commercially important forestry genera, pine and eucalyptus, are involved in the plant cell cycle and are, at least in part, responsible for expression of phenotypic characteristics important in commercial wood, such as stiffness, strength, density, fiber dimensions, coarseness, cellulose and lignin content, and extractives content. Generally speaking, the genes and polynucleotides encode a protein which can be a cyclin, cyclin dependent kinase, cyclin dependent kinase inhibitor, histone acetyltransferase, histone deacetylase, peptidyl-prolyl cis-trans isomerase, retinoblastoma-related protein, WEE1-like protein, or WD40 repeat protein, or a catalytic domain thereof, or a polypeptide having the same function, and the invention further includes such proteins and polypeptides.
  • The methods of the present invention for selecting cell cycle gene sequences to target for manipulation will permit better design and control of transgenic plants with more highly engineered phenotypes. The ability to control plant architecture and agronomically important traits in commercially important forestry species will be improved by the information obtained from the methods, such as which genes affect which phenotypes, which genes affect entry into which stage of the cell cycle, which genes are active in which stage of plant development, and which genes are expressed in which tissue at a given point in the cell cycle or plant development.
  • Unless indicated otherwise, all technical and scientific terms are used herein in a manner that conforms to common technical usage. Generally, the nomenclature of this description and the described laboratory procedures, including cell culture, molecular genetics, and nucleic acid chemistry and hybridization, respectively, are well known and commonly employed in the art. Standard techniques are used for recombinant nucleic acid methods, oligonucleotide synthesis, cell culture, tissue culture, transformation, transfection, transduction, analytical chemistry, organic synthetic chemistry, chemical syntheses, chemical analysis, and pharmaceutical formulation and delivery. Generally, enzymatic reactions and purification and/or isolation steps are performed according to the manufacturers' specifications. Absent an indication to the contrary, the techniques and procedures in question are performed according to conventional methodology disclosed, for example, in Sambrook et al., MOLECULAR CLONING A LABORATORY MANUAL, 2d ed. (Cold Spring Harbor Laboratory Press, 1989), and CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, 1989). Specific scientific methods relevant to the present invention are discussed in more detail below. However, this discussion is provided as an example only, and does not limit the manner in which the methods of the invention can be carried out.
  • A. Plant Cell Cycle Genes and Proteins
  • 1. Cell Cycle Genes, Polynucleotide and Polypeptide Sequences
  • One aspect of the present invention relates to novel plant cell cycle genes and polypeptides encoded by such genes. As used herein, the term “plant cell cycle genes” refers to genes encoding proteins that function during the plant cell cycle, and the term “plant cell cycle proteins” refers to proteins that function during the plant cell cycle. There are several known families of plant cell cycle proteins, including cyclin, cyclin dependent kinase, cyclin dependent kinase inhibitor, histone acetyltransferase, histone deacetylase, peptidyl-prolyl cis-trans isomerase, retinoblastoma-related protein, WEE1-like protein, and WD40 repeat protein. Although there is significant sequence homology within each gene and protein family, each member of each family can display different biochemical properties and altering the expression of at least one of these genes can result in a different plant phenotype.
  • The present invention provides novel plant cell cycle genes and polynucleotides and novel cell cycle proteins and polypeptides. In accordance with one embodiment of the invention, the novel plant cell cycle genes are the same as those expressed in a wild-type plant of a species of Pinus or Eucalyptus. Exemplary novel plant cell cycle gene sequences of the invention are set forth in Tables 9 and 10, which depict Eucalyptus grandis sequences and Pinus radiata sequences, respectively. Corresponding gene products, i.e., oligonucleotides and polypeptides, are also listed in Tables 14, 15, and 16. The Sequence Listing in APPENDIX 1 provides the sequences of these aspects of the invention.
  • The sequences of the invention have cell cycle activity and encode proteins that are active in the cell cycle, such as proteins of the cell cycle families discussed above. As discussed in more detail below, manipulation of the expression of the cell cycle genes and polynucleotides, or manipulation of the activity of the encoded proteins and polypeptides, can result in a transgenic plant with a desired phenotype that differs from the phenotype of a wild-type plant of the same species.
  • Throughout this description, reference is made to cell cycle gene products. As used herein, a “cell cycle gene product” is a product encoded by a cell cycle gene, and includes both nucleotide products, such as RNA, and amino acid products, such as proteins and polypeptides. Examples of specific cell cycle genes of the invention include SEQ ID NOs: 1-237. Examples of specific cell cycle gene products of the invention include products encoded by any one of SEQ ID NOs: 1-237. Reference also is made herein to cell cycle proteins and cell cycle polypeptides. Examples of specific cell cycle proteins and polypeptides of the invention include polypeptides encoded by any of SEQ ID NOs: 1-237 or polypeptides comprising the amino acid sequence of any of SEQ ID NOs: 261-497. One aspect of the invention is directed to a subset of these cell cycle genes and cell cycle gene products, namely SEQ ID NOs: 1-12, 14-58, 60-62, 64-70, 72-75, 77-83, 85-86, 88-91, 93-119, 121-130, 132-148, 150-156, 158-191, 193-207, 209-218, 220-221, 223-231, 233-237, their respective conservative variants (as that term is defined below), and the nucleotide and amino acid products encoded thereby. Another aspect of the invention is directed to a subset of the cell cycle genes and cell cycle gene products, namely SEQ ID NOs: 1-12, 14, 16-26, 30-37, 40-41, 43-76, 78-103, 106, 108-113, 116-121, 124-125, 128-147, 150-152, 154-155, 161-162, 164-172, 174, 177-183, 185-191, 193-197, 200-204, 208-213, and 215-234 their respective conservative variants, and the nucleotide and amino acid products encoded thereby. A further aspect of the invention is directed to a subset of the cell cycle genes and cell cycle gene products, namely SEQ ID NOs: 1-12, 14, 16-26, 30-37, 40-41, 43-58, 60-62, 64-70, 72-75, 78-83, 85-86, 88-91, 93-103, 106, 108-113, 116-119, 121, 124-125, 128-130, 132-147, 150-152, 154-155, 161-162, 164-172, 174, 177-183, 185-191, 193-197, 200-204, 209-213, 215-218, 220-221, 223-231, and 233-234 their respective conservative variants, and the nucleotide and amino acid products encoded thereby.
  • The present invention also includes sequences that are complements, reverse sequences, or reverse complements to the nucleotide sequences disclosed herein.
  • The present invention also includes conservative variants of the sequences disclosed herein. The term “variant,” as used herein, refers to a nucleotide or amino acid sequence that differs in one or more nucleotide bases or amino acid residues from the reference sequence of which it is a variant.
  • Thus, in one aspect, the invention includes conservative variant polynucleotides. As used herein, the term “conservative variant polynucleotide” refers to a polynucleotide that hybridizes under stringent conditions to an oligonucleotide probe that, under comparable conditions, binds to the reference gene the conservative variant is a variant of. Thus, for example, a conservative variant of SEQ ID NO: 1 hybridizes under stringent conditions to an oligonucleotide probe that, under comparable conditions, binds to SEQ ID NO: 1. One aspect of the invention provides conservative variant polynucleotides that exhibit at least about 75% sequence identity to their respective reference sequences.
  • “Sequence identity” has an art-recognized meaning and can be calculated using published techniques. See COMPUTATIONAL MOLECULAR BIOLOGY, Lesk, ed. (Oxford University Press, 1988), BIOCOMPUTING: INFORMATICS AND GENOME PROJECTS, Smith, ed. (Academic Press, 1993), COMPUTER ANALYSIS OF SEQUENCE DATA, PART I, Griffin & Griffin, eds., (Humana Press, 1994), SEQUENCE ANALYSIS IN MOLECULAR BIOLOGY, Von Heinje ed., Academic Press (1987), SEQUENCE ANALYSIS PRIMER, Gribskov & Devereux, eds. (Macmillan Stockton Press, 1991), and Carillo & Lipton, SIAM J. Applied Math. 48: 1073 (1988). Methods commonly employed to determine identity or similarity between two sequences include but are not limited to those disclosed in GUIDE TO HUGE COMPUTERS, Bishop, ed., (Academic Press, 1994) and Carillo & Lipton, supra. Methods to determine identity and similarity are codified in computer programs. Preferred computer program methods to determine identity and similarity between two sequences include but are not limited to the GCG program package (Devereux et al., Nucleic Acids Research 12: 387 (1984)), BLASTP, BLASTN, FASTA (Atschul et al., J. Mol. Biol. 215: 403 (1990)), and FASTDB (Brutlag et al., Comp. App. Biosci. 6: 237 (1990)).
  • The invention includes conservative variant polynucleotides having a sequence identity that is greater than or equal to 99%, 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, 90%, 89%, 88%, 87%, 86%, 85%, 84%, 83%, 82%, 81%, 80%, 79%, 78%, 77%, 76%, 75%, 74%, 73%, 72%, 71%, 70%, 69%, 68%, 67%, 66%, 65%, 64%, 63%, 62%, 61%, or 60% to any one of SEQ ID NOs: 1 to 237. In such variants, differences between the variant and the reference sequence can occur at the 5′ or 3′ terminal positions of the reference nucleotide sequence or anywhere between those terminal positions, interspersed either individually among nucleotides in the reference sequence or in one or more contiguous groups within the reference sequence.
  • Additional conservative variant polynucleotides contemplated by and encompassed within the present invention include polynucleotides comprising sequences that differ from the polynucleotide sequences of SEQ ID NO: 1-237, or complements, reverse complements or reverse sequences thereof, as a result of deletions and/or insertions totaling less than 10% of the total sequence length.
  • The invention also includes conservative variant polynucleotides that, in addition to sharing a high degree of similarity in their primary structure (sequence) to SEQ ID NOs: 1 to 237, have at least one of the following features: (i) they contain an open reading frame or partial open reading frame encoding a polypeptide having substantially the same functional properties in the cell cycle as the polypeptide encoded by the reference polynucleotide, or (ii) they have nucleotide domains or encoded protein domains in common. The invention includes conservative variants of SEQ ID NOs: 1-237 that encode proteins having the enzyme or biological activity or binding properties of the protein encoded by the reference polynucleotide. Such conservative variants are functional variants, in that they have the enzymatic or binding activity of the protein encoded by the reference polynucleotide.
  • In accordance with the invention, polynucleotide variants can include a “shuffled gene” such as those described in e.g. U.S. Pat. Nos. 6,500,639, 6,500,617 6,436,675, 6,379,964, 6,352,859 6,335,198 6,326,204, and 6,287,862. A variant of a nucleotide sequence of the present invention also can be a polynucleotide modified as disclosed in U.S. Pat. No. 6,132,970, which is incorporated herein by reference.
  • In accordance with one embodiment, the invention provides a polynucleotide that encodes a cell cycle protein from one of the following families: cyclin, cyclin dependent kinase, cyclin dependent kinase inhibitor, histone acetyltransferase, histone deacetylase, peptidyl-prolyl cis-trans isomerase, retinoblastoma-related protein, WEE1-like protein, or WD40 repeat protein. SEQ ID NOs: 1-237 provide examples of such polynucleotides.
  • In accordance with another embodiment, a polynucelotide of the invention encodes the catalytic or protein binding domain of a polypeptide encoded by any of SEQ ID NOs: 1-237 or of a polypeptide comprising any of SEQ ID NOs: 261-497. The catalytic and protein binding domains of the cell cycle proteins of the invention are known in the art. The conserved sequences of these proteins are shown in Entries 1-195 as underlined, bold, and/or italicized text.
  • The invention also encompasses as conservative variants polynucleotides that differ from the sequences discussed above but that, as a consequence of the degeneracy of the genetic code, encode a polypeptide which is the same as that encoded by a polynucleotide of the present invention. The invention also includes as conservative variants polynucleotides comprising sequences that differ from the polynucleotide sequences discussed above as a result of substitutions that do not affect the amino acid sequence of the encoded polypeptide sequence, or that result in conservative substitutions in the encoded polypeptide sequence.
  • The present invention also includes an isolated polypeptide encoded by a polynucleotide comprising any of SEQ ID NOs: 1-237 or any of the conservative variants thereof discussed above. The invention also includes polypeptides comprising SEQ ID NOs: 261-497 and 495-497 and conservative variants of these polypeptides. Another aspect of the invention include polypeptides comprising SEQ ID NOs: 261-272, 274-318, 320-322, 324-330, 332-335, 337-343, 345-346, 348-351, 353-379, 381-390, 392-408, 410-416, 418-451, 453-467, 469-478, 480-481, 483-491, and 493-494 and conservative variants thereof. A further aspect of the invention includes polypeptides comprising SEQ ID NOs: 261-272, 274, 276-286, 289, 290-297, 300-301, 303-345, 347-363, 366, 368-373, 376-381, 384-385, 388-407, 410-412, 414-415, 420-422, 424-432, 434, 437-443, 445-451, 453-457, 460-464, 468-473, and 475-494 and conservative variants thereof. Another aspect of the invention includes polypeptides comprising SEQ ID NOs: 261-272, 274, 276-286, 290-297, 300-301, 303-318, 320-322, 324-330, 332-335, 337-343, 345, 348-351, 353-363, 366, 368-373, 376-381, 384-385, 388-390, 392-407, 410-412, 414-415, 421-422, 424-432, 434, 437-443, 445-451, 453-457, 460-464, 469-473, 475-478, 480-481, 483-491, and 493-494 and conservative variants thereof.
  • In accordance with the invention, a variant polypeptide or protein refers to an amino acid sequence that is altered by the addition, deletion or substitution of one or more amino acids.
  • The invention includes conservative variant polypeptides. As used herein, the term “conservative variant polypeptide” refers to a polypeptide that has similar structural, chemical or biological properties to the protein it is a conservative variant of. Guidance in determining which amino acid residues can be substituted, inserted, or deleted can be found using computer programs well known in the art such as Vector NTI Suite (InforMax, MD) software. In one embodiment of the invention, conservative variant polypeptides that exhibit at least about 75% sequence identity to their respective reference sequences.
  • Conservative variant protein includes an “isoform” or “analog” of the polypeptide. Polypeptide isoforms and analogs refers to proteins having the same physical and physiological properties and the same biological function, but whose amino acid sequences differs by one or more amino acids or whose sequence includes a non-natural amino acid.
  • Polypeptides comprising sequences that differ from the polypeptide sequences of SEQ ID NO: 261-497 as a result of amino acid substitutions, insertions, and/or deletions totaling less than 10% of the total sequence length are contemplated by and encompassed within the present invention.
  • One aspect of the invention provides conservative variant polypeptides that have the same function in the cell cycle as the proteins of which they are variants, as determined by one or more appropriate assays, such as those described below. The invention includes variant polypeptides that function as cell cycle proteins, such as those having the biological activity of cyclin, cyclin dependent kinase, cyclin dependent kinase inhibitor, histone acetyltransferase, histone deacetylase, peptidyl-prolyl cis-trans isomerase, retinoblastoma-related protein, WEE1-like protein, and WD40 repeat protein, and are thus capable of modulating the cell cycle in a plant. As discussed above, the invention includes variant polynucleotides that encode polypeptides that function as cell cycle proteins.
  • The activities and physical properties of cell cycle proteins can be examined using any method known in the art. The following examples of assay methods are not exhaustive and are included to provide some guidance in examining the activity and distinguishing protein characteristics of cell cycle protein variants.
  • CDK activity can be assessed using roscovitine as described in Yamaguchi et al., Proc. Natl. Acad. Sci. U.S.A. 100:8019 (2003). CDK histone kinase activity can be assayed using autoradiography to detect histone H1 phosphorylation by CDK as described in Joubés et al., Plant Physiol. 121:857 (1999).
  • CKI activity can be assayed using a variation of the method described in Zhou et al., Planta. 6:604 (2003). The modified method can employ co-transformation or subsequent transformations to identify the interaction of CKI and cyclins in vivo. For example, in the first transformation pine tissue can be transformed using the method described in U.S. Patent Application Publication No. 2002/0100083 using geneticin selection to obtain transgenic plants possessing cycD3 and cdc2a homologs. The second transformation can be performed using alpha-methyltryptophan as a selectable marker to obtain transformants having an ICK1 homologue as described in U.S. Provisional Application No. 60/476,189. Tissue capable of growing on both on geneticin and on alpha-methyltryptophan contains the ICK1 homologue and the cycD3 and cdc2a homologues. The CKI activity is determined by comparison of the phenotype of transformants having the cycD3 and cdc2a homologues to the transformants having ICK1 homologue and the cycD3 and cdc2a homologs.
  • Histone deacetylase activity can be assessed by complementation of the Arabidopsis mutants described in Tian et al., Genetics 165:399 (2003). Histone acetyltransferase activity can be assayed using anacardic acid as described in Balasubramanyam et al., J. Biol. Chem. 278:19134 (2003). Histone acetyltransferase also can be assayed using trichostatin A-treated plant lines as is described in Bhat et al., Plant J. 33:455 (2003). The plant lines described in Bhat et al., supra, also can be used to assay retinoblastoma-related proteins using the co-precipitation method described in Rossi et al., Plant Mol. Biol. 51:401 (2003).
  • Peptidyl-prolyl isomerase can be assayed as described in Edvardsson et al., FEBS Lett. 542:137 (2003). WD40 proteins can be evaluated based on the possession of the WD40 motif as well as their ability to interact with cdc2. WEE-1 can be assayed using any kinase activity assay known in the art.
  • 2. Methods of Using Cell Cycle Genes, Polynucleotide and Polypeptide Sequences
  • The present invention provides methods of using plant cell cycle genes and conservative variants thereof. The invention includes methods and constructs for altering expression of plant cell cycle genes and/or gene products for purposes including, but not limited to (i) investigating function during the cell cycle and ultimate effect on plant phenotype and (ii) to effect a change in plant phenotype. For example, the invention includes methods and tools for modifying wood quality, fiber development, cell wall polysaccharide content, fruit ripening, and plant growth and yield by altering expression of one or more plant cell cycle genes.
  • The invention comprises methods of altering the expression of any of the cell cycle genes and variants discussed above. Thus, for example, the invention comprises altering expression of a cell cycle gene present in the genome of a wild-type plant of a species of Eucalyptus or Pinus. In one embodiment, the cell cycle gene comprises a nucleotide sequence selected from SEQ ID NOs: 1-237, from the subset thereof comprising SEQ ID NOs: SEQ ID NOs: 1-12, 14-58, 60-62, 64-70, 72-75, 77-83, 85-86, 88-91, 93-119, 121-130, 132-148, 150-156, 158-191, 193-207, 209-218, 220-221, 223-231, and 233-237, from the subset thereof comprising SEQ ID NOs: 1-12, 14, 16-26, 30-37, 40-41, 43-76, 78-103, 106, 108-113, 116-121, 124-125, 128-147, 150-152, 154-155, 161-162, 164-172, 174, 177-183, 185-191, 193-197, 200-204, 208-213, and 215-234, from the subset thereof comprising SEQ ID NOs: 1-12, 14, 16-26, 30-37, 40-41, 43-58, 60-62, 64-70, 72-75, 78-83, 85-86, 88-91, 93-103, 106, 108-113, 116-119, 121, 124-125, 128-130, 132-147, 150-152, 154-155, 161-162, 164-172, 174, 177-183, 185-191, 193-197, 200-204, 209-213, 215-218, 220-221, 223-231, and 233-234, or the conservative variants thereof, as discussed above.
  • Techniques which can be employed in accordance with the present invention to alter gene expression, include, but are not limited to: (i) over-expressing a gene product, (ii) disrupting a gene's transcript, such as disrupting a gene's mRNA transcript; (iii) disrupting the function of a polypeptide encoded by a gene, or (iv) disrupting the gene itself Over-expression of a gene product, the use of antisense RNAs, ribozymes, and the use of double-stranded RNA interference (dsRNAi) are valuable techniques for discovering the functional effects of a gene and for generating plants with a phenotype that is different from a wild-type plant of the same species.
  • Over-expression of a target gene often is accomplished by cloning the gene or cDNA into an expression vector and introducing the vector into recipient cells. Alternatively, over-expression can be accomplished by introducing exogenous promoters into cells to drive expression of genes residing in the genome. The effect of over-expression of a given gene on cell function, biochemical and/or physiological properties can then be evaluated by comparing plants transformed to over-express the gene to plants that have not been transformed to over-express the gene.
  • Antisense RNA, ribozyme, and dsRNAi technologies typically target RNA transcripts of genes, usually mRNA. Antisense RNA technology involves expressing in, or introducing into, a cell an RNA molecule (or RNA derivative) that is complementary to, or antisense to, sequences found in a particular mRNA in a cell. By associating with the mRNA, the antisense RNA can inhibit translation of the encoded gene product. The use of antisense technology to reduce or inhibit the expression of specific plant genes has been described, for example in European Patent Publication No. 271988, Smith et al., Nature, 334:724-726 (1988); Smith et. al., Plant Mol. Biol., 14:369-379 (1990)).
  • A ribozyme is an RNA that has both a catalytic domain and a sequence that is complementary to a particular mRNA. The ribozyme functions by associating with the mRNA (through the complementary domain of the ribozyme) and then cleaving (degrading) the message using the catalytic domain.
  • RNA interference (RNAi) involves a post-transcriptional gene silencing (PTGS) regulatory process, in which the steady-state level of a specific mRNA is reduced by sequence-specific degradation of the transcribed, usually fully processed mRNA without an alteration in the rate of de novo transcription of the target gene itself. The RNAi technique is discussed, for example, in Elibashir, et al., Methods Enzymol. 26: 199 (2002); McManus & Sharp, Nature Rev. Genetics 3: 737 (2002); PCT application WO 01/75164; Martinez et al., Cell 110: 563 (2002); Elbashir et al., supra; Lagos-Quintana et al., Curr. Biol. 12: 735 (2002); Tuschl et al., Nat. Biotechnol. 20:446 (2002); Tuschl, Chembiochem. 2: 239 (2001); Harborth et al., J. Cell Sci. 114: 4557 (2001); et al., EMBO J. 20:6877 (2001); Lagos-Quintana et al., Science. 294: 8538 (2001); Hutvagner et al., loc cit, 834; Elbashir et al., Nature. 411: 494 (2001).
  • The present invention provides a DNA construct comprising at least one polynucleotide of SEQ ID NOs: 1-235 or conservative variants thereof, such as the conservative variants discussed above. Any method known in the art can be used to generate the DNA constructs of the present invention. See, e.g. Sambrook et al., supra.
  • The invention includes DNA constructs that optionally comprise a promoter. Any suitable promoter known in the art can be used. A promoter is a nucleic acid, preferably DNA, that binds RNA polymerase and/or other transcription regulatory elements. As with any promoter, the promoters of the invention facilitate or control the transcription of DNA or RNA to generate an mRNA molecule from a nucleic acid molecule that is operably linked to the promoter. The RNA can encode a protein or polypeptide or can encode an antisense RNA molecule or a molecule useful in RNAi. Promoters useful in the invention include constitutive promoters, inducible promoters, temporally regulated promoters and tissue-preferred promoters.
  • Examples of useful constitutive plant promoters include: the cauliflower mosaic virus (CaMV) 35S promoter, which confers constitutive, high-level expression in most plant tissues (Odel et al. Nature 313:810(1985)); the nopaline synthase promoter (An et al. Plant Physiol. 88:547 (1988)); and the octopine synthase promoter (Fromm et al., Plant Cell 1: 977 (1989)). It should be noted that, although the CaMV 35S promoter is commonly referred to as a constitutive promoter, some tissue preference can be seen. The use of CaMV 35S is envisioned by the present invention, regardless of any tissue preference which may be exhibited during use in the present invention.
  • Inducible promoters regulate gene expression in response to environmental, hormonal, or chemical signals. Examples of hormone inducible promoters include auxin-inducible promoters (Baumann et al. Plant Cell 11:323-334(1999)), cytokinin-inducible promoters (Guevara-Garcia, Plant Mol. Biol. 38:743-753(1998)), and gibberellin-responsive promoters (Shi et al. Plant Mol. Biol. 38:1053-1060(1998)). Additionally, promoters responsive to heat, light, wounding, pathogen resistance, and chemicals such as methyl jasmonate or salicylic acid, can be used in the DNA constructs and methods of the present invention.
  • Tissue-preferred promoters allow for preferred expression of polynucleotides of the invention in certain plant tissue. Tissue-preferred promoters are also useful for directing the expression of antisense RNA or siRNA in certain plant tissues, which can be useful for inhibiting or completely blocking the expression of targeted genes as discussed above. As used herein, vascular plant tissue refers to xylem, phloem or vascular cambium tissue. Other preferred tissue includes apical meristem, root, seed, and flower. In one aspect, the tissue-preferred promoters of the invention are either “xylem-preferred,” “cambium-preferred” or “phloem-preferred,” and preferentially direct expression of an operably linked nucleic acid sequence in the xylem, cambium or phloem, respectively. In another aspect, the DNA constructs of the invention comprise promoters that are tissue-specific for xylem, cambium or phloem, wherein the promoters are only active in the xylem, cambium or phloem.
  • A vascular-preferred promoter is preferentially active in any of the xylem, phloem or cambium tissues, or in at least two of the three tissue types. A vascular-specific promoter is specifically active in any of the xylem, phloem or cambium, or in at least two of the three. In other words, the promoters are only active in the xylem, cambium or phloem tissue of plants. Note, however, that because of solute transport in plants, a product that is specifically or preferentially expressed in a tissue may be found elsewhere in the plant after expression has occurred.
  • In another embodiment, the promoter is under temporal regulation, wherein the ability of the promoter to initiate expression is linked to factors such as the stage of the cell cycle or the stage of plant development. For example, the promoter of a cyclin D2 gene may be expressed only during the G1 and early S-phase, and the promoters of particular cyclin genes may be expressed only within the primary vascular poles of the developing seedling.
  • Additionally, the promoters of particular cell cycle genes may be expressed only within the cambium in developing secondary vasculature. Within the cambium, particular cell cycle gene promoters may be expressed exclusively in the stem or in the root. Moreover, the cell cycle promoters may be expressed only in the spring (for early wood formation) or only in the summer.
  • A promoter may be operably linked to the polynucleotide. As used in this context, operably linked refers to linking a polynucleotide encoding a structural gene to a promoter such that the promoter controls transcription of the structural gene. If the desired polynucleotide comprises a sequence encoding a protein product, the coding region can be operably linked to regulatory elements, such as to a promoter and a terminator, that bring about expression of an associated messenger RNA transcript and/or a protein product encoded by the desired polynucleotide. In this instance, the polynucleotide is operably linked in the 5′- to 3′-orientation to a promoter and, optionally, a terminator sequence.
  • Alternatively, the invention provides DNA constructs comprising a polynucleotide in an “antisense” orientation, the transcription of which produces nucleic acids that can form secondary structures that affect expression of an endogenous cell cycle gene in the plant cell. In another variation, the DNA construct may comprise a polynucleotide that yields a double-stranded RNA product upon transcription that initiates RNA interference of a cell cycle gene with which the polynucleotide is associated. A polynucleotide of the present invention can be positioned within a t-DNA, such that the left and right t-DNA border sequences flank or are on either side of the polynucleotide.
  • It should be understood that the invention includes DNA constructs comprising one or more of any of the polynucleotides discussed above. Thus, for example, a construct may comprise a t-DNA comprising one, two, three, four, five, six, seven, eight, nine, ten, or more polynucleotides.
  • The invention also includes DNA constructs comprising a promoter that includes one or more regulatory elements. Alternatively, the invention includes DNA constructs comprising a regulatory element that is separate from a promoter. Regulatory elements confer a number of important characteristics upon a promoter region. Some elements bind transcription factors that enhance the rate of transcription of the operably linked nucleic acid. Other elements bind repressors that inhibit transcription activity. The effect of transcription factors on promoter activity can determine whether the promoter activity is high or low, i.e. whether the promoter is “strong” or “weak.”
  • A DNA construct of the invention can include a nucleotide sequence that serves as a selectable marker useful in identifying and selecting transformed plant cells or plants. Examples of such markers include, but are not limited to, a neomycin phosphotransferase (nptII) gene (Potrykus et al., Mol. Gen. Genet. 199:183-188 (1985)), which confers kanamycin resistance. Cells expressing the nptII gene can be selected using an appropriate antibiotic such as kanamycin or G418. Other commonly used selectable markers include a mutant EPSP synthase gene (Hinchee et al., Bio/Technology 6:915-922 (1988)), which confers glyphosate resistance; and a mutant acetolactate synthase gene (ALS), which confers imidazolinone or sulphonylurea resistance (European Patent Application 154,204, 1985).
  • The present invention also includes vectors comprising the DNA constructs discussed above. The vectors can include an origin of replication (replicons) for a particular host cell. Various prokaryotic replicons are known to those skilled in the art, and function to direct autonomous replication and maintenance of a recombinant molecule in a prokaryotic host cell.
  • In one embodiment, the present invention utilizes a pWVR8 vector as described in U.S. Application No. 60/476,222, filed Jun. 6, 2003, or pART27 as described in Gleave, Plant Mol. Biol, 20:1203-27 (1992).
  • The invention also provides host cells which are transformed with the DNA constructs of the invention. As used herein, a host cell refers to the cell in which a polynucleotide of the invention is expressed. Accordingly, a host cell can be an individual cell, a cell culture or cells that are part of an organism. The host cell can also be a portion of an embryo, endosperm, sperm or egg cell, or a fertilized egg. In one embodiment, the host cell is a plant cell.
  • The present invention further provides transgenic plants comprising the DNA constructs of the invention. The invention includes transgenic plants that are angiosperms or gymnosperms. The DNA constructs of the present invention can be used to transform a variety of plants, both monocotyledonous (e.g. grasses, corn, grains, oat, wheat and barley), dicotyledonous (e.g., Arabidopsis, tobacco, legumes, alfalfa, oaks, eucalyptus, maple), and Gymnosperms (e.g., Scots pine; see Aronen, Finnish Forest Res. Papers, Vol. 595, 1996), white spruce (Ellis et al., Biotechnology 11:84-89, 1993), and larch (Huang et al., In Vitro Cell 27:201-207, 1991).
  • The plants also include turfgrass, wheat, maize, rice, sugar beet, potato, tomato, lettuce, carrot, strawberry, cassava, sweet potato, geranium, soybean, and various types of woody plants. Woody plants include trees such as palm oak, pine, maple, fir, apple, fig, plum and acacia. Woody plants also include rose and grape vines.
  • In one embodiment, the DNA constructs of the invention are used to transform woody plants, i.e., trees or shrubs whose stems live for a number of years and increase in diameter each year by the addition of woody tissue. The invention includes methods of transforming plants including eucalyptus and pine species of significance in the commercial forestry industry such as plants selected from the group consisting of Eucalyptus grandis and its hybrids, and Pinus taeda, as well as the transformed plants and wood and wood pulp derived therefrom. Other examples of suitable plants include those selected from the group consisting of Pinus banksiana, Pinus brutia, Pinus caribaea, Pinus clausa, Pinus contorta, Pinus coulteri, Pinus echinata, Pinus eldarica, Pinus ellioti, Pinus jeffreyi, Pinus lambertiana, Pinus massoniana, Pinus monticola, Pinus nigra, Pinus palustris, Pinus pinaster, Pinus ponderosa, Pinus radiata, Pinus resinosa, Pinus rigida, Pinus serotina, Pinus strobus, Pinus sylvestris, Pinus taeda, Pinus virginiana, Abies amabilis, Abies balsamea, Abies concolor, Abies grandis, Abies lasiocarpa, Abies magnifica, Abies procera, Chamaecyparis lawsoniona, Chamaecyparis nootkatensis, Chamaecyparis thyoides, Juniperus virginiana, Larix decidua, Larix laricina, Larix leptolepis, Larix occidentalis, Larix siberica, Libocedrus decurrens, Picea abies, Picea engelmanni, Picea glauca, Picea mariana, Picea pungens, Picea rubens, Picea sitchensis, Pseudotsuga menziesii, Sequoia gigantea, Sequoia sempervirens, Taxodium distichum, Tsuga canadensis, Tsuga heterophylla, Tsuga mertensiana, Thuja occidentalis, Thuja plicata, Eucalyptus alba, Eucalyptus bancroftii, Eucalyptus botryoides, Eucalyptus bridgesiana, Eucalyptus calophylla, Eucalyptus camaldulensis, Eucalyptus citriodora, Eucalyptus cladocalyx, Eucalyptus coccifera, Eucalyptus curtisii, Eucalyptus dalrympleana, Eucalyptus deglupta, Eucalyptus delagatensis, Eucalyptus diversicolor, Eucalyptus dunnii, Eucalyptus ficifolia, Eucalyptus globulus, Eucalyptus gomphocephala, Eucalyptus gunnii, Eucalyptus henryi, Eucalyptus laevopinea, Eucalyptus macarthurii, Eucalyptus macrorhyncha, Eucalyptus maculata, Eucalyptus marginata, Eucalyptus megacarpa, Eucalyptus melliodora, Eucalyptus nicholii, Eucalyptus nitens, Eucalyptus nova-angelica, Eucalyptus obliqua, Eucalyptus occidentalis, Eucalyptus obtusiflora, Eucalyptus oreades, Eucalyptus pauciflora, Eucalyptus polybractea, Eucalyptus regnans, Eucalyptus resinifera, Eucalyptus robusta, Eucalyptus rudis, Eucalyptus saligna, Eucalyptus sideroxylon, Eucalyptus stuartiana, Eucalyptus tereticornis, Eucalyptus torelliana, Eucalyptus urnigera, Eucalyptus urophylla, Eucalyptus viminalis, Eucalyptus viridis, Eucalyptus wandoo, and Eucalyptus youmanni.
  • As used herein, the term “plant” also is intended to include the fruit, seeds, flower, strobilus, etc. of the plant. A transformed plant of the current invention can be a direct transfectant, meaning that the DNA construct was introduced directly into the plant, such as through Agrobacterium, or the plant can be the progeny of a transfected plant. The second or subsequent generation plant can be produced by sexual reproduction, i.e., fertilization. Furthermore, the plant can be a gametophyte (haploid stage) or a sporophyte (diploid stage).
  • As used herein, the term “plant tissue” encompasses any portion of a plant, including plant cells. Plant cells include suspension cultures, callus, embryos, meristematic regions, callus tissue, leaves, roots, shoots, gametophytes, sporophytes, pollen, seeds and microspores. Plant tissues can be grown in liquid or solid culture, or in soil or suitable media in pots, greenhouses or fields. As used herein, “plant tissue” also refers to a clone of a plant, seed, progeny, or propagule, whether generated sexually or asexually, and descendents of any of these, such as cuttings or seeds.
  • In accordance with one aspect of the invention, a transgenic plant that has been transformed with a DNA construct of the invention has a phenotype that is different from a plant that has not been transformed with the DNA construct.
  • As used herein, “phenotype” refers to a distinguishing feature or characteristic of a plant which can be altered according to the present invention by integrating one or more DNA constructs of the invention into the genome of at least one plant cell of a plant. The DNA construct can confer a change in the phenotype of a transformed plant by modifying any one or more of a number of genetic, molecular, biochemical, physiological, morphological, or agronomic characteristics or properties of the transformed plant cell or plant as a whole.
  • In one embodiment, transformation of a plant with a DNA construct of the present invention can yield a phenotype including, but not limited to any one or more of increased drought tolerance, herbicide resistance, reduced or increased height, reduced or increased branching, enhanced cold and frost tolerance, improved vigor, enhanced color, enhanced health and nutritional characteristics, improved storage, enhanced yield, enhanced salt tolerance, enhanced resistance of the wood to decay, enhanced resistance to fungal diseases, altered attractiveness to insect pests, enhanced heavy metal tolerance, increased disease tolerance, increased insect tolerance, increased water-stress tolerance, enhanced sweetness, improved texture, decreased phosphate content, increased germination, increased micronutrient uptake, improved starch composition, improved flower longevity, production of novel resins, and production of novel proteins or peptides.
  • In another embodiment, the affected phenotype includes one or more of the following traits: propensity to form reaction wood, a reduced period of juvenility, an increased period of juvenility, self-abscising branches, accelerated reproductive development or delayed reproductive development, as compared to a plant of the same species that has not been transformed with the DNA construct.
  • In a further embodiment, the phenotype that is different in the transgenic plant includes one or more of the following: lignin quality, lignin structure, wood composition, wood appearance, wood density, wood strength, wood stiffness, cellulose polymerization, fiber dimensions, lumen size, other plant components, plant cell division, plant cell development, number of cells per unit area, cell size, cell shape, cell wall composition, rate of wood formation, aesthetic appearance of wood, formation of stem defects, average microfibril angle, width of the S2 cell wall layer, rate of growth, rate of root formation ratio of root to branch vegetative development, leaf area index, and leaf shape.
  • Phenotype can be assessed by any suitable means. The plants can be evaluated based on their general morphology. Transgenic plants can be observed with the naked eye, can be weighed and their height measured. The plant can be examined by isolating individual layers of plant tissue, namely phloem and cambium, which is further sectioned into meristematic cells, early expansion, late expansion, secondary wall formation, and late cell maturation. See, e.g., Hertzberg, supra. The plants also can be assessed using microscopic analysis or chemical analysis.
  • Microscopic analysis includes examining cell types, stage of development, and stain uptake by tissues and cells. Fiber morphology, such as fiber wall thickness and microfibril angle of wood pulp fibers can be observed using, for example, microscopic transmission ellipsometry. See Ye and Sundström, Tappi J., 80:181 (1997). Wood strength, density, and grain slope in wet wood and standing trees can be determined by measuring the visible and near infrared spectral data in conjunction with multivariate analysis. See, U.S. Patent Application Publication Nos. 2002/0107644 and 2002/0113212. Lumen size can be measured using scanning electron microscopy. Lignin structure and chemical properties can be observed using nuclear magnetic resonance spectroscopy as described in Marita et al., J. Chem. Soc., Perkin Trans. I 2939 (2001).
  • The biochemical characteristic of lignin, cellulose, carbohydrates and other plant extracts can be evaluated by any standard analytical method known including spectrophotometry, fluorescence spectroscopy, HPLC, mass spectroscopy, and tissue staining methods.
  • As used herein, “transformation” refers to a process by which a nucleic acid is inserted into the genome of a plant cell. Such insertion encompasses stable introduction into the plant cell and transmission to progeny. Transformation also refers to transient insertion of a nucleic acid, wherein the resulting transformant transiently expresses the nucleic acid. Transformation can occur under natural or artificial conditions using various methods well known in the art. Transformation can be achieved by any known method for the insertion of nucleic acid sequences into a prokaryotic or eukaryotic host cell, including Agrobacterium-mediated transformation protocols, viral infection, whiskers, electroporation, microinjection, polyethylene glycol-treatment, heat shock, lipofection, and particle bombardment. Transformation can also be accomplished using chloroplast transformation as described in e.g. Svab et al., Proc. Natl Acad. Sci. 87:8526-30 (1990).
  • In accordance with one embodiment of the invention, transformation in Eucalyptus is performed as described in U.S. Patent Application No. 60/476,222 (supra) which is incorporated herein by reference in its entirety. In accordance with another embodiment, transformation of Pinus is accomplished using the methods described in U.S. Patent Application Publication No. 2002/0100083.
  • Another aspect of the invention provides methods of obtaining wood and/or making wood pulp from a plant transformed with a DNA construct of the invention. Methods of producing a transgenic plant are provided above and are known in the art. A transformed plant can be cultured or grown under any suitable conditions. For example, pine can be cultured and grown as described in U.S. Patent Application Publication No. 2002/0100083. Eucalyptus can be cultured and grown as in, for example, Rydelius, et al., GROWING EUCALYPTUS FOR PULP AND ENERGY, presented at the Mechanization in Short Rotation, Intensive Culture Forestry Conference, Mobile, Ala., 1994. Wood and wood pulp can be obtained from the plant by any means known in the art.
  • As noted above, the wood or wood pulp obtained in accordance with this invention may demonstrate improved characteristics including, but not limited to any one or more of lignin composition, lignin structure, wood composition, cellulose polymerization, fiber dimensions, ratio of fibers to other plant components, plant cell division, plant cell development, number of cells per unit area, cell size, cell shape, cell wall composition, rate of wood formation, aesthetic appearance of wood, formation of stem defects, rate of growth, rate of root formation ratio of root to branch vegetative development, leaf area index, and leaf shape include increased or decreased lignin content, increased accessibility of lignin to chemical treatments, improved reactivity of lignin, increased or decreased cellulose content increased dimensional stability, increased tensile strength, increased shear strength, increased compression strength, increased shock resistance, increased stiffness, increased or decreased hardness, decreased spirality, decreased shrinkage, and differences in weight, density, and specific gravity.
  • B. Expression Profiling of Cell Cycle Genes
  • The present invention also provides methods and tools for performing expression profiling of cell cycle genes. Expression profiling is useful in determining whether genes are transcribed or translated, comparing transcript levels for particular genes in different tissues, genotyping, estimating DNA copy number, determining identity of descent, measuring mRNA decay rates, identifying protein binding sites, determining subcellular localization of gene products, correlating gene expression to a phenotype or other phenomenon, and determining the effect on other genes of the manipulation of a particular gene. Expression profiling is particularly useful for identifying gene expression in complex, multigenic events. For this reason, expression profiling is useful in correlating gene expression to plant phenotype and formation of plant tissues and the interconnection thereof to the cell cycle.
  • Only a small fraction of the genes of a plant's genome are expressed at a given time in a given tissue sample, and all of the expressed genes may not affect the plant phenotype. To identify genes capable of affecting a phenotype of interest, the present invention provides methods and tools for determining, for example, a gene expression profile at a given point in the cell cycle, a gene expression profile at a given point in plant development, and a gene expression profile a given tissue sample. The invention also provides methods and tools for identifying cell cycle genes whose expression can be manipulated to alter plant phenotype or to alter the biological activity of cell cycle gene products. In support of these methods, the invention also provides methods and tools that distinguish expression of different genes of the same family.
  • As used herein, “gene expression” refers to the process of transcription of a DNA sequence into an RNA sequence, followed by translation of the RNA into a protein, which may or may not undergo post-translational processing. Thus, the relationship between cell cycle stage and/or developmental stage and gene expression can be observed by detecting, quantitatively or qualitatively, changes in the level of an RNA or a protein. As used herein, the term “biological activity” includes, but is not limited to, the activity of a protein gene product, including enzyme activity.
  • The present invention provides oligonucleotides that are useful in these expression profiling methods. Each oligonucleotide is capable of hybridizing under a given set of conditions to a cell cycle gene or gene product. In one aspect of the invention, a plurality of oligonucleotides is provided, wherein each oligonucleotide hybridizes under a given set of conditions to a different cell cycle gene product. Examples of oligonucleotides of the present invention include SEQ ID NOs: 471-697. Each of the oligos of SEQ ID NOs 471-697 hybridizes under standard conditions to a different gene product of one of SEQ ID NOs: 1-237. The oligonucleotides of the invention are useful in determining the expression of one or more cell cycle genes in any of the above-described methods.
  • 1. Cell, Tissue, Nucleic Acid, and Protein Samples
  • Samples for use in methods of the present invention may be derived from plant tissue. Suitable plant tissues include, but are not limited to, somatic embryos, pollen, leaves, stems, calli, stolons, microtubers, shoots, xylem, male strolbili, pollen cones, vascular tissue, apical meristem, vascular cambium, xylem, root, flower, and seed.
  • According to the present invention “plant tissue” is used as described previously herein. Plant tissue can be obtained from any of the plants types or species described supra.
  • In accordance with one aspect of the invention, samples are obtained from plant tissue at different stages of the cell cycle, from plant tissue at different developmental stages, from plant tissue at various times of the year (e.g. spring versus summer), from plant tissues subject to different environmental conditions (e.g. variations in light and temperature) and/or from different types of plant tissue and cells. In accordance with one embodiment, plant tissue is obtained during various stages of maturity and during different seasons of the year. For example, plant tissue can be collected from stem dividing cells, differentiating xylem, early developing wood cells, differentiated spring wood cells, and differentiated summer wood cells. As another example, gene expression in a sample obtained from a plant with developing wood can be compared to gene expression in a sample obtained from a plant which does not have developing wood.
  • Differentiating xylem includes samples obtained from compression wood, side-wood, and normal vertical xylem. Methods of obtaining samples for expression profiling from pine and eucalyptus are known. See, e.g., Allona et al., Proc. Nat'l Acad. Sci. 95:9693-8 (1998) and Whetton et al., Plant Mol. Biol. 47:275-91, and Kirst et al., INT'L UNION OF FORESTRY RESEARCH ORGANIZATIONS BIENNIAL CONFERENCE, S6.8 (June 2003, Umea, Sweden).
  • In one embodiment of the invention, gene expression in one type of tissue is compared to gene expression in a different type of tissue or to gene expression in the same type of tissue in a difference stage of development. Gene expression can also be compared in one type of tissue which is sampled at various times during the year (different seasons). For example, gene expression in juvenile secondary xylem can be compared to gene expression in mature secondary xylem. Similarly, gene expression in cambium can be compared to gene expression in xylem. Furthermore, gene expression in apical meristems can be compared to gene expression in cambium.
  • In an alternative embodiment, differences in gene expression are determined as cells from different tissues advance during the cell cycle. In this method, the cells from the different tissues are synchronized and their gene expression is profiled. Methods of synchronizing the stage of cell cycle in a sample are known. These methods include, e.g., cold acclimation, photoperiod, and aphidicoline. See, e.g., Nagata et al., Int. Rev. Cytol. 132:1-30 (1992), Breyne and Zabeau, Curr. Opin. Plant Biol. 4:136-42, 140 (2001). A sample is obtained during a specific stage of the cell cycle and gene expression in that sample is compared to a sample obtained during a different stage of the cell cycle. For example, tissue can be examined in any of the phases of the cell cycle, such as mitosis, G1, G0, S, and G2. In particular, one can examine the changes in gene expression at the G1, G2, and metaphase checkpoints.
  • In another embodiment of the invention, a sample is obtained from a plant having a specific phenotype and gene expression in that sample is compared to a sample obtained from a plant of the same species that does not have that phenotype. For example, a sample can be obtained from a plant exhibiting a fast rate of growth and gene expression can be compared with that of a sample obtained from a plant exhibiting a normal or slow rate of growth. Differentially expressed genes identified from such a comparison can be correlated with growth rate and, therefore, useful for manipulating growth rate.
  • In a further embodiment, a sample is obtained from clonally propagated plants. In one embodiment the clonally propagated plants are of the species Pinus or Eucalyptus. Individual ramets from the same genotype can be sacrificed at different times of year. Thus, for any genotype there can be at least two genetically identical trees sacrificed, early in the season and late in the season. Each of these trees can be divided into juvenile (top) to mature (bottom) samples. Further, tissue samples can be divided into, for example, phloem to xylem, in at least 5 layers of peeling. Each of these samples can be evaluated for phenotype and gene expression. See Entry 196.
  • Where cellular components may interfere with an analytical technique, such as a hybridization assay, enzyme assay, a ligand binding assay, or a biological activity assay, it may be desirable to isolate the gene products from such cellular components. Gene products, including nucleic acid and amino acid gene products, can be isolated from cell fragments or lysates by any method known in the art.
  • Nucleic acids used in accordance with the invention can be prepared by any available method or process, or by other processes as they become known in the art. Conventional techniques for isolating nucleic acids are detailed, for example, in Tijssen, LABORATORY TECHNIQUES IN BIOCHEMISTRY AND MOLECULAR BIOLOGY: HYBRIDIZATION WITH NUCLEIC ACID PROBES, chapter 3 (Elsevier Press, 1993), Berger and Kimmel, Methods Enzymol. 152:1 (1987), and GIBCO BRL & LIFE TECHNOLOGIES TRIZOL RNA ISOLATION PROTOCOL, Form No. 3786 (2000). Techniques for preparing nucleic acid samples, and sequencing polynucleotides from pine and eucalyptus are known. See, e.g., Allona et al., supra and Whetton et al., supra, and U.S. Application No. 60/476,222.
  • A suitable nucleic acid sample can contain any type of nucleic acid derived from the transcript of a cell cycle gene, i.e., RNA or a subsequence thereof or a nucleic acid for which an mRNA transcribed from a cell cycle gene served as a template. Suitable nucleic acids include cDNA reverse-transcribed from a transcript, RNA transcribed from that cDNA, DNA amplified from the cDNA, and RNA transcribed from the amplified DNA. Detection of such products or derived products is indicative of the presence and/or abundance of the transcript in the sample. Thus, suitable samples include, but are not limited to, transcripts of the gene or genes, cDNA reverse-transcribed from the transcript, cRNA transcribed from the cDNA, DNA amplified from the genes, and RNA transcribed from amplified DNA. As used herein, the category of “transcripts” includes but is not limited to pre-mRNA nascent transcripts, transcript processing intermediates, and mature mRNAs and degradation products thereof.
  • It is not necessary to monitor all types of transcripts to practice the invention. For example, the expression profiling methods of the invention can be conducted by detecting only one type of transcript, such as mature mRNA levels only.
  • In one aspect of the invention, a chromosomal DNA or cDNA library (comprising, for example, fluorescently labeled cDNA synthesized from total cell mRNA) is prepared for use in hybridization methods according to recognized methods in the art. See Sambrook et al., supra.
  • In another aspect of the invention, mRNA is amplified using, e.g., the MessageAmp kit (Ambion). In a further aspect, the mRNA is labeled with a detectable label. For example, mRNA can be labeled with a fluorescent chromophore, such as CyDye (Amersham Biosciences).
  • In some applications, it may be desirable to inhibit or destroy RNase that often is present in homogenates or lysates, before use in hybridization techniques. Methods of inhibiting or destroying nucleases are well known. In one embodiment of the invention, cells or tissues are homogenized in the presence of chaotropic agents to inhibit nuclease. In another embodiment, RNase is inhibited or destroyed by heat treatment, followed by proteinase treatment.
  • Protein samples can be obtained by any means known in the art. Protein samples useful in the methods of the invention include crude cell lysates and crude tissue homogenates. Alternatively, protein samples can be purified. Various methods of protein purification well known in the art can be found in Marshak et al., STRATEGIES FOR PROTEIN PURIFICATION AND CHARACTERIZATION: A LABORATORY COURSE MANUAL (Cold Spring Harbor Laboratory Press 1996).
  • 2. Detecting Level of Gene Expression
  • For methods of the invention that comprise detecting a level of gene expression, any method for observing gene expression can be used, without limitation. Such methods include traditional nucleic acid hybridization techniques, polymerase chain reaction (PCR) based methods, and protein determination. The invention includes detection methods that use solid support-based assay formats as well as those that use solution-based assay formats.
  • Absolute measurements of the expression levels need not be made, although they can be made. The invention includes methods comprising comparisons of differences in expression levels between samples. Comparison of expression levels can be done visually or manually, or can be automated and done by a machine, using for example optical detection means. Subrahmanyam et al., Blood. 97: 2457 (2001); Prashar et al., Methods Enzymol. 303: 258 (1999). Hardware and software for analyzing differential expression of genes are available, and can be used in practicing the present invention. See, e.g., GenStat Software and GeneExpress® GX Explorer™ Training Manual, supra; Baxevanis & Francis-Ouellette, supra.
  • In accordance with one embodiment of the invention, nucleic acid hybridization techniques are used to observe gene expression. Exemplary hybridization techniques include Northern blotting, Southern blotting, solution hybridization, and S1 nuclease protection assays.
  • Nucleic acid hybridization typically involves contacting an oligonucleotide probe and a sample comprising nucleic acids under conditions where the probe can form stable hybrid duplexes with its complementary nucleic acid through complementary base pairing. For example, see PCT application WO 99/32660; Berger & Kimmel, Methods Enzymol. 152: 1 (1987). The nucleic acids that do not form hybrid duplexes are then washed away leaving the hybridized nucleic acids to be detected, typically through detection of an attached detectable label. The detectable label can be present on the probe, or on the nucleic acid sample. In one embodiment, the nucleic acids of the sample are detectably labeled polynucleotides representing the mRNA transcripts present in a plant tissue (e.g., a cDNA library). Detectable labels are commonly radioactive or fluorescent labels, but any label capable of detection can be used. Labels can be incorporated by several approached described, for instance, in WO 99/32660, supra. In one aspect RNA can be amplified using the MessageAmp kit (Ambion) with the addition of aminoallyl-UTP as well as free UTP. The aminoallyl groups incorporated into the amplified RNA can be reacted with a fluorescent chromophore, such as CyDye (Amersham Biosciences)
  • Duplexes of nucleic acids are destabilized by increasing the temperature or decreasing the salt concentration of the buffer containing the nucleic acids. Under low stringency conditions (e.g., low temperature and/or high salt) hybrid duplexes (e.g., DNA:DNA, RNA:RNA or RNA:DNA) will form even where the annealed sequences are not perfectly complementary. Thus, specificity of hybridization is reduced at lower stringency. Conversely, at higher stringency (e.g., higher temperature and/or lower salt and/or in the presence of destabilizing reagents) hybridization tolerates fewer mismatches.
  • Typically, stringent conditions for short probes (e.g., 10 to 50 nucleotide bases) will be those in which the salt concentration is at least about 0.01 to 1.0 M at pH 7.0 to 8.3 and the temperature is at least about 30° C. Stringent conditions can also be achieved with the addition of destabilizing agents such as formamide.
  • Under some circumstances, it can be desirable to perform hybridization at conditions of low stringency, e.g., 6×SSPE-T (0.9 M NaCl, 60 mM NaH2PO4, pH 7.6, 6 mM EDTA, 0.005% Triton) at 37° C., to ensure hybridization. Subsequent washes can then be performed at higher stringency (e.g., 1×SSPE-T at 37° C.) to eliminate mismatched hybrid duplexes. Successive washes can be performed at increasingly higher stringency (e.g., down to as low as 0.25×SSPE-T at 37° C. to 50° C.) until a desired level of hybridization specificity is obtained.
  • In general, standard conditions for hybridization is a compromise between stringency (hybridization specificity) and signal intensity. Thus, in one embodiment of the invention, the hybridized nucleic acids are washed at successively higher stringency conditions and read between each wash. Analysis of the data sets produced in this manner will reveal a wash stringency above which the hybridization pattern is not appreciably altered and which provides adequate signal for the particular oligonucleotide probes of interest. For example, the final wash may be selected as that of the highest stringency that produces consistent results and that provides a signal intensity greater than approximately 10% of the background intensity.
  • a. Oligonucleotide Probes
  • Oligonucleotide probes useful in nucleic acid hybridization techniques employed in the present invention are capable of binding to a nucleic acid of complementary sequence through one or more types of chemical bonds, usually through complementary base pairing via hydrogen bond formation. A probe can include natural bases (i.e., A, G, U, C or T) or modified bases (7-deazaguanosine, inosine, etc.). In addition, the nucleotide bases in the probes can be joined by a linkage other than a phosphodiester bond, so long as it does not interfere with hybridization. Thus, probes can be peptide nucleic acids in which the constituent bases are joined by peptide bonds rather than phosphodiester linkages.
  • Oligonucleotide probes can be prepared by any means known in the art. Probes useful in the present invention are capable of hybridizing to a nucleotide product of cell cycle genes, such as one of SEQ ID NOs: 1-237. Probes useful in the invention can be generated using the nucleotide sequences disclosed in SEQ ID NOs: 1-237. The invention includes oligonucleotide probes having at least a 2, 10,15, 20, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 100 nucleotide fragment of a corresponding contiguous sequence of any one of SEQ ID NOs: 1-237. The invention includes oligonucleotides of less than 2, 1, 0.5, 0.1, or 0.05 kb in length. In one embodiment, the oligonucleotide is 60 nucleotides in length.
  • Oligonucleotide probes can be designed by any means known in the art. See, e.g., Li and Stormo, Bioinformatics 17: 1067-76 (2001). Oligonucleotide probe design can be effected using software. Exemplary software includes ArrayDesigner, GeneScan, and ProbeSelect. Probes complementary to a defined nucleic acid sequence can be synthesized chemically, generated from longer nucleotides using restriction enzymes, or can be obtained using techniques such as polymerase chain reaction (PCR). PCR methods are well known and are described, for example, in Innis et al. eds., PCR PROTOCOLS: A GUIDE TO METHODS AND APPLICATIONS, Academic Press Inc. San Diego, Calif. (1990). The probes can be labeled, for example, with a radioactive, biotinylated, or fluorescent tag. Optimally, the nucleic acids in the sample are labeled and the probes are not labeled. Oligonucleotide probes generated by the above methods can be used in solution or solid support-based methods.
  • The invention includes oligonucleotide probes that hybridize to a product of the coding region or a 3′ untranslated region (3′ UTR) of a cell cycle gene. In one embodiment, the oligonucleotide probe hybridizes to the 3′UTR of any one of SEQ ID NOs: 1-237. The 3′ UTR is generally a unique region of the gene, even among members of the same family. Therefore, the probes capable of hybridizing to a product of the 3′ UTR can be useful for differentiating the expression of individual genes within a family where the coding region of the genes likely are highly homologous. This allows for the design of oligonucleotide probes to be used as members of a plurality of oligonucleotides, each capable of uniquely binding to a single gene. In another embodiment, the oligonucleotide probe comprises any one of SEQ ID NOs: 471-697. In another embodiment, the oligonucleotide probe consists of any one of SEQ ID NOs:471-697.
  • b. Oligonucleotide Array Methods
  • One embodiment of the invention employs two or more oligonucleotide probes in combination to detect a level of expression of one or more cell cycle genes, such as the genes of SEQ ID NOs: 1-237. In one aspect of this embodiment, the level of expression of two or more different genes is detected. The two or more genes may be from the same or different cell cycle gene families discussed above. Each of the two or more oligonucleotides may hybridize to a different one of the genes.
  • One embodiment of the invention employs two or more oligonucleotide probes, each of which specifically hybridize to a polynucleotide derived from the transcript of a gene provided by SEQ ID NOs: 1-237. Another embodiment employs two or more oligonucleotide probes, at least one of which comprises a nucleic acid sequence of SEQ ID NOs: 471-697. Another embodiment employs two or more oligonucleotide probes, at least one of which consists of SEQ ID NOs: 471-697.
  • The oligonucleotide probes may comprise from about 5 to about 60, or from about 5 to about 500, nucleotide bases, such as from about 60 to about 100 nucleotide bases, including from about 15 to about 60 nucleotide bases.
  • One embodiment of the invention uses solid support-based oligonucleotide hybridization methods to detect gene expression. Solid support-based methods suitable for practicing the present invention are widely known and are described, for example, in PCT application WO 95/11755; Huber et al., Anal. Biochem. 299: 24 (2001); Meiyanto et al., Biotechniques. 31: 406 (2001); Relogio et al., Nucleic Acids Res. 30:e51 (2002). Any solid surface to which oligonucleotides can be bound, covalently or non-covalently, can be used. Such solid supports include filters, polyvinyl chloride dishes, silicon or glass based chips, etc.
  • One embodiment uses oligonucleotide arrays, i.e. microarrays, which can be used to simultaneously observe the expression of a number of genes or gene products. Oligonucleotide arrays comprise two or more oligonucleotide probes provided on a solid support, wherein each probe occupies a unique location on the support. The location of each probe may be predetermined, such that detection of a detectable signal at a given location is indicative of hybridization to an oligonucleotide probe of a known identity. Each predetermined location can contain more than one molecule of a probe, but each molecule within the predetermined location has an identical sequence. Such predetermined locations are termed features. There can be, for example, from 2, 10, 100, 1,000, 2,000 or 5,000 or more of such features on a single solid support. In one embodiment, each oligonucleotide is located at a unique position on an array at least 2, at least 3, at least 4, at least 5, at least 6, or at least 10 times.
  • Oligonucleotide probe arrays for detecting gene expression can be made and used according to conventional techniques described, for example, in Lockhart et al., Nat'l Biotech. 14: 1675 (1996), McGall et al., Proc. Nat'l Acad. Sci. USA 93: 13555 (1996), and Hughes et al., Nature Biotechnol. 19:342 (2001). A variety of oligonucleotide array designs is suitable for the practice of this invention.
  • In one embodiment the one or more oligonucleotides include a plurality of oligonucleotides that each hybridize to a different gene expressed in a particular tissue type. For example, the tissue can be developing wood.
  • In one embodiment, a nucleic acid sample obtained from a plant can be amplified and, optionally labeled with a detectable label. Any method of nucleic acid amplification and any detectable label suitable for such purpose can be used. For example, amplification reactions can be performed using, e.g. Ambion's MessageAmp, which creates “antisense” RNA or “aRNA” (complementary in nucleic acid sequence to the RNA extracted from the sample tissue). The RNA can optionally be labeled using CyDye fluorescent labels. During the amplification step, aaUTP is incorporated into the resulting aRNA. The CyDye fluorescent labels are coupled to the aaUTPs in a non-enzymatic reaction. Subsequent to the amplification and labeling steps, labeled amplified antisense RNAs are precipitated and washed with appropriate buffer, and then assayed for purity. For example, purity can be assay using a NanoDrop spectrophotometer. The nucleic acid sample is then contacted with an oligonucleotide array having, attached to a solid substrate (a “microarray slide”), oligonucleotide sample probes capable of hybridizing to nucleic acids of interest which may be present in the sample. The step of contacting is performed under conditions where hybridization can occur between the nucleic acids of interest and the oligonucleotide probes present on the array. The array is then washed to remove non-specifically bound nucleic acids and the signals from the labeled molecules that remain hybridized to oligonucleotide probes on the solid substrate are detected. The step of detection can be accomplished using any method appropriate to the type of label used. For example, the step of detecting can accomplished using a laser scanner and detector. For example, on can use and Axon scanner which optionally uses GenePix Pro software to analyze the position of the signal on the microarray slide.
  • Data from one or more microarray slides can analyzed by any appropriate method known in the art.
  • Oligonucleotide probes used in the methods of the present invention, including microarray techniques, can be generated using PCR. PCR primers used in generating the probes are chosen, for example, based on the sequences of SEQ ID NOs:1-237, to result in amplification of unique fragments of the cell cycle genes (i.e., fragments that hybridize to only one polynucleotide of any one of SEQ ID NOs: 1-237 under standard hybridization conditions). Computer programs are useful in the design of primers with the required specificity and optimal hybridization properties. For example, Li and Stormo, supra at 1075, discuss a method of probe selection using ProbeSelect which selects an optimum oligonucleotide probe based on the entire gene sequence as well as other gene sequences to be probed at the same time.
  • In one embodiment, oligonucleotide control probes also are used. Exemplary control probes can fall into at least one of three categories referred to herein as (1) normalization controls, (2) expression level controls and (3) negative controls. In microarray methods, one or more of these control probes may be provided on the array with the inventive cell cycle gene-related oligonucleotides.
  • Normalization controls correct for dye biases, tissue biases, dust, slide irregularities, malformed slide spots, etc. Normalization controls are oligonucleotide or other nucleic acid probes that are complementary to labeled reference oligonucleotides or other nucleic acid sequences that are added to the nucleic acid sample to be screened. The signals obtained from the normalization controls, after hybridization, provide a control for variations in hybridization conditions, label intensity, reading efficiency and other factors that can cause the signal of a perfect hybridization to vary between arrays. In one embodiment, signals (e.g., fluorescence intensity or radioactivity) read from all other probes used in the method are divided by the signal from the control probes, thereby normalizing the measurements.
  • Virtually any probe can serve as a normalization control. Hybridization efficiency varies, however, with base composition and probe length. Preferred normalization probes are selected to reflect the average length of the other probes being used, but they also can be selected to cover a range of lengths. Further, the normalization control(s) can be selected to reflect the average base composition of the other probes being used. In one embodiment, only one or a few normalization probes are used, and they are selected such that they hybridize well (i.e., without forming secondary structures) and do not match any test probes. In one embodiment, the normalization controls are mammalian genes.
  • Expression level controls probes hybridize specifically with constitutively expressed genes present in the biological sample. Virtually any constitutively expressed gene provides a suitable target for expression level control probes. Typically, expression level control probes have sequences complementary to subsequences of constitutively expressed “housekeeping genes” including, but not limited to certain photosynthesis genes.
  • “Negative control” probes are not complementary to any of the test oligonucleotides (i.e., the inventive cell cycle gene-related oligonucleotides), normalization controls, or expression controls. In one embodiment, the negative control is a mammalian gene which is not complementary to any other sequence in the sample.
  • The terms “background” and “background signal intensity” refer to hybridization signals resulting from non-specific binding or other interactions between the labeled target nucleic acids (i.e., mRNA present in the biological sample) and components of the oligonucleotide array. Background signals also can be produced by intrinsic fluorescence of the array components themselves.
  • A single background signal can be calculated for the entire array, or a different background signal can be calculated for each target nucleic acid. In a one embodiment, background is calculated as the average hybridization signal intensity for the lowest 5 to 10 percent of the oligonucleotide probes being used, or, where a different background signal is calculated for each target gene, for the lowest 5 to 10 percent of the probes for each gene. Where the oligonucleotide probes corresponding to a particular cell cycle gene hybridize well and, hence, appear to bind specifically to a target sequence, they should not be used in a background signal calculation. Alternatively, background can be calculated as the average hybridization signal intensity produced by hybridization to probes that are not complementary to any sequence found in the sample (e.g., probes directed to nucleic acids of the opposite sense or to genes not found in the sample). In microarray methods, background can be calculated as the average signal intensity produced by regions of the array that lack any oligonucleotides probes at all.
  • c. PCR-Based Methods
  • In another embodiment, PCR-based methods are used to detect gene expression. These methods include reverse-transcriptase-mediated polymerase chain reaction (RT-PCR) including real-time and endpoint quantitative reverse-transcriptase-mediated polymerase chain reaction (Q-RTPCR). These methods are well known in the art. For example, methods of quantitative PCR can be carried out using kits and methods that are commercially available from, for example, Applied BioSystems and Stratagene®. See also Kochanowski, QUANTITATIVE PCR PROTOCOLS (Humana Press, 1999); Innis et al., supra.; Vandesompele et al., Genome Biol. 3: RESEARCH0034 (2002); Stein, Cell Mol. Life Sci. 59: 1235 (2002).
  • Gene expression can also be observed in solution using Q-RTPCR. Q-RTPCR relies on detection of a fluorescent signal produced proportionally during amplification of a PCR product. See Innis et al., supra. Like the traditional PCR method, this technique employs PCR oligonucleotide primers, typically 15-30 bases long, that hybridize to opposite strands and regions flanking the DNA region of interest. Additionally, a probe (e.g., TaqMan®, Applied Biosystems) is designed to hybridize to the target sequence between the forward and reverse primers traditionally used in the PCR technique. The probe is labeled at the 5′ end with a reporter fluorophore, such as 6-carboxyfluorescein (6-FAM) and a quencher fluorophore like 6-carboxy-tetramethyl-rhodamine (TAMRA). As long as the probe is intact, fluorescent energy transfer occurs which results in the absorbance of the fluorescence emission of the reporter fluorophore by the quenching fluorophore. As Taq polymerase extends the primer, however, the intrinsic 5′ to 3′ nuclease activity of Taq degrades the probe, releasing the reporter fluorophore. The increase in the fluorescence signal detected during the amplification cycle is proportional to the amount of product generated in each cycle.
  • The forward and reverse amplification primers and internal hybridization probe is designed to hybridize specifically and uniquely with one nucleotide derived from the transcript of a target gene. In one embodiment, the selection criteria for primer and probe sequences incorporates constraints regarding nucleotide content and size to accommodate TaqMan® requirements.
  • SYBR Green® can be used as a probe-less Q-RTPCR alternative to the Taqman®-type assay, discussed above. ABI PRISM® 7900 SEQUENCE DETECTION SYSTEM USER GUIDE APPLIED BIOSYSTEMS, chap. 1-8, App. A-F. (2002).
  • A device measures changes in fluorescence emission intensity during PCR amplification. The measurement is done in “real time,” that is, as the amplification product accumulates in the reaction. Other methods can be used to measure changes in fluorescence resulting from probe digestion. For example, fluorescence polarization can distinguish between large and small molecules based on molecular tumbling (see U.S. Pat. No. 5,593,867).
  • d. Protein Detection Methods
  • Proteins can be observed by any means known in the art, including immunological methods, enzyme assays and protein array/proteomics techniques.
  • Measurement of the translational state can be performed according to several protein methods. For example, whole genome monitoring of protein—the “proteome”—can be carried out by constructing a microarray in which binding sites comprise immobilized, preferably monoclonal, antibodies specific to a plurality of proteins having an amino acid sequence of any of SEQ ID NOs: 261-497 or proteins encoded by the genes of SEQ ID NOs:1-237 or conservative variants thereof. See Wildt et al., Nature Biotechnol. 18: 989 (2000). Methods for making polyclonal and monoclonal antibodies are well known, as described, for instance, in Harlow & Lane, ANTIBODIES: A LABORATORY MANUAL (Cold Spring Harbor Laboratory Press, 1988).
  • Alternatively, proteins can be separated by two-dimensional gel electrophoresis systems. Two-dimensional gel electrophoresis is well-known in the art and typically involves isoelectric focusing along a first dimension followed by SDS-PAGE electrophoresis along a second dimension. See, e.g., Hames et al, GEL ELECTROPHORESIS OF PROTEINS: A PRACTICAL APPROACH (IRL Press, 1990). The resulting electropherograms can be analyzed by numerous techniques, including mass spectrometric techniques, western blotting and immunoblot analysis using polyclonal and monoclonal antibodies, and internal and N-terminal micro-sequencing.
  • 3. Correlating Gene Expression to Phenotype and Tissue Development
  • As discussed above, the invention provides methods and tools to correlate gene expression to plant phenotype. Gene expression may be examined in a plant having a phenotype of interest and compared to a plant that does not have the phenotype or has a different phenotype. Such a phenotype includes, but is not limited to, increased drought tolerance, herbicide resistance, reduced or increased height, reduced or increased branching, enhanced cold and frost tolerance, improved vigor, enhanced color, enhanced health and nutritional characteristics, improved storage, enhanced yield, enhanced salt tolerance, enhanced resistance of the wood to decay, enhanced resistance to fungal diseases, altered attractiveness to insect pests, enhanced heavy metal tolerance, increased disease tolerance, increased insect tolerance, increased water-stress tolerance, enhanced sweetness, improved texture, decreased phosphate content, increased germination, increased micronutrient uptake, improved starch composition, improved flower longevity, production of novel resins, and production of novel proteins or peptides.
  • In another embodiment, the phenotype includes one or more of the following traits: propensity to form reaction wood, a reduced period of juvenility, an increased period of juvenility, self-abscising branches, accelerated reproductive development or delayed reproductive development.
  • In a further embodiment, the phenotype that is differs in the plants compares includes one or more of the following: lignin quality, lignin structure, wood composition, wood appearance, wood density, wood strength, wood stiffness, cellulose polymerization, fiber dimensions, lumen size, other plant components, plant cell division, plant cell development, number of cells per unit area, cell size, cell shape, cell wall composition, rate of wood formation, aesthetic appearance of wood, formation of stem defects, average microfibril angle, width of the S2 cell wall layer, rate of growth, rate of root formation ratio of root to branch vegetative development, leaf area index, and leaf shape.
  • Phenotype can be assessed by any suitable means as discussed above.
  • In a further embodiment, gene expression can be correlated to a given point in the cell cycle, a given point in plant development, and in a given tissue sample. Plant tissue can be examined at different stages of the cell cycle, from plant tissue at different developmental stages, from plant tissue at various times of the year (e.g. spring versus summer), from plant tissues subject to different environmental conditions (e.g. variations in light and temperature) and/or from different types of plant tissue and cells. In accordance with one embodiment, plant tissue is obtained during various stages of maturity and during different seasons of the year. For example, plant tissue can be collected from stem dividing cells, differentiating xylem, early developing wood cells, differentiated spring wood cells, differentiated summer wood cells.
  • It will be apparent to those skilled in the art that various modifications and variations can be made in the methods and compositions of the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention cover the modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents.
  • The following examples are given to illustrate the present invention. It should be understood, however, that the invention is not to be limited to the specific conditions or details described in these examples. Throughout the specification, any and all references to a publicly available document, including a U.S. patent, are specifically incorporated by reference.
  • Examples Example 1
  • Example 1 illustrates a procedure for RNA extraction and purification, which is particularly useful for RNA obtained from conifer needle, xylem, cambium, and phloem.
  • Tissue is obtained from conifer needle, xylem, cambium or phloem. The tissue is frozen in liquid nitrogen and ground. The total RNA is extracted using Concert Plant RNA reagent (Invitrogen). The resulting RNA sample is extracted into phenol:chloroform and treated with DNase. The RNA is then incubated at 65° C. for 2 minutes followed by centrifugation at 4° C. for 30 minutes. Following centrifugation, the RNA is extracted into phenol at least 10 times to remove contaminants.
  • The RNA is further cleaned using RNeasy columns (Qiagen). The purified RNA is quantified using RiboGreen reagent (Molecular Probes) and purity assessed by gel electrophoresis.
  • RNA is then amplified using MessageAmp (Ambion). Aminoallyl-UTP and free UTP are added to the in vitro transcription of the purified RNA at a ratio of 4:1 aminoallyl-UTP-to-UTP. The aminoallyl-UTP is incorporated into the new RNA strand as it is transcribed. The amino-allyl group is then reacted with Cy dyes to attach the colorimetric label to the resulting amplified RNA using the Amersham procedure modified for use with RNA. Unincorporated dye is removed by ethanol precipitation. The labeled RNA is quantified spectrophotometrically (NanoDrop). The labeled RNA is fragmented by heating to 95° C. as described in Hughes et al., Nature Biotechnol. 19:342 (2001).
  • Example 2
  • Example 2 illustrates how cell cycle genes important for wood development in Pinus radiata can be determined and how oligonucleotides which uniquely bind to those genes can be designed and synthesized for use on a microarray.
  • Pine trees of the species Pinus radiata are grown under natural light conditions. Tissue samples are prepared as described in, e.g., Sterky et al., Proc. Nat'l Acad. Sci. 95:13330 (1998). Specifically, tissue samples are collected from woody trees having a height of 5 meters. Tissue samples of the woody trees are prepared by taking tangential sections through the cambial region of the stem. The stems are sectioned horizontally into sections ranging from juvenile (top) to mature (bottom). The stem sections separated by stage of development are further separated into 5 layers by peeling into sections of phloem, differentiating phloem, cambium, differentiating xylem, developing xylem, and mature xylem. Tissue samples, including leaves, buds, shoots, and roots are also prepared from seedlings of the species Pinus radiata.
  • RNA is isolated and ESTs generated as described in Example 1 or Sterky et al., supra. The nucleic acid sequences of ESTs derived from samples containing developing wood are compared with nucleic acid sequences of genes known to be involved in the plant cell cycle. ESTs from samples that do not contain developing wood are also compared with sequences of genes known to be involved in the plant cell cycle. An in silico hybridization analysis is performed using BLAST (NCBI). Sequences from among the known cell cycle genes that show hybridization in silico to ESTs made from samples containing developing wood, but that do not hybridize to ESTs from samples not containing developing wood are selected for further examination.
  • cDNA clones containing sequences that hybridize to the genes showing wood-preferred expression are selected from cDNA libraries using techniques well known in the art of molecular biology. Using the sequence information, oligonucleotides are designed such that each oligonucleotide is specific for only one cDNA sequence in the library. The oligonucleotide sequences are provided in Table 14. 60-mer oligonucleotide probes are designed using the method of Li and Stormo, supra or using software such as ArrayDesigner, GeneScan, and ProbeSelect.
  • The oligonucleotides are then synthesized in situ described in Hughes et al., Nature Biotechnol. 19:324 (2002) or as described in Kane et al., Nucleic Acids Res. 28:4552 (2000) and affixed to an activated glass slide (Sigma-Genosis, The Woodlands, Tex.) using a 5′ amino linker. The position of each oligonucleotide on the slide is known.
  • Example 3
  • Example 3 illustrates how cell cycle genes important for wood development in Eucalyptus grandis can be determined and how oligonucleotides which uniquely bind to those genes can be designed and synthesized for use on a microarray.
  • Eucalyptus trees of the species Eucalyptus grandis are grown under natural light conditions. Tissue samples are prepared as described in, e.g., Sterky et al., Proc. Nat'l Acad. Sci. 95:13330 (1998). Specifically, tissue samples are collected from woody trees having a height of 5 meters. Tissue samples of the woody trees are prepared by taking tangential sections through the cambial region of the stem. The stems are sectioned horizontally into sections ranging from juvenile (top) to mature (bottom). The stem sections separated by stage of development are further separated into 5 layers by peeling into sections of phloem, differentiating phloem, cambium, differentiating xylem, developing xylem, and mature xylem. Tissue samples, including leaves, buds, shoots, and roots are also prepared from seedlings of the species Pinus radiata.
  • RNA is isolated and ESTs generated as described in Example 1 or Sterky et al., supra. The nucleic acid sequences of ESTs derived from samples containing developing wood are compared with nucleic acid sequences of genes known to be involved in the plant cell cycle. ESTs from samples that do not contain developing wood are also compared with sequences of genes known to be involved in the plant cell cycle. An in silico hybridization analysis is performed as described in, for example, Audic and Claverie, Genome Res. 7:986 (1997). Sequences from among the known cell cycle genes that show hybridization in silico to ESTs made from samples containing developing wood, but do not hybridize to ESTs from samples not containing developing wood are selected for further examination.
  • cDNA clones containing sequences that hybridize to the genes showing wood-preferred expression are selected from cDNA libraries using techniques well known in the art of molecular biology. Using the sequence information, oligonucleotides are designed such that each oligonucleotide is specific for only one cDNA sequence in the library. The oligonucleotide sequences are provided in Table 14. 60-mer oligonucleotide probes are designed using the method of Li and Stormo, supra or using software such as ArrayDesigner, GeneScan, and ProbeSelect.
  • The oligonucleotides are then synthesized in situ described in Hughes et al., Nature Biotechnol. 19:324 (2002) or as described in Kane et al., Nucleic Acids Res. 28:4552 (2000) and affixed to an activated glass slide (Sigma-Genosus, The Woodlands, Tex.) using a 5′ amino linker. The position of each oligonucleotide on the slide is known.
  • Example 4
  • Example 4 illustrates how to detect expression of Pinus radiata cell cycle genes which are important in wood formation using an oligonucleotide microarray prepared as in Example 2. This is an example of a balanced incomplete block designed experiment carried out using aRNA samples prepared from mature-phase phloem (P), cambium (C), expanding xylem found in a layer below the cambium (X1) and differentiating, lignifying xylem cells found deeper in the same growth ring (X2). In this example, cell cycle gene expression is compared among the four samples, namely P, C, X1, and X2.
  • In the summer, plants of the species Pinus radiata are felled and the bark of the main stem is immediately pulled gently away to reveal the phloem and xylem. The phloem and xylem are then peeled with a scalpel into separate containers of liquid nitrogen. Needles (leaves) and buds from the trees are also harvested with a scalpel into separate containers of liquid nitrogen. RNA is subsequently isolated from the frozen tissue samples as described in Example 1. Equal microgram quantities of total RNA are purified from each sample using RNeasy Mini columns (Qiagen, Valencia, Calif.) according to the manufacturers instructions.
  • Amplification reactions are carried out for each of the P, C, X1, and X2 tissue samples. Amplification reactions are performed using Ambion's MessageAmp kit, a T7-based amplification procedure, following the manufacturer's instructions, except that labeled aaUTP is added to the reagent mix during in the amplification step. aaUTP is incorporated into the resulting antisense RNA formed during this step. CyDye fluorescent labels are coupled to the aaUTPs in a non-enzymatic reaction as described in Example 1. Labeled amplified antisense RNAs are precipitated and washed, and then assayed for purity using a NanoDrop spectrophotometer. These labeled antisense RNAs, corresponding to the RNA isolated from the P, C, X1, and X2 tissue samples, constitute the sample nucleic acids, which are referred to as the P, C, X1, and X2 samples.
  • Normalization control samples of known nucleic acids are added to each sample in a dilution series of 500, 200, 100, 50, 25 and 10 pg/μl for quantitation of the signals. Positive controls corresponding to specific genes showing expression in all tissues of pine, such as housekeeping genes, are also added to the plant sample.
  • Each of four microarray slides is incubated with 125 μL of a P, C, X1 or X2 sample under a coverslip at 42° C. for 16-18 hours. The arrays are washed in 1×SSC, 0.1% SDS for 10 minutes and then in 0.1×SSC, 0.1% SDS for 10 minutes and the allowed to dry.
  • The array slides are scanned using an Axon laser scanner and analyzed using GenePix Pro software. Data from the microarray slides are subjected to microarray data analysis using GenStat SAS or Spotfire software. Outliers are removed and ratiometric data for each of the datasets are normalized using a global normalization which employs a cubic spline fit applied to correct for differential dye bias and spatial effects. A second transformation is performed to fit control signal ratios to a mean log2=0 (i.e. 1:1 ratio). Normalized data are then subjected to a variance analysis.
  • Mean signal intensity for each signal at any given position on the microarray slide is determined for each of three of P, C, X1, and X2 sample microarray slides. This mean signal/probe position is compared to the signal at the same position on sample slide which was not used for calculating the mean. For example, a mean signal at a given position is determined for P, C, and X1 and the signal at that position in the X2 microarray slide is compared to the P, C, and X1 mean signal value.
  • Table 1 shows genes having greater than doubled signal with any one sample as compared to the mean signal of the other three samples.
  • TABLE 1
    Gene PvCX12 PvX12 CvX12
    WD40 repeat protein A −1.24 −0.88 −1.07
    CDC2 −1.09 −0.78 −0.92
    CYCLIN −1.08 −1 −0.26
    WD-40 repeat protein B −1.01 −0.87 −0.42
    CDC2 −0.83 −0.49 −1.01
    P = Phloem
    C = Cambium
    X1 = xylem layer-1
    X2 = xylem layer-2
    PvCX12 = Ratio of the signal for Phloem target versus mean signal for Cambium, Xylem1, and Xylem2 targets
  • The data shows that WD40 repeat protein A encodes a WD40 repeat protein is less highly expressed in cambium than in developing xylem, while WD40 repeat protein B encodes a WD40 repeat protein that is more highly expressed in phloem than in the other tissues.
  • Signal data are then verified with RT-PCR to confirm gene expression in the target tissue of the genes corresponding to the unique oligonucleotides in the probe.
  • Example 5
  • Example 5 demonstrates how one can correlate cell cycle gene expression with agronomically important wood phenotypes such as density, stiffness, strength, distance between branches, and spiral grain.
  • Mature clonally propagated pine trees are selected from among the progeny of known parent trees for superior growth characteristics and resistance to important fungal diseases. The bark is removed from a tangential section and the trees are examined for average wood density in the fifth annual ring at breast height, stiffness and strength of the wood, and spiral grain. The trees are also characterized by their height, mean distance between major branches, crown size, and forking.
  • To obtain seedling families that are segregating for major genes that affect density, stiffness, strength, distance between branches, spiral grain and other characteristics that may be linked to any of the genes affecting these characteristics, trees lacking common parents are chosen for specific crosses on the criterion that they exhibit the widest variation from each other with respect to the density, stiffness, strength, distance between branches, and spiral grain criteria. Thus, pollen from a plus tree exhibiting high density, low mean distance between major branches, and high spiral grain is used to pollinate cones from the unrelated plus tree among the selections exhibiting the lowest density, highest mean distance between major branches, and lowest spiral grain. It is useful to note that “plus trees” are crossed such that pollen from a plus tree exhibiting high density are used to pollinate developing cones from another plus tree exhibiting high density, for example, and pollen from a tree exhibiting low mean distance between major branches would be used to pollinate developing cones from another plus tree exhibiting low mean distance between major branches.
  • Seeds are collected from these controlled pollinations and grown such that the parental identity is maintained for each seed and used for vegetative propagation such that each genotype is represented by multiple ramets. Vegetative propagation is accomplished using micropropagation, hedging, or fascicle cuttings. Some ramets of each genotype are stored while vegetative propagules of each genotype are grown to sufficient size for establishment of a field planting. The genotypes are arrayed in a replicated design and grown under field conditions where the daily temperature and rainfall are measured and recorded.
  • The trees are measured at various ages to determine the expression and segregation of density, stiffness, strength, distance between branches, spiral grain, and any other observable characteristics that may be linked to any of the genes affecting these characteristics. Samples are harvested for characterization of cellulose content, lignin content, cellulose microfibril angle, density, strength, stiffness, tracheid morphology, ring width, and the like. Samples are also examined for gene expression as described in Example 4. Ramets of each genotype are compared to ramets of the same genotype at different ages to establish age:age correlations for these characteristics.
  • Example 6
  • Example 6 demonstrates how the stage of plant development and responses to environmental conditions such as light and season can be correlated to cell cycle gene expression using microarrays prepared as in Example 4. In particular, the changes in gene expression associated with wood density are examined.
  • Trees of three different clonally propagated Eucalyptus grandis hybrid genotypes are grown on a site with a weather station that measures daily temperatures and rainfall. During the spring and subsequent summer, genetically identical ramets of the three different genotypes are first photographed with north-south orientation marks, using photography at sufficient resolution to show bark characteristics of juvenile and mature portions of the plant, and then felled as in Example 4. The age of the trees is determined by planting records and confirmed by a count of the annual rings. In each of these trees, mature wood is defined as the outermost rings of the tree below breast height, and juvenile wood as the innermost rings of the tree above breast height. Each tree is accordingly sectored as follows:
  • NM—NORTHSIDE MATURE
  • SM—SOUTHSIDE MATURE
  • NT—NORTHSIDE TRANSITION
  • ST—SOUTHSIDE TRANSITION
  • NJ—NORTHSIDE JUVENILE
  • SJ—SOUTHSIDE JUVENILE
  • Tissue is harvested from the plant trunk as well as from juvenile and mature form leaves. Samples are prepared simultaneously for phenotype analysis, including plant morphology and biochemical characteristics, and gene expression analysis. The height and diameter of the tree at the point from which each sector was taken is recorded, and a soil sample from the base of the tree is taken for chemical assay. Samples prepared for gene expression analysis are weighed and placed into liquid nitrogen for subsequent preparation of RNA samples for use in the microarray experiment. The tissues are denoted as follows:
  • P—phloem
  • C—cambium
  • X1—expanding xylem
  • X2—differentiating and lignifying xylem
  • Thin slices in tangential and radial sections from each of the sectors of the trunk are fixed as described in Ruzin, Plant Microtechnique and Microscopy, Oxford University Press, Inc., New York, N.Y. (1999) for anatomical examination and confirmation of wood developmental stage. Microfibril angle is examined at the different developmental stages of the wood, for example juvenile, transition and mature phases of Eucalyptus grandis wood. Other characteristics examined are the ratio of fibers to vessel elements and ray tissue in each sector. Additionally, the samples are examined for characteristics that change between juvenile and mature wood and between spring wood and summer wood, such as fiber morphology, lumen size, and width of the S2 (thickest) cell wall layer. Samples are further examined for measurements of density in the fifth ring and determination of modulus of elasticity using techniques well known to those skilled in the art of wood assays. See, e.g., Wang, et al., Non-destructive Evaluations of Trees, EXPERIMENTAL TECHNIQUES, pp. 28-30 (2000).
  • For biochemical analysis, 50 grams from each of the harvest samples are freeze-dried and analyzed, using biochemical assays well known to those skilled in the art of plant biochemistry for quantities of simple sugars, amino acids, lipids, other extractives, lignin, and cellulose. See, e.g., Pettersen & Schwandt, J. Wood Chem. & Technol. 11:495 (1991).
  • In the present example, the phenotypes chosen for comparison are high density wood, average density wood, and low density wood. Nucleic acid samples are prepared as described in Example 3, from trees harvested in the spring and summer. Gene expression profiling by hybridization and data analysis is performed as described in Examples 3 and 4.
  • Using similar techniques and clonally propagated individuals one can examine cell cycle gene expression as it is related to other complex wood characteristics such as strength, stiffness and spirality.
  • Example 7
  • Example 7 demonstrates the ability of the oligonucleotide probes of the invention to distinguish between highly homologous members of a family of cell cycle genes. Hybridization to a particular oligonucleotide on the array identifies a unique WD40 gene that is expressed more strongly in a genotype having a higher density wood than in observed in other genotypes examined. The WD40 gene is also expressed more strongly in mature wood than in juvenile wood and more strongly in summer wood than in spring wood. This gene is not found to be expressed at high levels either in leaves or buds.
  • The gene expression pattern is confirmed by RT-PCR. This gene, the putative “density-related” gene, is used for in situ hybridization of fixed radial sections. The density-related WD40 gene hybridizes most strongly to the vascular cambium in regions of the stem where the xylem is comprised primarily of fibers with few vessel elements and few xylem ray cells.
  • These results suggest that the WD40 gene product functions in radial cell division, which occurs in the cambium and results in diameter growth, rather than in axial cell division such as may be important in the apex or leaves. Such a gene would be difficult to identify by cDNA microarrays or other traditional hybridization means because the highly conserved regions present in the gene would result in confusing it with genes encoding enzymes having similar catalytic functions, but acting in axial or radial divisions. Furthermore, from the sequence similarity-based annotation suggesting a function of this gene product in cell division and the observation of this microarray hybridization pattern, confirmed by RT-PCR and in silico hybridization, this gene product functions specifically in developing secondary xylem to guide the cell division patterns of fibers, such that higher expression of this gene results in greater fiber production relative to vessel element or ray production. The fiber content is correlated with a principal components analysis (PCA) variable that accounts for at least 10% of the variation in basic density.
  • Example 8
  • Example 8 demonstrates how the use of oligonucleotide probes of the invention can be used to identify one wood “density related” WD40 repeat protein gene and its promoter from among the family of homologous genes. Further, this example demonstrates how a promoter sequence identified using this method is used to transform other hardwood species to result in increased diameter growth rates as compared to wild-type plants of the same species.
  • The sequence of the WD40 gene is used to probe a Genome Walker library in order to isolate 5′ flanking sequences comprising a promoter region. The promoter region is then operably linked to a beta-glucuronidase reporter gene and cloned into a binary vector for transformation into Eucalyptus using the method described in U.S. Application Ser. No. 60/476,222. Regenerated transgenic tobacco and Eucalyptus plants are then sectioned and stained using X-gluc, demonstrating that the microarray data results in isolation of a promoter capable of highly cambial-specific expression solely in those portions of the stem that develop more fibers than vessel elements or xylem rays.
  • Using techniques well known to those skilled in the art of molecular biology, the promoter is then operably linked to a cell division promoting gene and this construct placed in a binary vector for transformation into hardwood plants such as Sweetgum and Populus, such that the cell division promoting gene is expressed more strongly than normally in the vascular cambium. This results in increased diameter growth rate in the transgenic hardwood plants relative to control hardwood plants.
  • Example 9
  • Example 9 demonstrates how a density related polypeptide can be linked to a tissue-preferred promoter and expressed in pine resulting in a plant with increased wood density.
  • A density-related polypeptide, which is more highly expressed during the early spring, is identified by the method described in Example 7. A DNA construct having the density-related polypeptide operably linked to a promoter is placed into an appropriate binary vector and transformed into pine using the method of Connett et al. (U.S. patent application Ser. Nos. 09/973,088 and 09/973,089). Pine plants are transformed as described in Connett et al., supra, and the transgenic pine plants are used to establish a forest planting. Increased density even in the spring wood (early wood) is observed in the transgenic pine plants relative to control pine plants which are not transformed with the density related DNA construct.
  • Example 10
  • Using techniques well known to those skilled in the art of molecular biology, the sequence of the putative density-related gene isolated in Example 7 is analyzed in genomic DNA isolated from alfalfa. This enables the identification of an orthologue in alfalfa whose sequence is then used to create an RNAi knockout construct. This construct is then transformed into alfalfa. See, e.g., Austin et al., Euphytica 85, 381 1995. The regenerated transgenic plants show lower fiber content and increased ray cells content in the xylem. Such properties improved digestability which results in higher growth rates in cattle fed on this alfalfa as compared to wild-type alfalfa of the same species.
  • Example 11
  • Example 11 demonstrates how gene expression analysis can be used to find gene variants which are present in mature plants having a desirable phenotype. The presence or absence of such a variant can be used to predict the phenotype of a mature plant, allowing screening of the plants at the seedling stage. Although this example employs eucalyptus, the method used herein is also useful in breeding programs for pine and other tree species.
  • The sequence of a putative density-related gene is used to probe genomic DNA isolated from Eucalyptus that vary in density as described in previous examples. Non-transgenically produced Eucalyptus hybrids of different wood phenotypes are examined. One hybrid exhibits high wood density and another hybrid exhibits lower wood density. A molecular marker in the 3′ portion of the coding region is found which distinguishes a high-density gene variant from a lower density gene variant.
  • This molecular marker enables tree breeders to assay non-transgenic Eucalyptus hybrids for likely density profiles while the trees are still at seedling stage, whereas in the absence of the marker, tree breeders must wait until the trees have grown for multiple years before density at harvest age can be reliably predicted. This enables selective outplanting of the best trees at seedling stage rather than an expensive culling operation and resultant erosion at thinning age. This molecular marker is further useful in the breeding program to determine which parents will give rise to high density outcross progeny.
  • Molecular markers found in the 3′ portion of the coding region of the gene that do not correspond to variants seen more frequently in higher or lower wood density non-transgenic Eucalyptus hybrid trees are also useful. These markers are found to be useful for fingerprinting different genotypes of Eucalyptus, for use in identity-tracking in the breeding program and in plantations.
  • Example 12
  • This Example describes microarrays for identifying gene expression differences that contribute to the phenotypic characteristics that are important in commercial wood, namely wood appearance, stiffness, strength, density, fiber dimensions, coarseness, cellulose and lignin content, extractives content and the like.
  • As in Examples 2-4, woody trees of genera that produce commercially important wood products, in this case Pinus and Eucalyptus, are felled from various sites and at various times of year for the collection and isolation of RNA from developing xylem, cambium, phloem, leaves, buds, roots, and other tissues. RNA is also isolated from seedlings of the same genera.
  • All contigs are compared to both the ESTs made from RNA isolated from samples containing developing wood and the sequences of the ESTs made from RNA of various tissues that do not contain developing wood. Contigs containing primarily ESTs that show more hybridization in silico to ESTs made from RNA isolated from samples containing developing wood than to ESTs made from RNA isolated from samples not containing developing wood are determined to correspond to possible novel genes particularly expressed in developing wood. These contigs are then used for BLAST searches against public domain sequences. Those contigs that hybridize with high stringency to no known genes or genes annotated as having only a “hypothetical protein” are selected for the next step. These contigs are considered putative novel genes showing wood-preferred expression.
  • The longest cDNA clones containing sequences hybridizing to the putative novel genes showing wood-preferred expression are selected from cDNA libraries using techniques well known to those skilled in the art of molecular biology. The cDNAs are sequenced and full-length gene-coding sequences together with untranslated flanking sequences are obtained where possible. Stretches of 45-80 nucleotides (or oligonucleotides) are selected from each of the sequences of putative novel genes showing wood-preferred expression such that each oligonucleotide probe hybridizes at high stringency to only one sequence represented in the ESTs made from RNA isolated from trees or seedlings of the same genus.
  • Oligomers are then chemically synthesized and placed onto a microarray slide as described in Example 3. Each oligomer corresponds to a particular sequence of a putative novel gene showing wood-preferred expression and to no other gene whose sequence is represented among the ESTs made from RNA isolated from trees or seedlings of the same genus.
  • Sample preparation and hybridization are carried out as in Example 4. The technique used in this example is more effective than use of a microarray using cDNA probes because the presence of a signal represents significant evidence of the expression of a particular gene, rather than of any of a number of genes that may contain similarities to the cDNA due to conserved functional domains or common evolutionary history. Thus, it is possible to differentiate homologous genes, such as those in the same family, but which may have different functions in phenotype determination.
  • Thus hybridization data, gained using the method of Example 4, enable the user to identify which of the putative novel genes actually has a pattern of coordinate expression with known genes, a pattern of expression consistent with a particular developmental role, and/or a pattern of expression that suggests that the gene has a promoter that drives expression in a valuable way.
  • The hybridization data thus using this method can be used, for example, to identify a putative novel gene that shows an expression pattern particular to the tracheids with the lowest cellulose microfibril angle in developing spring wood (early wood). The promoter of this gene can also be isolated as in Example 8, and operably linked to a gene that has been shown as in Example 9 to be associated with late wood (summer wood). Transgenic pine plants containing this construct are generated using the methods of Example 9, and the early wood of these plants is then shown to display several characteristics of late wood, such as higher microfibril angle, higher density, smaller average lumen size, etc.
  • Example 13
  • Example 13 demonstrates the use of a cambium-specific promoter functionally linked to a cell cycle gene for increased plant biomass.
  • Cambium-specific cell cycle transcripts are identified via array analyses of different secondary vasculature layers as described in Example 4. Candidate promoters linked to the genes corresponding to these transcripts are cloned from pine genomic DNA using, e.g., the BD Clontech GenomeWalker kit and tested in transgenic tobacco via a reporter assay(s) for cambium specificity/preference. The cambium-specific promoter overexpressing a cell cycle gene involved in secondary xylem cell division is used to increased wood biomass. A tandem cambium-specific promoter is constructed driving the cell cycle ORF. Boosted transcript levels of the candidate cell cycle gene result in an increased xylem biomass phenotype.
  • Example 14
  • Isolation and Characterization of cDNA Clones from Eucalyptus Grandis
  • Eucalyptus grandis cDNA expression libraries were prepared from mature shoot buds, early wood phloem, floral tissue, leaf tissue (two independent libraries), feeder roots, structural roots, xylem or early wood xylem and were constructed and screened as follows.
  • Total RNA was extracted from the plant tissue using the protocol of Chang et al. (Plant Molecular Biology Reporter 11:113-116 (1993). mRNA was isolated from the total RNA preparation using either a Poly(A) Quik mRNA Isolation Kit (Stratagene, La Jolla, Calif.) or Dynal Beads Oligo (dT)25 (Dynal, Skogen, Norway). A cDNA expression library was constructed from the purified mRNA by reverse transcriptase synthesis followed by insertion of the resulting cDNA clones in Lambda ZAP using a ZAP Express cDNA Synthesis Kit (Stratagene), according to the manufacturer's protocol. The resulting cDNAs were packaged using a Gigapack II Packaging Extract (Stratagene) using an aliquot (1-5 αl) from the 5 μl ligation reaction dependent upon the library. Mass excision of the library was done using XL1-Blue MRF′ cells and XLOLR cells (Stratagene) with ExAssist helper phage (Stratagene). The excised phagemids were diluted with NZY broth (Gibco BRL, Gaithersburg, Md.) and plated out onto LB-kanamycin agar plates containing X-gal and isopropylthio-beta-galactoside (IPTG).
  • Of the colonies plated and selected for DNA miniprep, 99% contained an insert suitable for sequencing. Positive colonies were cultured in NZY broth with kanamycin and cDNA was purified by means of alkaline lysis and polyethylene glycol (PEG) precipitation. Agarose gel at 1% was used to screen sequencing templates for chromosomal contamination. Dye primer sequences were prepared using a Turbo Catalyst 800 machine (Perkin Elmer/Applied Biosystems Division, Foster City, Calif.) according to the manufacturer's protocol.
  • DNA sequence for positive clones was obtained using a Perkin Elmer/Applied Biosystems Division Prism 377 sequencer. cDNA clones were sequenced first from the 5′ end and, in some cases, also from the 3′ end. For some clones, internal sequence was obtained using either Exonuclease III deletion analysis, yielding a library of differentially sized subclones in pBK-CMV, or by direct sequencing using gene-specific primers designed to identified regions of the gene of interest.
  • The determined cDNA sequences were compared with known sequences in the EMBL database using the computer algorithms FASTA and/or BLASTN. Multiple alignments of redundant sequences were used to build reliable consensus sequences. Based on similarity to known sequences from other plant species, the isolated polynucleotide sequences were identified as encoding transcription factors, as detailed herein. The predicted polypeptide sequences corresponding to the polynucleotide sequences are also depicted therein.
  • Example 15
  • Isolation and Characterization of cDNA Clones from Pinus Radiata
  • Pinus radiata cDNA expression libraries (prepared from either shoot bud tissue, suspension cultured cells, early wood phloem (two independent libraries), fascicle meristem tissue, male strobilus, root (unknown lineage), feeder roots, structural roots, female strobilus, cone primordia, female receptive cones and xylem (two independent libraries) were constructed and screened as described above in Example 14.
  • DNA sequence for positive clones was obtained using forward and reverse primers on a Perkin Elmer/Applied Biosystems Division Prism 377 sequencer and the determined sequences were compared to known sequences in the database as described above.
  • Based on similarity to known sequences from other plant species, the isolated polynucleotide sequences were identified as encoding transcription factors, as detailed herein. The predicted polypeptide sequences corresponding to the polynucleotide sequences are also depicted therein.
  • Example 16
  • 5′ RACE Isolation
  • To identify additional sequence 5′ or 3′ of a partial cDNA sequence in a cDNA library, 5′ and 3′ rapid amplification of cDNA ends (RACE) was performed using the SMART RACE cDNA amplification kit (Clontech Laboratories, Palo Alto, Calif.). Generally, the method entailed first isolating poly(A) mRNA, performing first and second strand cDNA synthesis to generate double stranded cDNA, blunting cDNA ends, and then ligating of the SMART RACE. Adaptor to the cDNA to form a library of adaptor-ligated ds cDNA. Gene-specific primers were designed to be used along with adaptor specific primers for both 5′ and 3′ RACE reactions. Using 5′ and 3′ RACE reactions, 5′ and 3′ RACE fragments were obtained, sequenced, and cloned. The process may be repeated until 5′ and 3′ ends of the full-length gene were identified. A full-length cDNA may generated by PCR using primers specific to 5′ and 3′ ends of the gene by end-to-end PCR.
  • For example, to amplify the missing 5′ region of a gene from first-strand cDNA, a primer was designed 5′→3′ from the opposite strand of the template sequence, and from the region between ˜100-200 bp of the template sequence. A successful amplification should give an overlap of ˜100 bp of DNA sequence between the 5′ end of the template and PCR product.
  • RNA was extracted from four pine tissues, namely seedling, xylem, phloem and structural root using the Concert Reagent Protocol (Invitrogen, Carlsbad, Calif.) and standard isolation and extraction procedures. The resulting RNA was then treated with DNase, using 10 U/ul DNase I (Roche Diagnostics, Basel, Switzerland). For 100 μg of RNA, 9 μl 10× DNase buffer (Invitrogen, Carlsbad, Calif.), 10 μl of Roche DNase I and 90 μl of Rnase-free water was used. The RNA was then incubated at room temperature for 15 minutes and 1/10 volume 25 mM EDTA is added. A RNeasy mini kit (Qiagen, Venlo, The Netherlands) was used for RNA clean up according to manufacturer's protocol.
  • To synthesize cDNA, the extracted RNA from xylem, phloem, seedling and root was used and the SMART RACE cDNA amplification kit (Clontech Laboratories Inc, Palo Alto, Calif.) was followed according to manufacturer's protocol. For the RACE PCR, the cDNA from the four tissue types was combined. The master mix for PCR was created by combining equal volumes of cDNA from xylem, phloem, root and seedling tissues. PCR reactions were performed in 96 well PCR plates, with 1 μl of primer from primer dilution plate (10 mM) to corresponding well positions. 49 μl of master mix is aliquoted into the PCR plate with primers. Thermal cycling commenced on a GeneAmp 9700 (Applied Biosystems, Foster City, Calif.) at the following parameters:
  • 94° C. (5 sec),
  • 72° C. (3 min), 5 cycles;
  • 94° C. (5 sec),
  • 70° C. (10 sec),
  • 72° C. (3 min), 5 cycles;
  • 94° C. (5 sec),
  • 68° C. (10 sec),
  • 72° C. (3 min), 25 cycles.
  • cDNA was separated on an agarose gel following standard procedures. Gel fragments were excised and eluted from the gel by using the Qiagen 96-well Gel Elution kit, following the manufacturer's instructions.
  • PCR products were ligated into pGEMTeasy (Promega, Madison, Wis.) in a 96 well plate overnight according to the following specifications: 60-80 ng of DNA, 5 μl 2× rapid ligation buffer, 0.5 μl pGEMT easy vector, 0.1 μl DNA ligase, filled to 10 μl with water, and incubated overnight.
  • Each clone was transformed into E. coli following standard procedures and DNA was extracted from 12 clones picked by following standard protocols. DNA extraction and the DNA quality was verified on an 1% agarose gel. The presence of the correct size insert in each of the clones was determined by restriction digests, using the restriction endonuclease EcoRI, and gel electrophoresis, following standard laboratory procedures.
  • Example 17
  • Curation of an EST Sequence.
  • During the production of cDNA libraries, the original transcripts or their DNA counterparts may have features that prevent them from coding for functional proteins. There may be insertions, deletions, base substitutions, or unspliced or improperly spliced introns. If such features exist, it is often possible to identify them so that they can be changed. Similar curation can be performed on any other sequences that have homology to sequences in the public databases.
  • After determination of the DNA sequence, BLAST analysis shows that it is related to an Arabidopsis gene on the publicly available Arabidopsis genome sequence). However, instead of coding for an approximately 240 amino acid polypeptide, the consensus being curated is predicted to code for a product of only 157 amino acid residues, suggesting an error in the DNA sequence. To identify where the genuine coding region might be, the DNA sequence to the end of each EST is translated in each of the three reading frames and the predicted sequences are aligned with the Arabidopsis gene's amino acid sequence. It is found that the DNA segment in one portion of the EST codes for a sequence with similarity to the carboxyl terminus of the Arabidopsis gene. Therefore, it appears that an unspliced intron is present in the EST.
  • Unspliced introns are a relatively minor issue with regard to use of a cloned sequence for overexpression of the gene of interest. The RNA resulting from transcription of the cDNA can be expected to undergo normal processing to remove the intron. Antisense and RNAi constructs are also expected to function to suppress the gene of interest. On other occasions, it may be desirable to identify the precise limits of the intron so that it can be removed. When the sequence in question has a published sequence that is highly similar, it may be possible to find the intron by aligning the two sequences and identifying the locations where the sequence identity falls off, aided by the knowledge that introns start with the sequence GT and end with the sequence AG.
  • When there is some doubt about the site of the intron because highly similar sequences are not available, the intron location can be verified experimentally. For example, DNA oligomers can be synthesized flanking the region where the suspected intron is located. RNA from the source species, either Pinus or Eucalyptus, is isolated and used as a template to make cDNA using reverse transcriptase. The selected primers are then used in a PCR reaction to amplify the correctly spliced DNA segment (predicted size of approximately 350 by smaller than the corresponding segment of the original consensus) from the population of cDNAs. The amplified segment is then subjected to sequence analysis and compared to the consensus sequence to identify the differences.
  • The same procedure can be used when an alternate splicing event (partial intron remaining, or partial loss of an exon) is suspected. When an EST has a small change, such as insertion or deletion of a small number of bases, computer analysis of the EST sequence can still indicate its location when a translation product of the wrong size is predicted or if there is an obvious frameshift. Verification of the true sequence is done by synthesis of primers, production of new cDNA, and PCR amplification as described above.
  • Example 18
  • Transformation of Populus deltoides with constructs containing cell cycle genes.
  • Constructs made as described in the preceding example and shown in Table 2 below were each inoculated into Agrobacterium cultures by standard techniques.
  • Table 2 identifies plasmid(s), genes, and Genesis ID numbers for constructions described in Example 17.
  • TABLE 2
    Plasmid(s) Gene Genesis ID
    pGrw14 Cyclin A prga001823
    pGrw15 Cyclin A prpe001264
    pGrw16 Cyclin D prxa004540
    pGrw18 Cyclin D prxl006271
    PGrw19 Cyclin D prpb019661
    PGrw20 WEE1-like protein prrd041233
  • Populus deltoides stock plant cultures were maintained on DKW medium (Driver and Kuniyuki, 1984, McGranahan et al. 1987, available commercially from Sigma/Aldrich) with 2.5 uM zeatin in a growth room with a 16 h photoperiod. For transformation, petioles were excised aseptically using a sharp scalpel blade from the stock plants, cut into 4-6 mm lengths, placed on DKW medium with 1 ug/ml BAP and 1 ug/ml NAA immediately after harvest, and incubated in a dark growth chamber (28 degrees) for 24 hours.
  • Agrobacterium cultures containing the desired constructs were grown to log phase, indicated by an OD600 between 0.8-1.0 A, then pelleted and resuspended in an equal volume of Agrobacterium Induction Medium (AIM), which contains Woody Plant Medium salts (Lloyd, G., and McCown, B., 1981. Woody plant medium. Proc. Intern. Plant Prop. Soc. 30:421, available commercially from Sigma/Aldrich), 5 g/L glucose and 0.6 g/L MES at pH 5.8, with the addition of 1 ul of a 100 mM stock solution of acetosyringone per ml of AIM. The pellet was resuspended by vortexing. The bacterial cells were incubated for an hour in this medium at 28 degrees C. in an environmental chamber, shaking at 100 rpm.
  • After the induction period, Populus deltoides explants were exposed to the Agrobacterium mixture for 15 minutes. The explants were then lightly blotted on sterile paper towels, replaced onto the same plant medium and cultured in the dark at 18-20 degrees C. After a three-day co-cultivation period, the explants were transferred to DKW medium in which the NAA concentration was reduced to 0.1 ug/ml and to which was added 400 mg/L timentin to eradicate the Agrobacterium.
  • After 4 days on eradication medium, explants were transferred to small magenta boxes containing the same medium supplemented with timentin (400 mg/L) as well as the selection agent geneticin (50 mg/L). Explants were transferred every two weeks to fresh selection medium. Calli that grow in the presence of selection were isolated and sub-cultured to fresh selection medium every three weeks. Calli were observed for the production of adventitious shoots.
  • Adventitious shoots were normally observed within two months from the initiation of transformation. These shoot clusters were transferred to DKW medium to which no NAA was added, and in which the BAP concentration was reduced to 0.5 ug.ml, for shoot elongation, typically for about 14 weeks. Elongated shoots were excised and transferred to BTM medium (Chalupa, Communicationes Instituti Forestalis Checosloveniae 13:7-39, 1983, available commercially from Sigma/Aldrich) at pH5.8, containing 20 g/l sucrose and 5 g/l activated charcoal. See Table 3 below.
  • TABLE 3
    Rooting medium for Populus deltoids.
    BTM-1 Media Components mg/L
    NH4NO3 412
    KNO3 475
    Ca(NO3)2•4H2O 640
    CaCl2•2H2O  440*
    MgSO4•7H2O 370
    KH2PO4 170
    MnSO4•H2O    2.3
    ZnSO4•7H2O    8.6
    CuSO4•5H2O    0.25
    CoCl2•6H2O    0.02
    KI    0.15
    H3BO3    6.2
    Na2MoO4•2H2O    0.25
    FeSO4•7H2O   27.8
    Na2EDTA•2H2O   37.3
    Myo-inositol 100
    Nicotinic acid    0.5
    Pyridoxine HCl    0.5
    Thiamine HCl  1
    Glycine  2
    Sucrose 20000 
    Activated Carbon 5000 
  • After development of roots, typically four weeks, transgenic plants were propagated in the greenhouse by rooted cutting methods, or in vitro through axillary shoot induction for four weeks on DKW medium containing 11.4 uM zeatin, after which the multiplied shoots were separated and transferred to root induction medium. Rooted plants were transferred to soil for evaluation of growth in glasshouse and field conditions.
  • Example 19
  • Production of disproportionately large leaves mediated by ectopic expression of certain cyclin D genes
  • Approximately 100 explants of Populus deltoides per construct were transformed with pGRW16 and pGRW19, which contain genes that are normally show preferred expression in the vasculature, driven by a constitutive promoter (the Pinus radiata superubiquitin promoter). Upon regeneration, many of the ramets of many of the translines were observed to have disproportionately large leaves relative to control plants. The leaves were both longer and broader than those of control plants.
  • Disproportionately large leaves could be a very useful early indicator of growth potential large leaf size and thus high growth potential. Lage leaf size can be a function of either increased numbers of leaf cells or increased leaf cell size or both.
  • Example 20
  • Production of unusual vascular development mediated by ectopic expression of a cyclin D gene.
  • Approximately 100 explants of Populus deltoides per construct were transformed with pGRW18. Multiple transgenic lines regenerated from this experiment showed a very unique pleiotropic phenotype. Leaves of these transgenic lines symmetrically folded on both sides of the midrib down the entire length of the leaf. Many petioles of these lines spiraled, and in many cases turned 360 degrees, in a right-handed fashion towards the leaf. The stem showed some thickening and slight bending near the middle.
  • One ramet of the transgenic line TDL002534 showing these phenotypes was sacrificed to investigate these aberrancies at the tissue level. Transverse sections of a curling petiole stained with toluidine blue revealed retardation of vascular development, but the presence of additional vascular cylinders developing as indicated by the black arrows. The xylem and phloem within the vascular cylinders of the curling petiole appeared to be developmentally similar and spatially oriented correctly. Longitudinal sections of straight and curled petioles may offer an explanation for the spiraling phenomenon. Curled petioles showed more elongated cells on the outside turn of the curl and more compressed cells on the opposite side of the petiole.
  • Perhaps the most striking phenotype was identified in the leaves. As with the petioles, aberrant vascular development was noted, comprising additional forming vascular cylinders lateral to the larger midrib. In some sections almost fully-formed veins could be seen immediately adjacent to the midrib. In all instances where the folding phenotype was noted, this type of leaf configuration was associated with the phenotype.
  • The development of additional vascular cylinders in the space where normally a small number of vascular bundles or a single midrib are seen is indicative of unusual cell division activity at the level of early vascular development. Thus, this gene expressed under the control of a vascular-preferred promoter rather than a constitutive promoter could have utility in increasing cell division in later vascular development, creating additional wood.
  • Example 21
  • This example illustrates how polynucleotides important for wood development in P. radiata can be determined and how oligonucleotides which uniquely bind to those genes can be designed and synthesized for use on a microarray.
  • Open pollinated trees of approximately 16 years of age are selected from plantation-grown sites, in the United States for loblolly pine, and in New Zealand for radiata pine. Trees are felled during the spring and summer seasons to compare the expression of genes associated with these different developmental stages of wood formation. Trees are felled individually and trunk sections are removed from the bottom area approximately one to two meters from the base and within one to two meters below the live crown. The section removed from the basal end of the trunk contains mature wood. The section removed from below the live crown contains juvenile wood. Samples collected during the spring season are termed earlywood or springwood, while samples collected during the summer season are considered latewood or summerwood (Larson et al., Gen. Tech. Rep. FPL-GTR-129. Madison, Wis.: U.S. Department of Agriculture, Forest Service, Forest Products Laboratory. p. 42).
  • Tissues are isolated from the trunk sections such that phloem, cambium, developing xylem, and maturing xylem are removed. These tissues are collected only from the current year's growth ring. Upon tissue removal in each case, the material is immediately plunged into liquid nitrogen to preserve the nucleic acids and other components. The bark is peeled from the section and phloem tissue removed from the inner face of the bark by scraping with a razor blade. Cambium tissue is isolated from the outer face of the peeled section by gentle scraping of the surface. Developing xylem and lignifying xylem are isolated by sequentially performing more vigorous scraping of the remaining tissue. Tissues are transferred from liquid nitrogen into containers for long term storage at −70 until RNA extraction and subsequent analysis is performed.
  • Example 22
  • This example illustrates a procedure for RNA extraction and purification, which is particularly useful for RNA obtained from conifer needle, xylem, cambium, and phloem.
  • Tissue is obtained from conifer needle, xylem, cambium or phloem. The tissue is frozen in liquid nitrogen and ground. The total RNA is extracted using Concert Plant RNA reagent (Invitrogen). The resulting RNA sample is extracted into phenol:chloroform and treated with DNase. The RNA is then incubated at 65° C. for 2 minutes followed by centrifugation at 4° C. for 30 minutes. Following centrifugation, the RNA is extracted into phenol at least 10 times to remove contaminants.
  • The RNA is further cleaned using RNeasy columns (Qiagen). The purified RNA is quantified using RiboGreen reagent (Molecular Probes) and purity assessed by gel electrophoresis.
  • RNA is then amplified using MessageAmp (Ambion). Aminoallyl-UTP and free UTP are added to the in vitro transcription of the purified RNA at a ratio of 4:1 aminoallyl-UTP-to-UTP. The aminoallyl-UTP is incorporated into the new RNA strand as it is transcribed. The amino-allyl group is then reacted with Cy dyes to attach the colorimetric label to the resulting amplified RNA using the Amersham procedure modified for use with RNA. Unincorporated dye is removed by ethanol precipitation. The labeled RNA is quantified spectrophotometrically (NanoDrop). The labeled RNA is fragmented by heating to 95° C. as described in Hughes et al., Nature Biotechnol. 19:342 (2001).
  • Example 23
  • This Example illustrates how genes important for wood development in P. radiata can be determined and how oligonucleotides which uniquely bind to those genes can be designed and synthesized for use on a microarray.
  • Pine trees of the species P. radiata are grown under natural light conditions. Tissue samples are prepared as described in, e.g., Sterky et al., Proc. Nat'l Acad. Sci. 95:13330 (1998). Specifically, tissue samples are collected from woody trees having a height of 5 meters. Tissue samples of the woody trees are prepared by taking tangential sections through the cambial region of the stem. The stems are sectioned horizontally into sections ranging from juvenile (top) to mature (bottom). The stem sections separated by stage of development are further separated into 5 layers by peeling into sections of phloem, differentiating phloem, cambium, differentiating xylem, developing xylem, and mature xylem. Tissue samples, including leaves, buds, shoots, and roots are also prepared from seedlings of the species P. radiata.
  • RNA is isolated and ESTs generated as described in the Example above or Sterky et al., supra. The nucleic acid sequences of ESTs derived from samples containing developing wood are compared with nucleic acid sequences of genes known to be involved in polysaccharide synthesis. ESTs from samples that do not contain developing wood are also compared with sequences of genes known to be involved in the plant cell cycle. An in silico hybridization analysis is performed using BLAST (NCBI) as follows.
  • Example 24 Eucalyptus in Silico Data
  • In silico gene expression can be used to determine the membership of the consensi EST libraries. For each library, a consensus is determined from the number of ESTs in any tissue class divided by the total number of ESTs in a class multiplied by 1000. These values provide a normalized value that is not biased by the extent of sequencing from a library. Several libraries were sampled for a consensus value, including reproductive, bud reproductive, bud vegetative, fruit, leaf, phloem, cambium, xylem, root, stem, sap vegetative, whole plant libraries.
  • As shown below, a number of the inventive sequences exhibit vascular-preferred expression (more than 50% of the hits by these sequences if the databases were searched at random would be in libraries made from developing vascular tissue) and thus are likely to be involved in wood-related developmental processes. The data are shown in Table 12.
  • Example 25 Pinus in Silico Data
  • In silico gene expression can be used to determine the membership of the consensi EST libraries. For each library, a consensus is determined from the number of ESTs in any tissue class divided by the total number of ESTs in a class multiplied by 1000. These values provide a normalized value that is not biased by the extent of sequencing from a library. Several libraries were sampled for a consensus value, including needles, phloem, cambium, xylem, root, stem and, whole plant libraries.
  • As shown below, a number of the inventive sequences exhibit vascular-preferred expression (more than 50% of the hits by these sequences if the databases were searched at random would be in libraries made from developing vascular tissue) and thus are likely to be involved in wood-related developmental processes. The data are shown in Table 13.
  • Example 26
  • Sequences that show hybridization in silico to ESTs made from samples containing developing wood, but that do not hybridize to ESTs from samples not containing developing wood are selected for further examination.
  • cDNA clones containing sequences that hybridize to the genes showing wood-preferred expression are selected from cDNA libraries using techniques well known in the art of molecular biology. Using the sequence information, oligonucleotides are designed such that each oligonucleotide is specific for only one cDNA sequence in the library. The oligonucleotide sequences are provided in Table 14. 60-mer oligonucleotide probes are designed using the method of Li and Stormo, supra or using software such as ArrayDesigner, GeneScan, and ProbeSelect.
  • The oligonucleotides are then synthesized in situ described in Hughes et al., Nature Biotechnol. 19:324 (2002) or as described in Kane et al., Nucleic Acids Res. 28:4552 (2000) and affixed to an activated glass slide (Sigma-Genosis, The Woodlands, Tex.) using a 5′ amino linker. The position of each oligonucleotide on the slide is known.
  • Example 27
  • This example illustrates how to detect expression of Pinus radiata genes of the instant application which are important in wood formation using an oligonucleotide microarray prepared as described above. This is an example of a balanced incomplete block designed experiment carried out using aRNA samples prepared from mature-phase phloem (P), cambium (C), expanding xylem found in a layer below the cambium (X1) and differentiating, lignifying xylem cells found deeper in the same growth ring (X2). In this example, cell cycle gene expression is compared among the four samples, namely P, C, X1, and X2.
  • In the summer, plants of the species Pinus radiata are felled and the bark of the main stem is immediately pulled gently away to reveal the phloem and xylem. The phloem and xylem are then peeled with a scalpel into separate containers of liquid nitrogen. Needles (leaves) and buds from the trees are also harvested with a scalpel into separate containers of liquid nitrogen. RNA is subsequently isolated from the frozen tissue samples as described in Example 1. Equal microgram quantities of total RNA are purified from each sample using RNeasy Mini columns (Qiagen, Valencia, Calif.) according to the manufacturers instructions.
  • Amplification reactions are carried out for each of the P, C, X1, and X2 tissue samples. Amplification reactions are performed using Ambion's MessageAmp kit, a T7-based amplification procedure, following the manufacturer's instructions, except that labeled aaUTP is added to the reagent mix during in the amplification step. aaUTP is incorporated into the resulting antisense RNA formed during this step. CyDye fluorescent labels are coupled to the aaUTPs in a non-enzymatic reaction as described in Example 1. Labeled amplified antisense RNAs are precipitated and washed, and then assayed for purity using a NanoDrop spectrophotometer. These labeled antisense RNAs, corresponding to the RNA isolated from the P, C, X1, and X2 tissue samples, constitute the sample nucleic acids, which are referred to as the P, C, X1, and X2 samples.
  • Normalization control samples of known nucleic acids are added to each sample in a dilution series of 500, 200, 100, 50, 25 and 10 pg/μl for quantitation of the signals. Positive controls corresponding to specific genes showing expression in all tissues of pine, such as housekeeping genes, are also added to the plant sample.
  • Each of four microarray slides is incubated with 125 μL of a P, C, X1 or X2 sample under a coverslip at 42° C. for 16-18 hours. The arrays are washed in 1×SSC, 0.1% SDS for 10 minutes and then in 0.1×SSC, 0.1% SDS for 10 minutes and the allowed to dry.
  • The array slides are scanned using an Axon laser scanner and analyzed using GenePix Pro software. Data from the microarray slides are subjected to microarray data analysis using GenStat SAS or Spotfire software. Outliers are removed and ratiometric data for each of the datasets are normalized using a global normalization which employs a cubic spline fit applied to correct for differential dye bias and spatial effects. A second transformation is performed to fit control signal ratios to a mean log2=0 (i.e. 1:1 ratio). Normalized data are then subjected to a variance analysis.
  • Mean signal intensity for each signal at any given position on the microarray slide is determined for each of three of P, C, X1, and X2 sample microarray slides. This mean signal/probe position is compared to the signal at the same position on sample slide which was not used for calculating the mean. For example, a mean signal at a given position is determined for P, C, and X1 and the signal at that position in the X2 microarray slide is compared to the P, C, and X1 mean signal value.
  • Table 5 shows genes having greater than doubled signal with any one sample as compared to the mean signal of the other three samples.
  • TABLE 5
    Gene PvCX12 PvX12 CvX12
    WD40 repeat protein A −1.24 −0.88 −1.07
    CDC2 −1.09 −0.78 −0.92
    CYCLIN −1.08 −1 −0.26
    WD-40 repeat protein B −1.01 −0.87 −0.42
    CDC2 −0.83 −0.49 −1.01
    P = Phloem
    C = Cambium
    X1 = xylem layer-1
    X2 = xylem layer-2
    PvCX12 = Ratio of the signal for Phloem target versus mean signal for Cambium, Xylem1, and Xylem2 targets
  • The data shows that WD40 repeat protein A encodes a WD40 repeat protein is less highly expressed in cambium than in developing xylem, while WD40 repeat protein B encodes a WD40 repeat protein that is more highly expressed in phloem than in the other tissues.
  • Signal data are then verified with RT-PCR to confirm gene expression in the target tissue of the genes corresponding to the unique oligonucleotides in the probe.
  • Example 28
  • This example illustrates how RNAs of tissues from multiple pine species, in this case both P. radiata and loblolly pine P. taeda trees, are selected for analysis of the pattern of gene expression associated with wood development in the juvenile wood and mature wood forming sections of the trees using the microarrays derived from P. radiata cDNA sequences described in Example 4.
  • Open pollinated trees of approximately 16 years of age are selected from plantation-grown sites, in the United States for loblolly pine, and in New Zealand for radiata pine. Trees are felled during the spring and summer seasons to compare the expression of genes associated with these different developmental stages of wood formation. Trees are felled individually and trunk sections are removed from the bottom area approximately one to two meters from the base and within one to two meters below the live crown. The section removed from the basal end of the trunk contains mature wood. The section removed from below the live crown contains juvenile wood. Samples collected during the spring season are termed earlywood or springwood, while samples collected during the summer season are considered latewood or summerwood. Larson et al., Gen. Tech. Rep. FPL-GTR-129. Madison, Wis.: U.S. Department of Agriculture, Forest Service, Forest Products Laboratory. p. 42.
  • Tissues are isolated from the trunk sections such that phloem, cambium, developing xylem, and maturing xylem are removed. These tissues are collected only from the current year's growth ring. Upon tissue removal in each case, the material is immediately plunged into liquid nitrogen to preserve the nucleic acids and other components. The bark is peeled from the section and phloem tissue removed from the inner face of the bark by scraping with a razor blade. Cambium tissue is isolated from the outer face of the peeled section by gentle scraping of the surface. Developing xylem and lignifying xylem are isolated by sequentially performing more vigorous scraping of the remaining tissue. Tissues are transferred from liquid nitrogen into containers for long term storage at −70° C. until RNA extraction and subsequent analysis is performed.
  • Example 29
  • This example illustrates procedures alternative to those used in the example above for RNA extraction and purification, particularly useful for RNA obtained from a variety of tissues of woody plants, and a procedure for hybridization and data analysis using the arrays described in Example 4.
  • RNA is isolated according to the protocol of Chang et al., Plant Mol. Biol. Rep. 11:113. DNA is removed using DNase I (Invitrogen, Carlsbad, Calif.) according to the manufacturer's recommendations. The integrity of the RNA samples is determined using the Agilent 2100 Bioanalyzer (Agilent Technologies, USA).
  • 10 μg of total RNA from each tissue is reverse transcribed into cDNA using known methods.
  • In the case of Pinus radiata phloem tissue, it can be difficult to extract sufficient amounts of total RNA for normal labelling procedures. Total RNA is extracted and treated as previously described and 100 ng of total RNA is amplified using the Ovation™ Nanosample RNA Amplification system from NuGEN™ (NuGEN, CA, USA). Similar amplification kits such as those manufactured by Ambion may alternatively be used. The amplified RNA is reverse transcribed into cDNA and labelled as described above.
  • Hybridization and stringency washes are performed using the protocol as described in the US Patent Application for “Methods and Kits for Labeling and Hybridizing cDNA for Microarray Analysis” (supra) at 42 C. The arrays (slides) are scanned using a ScanArray 4000 Microarray Analysis System (GSI Lumonics, Ottawa, ON, Canada). Raw, non-normalized intensity values are generated using QUANTARRAY software (GSI Lumonics, Ottawa, ON, Canada).
  • A fully balanced, incomplete block experimental design (Kerr and Churchill, Gen. Res. 123:123, 2001) is used in order to design an array experiment that would allow maximum statistical inferences from analyzed data.
  • Gene expression data is analyzed using the SAS® Microarray Solution software package (The SAS Institute, Cary, N.C., USA). Resulting data was then visualized using JMP® (The SAS Institute, Cary, N.C., USA).
  • Analysis done for this experiment is an ANOVA approach with mixed model specification (Wolfinger et al., J. Comp. Biol. 8:625-637). Two steps of linear mixed models are applied. The first one, normalization model, is applied for global normalization at slide-level. The second one, gene model, is applied for doing rigorous statistical inference on each gene. Both models are stated in Models (1) and (2).

  • log2(Y ijkls)=θij +D k +S l +DS klijkls   (1)

  • R ijkls (g)ij (g) +D k (g) +S l (g) +DS kl (g) +SS ls (g)ijkls (g)   (2)
  • Yijkls represents the intensity of the sth spot in the 1th slide with the kth dye applying the jth treatment for the ith cell line. θij, Dk, Sl, and DSkl represent the mean effect of the jth treatment in the ith cell line, the kth dye effect, the lth slide random effect, and the random interaction effect of the kth dye in the lth slide. ωijkls is the stochastic error term. represent the similar roles as θij, Dk, Sl, and DSkl except they are specific for the gth gene. Rijkls (g) represents the residual of the gth gene from model (1). μij (g), Dk (g), Sl (g), and DSkl (g) represent the similar roles as θij, Dk, Sl, and DSkl except they are specific for the gth gene. SSls (g) represent the spot by slide random effect for the gth gene. εijkls (g) represent the stochastic error term. All random terms are assumed to be normal distributed and mutually independent within each model.
  • According to the analysis described above, certain cDNAs, some of which are shown in Table 6 below, are found to be differentially expressed.
  • TABLE 6
    Gene corresponding
    to SEQ ID Oligo ID Gene_Family Expression
    162 Pra_000171_O_4 Peptidylprolyl isomerase steady state RNA higher
    in xylem than cambium
    164 Pra_001480_O_3 Peptidylprolyl isomerase steady state RNA lower
    in xylem than cambium
    control Pra_000218_O_2 RIBONUCLEOSIDE-DIPHOSPHATE steady state RNA lower
    REDUCTASE LARGE CHAIN (EC1.17.4.1). in xylem than cambium
    control Pra_000193_O_2 PUTATIVE SURFACE PROTEIN. steady state RNA lower
    in xylem than cambium
  • The involvement of these specific genes in wood development is inferred through the association of the up-regulation or down-regulation of genes to the particular stages of wood development. Both the spatial continuum of wood development across a section (phloem, cambium, developing xylem, maturing xylem) at a particular season and tree trunk position and the relationships of season and tree trunk position are considered when making associations of gene expression to the relevance in wood development.
  • Example 30
  • This example demonstrates how one can correlate polysaccharide gene expression with agronomically important wood phenotypes such as density, stiffness, strength, distance between branches, and spiral grain.
  • Mature clonally propagated pine trees are selected from among the progeny of known parent trees for superior growth characteristics and resistance to important fungal diseases. The bark is removed from a tangential section and the trees are examined for average wood density in the fifth annual ring at breast height, stiffness and strength of the wood, and spiral grain. The trees are also characterized by their height, mean distance between major branches, crown size, and forking.
  • To obtain seedling families that are segregating for major genes that affect density, stiffness, strength, distance between branches, spiral grain and other characteristics that may be linked to any of the genes affecting these characteristics, trees lacking common parents are chosen for specific crosses on the criterion that they exhibit the widest variation from each other with respect to the density, stiffness, strength, distance between branches, and spiral grain criteria. Thus, pollen from a tree exhibiting high density, low mean distance between major branches, and high spiral grain is used to pollinate cones from the unrelated plus tree among the selections exhibiting the lowest density, highest mean distance between major branches, and lowest spiral grain. It is useful to note that “plus trees” are crossed such that pollen from a plus tree exhibiting high density are used to pollinate developing cones from another plus tree exhibiting high density, for example, and pollen from a tree exhibiting low mean distance between major branches would be used to pollinate developing cones from another plus tree exhibiting low mean distance between major branches.
  • Seeds are collected from these controlled pollinations and grown such that the parental identity is maintained for each seed and used for vegetative propagation such that each genotype is represented by multiple ramets. Vegetative propagation is accomplished using micropropagation, hedging, or fascicle cuttings. Some ramets of each genotype are stored while vegetative propagules of each genotype are grown to sufficient size for establishment of a field planting. The genotypes are arrayed in a replicated design and grown under field conditions where the daily temperature and rainfall are measured and recorded.
  • The trees are measured at various ages to determine the expression and segregation of density, stiffness, strength, distance between branches, spiral grain, and any other observable characteristics that may be linked to any of the genes affecting these characteristics. Samples are harvested for characterization of cellulose content, lignin content, cellulose microfibril angle, density, strength, stiffness, tracheid morphology, ring width, and the like. RNA is then collected from replicated samples of trees showing divergent stiffness and density, or other characteristics, from genotypes that are otherwise as similar as possible in growth habit, in spring and fall so that early and late wood development is assayed. These samples are examined for gene expression similarly as described in above examples.
  • TABLE 7
    Concensus ID Information.
    Patent app SEQ ID Gene Family Consensus_ID Expression
    control Ribonucleoside- pinusRadiata_000218 up in early spring xylem
    diphosphate reductase vs late summer xylem
    Cell Cycle 168 Peptidylprolyl pinusRadiata_001692 up in juvenile
    isomerase developing wood vs
    mature developing xylem
    control Nitrite transporter pinusRadiata_016801 up mature developing xylem
    vs juvenile cambium
  • Ramets of each genotype are compared to ramets of the same genotype at different ages to establish age:age correlations for these characteristics.
  • Example 31
  • Example 8 demonstrates how responses to environmental conditions such as light and season alter plant phenotype and can be correlated to polysaccharide synthesis gene expression using microarrays. In particular, the changes in gene expression associated with wood density are examined.
  • Trees of three different clonally propagated E. grandis hybrid genotypes are grown on a site with a weather station that measures daily temperatures and rainfall. During the spring and subsequent summer, genetically identical ramets of the three different genotypes are first photographed with north-south orientation marks, using photography at sufficient resolution to show bark characteristics of juvenile and mature portions of the plant, and then felled. The age of the trees is determined by planting records and confirmed by a count of the annual rings. In each of these trees, mature wood is defined as the outermost rings of the tree below breast height, and juvenile wood as the innermost rings of the tree above breast height. Each tree is accordingly sectored as follows:
  • NM—NORTHSIDE MATURE
  • SM—SOUTHSIDE MATURE
  • NT—NORTHSIDE TRANSITION
  • ST—SOUTHSIDE TRANSITION
  • NJ—NORTHSIDE JUVENILE
  • SJ—SOUTHSIDE JUVENILE
  • Tissue is harvested from the plant trunk as well as from juvenile and mature form leaves. Samples are prepared simultaneously for phenotype analysis, including plant morphology and biochemical characteristics, and gene expression analysis. The height and diameter of the tree at the point from which each sector was taken is recorded, and a soil sample from the base of the tree is taken for chemical assay. Samples prepared for gene expression analysis are weighed and placed into liquid nitrogen for subsequent preparation of RNA samples for use in the microarray experiment. The tissues are denoted as follows:
  • P—phloem
  • C—cambium
  • X1—expanding xylem
  • X2—differentiating and lignifying xylem
  • Thin slices in tangential and radial sections from each of the sectors of the trunk are fixed as described in Ruzin, PLANT MICROTECHNIQUE AND MICROSCOPY, Oxford University Press, Inc., New York, N.Y. (1999) for anatomical examination and confirmation of wood developmental stage. Microfibril angle is examined at the different developmental stages of the wood, for example juvenile, transition and mature phases of Eucalyptus grandis wood. Other characteristics examined are the ratio of fibers to vessel elements and ray tissue in each sector. Additionally, the samples are examined for characteristics that change between juvenile and mature wood and between spring wood and summer wood, such as fiber morphology, lumen size, and width of the S2 (thickest) cell wall layer. Samples are further examined for measurements of density in the fifth ring and determination of modulus of elasticity using techniques well known to those skilled in the art of wood assays. See, e.g., Wang, et al., Non-destructive Evaluations of Trees, EXPERIMENTAL TECHNIQUES, pp. 28-30 (2000).
  • For biochemical analysis, 50 grams from each of the harvest samples are freeze-dried and analyzed, using biochemical assays well known to those skilled in the art of plant biochemistry for quantities of simple sugars, amino acids, lipids, other extractives, lignin, and cellulose. See, e.g., Pettersen & Schwandt, J. Wood Chem. & Technol. 11:495 (1991).
  • In the present example, the phenotypes chosen for comparison are high density wood, average density wood, and low density wood. Nucleic acid samples are prepared as described in Example 3, from trees harvested in the spring and summer. Gene expression profiling by hybridization and data analysis is performed as described above.
  • Using similar techniques and clonally propagated individuals one can examine polysaccharide gene expression as it is related to other complex wood characteristics such as strength, stiffness and spirality.
  • Example 32
  • Example 32 demonstrates the use of a vascular-preferred promoter functionally linked to one of the genes of the instant application.
  • A vascular-preferred promoter is then linked to one of the genes in the instant application and used to transform tree species. Boosted transcript levels of the candidate gene in the xylem of the transformants results in an increased xylem biomass phenotype.
  • In another example, a vascular-preferred promoter such as any of those in ArborGen's November 2003 patent applications is then linked to an RNAi construct containing sequences from one of the genes in the instant application and used to transform a tree of the genus from which the gene was isolated. Reduced transcript levels of the candidate gene in the xylem of the transformants results in an increased xylem biomass phenotype.
  • Example 33
  • The vector pARB476 was developed using the following steps. The Bluescript vector (Stratagene, La Jolla, Calif.) was modified by adding the Superubiquitin 3′UTR and nos 3′terminator sequence at the KpnI and ClaI sites to produce the vector pARB005 (SEQ ID NO. 773). To this vector the P. radiata superubiquitin promoter with intron was added. The promoter/intron sequence was first amplified from the P. radiata superubiquitin sequence identified in U.S. Pat. No. 6,380,459 using standard PCR techniques and the primers of SEQ ID NOS 774 and 775. The amplified fragment was then ligated into pARB005 using XbaI and PstI restriction digestion to produce the vector pARB119 (SEQ ID NO. 776).
  • The poplus tremuloises UDB Glucose binding domain gene (patent WO 0071670, ptCelA Genbank number AF072131) was amplified using standard PCR techniques and primers including and ATG and a ClaI site as part of the 5′ primer and a TGA and a ClaI site as part of the 3′ primer. The amplified fragment was then cloned into the ClaI site of pARB119 to produce the vector pARB476 (SEQ ID NO. 777).
  • The NotI cassette containing the P. radiata superubiquitin promoter with intron::UDP Glucose Binding domain::3′UTR: nos terminator from pARB476 was removed and cloned into the NotI site of pART29 to produce the vector pARB483. The binary vector pART29 is a modified pART27 vector (Gleave, Plant Mol. Biol. 20:1203-1207, 1992) that contains the Arabidopsis thaliana ubiquitin 3 (UBQ3) promoter instead of the nos5′ promoter and no lacZ sequences.
  • SEQ ID 773
    CGATGGGTGTTATTTGTGGATAATAAATTCGGGTGATGTTCAGTGTTTGTCGTATTTCTCACGAATAAA
    TTGTGTTTATGTATGTGTTAGTGTTGTTTGTCTGTTTCAGACCCTCTTATGTTATATTTTTCTTTTCGT
    CGGTCAGTTGAAGCCAATACTGGTGTCCTGGCCGGCACTGCAATACCATTTCGTTTAATATAAAGACTC
    TGTTATCCGTGAGCTCGAATTTCCCCGATCGTTCAAACATTTGGCAATAAAGTTTCTTAAGATTGAATC
    CTGTTGCCGGTCTTGCGATGATTATCATATAATTTCTGTTGAATTACGTTAAGCATGTAATAATTAACA
    TGTAATGCATGACGTTATTTATGAGATGGGTTTTTATGATTAGAGTCCCGCAATTATACATTTAATACG
    CGATAGAAAACAAAATATAGCGCGCAAACTAGGATAAATTATCGCGCGCGGTGTCATCTATGTTACTAG
    ATCGCGGCCGCATTTAAATGGTACCCAATTCGCCCTATAGTGAGTCGTATTACGCGCGCTCACTGGCCG
    TCGTTTTACAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCC
    CTTTCGCCAGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGA
    ATGGCGAATGGGACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGA
    CCGCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCG
    CCGGCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACC
    TCGACCCCAAAAAACTTGATTAGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTC
    GCCCTTTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACC
    CTATCTCGGTCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGC
    TGATTTAACAAAAATTTAACGCGAATTTTAACAAAATATTAACGCTTACAATTTAGGTGGCACTTTTCG
    GGGAAATGTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAG
    ACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGT
    CGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGT
    AAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGAT
    CCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGC
    GGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTT
    GGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGC
    TGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCT
    AACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGA
    AGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATT
    AACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGC
    AGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCG
    TGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACAC
    GACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAA
    GCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATT
    TAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTT
    CCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAAT
    CTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAAC
    TCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTA
    GTTAGGCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGT
    GGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGC
    GCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACT
    GAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCC
    GGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTA
    TAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAG
    CCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACAT
    GTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGC
    TCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCCAATACGCAA
    ACCGCCTCTCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGC
    GGGCAGTGAGCGCAACGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTTACACTTTAT
    GCTTCCGGCTCGTATGTTGTGTGGAATTGTGAGCGGATAACAATTTCACACAGGAAACAGCTATGACCA
    TGATTACGCCAAGCGCGCAATTAACCCTCACTAAAGGGAACAAAAGCTGGGGCCGCTCTAGAACTAGTG
    GATCCCCCGGGCTGCAGGAATTCGTCCAGCAGTTGTCTGGAGCTCCACCAGAAATCTGGAAGCTTAT
    SEQ ID 774
    AAATCTAGAGGTACCATTTAAATGCGGCCGCAAAACCCCTCACAAATACATAA
    SEQ ID 775
    TTTCTGCAGCTTGAAATTGAAATATGACTAACGAAT
    SEQ ID 776
    tctagaggtaccatttaaatgcggccgcaaaacccctcacaaatacataaaaaaaattctttatttaat
    tatcaaactctccactacctttcccaccaaccgttacaatcctgaatgttggaaaaaactaactacatt
    gatataaaaaaactacattacttcctaaatcatatcaaaattgtataaatatatccactcaaaggagtc
    tagaagatccacttggacaaattgcccatagttggaaagatgttcaccaagtcaacaagatttatcaat
    ggaaaaatccatctaccaaacttactttcaagaaaatccaaggattatagagtaaaaaatctatgtatt
    attaagtcaaaaagaaaaccaaagtgaacaaatattgatgtacaagtttgagaggataagacattggaa
    tcgtctaaccaggaggcggaggaattccctagacagttaaaagtggccggaatcccggtaaaaaagatt
    aaaatttttttgtagagggagtgcttgaatcatgttttttatgatggaaatagattcagcaccatcaaa
    aacattcaggacacctaaaattttgaagtttaacaaaaataacttggatctacaaaaatccgtatcgga
    ttttctctaaatataactagaattttcataactttcaaagcaactcctcccctaaccgtaaaacttttc
    ctacttcaccgttaattacattccttaagagtagataaagaaataaagtaaataaaagtattcacaaac
    caacaatttatttcttttatttacttaaaaaaacaaaaagtttatttattttacttaaatggcataatg
    acatatcggagatccctcgaacgagaatcttttatctccctggttttgtattaaaaagtaatttattgt
    ggggtccacgcggagttggaatcctacagacgcgctttacatacgtctcgagaagcgtgacggatgtgc
    gaccggatgaccctgtataacccaccgacacagccagcgcacagtatacacgtgtcatttctctattgg
    aaaatgtcgttgttatccccgctggtacgcaaccaccgatggtgacaggtcgtctgttgtcgtgtcgcg
    tagcgggagaagggtctcatccaacgctattaaatactcgccttcaccgcgttacttctcatcttttct
    cttgcgttgtataatcagtgcgatattctcagagagcttttcattcaaaggtatggagttttgaagggc
    tttactcttaacatttgtttttctttgtaaattgttaatggtggtttctgtgggggaagaatcttttgc
    caggtccttttgggtttcgcatgtttatttgggttatttttctcgactatggctgacattactagggct
    ttcgtgctttcatctgtgttttcttcccttaataggtctgtctctctggaatatttaattttcgtatgt
    aagttatgagtagtcgctgtttgtaataggctcttgtctgtaaaggtttcagcaggtgtttgcgtttta
    ttgcgtcatgtgtttcagaaggcctttgcagattattgcgttgtactttaatattttgtctccaacctt
    gttatagtttccctcctttgatctcacaggaaccctttcttctttgagcattttcttgtggcgttctgt
    agtaatattttaattttgggcccgggttctgagggtaggtgattattcacagtgatgtgctttccctat
    aaggtcctctatgtgtaagctgttagggtttgtgcgttactattgacatgtcacatgtcacatattttc
    ttcctcttatccttcgaactgatggttctttttctaattcgtggattgctggtgccatattttatttct
    attgcaactgtattttagggtgtctctttctttttgatttcttgttaatatttgtgttcaggttgtaac
    tatgggttgctagggtgtctgccctcttcttttgtgcttctttcgcagaatctgtccgttggtctgtat
    ttgggtgatgaattatttattccttgaagtatctgtctaattagcttgtgatgatgtgcaggtatattc
    gttagtcatatttcaatttcaagcgatcccccgggctgcaggaattcgtccagcagttgtctggagctc
    caccagaaatctggaagcttatcgatgggtgttatttgtggataataaattcgggtgatgttcagtgtt
    tgtcgtatttctcacgaataaattgtgtttatgtatgtgttagtgttgtttgtctgtttcagaccctct
    tatgttatatttttcttttcgtcggtcagttgaagccaatactggtgtcctggccggcactgcaatacc
    atttcgtttaatataaagactctgttatccgtgagctcgaatttccccgatcgttcaaacatttggcaa
    taaagtttcttaagattgaatcctgttgccggtcttgcgatgattatcatataatttctgttgaattac
    gttaagcatgtaataattaacatgtaatgcatgacgttatttatgagatgggtttttatgattagagtc
    ccgcaattatacatttaatacgcgatagaaaacaaaatatagcgcgcaaactaggataaattatcgcgc
    gcggtgtcatctatgttactagatcgcggccgcatttaaatggtacccaattcgccctatagtgagtcg
    tattacgcgcgctcactggccgtcgttttacaacgtcgtgactgggaaaaccctggcgttacccaactt
    aatcgccttgcagcacatccccctttcgccagctggcgtaatagcgaagaggcccgcaccgatcgccct
    tcccaacagttgcgcagcctgaatggcgaatgggacgcgccctgtagcggcgcattaagcgcggcgggt
    gtggtggttacgcgcagcgtgaccgctacacttgccagcgccctagcgcccgctcctttcgctttcttc
    ccttcctttctcgccacgttcgccggctttccccgtcaagctctaaatcgggggctccctttagggttc
    cgatttagtgctttacggcacctcgaccccaaaaaacttgattagggtgatggttcacgtagtgggcca
    tcgccctgatagacggtttttcgccctttgacgttggagtccacgttctttaatagtggactcttgttc
    caaactggaacaacactcaaccctatctcggtctattcttttgatttataagggattttgccgatttcg
    gcctattggttaaaaaatgagctgatttaacaaaaatttaacgcgaattttaacaaaatattaacgctt
    acaatttaggtggcacttttcggggaaatgtgcgcggaacccctatttgtttatttttctaaatacatt
    caaatatgtatccgctcatgagacaataaccctgataaatgcttcaataatattgaaaaaggaagagta
    tgagtattcaacatttccgtgtcgcccttattcccttttttgcggcattttgccttcctgtttttgctc
    acccagaaacgctggtgaaagtaaaagatgctgaagatcagttgggtgcacgagtgggttacatcgaac
    tggatctcaacagcggtaagatccttgagagttttcgccccgaagaacgttttccaatgatgagcactt
    ttaaagttctgctatgtggcgcggtattatcccgtattgacgccgggcaagagcaactcggtcgccgca
    tacactattctcagaatgacttggttgagtactcaccagtcacagaaaagcatcttacggatggcatga
    cagtaagagaattatgcagtgctgccataaccatgagtgataacactgcggccaacttacttctgacaa
    cgatcggaggaccgaaggagctaaccgcttttttgcacaacatgggggatcatgtaactcgccttgatc
    gttgggaaccggagctgaatgaagccataccaaacgacgagcgtgacaccacgatgcctgtagcaatgg
    caacaacgttgcgcaaactattaactggcgaactacttactctagcttcccggcaacaattaatagact
    ggatggaggcggataaagttgcaggaccacttctgcgctcggcccttccggctggctggtttattgctg
    ataaatctggagccggtgagcgtgggtctcgcggtatcattgcagcactggggccagatggtaagccct
    cccgtatcgtagttatctacacgacggggagtcaggcaactatggatgaacgaaatagacagatcgctg
    agataggtgcctcactgattaagcattggtaactgtcagaccaagtttactcatatatactttagattg
    atttaaaacttcatttttaatttaaaaggatctaggtgaagatcctttttgataatctcatgaccaaaa
    tcccttaacgtgagttttcgttccactgagcgtcagaccccgtagaaaagatcaaaggatcttcttgag
    atcctttttttctgcgcgtaatctgctgcttgcaaacaaaaaaaccaccgctaccagcggtggtttgtt
    tgccggatcaagagctaccaactctttttccgaaggtaactggcttcagcagagcgcagataccaaata
    ctgtccttctagtgtagccgtagttaggccaccacttcaagaactctgtagcaccgcctacatacctcg
    ctctgctaatcctgttaccagtggctgctgccagtggcgataagtcgtgtcttaccgggttggactcaa
    gacgatagttaccggataaggcgcagcggtcgggctgaacggggggttcgtgcacacagcccagcttgg
    agcgaacgacctacaccgaactgagatacctacagcgtgagctatgagaaagcgccacgcttcccgaag
    ggagaaaggcggacaggtatccggtaagcggcagggtcggaacaggagagcgcacgagggagcttccag
    ggggaaacgcctggtatctttatagtcctgtcgggtttcgccacctctgacttgagcgtcgatttttgt
    gatgctcgtcaggggggcggagcctatggaaaaacgccagcaacgcggcctttttacggttcctggcct
    tttgctggccttttgctcacatgttctttcctgcgttatcccctgattctgtggataaccgtattaccg
    cctttgagtgagctgataccgctcgccgcagccgaacgaccgagcgcagcgagtcagtgagcgaggaag
    cggaagagcgcccaatacgcaaaccgcctctccccgcgcgttggccgattcattaatgcagctggcacg
    acaggtttcccgactggaaagcgggcagtgagcgcaacgcaattaatgtgagttagctcactcattagg
    caccccaggctttacactttatgcttccggctcgtatgttgtgtggaattgtgagcggataacaatttc
    acacaggaaacagctatgaccatgattacgccaagcgcgcaattaaccctcactaaagggaacaaaagc
    tggggccgctctag
    SEQ ID 777
    TCTAGAGGTACCATTTAAATGCGGCCGCAAAACCCCTCACAAATACATAAAAAAAATTCTTTATTTAAT
    TATCAAACTCTCCACTACCTTTCCCACCAACCGTTACAATCCTGAATGTTGGAAAAAACTAACTACATT
    GATATAAAAAAACTACATTACTTCCTAAATCATATCAAAATTGTATAAATATATCCACTCAAAGGAGTC
    TAGAAGATCCACTTGGACAAATTGCCCATAGTTGGAAAGATGTTCACCAAGTCAACAAGATTTATCAAT
    GGAAAAATCCATCTACCAAACTTACTTTCAAGAAAATCCAAGGATTATAGAGTAAAAAATCTATGTATT
    ATTAAGTCAAAAAGAAAACCAAAGTGAACAAATATTGATGTACAAGTTTGAGAGGATAAGACATTGGAA
    TCGTCTAACCAGGAGGCGGAGGAATTCCCTAGACAGTTAAAAGTGGCCGGAATCCCGGTAAAAAAGATT
    AAAATTTTTTTGTAGAGGGAGTGCTTGAATCATGTTTTTTATGATGGAAATAGATTCAGCACCATCAAA
    AACATTCAGGACACCTAAAATTTTGAAGTTTAACAAAAATAACTTGGATCTACAAAAATCCGTATCGGA
    TTTTCTCTAAATATAACTAGAATTTTCATAACTTTCAAAGCAACTCCTCCCCTAACCGTAAAACTTTTC
    CTACTTCACCGTTAATTACATTCCTTAAGAGTAGATAAAGAAATAAAGTAAATAAAAGTATTCACAAAC
    CAACAATTTATTTCTTTTATTTACTTAAAAAAACAAAAAGTTTATTTATTTTACTTAAATGGCATAATG
    ACATATCGGAGATCCCTCGAACGAGAATCTTTTATCTCCCTGGTTTTGTATTAAAAAGTAATTTATTGT
    GGGGTCCACGCGGAGTTGGAATCCTACAGACGCGCTTTACATACGTCTCGAGAAGCGTGACGGATGTGC
    GACCGGATGACCCTGTATAACCCACCGACACAGCCAGCGCACAGTATACACGTGTCATTTCTCTATTGG
    AAAATGTCGTTGTTATCCCCGCTGGTACGCAACCACCGATGGTGACAGGTCGTCTGTTGTCGTGTCGCG
    TAGCGGGAGAAGGGTCTCATCCAACGCTATTAAATACTCGCCTTCACCGCGTTACTTCTCATCTTTTCT
    CTTGCGTTGTATAATCAGTGCGATATTCTCAGAGAGCTTTTCATTCAAAGGTATGGAGTTTTGAAGGGC
    TTTACTCTTAACATTTGTTTTTCTTTGTAAATTGTTAATGGTGGTTTCTGTGGGGGAAGAATCTTTTGC
    CAGGTCCTTTTGGGTTTCGCATGTTTATTTGGGTTATTTTTCTCGACTATGGCTGACATTACTAGGGCT
    TTCGTGCTTTCATCTGTGTTTTCTTCCCTTAATAGGTCTGTCTCTCTGGAATATTTAATTTTCGTATGT
    AAGTTATGAGTAGTCGCTGTTTGTAATAGGCTCTTGTCTGTAAAGGTTTCAGCAGGTGTTTGCGTTTTA
    TTGCGTCATGTGTTTCAGAAGGCCTTTGCAGATTATTGCGTTGTACTTTAATATTTTGTCTCCAACCTT
    GTTATAGTTTCCCTCCTTTGATCTCACAGGAACCCTTTCTTCTTTGAGCATTTTCTTGTGGCGTTCTGT
    AGTAATATTTTAATTTTGGGCCCGGGTTCTGAGGGTAGGTGATTATTCACAGTGATGTGCTTTCCCTAT
    AAGGTCCTCTATGTGTAAGCTGTTAGGGTTTGTGCGTTACTATTGACATGTCACATGTCACATATTTTC
    TTCCTCTTATCCTTCGAACTGATGGTTCTTTTTCTAATTCGTGGATTGCTGGTGCCATATTTTATTTCT
    ATTGCAACTGTATTTTAGGGTGTCTCTTTCTTTTTGATTTCTTGTTAATATTTGTGTTCAGGTTGTAAC
    TATGGGTTGCTAGGGTGTCTGCCCTCTTCTTTTGTGCTTCTTTCGCAGAATCTGTCCGTTGGTCTGTAT
    TTGGGTGATGAATTATTTATTCCTTGAAGTATCTGTCTAATTAGCTTGTGATGATGTGCAGGTATATTC
    GTTAGTCATATTTCAATTTCAAGCGATCCCCCGGGCTGCAGGAATTCGTCCAGCAGTTGTCTGGAGCTC
    CACCAGAAATCTGGAAGCTTATCGATATGGATCAGTTCCCCAAGTGGAATCCTGTCAATAGAGAAACGT
    ATATCGAAAGGCTGTCGGCAAGGTATGAAAGAGAGGGTGAGCCTTCTCAGCTTGCTGGTGTGGATTTTT
    TCGTGAGTACTGTTGATCCGCTGAAGGAACCGCCATTGATCACTGCCAATACAGTCCTTTCCATCCTTG
    CTGTGGACTATCCCGTCGATAAAGTCTCCTGCTACGTGTCTGATGATGGTGCAGCTATGCTTTCATTTG
    AATCTCTTGTAGAAACAGCTGAGTTTGCAAGGAAGTGGGTTCCGTTCTGCAAAAAATTCTCAATTGAAC
    CAAGAGCACCGGAGTTTTACTTCTCACAGAAAATTGATTACTTGAAAGACAAGGTTCAACCTTCTTTCG
    TGAAAGAACGTAGAGCAATGAAAAGGGATTATGAAGAGTACAAAGTCCGAGTTAATGCCCTGGTAGCAA
    AGGCTCAGAAAACACCTGAAGAAGGATGGACTATGCAAGATGGAACACCTTGGCCTGGGAATAACACAC
    GTGATCACCCTGGCATGATTCAGGTCTTCCTTGGAAATACTGGAGCTCGTGACATTGAAGGAAATGAAC
    TACCTCGTCTAGTATATGTCTCCAGGGAGAAGAGACCTGGCTACCAGCACCACAAAAAGGCTGGTGCAG
    AAAATGCTCTGGTGAGAGTGTCTGCAGTACTCACAAATGCTCCCTACATCCTCAATGTTGATTGTGATC
    ACTATGTAAACAATAGCAAGGCTGTTCGAGAGGCAATGTGCATCCTGATGGACCCACAAGTAGGTCGAG
    ATGTATGCTATGTGCAGTTCCCTCAGAGGTTTGATGGCATAGATAAGAGTGATCGCTACGCCAATCGTA
    ACGTAGTTTTCTTTGATGTTAACATGAAAGGGTTGGATGGCATTCAAGGACCAGTATACGTAGGAACTG
    GTTGTGTTTTCAACAGGCAAGCACTTTACGGCTACGGGCCTCCTTCTATGCCCAGCTTACGCAAGAGAA
    AGGATTCTTCATCCTGCTTCTCATGTTGCTGCCCCTCAAAGAAGAAGCCTGCTCAAGATCCAGCTGAGG
    TATACAGAGATGCAAAAAGAGAGGATCTCAATGCTGCCATATTTAATCTTACAGAGATTGATAATTATG
    ACGAGCATGAAAGGTCAATGCTGATCTCCCAGTTGAGCTTTGAGAAAACTTTTGGCTTATCTTCTGTCT
    TCATTGAGTCTACACTAATGGAGAATGGAGGAGTACCCGAGTCTGCCAACTCACCAACACTCATCAAGG
    AAGCAATTCATGTCATCGGCTGTGGCTATGAAGAGAAGACTGAATGGGGAAAAGAGATTGGTTGGATAT
    ATGGGTCAGTCACTGAGGATATCTTAAGTGGCTTCAAGATGCACTGCCGAGGATGGAGATCAATTTACT
    GCATGCCCGTAAGGCCTGCATTCAAAGGATCTGCACCCATCAACCTGTCTGATAGATTGCACCAGGTCC
    TCCGATGGGCTCTTGGTTCTGTGGAAATTTTCTTTAGCAGACACTGTCCCCTCTGGTACGGGTTTGGAG
    GAGGCCGTCTTAAATGGCTCCAAAGGCTTGCGTATATAAACACCATTGTGTACCCATGAATCGATGGGT
    GTTATTTGTGGATAATAAATTCGGGTGATGTTCAGTGTTTGTCGTATTTCTCACGAATAAATTGTGTTT
    ATGTATGTGTTAGTGTTGTTTGTCTGTTTCAGACCCTCTTATGTTATATTTTTCTTTTCGTCGGTCAGT
    TGAAGCCAATACTGGTGTCCTGGCCGGCACTGCAATACCATTTCGTTTAATATAAAGACTCTGTTATCC
    GTGAGCTCGAATTTCCCCGATCGTTCAAACATTTGGCAATAAAGTTTCTTAAGATTGAATCCTGTTGCC
    GGTCTTGCGATGATTATCATATAATTTCTGTTGAATTACGTTAAGCATGTAATAATTAACATGTAATGC
    ATGACGTTATTTATGAGATGGGTTTTTATGATTAGAGTCCCGCAATTATACATTTAATACGCGATAGAA
    AACAAAATATAGCGCGCAAACTAGGATAAATTATCGCGCGCGGTGTCATCTATGTTACTAGATCGCGGC
    CGCATTTAAATGGTACCCAATTCGCCCTATAGTGAGTCGTATTACGCGCGCTCACTGGCCGTCGTTTTA
    CAACGTCGTGACTGGGAAAACCCTGGCGTTACCCAACTTAATCGCCTTGCAGCACATCCCCCTTTCGCC
    AGCTGGCGTAATAGCGAAGAGGCCCGCACCGATCGCCCTTCCCAACAGTTGCGCAGCCTGAATGGCGAA
    TGGGACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCGCAGCGTGACCGCTACA
    CTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCCACGTTCGCCGGCTTT
    CCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTACGGCACCTCGACCCC
    AAAAAACTTGATTAGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGTTTTTCGCCCTTTG
    ACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTCAACCCTATCTCG
    GTCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATGAGCTGATTTAA
    CAAAAATTTAACGCGAATTTTAACAAAATATTAACGCTTACAATTTAGGTGGCACTTTTCGGGGAAATG
    TGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAAC
    CCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTA
    TTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATG
    CTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGA
    GTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTAT
    CCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGT
    ACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAA
    CCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTT
    TTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATAC
    CAAACGACGAGCGTGACACCACGATGCCTGTAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCG
    AACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCAC
    TTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTC
    GCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGA
    GTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGT
    AACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGA
    TCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAG
    CGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGCT
    TGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTC
    CGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCC
    ACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTG
    CCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGT
    CGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACC
    TACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCG
    GCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTG
    TCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGA
    AAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTC
    CTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCA
    GCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCCAATACGCAAACCGCCTC
    TCCCCGCGCGTTGGCCGATTCATTAATGCAGCTGGCACGACAGGTTTCCCGACTGGAAAGCGGGCAGTG
    AGCGCAACGCAATTAATGTGAGTTAGCTCACTCATTAGGCACCCCAGGCTTTACACTTTATGCTTCCGG
    CTCGTATGTTGTGTGGAATTGTGAGCGGATAACAATTTCACACAGGAAACAGCTATGACCATGATTACG
    CCAAGCGCGCAATTAACCCTCACTAAAGGGAACAAAAGCTGGGGCCGCTCTAG
  • TABLE 8
    pGrowth Information.
    CW AR Plasmid(s) Promoter Gene Genesis ID
    88 pGrowth14 SUBIN Cyclin A prga001823
    88 pGrowth15 SUBIN Cyclin A prpe001264
    88 pGrowth16 SUBIN Cyclin D prxa004540
    88 pGrowth18 SUBIN Cyclin D prxl006271
    88 pGrowth19 SUBIN Cyclin D prpb019661
    88 pGrowth20 SUBIN WEE1-like protein prrd041233
  • To make the growth100 plasmids, an acceptor vector (pWVK202) was built by first inserting the NotI-SUBIN::UDPGBD::nos term-NotI cassette from pARB483a into plasmid pWVK147 at NotI. Next, the UDPGBD gene was removed using restriction sites PstI and ClaI. A polylinker containing the restriction sites PstI, NheI, AvrII, ScaI, and ClaI was inserted in place of the UDPGBD gene. Sites AvrII and NheI are both compatible with SpeI, a site found often in the plasmids provided by Genesis. ScaI is blunt, so any fragment can be blunted and then inserted at that position into the acceptor vector. Plasmids were received from Genesis and analyzed to determine which restriction sites would be most suitable for subcloning into the acceptor vector pWVK202. After the ligations were performed, the resulting products were checked by extensive restriction digest analysis to make sure that the desired plasmid had been created.
  • TABLE 9
    Eucalyptus grandis Cell Cycle Genes and Proteins.
    Patent Patent
    DNA SEQ Protein SEQ ORF ORF
    ID NO ID NO Sequence Identifier start stop
    1 236 eucalyptusSpp_003910 387 1820
    2 237 eucalyptusSpp_019213 99 1007
    3 238 eucalyptusSpp_036800 120 1004
    4 239 eucalyptusSpp_040260 23 937
    5 240 eucalyptusSpp_041965 149 1033
    6 241 eucalyptusSpp_002906 199 1116
    7 242 eucalyptusSpp_001518 41 982
    8 243 eucalyptusSpp_008078 291 2042
    9 244 eucalyptusSpp_009826 107 2236
    10 245 eucalyptusSpp_010364 82 1749
    11 246 eucalyptusSpp_011523 151 1560
    12 247 eucalyptusSpp_024358 82 1644
    13 248 eucalyptusSpp_039125 626 2782
    14 249 eucalyptusSpp_005362 13 1467
    15 250 eucalyptusSpp_044857 113 1558
    16 251 eucalyptusSpp_001743 187 1686
    17 252 eucalyptusSpp_012405 238 1653
    18 253 eucalyptusSpp_003739 235 1539
    19 254 eucalyptusSpp_022338 158 1618
    20 255 eucalyptusSpp_028605 205 1530
    21 256 eucalyptusSpp_041006 174 1499
    22 257 eucalyptusSpp_006643 94 1332
    23 258 eucalyptusSpp_045338 176 1342
    24 259 eucalyptusSpp_046486 150 1283
    25 260 eucalyptusSpp_012070 101 367
    26 261 eucalyptusSpp_006617 9 1352
    27 262 eucalyptusSpp_007827 89 1486
    28 263 eucalyptusSpp_008036 80 1477
    29 264 010212EGLA007017HT 160 1062
    30 265 eucalyptusSpp_001596 172 1077
    31 266 eucalyptusSpp_005870 66 989
    32 267 eucalyptusSpp_006901 111 1541
    33 268 eucalyptusSpp_006902 116 1615
    34 269 eucalyptusSpp_007440 155 1453
    35 270 eucalyptusSpp_008994 228 2033
    36 271 eucalyptusSpp_024580 110 1258
    37 272 eucalyptusSpp_037831 50 1462
    38 273 eucalyptusSpp_034958 176 739
    39 274 001209EGXC004488HT 150 1529
    40 275 010310EGXD012820HT 247 1971
    41 276 010310EGXD013036HT 136 1644
    42 277 010316EGXF999037HT 48 836
    43 278 010324EGXF002118HT 49 822
    44 279 011019EGKA001923HT 185 751
    45 280 eucalyptusSpp_000966 103 621
    46 281 eucalyptusSpp_001037 41 559
    47 282 eucalyptusSpp_004603 127 693
    48 283 eucalyptusSpp_005465 28 639
    49 284 eucalyptusSpp_006571 135 812
    50 285 eucalyptusSpp_006786 119 613
    51 286 eucalyptusSpp_007057 38 562
    52 287 eucalyptusSpp_008670 109 1872
    53 288 eucalyptusSpp_009137 74 1159
    54 289 eucalyptusSpp_010285 54 2045
    55 290 eucalyptusSpp_010600 53 1879
    56 291 eucalyptusSpp_011551 7 690
    57 292 eucalyptusSpp_020743 83 601
    58 293 eucalyptusSpp_023739 125 535
    59 294 eucalyptusSpp_024103 55 573
    60 295 eucalyptusSpp_031985 147 842
    61 296 eucalyptusSpp_032025 167 487
    62 297 eucalyptusSpp_032173 195 890
    63 298 eucalyptusSpp_033340 68 586
    64 299 eucalyptusSpp_009143 182 3265
    65 300 eucalyptusSpp_000349 165 1145
    66 301 eucalyptusSpp_000575 529 1569
    67 302 eucalyptusSpp_000804 156 1136
    68 303 eucalyptusSpp_000805 90 1073
    69 304 eucalyptusSpp_000806 66 1049
    70 305 eucalyptusSpp_002248 277 1512
    71 306 eucalyptusSpp_003203 33 1076
    72 307 eucalyptusSpp_003209 65 973
    73 308 eucalyptusSpp_004429 82 1047
    74 309 eucalyptusSpp_004607 43 1101
    75 310 eucalyptusSpp_004682 142 1095
    76 311 eucalyptusSpp_005786 61 1257
    77 312 eucalyptusSpp_005887 193 1527
    78 313 eucalyptusSpp_005981 109 1155
    79 314 eucalyptusSpp_006766 71 1213
    80 315 eucalyptusSpp_006769 109 1785
    81 316 eucalyptusSpp_006907 364 2685
    82 317 eucalyptusSpp_007518 96 1412
    83 318 eucalyptusSpp_007717 116 1702
    84 319 eucalyptusSpp_007718 46 1101
    85 320 eucalyptusSpp_007741 23 1258
    86 321 eucalyptusSpp_007884 404 2644
    87 322 eucalyptusSpp_008258 107 2383
    88 323 eucalyptusSpp_008465 243 1625
    89 324 eucalyptusSpp_008616 126 1127
    90 325 eucalyptusSpp_008690 257 1390
    91 326 eucalyptusSpp_008708 178 1632
    92 327 eucalyptusSpp_008850 290 2917
    93 328 eucalyptusSpp_009072 148 1197
    94 329 eucalyptusSpp_009465 140 1567
    95 330 eucalyptusSpp_009472 376 1737
    96 331 eucalyptusSpp_009550 69 1010
    97 332 eucalyptusSpp_010284 149 1423
    98 333 eucalyptusSpp_010595 365 2677
    99 334 eucalyptusSpp_010657 24 923
    100 335 eucalyptusSpp_012636 221 3598
    101 336 eucalyptusSpp_012748 44 1447
    102 337 eucalyptusSpp_012879 196 1314
    103 338 eucalyptusSpp_015515 193 1668
    104 339 eucalyptusSpp_015724 78 1634
    105 340 eucalyptusSpp_016167 85 2826
    106 341 eucalyptusSpp_016633 74 1246
    107 342 eucalyptusSpp_017485 100 4377
    108 343 eucalyptusSpp_018007 58 2439
    109 344 eucalyptusSpp_020775 159 1064
    110 345 eucalyptusSpp_023132 118 1665
    111 346 eucalyptusSpp_023569 57 1628
    112 347 eucalyptusSpp_023611 250 1566
    113 348 eucalyptusSpp_024934 106 1434
    114 349 eucalyptusSpp_025546 190 1917
    115 350 eucalyptusSpp_030134 102 2942
    116 351 eucalyptusSpp_031787 75 1079
    117 352 eucalyptusSpp_034435 99 1148
    118 353 eucalyptusSpp_034452 232 1806
    119 354 eucalyptusSpp_035789 72 1124
    120 355 eucalyptusSpp_035804 315 2069
    121 356 eucalyptusSpp_043057 145 1968
    122 357 eucalyptusSpp_046741 130 1488
    123 358 eucalyptusSpp_047161 269 1693
    698 718 eucalyptusSpp_008994
    699 719 eucalyptusSpp_009143
    700 720 eucalyptusSpp_006366
    701 721 eucalyptusSpp_006907
    702 722 eucalyptusSpp_012636
    703 723 eucalyptusSpp_015724
    704 724 eucalyptusSpp_016167
    705 725 eucalyptusSpp_017485
    706 726 eucalyptusSpp_030134
    707 727 eucalyptusSpp_046741
    708 728 eucalyptusSpp_047161
    709 729 eucalyptusSpp_017378
  • TABLE 10
    Pinus radiata cell cycle genes and proteins.
    Patent Patent
    DNA SEQ Protein SEQ ORF ORF
    ID NO ID NO Sequence Identifier start stop
    124 359 pinusRadiata_001766 1163 2545
    125 360 pinusRadiata_002927 152 1582
    126 361 990309PRCA009171HT 389 1297
    127 362 pinusRadiata_013714 38 946
    128 363 pinusRadiata_016332 180 1088
    129 364 pinusRadiata_021677 40 948
    130 365 pinusRadiata_027562 229 1134
    131 366 pinusRadiata_001504 105 2642
    132 367 pinusRadiata_015211 187 2580
    133 368 pinusRadiata_020421 220 1749
    134 369 pinusRadiata_003187 438 1748
    135 370 pinusRadiata_015661 240 1631
    136 371 pinusRadiata_013874 252 1604
    137 372 pinusRadiata_014615 261 1817
    138 373 pinusRadiata_004578 167 1576
    139 374 pinusRadiata_023387 183 1598
    140 375 pinusRadiata_006970 98 1126
    141 376 pinusRadiata_010322 148 894
    142 377 pinusRadiata_022721 287 1363
    143 378 pinusRadiata_023407 251 1348
    144 379 pinusRadiata_001945 229 510
    145 380 pinusRadiata_008233 92 409
    146 381 pinusRadiata_008234 64 381
    147 382 pinusRadiata_022054 68 349
    148 383 pinusRadiata_012137 125 1849
    149 384 pinusRadiata_012582 70 1602
    150 385 pinusRadiata_015285 140 1465
    151 386 pinusRadiata_017229 628 2565
    152 387 pinusRadiata_020724 55 1818
    153 388 pinusRadiata_004555 259 1710
    154 389 pinusRadiata_004556 356 1807
    155 390 pinusRadiata_005729 261 1298
    156 391 pinusRadiata_007395 365 2251
    157 392 pinusRadiata_009503 156 1454
    158 393 pinusRadiata_011283 203 1348
    159 394 pinusRadiata_012322 229 1644
    160 395 pinusRadiata_018671 156 1454
    161 396 pinusRadiata_023236 27 2222
    162 397 pinusRadiata_000171 71 1759
    163 398 pinusRadiata_000172 358 2040
    164 399 pinusRadiata_001480 238 756
    165 400 pinusRadiata_001481 285 803
    166 401 pinusRadiata_001483 190 708
    167 402 pinusRadiata_001484 156 674
    168 403 pinusRadiata_001692 176 1912
    169 404 pinusRadiata_005313 64 765
    170 405 pinusRadiata_006362 93 881
    171 406 pinusRadiata_006493 372 1070
    172 407 pinusRadiata_006983 28 594
    173 408 pinusRadiata_006984 34 648
    174 409 pinusRadiata_007665 481 1611
    175 410 pinusRadiata_012196 93 584
    176 411 pinusRadiata_013382 250 1869
    177 412 pinusRadiata_016461 84 422
    178 413 pinusRadiata_017611 128 1213
    179 414 pinusRadiata_019776 265 837
    180 415 pinusRadiata_020659 38 781
    181 416 pinusRadiata_022559 38 526
    182 417 pinusRadiata_024188 37 1158
    183 418 pinusRadiata_027973 61 768
    184 419 pinusRadiata_001353 421 2172
    185 420 pinusRadiata_001978 163 1647
    186 421 pinusRadiata_002810 192 1172
    187 422 pinusRadiata_002811 131 1111
    188 423 pinusRadiata_002812 149 1726
    189 424 pinusRadiata_003514 948 2228
    190 425 pinusRadiata_004104 332 1465
    191 426 pinusRadiata_005595 232 1590
    192 427 pinusRadiata_005754 207 1550
    193 428 pinusRadiata_006463 221 1171
    194 429 pinusRadiata_006665 221 3679
    195 430 pinusRadiata_006750 269 1252
    196 431 pinusRadiata_007030 214 1242
    197 432 pinusRadiata_007854 119 2065
    198 433 pinusRadiata_007917 186 1550
    199 434 pinusRadiata_007989 244 3671
    200 435 pinusRadiata_008506 163 1431
    201 436 pinusRadiata_008692 155 1081
    202 437 pinusRadiata_008693 537 1463
    203 438 pinusRadiata_009170 284 1909
    204 439 pinusRadiata_009408 610 1659
    205 440 pinusRadiata_009522 241 1452
    206 441 pinusRadiata_009734 223 1173
    207 442 pinusRadiata_009815 251 1777
    208 443 pinusRadiata_010670 367 1419
    209 444 pinusRadiata_011297 284 1303
    210 445 pinusRadiata_013098 684 1784
    211 446 pinusRadiata_013172 336 2738
    212 447 pinusRadiata_013589 81 1622
    213 448 pinusRadiata_013608 399 1460
    214 449 pinusRadiata_014299 207 1673
    215 450 pinusRadiata_014498 263 1309
    216 451 pinusRadiata_014548 232 2529
    217 452 pinusRadiata_014610 56 2950
    218 453 pinusRadiata_015460 56 1234
    219 454 pinusRadiata_016090 193 2577
    220 455 pinusRadiata_016722 187 1233
    221 456 pinusRadiata_016785 51 1436
    222 457 pinusRadiata_017094 525 2351
    223 458 pinusRadiata_017527 152 1099
    224 459 pinusRadiata_017591 470 4114
    225 460 pinusRadiata_017769 196 2007
    226 461 pinusRadiata_018047 214 1323
    227 462 pinusRadiata_018414 68 2146
    228 463 pinusRadiata_018986 874 3705
    229 464 pinusRadiata_019479 360 1754
    230 465 pinusRadiata_020144 185 1384
    231 466 pinusRadiata_022480 241 1533
    232 467 pinusRadiata_023079 230 1435
    233 468 pinusRadiata_026739 101 2857
    234 469 pinusRadiata_026951 43 1548
    235 470 pinusRadiata_026529 206 1657
    710 730 pinusRadiata_000888
    711 731 pinusRadiata_004578
    712 732 pinusRadiata_007989
    713 733 pinusRadiata_009522
    714 734 pinusRadiata_014610
    715 735 pinusRadiata_017591
    716 736 pinusRadiata_017769
    717 737 pinusRadiata_026951
  • TABLE 11
    Annotated Peptide Sequences of the Present Invention.
    Entry Sequence Description Annotated Peptide Sequence
    1 The amino acid sequence of SEQ ID MGDGSLGSGGRGNSGGGGGGGSRPEWLQQYDLIGKIGEG
    261. The conserved eukaryotic TYGLVFLARIKHPSTNRGKYIAIKKFKQSKDGDGVSPTA
    protein kinase domain is IREIMLLREISHENVVKLVNVHINPVDMSLYLAFDYADH
    underlined and the DLYEIIRHHRDKVNQAINPYTVKSLLWQLLNGLNYLHSN
    serine/threonine protein kinases WIIHRDLKPSNILVMGEGEEQGVVKIADFGLARVYQAPL
    active-site signature is in bold. KPLSDNGVVVTIWYRAPELLLGAKHYTSAVDMWAVGCIF
    AELLTLKPLFQGQEVKANPNPFQLDQLDKIFKVLGHPTQ
    EKWPMLVNLPHWQSDVQHIQRHKYDDNALGNVVRLSSKN
    ATFDLLSKMLEYDPQKRITAAQALEHEYFRMEPLPGRNA
    LVPSSPGDKVNYPTRPVDTTTDIEGTTSLQPSQSASSGN
    AVPGNMPGPHVVTNRPMPRPMHMVGMQRVPASGMAGYNL
    NPSGMGGGMNPSGIPMQRGVANQAQQSRRKDPGMGMGGY
    PPQQKQRRF
    2 The amino acid sequence of SEQ ID MEKYQQLAKIGEGTYGIVYKAKDKKSGELLALKKIRLEA
    262. The conserved eukaryotic EDEGIPSTAIREISLLKQLQHPNIVRLYDVVHTEKKLTL
    protein kinase domain is VFEFLDQDLKKYLDACGDNGLEPYTVKSFLYQLLQGIAF
    underlined and the protein kinases CHEHRVLHRDLKPQNLLINMEGELKLADFGLARAFGIPV
    ATP-binding region and RNYTHEVVTLWYRAPDVLMGSRKYSTQVDIWSVGCIFAE
    serine/threonine protein kinases MVNGRPLFPGSSEQDQLLRIFKTLGTPSLKTWPGMAELP
    active-site signatures are in DFKDNFPKYVVQSFKKICPKKLDKTGLDLLSRMLQYDPA
    bold. KRISAEQAMGHPYF KDLKLRKPKAAGPGP
    3 The amino acid sequence of SEQ ID MDQYEKIEKIGEGTYGVVYKAIDRSTNKTIALKKIRLEQ
    263. The conserved eukaryotic EDEGVPSTAIREISLLKEMQHGNIVKLQDVVHSERRLYL
    protein kinase domain is VFEYLDLDLKKHMDSCPEFSKDTHTIKMFLYQILRGISY
    underlined and the protein kinases CHSHRVLHRDLKPQNLLLDRRTNSLKLADFGLARAFGIP
    ATP-binding region and VRTFTHEVVTLWYRAPEILLGSRHYSTPVDVWSVGCIFA
    serine/threonine protein kinases EMVNRRPLFPGDSEIDELFKIFRIMGTPNEDSWPGVTSL
    active-site signatures are in PDFKSTFPKWASQDLKTVTPTVDPAGIDLLSKMLCMDPR
    bold. RRITAKVALEHEYFKDVGVIP
    4 The amino acid sequence of SEQ ID MVMKSKLDKYEKLEKLGEGTYGVVYKAQDKTTKEIYALK
    264. The conserved eukaryotic KIRLESEDEGIPSTAIREIALLKELQHPNVVRIHDVIHT
    protein kinase domain is NKKLILVFEFVDYDLKKFLHNFDKGIDPKIVKSLLYQLV
    underlined and the protein kinases RGVAHCHQQKVLHRDLKPQNLLVSQEGILKLGDFGLARA
    ATP-binding region and FGIPVKNYTNEVVTLWYRAPDILLGSKNYSTSVDIWSIG
    serine/threonine protein kinases CIFVEMLNQKPLFPGSSEQDQLKKIFKIMGTPDATKWPG
    active-site signatures are in IAELPDWKPENFEKYPGEPLNKVCPKMDPDGLDLLDKML
    bold. KCNPSERIAAKNAMSHPYFKDIPDNLKKLYN
    5 The amino acid sequence of SEQ ID MDQYEKVEKIGEGTYGVVYKAIDRLTNETIALKKIRLEQ
    265. The conserved eukaryotic EDEGVPSTAIREISLLKEMQHGNIVRLQDVVHSENRLYL
    protein kinase domain is VFEYLDLDLKKHMDSSPDFAKDPRLVKIFLYQILRGIAY
    underlined and the protein kinases CHSHRVLHRDLKPQNLLIDRRTNALKLADFGLARAFGIP
    ATP-binding region and VRTFTHEVVTLWYRAPEILLGSRHYSTPVDVWSVGCIFA
    serine/threonine protein kinases EMVNQRPLFPGDSEIDELFKIFRILGTPNEDTWPGVTAL
    active-site signatures are in PDFKSAFPKWPAKNLQDMVPGLNSAGIDLLSKMLCLDPS
    bold. KRITARSALEHEYFKDIGFVP
    6 The amino acid sequence of SEQ ID MEKYEKLEKVGEGTYGKVYKAKDKATGQLVALKKTRLEM
    266. The conserved eukaryotic DEEGVPPTALREVSLLQLLSQSLYVVRLLSVEHVDGGSK
    protein kinase domain is RKAAAAAAAEGGGGEAHGGGAVGGGKPMLYLVFEYLDTD
    underlined and the protein kinases LKKFIDSHRKGPNPRPVPAATVQNFLYQLLKGVAHCHSH
    ATP-binding region and GVLHRDLKPQNLLVDKEKGILKIADLGLGRAFTVPLKSY
    serine/threonine protein kinases THEVFAFLAILLWRSEGESAADFDSXFRVSPVQVVTLWY
    active-site signatures are in RAPEVLLGSAHYSIGVDMWSVGCIFAEMVRRQALFPGDS
    bold. EFQQLLHIFRLLGTPTEKQWPGVTTLRDWHVYPQWEPQN
    LARAVPSLGPDGVDLLSKMLKYDPAERISAKAALDHPFF
    DSLDKSQF
    7 The amino acid sequence of SEQ ID MERPATAAVSAMEAFEKLEKVGEGTYGKVYRAREKATGK
    267. The conserved eukaryotic IVALKKTRLHEDEEGVPPTTLREISILRMLSRDPHIVRL
    protein kinase domain is MDVKQGQNKEGKTVLYLVFEYMETDLKKYIRGFRSSGES
    underlined and the protein kinases IPVNIVKSLMYQLCKGVAFCHGHGVLHRDLKPHNLLMDK
    ATP-binding region and KTLTLKIADLGLARAFTVPIKKYTHEILTLWYRAPEVLL
    serine/threonine protein kinases GATHYSTAVDMWSVGCIFAELVTKQALFPGDSELQQLLH
    active-site signatures are in IFRLLGTPNEKMWPGVSSLMNWHEYPQWKPQSLSTAVPN
    bold. LDKDGLDLLSQMLHYEPSRRISAKAAMEHPYFDDVNKTCL
    8 The amino acid sequence of SEQ ID MGCVLGREVSSGIVTESKGRDSSEVETSKRDDSVAAKVE
    268. The conserved eukaryotic GEGKAEEVRTEETQKKEKVEDDQQSREQRRRSKPSTKLG
    protein kinase domain is NLPKHIRGEQVAAGWPSWLSDICGEALNGWIPRRANTFE
    underlined and the KIDKIGQGTYSNVYKAKDLLTGKIVALKKVRFDNLEPES
    serine/threonine protein kinases VRFMAREILILRHLDHPNVVKLEGLVTSRMSCSLYLVFE
    active-site signature is in bold. YMEHDLAGLAASPAIKFTEPQVKCYMHQLLSGLEHCHNR
    RVLHRDIKGSNLLIDNGGVLKIGDFGLASFYDPDHKHRM
    TSRVVTLWYRPPELLLGANDYGVGIDLWSAGCILAELLA
    GKPIMPGRTEVEQLHKIYKLCGSPSEEYWKKYKLPNATL
    FKPREPYRRCIRETFKDFPPSSLPLIETLLAIDPAERGT
    ATDALQSEFFRTEPYACEPSSLPQYPPSKEMDAKKRDDE
    ARRLRAASKGQADGSKKERTRDRRVRAVPAPEANAELQH
    NIDRRRLISHANAKSKSEKFPPPHQDGALGFPLGASHRF
    DPAVVPPDVPFTSTSFTSSKEHDQTWSGPLVDPPGAPRR
    KKHSAGGQRESSKLSMGTNKGRRADSHLKAYESKSIA
    9 The amino acid sequence of SEQ ID MYSKSSAVDDSRESPKDRVSSSRRLSEVKTSRLDSSRRE
    269. The conserved eukaryotic NGFRARDKVGDVSVMLIDKKVNGSARFCDDQIEKKSDRL
    protein kinase domain is QKQRRERAEAAAAADHPGAGRVPKAVEGEQVAAGWPVWL
    underlined and the SAVAGEAIKGWLPRRADTFEKLDKIGQGTYSSVYKARDV
    serine/threonine protein kinase TNNKIVALKRVRFDNLDTESVKFMAREIHILRMLDHPNV
    active-site signature is in bold. IKLEGLITSRMSCSLYLVFEYMEHDLTGLASRPDVKFSE
    PQIKCYMKQLLSGLDHCHKHGVLHRDIKGSNLLIDNNGI
    LKIADFGLASVFDPHQTAPLTSRVVTLWYRPPELLLGAS
    RYGVEVDLWSTGCILGELYTGKPILPGKTEVEQLHKIFK
    LCGSPSDDYWRRLHLPHAAVFKPPQPYRRCVAEIFKELP
    PVALGLLETLISVDPSQRGTAAFALRSEFFTASPLPCDP
    SSLPKYPPSKEIDMKLREEEARRRGAAGGKNELEKRGTK
    DSRTNSAYYPNAGQLQVKQCHSNANGRSEIFGPYQEKTV
    SGFLVAPPKQARVSKETRKDYAEQPDRASFSGPLVPGPG
    FSKAGKELGHSITVSRNTNLSTLSSLVTSRTGDNKQKSG
    PLVSESANQASRYSGPIREMEPARKQDRRSHVRTNIDYR
    SREDGNSSTKEPALYGRGSAGNKIYVSGPLLVSSNNVDQ
    MLKEHDRRIQEHARRARFDKARVGNNHPQAAVDSKLVSV
    HDAG
    10 The amino acid sequence of SEQ ID MGCIPTIISDGRRRSAAPDKRRPRPRRSSSEGEAPPHAT
    270. The conserved eukaryotic AAGSEGGESARGAPGKERPEPAPRFVVRSPQGWPPWLVA
    protein kinase domain is AVGHAIGEFVPRCADSFRKLAKIGEGTYSNVYKARDLVT
    underlined and the GKTVALKKVRFDNLEAESIKFMAREILVLTRLNHPNVIK
    serine/threonine protein kinase LEGPVTSRMSSGLYLAFEYMEHDLSGIAARQNGKFTEPQ
    active-site is in bold VKCFMRQLLSGLEHCHNHDVLHRDIKCSNLLIDNEGNLK
    IADFGLATFYDPERKQVMTNRVVTLWYRAPELLLGATSY
    GIGIDLWSAGCILAELLYGKPIMPGRTEVEQLHKIFKLC
    GSPSEAYWNKFKLPNANIFKPPQPYARCIAETFKDFPPS
    ALPLLETLLSIDPDERGTATTALNSEFFAAEPHACEPSS
    LPKYPPSKEMDLKLIKEKTRRDSSKRPSAIHGSRRDGIH
    DRAGRVIPAPEATAENQATLHRPRAMKKANPMSRSEKFP
    PAHMDGVVGSSANAWLSGPASNAAPDSRRHRSLNQNPSS
    SVGKASTGSSTTQETLKVAPELLQVGSSSLHPCHRMLVY
    GSNLTIRSK
    11 The amino acid sequence of SEQ ID MGCICAKQADRGPASPGSGILTGAGTGTGTRSSKIPSGL
    271. The conserved protein kinase FEFEKSGVKEHGGRSGELRKLEEKGSLSKRLRLELGFSH
    family domain is underlined, and RYVEAEQAAAGWPSWLTAVAGDAIQGLVPLKADSFEKLE
    the serine/threonine protein KIGQGTYSSVFRARELANGRMVALKKVRFDNFQPESIQF
    kinases active-site signature is MAREISILRRLDHPNIMKLEGIITSRMSNSIYLVFEYME
    in bold HDLYGLISSPQVKFSDAQVKCYMKQLLSGIEHCHQHGVI
    HRDVKSSNILVNNEGILRIGDFGLANILNPKDRQQLTSH
    VVTLWYRPPELLMGSTSYGVTVDLWSVGCVFAELMFRKP
    ILRGRTEVEQLHKIFKLCGSPPDGYWKMCKVPQATMFRP
    RHAYECTLRERCKGIATSAMKLMETFLSIEPHKRGTASS
    ALISEYFRTVPYACDPSSLPKYPPNKEIDAKHREEARRK
    KARSRVREAEVGKRPTRIHRASQEQGFSSNIAPKEKRSYA
    12 The amino acid sequence of SEQ ID MAVAAPGHLNVNESPSWGSRSVDCFEKLEQIGEGTYGQV
    272. The conserved eukaryotic YMAKEKKTGEIVALKKIRMDNEREGFPITAIREIKILKK
    protein kinase domain is LHHENVIKLKEIVTSPGPEKDEQGRPEGNKYKGGIYMVF
    underlined and the protein kinases EYMDHDLTGLADRPGMRFSVPQIKCYMRQLLTGLHYCHI
    ATP-binding region and NQVLHRDIKGSNLLIDNEGNLKLADFGLARSFSNDHNAN
    serine/threonine protein kinases LTNRVITLWYRPPELLLGATKYGPAVDMWSVGCIFAELL
    active-site signatures are in HGKPIFPGKDEPEQLNKIFELCGAPDEINWPGVSKIPWY
    bold. NNFKPTRPMKRRLREVFRHFDRHALELLERMLTLDPSQR
    ISAKDALDAEYFWADPLPCDPKSLPKYESSHEFQTKKKR
    QQQRQHEETAKRQKLQHPPQHPRLPPVQQSGQAHAQMRP
    GPNQLMHGSQPPVATGPPGHHYGKPRGPSGGAGRYPSSG
    NPGGGYNHPSRGGQGGSGGYNSGPYPPQGRAPPYGSSGM
    PGAGPRGGGGNNYGVGPSNYPQGGGGPYGGSGAGRGSNM
    MGGNRNQQYGWQQ
    13 The amino acid sequence of SEQ ID MGCICTKGILPAHYRIKDGGLKLSKSSKRSVGSLRRDEL
    273. The conserved AVSANGGGNDAADRLISSPHEVENEVEDRKNVDFNEKLS
    serine/threonine protein kinase KSLQRRATMDVASGGHTQAQLKVGKVGGFPLGERGAQVV
    domain is underlined, and the AGWPSWLTAVAGEAINGWVPRRADSFEKLEKIGQGTYSS
    serine/threonine protein kinase VYRARDLETNTIVALKKVRFANMDPESVRFMAREIIIMR
    active-site signature is in bold. KLDHPNVMKLEGLITSRVSGSLYLVFEYMDHDLAGLAAT
    PSIKLTESQIKCYMQQLLRGLEYCHSHGVLHRDIKGSNL
    LVDNNGNLKIGDFGLATFFRTNQKQPLTSRVVTLWYRPP
    ELLLGSSDYGASVDLWSSGCILAELFAGKPIMPGRTEVE
    QLHKIFKLCGSPSEEYWKKSKLPHATIFKPQQPYKRCLL
    ETFKDFPSSALGLLDVLLAVEPECRGTASSALQNEFFTS
    NPLPSDPSSLPKYPSSKEFDARLRDEEARKHKATAGKAR
    GLESIRKGSKESKVVPTSNANADLKASIQKRQEQSNPRS
    TGEKPGGTTQNNFILSGQSAKPSLNGSTQIGNANEVEAL
    IVPDRELDSPRGGAELRRQRSFMQRRASQLSRFSNSVAV
    GGDSHLDCSREKGANTQWRDEGFVARCSHPDGGELAGKH
    DWSHHLLHRPISLFKKGGEHSRRDSIASYSPKKGRIHYS
    GPLLPSGDNLDEMLKEHERQIQNAVRKARLDKVKTKREY
    ADHGQTESLLCWANGR
    14 The amino acid sequence of SEQ ID MDPDPSPDPDPPKSWSIHTRREIIARYEILERVGSGAYS
    274. The conserved protein kinase DVYRGRRLSDGLAVALKEVHDYQSAFREIEALQILRGSP
    family domain is underlined and HVVLLHEYFWREDEDAVLVLEFLRSDLAAVIADASRRPR
    the serine/threonine protein DGGGGGAAALRAGEVKRWMLQVLEGVDACHRNSIVHRDL
    kinases active-site signature is KPGNLLISEEGVLKIADFGQARILLDDGNVAPDYEPESF
    in bold. EERSSEQADILQQPETMEADTTCPEGQEQGAITREAYLR
    EVDEFKAKNPRHEIDKETSIFDGDTSCLATCTTSDIGED
    PFKGSYVYGAEEAGEDAQGCLTSCVGTRWFRAPELLYGS
    TDYGLEVDLWSLGCIFAELLTLEPLFPGISDIDQLSRIF
    NVLGNLSEEVWPGCTKLPDYRTISFCKIENPIGLESCLP
    NCSSDEVSLVRRLLCYDPAARATPMELLQDKYFTEEPLP
    VPISALQVPQSKNSHDEDSAGGWYDYNDMDSDSDFEDFG
    PLKFTPTSTGFSIQFP
    15 The amino acid sequence of SEQ ID MDPDPSPSPDPPKSWSIHTRREIIARYEILERVGSGAYS
    275. The conserved DVYRGRRLSDGLAVALKEVHDYQSAFREIEALQILRGSP
    serine/threonine protein kinase HVVLLHEYFWREDEDAVLVLEFLRSDLAAVIADASRRPR
    domain is underlined, and the GGGVAPLRAGEGKRWMLQVLEGVDACHRNSIVHRDLKPG
    serine/threonine protein kinase NLLISEEGVLKIADFGQARILLDDGNVAPDYEPESFEER
    active-site signature is in bold. SSEQADILQQPETMEADTTCPEGQEQGAITREAYLREVD
    EFKAKNPRHEIDKETSIYDGDTSCLATCTTSDIGEDPFK
    GSYVYGAEEAGEDAQGSLTSCVGTRWFRAPELLYGSTDY
    GLEVDLWSLGCIFAELLTLEPLFPGISDIDQLSRIFNVL
    GNLSEEVWPGCTKLPDYRTISFCKIENPIGLESCLPNCS
    SDEVSLVRRLLCYDPAARATPMELLQDKYFTEEPLPVPI
    SALQVPQSKNSHDEDSAGGWYDYNDMDSDSDFEDFGPLK
    FTPTSTGFSIQFP
    16 The amino acid sequence of SEQ ID MSNQHRRSSFSSSTTSSLAKRHASSSSSSLENAGKAFAA
    276. The conserved cyclin and AAVPSHLAKKRAPLGNLTNLKAGDGNSRSSSAPSTLVAN
    cyclin C-terminal domains are ATKLAKTRKGSSTSSSIMGLSGSALPRYASTKPSGVLPS
    underlined and the cyclins VNPSIPRIEIAVDPMSCSMVVSPSRSDMQSVSLDESMST
    signature is in bold. CESFKSPDVEYIDNEDVSAVDSIDRKTFSNLYISDAAAK
    TAVNICERDVLMEMETDEKIVNVDDNYSDPQLCATIACD
    IYQHLRASEAKKRPSTDFMDRVQKDITASMRAILIDWLV
    EVAEEYRLVPDTLYLTVNYIDRYLSGNVMNRQRLQLLGV
    ACMMIAAKYEEICAPQVEEFCYITDNTYFKEEVLQMESS
    VLNYLKFEMTAPTVKCFLRRFVRAAQGVNEVPSLQLECM
    ANYIAELSLLEYDMLCYAPSLVAASAIFLAKFVITPSKR
    PWDPTLQHYTLYQPSDLGNCVKDLHRLCFNNHGSTLPAI
    REKYSQHKYKYVAKKYCPPSIPPEFFHNLVY
    17 The amino acid sequence of SEQ ID MNKENAVGTKSEAPTIRITRSRSKALGTSTGMLPSSRPS
    277. The conserved cyclin and FKQEQKRTVRANAKRSASDENKGTMVGNASKQHKKRTVL
    cyclin C-terminal domains are NDVTNIFCENSYSNCLNAAKAQTSRQGRKWSMKKDRDVH
    underlined. QSGAVQIMQEDVQAQFVEESSKIKVAESMEITIPDKWAK
    RENSEHSISMKDTVAESSRKPQEFICGEKSAALVQPSIV
    DIDSKLEDPQACTPYALDIYNYKRSTELERRPSTIYMET
    LQKDVTPNMRGILVDWLVEVSEEYKLVPDTLYLTVNLID
    RSLSQKFIEKQRLQLLGVTCMLIASKYEEICPPRVEEFC
    FITDNTYTSLEVLKMESRVLNLLHFQLSVPTVKTFLRRF
    VQAAQVSSEVPSVELEYLANYLAELTLVEYSFLKFLPSL
    MAASAVLLARWTLNQSDNPWNLTLEHYTKYKASELKAAV
    LALEDLQLNTSGSTLNAIREKYRQQKVNYSLLIHSKANH
    EIL
    18 The amino acid sequence of SEQ ID MAGSDENNPGVVGGAHVQEGLRVGAGKMGAGNVQQRRAL
    278. The conserved cyclin N- and SNINSNIIGAPPYPCAVNKRVLSEKNVNSENDLLNAAHR
    C-terminal family domains are PITRQFAAQMAYKQQLRPEENKRTTQSVSNPSKSEDCAI
    underlined and the cyclins LDVDDDKMADDFPVPMFVQHTEAMLEEIDRMEEVEMEDV
    signature is in bold. AEEPVTDIDSGDKENQLAVVEYIDDLYMFYQKAEASSCV
    PPNYMDRQQDINERMRGILIDWLIEVHYKFELMDETLYL
    TVNLIDRFLAVQPVVKKKLQLVGVTAMLLACKYEEVSVP
    VVEDLILISDRAYSRKEVLEMERLMVNTLHFNMSVPTPY
    VFMRRFLKAAQSDKKLELLSFFIIELSLVEYDMLKFPPS
    LLAASAIYTALSTITRTKQWSTTCEWHTSYSEEQLLECA
    RLMVTFHQRAGSGKLTGVHRKYSTSKFGHAARTEPANFL
    LDFRL
    19 The amino acid sequence of SEQ ID MASRPIVPVQARGEAAIGGGAGKAAIGGGAGKQQKKNGA
    279. The conserved cyclin and AEGRNRKALGDIGNLVTVRGIEGKVQPHRPITRSFCAQL
    cyclin C-terminal domains are LANAQAAAAAENNKKQAVVNVNGAPSILDVPGAGKRAEP
    underlined. AAAAAAAVAKAAQKKVVKPKQKAEVIDLTSDSEERSRPR
    RSNNIMSLRRRKERNHREGICPLSLRSSLLEARLVDWLI
    EIHNKFDLMPETLYLTINIIDRFLSVKAVPRRELQLLGM
    GALFTASKYEEIWAPEVNDLVCIADRAYSHEQVLAMEKT
    ILGKLEWTLTVPTHYVFLVRFIKASLGDRKLENMVYFLA
    ELGVMNYATLTYCPSMVAASAVYAARCTLGLTPLWNDTL
    KLHTGFSESQLMDCARLLVGYHAKAKENKLQVVYKKYSS
    SQREGVALIPPAKALLCEGGGLSSSSSLASSS
    20 The amino acid sequence of SEQ ID MGLPDENNAALSKPTNLQVGGLEIGGRKFGQEIRQTRRA
    280. The conserved cyclin and LSVINQNLVGDRAYPCHVVNKRGHSKRDAVCGKDQVDPV
    cyclin C-terminal domains are HRPLTRKFAAQTASTQQHCIEEAKKPRTAVQERNEFGDC
    underlined and the cyclins IFVDVEDCQPSSENQPVPMFLEIPESRLDDDMEEVEMED
    signature is in bold. IVEEEEEEPIMDIDGRDKKNPLAVVDYIEDIYANYRRTE
    NCSCVSANYMAQQADINEKMRSILIDWLIEVHDKFDLMH
    ETLFLTVNLIDRFLARQSVVRKKLQLVGLVAMLLACKYE
    EVSVPVVGDLILISDKAYTRKEVLEMESLMLNSLQFNMS
    VPTPYVFMRRFLKAAESDKKLEVLSFFLIELSLVEYEMV
    KFPPSLLAAAAIFTAQCTLYGFKQWTKTCEWHSNYTEDQ
    LLECARMMVGFHQKAATGKLTGVHRKYGTSKFGYTSKCE
    PANFLLGEMKNP
    21 The amino acid sequence of SEQ ID MGLPDENNAALSKPTNLQVGGLEIGGRKFGQEIRQTRRA
    281. The conserved cyclin and LSVINQNLVGDRAYPCHVVNKRGHSKRDAVCGKDQVDPV
    cyclin C-terminal domains are HRPLTRKFAAQTASTQQHCIEEAKKPRTAVQERNEFGDC
    underlined and the cyclins IFVDVEDCQPSSENQPVPMFLEIPESRLDDDMEEVEMED
    signature is in bold. IVEEEEEEPIMDIDGRDKKNPLAVVDYIEDIYANYRRTE
    NCSCVSANYMAQQADINEKMRSILIDWLIEVHDKFDLMH
    ETLFLTVNLIDRFLARQSVVRKKLQLVGLVAMLLACKYE
    EVSVPVVGDLILISDKAYTRKEVLEMEKLMLNSLQFNMS
    VPTPYVFMRRFLKAAESDKKLEVLSFFLIELSLVEYEMV
    KFPPSLLAAAAIFTAQCTLYGFKQWTKTCEWHSNYTEDQ
    LLECARMMVGFHQKAATGKLTGVHRKYGTSKFGYTSKCE
    AANFLLGEMKNP
    22 The amino acid sequence of SEQ ID MAMVQRQGHDPSSPQEQEDGPSSFLSDDALYCEEGRFEE
    282. The conserved cyclin N- and DDGGGGGQVDGIPLFPSQPADRQQDSPWADEDGEEKEEE
    C-terminal family domains are EAELQSLFSKERGARPELAKDDGGAVAARREAVEWMLMV
    underlined. RGVYGFSALTAVLAVDYLDRFLAGFRLQRDNRPWMTQLV
    AVACLALAAKVEETDVPLLVELQEVGDARYVFEAKTVQR
    MELLVLSTLGWEMHPVTPLSFVHHVARRLGASPHHGEFT
    HWAFLRRCERLLVAAVSDARSLKHLPSVLAAAAMLRVIE
    EVEPFRSSEYKAQLLSALHMSQEMVEDCCRFILGIAETA
    GDAVTSSLDSFLKRKRRCGHLSPRSPSGVIDASFSCDDE
    SNDSWATDPPSDPDDNDDLNPLPKKSRSSSPSSSPSSVP
    DKVLDLPFMNRIFEGIVNGSPI
    23 The amino acid sequence of SEQ ID MEASYQPHHHGHLRQHDPSSSQQEEQVPFDALYCSEEHW
    283. The conserved cyclin and GEEDEEEGLASDGLLSEERDHRLLSPRALLDQDLLWEDE
    cyclin C-terminal domains are ELASLFSKEEPGGMRLNLENDPSLADARREAVEWIMRVH
    underlined. AHYAFSALTALLAVNYWDRFTCSFALQEDKPWMTQLSAV
    ACLSLAAKVEETQVPLLIDFQVEDSSPVFEAKNIQRMEL
    LVLSSLEWKMNPVTPLSFLDYMTRRLGLTGHLCWEFLRR
    CENVLLSVISDCRFTCYLPSVIAASTMLHVINGLKPRLD
    VEDQTQLLGILAMGMDKIDACYKLIDDDHALRSQRYSHN
    KRKFGSVPGSPRGVMELCFSSDGSNDSWSVAASVSSSPE
    PHSKKSRAGEEAEDRLLRGLEGEEDDPASADIFSFPH
    24 The amino acid sequence of SEQ ID MALQEEDTRRHYPTAPPFSPDGLYCEDETFGEDLADNAC
    284. The conserved cyclin and EYAGGGARDGLCEIKDPTLPPSLLGQDLFWEDGELASLV
    cyclin C-terminal domains are SRETGTHPCWDELISDGSVALARKDAVGWILRVHGHYGF
    underlined. RPLTAMLAVNYLDRFFLSRSYQRDRPWISQLVAVACLSV
    AAKVEETQVPILLDLQVANAKFVFESRTIQRMELLLMST
    LDWRMNSVTPISFFDHILRRFGLTTNLHRQFFWMCERLL
    LSVVADVRLASFLPSVVATAAMLYVNKEIEPCICSEFLD
    QLLSLLKINEDRVNECYELILELSIDHPEILNYKHKRKR
    GSVPSSPSGVIDTSFSCDSSNDSWGVASSVSSSLEPRFK
    RSRFQDQQMGLPSVNVSSMGVLNSSY
    25 The amino acid sequence of SEQ ID MGQIQYSEKYFDDTYEYRHVVLPPDVAKLLPKNRLLSEN
    285. The conserved cyclin- EWRAIGVQQSRGWVHYAIHRPEPHIMLFRRPLNYQQQQE
    dependent kinases regulatory NQAQQNMLAK
    subunit domain is underlined and
    the cyclin-dependent kinases
    regulatory subunits signature 1 is
    in bold.
    26 The amino acid sequence of SEQ ID MGSIDPPKAEQNGTAAAAVADPGQKPGAGDAMPPPPPVK
    286. The conserved chromo domain HSNGTAAEPDVATKRRRMSVLPLEVGTRVMCRWRDGKYH
    is underlined and the MOZ/SAS-like PVKVIERRKLNPGDPNDYEYYVHYTEFNRRLDEWVKLEQ
    protein domain is in bold/italics. LDLNSVETVVDEKVEDKVTGLKMTRHQKRKIDETHVEGH
    EELDAASLREHEEFTKVKNIATIELGRYEIETWYFSPFP
    PEYNDCSKLYFCEFCLNFMKRKEQLQRHMKKCD
    Figure US20100122382A1-20100513-P00001
    Figure US20100122382A1-20100513-P00002
    Figure US20100122382A1-20100513-P00003
    Figure US20100122382A1-20100513-P00004
    Figure US20100122382A1-20100513-P00005
    Figure US20100122382A1-20100513-P00006
    Figure US20100122382A1-20100513-P00007
    Figure US20100122382A1-20100513-P00008
    Figure US20100122382A1-20100513-P00009
    Figure US20100122382A1-20100513-P00010
    Figure US20100122382A1-20100513-P00011
    PKVLDRHLKAAGRG
    GLEVDVSKLIWTPYREQG
    27 The amino acid sequence of SEQ ID MDTGGNSLPSGPDGVKRKVCYFYDPEVGNYYLLQHMQVL
    292. The conserved histone KPVPARDRDLCRFHADDYVAFLRSITPETQQDQLRQLKR
    deacetylase family domain is FNVGEDCPVFDGLHSFCQTYAGGSVGGAVKLNHGLCDIA
    underlined. INWAGGLHHAKKCEASGFCYVNDIVLGILELLKQHERVL
    YVDIDIHHGDGVEEAFYTTDRVMTVSFHKFGDYFPGTGD
    IRDIGYGKGKYYSLNVPLDDGIDDESYHSLFKPIIGKVM
    EVFKPGAVVLQCGADSLSGDRLGCFNLSIKGHAECVRYM
    RSFNVPVLLLGGGGYTIRNVARCWCYETGVALGLEVDDK
    MPQHEYYEYFGPDYTLHVAPSNMENKNSRQLLEEIRSKL
    LENLSKLQHAPSVPFQERPPDTELPEADEDQEDPDERWD
    PDSDMDVDEDRKPLPSRVKRELIVEPEVKDQDSQKASID
    HGRGLDTTQEDNASIKVSDMNSMITDEQSVKMEQDNVNK
    PSEQIFPK
    28 The amino acid sequence of SEQ ID MDTGGNSLPSGPDGVKRKVCYFYDPEVGNYYYGQGHPMK
    293. The conserved histone PHRIRMTHALLAHYGLLQHMQVLKPVPARDRDLCRFHAD
    deacetylase family domain is DYVAFLRSITPETQQDQLRQLKRFNVGEDCPVFDGLHSF
    underlined. CQTYAGGSVGGAVKLNHGLCDIAINWAGGLHHAKKCEAS
    GFCYVNDIVLGILELLKQHERVLYVDIDIHHGDGVEEAF
    YTTDRVMTVSFHKFGDYFPGTGDIRDIGYGKGKYYSLNV
    PLDDGIDDESYHSLFKPIIGKVMEVFKPGAVVLQCGADS
    LSGDRLGCFNLSIKGHAECVRYMRSFNVPVLLLGGGGYT
    IRNVARCWCYETGVALGLEVDDKMPQHEYYEYFGPDYTL
    HVAPSNMENKNSRQLLEDIRSKLLENLSKLQHAPSVPFQ
    ERPPDTELPEADEDQEDPDERWDPDSDMDVDEDRKPLPS
    RVKRELIVEPEVKDQDSQKASIDHGRGLDTTQEDNASIK
    VSDMNSMITDEQSVKMEQDNVNKPSEQIFPK
    29 The amino acid sequence of SEQ ID MRPKDRISYFYDGDVGSVYFGPNHPMKPHRLCMTHHLVL
    294. The conserved histone SYELHTKMEIYRPHKAYPAELAQFHSPDYVEFLHRITPD
    deacetylase domain is underlined. TQHLFPNDLAKYNLGEDCPVFENLFEFCQIYAGGTIDAA
    RRLNNQLCDIAINWAGGLHHAKKCEASGFCYINDLVLGI
    LELLKYHARVLYIDIDVHHGDGVEEAFYFTDRVMTVSFH
    KFGDMFFPGTGDVKEIGGKEGKFYAINVPLKDGIDDTSF
    TRLFKAIISKVVETYQPGAIVLQCGADSLAGDRLGCFNL
    SIDGHSECVRFVKKFNLPLLVTGGGGYTKENVARCWVVE
    TGVLLDTELPNEIPENEYFKYFAPDYSLKIPRGNIVLEN
    LNSKSYLSAIKVQVLENLRNIQHAPSVQMQEVPPDFYIP
    DFDEDEQNPDERMDQHTQDKQIQRDDEYYDGDNDNDHNM
    DD
    30 The amino acid sequence of SEQ ID MTVAEDFHVNNRSKMVSQATPESRLTGGEDDNSLHNQVD
    295. The conserved histone ELLCQELPERQVILEFEGTRPKPYFSDHNGGENSALGVR
    deacetylase family domain is ATEDDLNSDVEAEEKQKEMTLEDMYKNDGTLYDDDEDDS
    underlined and the Zinc finger DWEPVKRQVELMRWFCTNCTMVNVEDVFLCDICGEHRDS
    RanBP2-type profile is in bold. GILRHGFYASPFMQDVGAPSVEAEVQESREDHARSSPPS
    SSTVVGFDEKMLLHSEVEMKSHPHPERADRLQAIAASLA
    TAGIFPGRCRSLPVREITKEELQMVHSSEHVDAVEMTSH
    MFSSYFTPDTYANEHSARAARIAAGLCADLASTIISGRS
    KNGFALVRPPGHHAGIKHAMGFCLHNNAAVAALAAQGAG
    AKKVLIVDWDVHHGNGTQEIFDGNKSVLYISLHRHEGGN
    FYPGTGAAHEVGTMGAEGYCVNIPWSRRGVGDNDYVFAF
    HHIVLPIASAFAPDFTIISAGFDAARGDPLGCCDVTPAG
    YAQMTHMLSALSGGKLLVILEGGYNLRSISSSAVAVIKV
    LLGDSPISEIADAVPSKAGLRTVLEVLKIQRSYWPSLES
    IFWELQSQWGMFLVDNRRKQIRKRRRVLVPIWWKWGRKS
    VLYHLLNGHLHVKTKR
    31 The amino acid sequence of SEQ ID MAAAPSSPPTNRVDVFWHDGMLSHDTGRGVFDTGSDPGF
    296. The conserved histone LDVLEKHPENPDRVRNMVSILKRGPISPFISWHTATPAL
    deacetylase family domain is ISQLLSFHSPEYINELVEADKNGGKVLCAGTFLNPGSWD
    underlined. AALLAAGNTLSAMKYVLDGKGKIAYALVRPPGHHAQPSQ
    ADGYCFLNNAGLAVRLALDSGCKRVVVVDIDVHYGNGTA
    EGFYQSSDVLTISLHMNHGSWGPSHPQSGSVDELGEDEG
    YGYNMNIPLPNGTGDRGYEYAVTELVVPAVESFKPEMVV
    LVVGQDSSAFDPNGRQCLTMDGYRAIGRTIRGLADRHSG
    GRILIVQEGGYHVTYSAYCLHATVEGILDLPDPLLADPI
    AYYPEDEAFPVKVVDSIKRYLVDKVPFLKEH
    32 The amino acid sequence of SEQ ID MVESSGGASLPSVGQDARKRRVSYFYEPTIGDYYYGQGH
    297. The conserved histone PMKPHRIRMAHNLIVHYYLHRRMEISRPFPAATTDIRRF
    deacetylase family domain is HSEDYVTFISSVTPETVSDPAFSRQLKRFNVGEDCPVFD
    underlined. GIFGFCQASAGGSMGAAVKLNRGDSDIALNWAGGLHHAK
    KSEASGFCYVNDIVLGILELLKVHKRVLYVDIDVHHGDG
    VEEAFYTTDRVMTVSFHKFGDFFPGSGHIKDTGAGPGKN
    YALNVPLNDGIDDESFRGMFRPIIQKVMEVYQPDAVVLQ
    CGADSLSGDRLGCFNLSVKGHADCLRFLRSFNVPLMVLG
    GGGYTMRNVARCWCYETAVAVGVEPENDLPYNEYYEYFG
    PDYTLHVEPCSMENLNAPKDLERIRNMLLEQLSRIPHAP
    SVPFQMTPPITQEPEEAEEDMDERPKPRIWNGEDYESDA
    EEDKSQHRSSNADALHDENVEMRDSVGENSGDKTREDRS
    PS
    33 The amino acid sequence of SEQ ID MAAIISCHHYHSCCSSLIASKWVGARIPTSCFGRSSTQS
    299. The conserved cyclophilin- NNAASVRQFVTRCSSSPSSRGQWQPHQNGEKGRSFSLRE
    type peptidyl-prolyl cis-trans CAISIALAVGLVTGVPSLDMSTGNAYAASPALPDLSVLI
    isomerase family domain is SGPPIKDPEALLRYALPINNKAIREVQKPLEDITDSLKV
    underlined. AGLRALDSVERNVRQASRVLKQGKNLIVSGLAESKKDHG
    VELLDKLEAGMDELQQIVEDGNRDAVAGKQRELLNYVGG
    VEEDMVDGFPYEVPEEYKNMPLLKGRAAVDMKVKVKDNP
    NLEECVFRIVLDGYNAPVTAGNFVDLVERHFYDGMEIQR
    ADGFVVQTGDPEGPAESFIDPSTEKPRTIPLEIMVDGEK
    APVYGATLEELGLYKAQTKLPFNAFGTMAMARDEFEDNS
    ASSQIFWLLKESELTPSNANILDGRYAVFGYVTENQDFL
    ADLKVGDVIESVQVVSGLDNLANPSYKIAG
    34 The amino acid sequence of SEQ ID MAGEDFDIPPADEMNEDFDLPDDDDDAPVMKAGDEKEIG
    300. The conserved FKBP-type KQGLKKKLVKEGDAWETPDNGDEVEVHYTGTLLDGTQFD
    peptidylprolyl isomerase domains SSRDRGTPFKFTLGQGQ
    Figure US20100122382A1-20100513-P00012
    are underlined. The FKBP-type
    Figure US20100122382A1-20100513-P00013
    EAGSPPTIPPNATLQFDVELLSWTSVKDICKD
    peptidyl-prolyl cis-trans GGIFKKILVEGEKWENPKDLDEVLVKYEFQLEDGTTIAR
    isomerase signature
    1 is in bold SDGVEFTVKEGHFCPAVAKAVKTMKKGEKVLLTVKPQYG
    and the FKBP-type peptidyl-prolyl FGEKGKPASGDEGAVPPNATLQITLELVSWKTVSEVTDD
    cis-trans isomerase signature 2 is KKVIKKILKEGEGYERPNEGAVVEVKLIGKLQDGTVFVK
    in bold/italics. KGHDDCEELFKFKIDEEQ
    Figure US20100122382A1-20100513-P00014
    Figure US20100122382A1-20100513-P00015
    SSESKQDLAVVPPSSTVYYEVELVSFVKDKE
    SWDMNTEEKIEAAGKKKEEGNVIFKAGKYAKASKRYEKA
    VKYIEYDTSFSEDEKKQAKALKVACNLNDAACKLKLKDY
    NQAEKLCTKVLELDSRNVKALYRRAQAYIELSDLDLAEF
    DIKKALEIDPHNRDVKLEYKVLKEKVKEFNKKDAKFYGN
    MFAKMSKLEPVEKTAAKEPEPMSIDSKA
    35 The amino acid sequence of SEQ ID MSTVYVLEPPTKGKVVLNTTHGPLDVELWPKEAPKAVRN
    301. The conserved cyclophilin- FVQLCLEGYYDNTIFHRIIKDFLVQGGDPTGSGTGGESI
    type peptidyl-prolyl cis-trans YGDAFSDEFHSRLRFKHRGLVACANAGSPHSNGSQFFIT
    isomerase family domain is LDRCDWLDRKNTIFGKITGDSIYNLSGLAEVETDKSDRP
    underlined and the cyclophilin- LDPPPKIISVEVLWNPFEDIVPRAPVRSLVPTVPDVQNK
    type peptidyl-prolyl cis-trans EPKKKAVKKLNLLSFGEEAEEEEKALVVVKQKIKSSHDV
    isomerase signature is in bold. LDDPRLLKEHIPSKQVDSYDSKTARDVQSVREALSSKKQ
    ELQKESGAEFSNSFREIADDEDDDDDDASFDARMRRQIL
    QKRKELGDLPPKPKPKSRDGISARKERETSISRDKDDDD
    DDDQPRVEKLSLKKKGIGSEARGERMANADADLQLLNDA
    ERGRQLQKQKKHRLRGREDEVLTKLETFKASVFGKPLAS
    SAKVGDGDGDLSDWRSVKLKFAPEPGKDRMTRNEDPNDY
    VVVDPLLEKGKEKFNRMQAKEKRRGREWAGKSLT
    36 The amino acid sequence of SEQ ID MASAISMHSSGLLLLQGTNGKDVTEMGKAPASSRVANMQ
    302. The conserved cyclophilin- QRKYGATCCVARGLTSRSHYASSLAFKQFSKTPSIKYDR
    type peptidyl-prolyl cis-trans MVEIKAMATDLGLQAKVTNKCFFDVEIGGEPAGRIVIGL
    isomerase family domain is FGDDVPKTVENFRALCTGEKGFGYKGCSFHRIIKDFMIQ
    underlined and the cyclophilin- GGDFTRGNGTGGKSIYGSTFEDENFALKHVGPGVLSMAN
    type peptidyl-prolyl cis-trans AGPSTNGSQFFICTVKTPWLDNRHVVFGQVVDGMDVVQK
    isomerase signature is in bold. LESQETSRSDVPRQPCRIVNCGELPLDG
    37 The amino acid sequence of SEQ ID MAASFTALSNVGSLSSPRNGSEIRRFRPSCNVAASVRPP
    303. The conserved cyclophilin- PLKAGLSASSSSSFSGSLRLIPLSSSPQRKSRPCSVRAS
    type peptidyl-prolyl cis-trans AEAAAAQSKVTNKVYLDISIGNPVGKLVGRIVIGLYGDD
    isomerase signature is underlined. VPQTAENFRALCTGEKGFGYKGSTVHRVIKDFMIQGGDF
    DKGNGTGGKSIYGRTFKDENFKLSHVGPGVVSMANAGPN
    TNGSQFFICTVKTPWLDQRHVVFGQVLEGMDIVRLIESQ
    ETDRGDRPRKRVVVSDCGELPVV
    38 The amino acid sequence of SEQ ID MAEAIDLTGDGGVMKTIVRRAKPDAVSPSETLPLVDVRY
    304. The conserved FKBP-type EGVLAETGEVFDSTHEDNTLFSFEIGKGSVISAWDTALR
    peptidyl-prolyl cis-trans TMKVGEVAKITCKPEYAYGSTGSPPDIPPDATLIFEVEL
    isomerase signature is underlined VACKPCKGFSVTSVTEDKARLEELKKQREIAAATKEEEK
    and the FKBP-type peptidyl-prolyl KRREEAKAAAAARVQAKLDAKKGHGKGKGKAK
    cis-trans isomerase signature 2 is
    in bold.
    39 The amino acid sequence of SEQ ID MGNPKVFFDMSIGGQPAGRIVMELYADVVPRTAENFRAL
    305. The conserved cyclophilin- CTGEKGAGRSGKPLHYKGSSFHRVIPGFMCQGGDFTAGN
    type peptidyl-prolyl cis-trans GTGGESIYGSKFADENFVKKHTGPGVLSMANAGPGTNGS
    isomerase family domain is 1QFFVCTAKTEWLDGKHVVFGQIVDGMDVVKAIEKVGSSS
    underlined and the cyclophilin- GRTSKPVVVADCGQLS
    type peptidyl-prolyl cis-trans
    isomerase signature is in bold.
    40 The amino acid sequence of SEQ ID MPNPKVFFDMTIGGAAAGRVVMELYADTTPRTAENFRAL
    306. The conserved cyclophilin- CTGEKGVGRSKKPLHYKGSKFHRVIPSFMCQGGDFTAGN
    type peptidyl-prolyl cis-trans GTGGESIYGVKFADENFIKKHTGPGILSMANAGPGTNGS
    isomerase signature is underlined QFFICTTKTEWLDGKHVVFGKVVEGMEVVKAIEKVGSSS
    and the cyclophilin-type peptidyl- GRTSKPVVVADCGQLP
    prolyl cis-trans isomerase
    signature is in bold.
    41 The amino acid sequence of SEQ ID MAEAIDLTGDGGVMKTIVRRAKPDAVSPSETLPLVDVRY
    307. The conserved FKBP-type EGVLAETGEVFDSTHEDNTLFSFEIGKGSVISAWDTALR
    peptidyl-prolyl cis-trans TMKVGEVAKITCKPEYAYGSTGSPPDIPPDATLIFEVEL
    isomerase signature is underlined VACKPCKGFSVTSVTEDKARLEELKKQREIAAATKEEEK
    and the FKBP-type peptidyl-prolyl KRREEAKAAAAARVQAKLDAKKGHGKGKGKAK
    cis-trans isomerase signature 2 is
    in bold.
    42 The amino acid sequence of SEQ ID MATARSFFLCALLLLATLYLAQAKKSEDLKEVTHKVYFD
    308. The conserved cyclophilin- VEIAGKPAGRIVMGLYGKAVPKTAENFRALCTGEKGTGK
    type peptidyl-prolyl cis-trans SGKPLHYKGSSFHRIIPSFMLQGGDFTLGDGRGGESIYG
    isomerase signature is underlined EKFADENFKLKHTGPGLLSMANAGPDTNGSQFFITTVTT
    and the cyclophilin-type peptidyl- SWLDGRHVVFGKVLSGMDVVYKVEAEGRQSGTPKSKVVI
    prolyl cis-trans isomerase ADSGELPL
    signature is in bold.
    43 The amino acid sequence of SEQ ID MMRREISVLLQPRFVLAFLALAVLLLVFAFPFSRQRGDQ
    309. The conserved cyclophilin- VEEEPEITHRVYLDVDIDGQHLGRIVIGLYGEVVPRTVE
    type peptidyl-prolyl cis-trans NFRALCTGEKGKSANGKKLHYKGTPFHRIISGFMIQGGD
    isomerase family domain is VIYGDGKGYESIYGGTFADENFRIKHSHAGIISMVNSGP
    underlined and the cyclophilin- DSNGSQFFITTVKASWLDGEHVVFGRVIQGMDTVYAIEG
    type peptidyl-prolyl cis-trans GAGTYNGKPRKKVIIADSGEIPKSKWDEER
    isomerase signature is in bold.
    44 The amino acid sequence of SEQ ID MWATAEGGPPEVTLETSMGSFTVELYFKHAPRTSRNFIE
    310. The conserved cyclophilin- LSRRGYYDNVKFHRIIKDFIVQGGDPTGTGRGGESIYGK
    type peptidyl-prolyl cis-trans KFEDEIKPELKHTGAGILSMANAGPNTNGSQFFITLAPC
    isomerase family domain is PSLDGKHTIFGRVCRGMEIIKRLGSVQTDNNDRPIHDVK
    underlined and the cyclophilin- ILRTSVKD
    type peptidyl-prolyl cis-trans
    isomerase signature is in bold.
    45 The amino acid sequence of SEQ ID MSNPKVFFDILIGKMKAGRVVMELFADVTPKTAENFRAL
    311. The conserved cyclophilin- CTGEKGIGRSGKPLHYKGSTFHRIIPNFMCQGGDFTRGN
    type peptidyl-prolyl cis-trans GTGGESIYGMKFADENFKIKHTGLGVLSMANAGPDTNGS
    isomerase family domain is QFFICTEKTPWLDGKHVVFGKVIDGYNVVKEMESVGSDS
    underlined and the cyclophilin- GSTRETVAIEDCGQLSEN
    type peptidyl-prolyl cis-trans
    isomerase signature is in bold.
    46 The amino acid sequence of SEQ ID MDDDFEFPASSNVENDDDDGMDMDDMGGDVPEEEDPVAS
    312. The conserved FKBP-type PAVLKVGEEREIGKAGFKKKLVKEGEGWETPSSGDEVEV
    peptidylprolyl isomerase domains HYTGTLLDGTKFDSSRDRGTPFKFKLGRGQ
    Figure US20100122382A1-20100513-P00016
    are underlined. The FKBP-type
    Figure US20100122382A1-20100513-P00017
    ESGSPPTIPPNATLQFDVE
    peptidyl-prolyl cis-trans LL SWSSVKDICKDGGILKKVLVEGEKWDNPKDLDEVFVK
    isomerase signature
    1 is in bold YEASLEDGTLISKSDGVEFTVGDGYFCAALAKAVKTMKK
    and the FKBP-type peptidyl-prolyl GEKVLLTVMPQYAFGETGRPASGDEAAVPPDASLQIMLE
    cis-trans isomerase signature 2 is LVSWKTVSDVTKDKKVLKKTLKEGEGYERPNDGAAVQVR
    in bold/italics. The TPR repeat LCGKLQDGTVFVKKDDEEPFEFKIDEEQ
    Figure US20100122382A1-20100513-P00018
    is in italics.
    Figure US20100122382A1-20100513-P00019
    PTESQQDLAVVPANSTVYYEV
    ELLSFVKEKESWEMNNQEKIEAAARKKEEGNAAFKAGKY
    VRASKRYEKAVRFIEYDSSFSDEEKQQAKTLKNTCNLND
    AACKLKLKDFKEAEKLCTKVLEGDGKNVKALYRRAQAYI
    QLVDLDLAEQDIKKALEIDPNNRDVKLEYKILKEKVREY
    NKRDAQFYGNMFAKMNKLEHSRTAGMGAKHEAAPMTIDS
    KA
    47 The amino acid sequence of SEQ ID MAKPRCFMDISIGGELEGRIVGELYTDVAPKTAENFRAL
    313. The conserved cyclophilin- CTGEKGIGPHTGAPLHYKGVRFHRVIKGFMVQGGDISAG
    type peptidyl-prolyl cis-trans DGTGGESIYGLKFEDENFDLKHERKGMLSMANSGPNTNG
    isomerase family domain is SQFFITTTRTSHLDGKHVVFGRVVKGMGVVRSVEHVTTA
    underlined and the cyclophilin- AGDCPTVDVVIADCGEIPAGADDGIRNFFKDGDTYPDWP
    type peptidyl-prolyl cis-trans ADLDESPAELSWWMDAVDSIKAFGNGSYKKQDYKMALRK
    isomerase signature is in bold. YRKALRYLDICWEKEGIDEVESSSLRKTKSQIFTNSSAC
    The TPR repeat is in bold/italics. KLKLCDLKGALLDAEFAVRDGENN
    Figure US20100122382A1-20100513-P00020
    Figure US20100122382A1-20100513-P00021
    GIKKELNAAKKKIFERREQ
    EKRAYRKMFL
    48 The amino acid sequence of SEQ ID MTKRKNPLVFLDVSIDGDPVERIVIELFADTVPRTAENF
    314. The conserved cyclophilin- RSLCTGEKGVGKTTGKPLHYKGSYFHRIIKGFMAQGGDF
    type peptidyl-prolyl cis-trans SNGNGTGGESIYGGKFADENFKLAHDGPGLLSMANGGPN
    isomerase signature is underlined TNGSQFFIIFKRQPHLDGKHVVFGKVMRGMEVVKKIEQV
    and the cyclophilin-type peptidyl- GSANGKPLQPVKIVDCGETSETGTQDAVVEEKSKSATLK
    prolyl cis-trans isomerase AKKKRSARDSSSESRGKRRQRKSRKERTRKRRRYSSSDS
    signature is in bold. YSSESSDSDSESYSSDTESESKSHSESSVSDSSSSDGRR
    RKRKSTKREKLRRQRGKDSRGEQKSARYDKKSRHKSADS
    SSDSESESSSRSRSRDDKKKSSRRESARSVSKLKDAEAN
    SPENLESPRDREIKKVEDNSSHEEGEFSPKNDVQHNGHG
    TDAKFGKYDDQRPRSDGSKKSSGSMRDSPKRLANSVPQG
    SPSSSPAHKASEPSSSIRARNPSRSPAPDGNSKRIRKGR
    GFTERFSYARRYRTPSPEDVTYRPYHYGRRNFHDRRNDR
    YSNYRSYSERSPHRRYRSPPRGRSPPRYQRRRSRSRSVS
    RSPGGNKGRYRGRDQSRSRSRSRSRSPRRGSSPANKQLP
    LSERLKSRLGTRVDEHSPRRRRSSSRSHDSSRSRSPDEV
    PDKHEGKAAPVSPARSRSSSPSGRGLVSYGDASPDSGIN
    49 The amino acid sequence of SEQ ID MSVLLVTSLGDIVVDLHADRCPLTCKNFLKLCRIKYYNG
    315. The conserved cyclophilin- CVFHTVQKDFTAQTGDPTGTGTGGDSVYKFLYGDQARFF
    type peptidyl-prolyl cis-trans MDEIHLDLKHSKTGTVAMASGGENLNASQFYFTLRDDLD
    isomerase signature is underlined. YLDGKHTVFGEVAEGLETLTRINEAYVDEKGRPYKNIRI
    The CCHC type zinc finger is in RHTYILDDPFDDPPQLAELIPDASPEGKPKDEVVDDVRL
    bold and the RNA-binding region EDDWVPLDEQLGPAQLEEAIRAKEAHSRAVVLESIGDIP
    RNP-1 (RNA recognition motif) is DAEIKPPDNV
    Figure US20100122382A1-20100513-P00022
    Figure US20100122382A1-20100513-P00023
    in bold/italics.
    Figure US20100122382A1-20100513-P00024
    Figure US20100122382A1-20100513-P00025
    Figure US20100122382A1-20100513-P00026
    DFSQSVAKLWSQFKRKDSQAAKGKGCFKCGAPDHM
    ARECPGSSTRQPLSKYILKEDNAQRGGDDSRYEMVFDED
    APESPSHGKKRRGRDDRDDRHKMSRQSVEETKFNDREGG
    HSVDKHRQSERSKHREDEMSRDSKASEAGRRRIDRDFPE
    EERDGEKYTESHRDRDGKRGDYRDYRKGRADVQTHGDRR
    GDENYRRKSAAYDDGHEGAGAARRKDSNDDHHAYRRGYG
    DSRKGTRDEDDDGRGRRDDPSYRRSSGHKDSSNGGREEQ
    KYRSGETDGKSHPERSHRGDRRR
    50 The amino acid sequence of SEQ ID MRPFNGGSSIACLVLVIAAGALAESQGPHLGSARVVFQT
    316. The conserved cyclophilin- NYGDIEFGFFPGVAPRTVDHIFKLVRLGCYNTNHFFRVD
    type peptidyl-prolyl cis-trans KGFVAQVADVANGRTAPMNDEQRTEAEKTIVGEFSNVKH
    isomerase signature is underlined. VRGILSMGRYDDPDSAQSSFSILLGDAPHLDGKYAIFGR
    VTKGDETLKKLEQLPTRREGMFVMPTERITILSSYYYDT
    GAESCEEENSTLRRRLAASAVEVERQRMKCFP
    51 The amino acid sequence of SEQ ID MPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRAL
    317. The conserved cyclophilin- CTGEKGTGRSGKPLHFKGSSFHRVIPGFMCQGGDFTRGN
    type peptidyl-prolyl cis-trans GTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGS
    isomerase signature is underlined QFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGS
    and the cyclophilin-type peptidyl- GRTSKPVVIADSGQLA
    prolyl cis-trans isomerase
    signature is in bold.
    52 The amino acid sequence of SEQ ID MRFTSITSAIALFAAAASALDKPLDIKVDKAVECSRKTK
    318. The conserved FKBP-type AGDKIQVHYRGTLEADGSEFDASYKRGQPLSFHVGKGQV
    peptidyl-prolyl cis-trans IKGWDQGLLDMCPGEKRTLTIQPDWGYGSRGMGPIPANS
    isomerase signature is underlined VLIFETELVEIAGVAREEL
    and the FKBP-type peptidyl-prolyl
    cis-trans isomerase signature 2 is
    in bold.
    53 The amino acid sequence of SEQ ID MGNPKVFFDMSIGGQPAGRIVMELYADVVPRTAENFRAL
    319. The conserved cyclophilin- CTGEKGAGRSGKPLHYKGSSFHRVIPGFMCQGGDFTAGN
    type peptidyl-prolyl cis-trans GTGGESIYGSKFADENFVKKHTGPGVLSMANAGPGTNGS
    isomerase signature is underlined QFFVCTAKTEWLDGKHVVFGQIVDGMDVVKAIEKVGSSS
    andThe cyclophilin-type peptidyl- GRTSKPVVVADCGQLS
    prolyl cis-trans isomerase
    signature
    2 is in bold.
    54 The amino acid sequence of SEQ ID MAVATRSRWVAMSVAWILVLFGTLALIQNRLSDTGASSD
    320. The conserved FKBP-type PKLVHRKVGEEKKKPDDLEEVTHKVFFDVEIGGKPAGRI
    peptidyl-prolyl cis-trans VMGLFGKTVPKTVENFRALCTGEKGIGKSGKPLNYKGSQ
    isomerase signature is underlined FHRIIPKFMIQGGDFTLGDGRGGESIYGNKFSDENFKLK
    and the Cyclophilin-type peptidyl- HTDAGRLSMTNAGPDTNGSQFFITTVTTSWLDGRHVVFG
    prolyl cis-trans isomerase KVLSGMDVVHKIEAEGGQSGQPKSIVVISDSGELDL
    signature is in bold.
    55 The amino acid sequence of SEQ ID MAVTLHTNLGDIKCEIFCDEVPKAAEHNARGILSMANSG
    321. The conserved cyclophilin- PNTNGSQFFIAYAKQPHLNGLYTIFGRVIHGFEVLDIME
    type peptidyl-prolyl cis-trans KTQTGPGDRPLAEIRLNRVTIHANPLAG
    isomerase signature is underlined
    56 The amino acid sequence of SEQ ID MAVATRSRWVAMSVAWILVLFGTLALIQNRLSDTGASSD
    322. The conserved FKBP-type PKLVHRKVGEEKKKPDDLEEVTHKVFFDVEIGGKPAGRI
    peptidyl-prolyl cis-trans VMGLFGKTVPKTVENFRALCTGEKGIGKSGKPLNYKGSQ
    isomerase signature is underlined FHRIIPKFMIQGGDFTLGDGRGGESIYGNKFSDENFKLK
    and the Cyclophilin-type peptidyl- HTDAGRLSMANAGPDTNGSQFFITTVTTSWLDGRHVVFG
    prolyl cis-trans isomerase KVLSGMDVVHKIEAEGGQSGQPKSIVVISDSGELDL
    signature is in bold.
    57 The amino acid sequence of SEQ ID MGNPKVFFDMSIGGQPAGRIVMELYADVVPRTAENFRAL
    323. The conserved cyclophilin- CTGEKGAGRSGKPLHYKGSSFHRVIPGFMCQGGDFTAGN
    type peptidyl-prolyl cis-trans GTGGESIYGSKFADENFVKKHTGPGVLSMANAGPGTNGS
    isomerase signature is underlined QFFVCTAKTEWLDGKHVVFGQIVDGMDVVKAIEKVGSSS
    andThe cyclophilin-type peptidyl- GRTSKPVVVADCGQLS
    prolyl cis-trans isomerase
    signature
    2 is in bold.
    58 The amino acid sequence of SEQ ID MSPVAANAMEEAAEPEVPAPVTPSKDDADTDAAVSRFLG
    324. The conserved A-box of the FCKSKLGLAEGNCVQSSTLLRKTAHVLRSSGTVIGTGTA
    Retinoblastoma-associated protein EEAERYWFAFVLYTVRRVGERKAEDEQNGSDETEVPLSR
    is underlined and the B-box of the ILKASVLNLIDFFKEIPQFVIKAGAIVSGIYGANWDSRL
    Retinoblastoma-associated protein EAREMQTNYVHLCILCKFYKRICGEFFILNDAKDDMKSA
    is in bold. DSSTSDPVIMYQPFGWLLFLALRIHALSRFKDLVSSTNA
    LVSVLAILIIHLPTRFRKFSISDSSQLVKRSEKGVDLVG
    SLAYRYDTSEDEIKRTLEKANNVIAEILGITPPPASECK
    AENLENVDTDGLIYFGNLMEETSLSSILSTLEKIYEDAT
    RNDSEFDERVFINDDDSLLVSGSLSGAAINLTGAKRKYD
    SFASPAKTITRPLSPSRSPASHINGIIGGTNLRITATPV
    ATAMTTAKWLRTFVSPLPSKPSTDLQGFLASCDRDVTSD
    VIRRANIILEAIFPNSPIGERTVTGGLQNANLMDNMWAE
    QRRLEALKLYYRVLEAMCRAEAQILHSNNLTSLLTNERF
    HRCMLACSAELVLATHKTVTMLFPAVLERTGITAFDLSK
    VIESFVRHEETLPRELRRHLNTLEERLLENMVWERGSSM
    YNSLVVARPALAPEINRLGLLPEPMPSLDAIALLINFSS
    SGLPQSPVQKHEASPGQNGDIRSPKRISTEYRSVLVERN
    FTSPVKDRLLALSNIKSKLPPPPLQSAFASPTRPHPGGG
    GETCAETAIHIFFSKITKLAAVRINAMLERLQLSQQIKE
    GVYCLFQQILSQRTNLFFNRHIDQVILCCFYGVAKINQI
    NLTFREIIYNYRKQPQCKPQVFRNVFVDWSTRRNGKAGN
    EHVDIISFYNEIFIPSVKPLLVELGPTGATTRTNRTSEV
    GNKNDAQCPGSPKISSFPTLPDMSPKKVSASHNVYVSPL
    RSSKMDASISHSSKSYYACVGESTHAYQSPSKDLVAINS
    RLNGNRKVRGTLNFDDVDAGLVSDSMVANSLYLQNGSSM
    SSSTAKSSEK
    59 The amino acid sequence of SEQ ID MRPILMKGHERPLTFLKYNREGDLLFSCAKDHTPTVWFA
    325. The conserved G-protein beta DNGERLGTYRGHNGAVWCCDVSRDSMRLITGSADTTAKL
    WD-40 repeat domains are WSVQNGTQLFTFNFDSPARSVDFSIGDKLAVITTDPFME
    underlined. LPSAIHVKRIARDPADQASESVLVLRGHQGRIARAVWGP
    LNKTIISAGEDAVIRIWDSETGKLLRESDKETGHKKAVT
    SLMKSVDGSHFVTGSQDKSAKLWDIRTLTLIKTYVTERP
    VNAVTMSPLLDHVVLGGGQDASAVTMTDHRAGKFEAKFF
    DKILQEEIGGVKGHFGPINALAFNPDGKSFSSGGEDGYV
    RLHHFDPDYFNIKI
    60 The amino acid sequence of SEQ ID MDKKR TVVPLVCHGHSRPVVDLFYSPITPDGFFLISASK
    326. The conserved G-protein beta DSSPMLRNGETGDWIGTFEGHKGAVWSCCLDTNALRAAS
    domain is underlined and the WD-40 GSADFSAKLWDALSGDELHSFEHKHIVRSCAFSEDTHLL
    repeat domains are in bold LTGGVEKILRIFDLNRPDAPPREVDNSPGSIRTVAWLHS
    DQTILSSCTDIGGVRLWDVRSGKIVQTLETKSPVTSSEV
    SQDGRYITTADGSTVKFWDANHFGLVKSYNMPCNIESAS
    LEPKLGNKFIAGGEDMWVHIFDFHTGEEIGCNKGHHGPV
    HCVRFSPGGESYASGSEDGTIRIWQ TGPANNVEGDANPS
    NGPVTGKAKVGADEVTRKVEDLQIGKEGKDWREG
    61 The amino acid sequence of SEQ ID MAEGLILKGTMRAHTDMVTAIAIPIDNSDMVVTSSRDKS
    327. The conserved G-protein beta IILWHLTKEEKVYGVPRRRLTGHSHFVQDVVLSSDGQFA1
    WD-40 repeat domains are LSGSWDGELRLWDLATGVSARRFVGHTKDVLSVAFSIDN
    underlined. RQIVSASRDRTIKLWNTLGECKYTIQEGEAHTDWVSCVR
    FSPNTLQPTIVSASWDRTIKVWNLTNCKRNTLAGHNGY
    VNTVAVSPDGSLCASGGKDGVILLWDLAEGKRLYNLEAG
    AIIHSLCFSPNRYWLCAATENSIKIWDLESKSIVEDLRV
    DLKNEADKTDGTTTAASNKKVIYCTSLNWSADGSTLFSG
    YNDGVIRVWGTGRY
    62 The amino acid sequence of SEQ ID MAEGLHLKGTMKAHTDMVTAIAVPIDNADMIVTSSRDKS
    328. The conserved G-protein beta IILWHLTKEDKVYGVPRRRLTGHSHFVQDVVLSSDGQFA
    WD-40 repeat domains are LSGSWDGELRLWDLATGVSARRFVGHTKDVLSVAFSIDN
    underlined. RQIVSASRDRTIKLWNTLGECKYTIQEGEAHNDWVSCVR
    FSPNTLQPTIVSASWDRTVKVWNLTNCKLRNTLQGHSGY
    VNTVAVSPDGSLCASGGKDGVILLWDLAEGKKLYSLEAG
    AIIHSLCFSPNRYWLCAATENSIKIWDLESKSIVEDLRV
    DLKNEADMSDGTTGAMSSNKKVIYCTSLNWSADGSTLFS
    GYNDGVIRVWGIGRY
    63 The amino acid sequence of SEQ ID MAEGLHLKGTMKAHTDMVTAIAVPIDNADMIVTSSRDKS
    329. The conserved G-protein beta IILWHLTKEDKVYGVPRRRLTGHSHFVQDVVLSSDGQFA
    WD-40 repeat domains are LSGSWDGELRLWDLATGVSARRFVGHTKDVLSVAFSIDN
    underlined and the Trp-Asp (WD) RQIVSASRDRTIKLWN TLGECKYTIQEGEAHNDWVSCVR
    repeats signature is in bold. FSPNTLQPTIVSASWDRTVKVWN LTNCKLRNTLQGHSGY
    VNTVAVSPDGSLCASGGKDGVILLWDLAEGKKLYSLEAG
    AIIHSLCFSPNRYWLCAATENSIKIWDLESKSIVEDLRV
    DLKNEADMSDGTTGAMSSNKKVIYCTSLNWSADGSTLFS
    GYNDGVIRVWGIGRY
    64 The amino acid sequence of SEQ ID MSGVPAPPFATTTPENGTMSSNSPAFHRDSDDDDDQGEV
    330. The conserved G-protein beta FLDDSDIIHEVAVDDEDLPDADDEADEAEEADDSLHIFT
    WD-40 repeat domains are GHNGEVYSLACSPTDATLVATGAGDDKGFLWRIGHGDWA
    underlined. VELQGHKDSISSLAFSLDGQLLASGSLDGVIQIWDVPSG
    NLKGTLDGPGGGIEWIRWHPKGHIILAGSEDSTVWMWNA
    DKMAYLNMFSGHGNSVTCGDFTPDGKTICTGSDDATLRI
    WNPKSGENIHVVKGHPYHAEGLTSMAISSDSGLAITGAK
    DGSVRIVNISSGRVVSSLDAHADSVEFVGLALSSPWAAT
    GSLDQKLIIWDLQHSSPRATCDHEDGVTCLSWVGASRFL
    ASGCVDGKVRVWDSLSGDCVRTFHGHSDAIQSLSVSANE
    EFLVSVSIDGTARVFEIAEFH
    65 The amino acid sequence of SEQ ID MGTSQHQLSSCLQLLPRRRGNKNLIFRRTMASGGAAAVA
    331. The conserved G-protein beta PPPGYKPYRHLKTLTGHVAAVSCVKFSNDGTLLASASLD
    WD-40 repeat domains are KTLIIWSSAALSLLHRLVGHSEGVSDLAWSSDSHYICSA
    underlined. SDDRTLRIWSSRSPFDCLKTLRGHTDFVFCVNFNPQSSL
    IVSGSFDETIRIWEVKTGRCLNVIRAHSMPVTSVHFNRD
    GSLIVSGSHDGSCKIWDTKNGACLKTLIDDTVPAVSFAK
    FSPNGKFILVATLNDTLKLWNYATGKFLKIYTGHKNSVY
    CLTSTFSVTNGKYIVSGSEDRCICIWDLQGKNLIQKLEG
    HSDTVISVTCHPSENKIASAGLDSDRTVRIWLQDA
    66 The amino acid sequence of SEQ ID MPSQKIETGHQDIVHDVAMDYYGKRVATASSDTTIKIIG
    332. The conserved G-protein beta VSNSSGSQHLASLSGHKGPVWQVAWAHPKFGSILASCSY
    WD-40 repeat domains are DGQVILWKEGNQNDWAQAHVFNDHKSSVNSIAWAPHELG
    underlined. LCLACGSSDGNISVFTARPDGGWDTTRIEQAHPVGVTSV
    SWAPSMAPGALVGSGLLDPVQKLASGGCDNTVKVWKLYN
    GTWKMDCFPALQMHSDWVRDVAWAPNLGLPKSTIASASQ
    DGTVVIWTVAKEGEQWQGKVLKDFKTPVWRVSWSLTGNL
    LAVADGNNNVTLWNEAVDGEWQQVTTVEP
    67 The amino acid sequence of SEQ ID MKIAGLKSVENAHDESVWAAAWVPATESRPALLLTGSLD
    333. The conserved G-protein beta ETVKLWRPDELALERTNAGHFLGVVSVAAHPSGVIAASA
    WD-40 repeat domains are SIDSFVRVFDVDTNATIATLEAPPSEVWQMQFDPKGTTL
    underlined and the Trp-Asp (WD) AVAGGGSASIKLWDTATWELNATLSIPRPEQPKPSEKGN
    repeats signature is in bold. KKFVLSVAWSPDGRRLACGSMDGTISIFDVARAKFLHHL
    EGHFMPVRSLVFSPVEPRLLFSASDDAHVHMYDSEGKSL
    VGSMSGHASWVLSVDVSPDGAALATGSSDRTVRLWD LSM
    RAAVQTMSNHSDQVWGVAFRPMAGAGVRAGGRLASVSDD
    KSISLYDYS
    68 The amino acid sequence of SEQ ID MEIDLGNLAFDVDFHPSEQLVASGLITGDLLLYRYGDGS
    334. The conserved G-protein beta SPEKLLEVRAHGESCRAVRFINDGKAILTGSPDCSILAT
    WD-40 repeat domains are DVETGSVVARVENAHEAAVNRLVNLTESTIATGDDNGCI
    underlined and the Trp-Asp (WD) KVWDTRQRSCCNTFSAHEDFISDMTFASDSMKLVVTSGD
    repeats signature is in bold. GTLSVCNLRSNKVQTRSEFSEDELLSVVIMKNGRKVVCG
    TQSGTLLLYSWGFFKDCSDRFVDLSPSSVDALLKLDEDR
    IIAGTENGLISLIGILPNRIIQPIAEHSDHPIERLAFSH
    DKKFLGSISHDQTLKLWD LNDILGSEDSPSSQAAIDDSD
    SDEMDVDANPPDSSKGNKKKHSGKGNDVGNANNFFADLGD
    69 The amino acid sequence of SEQ ID MSQQPSVILATASYDHTIRFWEAKSGRCYRTIQYPDSQV
    335. The conserved G-protein beta NRLEITPHKRYLAVAGNPSIRLFDVNSNTPQPVMSFDSH
    WD-40 repeat domains are TNNVMAVGFQYDGNWMYSGSEDGTVRIWDLRARGCQREY
    underlined and the Trp-Asp (WD) ESRGAVNTVVLHPNQTELISGDQNGNIRVWDLTANSCSC
    repeats signature is in bold. ELVPEVDTAVRSLTVMWDGSLVVAANNNGTCYVWRLLRG
    SQTMTNFEPLHKLQAHNGYILKCLLSPEFCEPHRYLATA
    SSDHTVKIWN VEGFTLEKTLIGHQRWVWDCVFSVDGAYL
    ITASSDTTARLWSMSTSQDIRVYQGHHKATTCCALHDGA
    EGSPG
    70 The amino acid sequence of SEQ ID MEDAMDMEVEVEVEAEEHSPSSSNPSGSSFRRFGLKNSI
    336. The conserved G-protein beta QTNFGSDYVFEITPKFDWSLMGVSLSSNAVKLYSPTTGQ
    WD-40 repeat domains are YCGECRGHSDTVNGISFSGPSSPHVLHSCSSDGTIRAWD
    underlined. TRSFKEVSCISAGPSQEIFSFSFGGSSDSLLSAGCKSQI
    LFWDWRNKKQVACLEDSHVDDVTQVCFVPHHQNKLISAS
    VDGLICIFDTAGDINDDEHMESVINVGTSIGKVGIFGQT
    FEKLWCLTHIETLSVWDWKEGTNEANFEDARKLASDSWS
    LDHIDYFVDCHSAEEGEGLWVIGGTNAGTLGYFPVKYKG
    GAAIGSPEAVLGGGHSDVVRSVLPMSGMAGTTSKTRGIF
    GWTGGEDGRLCCWLSDDSSATSRSWMSSNLVLKSSRSHH
    KKNRHQPY
    71 The amino acid sequence of SEQ ID MSQHQEYPMEYAADDYDVGEVEDDMYFHERVMGDSDTDE
    337. The conserved G-protein beta DEEYDHLDNKITDTSAADARRGKDIQGIPWERLSVTREK
    domain is underlined and the WD-40 YRRTRIEQYKNYENVPQSGESSEKDCKPTRKGGNYYEFW
    repeat domains are in bold RNTRSVKSTILHFQLRNLVWSTTKHDVYLMSHFSIIHWS
    SLTCKKTEVLDVYGHVAPREKHPGSLLEGFTQTQVSTLA
    VRDKLLIAGGFQGELICKNLDRPGVSYCCRTTYDDNAIT
    NAVEIYDYPSGAVHFMASNNDCGVRDFDMEKFELSRHFT
    FPWPVNHTSLSPDGKLLVIVGDNPEGIVVDSQR GKTIRP
    LQGHLDFSFASAWHPDGHIFATGNQDKTCRIWDIRNLSK
    SVAVLKGNLGAIRSIRFTSDGRFMAMAEPADFVHVYD VK
    SGYEKEQEIDFFGEISGVSFSPDTESLFVGVWDRTYGSL
    LQYNRCRNYSYLDSM
    72 The amino acid sequence of SEQ ID MGASSDPNPDVSDEHQKRSEIYTYEAPWHIYAMNWSVRR
    338. The conserved G-protein beta DKKYRLAIASLLDHPAAAAAVPNRVEIVQLDDSTGEIRA
    WD-40 repeat domains are DPNLSFDHPYPATKAAFVPDKDCQRADLLATSSDFLRIW
    underlined. RIADDSSRVDLRSFLNGNKNSEFCRPLTSFDWNEAEPKR
    IGTSSIDTTCTIWDIERETVDTQLIAHDKEVYDIAWGGV
    SVFASVSADGSVRVFDLRDKEHSTIIYESSEPDTPLVRL
    GWNKQDPRYMATIIMDSAKVVVLDIRYPTMPVVELQRHQ
    ASVNAIAWAPHSSCHICTAGDDSQALIWDLSSMAQPVEG
    GLDPILAYTAGAEIEQLQWSSSQPDWVAIAFSLKLQ
    73 The amino acid sequence of SEQ ID MRGGGGGGDATGWDEDAYRESVLKEREVQTRTVFRAAFA
    339. The conserved G-protein beta PSPSPSPSPDAVVVASSDGSVASYSISACLSDHRLQSLR
    WD-40 repeat domains are FADAKSQNVLEAEPACFLQGHDGPAYDVKFYGEGEDSLL
    underlined. LSCGDDGRIRGWMWRDITSSEAHDHSQGNSAKPVLDLVN
    PQSRGPWGALSPIPENNALAVDVKRGSIYAAAGDSCAYC
    WDVECGKIKTVFKGHSDYLHCIAARNSSSQIITGSEDGT
    ARIWDCRSGKCVQVIDPDKDHKKGFFASVSCLALDASES
    WLVCGRGRDLSVWSISASDCIAKISTNAPAQDVLFDDNQ
    ILLVGAEPLISRLDMNGAVLSQIHCAPQSVFSVSLHQSG
    VTAVGGYGGLVDVISQFGSHLCTFRCKCI
    74 The amino acid sequence of SEQ ID MEAPIIDPLQGDFPEVIEEYLEHGIMKCIAFNRRGTLLA
    340. The conserved G-protein beta AGCTDGSCIIWDFETRGVAKELRDKECTAAITSVCWSKY
    WD-40 repeat domains are GHRILVSASDKSLILWDVLSGEKIAHTTLQHTVLQACLH
    underlined. PGSSTPSICLACPFSSAPMIVDLNTGSTTALPVLTADVS
    NGATPLSRNKTSDTSVTYSPCNACFNKHGDLVYAGTSKG
    EILIIDHKNVRVCAIVLVSGGAVIKNVVFSRNGQYMLTN
    SNDRLIRIYKNLLPPKDGLKMLDELNESFNESDDVEKLK
    AIGSKCLELLHEFQDSITRVQWKAPCFSGDGEWVIGGAA
    SRGEHKIYIWDRAGHLVKILEGPKEALMDLAWHPVHPII
    ISVSLTGLVYIWAKDYTENWSAFAPDFKELEENEEYVER
    EDEFDLVPETEKVKGLDVHEDDEVDVLTVERDSVFSDSD
    MSQEELCFLPAVPCLDIPEQQDKCVGSCSKLPDGNHSGS
    PLSVEAGQNGNASNHNSSPLEPMENSTADDTDGVRLKRK
    RKPSEKGLELQAEKVKKPVKPLKSSGRLSKTNKPVIDPD
    SSNGVYGDDGSD
    75 The amino acid sequence of SEQ ID MRGVSWPEDGNNPSTSSSSQRNQQQAHAPRAVSGHAASH
    341. The conserved G-protein beta PSASNIFKLLVQREVSPRSKHSSKKLWREASKCQPYPFQ
    WD-40 repeat domains are QSCEAVRDVRQGLISWVESASLRHLSAKYCPLVPPPRST
    underlined. IAAAFSPDGKILASTHGDHTVKLIDSQTGSCLKVLRGHR
    RTPWVVRFHPLYPEILASGSLDHEVRLWDANTAECIGSR
    NFYRPIASIAFHARGELLAVASGHKLYIWHYNRRGETSS
    PTIVLRTQRSLRAVHFHPHAAPFLLTAEVNDLDSADSAM
    TLATSPGYLHYPPPTVYFADAHSHERSRLADELPLMPLP
    LLMWPSFTRDDGRVPLQRIDGDVGLNGQQRVDSSSSVRL
    WTYSTPSGQYELLLSPVESGNSPSMPEETGNNAFSSAVE
    AEVSQSAMDTVEDMEVQPEERNTQFFSFSDPRFWELPLL
    HGWLVGQTQAGPRSVRQSSPGDIETQSAFGEVASVSPIT
    SGVMPVSMDPSRFGGRSGSRYRSPGSRGVHVTGPNNDGP
    RDENDPQSVVSKLRSELAASLAAAASTELPCTVKLRIWP
    HDVKDPCAQLDLESCRLTIPHAVLCSEMGAHFSPCGRFL
    AACVACVLPHLESDPGLHGQVNQDVTGVATSPTRHPISA
    HQIMYELRIYSLEEATFGIVLASRPVRAAHCLTSIQFSP
    TSEHLLLAYGRRHSSLLKSIVIDGENTVPIYTILEVYRV
    SDMELVRVLPSAEDEVNVACFHPSVGGGLIYGTKEGKLR
    ILHYDSSHGLNLKSSGFLDENVPEVQTYALEC
    76 The amino acid sequence of SEQ ID MDSAVAIAALSLVVGAAIALLFFGNYFRKRRSEVVAMAE
    342. The conserved G-protein beta ADLQPHPKNPSRPPPQPAAKKVHAKSHAHGADKDKNKRH
    WD-40 repeat domains are HPLDLNTLKGHGDSVTGLCFASDGRSLATACADGVVRVF
    underlined and the Trp-Asp (WD) KLDDASNKSFKFLRINLPAGGHPTAVAFGDGVSSVIVAS
    repeats signature is in bold. QHLSGCSLYMYGEEKPTNLDSNKQQTKLPMPEIKWEHHK
    VHEQKAILTLSGAAANYDSGDGSTIIASCSEGTDIIIWH
    AKTGKILGNVDTNQLKNTMSAISPNGRFIAAAAFTADVK
    VWEIVYSKDGSVKGVTKVMQLKGHKSAVTWLCFTPNSEQ
    IVTASKDGSIRIWN INVRYHLDEDTKTLKVFPIPLQDSS
    GTTLHYERLSLSPDGKILAATHGSMLQWLCIETGKVLDT
    AEKAHDGDITCMSWAPQSIPTGDKKVNVLATASGDKKVK
    LWAAPPLPS
    77 The amino acid sequence of SEQ ID MEVEPKKASKTFPVKPKLKPKPRTPSGKTPESKYWSSFK
    343. The conserved G-protein beta TTHPLDNLSFSVPSLAFSPSPPHLLAAAHSATVSLFSPH
    WD-40 repeat domains are RTTISSFSDVVSSLSFRSDGQLLAASDLSGLIQVFDVRS
    underlined. RTPLRRLRSHARPVRFVRYPVLDKLHLVSGGDDALVKYW
    DVAGESVVSELRGHKDYVRCGDCSPADANCFVTGSYDHV
    VKLWDVRVRDGNRAATEVNHGSPVQDVIFLPSGSLVATA
    GGNSVKIWDLIGGGRMVYSMESHNKTVTSICVGTMGAQQ
    SGEEGVQLRILSVGLDGYMKVFDYSRMKVTHSMRFPAPL
    LSIGFSPDSNVRAIGTSNGILYVGKRKAKENAEGGANGI
    LGLGSVEEPRRRVLKPSFYRYFHRGQSEKPSEGDYLVMR
    PKKVKLAEHDKLLKKFQHKNALISVLGGNDPEKVVAVME
    ELVARRALLKCVLNLDADELGLILTFLHKNSTVPRYSSL
    LLGLAKKVIDLRLEDIRASDALKGHIRNLKRSVDEEIRI
    QEGLQEIQGMVSPLLRIAGRR
    78 The amino acid sequence of SEQ ID MQGGSSGVGYGLKYQARCISDVKADTDHTSFLTGTLSLK
    344. The conserved G-protein beta EENEVHLLRLSSGGTELICEGLFSHPSEIWDLSSCPFDQ
    WD-40 repeat domains are RIFSTVFSTGESYGAAVWQIPELYGQLNSPQLEKIASLD
    underlined. AHSRKISCVLWWPSGRHDKLVSIDEENIFLWGLDCSKKS
    AQVQSQESAGMLHNLSGGAWDPHDVNTVAATCESSIQFW
    DLRTMKKANSLESVHARDLDYDMRKKHLLVTSEDESGVR
    VWDLRMPKAPIQEFPGHTHWTWAVRCNPDYEGLILSAGT
    DSAVNLWWSSTASSDELISERLIDSPTRKLDPLLHSYND
    YEDSVYGLAWSSREPWIFASLSYDGRVVVESVKPFLSRK
    79 The amino acid sequence of SEQ ID MAEEEGSAELEQQLEEEFAVWKKNTPILYDLLISHALEW
    345. The conserved G-protein beta PSLTVHWAPLLPQPSSSAAAAAGDPSLAAHRLVLGTHTS
    WD-40 repeat domains are DGAPNFLILADALLPSSESDHCGDDAVLPKVEISQKIRV
    underlined. DGEVNRARFMPQNHNIVGAKTNGCEVYVFDCSKQAAKQH
    DGGFDPDLRLTGHDGEGYGLSWSPLKENYLLSASHDKKI
    CLWDISAAAQDKVLGAMHVFEAHEGAVGDASWHSKNDNL
    FGSAGDDCQLMIWDLRTNKAQQCVKAHEKEVNSVSFNSY
    NDWILATASSDTTVGLFDMRKLTTPLHVFSSHEGEVLQV
    EWDPNHEAVLASSSEDRRVMVWDLNRIGDEQQEGDASDG
    PAELLFSHGGHKAKISDFSWNKNEPWVISSVAEDNSVQV
    WQMAESICGDDDDMQAMEGYI
    80 The amino acid sequence of SEQ ID MGNYGEEDEDQYFDALEETASVSDRGSNSSDCCSSGSGL
    346. The conserved G-protein beta DENVLDSLGFEFWTKFPESVRARRNRFLMLTGLGIEANS
    WD-40 repeat domains are VDKEDAFPPSCNEIEVYTCKVTRDDGAVQRSLDSYNCIS
    underlined. LLQSSTSIRSNQEVESLRGDSLLSSFRGRSKESDDLTEL
    CGMGCPESKRNAVSEFGSVSQGSIEELRRIVASSPLVHP
    LLHRKLEYERELIETKQKMGAGWLRKFGSATCISGRQGD
    TWSDPDDLEITAGMKMRRVRAHSSKKKYKELSSLYAAQE
    FLAHEGSISTMKFSMDGQYLASAGEDTVVRVWKVTEEDR
    SERVNVTVDPSCLYFALNESTQLASLNTNKEHIGKAKTF
    QRSSDSSCVILPLKVFQITEKPWHEFKGHNGEVLDLSWS
    SKGYLLSSSTDKTVRLWRVGCDRCQRVYSHNDYVTCISF
    NPVNENFFISGSIDGKVRIWNVFGGQVVAYIDCREIVSA
    VCYRSDGKGAIVGTMTGNCLFYSIKDNHLQMDAQVYLHG
    KKKSPGKRITGFQFPPNDPGKLMITSADSVIRVLSGLDV
    VCKLKGPRNSGGPMIATFTSDGKHVISASEDSNVYIWNY
    AGQDKTSSRVKKIWSCESFWSSNASVALPWCGIRTVPEA
    LAPPSRSEERRASCAENGENHHMLEEYFQKMPPYSPDCF
    SLSRGFFLELLPKGSATWPEEKLSDTSPPTVSSQAISKL
    EYKFLKSACHSVLSSAHMWGLVIVTAGWDGRIRTYHNYG
    LPVRS
    81 The amino acid sequence of SEQ ID MDIDFKEYRLRCELRGHEDDVRGVCVCGDGSIGTSSRDR
    347. The conserved G-protein beta TVRLWAPSAGERRKYEVARVLLGHKSFVGPLAWVPPSEE
    WD-40 repeat domains are LPEGGIVSGGMDTLVMAWDLRNGEAQTLKGHQLQVTGIV
    underlined. LDGGDIVSASVDCTLIRWKNGQLTEHWEAHKAPIQAVIR
    LPSGELVTGSSDTTLKLWRGKTCTQTFVGHTDTVRGLAV
    MPDLGILSASHDGSIRLWAVSGECLMEMVDHTSIVYSVD
    SHASGLIVSGSEDRFAKIWKDGVCFQSIEHPGCVWDVKF
    LEDGDIVTACSDGTIRIWTNQEDRMANSTELELFDLELS
    SYKRSRKRVGGLKLEELPGLEALQVPGTSDGQTKVIREG
    DNGVAYAWNSTELKWDKIGEVVDGPEDSMNRPALDGVQY
    DYVFDVDIGDGEPTRKLPYNRSDNPYDTADKWLLKENLP
    LSYRQQIVEFILANSGQRDFNLDPSFRDPYTGSSAYVPG
    APSQLAAKQARPTFKHIPKKGMLVFDAAQFDGILKKINE
    FNNTLLSNQEKKNLSLTDIEISRLGAVVKILKDTSHYHS
    SKFADADFDLMLKLLESWPYEMMFPVIDIFRMVILHPDG
    ADGLLRHQEDKKDVLMESIKRATGNPSVPANFLTSIRAV
    TNLFKNSAYYSWLQKHRSEMLDAFSSCSSSSNKNLQLSY
    ATLLLNYAVLLIEKKDEEGQSQVLSAALELAENESLEVD
    ARYRALVAIGSLMLDGLVKRIALDFDVEHIAKAARTSKE
    AKIAEVGADIELLIKQS
    82 The amino acid sequence of SEQ ID MEFTEAYKQSGPCCFSPNARFIAVAVDYRLVIRDTLSLK
    348. The conserved G-protein beta VVQLFSCLDKISYIEWALDSEYILCGLYKRPMIQAWSLI
    domain is underlined and the WD-40 QPEWTCKIDEGPAGIAYARWSPDSRHILTTSDFQLRLTV
    repeat domains are in bold WSLVNTACVHVQWPKHASKGVSFTRDGKFAAICTRHDCK
    DYINLLSCHNWEIMGVFAVDTLDLADIQWSPDDSAIVIW
    DSPLEYKVLVYSPDGR CLFKYQAYESGLGVKSVSWSPCG
    QFLAVGSYDQMLRVLSHLTWKTFAEFTHLSNVRAPCCAA
    IFKEVDEPLQIDMSELSLSDDYMQGNSGDAPEGHYRVRY
    DVTEVPITLPCQKPPADRPNPKQGIGLMSWSNDSQYICT
    RNDSMPTILWIWDMRHLELAAILVQKDPIRAAVWDPTGT
    RLVLCTGSSHLYMWT PSGAYCVSVPLSQFNITDLKWNSD
    GSCLLLKDKESFCCAAAPLPPDESSDYSSDD
    83 The amino acid sequence of SEQ ID MATIAALDDDMVRSMSIGAVFSDFVGKLNSLDFHRKDDI
    349. The conserved G-protein beta LVTAGEDDSVRLYDIANARLLKTTFHKKHGTDRVCFTHH
    WD-40 repeat domains are PNSLICSSTKNLDTGESLRYISMYDNRSLRYFKGHKQRV
    underlined. VSLCMSPINDSFMSGSLDHSVRMWDLRVNACQGILRLRG
    RPTVAYDQQGLVFAVAMEGGAIKLFDSRSYDKGPFDAFL
    VGGDTSEVCDIKFSNDGKSVLLSTTNNNIYVLDAYAGDK
    QCGFNLEPSPSTPIEASFSPDGQYVVSGSGDGTLHAWNI
    SRRNEVACWNSHIGVASCLKWAPRRAMFVAASTVLTFWI
    PNSEPELASAKGEAGVPPEQV
    84 The amino acid sequence of SEQ ID MSVAELKERHRAATETVNSLRERLKQKRVQLLDTDVAGY
    350. The conserved G-protein beta ARTQGKTPVTFGATDLVCCRTLQGHTGKVYSLDWTPERN
    WD-40 repeat domains are RIVSVSQDGRFIVWNALTSQKTHAIRLPCAWVMTCAFAP
    underlined and the beta G-protein NGQSVACGGLDSVCSIFNLNSPVDRDGNLPVSRMLSGHK
    (transducin) is in bold. GYVSSCQYVPDGDAHLITGSGDQTCVLWDITTGLRTSVF
    GGEFQSGHTADVLSVSINGSSPRIFVSGSCDSTARMWDT
    RVASRAVHTYHGHEGDVNAVKFFPDGNRFGTGSDDGTCR
    LFDIRTGHELQVYYQQRGIDEIPHVTSIAFSISGRLLIA
    GYSNGDCFVWDTLLAQVVLNLGSLQNSHEGRISCLGVSA
    DGSALCTGSWDTNLKIWAFGGIRRVT
    85 The amino acid sequence of SEQ ID MKKRPRGASLDQAVVDIRRREVGGLSGLSFARRLAASEG
    351. The conserved G-protein beta LVLR LDIYNKLKGHRGCVNTVGFNLDGDIVISGSDDRHV
    domain is underlined and the WD-40 KLWDWQTGKVKLSFDSGHLSNVFQAKIMPYTDDRSIVTC
    repeat domains are in bold AADGQARHAQILEGGQVQTMLLAKHRGRAHKLAIDPGSP
    HIVYTCGEDGLVQRLDLRSNTARELFTCREVYGTHVEVV
    HLNAIAIDPRNPNLFVIGGSDEYARVYDIRNYKWNGSHN
    FGRSANYFCPSHLIGEAHVGITGLAFSGQSELLVSYNDE
    SIYLFTQEMGLGPDPLSASTKSVDSNSSEVTSPTAVNVD
    DNVTPQVYKGHRNCETVKGVGFFGPKCEYVVSGSDCGRI
    FIWKKKGGQLIRVMAADKHVVNCIEPHPHIPALASSGIE
    NDIKIWT PKAIERATLPMNVEQLKPKARGWMNRISSPRQ
    LLLQLYSLERWPEHGGETSSGLAASQEELTELFFALSAN
    GNGSPDGGGDPSGPLL
    86 The amino acid sequence of SEQ ID MSKRGYKLQEFVAHSSNVNCLSIGKKACRLFLTGGDDCK
    352. The conserved G-protein beta VNLWAIGKPNSLMSLCGHTNAVESVAFDSAEVLVLAGAS
    WD-40 repeat domains are SGVIKLWDVEEAKLVRGLTGHRSNCTAMEFHPFGEFFAS
    underlined and the Trp-Asp (WD) GSTDTNLKIWDIRKKGCIHTYKGHTRGISTIRFSPDGRW
    repeats signature is in bold. VVSGGNDNVVKVWDLTAGKLLHDFKFHENHIRSIDFHPL
    EFLLATGSADRTVKFWD LETFELIGSSRPEAAGVRAIAF
    HPDGRTLFCGLEDSLKVYSWEPVICHDGVDMGWSTLADL
    CIHDGKLLGCSYYQSSVGVWVADASLIEPYGTNVKPQQK
    DSGDDEIEHQESRPSAKVGTTIRSTSIMRCASPDYETKD
    IKNIYVDTASGNPVSSQRVGTTNFAKVTQPLDFNDTPNL
    TLRRQGLVTETPDGLSGHVPSKSITQPKVVSRDSPDGKD
    SSRRESITFSRTKPGMLLRPAHSRRPSSTKYDVDRLSAC
    AEIGVLSSAKSGSESLVDSFLNIKVAPEDGARNGCEDNH
    SSVKNVSVESEKVLPLQTPKTEKCDQTVGFKEEINSVKF
    VNGVAVVPGRTRTLVEKFEKREKLNSTEDQTINTPENPT
    LDKTPPPSLAENEEKSDRLNIVERKATRMSSHMVTAEDR
    TPVTLVGSPEDQSTVMAPQRELPADESSKTPPLPVEDLE
    IHHGSNVSEDKATILSSQTVSEEDSKRSTLIRNFRRRDR
    FKSTEGRSPVMATQRKLPTDESGKTSSLPMEDLEIKGGL
    NVSEDKATSFSSRAPPREDRAHSALVRNVRKRDKFKSTN
    DTITVMVHQRGLSTDEASTVSVERVERRQLSNNVENPLN
    NLPPHSVPPTTTRGEPQYVGSESDSVNHEDVTELLLGNH
    EVFLSTLRSRLTKLQVV
    87 The amino acid sequence of SEQ ID MSTFLTGTALSNPNPNKSYEVVQPPNDSVSSLSFNPKAN
    353. The conserved G-protein beta FLVATSWDNQVRCWEIVRSGTSLGTTPKASISHDQPVLC
    WD-40 repeat domains are STWKDDGTTVFSGGCDKQVKMWPLSGGQPMTVAMHDAPI
    underlined. KEISWIPEMNLLVTGSWDKTLRYWDTRQANPVHIQQLPE
    RCYALTVRHPLMVVGTADRNLIIYNLQSPQTEFKRISSP
    LKYQTRCLAAFPDQQGFLVGSIEGRVGVHHLDDSQQSKN
    FTFKCHREGSEIYSVNSLNFHPVHHTFATAGSDGAFNFW
    DKDSKQRLKAMSRCSQPIPCSTFNNDGSIFAYSACYDWS
    KGAENHNPATAKTYIFLHLPQESEVKGKPRLGTTGRK
    88 The amino acid sequence of SEQ ID MEVEAQQRDVNNVMCQLVDPEGTTLGPPMYLPQDVGPQQ
    354. The conserved G-protein beta LQQMVNKLLSNEDKLPYTFYISDQELVVPLESYLQKNKV
    WD-40 repeat domains are SVEKVLSIVYQPQAIFRIRPVNRCSATIAGHSEAVLSVA
    underlined and the Trp-Asp (WD) FSPDGKQLASGSGDTTVRLWD LSTQTPMFTCKGHKNWVL
    repeats signatures are in bold. SIAWSPDGKHLVSGSKAGEIQCWDPLTGQPSGNPLVGHK
    KWITGISWEPVHLSSPCRRFVSSSKDGDARIWDVTLRRC
    VICLSGHTLAVTCVKWGGDGVIYTGSQDCTIKVWETSQG
    KLIRELKGHGHWVNSLALSTEYVLRTGAFDHTGKQYSSA
    EEMKQVALERYKKMKGNAPERLVSGSDDFTMFLWEPSVS
    KHPKTRMTGHQQLVNHVYFSPDGQWVASASFDKSVKLWN
    GITGKFVAAFRGHVGPVYQISWSADSRLLLSGSKDSTLK
    IWD IRTKKLKRDLPGHADEVFAVDWSPDGEKVVSGGKDK
    VLKLWMG
    89 The amino acid sequence of SEQ ID MDAGSAHSSSNMKTQSRSPLQEQFLQRRNSRENLDRFIP
    355. The conserved G-protein beta NRSAMDFDYAHYMLTEGRKGKENPAVSSPSREAYRKQLA
    WD-40 repeat domains are ETLNMNRTRILAFKNKPPTPVELIPHELTSAQPAKPTKT
    underlined. RRYIPQTSERTLDAPDLLDDYYLNLLDWGSSNVLSIALG
    NTVYLWNASDGSTSELVTIDDETGPVTSVSWAPDGRHIA
    VGLNNSDVQLWDSADNRLLRTLRGGHRSRVGSLAWNNHI
    LTTGGMDGLIVNNDVRVRSHIVDTYRGHTQEVCGLKWSA
    SGQQLASGGNDNILHIWDRSTASSNSPTQWLHRLEEHTA
    AVKALAWCPFQGNLLASGGGGGDRTIKFWNTHTGACLNS
    VDTGSQVCALLWNKNERELLSSHGFTQNQLTLWKYPSMV
    KIAELTGHTSRVLFMAQSPDGCTVASAAGDETLRFWNVF
    GVPEVAKPAPKANPEPFAHLNRIR
    90 The amino acid sequence of SEQ ID MEEAIPFKNLPSREYQGHKKKVHSVAWNCTGTKLASGSV
    356. The conserved G-protein beta DQTARVWHIEPHGHGKVKDIELKGHTDSVDQLCWDPKHA
    WD-40 repeat domains are DLIATASGDKTVRLWD ARSGKCSQQAELSGENINITYKP
    underlined and the Trp-Asp (WD) DGTHVAVGNRDDELTILDVRKFKPIHKRKFNYEVNEIAW
    repeats signature is in bold. NMSGEMFFLTTGNGTVEVLAYPSLRPVDTLMAHTAGCYC
    IAIDPVGRYFAVGSADSLVSLWDISEMLCVRTFTKLEWP
    VRTISFNHTGDYVASASEDLFIDISNVQTGRTVHQIPCR
    AAMNSVEWNPKYNLLAYAGDDKNKYQADEGVFRIFGFESA
    91 The amino acid sequence of SEQ ID MGKDEEEMRGEIEERLINEEYKVWKKNTPFLYDLVITHA
    357. The conserved G-protein beta LEWPSLTVEWLPDREEPPGKDYSVQKLVLGTHTSENEPN
    WD-40 repeat domains are YLMLAQVQLPLEDAENDARHYDDDRADVGGFGCANGKVQ
    underlined. IIQQINHDGEVNRARYMPQNSFIIATKTVSAEVYVFDYS
    KHPSKPPLDGACSPDLRLRGHSTEGYGLSWSKFKQGHLL
    SGSDDAQICLWDINATPKNKSLDAMQIFKVHEGVVEDVA
    WHLRHEYLFGSVGDDQYLLIWDLRTPSVTKPVQSVVAHQ
    SEVNCLAFNPFNEWVVATGSTDKTVKLFDLRKISTALHT
    FDAHKEEVFQVGWNPKNETILASCCLGRRLMVWDLSRID
    EEQTPEDAEDGPPELLFIHGGHTSKISDFSWNTCEDWVV
    ASVAEDNILQIWQMAENIYHDEDDVPGEESNKGS
    92 The amino acid sequence of SEQ ID MMRGFSCTEDGDAPSTSSTSPPPPPPPPHRQQMQAPRAS
    358. The conserved G-protein beta SSSSGQPTSRRSTGNVFKLLARREVSPRSKHSLKKFWGE
    WD-40 repeat domains are ASECQLCPFQQSYEAVRDVRRSLISWVEAFSLQHLSAKY
    underlined. CPLMPPPRSTIAAAFSPDGKILASTHGDHTVKLIDSQTG
    SCLKVLRGHRRTPWVVRFHPLYPEILASGSLDHEVHLWD
    ANTAECIGSRNFYRPIASIAFHAQGDLLAVASGHKLYIW
    HYNRSGETSSPTIVLRTPRSLRAVHFHPHAAPFLLTAEV
    NDLDLTDSAMTLATSPGYLHYPPPTIYLADAHSNERSRL
    EDELPLMPSPLLMWPSFTRDDGRATLPHIGGDVGLSGQQ
    RVDSLSSGQYEFHPSPIEPSSSTSMHEEMGTDPFSSVRE
    SEVTQSAMNIVDNTEVQPEERSTYSFSFSDPRFWELPSV
    YGWLVGQTQAAPRTAPSPGALETASALGEVASVSPVRSE
    FMPGGMDQPRLGGRSGSGCRSSGSRMMRTAGLNDHPHDE
    NYPQSVVSKLRSELEASLAAAASTELPCTVKLRVWPYDM
    KDPCALFRSESCRLTIPHAVLCSEMGAHFSPCGRFFAAC
    VACVLPQLEADPVLHGQVDPDVTGVATSPTRHPVSAYQI
    MYELRIYSLEEATFGMVLASRSIRAAHCLTSIQFSPTSE
    HLLLAYGRRHNSLLKSIVIDGENTVPIYSILEVYRVSDM
    ELVRVLPSAEDEVNVACFHPSVGGGLVYGTKEGKLRILQ
    IDSSGGLNPKSTGFLDENMAEVPTYALEC
    93 The amino acid sequence of SEQ ID MGEGDLPRTEAGVLRGHEGAVLAARFNGDGNYCLSCGKD
    359. The conserved G-protein beta RTIRLWNPHRGIHIKTYKSHGREVRDVHCTSDNSKLISC
    WD-40 repeat domains are GGDRQIFYWDVSTGRVIRRFRGHDSEVNAVKFNDYASVV
    underlined. VSAGYDRSVRAWDCRSHSTEPIQIINTFQDSVMSVCLTK
    TEIIGGSVDGTVRTFDIRIGREISDDLGQPVNCISMSND
    GNCILASCLDSTLRLVDRSAGELLQEYKGHTCKSYKLDC
    CLTNTDAHVAGGSEDGYVFFWDLVDASVISKFRAHSSVV
    TSVSYHPKEDCMITASVDGTIKVWKT
    94 The amino acid sequence of SEQ ID MACIKGVGRSASVAMAPDGGYLATGTMAGTVDLSFSSSA
    360. The conserved G-protein beta SLEIFGLDFQSDDRDLPLIAESPSSERFNRLSWGKNGSG
    WD-40 repeat domains are SDEFSLGLIAGGLVDGTIGLWNPLSLIRSEAGDKAIVGH
    underlined LSRHKGPVRGLEFNVIAPNLLASGADDGEICIWDLAAPR
    EPSHFPPLRGSGSAAQGEISFLSWNSKVQHILASTSYNG
    TTVVWDLKKQKPVISFSDSVRRRCSVLQWNPDLATQLVV
    ASDEDSSPTLRLWDMRNIMSPVKEFAGHTRGVIAMSWCP
    NDSSYLVTCAKDNRTICWDTVTGEIVCELPAGSNWNFDV
    HWYPKIPGVISASSFDGKIGIYNVEGCSRYGVRENEFGA
    ATLRAPKWFKRPVGASFGFGGKVVSFHTRSTGGPSVNSS
    EVFVHDIITEQTLVSRSSEFEAAIQSGDRPSLRALCEKK
    SQHCESTDDQETWGFLKVLLEDDGTARSKLLAHLGFDIP
    TETNDGSQEDLSQQVNALGLEDVTADKVVQEDNNESMVF
    PTDNGEDFFNNLPSPRADTPVSTSADGFPTVNAAVEPSQ
    DEVDGLEESSDPSFDDSVQRALVVGDYKAAVALCMSANK
    LADALVIAHVGGASLWESTRDKYLKMSRLPYLKVVFAMV
    NNDLQSLVDTRPLKFWKETLAILCSFAQGEEWAMLCNSL
    ASKLMAAGNMLAATLCFICAGNIDKTVEIWSRSLATEHD
    GMSYMDLLQDLMEKTIVLALASGQKQFSASVCKLVEKYA
    EILASQGLLTTAMDYLKLLGTDDLSPELAVLRDRIAFSV
    EAEKGANISAFNGSQDPRGAVYGVDQSNYGMVDTSQHYY
    PEAAQPQVPHTVPGSPYGENYQQPFGSSFGKGYNTPMQY
    QAPSQASMFVPSEPPQNAQPSFVPTPVTSQPTTRSQFIP
    APPLALRNPEQYQQPTLGSHLYPGSVNPTFQPLPHAPGP
    VAPVPPQVSSVPGQNMPQAVAPTQMRGFMPVTNPGVVQN
    PGPISMQPATPIESAAAQPVVSPAAPPPTVQTADTSNVP
    APQKPVIATL
    95 The amino acid sequence of SEQ ID MKERGKGAGRSVDERYTQWKSLVPVLYDWLANHNLVWPS
    361. The conserved G-protein beta LSCRWGPQLEQATYKNRQRLYLSEQTDGSVPNTLVIANV
    WD-40 repeat domains are EVVKPRVAAAEHISQFNEEARSPFVKKFKTIIHPGEVNR
    underlined. IRELPQNSKIVATHTDSPDVLIWDVETQPNRHAVLGAST
    SRPDLILTGHKDNAEFALAMSPTEPFVLSGGKDRYVVLW
    SIQDHISTLAADPGSAKSPGSAGTNNKQSSKAAGGNDKT
    GDSPSIEPRGVYLGHGDTVEDVTFCPSSAQEFCSVGDDS
    CLILWDARTGSSPAIKVEKAHHADLHCVDWNPHDVNLIL
    TGSADNTVRMFDRRNLTSGGVGSPVHTFEGHNAAVLCVQ
    WSPDKSSVFGSSAEDGILNIWDHEKIGRKIETVGSKVPN
    SPPGLFFRHAGHRDKVVDFHWNSSDPWTIVSVSDDGEST
    GGGGTLQIWRMIDLIYRPEEEVLAELDKFKSHILSCTS
    96 The amino acid sequence of SEQ ID MAKIAPGCEPVAGTLTPSKKREYRVTNRLQEGKRPLYAV
    362. The conserved G-protein beta VFNFIDSRYFNVFATVGGNRVTVYQCLEGGVIAVLQSYI
    WD-40 repeat domains are DEDKDESFYTVSWACNIDRTPFVVAGGINGIIRVIDAGN
    underlined and the Trp-Asp (WD) EKIHRSFVGHGDSINEIRTQPLNPSLIVSASKDESVRLW
    repeats signature is in bold. N VHTGICILIFAGAGGHRNEVLSVDFHPSDKYRIASCGM
    DNTVKIWSMKEFWTYVEKSFTWTDLPSKFPTKYVQFPVF
    IAPVHSNYVDCNRWLGDFVLSKSVDNEIVLWEPKMKEQS
    PGEGSVDILQKYPVPECDIWFIKFSCDFHYHSIAIGNRE
    GKIYVWELQSSPPVLIAKLSHPQSKSPIRQTAMSFDGST
    ILSCCEDGTIWRWDAITASTS
    97 The amino acid sequence of SEQ ID MNTAMHFGAGWRSIAEMGYTMSRLEIEPESCEDEKSLDG
    363. The conserved G-protein beta VGNSQGPNELPRCLDHELAHLTNLKSRPHEHLIRDFPGR
    WD-40 repeat domains are RALPVSTVKMLAGRECNYSRRGRFSSADCCHMLSRYVPV
    underlined. NGPSPLDQMNSRAYVSQFSADGSLFVAGFQGSHIRIYNV
    DKGWKCQKNILTKSLRWTITDTSLSPDQRYLVYASMSPI
    VHIVDIGSAAMDSLANITEIHEGLDFSADSGPYSFGIFS
    VKFSTDGREVVAGSSDDSIYVYDLVANKLSLRIPAHESD
    VNTVCFADESGHIIYSGSDDTYCKVWDRRCLSARNKPAG
    VLMGHLEGITFIDSRGDGRYFISNGKDQTIKLWDIRKMG
    SDICRRGFRNFEWDYRWMDYPPRARDSKHPFDLSVATYK
    GHSVLRTLIRCYFSPVHSTGQKYIYTGSHDSCVYIYDVV
    TGAQVAALKHHKSPVRDCSWHPEYPMIVSSSWDGDIVKW
    EFFGNGETEIPAMKKRIRRRHLY
    98 The amino acid sequence of SEQ ID MEPQPQAPKKRGRKPKPKEDKKEEQLHQPPPPPPPQQQA
    364. The conserved G-protein beta APAPAPAATRSSTSGSAGGRDRRPQQQHAVDEKYARWKS
    WD-40 repeat domains are LVPVLYDWLANHNLLWPSLSCRWGPQLEQATYKNRQRLY
    underlined. ISEQTDGSVPNTLVIANCEVVKPRVAAAEHVSQFNEEAR
    SPFIRKYKTIIHPGEVNRVRELPQNPNIVATHTDSPDVL
    IWDVESQPNRHAVYGATASRPNLILTGHQENAEFALAMC
    PAEPFVLSGGKDKTVVLWSIQDHITASATDQTTNKSPGS
    GGSIIKKTGEGNEETGNGPSVGPRGIYCGHEDTVEDVAF
    CPSTAQEFCSVGDDSCLILWDARVGTNPVAKVEKAHNGD
    LHCVDWNPHDNNLILTGSADNSVNMFDRRNLTSNGVGSP
    VYKFEGHKAAVLCVQWSPDKPSVFGSSAEDGLLNIWDYE
    RVDKKVDRAPNAPAGLFFQHAGHRDKIVDFHWNAADPWT
    MVSVSDDCDTAGGGGTLQIWRMSDLIYRPEEEVLAELEN
    FKAHVLECSKA
    99 The amino acid sequence of SEQ ID MGIFEPYRAVGYITTGVPFSVQRLGTETFVTVSVGKAFQ
    365. The conserved G-protein beta VYNCAKLSLVLVGPQLPKKIRALASYREYTFAAYGSDIG
    WD-40 repeat domains are IFKRAHQLATWSGHTAKVCLLLLFGEHILSVDVDGNAYI
    underlined and the Trp-Asp (WD) WAFKGMNYNLSPVGHILLDSNFTPSCIMHPDTYLNKVIL
    repeats signature is in bold. The GSQEGPLQLWNISTKTKLYEFKGWNSSVSSCVSSPALDV
    Utp21 specific WD40 associated VAVGCADGKIHVHNIRYDEELVTFSHSMRGSVTALSFST
    putative domain is in italics. DGQPLLASGSSSGVVSIWNLDKRRLQSVIRDAHDGSIIS
    LHFFANEPVLMSSSADNSIKMWIFDTSDGDPRLLRFRSG
    HSAPPLCIRFYANGRHILSAGQDRAFRLFSVVQDQQSRE
    LSQRHVSKRAKKLKLKEEEIKLKPVIAFDVAEIRERDWC
    NVVTSHMDTPQAYVWRLQNFVIGEHILRPCPNKPTPVKA
    CMISACGNFAILGTAGGWIERFNLQSGISRGSYIDQLEG
    TNSAHDGEVVGVACDATNTLMISAGYAGDIKVWDFKGRE
    LKSRWEIGSSLVKISYHRLNGLLATVADDFIIRLFDAVA
    LRMVRKFEGHTDRITDLCFSEDGKWLLSSSMDGSLRIWD
    IILARQVDAVFVDVSITALSLSPNMDILATTHVDQNGVF
    LWVNQSMFSGDSDINLYASGKEVVTVKLPSVSSVEGSQV
    EESNEPTIRHSESKDVPSFRPSLEQIPDLVTLSLLPKSQ
    WQSLINLDIIKVRNKPVEPPKKPEKAPFFLPSIPSLSGE
    ILFKPSEMSDKGDMKADEDKSKITPEVPSSRFLQLLHSC
    SEAKNFSPFTTYIKGLSPSTLDLELRMLQIIDDDAVDAD
    ADDPQDVDKRQELLSIELLMDYFIHEISCRSNFEFVQAL
    VRLFLKIHGETIRRQSVLQNKAKVLLETQCSVWQRVDKL
    FQGARCMVAFLSNSQF
    100 The amino acid sequence of SEQ ID MEETKVTCGSWIRRPENVNLAVLGRSPRRRGSAALEIFA
    366. The conserved G-protein beta FDPKSTSLSSSPLVAHVIEEIEGDPLAIAVHPNGEDIVC
    WD-40 repeat domains are FASSGSCLSFELSGQESNLKLLTKELPPLRGIGPQKCMA
    underlined. FSVDGSRFATGGVDGRLRILEWPSLRIILDEPKAHKSIR
    DLDFSLDSEFLATTSTDGSARIWKAEDGLPCTTLTRRSD
    EKIELCRFSKDGTKPFLFCTVQRGDKAVTGVWDISTWNK
    IGHKRLLRKPAVVMSISLDGKYLAQGSKDGDMCVVEVKK
    MEVSHWSKRLHLGTSLTSLEFCPIERVVITTSDEWGVLV
    TKLNVPADWKAWQVYLLLLGLFLASLVAFYIFYENSDSF
    WGFPLGKDQPARPKIGSVLGDPKSADDQNMWGEFGPLDM
    101 The amino acid sequence of SEQ ID MADPVEHQHQQHQQHQLQQQRRRGWRIQGGQYLGEISAL
    367. The conserved G-protein beta CFLHLPPPPLSLSSSPVLSLSSGLDSESRDRPACSFRFP
    WD-40 repeat domains are SAGSGSQVSLFDLASGAMVRTFYVFRGIRVHGIVLGCAD
    underlined. FPGGSSSSSSTLDYVIAVYGERRVKLFRLSVRLGRGAGE
    GSGTVLSADLELVSAAPRLSHWVMDVRFLKENGTSEDEL
    QRCLTVAIGCSDNSIRLWDVDKCSFVLAVSSPERCLLYS
    MRLWGDNLEDLQVASGTIYNEILIWKVVPNHDAPSSNEL
    TEEGLTNSCAGNSVHECLRYEAYHICRLVGHEGSIFRIA
    WSSDGSKLVSVSDDRSARIWEVHCKVQYSEDAGEVGLLF
    GHSARVWDCYISDNLIVTAGEDCSCRVWGLDGQQHDVIK
    EHIGRGIWRCLYDPWSSLLVTGGFDSAIKVHKLDASLAE
    ASAKQSNIKDLSDGTELFTTHLPNSSGHSGHMDSKSEYV
    RCLSFSCEDVMYIATNHGYLYHAKLCNDGDLRWTELAQV
    SNEVQIICMELLPSNPYDPRIDADDWVAVGDGKGWTTVV
    RVVKNSDSPKVSTSFSWAAEMDRQLLGIHWCKSLGHRFI
    FTADPRGALKLWRFFEVSQSSSLYPENSPRISLIAEFKS
    DLGARIMCLDVAFESELLICGDLRGNLVLFPLLKDLLLD
    TFVVSAAKISPVNHFKGAHGISAVSSISVAHMSFNHIEL
    RSTGADGCICYMEYDKGLQSLNFVGMKQVKELSMIESVS
    TENESTGYRTSGSYASGFASTDFIIWNLVTEAKVLQVSC
    GGWRRPHSYYLGDVPEMKNCFAYVKDDIIYIRRHWIKDS
    KDKILPQNLRLQFHGREVHSLCFVTGDFQLRKNKQSSWI
    VTGCEDGTVRLTRYTQCTDNWSSSKLLGEHVGGSAVRSI
    CCVSNIHTTSSGTSVSDVKGIENLPKDIKGTLMEDECNP
    SLLISVGAKRVLTSWLLRRRKQDGKEDDVTDLQEAENSS
    LPSSAGSSTFSFQWLSTDMPVKYSVPSKKSGSIKKLIGV
    SDTNVRCKSL
    102 The amino acid sequence of SEQ ID MPYKLSATLSNHSSDVRAVASPSDDLILSASRDSTAISW
    368. The conserved G-protein beta FRQSPSSFTPASVIRAGSRFVNAIAYLPPTPRAPQGYAV
    WD-40 repeat domains are VGGQDTVVNVFALGPGDKEEPEYTLVGHTDNVCALSVNS
    underlined. DDTIISGSWDKTAKVWKDFALVYDLKGHQQSVWAVLAMN
    EKEFLTASADRTIKYWVQHKTMQTYEGHRDAVRGLALIP
    DIGFASCSNDSEIRVWTMGGDVVYTLSGHTSFVYSLSVL
    PNGDLVSAGEDRSVRVWRDGECSQVIVHPAISVWAVSTM
    PNGDIISGSSDGVVRVFSESEKRWATASELKALEDQIAS
    QSLPSQQVGDVKKTDLPGPEALSVPGKKAGEVKMIRSGD
    VVEAHQWDSLASSWQKIGEVVDAIGSGRKQLHDGKEYDY
    VFDVDIQEGAPPLKLPYNVSENPYTAAQRFLEQNDLPTG
    YLDQVVKFIEQNTAGVKLGNDGYVDPFTGASRYQPATQS
    TSNTASSSYMDPFTGGSRHIAESAPSNVPQGSHATGIIP
    FSKPIFFKLANVSAMQAKMFQFDEVLRNEISTATLAMRP
    DEVIMVNETFTYLSKVVTSTSSARTSLGWIHIETIMQIL
    DRWPVPQRFPVIDLGRLVTAYCMNAFSGPGDLEKFFSCL
    FRTSEWTSITSGSKALTKAQETNVLLLFRTIANSLDGAP
    LNDMEWIKQIFRELAQTPQLVLNKSHRLALASVLFNFSC
    IGLKGPVPADVRTLHLTIILQVLRSPNDDPEVAYRTCVA
    LGNMLYSDKTRGTPRDAQSPSPTELKSAVAAIKGGFSDP
    RINDVHREIMSLI
    103 The amino acid sequence of SEQ ID MPPQKIESGHKDTVHDLAMDYYGKRLATASSDHTINVVG
    369. The conserved G-protein beta VSSSGSQHLATLIGHQGPVWQISWAHPKFGSLLASCSYD
    domain is underlined and the WD-40 GRVIIWREGNPNEWTQAQVFEEHKSSVNSVAWAPHELGL
    repeat domains are in bold CLACGSSDGNISVFTARQDGGWDTSRIDQAHPVGVTSVS
    WAPSTAPGALVGSGMMEPVQKLCSGGCDNTVKVWKLYNR
    VWKLDCFPVLQMHTDWVRDVAWAPNLGLPKSTIASASQD
    GRVIIWTLAKEGDQWQGKVLYDFRTPVWRVSWSLTGNIL
    AVADGNNNVSLWN EAVDGEWIQVSTVEP
    104 The amino acid sequence of SEQ ID MSAPMLEIEARDVVKIVLQFCKENSLHQTFQTLQSECQV
    370. The conserved G-protein beta SLNTVDSIETFVADINSGRWDAILPQVAQLKLPRNTLED
    WD-40 repeat domains are LYEQIVLEMIELRELDTARAILRQTQAMGVMKQEQPERY
    underlined and the Trp-Asp (WD) LRLEHLLVRTYFDPNEAYQDSTKEKRRAQIAQALAAEVT
    repeats signature is in bold. VVPPSRLMALVGQALKWQQHQGLLPPGTQFDLFRGTAAM
    KQDVDDMYPTTLSHTIKFGTKSHAECARFSPDGQFLVSC
    SVDGFIEVWDYMSGKLKKDLQYQADETFMMHDDPVLCVD
    FSRDSEMLASGSQDGKIKVWRIRTGQCLRRLERAHSQGV
    TSVLFSRDGSQLLSTSFDGSARIHGLKSGKQLKEFRGHS
    SYVNDAIFSNDGSRVITASSDCTVKVWD VKTSDCLQTFK
    PPPPLRGGDASVNSVHLFPKNADHIVVCNKTSSIYIMTL
    QGQVVKSLSSGKREGGDFVAACVSPKGEWIYCVGEDRNL
    YCFSCQSGKLEHLMKVHEKDVIGVTHHPHRNLVATYSED
    STMKLWKP
    105 The amino acid sequence of SEQ ID MDLLQSYAEDNDGDLGRHSSPEPSPPRLLPSKSAAPKVD
    371. The conserved G-protein beta DTTLALTVAQTNQTLARPIDPSQHAVAFNPTYDQLWAPI
    WD-40 repeat domains are CGPAHPYAKDGIAQGMRNHKLGFVEDAAIGSFLFDEQYN
    underlined. TFQRYGYAADPCASTGNEYVGDLDALKQNDGISVYNIRQ
    QEQKKYAEEYAKKKGEERGEGGREKAEVVSDKSTFHGKE
    ERDYQGRSWIAPPKDAKATNDHCYIPKRLVHTWSGHTKG
    VSAIRFFPKHGHLILSAGMDTKVKIWDVFNSGKCMRTYM
    GHSKAVRDISFCNDGTKFLTAGYDKNIKYWDTETGKVIS
    TFSTGKIPYVVKLHPDDEKQNILLAGMSDKKIVQWDMNT
    GQITQEYDQHLGAVNTITFVDDNRRFVTSSDDKSLRVWE
    FGIPVVIKYISEPHMHSMPSISLHPNTNWLAAQSLDNQI
    LIYSTRERFQLNKKKRFAGHIVAGYACQVNFSPDGRFVM
    SGDGEGRCWFWDWKSCKVFRTLKCHEGVCIGCEWHPLEQ
    SKVATCGWDGLIKYWD
    106 The amino acid sequence of SEQ ID MESNGNLEQTLQDGRIYRQLNSLIVAHLRDHNFPQAASA
    372. The conserved G-protein beta VALATMTPLNVEAPRNRLLELVAKGLAVEKGELLRGVSH
    WD-40 repeat domains are AGTNDLGGSIPASYGLVPAPWTAIDFSSLRDTKGMSKSF
    underlined. TKHETRHLSDHKNVARCARFSTDGRFFATGSADTSIKLF
    EVSKIKQMMLPDSTDGAIRAVIRTFYDHTHPVNDLDFHP
    QNTVLISAAKDHTVKFFDYSKATAKRAFRVIQDTHNVRS
    VAFHPSGDFLLAGTDHPIPHLYDVNTFQCYLSANVPEFA
    VNAAINQVRYSSSGGMYVTASKDGTIRFWDGASANCVRS
    IAGAHGAAEVTSANFTKDQRYVLSCGKDSTVKLWEVGTG
    RLVKQYLGATHMQLRCQAVFNNTEEFVLSIDEPSNEIVV
    WDAMTAEKVARWPSNHNGPPRWIEHSPTEAAFVSCSTDR
    SIRFWKETH
    107 The amino acid sequence of SEQ ID MSNFQGEDGEYVADDFEAEDGDEELHGRESADPESDVDE
    373. The conserved G-protein beta IDTPSNRFTDTTADQARRGRDIQGIPWERLSITREKYRR
    WD-40 repeat domains are TRLEQYKNYENVPQSGEKSGKDCTVTEKGNSFYEFRRNS
    underlined. RSVKSTILHFQLRNLVWATSKHDVYLMSNYSVVHWSSLT
    GKKSEVLNLAGHVAPNEKHPGSLLEGFTQTQVSTLAVKD
    RFLVAGGFQGELICKFLDRPGISFCSRTTYDDNAITNAV
    EIYVSPSGGIHFIASNNDCGVRDFDMENFELSKHFRFPW
    PVNHTSLSPDGKLLVIVGDDPEGILVDAKTGKTIMPLRG
    HLDFSFASEWHPDGVTFATGNQDKTCRIWDIRNLSKSIA
    VLKGNLGAIRSIRYTSDGRYMAIAEPADFVHVYDTKTGY
    KKEQEIDFFGEISGMSFSPDTESLFIGVWDRTYGSLLEY
    GRRRNFSYLDCLV
    108 The amino acid sequence of SEQ ID MGVEEDLEDLNALAESTDAAVDGQAALASAVDSVTLQPA
    374. The conserved G-protein beta PPILPPVIPPPAVPVVAPVPTIPPVLRPLAPLPIRPPVL
    WD-40 repeat domains are RPPAPKRDEAGSSDSDSDHDGTAAGSTAEYEITEESRLV
    underlined and the splicing factor RERHEKAMQDLMMKRRGAALAVPTNDKAVRARLRRLGEP
    motif is in bold. MTLFGEREMERRDRLRMLMAKLDAEGQLEKLMKAHEDEE
    AAASAAPEDVEEEMLQYPFYTEGSKALFNARIDIAKFSI
    TRAALRLERARRRRDDPDEDVDAEIDWALKKAESLSLHC
    SEIGDDRPLSGCSFSHDGKLLATCSMSGVAKLWDTCRMP
    QVNRVLTLKGHTERATDVAFSPVQNHIATASADRTAKLW
    NTEGTILKTFEGHLDRLGRIAFHPSGKYLGTTSFDKTWR
    LWDIESGEELLLQEGHSRSIYGIDFHRDGSLVASCGLDA
    LARVWDLRTGRSILALEGHVKPVLGVSFSPNGYHLATGG
    EDNTCRIWDLRKKKSLYTIPAHANLISEVKFEPQEGYFL
    VTASYDTTAKVWSARDFKPVKTLSVHEAKITSVDITADA
    SHIVTVSHDRTIKLWTSNDDVKEQAMDVD
    109 The amino acid sequence of SEQ ID MVKAYLRYEPAAAFGVIASVESNIAYDASGKHLLAPALE
    375. The conserved G-protein beta KVGVWHVRQGVCTKALAPSASSAAGPSLAVTAIASSPSS
    WD-40 repeat domains are LIASGYADGSIRIWDFEKGSCETTLNGHKGAVSVLRYGK
    underlined, and the conserved LGSLLASGSKDNDIILWDVVGETGLYRLRGHRDQVTDLV
    Dip2/Utp12 domain is in bold. FLDSDKKLVSSSKDKYLRVWDLETQHCMQIVGGHHSEIW
    SLDTDPEERYLVTGSADPELRFYTVKNDSSDERSEADAS
    GGVGNGDLASHNKWDVLKQFGEIQRQSKDRVATVRFNKN
    GNLLACQAAGKLVEVFRVLDEAEAKRKAKRRLHRKREKK
    GADVNENSDSSRGIGEGHDTMVTVADVFKLLQTIRASKK
    ICSISFCPVAPKSSLATLALSLNNNLLEFHSIEADKTSK
    MLTIELQGHRSDVRSVTLSSDNTLLMSTSHNSVKIWNPS
    TGSCLRTIDSGYGLCGLIVPQNKHALIGTKDGAIEIFDV
    GSGTCIEVVEAHGGSIRSIVAIPNQNGFVTGSADHDIKF
    WEYGMKQKPGDNSKHLTVSNVRTLKMNDDVLVVAVSPDA
    QKIAVALLDCTVKVFFMDSLKLMHSLYGHRLPVLCLDIS
    SDGDLIVTGSADKNLMIWGLDFGDRHKSIFAHGDSIMAV
    QFVGNTHYMFSVGKDRLVKYWDADKFELLLTLEGHHADI
    WCLAISNRGDFLVTGSHDRSIRRWDRTEEPFFIEEEKEK
    RLEEMFESDLDNAFGNKYVPKEEIPEEGAVALAGKKTQE
    TLSATDSIIEALDIAEVELKRIAEHEEEKNNGKTAEFHP
    NYVMLGLSPSDFILRALSNVQTNDLEQTLLALPFSDALK
    LLSYLKDWTTYPDKVELVSRIATVLLQTHYNQLVSTPAA
    RPLLTTLKDILHKKVKECKDTIGFNLAAMDHLKQLMALR
    SDALFQDAKVKLLEIRSQLSKRLEERTDPREAKRRKKKQ
    KKSTNMHAWP
    110 The amino acid sequence of SEQ ID MGGVQAEREDKDKVSLELTEEILQSMEVGMTFRDYSGRI
    376. The conserved G-protein beta SSMDFHRASSYLVTASDDESIRLYDVASATCLKTINSKK
    WD-40 repeat domains are YSVDLVSFTSHPMTVIYSSKNGWDESLRLLSLHDNKYLR
    underlined. YFKGHHDRVVSLSLCPRNECFISGSLDRTVLLWDQRAEK
    CQGLLRVQGRPATAYDDPGLVFAIAFGGCVRMFDARKYE
    KGPFEIFSVGGDVSDANVVKFSNDGRLMLLTTTDGHIHV
    LDSFRGTLLYTFNVKPTSSKSTLEASFSPEGMFVISGSG
    DGSVYAWSVRGGKEVASWLSTDTEPPVIKWAPGNLMFAT
    GSSELSFWIPDLSKLGAYVGRK
    111 The amino acid sequence of SEQ ID MAAFGAAPAGNHNPNKSSEVIQPPSDSVSSLCFSPRANH
    377. The conserved G-protein beta LVATSWDNQVRCWELTKNGASVTSVPKASMSHDQPVLCS
    WD-40 repeat domains are AWKDDGTTVFSGGCDKQAKMWSLMSGGQPVTVAMHDAPI
    underlined. KEIAWIPEMNVLVTGSWDKTLKYWDTRQSNPVHTQQLPE
    RCYAMTVRYPLMVVGTADRNLIVFNLQNPQAEFKRFSSP
    LKYQTRCVAAFPDQQGFLVGSIEGRVGVHHLDDSQISKN
    FTFKCHRDNNDIYSVNSLNFHPVHHTFATAGSDGTFNFW
    DKDSKQRLKAMSRCSQPIPCSTFNNDGTIYAYSVCYDWS
    KGAENHNPATAKTYIFLHLPQESEVKAKPRVGTTNRK
    112 The amino acid sequence of SEQ ID MNCSISGEVPEEPVVSTKSGHVFERRLIERYVSDYGKCP
    378. The conserved G-protein beta VSGEPLTMDDVLPVKMGKIVKPRPLQAASIPGLLSIFQN
    WD-40 repeat domains are EWDSLMLSNFALEQQLHTARQELSHALYQHDAACRVIAR
    underlined. LKKERDEARSLLALAERQIPMTASSDIAVNAPAMSNGRK
    ASLDEEPGYAGKKMRPGISASIIAEITDCNLALSQQRKK
    RQIPSTLAPVEDLERYTQLSSYPLHKTGKPGITSLDICH
    SKDIIATGGIDTSAVLFDRSSGQIMSTLSGHSKKVTSVN
    FDAQGDMVLTGSADKTVRIWQGSEDGSYNCRHILKDHTA
    EVQAITVHATNNYFATASLDNTWCFYEFSTGLCLTQVEG
    ASGSEGYTSAAFHPDGLILGTGTSNADVKIWDVKTQANV
    TTFSGHTGAITAISFSENGYFLATAAQDGVKLWDLRKLK
    NFRTFSAYDKDTGTNSVEFDHSGCYLGLAGSDIRVYQVA
    SVKSEWNCVKTFPDLSGTGKVTCVKFGPDSKYIAVGSMD
    HNLRIFGLPSEDGAMES
    113 The amino acid sequence of SEQ ID MAAPGVETLKKEIKELKEKIAQHRLDTDGEQPLPAAAKS
    379. The conserved G-protein beta KSVPEVSAALKQRRI LKGHFGKIYALHWSADSRHLVSAS
    domain is underlined and the WD-40 QDGKLIIWNGFTTNKVHAIPLRSSWVMTCAYSPSGNLVA
    repeat domains are in bold CGGLDNLCSVYKVPHGGNKESSSAQKTYGELAQHEGYLS
    CCRFIKDNEIVTSSGDSTCILWDVETKTPKAIFNDHTGD
    VMSLAVFDDKGVFVSGSCDATAKLWDHRVHKQCVMTFQG
    HESDINSVQFFPDGDAFGTGSDDSSCRLFDIRAYQQINK
    YSSDKILCGITSVAFSKTGKSLFAGYDDYNTYVWDTLSG
    NQVEVLTGHENRVSCLGVSEDGKALATGSWDTLLKIWA
    114 The amino acid sequence of SEQ ID MGGVEDESEPASKRMKLSSRVLRGLANGSSRTEPAAGSS
    380. The conserved G-protein beta LDLMARPLPIEGDEEVIGSKGVIKRVEFVRLIAKALYSL
    WD-40 repeat domains are GYEKSGARLEEESGIPLQSSVVNLFMQQISDGLWDESVV
    underlined. TLHKIGLSDENLVKSASFLILEQKFLELLDQEKAMDALK
    TLRTEITPLCIKNSRVRELSSCIISPSSCGLLNQNKRNS
    TRARSRSELLEELQKLLPPAVIIPERRLEHLVEQALVLQ
    TDACMLHNSIDMEMSLYTDHQCGKEHIPCRTLQILQSHN
    DEVWLVQFSHNGKYLASASNDRSAIIWEVDENGSVSLKH
    KLTGHQKPISSVCWSPDDRQLLTCGVGETVRRWDVSSGE
    CLRVYEKAGHGLISCAWFPDGKWICYGVSDRSICMCDLE
    GKEIECWKGQRTLSISDLEITSDGKQIISICRETAILLL
    DREAKYERMIEENQTITSFSLSKDNRYLLVNLLNQEIHL
    WDIKGDFRLVAKYKGLKRSRFVIRSCFGGLKQAFVASGS
    EDSQVYIWHKGSGELIEPLPGHSGAVNCVSWNPANHHML
    ASASDDRTIRIWGLNELNTRHKGARPNGVHYCNGNGTS
    115 The amino acid sequence of SEQ ID MTQLAETYACMPSTERGRGILIAGNPKPGSNSVLYTNGR
    381. The conserved G-protein beta SVVILNLDNPLDISVYAEHAYPATVARFSPNGEWVASAD
    WD-40 repeat domains are SSGAVRIWGAYNDHVLKKEFKVLSGRIDDLQWSPDGLRI
    underlined. VASGDGKGKSLVRAFMWDSGTNVGEFDGHSRRVLSCAFK
    PTRPFRIVTCGEDFLVNFYEGPPFKFKLSRRDHSNFVNC
    LRFSPDGNRFISVSSDKKGIIYDGKTGEKIGELSSDGGH
    TGSIYAVSWSPDSKQVITVSADKSAKIWDISEDGSGNLR
    KTLTSSGSGGVDDMLVGCLWQNNHLVTVSLGGTISIYTA
    GDLDKAPVSFSGHMKNVSSLSVLKGDPKVILSSSYDGLI
    IKWIQGIGFSGRVQRKESTQIKCLAAVDEEIVTSGYDNK
    VCRVSGSGDAEFIDIGCQPKDLSLALQCPEFALVSTDTG
    VVLLRGAKIVSTINLGFAVTASTVAPDGTEAIIGAQDGK
    LRIYSISGDTLTEEAVLEKHRGAISVIHYSPDLSMFASG
    DLNREAVVWDRASREVRLKNILYHTARINCLAWSPDSST
    VATGSLDTCVIIYEVDKPASNRLTIKGAHLGGVYGLAFT
    DDFSVVSSGEDACIRVWKINRQ
    116 The amino acid sequence of SEQ ID MKVKVISRSTDEFTRERSQDLQRVFRNFDPNLRTQEKAV
    382. The conserved G-protein beta EYVRALNAAKLDKVFARPFVGAMDGHVDSVSCMAKNPNY
    WD-40 repeat domains are LKGIFSGSMDGDIRLWDIASRRTVCQFPGHQGPVRGLAA
    underlined and the SOF1 protein STDGQILVSCGIDSTVRLWNVPVATLGESDGTHENLAKP
    domain is in bold. LAVYVWKNAFWAVDHQWDGELFATAGAQVDIWNQNRSQP
    ISSFEWGTDTVISVRFNPGEPNVLATSGSDRSITLYDLR
    MSSPTRKVIMRTKTNAISWNPMEPMNFTAANEDCNCYSY
    DARKLEEAKCVHKDHVSAVMDIDYSPTGREFVTGSYDRT
    VRIFQYNGGHSREVYHTKRMQRVFCVKFSCDASYVISGS
    DDTNLRLWK AKASEQLGVVLPRERRKHEYHEAVKSRYKH
    LPEVKRIVRHRHLPKPIYKAGILRRTVNEADRRKEERRK
    AHSAPGSSSAEPLRKRRIIKEIE
    117 The amino acid sequence of SEQ ID MVRSIKNPKKAKRKNKGSKNGDGSSSSSSIPSMPTKVWQ
    383. The conserved G-protein beta PGVDKLEEGEELQCDPSAYNSLHAFHIGWPCLSFDIVRD
    WD-40 repeat domains are TLGLVRTEFPHQVYFVAGTQAEKPTWNSIGIFKVSNITG
    underlined. KRRELVPSKPTDDADEESDSSDSDEDSDDEVGGSGTPIL
    QLRKVGHEGCVNRIRAMNQNPHICASWGDSGHVQIWDFS
    SHLNALAESEADVSQGASSVFNQAPLVKFGGHKDEGYAL
    DWSPLVPGRLVSGDCKNSIHLWEPTSGSTWNVDSTPFIG
    HAASVEDLQWSPTEENVFASCSVDGTIAIWDTRLGKTPA
    ASFKAHDADVNVISWNRLATCMLASGCDDGTFSIHDLRL
    LKEGDSVVAHFEYHKHPVTSIEWSPHEASTLAVSSADCQ
    LTIWDLSLEKDEEEEAEFKAKTKEQVNAPEDLPPQLLFV
    HQGQKDLKELHWHAQIPGMIVSTAADGFNILMPSNIQST
    LPSDGA
    118 The amino acid sequence of SEQ ID MERYKVIKELGDGTYGSVWKALNQQTHEIVAIKKMKRKY
    384. The conserved eukaryotic YIWEECINLREVKSLRKLNHPNIIKLKEVIRENNELFFI
    protein kinase domain is FEYMECNLYQIMKERSTPFSETAIIKFCYQILQGLSYMH
    underlined and the protein kinases RNGYFHRDLKPENLLVTSDLIKIADFGLAREVLTSPPYT
    ATP-binding region and DYVSTRWYRAPEVLLQSPTYTTAIDMWAVGAILAELFTL
    serine/threonine protein kinases HPLFPGESELDEIYKICGVLGTPDYETWPDGMQLAAFRN
    active-site signatures are in FIFPQFLPVNLSVLIPHASPEAIDLITRLCSWDPQKRPT
    bold. AEQALHHPFFRIGMSIPLSLGGHFQDNTCAAEVDTKFHS
    KKACKAWNGEKESSLECFLGLSLGLKPSLGHLGAMGSQG
    VGAVKQEVGSSPGCQSNPKQSLFQVLNSRAILPLFSSSP
    NLNVVPVKSSLPSAYTVNSQVMWPTIAGPPAAAVTVSTL
    QPSILGDFKIFGKSMGLASQYAGKEASPFS
    119 The amino acid sequence of SEQ ID MGEMGRGINNSSNNNNSNRPAWLQHYDLVGKIGEGTYGL
    385. The conserved eukaryotic VFLARSKLPNNRGLRIAIKKFKQSKDGDGVSPTAIREIM
    protein kinase domain is LLREFSHENVVKLVNVHINHVDMSLYLAFDYAEHDLYEI
    underlined and the protein kinases IRHHREKLNHHNINQYTVKSLLWQLLNGLNYLHSNWIVH
    ATP-binding region and RDLKPSNILVMGEGEEHGVVKIADFGLARIYQAPLKPLS
    serine/threonine protein kinases DNGVVVTIWYRAPELLLGAKHYTSAVDMWAVGCIFAELI
    active-site signatures are boxed TLKPLFQGVEVKASPNPFQLDQLDKIFKVLGHPTIEKWP
    in bold. TLMNLPHWSKNLQQIQQHKYDNAGLHIGPIPAKSPAYDL
    LSKMLEYDPRKRITAAQALEHEYFRIDPQPGRNALVPSQ
    PGEKAINYPPRLVDANTDFDGTIAPQPSQVSSGNAPSGS
    IASAAVPAVRPLPQQMQLMGMQRMQNPGMAAFNLGAQAS
    MSGLNHNNIALQRGSSQQQAHQQVRRKEPNSGFPNTGYP
    PPPKSRRL
    120 The amino acid sequence of SEQ ID MDKYEKLEKVGEGTYGKVYKARDKMTGQLVALKKTRLEM
    386. The conserved protein kinase DEEGVPPSSLREISLLQMLSQSIYVVRLLCVEHVTKKGK
    family domain is underlined. The PLLYLVFEYLDTDLKKFIDYRRSVNAGPLPQNVIQSFMY
    protein kinases ATP-binding region QLLKGVAHCHSHGVLHRDLKPQNLLVDKSKGLLKVGDLG
    is in bold and the LGRAFTVPLKCYTHEVVTLWYRAPEVLLGSTHYSTPVDI
    serine/threonine protein kinases WSVGCIFAEMVRRQPLFPGDCEIQQLLHIFTLLGTPTEE
    active-site signature is in MWPGVKRLRDWHEYPQWKPENLARAVPNLSPTGLDLISK
    bold/italics. MLQCDPAKRISAKAAMNHPYFDDLDKSQF
    121 The amino acid sequence of SEQ ID MDGYEKMDKVGEGTYGKVYMARDKKTGQLVALKKTRLEN
    387. The conserved protein kinase DGEGIPPTALREISLLQMLSQDIYIVRLLDVKHTENKLG
    family domain is underlined. The KPLLYLVFEYMESDLKKYIDSYRRSHTKMPPSMIKSFMY
    protein kinases ATP-binding region QLCRGVAYCHSRG DKEKGVLKIADLG
    is in bold and the LSRAFTVPVKKYTHEIVTLWYRAPEVLLGATHYSLPVDI
    serine/threonine protein kinases WSVGCIFAEMSRMQALFTGDSEVQQLMNIFRFLGTPNEE
    active-site signature is in VWPGVTKLKDWHIYPEWKPQDISHAVPDLEPSGLDLLSQ
    bold/italics. MLVYEPSKRISAKKALEHPYFDDLDKSQF
    122 The amino acid sequence of SEQ ID MDAYEKLEKVGEGTYGKVYKAKDKNTGQLVALKKTRLES
    388. The conserved eukaryotic DDEGIPPTALREISLLQMLSQDIHIVRLLDVEHTENKNG
    protein kinase domain is KPLLYLVFEYMDSDLKKYIDGYRRSHTKVPPNIIKSFMY
    underlined and the protein kinases QLCQGVAYCHSRGVMHRDLKPHNLLVDKQRGVVKIADLG
    ATP-binding region and LGRAFTIPIKKYTHEIVTLWYRAPEVLLGATHYSTPVDI
    serine/threonine protein kinases WSVGCIFAEMVRLQALFIGDSEVQQLFKIFSFLGTPNEE
    active-site signatures are in IWPGVTKFRDWHIYPQWKPQDISSAVPDLEPSGVDLLSK
    bold. MLVYEPSKRISAKKALEHPYFDDLDKSQF
    123 The amino acid sequence of SEQ ID MDSYEKLEKVGEGTYGKVYKAKDKKTGKLVALKKTRLEN
    389. The conserved protein kinase DGEGIPPTALREISLLQMLSQDMNIVRLLDVEHTENKNG
    family domain is underlined. The KPLLYLVFEYMDSDLKKYVDGYRRSHTKMPPKIIKSFMY
    protein kinases ATP-binding region QLCQGVAYCHSRG DKQRGVLKIADLG
    is in bold and the LGRAFTVPIKKYTHEIVTLWYRAPEVLLGATHYSTPVDI
    serine/threonine protein kinases WSVGCIFAEMSRMHALFCGDSEVQQLMSIFKFLGTPNEG
    active-site signature is in VWPGVTKLKDWHIYPEWRPQDLSRAVPDLEPSGVDLLTK
    bold/italics. MLVYEPSKRISAKKALQHPYFDDLDKSQF
    124 The amino acid sequence of SEQ ID MEKYEKLEKVGEGTYGKVYKGRDKRTGRLVALKKTPFHQ
    390. The conserved eukaryotic EEGIPPTAIREISLLKSLSQCIYIVKLLDVKASFNGKGK
    protein kinase domain is HVLFMVFEYADSDLKKHIDAHRQCNTKLSPRSIQSYMFQ
    underlined and the protein kinases LCKGIAYCHSHGVLHRDLKPQNILVDQKIGLLKIADLGL
    ATP-binding region and GRACTVPIKSYTFEVVTLWYRAPEVLLGAKRYSMALDIW
    serine/threonine protein kinases SLGCIFAELCNLQALFAGDSQIQQLINIFRLLGTPNEQL
    active-site signatures are in WPGVTQLSDWHEFPQWRPQDLSKVVFNLDPNGVDLLSKM
    bold. LQYDPAKRISAKEALDHPYFDSLDKSQF
    125 The amino acid sequence of SEQ ID MGCVCGKPSARAADYVESPAEKGASSNSRSSSMASRRLV
    391. The conserved eukaryotic APAVMDQGIDAENGHEGDYRTKLRGKQSNGADPVSLLSD
    protein kinase domain is DAEKQRHSRHHQHQQHHPIRPHHLRPQGEFVPNANSNPR
    underlined and the FGNPPRHIEGEQVAAGWPAWLTAVAGEAIKGWIPRRADS
    serine/threonine protein kinases FEKLDKIGQGTYSNVYKARDLDTGKIVALKKVRFDNLEP
    active-site signatures are in ESVRFMAREIQVLRRLDHPNVVKLEGLVTSRMSCSLYLV
    bold. FEYMDHDLAGLAACPGIKFTEPQVKCYMQQLLRGLDHCH
    SRGVLHRDIKGSNLLIDNGGILKIADFGLATFFHPDQRQ
    PLTSRVVTLWYRPPELLLGATEYGVAVDLWSTGCILAEL
    LAGKPIMPGRTEVEQLHKIFKLCGSPSEDYWKKSKLPHA
    TIFKPQQPYKRCVAETFKDFPPSALALMEVLLAIEPADR
    GTATSALKSDFFTTKPLACDPSSLPKYPPSKEFDAKIRD
    EEARRQRAAGGRGRDAARRPSRESRAIPAPEANAELAIS
    IQKRRLSSQGPSKSKSEKFNPQQEDGAVGFPIEPPRPMH
    IGIDAGATSRMYSQQFGPSHSGPLSNQISSSIWGKNQKE
    DEIQMAPGRPSRSSKATISDFRKPGACAPQPGADLSHLS
    SLVATARSNAGIDTHKDRSGMWQHNRIDAIDGVHNNGKH
    EFLEVPEHPNRQDWTRFQQPESFKGLDNYHLQDLPATHH
    RKDERVASKEATMNWQGYGGQGGDKIHYSGPLLPPSGNI
    DEILKEHERHIQHAVRRARQDKGRPQRSNLSQNERKAFE
    HRSFVSGVNGNAGYSDLVNELPISVGSNRLKVSKTRGTE
    EIVELRELEREPLSSVMEKYEREHEM
    126 The amino acid sequence of SEQ ID MGCVCAKQSDILGEPESPKVKGSNLASSRWSVSSETKQL
    392. The conserved eukaryotic PQHSDSGILHHQHYYHPRDESDEAKLKESNYGGSKRRTR
    protein kinase domain is QGRDPADLDMGIFVRTPSSQSEAELVAAGWPAWMAAFAG
    underlined and serine/threonine EAIHGWIPRRAESFEKLYKIGQGTYSNVYKARDLDNGKI
    protein kinases active-site VALKKVRFDSLDAESVRFMAREILVLRKLDHPNIVKLEG
    signatures is in bold. LVTSEVSSSLYLVFEYMEHDLAGLAACPGIKFTEPQVKC
    YMQQLLQGLDHCHRHGVLHRDIKGSNLLIDNGGILKIAD
    FGLATFFYPDQKQLLTSRVVTLWYRPPELLLGATDYGVA
    VDIWSAGCILAELLAGKPILPGRTEVEQLHKIFKLCGSP
    SEDYWKESKLPHATIFKPQHPYKSCIAEAFKDFSPSALA
    LLETLLAIEPGHRGEASGALKSEFFTTEPLSCDPSSLPK
    YPPSKEFDAKLRAQETRRQRDVGVRGHGSEAARRTSRLS
    RAGPTPNEGAELTALTQKQHSTSHATSNIGSEKPSTKKE
    DYTAGLHIDPPRPVNHSYETTGVSRAYDAIRGVAYSGPL
    SQTHVSGSTSGKKPKRDHVKGLSGQSSLQPSKPFIVSDS
    RSERIYEKSHVTDLSNHSRLAVGRNRDTTDPHKSLSTLM
    QQIQDGTLDGIDIGTHEYARAPVSSTKQKSAQLQRPSAL
    KYVDNVQLQNTRVGSRQSDERPANKESDMVSHRQGQRIH
    CSGPLLHPSANIEDLLQKHEQQIQQAVRRAHHGKREALS
    NKSSLPGKKPVDHRAWVSSGKGNKESPYFKGKGNKELSD
    LKGGPTAKVTNFRQKVM
    127 The amino acid sequence of SEQ ID MAVANPGQLNLQEAPSWGSRSVNCFEKLEQIGEGTYGQV
    393. The conserved protein kinase YMAKEIETGEIVALKKIRMDNEREGFPITAIREIKLLKK
    family domain is underlined. The LQHENVIKLKEIVTSPGPEKDEQGKSDGNKYNGSIYMVF
    protein kinases ATP-binding region EYMDHDLTGLAERPGMRFSVPQIKCYMKQLLIGLHYCHI
    is in bold and the NQ
    Figure US20100122382A1-20100513-P00028
    DNNGILKLADFGLARSFCSDQNGN
    serine/threonine protein kinases LTNRVITLWYRPPELLLGSTKYGPAVDMWSVGCIFAELL
    active-site signature is in YGKPILPGKNEPEQLTKIFELCGSPDESNWPGVSKLPWY
    bold/italics. SNFKPQRQMKRRVRESFKNFDRHALDLVEKMLTLDPSQR
    ISAKDALDAEYFWTDPVPCAPSSLPRYEPSHDFQTKRKR
    QQQRQHDEMTKRQKISQHPPQQHVRLPPIQNAGQGHLPL
    RPGPNPTMHNPPPQFPVGPSHYTGGPRGAGGQNRHPQNI
    RPLHAAQGGGYNANRGYGGPPQQQGGGYPPHGMGNQGPR
    GGQFGGRGAGYSQGGPYGGPVGGRGPNVGGGNRGPQFWS
    EQ
    128 The amino acid sequence of SEQ ID MQNMEDNVQSSWSLHGNKEICARYEILERVGSGTYSDVY
    394. The conserved eukaryotic RGRRKADGLIVALKEVHDYQSSWREIEALQRLCGCPNVV
    protein kinase domain is RLYEWFWRENEDAVLVLEFLPSDLYSVIKSGKNKGENGI
    underlined and the PEAEVKAWMIQILQGLADCHANWVIHRDLKPSNLLISAD
    serine/threonine protein kinases GILKLADFGQARILEEPEAIYEVEYELPQEDIVADAPGE
    active-site signature is in bold. RLMEEDDSVKGVRNEGEEDSSTAVETNFGDMAETANLDL
    SWKNEGDMVMQGFTSGVGTRWYRAPELLYGATIYGKEID
    LWSLGCILGELLILEPLFSGTSDIDQLSRLVKVLGTPTE
    ENWPGCSNLPDYRKLCFPGDGSPVGLKNHVPSCSDSVFS
    ILERLVCYDPAARLNAKEVLENKYFVEDPYPVLTHELRV
    PSPLREENNFSEDWAKWKDMEADSDLENIDEFNVVHSSD
    GFCIKFS
    129 The amino acid sequence of SEQ ID MDLNQYPEDLNPELPEGTDNVDNPDNNKGSPVPSPHPPL
    395. The conserved eukaryotic KPLDPSERYRKGITLGQGTYGIVYKAFDTVTNKTVAVKK
    protein kinase domain is IHLGKAKEGVNVTALREIKLLKELSHPNIIQLIDAYPHK
    underlined and the protein kinases QNLHIVFEFMETDLEAVIKDRNLVFSPADIKSYLQMTLK
    ATP-binding region and GLAVCHKKWVLHRDMKPNNLLIAADGQLKLGDFGLARLF
    serine/threonine protein kinases GSPDRKFTHQVFAVWYRAPELLFGAKQYGPAVDIWATGC
    active-site signatures are in IFAELLLRKPFLQGVSDLDQIGKIFAAFGTPRQSQWPDV
    bold. ASLPDFVEFQFVPAPSLRSLFPMASEDALDLLSKMFTLD
    PKNRITAQQALEHRYFSSVPAPTRPDLLPKPSKVDSSRP
    PKHASPDGPVVLSPSKARRVMLFPNNLAGILPKQVSQST
    TGGTPIEFDMPTQKLREVCPRSRITESGKKHLKRKTMDM
    SAALDECAREQEGQEGKTILDPDHQRSAKKEKHM
    130 The amino acid sequence of SEQ ID MAGGQENCVRITRARAACVSKASAPVIQSQVDEKKSRKR
    396. The conserved cyclin N- and APKRAAVDDLAANASGSQPKRRAVLGDVTNLHAAATDCL
    C-terminal family domains are STAEDQVDAPNPSIKGRARNKKKEARTSTKVVKDEIHPE
    underlined. SNPLADHSSNLSECQKPPAAKLAEQRSLRGVPSKAKQGG
    SSNSQSCSKHTDIDKDHTDPQMCTTYVEDIYEYLRNAEL
    KNRPSANFMETAQNDITPNMRAILVDWLVEVSEEYKLVP
    DTLYLTVSYIDRYLSANPTSRHKLQLLGVSCMLIASKYE
    EVCPPHVEEFCYITDNTYTRDEMLSMERKILIFLNFEMT
    KPTTKSFLRRFVRASQAGNKAPSLHMEFLANYLAELTLM
    ECSFLQYLPSLIAASTVFLSRLTLDFLTNPWNPTLAHYT
    GYKASQLKDCVMAIYNVQMNRKGSTLVAIREKYQQHKFK
    CVASLPPPPFIAERFFDTPN
    131 The amino acid sequence of SEQ ID MTGTQASNVRITRARAAKSTLNNALPPLPPAQGKPRGKR
    397. The conserved cyclin and AATESNISGFSVAAEPLKRRAVLSDVSNICKEAAAVDCL
    cyclin C-terminal domains are KKPKAVKVVSQNANAKGRGRGIPRNNKKITQEAEIKKET
    underlined and the cyclins SPAICNVDDASAGNAIGDDKQNNNVNPLKEVQDNPKELN
    signature is in bold. PIAEQISVHPHCKQSVEKPNEKEIVVSDNKAAIASLKQQ
    STLQSLRIPKQPKYSLKQGNPVPLANLHEDVGRSSCSDF
    IDIDSEYKDPQMCTAYVTDIYANMRVVELKRRPLPNFME
    TTQRDINANMRSVLIDWLVEVSEEYKLVPDTLYLTVSYI
    DRFLSANVVNRQRLQLLGVSCMLVASKYEEICAPPVEEF
    CYITDNTYKKEEVLEMEISVLNRLQYDLTTPTTKTFLRR
    FIRAAQASCKVSSLHLEFMGNYLAELTLVEYDFLKYLPS
    LIAAAAVFVARMTLDPMVHPWNSTLQHYTGYKVSDMRDC
    ICAIHDLQLNRKGCTLAAIREKYNQPKFKCVANLFPPPI
    ISPQFLIDNEV
    132 The amino acid sequence of SEQ ID MAAPNQNALLINNNNRRPLVDIGNLVGALNAQCNISKNG
    398. The conserved cyclin and ARKRAFGDIGNLVEDLDAKCTISKYWVRKRPRTNFGVNA
    cyclin C-terminal domains are NKGASSSTQGQGIVVRGEQKAWDRIVWGNKQSCAIKMNA
    underlined and the cyclins QHVTATQRGTAISISDIIDSSVQDGGIKAPSQLKARKQT
    signature is in bold. VRTVTATLTARSEDSLRDVLEVPPGIDDGDRDNPLAVVE
    YVEDIYHFYRKIEVRSCVPPDYMTRQLEIKDSMRGVIID
    WLIEVHRTFLLMPETLYLTVNIIDRYLSIQSVTRNELQL
    MGITAMFIASKYEEISPPKINDLVYITKDAYTSKQIVNM
    EHTILNRLKFKLTVPTPYVFLVRFLKAAGPDKVMKNLAF
    FLVDLCLLHYKMIKYSPSMLAAAAVYTAQCTLKKHPYWN
    KTLILHIGYSEAHLRECAHLMADLHLKAEGSNLKSVYKK
    YSYPIFGSVAFLSPAKIPAGTVAAPAIDKCAHQIYLRNLR
    133 The amino acid sequence of SEQ ID MFPNKQTQGLVQNKKMASKAAQPKAMVPPQRVPPAANNR
    399. The conserved cyclin N- and RALGDIGNIVADVGGKCNVTKDGVNGKPLAQVSRPITRS
    C-terminal family domains are FGAQLLAQAAANKGISAANNQTQVPVVIPKADVRGNKQR
    underlined. RTSKSKDIPPTTVVTNESDDCVIIEQAQRIKPTCNHNVG
    AVGNKEKPQLLTAKPKSLTASLTSRSAVALRGFRFDDEM
    TEAEEDPLPNIDVGDRDNQLAVVEYVEDIYKFYRRTEQM
    SCVPDYMPRQQEINPKMRAVLINWLIEVHYRFGLMPETL
    YLTTNLIDRYLATQLVSRSNYQLVGATAMLLASKYEEIW
    APEMNDFLDILENKFERKHVLVMEKAMLNKLKFHLTVPT
    PYVFLVRFLKAAASDEEMENLVFFLMELSLMQYVMIKFP
    PSMLAAAAVYTAQITLKKTTVWNDVLKRHTGYSEIDLKE
    CTRLMVAFHQSSEESKLNVVFKKYSMPEYDSVALIKPAK
    LPA
    134 The amino acid sequence of SEQ ID MAPSFDCVANAYIESCEDQEKLRQNAQILAQSGENDVDE
    400. The conserved cyclin and PVSMLVQRETHYMLPEDYLQRLRNRTLDVNVRREAVGWI
    cyclin C-terminal domains are LKVHSFYNFSAPTAYLAVNYLDRFLSRHRMPQGVKAWMI
    underlined QLMAVACLSLAAKMEETQVPLPSDLQREDARFIFDARTI
    QRMELLILSTLQWGMRSITPFSFIDYFAYRAVQGHGHGH
    DATPKAVMSRAIELILSTTEEIDFMEYRPSAIAAAALLC
    AAEEVVPLQAVHYKRALSSSITDVDKDKMFGCYNLIQET
    IIEGGCYWTPMSLQSTEKTPVGVLDAAACLSNTPTSSYS
    VKPYASVTAAKRRKLNEICSALLVSQAHPC
    135 The amino acid sequence of SEQ ID MAANFWTSSHCKELLDAEKVGIVHPLDKDQGLTQEDVKI
    401. The conserved cyclin and IKINMSNCIRTLAQYVKLRQRVVATAITYCRRVYTRKSF
    cyclin C-terminal domains are TEYDPQLVAPTCLYLASKAEESTVQAKLVIFYMKKYSKH
    underlined. RYEIKDMLEMEMKLLEALDYYLVIYHPYRPLIQFLQDAG
    LNDLKVTAWALVNDTYRTDLILTYPPYMIALACIYFACI
    MEEKDAQAWFEELRVDMNEIKNISMEIVDYYDNYRVIPD
    EKMNSALNKLPHRF
    136 The amino acid sequence of SEQ ID MAPALSSSYECLSHLLCAEDASNVVGCWDEDESKIFCEE
    402. The conserved cyclin domain EEGFGIQHFPDFPVPDDDEIRVLVRKESQYMPGKSYVQS
    is underlined. YQNLGLDFTARQNAIGWILKVHGSYNFGPLTAYLSINYL
    DRFLSRNPLPKAKVWMLQLLSVACLSLAAKMEETQVPLL
    LDLQAEEPDFLFEPRTIQRMELLVLSTLEWRMLSVTPFS
    FVDYFLQGGGGRKPPPRAMVARANELIFNTHTVLDFLEH
    RPSAIAAAAVICAAEEVLPLEAAQYKETILSCSLVDKEW
    VFGSYNLIQEVLIEKFSTPKKAKSASSSIPQSPVGVLDA
    FCLSNNSNNTSLEASLSVNLYASVAAKRRKLNDYCNTWR
    MFQHSTC
    137 The amino acid sequence of SEQ ID MAPNCIDCAPSDLFCAEDAFGVVEWGDAETGSLYGDEDQ
    403. The conserved cyclin domain LHYNLDICDQHDEHLWDDGELVAFAEKETLYVPNPVEKN
    is underlined. SAEAKARQDAVDWILKVHAHYGFGPVTAVLSINYLDRFL
    SANQLQQDKPWMTQLAAVACLSLAAKMDETEVPLLLDFQ
    VEEAKYIFESRTIQRMELLVLSTLEWRMSPVTPLSYIDH
    ASRMIGLENHHCWIFTMRCKEILLNTLRDAKFLGLLPSV
    VAAAIMLHVIKETELVNPCEYENRLLSAMKVNKDMCERC
    IGLLIAPESSSLGSFSLGLKRKSSTINIPVPGSPDGVLD
    ATFSCSSSSCGSGQSTPGSYDSNNSSILCISPAVIKKRK
    LNYEFCSDLHCLED
    138 The amino acid sequence of SEQ ID MPQIQYSEKYTDDTYEYRHVVLPPETAKLLPKNRLLNEN
    404. The conserved cyclin- EWRAIGVQQSRGWVHYAIHRPEPHIMLFRRPLNYQQNQQ
    dependent kinases regulatory QQAGAQSQPMGLKAQ
    subunit domain is underlined and
    the cyclin-dependent kinases
    regulatory subunits signature 1 is
    in bold.
    139 The amino acid sequence of SEQ ID MDQIEYSEKYYDDTYEYRHVELPPDVARLLPKNRLLTEN
    405. The conserved cyclin- EWRGIGVQQSRGWVHYAIHCSEPHIMLFRRPLNYEQNHQ
    dependent kinases regulatory HPEPHIMLFRRPLNCQPNHQPQAHHPT
    subunit domain is underlined and
    the cyclin-dependent kinases
    regulatory subunits signature 1 is
    in bold.
    140 The amino acid sequence of SEQ ID MDQIEYSEKYYDDTYEYRHVELPPDVARLLPKNRLLTEN
    406. The conserved cyclin- EWRGIGVQQSRGWVHYAIHCSEPHIMLFRRPLNYEQNHQ
    dependent kinases regulatory HPEPHIMLFRRPLNCQPNHQPQAHHPT
    subunit domain is underlined and
    the cyclin-dependent kinases
    regulatory subunits signature 1 is
    in bold.
    141 The amino acid sequence of SEQ ID MPQIQYSEKYYDDTYEYRHVVLPPDVARLLPKNRLLNEN
    407. The conserved cyclin- EWRGIGVQQSRGWVHYAIHRPEPHIMLFRRHLNYQQNQQ
    dependent kinases regulatory QQAQQQPAQAMGLQA
    subunit domain is underlined and
    the cyclin-dependent kinases
    regulatory subunits signature 1 is
    in bold.
    142 The amino acid sequence of SEQ ID MALVETEPVTLIHPEEPKKFKKKPTPGRGGVISHGLTEE
    408. The conserved GCN5-related N- EARVKAIAEIVGAMVEGCRKGEDVDLNALKAAACRRYGL
    acetyltransferase family domain is SRAPKLVEMIAALPDGERAAVLPKLKAKPVRTASGIAVV
    underlined and the radical SAM AVMSKPHRCPHIATTGNICVYCPGGPDSDFEYSTQSYTG
    family domain is in bold. YEPTSMRAIRARYNPYVQTRSRIDQLKRLGHTVDKVEFI
    LMGGTFMSLPADYRDYFIRNLHDALSGHTSSNVEEAVCY
    SEHSATKCIGLTIETRPDYCLGPHLRQMLSYGCTRLEIG
    VQSTYEDVARDTNRGHTVAAVADCFCLAKDAGFKVVAHM
    MPDLPNVGVERDMESFREFFENPAFRADGLKIYPTLVIR
    GTGLYELWKTGRYRNYPPEQLVDIIARVLALVPPWTRVY
    RVQRDIPMPLVTSGVEKGNLRELALARMDDLGLKCRDVR
    TREAGIQDIHHKIRPEVVELVRRDYCANEGWETFLSYED
    TRQDILVGLLRLRKCGHNTTCPELKGRCSIVRELHVYGT
    AVPVHGRDADKLQHQGYGTLLMEQAERIAWKEHRSIKIA
    VISGVGTRHYYRKLGYELEGPYMMKYLN
    143 The amino acid sequence of SEQ ID MLGFRDLYTSICEHLQRASGRLPIIAAATSLISTPEIAA
    409. The conserved chromo domain VEKENKAPNSVDKMGMGSADESGRFSTSNGQFMNMNNGV
    is underlined and the MOZ/SAS-like VKEEWKGGVPVVPSAPTTVPVITNVKLETPSSPDHDMAR
    protein domain is in bold. KRKLGFLPLEVGTRVLCKWRDGKFHPVKIIERRKLPNGA
    TNDYEYYVHYTEFNRRLDEWVKLEQLELDSVETDADEKV
    DDKAGSLKMTRHQKRKIDETHVEGNEELDAASLREHEEF
    TKVKNITKIELGRYEIETWYFSPFPSEYNNCEKLYFCEF
    CLNFMKRKEQLQRHMRKCDLKHPPGDEIYRSGTLSMFEV
    DGKKNKVYAQNLCYLAKLFLDHKTLYYDVDLFLFYILCE
    CDERGCHMVGYFSKEKHSEESYNLACILTLPPYQRKGYG
    KFLISFSYELSKKEGKVGTPERPLSDLGLLSYRGYWTRV
    LLDILKKHKSNISIKELSDMTAIKADDVLSTLQGLDLIQ
    YRKGQHAICADPKVLDRHLKAVGRGGLEVDVCKLIWTPY
    KEQ
    144 The amino acid sequence of SEQ ID MGSLDESTCSEEIRDEGKDSIRTKFKVESTVNNAQNGGN
    410. The conserved MOZ/SAS-like DNSKKKRAAGLPLEVGIRLLCKWRDSKLHPVKIIERRKL
    protein domain is underlined. PNGFPQDYEYYVHYTEFNRRLDEWVKLEQFELDSVETDA
    DEKIEDKGGSLKMTRHQKRKIDEIHVEEGQGHEDFDPAS
    LREHEEFTKVKNIAKVELGRYEIETWYFSPFPPEYSHCE
    KLFFCEFCLNFMKRKEQLQRHMRKCDLKHPPGDEIYRNG
    TLSMFEVDGKKNKIYGQNLCYLAKLFLDHKTLYYDVDLF
    LFYVLCECDDRGCHVVGYFSKEKHSDEAYNLACILTLPP
    YQRKGYGKFLIAFSYELSKKEGKVGTPERPLSDLGLLSY
    RGYWTRILLDILKKQRGNISIKELSDMTAIKVEDVISTL
    QVLDLIQYRKGQHVICADPKVLDRHLKAAGIAGLEVDVS
    KLIWTPYKEQCG
    145 The amino acid sequence of SEQ ID MASAPMVGCDDSRDKHRWVESKVYMRKGHGKGSKGNAGF
    411. The conserved bromo family NAQNSTAQVRRENDNMGNSIADNGKSEAASEGLSSLSRK
    domain is underlined. QITVNQDHPPNETSSMPAVGGLQNIDTHVTFKLEGCSKQ
    EIWELRKKLTNELEQVRGTFKKLEARELQLRGYSVSAGV
    NTSYSASQFSGNDMRNNGGKEVTSEVASGGAITPKQAQR
    ESNPPRQLSISLMENNQAASDMGEKGKRTPKANQYYRNS
    EFVLGKDKFPPAESKKSKSTGNKKISQSKVFSKETMQVG
    KEFMPQKSVNEVFKQCSLLLTKLMKHKYGWVFNLPVDAQ
    ALGLHDYHTIIKRPMDLGTVKSKLEKNLYNSPASFAEDV
    KLTFSNAMTYNPKGHEVHTMAEQLLQLFEERWKTIYEEH
    LDGKMRFGSGQGLGASSSTKKLPFQDSKKNIKKSEPAGG
    PSPPKPKSTNHHASRTPSAKKPKAKDPHKRDMTYEEKQK
    LSTNLQNLPQERLELIVQIIKKRNPSLCQHDEEIEVDID
    SFDTETLWELDRFVTNYKKSLSKNKKKALLADQAKRASE
    HGSARNKHPMIGRELPMNNKKGEQGEKVVEIDHMPPVNP
    PVVEVEKDGVYAKRSSSSSSSSSDSGSSSSDSDSGSSSG
    SESDAYAATSPPAGSNTSARG
    146 The amino acid sequence of SEQ ID MEGHSGALGFGQGFSRSSQSPNLSPSPSHSASASVTSSG
    412. The conserved GCN5-related N- QKRKRNEVEHAGVASNSTGMFAVPPSHIYSHLHPMSMSM
    acetyltransferase family domain is PMPMHNSHPSSLSESRDGALTSNDDDDNLTGGNQSQLDS
    underlined and the bromodomain is MSAGNTDGREDFDDEDDDDDDEEDDDEVEGDEEDQDHDP
    in bold. DADDDSDDGHDSMRTFTAARLDNGAPNSRNLKPKADAAG
    VAIAPTVKTEPILDTVKEEKVSGNNNNNSVSANNAQVAP
    SGSAVLLSAVKEEANKPTSTDHIQTSGAYCAREESLKRE
    EDADRLKFVCFGNDGIDQHMIWLIGLKNIFARQLPNMPK
    EYIVRLVMDRSHKSVMIIKQNQVVGGITYRPYLSQKFGE
    IAFCAITADEQVKGYGTRLMNHLKQHARDVDGLTHFLTY
    ADNNAVGYFIKQDFTKEIKLEKERWHGYIKDYDGGILME
    CKIDPKLPYTDLPAMIRWQRQTIDEKIRELSNCHIVYSG
    IDIQKKEAGIPRKPIKVEDIPGLKEAGWTTDQWGHSRFR
    LLNSPSEGLPNRQVLHAFMRSLHKAMVEHADAWPFKEPV
    DPRDVPDYYDIIKDPMDVKRMFTNARTYNTHETIYYKCA
    NR
    147 The amino acid sequence of SEQ ID MEESGNSLTSGPDGSKRRVSYFYDSDIGNYYYSQGHPMK
    413. The conserved histone PHRIRMAHSLIVHYALDEKMEVCRPNLLQSRELRVFHAD
    deacetylase family domain is DYISFLQSVTPETQHEQLRQLKRFNVGEDCPVFDGLYNF
    underlined. CQTYAGGSVGAAIKLNNKEADIAINWSGGLHHAKKCEAS
    GFCYVNDIVLAILELLKVHQRVLYIDIDIHHGDGVEEAF
    YSTDRVMSVSFHKFGDYFPGTGHLKDVGYGKGKYYSLNV
    PLNDGIDDESYKNLFRPIIQKVMEIYQPEAVVLQCGADS
    LSGDRLGCFNLSVKGHADCVRFLRSFNVPLVLVGGGGYT
    IRNVARCWCYETAVAVGVEPQDKLPYNEYYEYFGPDYTL
    HVAPSNMENQNSAKELAKIRNTLLEQLKRIQHVPSVPFQ
    ERPPDTKFPEEDEEDYEKRPKGHKWGGEYFGSESDEEQK
    PQNRDIDISDKPGIRRQSPPNVEAAKKIKVEEEDGDIGI
    VNENDGAKWPLGEAG
    148 The amino acid sequence of SEQ ID MEESGNSLTSGPDGSKRRVSYFYDSDIGNYYYSQGHPMK
    414. The conserve histone PHRIRMAHSLIVHYALDEKMEVCRPNLLQSRELRVFHAD
    deacetylase domain is underlined. DYISFLQSVTPETQHEQLRQLKRFNVGEDCPVFDGLYNF
    CQTYAGGSVGAAIKLNNKEADIAINWSGGLHHAKKCEAS
    GFCYVNDIVLAILELLKVHQRVYIDIDIHHGDGVEEAF
    YSTDRVMSVSFHKFGDYFPGTGHLKDVGYGKGKYYSLNV
    PLNDGIDDESYKNLFRPIIQKVMEIYQPEAVVLQCGADS
    LSGDRLGCFNLSVKGHADCVRFLRSFNVPLVLVGGGGYT
    IRNVARCWCYETAVGVEVEPQDKLPYNEYYEYFGPDYTL
    HVAPSNMENQNSAKELAKIRNTLLEQLKRIQHVPSVPFQ
    ERPPDTKFPEEDEEDYEKRPKGHKWGGEYFGSESDEEQK
    PQNRDIDISDKPGIRRQSPPNVEAAKKIKVEEEDGDIGI
    VNENDGAKWPLGEAG
    149 The amino acid sequence of SEQ ID MMETGGNSLPSGPDGVKRKVAYFYDPEVGNYYYGQGHPM
    416. The conserved histone KPHRIRMTHALLVQYGLHKEMQILKPYPARDRDLCRFHA
    deacetylase family domain is DDYVAFLRGITPETIQDQVKALKRFNVGDDCPVFDGLYQ
    underlined. YCQTYAGGSVGGAVKLNHKLCDIAINWAGGLHHAKKCEA
    SGFCYVNDIVLAILELLKYHKRVLYVDIDIHHGDGVEEA
    FYTTDRVMTVSFHKFGDYFPGTGDIRDIGCGKGKYYAVN
    VPLDDGIDDESFQSLFKPIIQQVMLVYNPEAIVLQCGAD
    SLSGDRLGCFNLSVKGHAECVRYMRSFNVPLLMVGGGGY
    TVRNVARCWCYETGVAVGVEIDDKMPQHEYYEYFGPDYT
    VHVAPSNMENKNTKQYLDKIRSKILENINSLPCAPSAQF
    QVQPPDTDFPELEEEDYDERTRSHKWDGASCDSDSENGD
    LKHRNHDVEESAFPRHNLANISYNTKIKLEGVGTGGLDM
    AAGTDTKKNDESFEAMDYESGEELRQDHFASTINASQPC
    DPALLTGVQNQLQSTDTVKPIEQSGNAPGIPPPSVATVS
    TGTRPSSISRTSSLNSMSSVKQGSILGPNPPQGLNASGL
    QFPVPTSNSPIRQGGSYSITVQAPDKQGLQNHMKGPQNM
    PGNS
    150 The amino acid sequence of SEQ ID MPPKDRVAYFYDGDVGSVYFGPNHPMKPHRLCMTHHLVL
    417. The conserved histone SYELHKKMEIYRPHKAYPVELAQFHSADYVEFLHRITPD
    deacetylase family domain is TQHLFTKELVKYNMGEDCPVFENLFEFCQIYAGGTIDAA
    underlined. HRLNNQICDIAINWSGGLHHAKKCEASGFCYINDLVLGI
    LELLKHHARVLYVDIDVHHGDGVEEAFYFTDRVMTVSFH
    KYGDMFFPGTGDVKEVGEREGKYYAINVPLKDGIDDASF
    TRLFKTIITKVVDIYQPGAIVLQCGADSLAGDRLGCFNL
    SIDGHAQCVRIVKKFNLPLLVTGGGGYTKENVARCWSVE
    TGVLLDTELPNEIPDNDYIKYFAPDYSLKINTAGNMENL
    NSKTYLSAIKVQVMENLRAIQHAPSVQMHEVPPDFYIPD
    IDEDELNPDERMDQHTQDRQIQRDDEYYDGDNDIDHDME
    EAS
    151 The amino acid sequence of SEQ ID MDSSKSEEANILHVFWHEGMLNHDLGTGVFDTLEDPGFL
    418. The conserved histone EVLEKHPENADRVRNMLSILRKGPIAPYTEWHTGRAAYL
    deacetylase family domain is SELYSFHRPDYVDMLAKTSTAGGKTLCHGTRLNPGSWEA
    underlined. ALLAAGTTLEAMRYILDGHGKLSYALVRPPGHHAQPTQA
    DGYCFLNNAGLAVELAVASGCKRVAVVDIDVHYGNGTAE
    GFYERDDVLTISLHMNHGSWGPSHPQTGFHDEVGRGKGL
    GFNLNVPLPNGTGDKGYEHAMHELVVPAISKFMPEMIVL
    VIGQDSSAFDPNGRECLTMEGYRKIGQIMRQQADQFSGG
    RLVVVQEGGYHITYAAYCLHATLEGVLCLPHPLLSDPIA
    YYPEHDIYSERVTFIKNYWQGGIISTTDKRN
    152 The amino acid sequence of SEQ ID MEESGNALVSGPDGSKRRVTYFYDADIGNYYYGQGHPMK
    419. The conserved histone PHRMRMAHNLIVHYGLHQRMEVCRPHLAQSKDIRAFHTD
    deacetylase family domain is DYIHFLSSVAPDTQQEQLRQLKRFNVGEDCPVFDGLFNF
    underlined. CQSSAGGSIGAALKLNRKDADIAINWAGGLHHAKKCEAS
    GFCYVNDIVLGILELLKVHQRVLYIDIDIHHGDGVEEAF
    YTTDRVMTVSFHKFGDYFPGTGHIKDVGYGKGKYYALNV
    PLNDGIDDESYKHLFRPIIQKVMEVYQPEAVVLQCGADS
    LSGDRLGCFNLSVKGHADCVRFVRSFNIPLMLVGGGGYT
    IRNVARCWCYETAVAVGVEPQDKLPYNEYYEYFGPDYTL
    YVAPSNMENLNTEKDLEKMRNVLLEQLSKIQHTPSVPFQ
    ERPPDTEFNDEEEEDMEKRSKCRIWDGEYVGSEPEEDGK
    LPRFDADTYERSVLKHENKRLVPVSNVEPLKRIKQEEDG
    AAV
    153 The amino acid sequence of SEQ ID MDLNLVSHGEEEEGVRRRKVGIVYDERMCKHATPEDQPH
    421. The conserved histone PEQPDRIRVIWDKLNSAGVLHKCVMVEAKEASEEQLAGV
    deacetylase family domain is HSRKHIEVMKSIGTARYNKKKRDKLAASYSSIYFSQGSS
    underlined. EAALLAAGSVVEISEKVASGELDAGVAIVRPPGHHAEAD
    KAMGFCLFNNIAIAAKHLVHERPELGVQKVLIVDWDVHH
    GNGTQHMFWTDPHVLYFSVHRFDAGTFYPGGDDGFYDKI
    GEGKGAGYNINVPWEQGKCGDADYLAVWDHVLVPVAKSY
    DPDMVLISGGFDAALGDPLGGCRLTPYGYSLMTKKLMEF
    AGGKIVLALEGGYNLKSLADSFLACVEALLKDGPGRSSV
    LTHPFGSTWRVIQAVRKELSSFWPALNEELQLPRLLKDA
    SESFDKLSSSSSDESSASEDEKKFAEVTSIMEVSPDPSS
    ILALTAEDIAQPLAGLKIEEAGTDSQRSSDHTLLDLTND
    DTQKLKQFEGEIFVMIGDEESVPSASSSKDQNESTVVLS
    KSNIKAHSWRLTFSSIYVWYASYGSNMWNPRFLCYIEGG
    QVEGMAKRCCGSEDKLLLKGYSGKLFLIECFLGDHTQIH
    GVQEECPFLIQIVVIRVKRMSACIK
    154 The amino acid sequence of SEQ ID MADEDLDLSDVGEVEDEPGEEIESTPPLAVGQEKEINSL
    422. The conserved FKBP-type ALKKKLLKVGTRWETPENGDEVTVHYTGTLPDGTKFDSS
    peptidyl-prolyl cis-trans RDRGEPFTFKLGQGQVIKGWDQGIVTMKKGERALFTIPP
    isomerase signature is underlined ELAYGSSGVRPTIPPNATLQFDVELLSWTNIVDVCNDGG
    and the FKBP-type peptidyl-prolyl ILKRIISEGEKYERPKDPDEVTVKYEAKLEDGTLVAKSP
    cis-trans isomerase signatures 1 EEGVEFYVNDGHFCPAIAKAVKTMKRGESVILTIKPTYA
    and 2 are in bold. FGERGKDAEEGFAAIPPNATLTTSLELVSFKAVIAVTED
    KKVIKKILKEADGYDKPSDGTVVQIRYTAKLQDGTIFEK
    KGYEGEEPFQFVVDEEQVIAGLDKAVETMKTGEIALITI
    GAEYGFGNFETQRDLAVIPPNSTLIYEVEMISFTKEKES
    WDMDTTEKIEASKQKKEQGNSLFKVGKYQRAAKKYEKAA
    KYIEHDSSFSAEEKKQSKVLKVSCNLNHAACRLKLKDFK
    EAVKLCSKVLELESQNVKALYRRAQAYIETADLDLAEFD
    IKKALEIEPQNREVQLEYKILKQKQIEYNKKDAKLYGNM
    FAKLNKLEAFEGKVLS
    155 The amino acid sequence of SEQ ID MADEGLELSDVAEVEDEPGEEFESAPPLVVGQEKELNSS
    423. The conserved FKBP-type GLKKKLLKAGTRCETPENGDEVTVHYTGTLLDGTKFDSS
    peptidyl-prolyl cis-trans RDRGEPFTFNIGQGQVIKGWDQGIVTMKKREHALFTIPP
    isomerase family domains are ELAYGASGMPPTIPPNATLQFDVELLSWTNIVDVCKDGG
    underlined. The FKBP-type ILKRIISDGEKYERPKDPDEVTVKYEAKLEDGMLVAKSP
    peptidyl-prolyl cis-trans EEGVEFYVNDGNFCPAIVKAVKTMKKGENVTLTIKPAYA
    isomerase signatures
    1 and 2 are FGEQGKDAEEGFAAIPPNATITINLQLVSFKAVKEVTED
    in bold. The TPR repeat is in KKVIKKILKEADGYDKPSDGTVVQIRYTAKLQDGTIFEK
    bold/italics. KGYAGEEPFQFVVDEEQVIAGLDKAVETMKTGEVALITI
    GPEYGFGNIETQRDLAVIPPYSTLIYEVEMVSFTKEKES
    WDMNTTENIEASKQKKEQGNSLFKVGKYLRAAKKYDKAA
    KYIEHDNSFSAEEKKQSKVLKVSCNLNHAACCLKLKDFK
    KAVKLCSKVLELESQN
    Figure US20100122382A1-20100513-P00029
    Figure US20100122382A1-20100513-P00030
    REVRLEYLILKQKQIEYNKKDAKLYGNM
    FARQNKLEAIEGKD
    156 The amino acid sequence of SEQ ID MPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRAL
    424. The conserved cyclophilin- CTGEKGTGRSGKPLHFKGSSFHRVIPGFMCQGGDFTRGN
    type peptidyl-prolyl cis-trans GTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGS
    isomerase signature is underlined QFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGS
    and the cyclophilin-type peptidyl- GRTSKPVVIADSGQLA
    prolyl cis-trans isomerase
    signature
    2 is in bold.
    157 The amino acid sequence of SEQ ID MPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRAL
    425. The conserved cyclophilin- CTGEKGNGRSGKPLHFKGSSFHRVIPGFMCQGGDFTRGN
    type peptidyl-prolyl cis-trans GTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGS
    isomerase signature is underlined QFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGS
    and The cyclophilin-type peptidyl- GRTSKPVVIADSGQLA
    prolyl cis-trans isomerase
    signature
    2 is in bold.
    158 The amino acid sequence of SEQ ID MPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRAL
    426. The conserved cyclophilin- CTGEKGTGRSGKPLHFKGSSFHRVIPGFMCQGGDFTRGN
    type peptidyl-prolyl cis-trans GTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGS
    isomerase signature is underlined QFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGS
    and The cyclophilin-type peptidyl- GRTSKPVVIADSGQLA
    prolyl cis-trans isomerase
    signature
    2 is in bold.
    159 The amino acid sequence of SEQ ID MPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRAL
    427. The conserved cyclophilin- CTGEKGTGRSGKPLHFKGSSFHRVIPGFMCQGGDFTRGN
    type peptidyl-prolyl cis-trans GTGGESIYGEKFADENFVKKHTGPGILSMANAGPNTNGS
    isomerase signature is underlined QFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGS
    and The cyclophilin-type peptidyl- GRTSKPVVIADSGQLA
    prolyl cis-trans isomerase
    signature
    2 is in bold.
    160 The amino acid sequence of SEQ ID MADDFELPESAGMMENEDFGDTVFKVGEEKEIGKQGLKK
    428. The conserved FKBP-type LLVKEGGSWETPETGDEVEVHYTGTLLDGTKFDSSRDRG
    peptidyl-prolyl cis-trans TPFKFKLGQGQVIKGWDQGIATMKKGENAVFTIPPDLAY
    isomerase signature is underlined GESGSQPTIPPNATLKFDVELLSWASVKDICKDGGIFKK
    and the FKBP-type peptidyl-prolyl IIKEGEKWEHPKEADEVLVKYEARLEDGTVVSKSEEGVE
    cis-trans isomerase signature 1 is FYVKDGYFCPAFAIAVKTMKKGEKVLLTVKPQYGFGHQG
    in bold and underlined. The TPR REAIGNDVARSTNATLLVDLELVSWKVVDEVTDDKKVLK
    repeat is in bold/italics. KILKQGEGYERPNDGAVVKVKYTGKLEDGTIFEEKGSDE
    EPFEFMAGEEQVVDGLDRAVMTMKKGEVALVSVAAEYGY
    QTEIKTDLAVVPPKSTLIYEVELVSFVKEKESWDMNTAE
    KIEAAGKKKEEGNALFKVGKYFRASKKYEKATKYIEYDT
    SFSEEEKKQSKPLK
    Figure US20100122382A1-20100513-P00031
    Figure US20100122382A1-20100513-P00032
    Figure US20100122382A1-20100513-P00033
    Figure US20100122382A1-20100513-P00034
    RDVKLEYRALKEKQKEYNKKEAKFYGNMFARMSKL
    EELESRKSGSQKVETANKEEGSDAMAVDGESA
    161 The amino acid sequence of SEQ ID MAASLTPLGAGLAYATIYDQAKVRKLEPTKRSLIALCQH
    429. The conserved FKBP-type SDSQHRRFITRKYHVNVQILNRRDAIRLIGLAAGLCIDL
    peptidylprolyl isomerase domain is SLMYDARGAGLPPQENAKLCDTTCEKELENAPMITTESG
    underlined. LQYKDIKIGNGPSPPIGFQVAANYVAMVPSGQVFDSSLD
    KGQPYIFRVGSGQVIKGLDEGLLSMKVGGKRRLYIPGPL
    AFPKGLNSAPGRPRVAPSSPVIFDVSLEFIPGLESEEE
    162 The amino acid sequence of SEQ ID MSAASLSADMAIRGTILGKTALHVLGPQVVSQCRQPVMF
    430. The conserved FKBP-type KCPPHTLRKMRFSAQDLQSKNFYSGFTPFKSVFISTSKR
    peptidylprolyl isomerase domain is SWQAGSARAMSQDAAFQSKVTTKCFLDIEIGGDPAGRIV
    underlined and the Cyclophilin- LGLFGEDVPKTAENFRALCTGEKGFGYKGSSFHRIIKDF
    type peptidyl-prolyl cis-trans MLQGGDFDRGDGTGGKSIYGRTFEDENFKLAHVGPGVLS
    isomerase signature is in bold. MANAGPNTNGSQFFICTVKTPWLDKRHVVFGQVIEGMEI
    VKKLESEETNRTDRPKRPCRIVDCGELP
    163 The amino acid sequence of SEQ ID MGRIKPQTLLQQSKKKKVPGRISVSTIIVCNLIIIFLMF
    431. The conserved FKBP-type SLVGIYRQRAKRNRATSRSDGDEEMENFGRSKINSVPHQ
    peptidylprolyl isomerase domain is AIVNTTKGLITLELFGKSSAHTVEKFVEWSERGYFNGLP
    underlined. FYRVIKHFVIQVGDPKFAGNREDWTVGGQLNVQLEFSPK
    HEAFMLGTSKLEDQGDGFELFITTAPIPDLNDKLNVFGR
    VIKGQDVVQEIEEVDTDEHFQPKSPIIINDVRLKDEL
    164 The amino acid sequence of SEQ ID MARQSTLLLFWSLVFLGAIVFTQAKHEELEEVTHKVYFD
    432. The conserved cyclophilin- VDIAGKPAGRVVIGLFGKAVPKTVENFRALCTGEKGVGK
    type peptidyl-prolyl cis-trans SGKPLHYKGSFFHRIIPSFMIQGGDFTLGDGRGGESIYG
    isomerase signature is underlined TKFADENFKLKHTGPVFITTVTTDWLDGRHVVFGKIISG
    and the cyclophilin-type peptidyl- MDVVYKVEAEGRQSGQPKRKVKIADSGELSMD
    prolyl cis-trans isomerase
    signature is in bold.
    165 The amino acid sequence of SEQ ID MEMDEIQEQSQPQSSEKQDISQESDTGNDKTINAEKITS
    434. The conserved FKBP-type ENAEVEEDDMLPPKVNTEVEVLHDKVTKQIIKEGSGNKP
    peptidyl-prolyl cis-trans SRNSTCFLHYRAWAESTMHKFQDTWQEQQPLELVLGREK
    isomerase signature is underlined KELSGFAIGVAGMKAGERALLHVDWQLGYGEEGNFSFPN
    and the TPR repeat is in bold. VPPRANLIYEAELIGFEEAKEGKARSDMTVEERIEAADR
    RRQQGNELFKEDKLAEAMQQYEMALAYMGDDFMFQLFGK
    YKDMANAVKNPCHLNMAQCLLKLNRYEEAIGQCNMVLAE
    DEKNIKALFRRGKARATLGQTDDAREDFQKVRKFSPEDK
    AVIRELRLLAEHDKQVYQKQKEMFKGLFGQKPEQKPKKL
    HWFVVFWQWLLSMIRTIFRMRSKTD
    166 The amino acid sequence of SEQ ID MAGAGEGTPEVTLETSMGPITVELYHKHAPKTCRNFLEL
    435. The conserved cyclophilin- SRRGYYNNVKFHRVIKDFMVQGGDPTGTGRGGESIYGPR
    type peptidyl-prolyl cis-trans FEDEITRDLKHTGAGILSMANAGPNTNGSQFFISLAPTP
    isomerase signature is underlined WLDEKHTIFGRVCKGMDVVKRLGNVQTDKNDRPIHDVKI
    and the cyclophilin-type peptidyl- LRTTVKD
    prolyl cis-trans isomerase
    signature is in bold.
    167 The amino acid sequence of SEQ ID MMDPELMRLAQEQMSKISPDELMKMQRQIMANPDLMRMA
    436. The conserved TPR repeat SENMKNLKPEDIRFAAEQMKNVRKEEMAEISERISRASP
    domain is underlined. EEIEAMKARANLQSAYQLQVAQNLKDQGNQLHARMKYSE
    AAEKYLQARNNLTGIPFSEAKSLLLASSSNLMSCYLKTG
    QYEECVQTGSEVLAYDAMNVKALYRRGQAYKQIGKLELA
    VADLRKAVEVSPEDETIAQALREASTELMEKGGTQDQNG
    PRIEEIIEEEAVQPTAEKYPQSAPMVTSVTEDVSDDEQG
    SEDQNGFSRDSFQATNAPDGQMYAESLRNLTENPDMLRT
    MQSLMKNVDPDSLVALSGGKLSPDMVKTVSGMFGRMSPE
    EIQNMMKMSSTLSRQNPSTSSRFDDITRGHSNMDSSPQS
    VSVDNDLFEENQNRVGESSTNLSSSAAFSGMPNFSAEMQ
    EQVRNQMNDPATRQMFTSMIQNMSPEMMASMSEQFGVKL
    SPEDAVKAQNAMASLSPNDLDRLMNWATRLQTAIDYARK
    IKNWILGRPGLIFAISMLLLAIILHRFGYIGD
    168 The amino acid sequence of SEQ ID MGVEKEILRPGNGPKPRPGQSVTVHCTGYGKNEDLSQKF
    437. The conserved FKBP-type WSTKDPGQKPFTFTIGQGRVIKGWDEGVLDMQLGEIFKL
    peptidylprolyl isomerase domain is RCSPDYGYGSNGFPAWGIRPNSVLVFEIEVLSVN
    underlined and the Cyclophilin-
    type peptidyl-prolyl cis-trans
    isomerase signature is in bold.
    169 The amino acid sequence of SEQ ID MPNPRCYLDITIGEELEGRILVELYSDVVPKTAENFRAL
    438. The conserved cyclophilin- CTGEKGIGPHTGVPLHYKGLPFHRVIKGFMIQGGDISAQ
    type peptidyl-prolyl cis-trans NGTGGESIYGLKFDDENFQLKHERRGMLSMANSGPNTNG
    isomerase family domain is SQFFITTTRTSHLDGKHVVFGKVIKGMGVVRGIEHTPTE
    underlined and the cyclophilin- SNDRPSLDVVISDCGEIPEGSDDGIANFFKDGDLYPDWP
    type peptidyl-prolyl cis-trans ADLDEKSAEISWWMNAVDSAKCFGNENYKKGDYKMALRK
    isomerase signature is in bold. YRKALRYLDICWEKEEIDEEKSNHLRKTKSQIFTNSSAC
    KLKLGDLKGALLDTEFAMRDGEDNVKALFRQGQAYMALK
    DVDSAVASFKKALQLEPNDAGIRKELAVATKMINDRRDQ
    ERRAYARMFQ
    170 The amino acid sequence of SEQ ID MGDVIDLNGDGGVLKTIIRSAKPGAMQPTEDLPNVDVHY
    439. The conserved FKBP-type EGTLADTGEVFDTTREDNTLFSFELGKGTVIKAWDIAVK
    peptidylprolyl isomerase domain is TMKVGEVARITCKPEYAYGSAGSPPDIPENATLIFEVEL
    underlined and the Cyclophilin- VACKPRKGSTFGSVSDEKARLEELKKQREIAAASKEEEK
    type peptidyl-prolyl cis-trans KRREEAKATAAARVQAKLEAKKGQGRGKGKSKGK
    isomerase signature is in bold.
    171 The amino acid sequence of SEQ ID MGLGLKIASASFLPIFNIMATRSLCILLVCFIPVLAHVL
    440. The conserved cyclophilin- SLQDPELGTVRVYFQTTYGDIEFGFFPHVAPKTVEHIYK
    type peptidyl-prolyl cis-trans LVRLGCYNSNHFFRVDKGFVAQVADVVGGREVPLNSEQR
    isomerase signature is underlined. KEGEKTIVGEFSEVKHVRGILSMGRYSDPDSASSSFSIL
    LGNAPHLDGQYAVFGKVTKGDDTLKRLEEVPTRQEGIFV
    MPLERIRILSTYYYDTNERESNLTCDHEVSILKRRLVES
    AYEIEYQRRKCLP
    172 The amino acid sequence of SEQ ID MASKRSLRTMNVWPTLPPLVLLLLLCFSSMSSSVVAKKS
    441. The conserved FKBP-type DVSELQIGVKHKPKSCDIQAHKGDRIKVHYRGSLTDGTV
    peptidylprolyl isomerase domain is FDSSFERGDPIEFELGSGQVIKGWDQGLLGMCVGEKRKL
    underlined and the Cyclophilin- RIPSKLGYGAQGSPPKIPGGATLIFDTELVAVNGKGISN
    type peptidyl-prolyl cis-trans DGDSDL
    isomerase signatures are in bold.
    173 The amino acid sequence of SEQ ID MSGAPAERPISYFDITIGGKPIGRIVFSLYADLVPKTAE
    442. The conserved FKBP-type NFRALCTGEKGIGKSGKPLCYAGSGFHRVIKGFMCQGGD
    peptidylprolyl isomerase domain is FTAGNGTGGESIYGEKFEDEAFPVKHTKPFLLSMANAGK
    underlined and the Cyclophilin- DTNGSQFFITVSQTPHLDDKHVVFGEVIKGKSIVRAIEN
    type peptidyl-prolyl cis-trans YPTASGDVPTSPIIISACGVLSPDDPSLAASEETIGDSY
    isomerase signatures are in bold. EDYPEDDDSDVQNPEVALDIARKIRELGNKLFKEGQIEL
    ALKKYLKSIRYLDVHPVLPDDSPPELKDSYDALLAPLLL
    NSALAALRTQPADAQTAVKNATRALERLELSDADKAKAL
    YRRASAHVILKQEDEAEEDLVAASQLSPEDMAISSKLKE
    VKDEKKKKREKEKKAFKKMFSS
    174 The amino acid sequence of SEQ ID MASSLRSSLFSSWALDSKSVCSLFNLNPGKMGLPSISTP
    443. The conserved FKBP-type LNWRTCCCSHSSELLELNEGLQSSRRKTVMGLSTVIALS
    peptidylprolyl isomerase domain is LVYCDEVGAVSTSKRALRSQKVPEDEYTTLPNGLKYYDL
    underlined. KVGSGTEAVKGSRVAVHYVAKWKGITFMTSRQGMGITGG
    TPYGFDVGASERGAVLKGLDLGVQGMRVGGQRILIVPPE
    LAYGNTGIQEIPPNATLEFDVELISIKQSPFGSSVKIVEG
    175 The amino acid sequence of SEQ ID MGAIEDEEPPLKRLKVSSPGLRRGLEEEAPSLSVGSVSI
    444. The conserved G-protein beta LMAKSLSLEEGETVGSKGLIRRVEFVRIITQALYSLGYQ
    WD-40 repeat domains are KAGALLEEESGILLQSSNVALFRKQILDGKWDESVVTLR
    underlined. GIDQVEVEGNTLKAASFLILQQKFFELLDKGNIPEAMKT
    LRLEISPMQLNTKRVHELASCIVFPSRCEELGYSKQGNP
    KSSQRMKVLQEIQQLLPPSIMIPEKRLERLVEQALNVQR
    EACIFHNSLDPALSLYTDHQCGRDQIPTTTLQVLESHKN
    EVWFLQFSNNGKYLASASKDCSAIIWEITEGDSFSMKHR
    LSAHQKPVSFVAWSPDDKLLLTCGIEEVVKLWNVETGEC
    KLTYDKANSGFTSCGWFPDGERFISGGVDKCIYIWDLEG
    KELDSWKGQGMPKISDLAVTSDGKEIISICGDNAIVMYN
    LDTKTERLIEEESGITSLCVSKDSRFLLLNLANQEIHLW
    DIGARSKLLLKYKSHRQSRYVIRSCFSSSDLAFVVSGSE
    DSQVYIWHRGNGELLAVLPGHSGTVNCVSWNPVNPHVFA
    SASDDYTIRIWGVNRNTFRSKNASSSNGVVHLANGGP
    176 The amino acid sequence of SEQ ID MPGTTAGAGIEPTEPQSLKKLSLKSLKRSFDLFASLHGE
    445. The conserved G-protein beta PQPPDQRSQRIRIACKVRAEYEVVKNLPTLPQREVGSSV
    WD-40 repeat domains are SNSNVGETHSSLTTNQAQGFPTDTSGDLSKDEGKEITSI
    underlined and the Trp-Asp (WD) AVHLQPQTGLIDGKAGAIAGTSTAISSVGSSDRYQPSAA
    repeats signature is in bold. IMKRLPSKWPRPIWHPPWKNYRVISGHLGWVRSVAFDPG
    NEWFCTGSADRTIKIWEVATGKLKLTLTGHIEQIRGLAV
    SSRHPYLFSAGDDKQVKCWDLEYNKAIRSYHGHLSGVYC
    LALHPTLDILCTGGRDSVCRVWDIRTKAQIFALSGHENT
    VCSVFTQAIDPQVVTGSHDTTIKLWD LAAGKTMSTLTYH
    KKSVRAIAKHPFEHTFASASADNIKKFKLPKGEFLHNML
    SQQKTIVNAMAINEDNVLVSAGDNGSLWFWDWKSGHNFQ
    QAQTIVQPGSLDSEAGIYALQYDITGSRLVSCEADKTIK
    MWKEDETATPESHPINFKAPKDIRRF
    177 The amino acid sequence of SEQ ID MRPILMKGHERPLTFLKYNRDGDLLFSCAKDHTPTVWYG
    446. The conserved G-protein beta HNGERLGTYRGHNGAVWCCDVSRDSTRLITSSADQTAKL
    WD-40 repeat domains are WNVETGAQLFSFNFESPARAVDLAIGDKLVVITTDPFME
    underlined. LPSAIHIKRIEKDLSKQTADSVLTITGIKGRINRAVWGP
    LNSTIISGGEDSVVRIWDSETGKLLRESDKETGHQKPIT
    SLCKSADGSHFLTGSLDKSARLWDIRTLTLIKTYVTERP
    VNAVAISPLLDHVVIGGGQEASHVTTTDREAGKFEAKFF
    HKILEEEIGGVKGHFGPINSLAFNPDGRSFASGGEDGYV
    RLHHFDPDYFHIKM
    178 The amino acid sequence of SEQ ID MRPILMKGHERPLTFLKYNRDGDLLFSCAKDHTPTVWYG
    447. The conserved G-protein beta HNGERLGTYRGHNGAVWCCDVSRDSTRLITSSADQTAKL
    WD-40 repeat domains are WNVETGNQLFSFNFESPARAVDLAIGDKLVVITTDPFME
    underlined. LPSAIHIKRIEKDLSKQTADSVLTITGIKGRINRAVWGP
    LNSTIISGGEDSVVRIWDSETGKLLRESDKETGHQKAIT
    SLCKSADGSHFLTGSLDKSARLWDIRTLTLIKTYVTERP
    VNAVAISPLLDHVVIGGGQEASHVTTTDRRAGKFEAKFF
    HKILEEEIGGVKGHFGPINSLAFNPDGRSFASGGEDGYV
    RLHHFDPDYFHIKM
    179 The amino acid sequence of SEQ ID MAENNVGDFIPLDRQEYPSKPAPGAVDSSFWKSFKKKEV
    448. The conserved G-protein beta SRQIAGVTCINFCPEPPHDFAVTSSTRVHIYDGKSCELK
    WD-40 repeat domains are KTITKFKDVAYSGVFRSDGQIIAAGGETGVIQVFNAKSQ
    underlined. MVLRQLKGHGRPVRVVRYSPQDKLHLLSGGDDSMVKWWD
    ITTQEELLNLEGHKDYVRCGAASPSSVNLWATGSYDHTV
    RLWDLRNSKTVLQLKHGKPLEDVLFFPSGGLLATAGGNV
    VKVWDILGGGRPIHTMETHQKTVMAMCISKVPRSGQALG
    DAPSRLVTASLDGYMKVFDLDHFKVTHSARYPAPILSMG
    ISSLCRTMAVGTSSGLLFIRQRKGQIEDKIHSDSSGLQV
    NPVNDEKDSAVLKPNQYRYYLRGRSEKPSEGDYVVKRMA
    KVYFQEYDKDLRHFNHSKALVSALKAADSKGTVAVIEEL
    VARKRLIQTLSILNLDELELLINFLSRFILVPKYSRFLI
    SLTDRVLDARAVDLGKSENLKKQIADLKGIVVQELRVQQ
    SMQELQGIIEPLIRASAR
    180 The amino acid sequence of SEQ ID MDVETSSKPTGNKRTYTRLPRQVCVFWQEGRCTRESCNF
    449. The conserved C-x8-C-x5-C-x3- LHVDEPGSVKRGGATNGFAPKRSYNGSDERDTLAAGPPG
    H type zinc finger is underlined GSRRNISARWGRGRGGIFISDERQKI RNKV
    Figure US20100122382A1-20100513-P00035
    NYWLAGN
    Figure US20100122382A1-20100513-P00035
    and in italics and the conserved QRGEE
    Figure US20100122382A1-20100513-P00035
    KYL
    Figure US20100122382A1-20100513-P00036
    SF VMGSDVKFLTQLSGHVKAIRGIAFPSD
    Cys and His residues in bold, The SGKLYSGGQDKKVIVWDCQTGQGTDIPLNDEVGCLMSEG
    conserved G-protein beta WD-40 PWIFVGLPNAVKAWNILTSTELSLVGPRGQVHALAVGNG
    repeat domains are underlined and MLFAGTHDGSILAWKFSPASNTFEPAASLVGHTQAVVSL
    the Trp-Asp (WD) repeats signature VSGADRLYSGSMDKTIRVW DL GTFQCLQTLRDHTSVVMS
    is in bold (non-italics). LLCWDQFLLSCSLDNTVKVWVATSSGALEVTYTHNEEHG
    VLALCGMNDEQAKPVLLCSCNDNTVRLYDLPSFSERGRI
    FSRNEVRTFQIAPGGLFFTGDATGELKVWNWATQKS
    181 The amino acid sequence of SEQ ID MSVQELRERHAAATAKVNALRERIKAKRLQLLDTDVATY
    450. The conserved G-protein beta ASSNGRTPISFSFTDLVCCRTLQGHTGKVYSLDWTSEKN
    WD-40 repeat domains are RIVSASQDGRLIVWNALTSQKTHAIKLPCAWVMTCAFSP
    underlined. SGQAVACGGLDSVCSIFQLNNQLDRDGHLPVSRILSGHR
    SYVSSCQYVPDGDTHVITGSGDRTCIQWDVTTGQRIAIF
    GGEFPLGHTADVMSVSISAANPKEFVSGSCDTTTRLWDT
    RIASRAIRTFHGHEADVNTVKFFPDGLRFGSGSDDGTCR
    LFDIRTGHQLQVYRQPPRENQSPTVTAIAFSFSGRLLFA
    GYSNGDCFVWDTILEKVVLNLGELQNTHNGRISCLGLSA
    DGSALCTGSWDKNLKIWAFGGHRKIV
    182 The amino acid sequence of SEQ ID MKVKIISRSTDEFTRERSNDLQRVFRNFDPNLHTQARAQ
    451. The conserved G-protein beta EYVRALNAAKLDKIFAKPFLAAMSGHIDGISAMAKSPRH
    WD-40 repeat domains are LKSIFSGSVDGDIRLWDIAARRTVQQFPGHRGAVRGLTV
    underlined. STEGGRLISCGDDCTVRLWDIPVAGIGESSYGSENVQKP
    LATYVGKNSFRAVDYQWDSNVFATGGAQVDIWDHDRSEP
    TNSFAWGSDTVISVRFNPAEKDIFATTASDRSIVLYDLR
    MASPLNKLIMQTRNNAIAWNPREPMNFTAANEDCNCYSY
    DMRRMNISTCVHQDHVSAVMDIDYSPSGREFVTGSYDRT
    VRIFPYNAGHSREIYHTKRMQRVFCVKFSGDATYVVSGS
    DDANIRLWKAKASEQLGVLLPRERKRHEYLDAVKERFKH
    LPEIKRIERHRHLPKPIYKAALLRHTVNAAAKRKEERKR
    AHSAPGSVVTNPLRKKRIVAQLE
    183 The amino acid sequence of SEQ ID MDHYYQDDFDYLVDDEMVDFADDVEDDVRTRRRSDIDSD
    452. The conserved G-protein beta SENDFDLNNKSPDTTALQAKRGKDIQGIPWNRLNFTREK
    WD-40 repeat domains are YRETRLQQYKNYENLPRPRRSRNLDKECTNFERGSSFYD
    underlined. FRHNTRSVKATIVHFQLRNLVWATSKHNVYLMQNYSIMH
    WSSLKQKGEEVLNVAGPIVPSVKHPGSSPQGLTRVQVSA
    MSVKDNLVVAGGFQGELICKYLDKPGVSFCTKISHDENG
    ITNAVEIYNDASGATRLMTANNDLAVRVFDTEKFTVLER
    FSFPWSVNHTSVSPDGKLVAVLGDNADCLLADCKTGKTV
    GTLRGHLDYSFAAAWHPDGYILATGNQDTTCRLWDVRKL
    SSSLAVLKGRMGAIRSIRFSSDGRFMAMAEPADFVHLYD
    TRQNYTKSQEIDLFGEIAGISFSPDTEAFFVGVADRTYG
    SLLEFNRRRMNYYLDSIL
    184 The amino acid sequence of SEQ ID MAEALVLRGTMEGHTDAVTAIATPIDNSDMIVSSSRDKS
    453. The conserved G-protein beta ILLWN LTKEPEKYGVPRRRLTGHSHFVQDVVISSDGQFA
    WD-40 repeat domains are LSGSWDSELRLWDLNTGLTTRRFVGHTKDVLSVAFSIDN
    underlined and the Trp-Asp (WD) RQIVSASRDRTIKLWN T LGECKYTIQPDAEGHSNWISCV
    repeats signatures are in bold. RFSPSATNPTIVSCSWDRTVKVWN LTNCKLRNTLVGHGG
    YVNTAAVSPDGSLCASGGKDGVTMLWDLAEGKRLYSLDA
    GDIIYALCFSPNRYWLCAATQQCVKIWDLESKSIVADLR
    PDFIPNKKAQIPYCTSLSWSADGSTLFSGYTDGKIRVWG
    IGHV
    185 The amino acid sequence of SEQ ID MAAIKSTSRSASVAFAPDAPLLAAGTMAGAIDLSFSSLA
    454. The conserved G-protein beta NLEIFKLDFQSDDPELPVVGECPSNERLNRLSWGSAGGS
    WD-40 repeat domains are FGIIAGGLVDGTINIWNPATLINSEDNGDALIARLEQHT
    underlined. GPVRGLEFNTISTNLLASGAEDGELCIWDLANPTAPTHF
    PPLKGVGSGAQGEISFLAWNRKVQHILASTSYSGTTVVW
    DLRRQKPIISFPDATRRRCSVLQWNPDASTQLIVASDDD
    NSPTLEAWDLRNTISPYKEFVGHSRGVIAMSWCPSDSLF
    LLTCAKDNRTLCWDTGSGEIVCELPAGANWNFDVQWSPK
    IPGILSTSSFDGKIGIHNIEACSRNVSGEVEFGGAIVRG
    GPSALLKAPKWLERPAGVSFGFGGKLASFRPSTVAQAAD
    HRHSEVFIHNLVTEDNLVIRSTEFEAAIADGEKVSLRAL
    CDRKAEESQSDEEKETWNFLRVMFEDEGTARTKLLEHLG
    FKVQSEENGDLQETHSSKIDDIGSEIGKTLTLDDKTEED
    VLPQLKGGQDAAIPQDNGEDFFDNLHSPKEEVSLSHVGN
    DFVGEKDKDMVVNGAEIEHETEDLTEYSDWNEAIQHSLV
    VGDYKGAVLQCLSANRMADALIIAHLGGNSLWEKTRDEY
    LKKAKSSYLKVVSAMVNNDLTGLVNSRPLKSWKETLAML
    CTYSQREEWTVLCDMLASRLIAAGNVMAATLCYICAGNI
    EKTVEIWSRSLKYDYDGRSFVDHLQDVMEKTVVLALATG
    QKRVSPSLSKLVENYAELLASQGLLTTAMEYLKLLGTEE
    SSHELSILRDRLYLSGTDNKVEASSFPFETRQDLTESQY
    NMHQTGFGAPETQKNYQENVHQVLPSGSYTDNYQPTANT
    HYIAGYQPAPQQQPSFQNYFTPASYQPAPSPNVFYPSQV
    SQAEQSNFAPPVNQPPMKTFVPSTPPILRNVDQYQTPSL
    NPQLYQGVSSATVETHPYQTGAPASVSVGTTPGQPSVVP
    NFMVPGPVTAPTVTPRGFMPVTTPTQHPLGSANPPVQPQ
    SPQSSQVQSV
    186 The amino acid sequence of SEQ ID MAGAADSQLQTLSERDSTPNFKNLHTREYAAHKKKVHSV
    455. The conserved G-protein beta AWNCTGTKLASGSVDQTARVWNIEPHGHSKTKDLELKGH
    WD-40 repeat domains are ADSVDQLCWDPKHSELLATASGDRTVRLWD ARSGKCSQQ
    underlined and the Trp-Asp (WD) VELSGENINITFKPDGTHIAVGNRDDELTIIDVRKFKPL
    repeats signature is in bold. HKRKFSYEVNEIAWNTTGELFFLTTGNGTVEVLSYPSLQ
    VLHTLVAHTAGCYCIAIDPIGRYFAVGSADALVSLWDLS
    EMLCVRTFTKLEWPVRTISFNHDGQYIASASEDLFIDIA
    DVQTGRTVHQISCRAAMNSVEWNPKYNLLAFAGDDKNKY
    MQDEGVFRVFGFETP
    187 The amino acid sequence of SEQ ID MAATSPVGAGSGRELANPPTDGISNLRFSNHSDHLLVSS
    456. The conserved G-protein beta WDRKVRLYDASANSLKGQFVHGGPVLDCCFHDDASGFSG
    WD-40 repeat domains are SADNTVRRYDFSTRKEDILGRHEAPVRCVEYSYAAGQVI
    underlined. TGSWDKTLKCWDPRGASGQEKTLVGTYSQLERVYSMSLV
    GHRLVVATAGRHINVYDLRNMSQPEQRRESSLKYQTRCV
    RCYPNGTGFALSSVEGRVAMEFFDLSEAGQAKKYAFKCH
    RKSEAGRDTVYPVNAIAFHPIYGTFATGGCDGYVNVWDG
    NNKKRLYQYSKYPTSIAALSFSRDGRLLAVASSYTFEEG
    EKPHEPDAVFVRSVNEAEVKPKPKVYAAPP
    188 The amino acid sequence of SEQ ID MASDDEEGFKNEEAPGVVDEAEVQEGLRACFPLSFGKQE
    457. The conserved G-protein beta KKQAPLESIHSATKRPEDPRPRRQLGPPRPPPSILAEQE
    WD-40 repeat domains are DSDRFVGPPRPPQFVRDDNDDGEAEIMIGPPRPPAQYSD
    underlined and the Trp-Asp (WD) DHDNEETIGPPKPSYLEKGEETDQMVGPSKRGSDDETSG
    repeats signature is in bold. DSDDGDDAVDFRVPLSNEIVLRGHTKVVSALAIDQTGSR
    VLTGSYDYSVRMYDFQGMTSQLKSFRQLEPAEGHQVRSL
    SWSPTSDRFLCVTGSAQAKIFDRDGLTLGEFVKGDMYLR
    DLKNTKGHISGLTCGEWHPKEKQTILTCSEDGSLRIWD V
    NDFNTQKQVIKPKLAKPGRVPVTACAWGRDGKCIAGGVG
    DGSIQVWNLKPGWGSRPDLYVAKGHDDDITGLQFSADGN
    ILLTRSTDETLKVWDLRKAITPLQVFRDLPNNYAQTNVA
    FSPDERLIFTGTSVERDGNSGGLLCFYDRQTLELVLRIG
    VSPVHSVVRCTWHPRHNQVFATVGDKKEGGAHILYDPAL
    SERGALVCVARAPRKKSLDDFEAKPVIHNPHALPLFRDE
    PSRKRQREKARMDPMKSQRPDLPVTGPGFGGRVGSTKGS
    LLTQYLLKEGGLIKETWMEEDPREAILKYADVAAKDPKF
    IAPAYAQTQPETVFAETDSEEEQK
    189 The amino acid sequence of SEQ ID MKERGQSHAGQPSVDERYTQWKSLVPVLYDWLANHNLVW
    458. The conserved G-protein beta PSLSCRWGPQMHQATYKNSQRLYLSEQTDGTVPNTLVIA
    WD-40 repeat domains are TCEVVKPRVAAAEHISQFNEEARSPFVKKFKTIIHPGEV
    underlined. NRIRELPQNSKIVATHTDGPDVLIWDVDTQPNRQATLGA
    ADSRPDLVLTGHKDNAEFALAMSPSAPFVLSGGKDKCVL
    LWSIQDHISAATEPSSAKASKTPSSAHGEKVPKIPSIGP
    RGVYKGHKDTVEDVQFCPSNAQEFCSVGDDSALILWDAR
    NGNEPVIKVEKAHNADLHCVDWNPHDENLILTGSADNSV
    RMFDRRNLTSSGVGSPVHKFEGHSAPVLCVQWCPDKASV
    FGSAAEDSYLNVWDYEKVGKNVGKKTPPGLFFQHAGHRD
    KVVDFHWNSFDPWTIVSVSDDGESTGGGGTLQIWRMSDL
    IYRPEDEVLAELERFEAHILSCQNK
    190 The amino acid sequence of SEQ ID MSSLSRELVFLILQFLDEEKFKESVHKLEQESG
    Figure US20100122382A1-20100513-P00037
    NMK
    459. The conserved G-protein beta YFDEKAQAGEWDEVERYLSGFTKVDDNRYSMKIFFEIRK
    WD-40 repeat domains are QKYLEALDRQDRAKAVDILVKDLKVFSTFNEELYKEITQ
    underlined. The Lissencephaly LLTLDNFRENEQLSKYGDTKSARTIMMSELKKLIEANPL
    type-1-like homology motif is in FREKLIYPNLKASRLRTLINQSLNWQHQLCKNPRPNPDI
    bold and the CTLH, C-terminal to KTLFTDHACGPPNGARTPTQPTASLGVLPKATTFTPIGP
    LisH motif is in italics. HGPFPSSSTATSGLASWMSNPNMVTSPQAPVAVGPSVPV
    PPNQATLLKRPRTPPGSSSVVDYQTADSEQLIKRLRPVS
    QSIDEATYPGPTLRVPWSTDDLPKTLARALNEPYPVTSI
    DFHPSQQTFLLVGTKNGEITLWEVGSREKLATRSFKIWD
    NANCSNHLEAAFVKDSSVSINRVLWSPDGTLIGIAFTKH
    LVHTYTFQGLDLRQHLEIDAHVGGVNDLAFSHPNKQLCV
    VTCGDDKMIKVWDAVTGRKLYNFEGHDAPVYSVCPHHKE
    NIQFIFSTAVDGKIKAWLYDHLGSRVDYDAPGHSCTTMM
    YSADGTRLFSCGTSKEGESFLVEWNESEGAIKRTYSGLR
    KKGSGVVQFDTTQNHFLAVGDEHLIKFWDMDSTNMLTSC
    DAEGGLLNLPRLRFNKEGSLLAVTTVNGIKILANADGQK
    LLKTMENRTFDLPSRAHIDAASATSSPATGRMERIERTS
    SANTVSGINGVDPAQSSEKLRLSDDLSEKTKIWKLTEIT
    DSIQCRCITLPENAAEPASKVSRLLYTNSGVGLLALGSN
    AVHKLWKWNRSEQNPSGKATASVHPQRWQPTSGLLMTND
    ITDINPEEAVPCIALSKNDSYVMSASGGKVSLFNMMTFK
    VMTTFMPPPPASTFLAFHPQDNNIIAIGMEDSTIHIYNV
    RVDEVKTKLKGHQKRITGLAFSSTQNILVSSGADAQLCV
    WNTETWEKRKSKTIQMPVGKTVSGDTRVQFHSDQLHILV
    VHETQLAIYDAYKLERQYQWVPQDALSAPILYATYSCNR
    QLIYATFSDG
    191 The amino acid sequence of SEQ ID MAKDEEEFRGEMEERLVNEEYKIWKKNTPFLYDLVITHA
    460. The conserved G-protein beta LEWPSLTVQWLPDREEPPGKDYSVQKMILGTHTSDNEPN
    WD-40 repeat domains are YLMLAQVQLPLEDAENDARQYDDERGEIGGFGCANGKVQ
    underlined. VIQQINHDGEVNRARYMPQNPFIIATKTVSAEVYVFDYS
    KHPSKPPQDGGCHPDLRLRGHNTEGYGLSWSPFKHGHLL
    SGSDDAQICLWDINVPAKNKVLEAQQIFKVHEGVVEDVA
    WHLRHEYLFGSVGDDRHLLIWDLRTSATNKPLHSVVAHQ
    GEVNCLAFNPFNEWVLATGSADRTVKLFDLRKISSALHT
    FSCHKEEVFQIGWSPKNETILASCSADRRLMVWDLSRID
    EFQTPEDALDGPPELLFIHGGHTSKISDFSWNPCEDWVI
    ASVAEDNILQIWQMAENIYHDEEDDMPPEEVV
    192 The amino acid sequence of SEQ ID MSPGVKQTGSQKFESGHQDVVHDVTMDYYGKRIATCSAD
    461. The conserved G-protein beta RTIKLFGLNASDTPSLLASLTGHEGPVWQVAWAHPKFGS
    WD-40 repeat domains are MLASCSYDGRVIIWREGQQENEWSQVQVFKEHEASVNSI
    underlined. SWAPHELGLCLACGSSDGSITVFTCREDGSWDKTKIDQA
    HQVGVTAVSWAPASAPGSLVGQPSDPIQKLVSGGCDNTA
    KVWKFYNGSWKLDCFPPLQMHTDWVRDVAWAPNLGLPKS
    TIASCSQDGKVVIWTQGKEGDKWEGRILNDFKIPVWRVN
    WSLTGNILAVADGNNSVTLWKEAVDGDWNQVTTVQ
    193 The amino acid sequence of SEQ ID MSSGVKQTGSQKFESGHQDVVHDVTMDYYGKRIATCSAD
    462. The conserved G-protein beta RTIKLFGMNTSDTPTLLASLTGHEGPVWQVAWAHPKFGS
    WD-40 repeat domains are MLASCSYDRRVIIWREGQQENEWSQVQVFKEHEASVNSI
    underlined. SWAPHELGLCLACGSSDGSITVFTGREDGSWDKTKIDQA
    HQVGVTAVSWAPASAPGSLVGQPSDPVQKLVSGGCDNTA
    KVWKFYNGSWKLDCFPPLQMHTDWVRDVAWAPNLGLPKS
    TIASCSQDGRVVIWTQGKEGDKWEGKILNDFKTPVWRIS
    WSLTGNILAVADGNNNVTLWKEAVDGEWNQVTTVQ
    194 The amino acid sequence of SEQ ID MKKRSRPSNGHLSTAAKNKSRKTAPITKDPFFDSAHNRN
    463. The conserved G-protein beta KSKGKGKSRGKGEEIFSSDEDDDAIGRDAPAEEEEEIAE
    WD-40 repeat domains are EERETADEKRLRVAKAYLDKIRAITKANEEDNEEEAGED
    underlined. EETEAERRGKRDSLVAEILQQEQLEESGRVQRQLASRVV
    TPSKLVECRVVKRHKQSVTAVALTEDDLRGFSASKDGTI
    IHWDVETGASEKYEWPSQAVSVSSSNEVSKTQKSKGSKK
    QGSKHVLSMAVSSDGRYLATGGLDRYIHLWDTRTQKHIQ
    AFRGHRGAVSCLAFRQGTQQLISGSFDRTIKLWSAEDRA
    YMDTLYGHQSEILAVDCLRKERVLSVGRDHTLRLWKVPE
    ETQLVFRGHAASLECCCFINNEDFLSGSDDGSIELWSML
    RKKPVFMAKNAHGHAIVENLSEDTSTREEPDEEVTTRQL
    PNGNSIGNGMTNQMGITPSVESWVGAVTVCRGTDLAASG
    AGNGVVRLWAIENSSKSLRALHDIPLTGFVNSLTFARSG
    RFLIAGVGQEPRLGRWGRIQAARNGVTLCPIELS
    195 The amino acid sequence of SEQ ID MAATFGTINTATSPHNPNKSFEIVQPPNDSISSLSFSPK
    464. The conserved G-protein beta ANYLVATSWDNQVRCWEVLQTGASMPKAAMSHDQPVLCS
    WD-40 repeat domains are TWKDDGTAVFSAGCDKQAKMWPLLTGGQPVTVAMHDAPI
    underlined. KDIAWIPEMNLLATGSWDKTLKYWDTRQSNPVHTQQLPE
    RCFALSVRHPLMVVGTADRNLIIFNLQNPQTEFKRISSP
    LKYQTRCVAAFPDKQGFLVGSIEGRVGVHHVEEAQQSKN
    FTFKCHRDSNDIYAVNSLNFHPVHQTFATAGSDGAFNFW
    DKDSKQRLKAMARSNQPIPCSTFNSDGSLYAYAVSYDWS
    KGAENHNPATAKHHILLHVPQESEIKGKPRVTTSGRK
    196 The amino acid sequence of SEQ ID MVVMDKGTHQTNEDESESEFIDEDDVIDEISIDEEDLPD
    465. The conserved G-protein beta ADVEGEDVQEDNKRSEPDENSSSLDDAIHTFEGHEDTLF
    WD-40 repeat domains are AVACSPVDATWVASGGGDDKAFMWRIGHATPFFELKGHT
    underlined. DSVVALSFSNDGLLLASGGLDGVVRIWDASTGNLIHVLD
    GPGGGIEWVRWHPKGHLVLAGSEDYSTWMWNADLGKCLS
    VYTGHCESVTCGDFTPDGKAICTGSADGSLRVWNPQTQE
    SKLTVKGYPYHTEGLTCLSISSDSTLVVSGSTDGSVHVV
    NIKNGKVVASLVGHSGSIECVRFSPSLTWVATGGMDKKL
    MIWELQSSSLRCTCQHEEGVMRLSWSLSSQHIITSSLDG
    IVRLWDSRSGVCERVFEGHNDSIQDMVVTVDQRFILTGS
    DDTTAKVFEIGAF
    197 The amino acid sequence of SEQ ID MPVFRTAFNGYAVKFSPFVETRLAVATAQNFGIIGNGRQ
    466. The conserved G-protein beta HVLELTPNGIVEVCAFDSSDGLYDCTWSEANENLVVSAS
    WD-40 repeat domains are GDGSVKIWD IALPPVANPIRSLEEHAREVYSVDWNLVRK
    underlined and the Trp-Asp (WD) DCFLSASWDDTIRLWTIDRPQSMRLFKEHTYCIYAAVWN
    repeats signature is in bold. PRHADVFASASGDCTVRIWDVREPNATIIIPAHEHEILS
    CDWNKYNDCMLVTGSVDKLIKVWDIRTYRTPMTVLEGHT
    YAIRRVKFSPHQESLIASCSYDMTTCMWDYRAPEDALLA
    RYDHHTEFAVGIDISVLVEGLLASTGWDETVYVWQHGMD
    PRAC
    198 The amino acid sequence of SEQ ID MDSRNRRSRLNLPPGMSPSSLHLETTAGSPGLSRVNSSP
    467. The conserved G-protein beta STPSPSRTTTYSDRFIPSRTGSRLNGFALIDKQPQPLPS
    WD-40 repeat domains are PTRSAAEGRDDASSSSASAYSTLLRNELFGEDVVGPATP
    underlined. ATPEKSTGLYGGSRDSIKSPMSPSRNLFRFKNDHGGNSP
    GSPYSASTVGSEGLFSSNVGTPPKPARKITRSPYKVLDA
    PALQDDFYLNLVDWSSNNVLAVGLGTCVYLWSACTSKVT
    KLCDLGVNDSVCSVGWTPQGTHLAVGTNIGEVQIWDTSR
    CKKVRTMGGHCTRAGALAWSSYILSSGSRDRNILHRDIR
    VQDDFIRKLVGHKSEVCGLKWSYDDRELASGGNDNQLLV
    WNQQSAQPLLRFNEHTAAVKAIAWSPHQHGILASGGGTA
    DRCLRFWNTATDTRLNCVDTGSQVCNLVWCKNVNELVST
    HGYSQNQIMVWRYPSMSKLATLTGHTLRVLYLAISPDGQ
    TIVTGAGDETLRFWSIFPSPKSQSAVHDSGLWSLGRTHIR
    199 The amino acid Sequence of SEQ ID MEKKKVVVPIVCHGHSRPIVDLFYSPVTPDGLFLISASK
    468. The Conserved G-protein beta DSSTMLRNGETGDWIGTFEGHKGAVWSCCLDNRALRAAS
    WD-40 repeat domains are GSADFSAKIWDALTGDELHCFVHKHIVRACAFSESTSLL
    underlined. LTGGHEKILRIFDLNRPDAPPKEVDNSPGSIRTVAWLHS
    DQTILSSNSDAGGVRLWDLRTEKIVRVLETKSPVTSAEV
    SQDGRYITTADGNSVKFWDANHFGMVKSYTMPCMVESAS
    LEPTMGNMFVAGGEDMWVRLFDFHTGEEIACNKGHHGPV
    HCVRFAPGGESYSSGSEDGTIRIWQTLNMNSEENESYGV
    NGLSGKVRVGVDDVVQKVEGFQITADGHLNDKPEKPNP
    200 The amino acid Sequence of SEQ ID MERYSQGTQKKSEIYTYEAPWQIYGMNWSVRKDKKFRLG
    469. The Conserved G-protein beta IGSFLEEYNNRVEIIELDEESGEFKSDPRLAFDHPYPTT
    WD-40 repeat domains are KIMFVPDKECQRPDLLATTGDYLRIWQVCEDRVEPKSLL
    underlined. NNNKNSEFCAPLTSFDWNDADPKRIGTSSIDTTCTIWDI
    EKEVVDTQLIAHDKEVYDIAWGEVGVFASVSADGSVRVF
    DLRDKEHSTIIYESSQPETPLLRLGWNKQDPRFIATILM
    DSCKVVILDIRFPTLPVAELQRHQASVNTIAWAPHSPCH
    ICTAGDDSQALIWELSSVSQPLVEGGGLDPILAYTAAAE
    INQLQWSSMQPDWVAIAFSNEVQILRV
    201 The amino acid sequence of SEQ ID MQSENNLDESLHLREVQELQGHTDTVWAVAWNPVTGIDG
    470. The conserved G-protein beta APSMLASCSGDKTVRIWENTHTLNSTSPSWACKAVLEET
    WD-40 repeat domains are HTRTVRSCAWSPNGKLLATASFDATTAIWENVGGEFECI
    underlined. ASLEGHENEVKSVSWSASGMLLATCGRDKSVWIWDVQPG
    NEFECVSVLQGHTQDVKMVQWHPNRDILVSASYDNSIKV
    WAEDGDGDDWACMQTLGNSVSGHTSTVWAVSFNSSGDRM
    VSCSDDLTLMVWDTSINPAERSGNAGPWKHLCTISGYHD
    RTIFSVHWSRSGLIASGASDDCIRLFS
    202 The amino acid sequence of SEQ ID MKRAYKLQEFVAHASNVNCLKIGKKSSRVLVTGGEDHKV
    471. The conserved G-protein beta NMWAIGKPNAILSLSGHSSAVESVTFDSAEALVVAGAAS
    WD-40 repeat domains are GTIKLWDLEEAKIVRTLTGHRSNCISVDFHPFGEFFASG
    underlined and the Trp-Asp (WD) SLDTNLKIWDIRRKGCIHTYKGHTRGVNSIRFSPDGRWV
    repeats signature is in bold. VSGGEDNIVKLWDLTAGKLMHDFKCHEGQIQCMDFHPQE
    FLLATGSADRTVKFWD LETFELIGSAGPETTGVRAMIFN
    PDGRTLLTGLHESLKVFSWEPLRCYDAVDVGWSKLADLN
    IHEGKLLGCSYNQSCVGVWVVDISRVGPYAAGNVSRTNG
    HNEAKLASSGHPSVQQLDNNLKTNMARLSLSHSTESGIK
    EPKTTTSLTTTEGLSSTPQRAGIAFSSKNLPASSGPPSY
    VSTPKKNSTSRVQPTTNFQTLSRPDIVPVIVPRSNSLRP
    ETTSDVKKEMNNFGRVVPSTVSTKSTDVIKSGSNRDESD
    KIDSINQKRMTGNDKTDLNIARAEQHVSSRLDNTNTSSV
    VCDGNQPAARWIGAAKFRRNSPVDPVVSPHDRSPTFPWS
    ATDDGVTCQPDRQVTAPELSKRVVEPGRARALVASWETR
    EKALTADTPVLVSGRPPTSPGVDMNSFIPRGSHGTSESD
    LTVSDDNSAIEELMQQHNAFTSILQARLTKLQVIRRFWQ
    RNDLKGAIDATGKMGDHSVSADVISVLIERSEIFTLDIC
    TVILPLLTRLLQSETDRHLTVAMETLLVLVKTFGDVIRA
    TISATPTIGVDLQAEQRLERCNLCYVELENIKQILVPLI
    RRGGAVAKSAQELSLALQEV
    203 The amino acid sequence of SEQ ID MSTLEIEARDVIKIVLQFCKENSLHQTFQTLQNECQVSL
    472. The conserved G-protein beta NTVDSLETFVADINSGRWDVILPQVAQLKLPRKKLEDLY
    WD-40 repeat domains are EQIVLEMIELRELDTARAILRQTQAMGFMKQEQPERYLR
    underlined and the Trp-Asp (WD) LEHLLVRTYFDPREAYHESSKEKRRSQIAQALASEVTVV
    repeats signature is in bold. PPSRLMALIGQSLKWQQHQGLLPPGTQFDLFRGTAAVKA
    DEEEMYPTTLAHTIKFGKQSHPECARFSPDGQYLVSCSV
    DGFIEVWDYISGKLKKDLQYQADDSFMMHDDAVLCVDFS
    RDSEMLASGSQDGKIKVWRIRTGQCLRRLERAHSQGVTS
    LSFSRDGSQLLSTSFDSTARIHGLKSGKALKEFRGHTSY
    VNDAIFTSDGGRVITASSDCTVKVWD VKTTDCIQTFKPP
    PPLKGGDVSVNSVHLFPKNSEHIVVCNKASSIYIMTLQG
    QVVKSFSSGKREGGDFVAACISPKGEWIYCVGEDRNIYC
    FSQQSGKLEHLMKAHDKDIIGVTPHPHRNLLVTYSEDST
    MKIWKP
    204 The amino acid sequence of SEQ ID MDIELEDQPFDLDFHPSAPIVAVALITGRLQLFRYVDIS
    473. The conserved G-protein beta SEPERLWTVTAHTESCRAARFINAGSSVLTASPDCSILA
    WD-40 repeat domains are TNVETGQPVARLDNAHGAAINCLTNLTESTIASGDENGI
    underlined. IKVWDTRQNSCCNKFKAHEDYISDMEFVPDTMQLLGTSG
    DGTLSVCNLRKNKVHARSEFSEDELLSVALMKNGKKVVC
    GSQEGVLLLYSWGYFKDCSDRFVGHPHSVDALLKLDEDT
    VLTGSSDGIIRVVSILPNKMIGVIGEHSSYPIERLAFSH
    DRNVLGSASHDQILKLWDIHYLHEDDEPETNKQEAVNDE
    NVDMDLDVDTEKRPRGSKRKKRAEKGQTSSQKQSSDFFA
    DI
    205 The amino acid sequence of SEQ ID MDRIQQIPHTCVARKINLPLGMSKESLALNLPANLAPTM
    474. The conserved G-protein beta SPPSITYSDRFIPSRKASNFEEFALPDKTSPSPNSAGGQ
    WD-40 repeat domains are SSSTNGEGRDDACAAYSALLRTELFPATPDKTEGCRRPV
    underlined. IGSPSGNVFRFKSQQCKSQSPFSLCPVGEDGDLSETGAV
    ARKTTRKIPRSPFKVLDAPALQDDFYLNLVDWSSHNILA
    VGLSACVYLWSASSSKVTKLCDLGLDDNVCSVAWTQRGT
    YLAVGTNNGGVQIWDAAHCKQVRTMEGHCTRVGTLAWNS
    HILSSGGRDRNILQRDIRAQDDFVSKFSGHKSEVCGLKW
    SYDNRELASGGNDNQLFVWNQQSQQPVLKYNEHTAAVKA
    IAWSPHQHGLLASGGGTADRCIRFWNTATNTSLNCVDTG
    SQVCNLVWSKNVNELVSTHGYSQNQIIVWRYPTMSKLAT
    LTGHTLRVLYLAISPDGQTIVTGAGDETLRFWNVFPSSK
    TQQNTIRDMGVWSSGRTHIR
    206 The amino acid sequence of SEQ ID MAGGQGEGEEKVDKLSMELTEDVMKSMEIGAVFKDYNGK
    475. The conserved G-protein beta INSLDFHRTNNYLVTASDDEAIRLFDTASATWQKTSYSK
    WD-40 repeat domains are KYGVDLICFTNHQTSVLYSSKNGWDESLRHLSLMDNKYL
    underlined. RYFKGHHDRVVSLCMSPKGECFMSGSLDRTVLLWDLRID
    KCQGLIRVRGRPAVAYDEQGLVFAISNEGGLIKMFDARL
    YDKGPFDTFVVEGDKSEASGIKFSNDGKLILLSTMDSNI
    HVLDAYQGTTVHSFSVEAVPNGGEAVPNGGTLEASFSPD
    GKFVISGSGNGNIHAWSVNSGKEVACWTTEGVIPAVVKW
    APRRLMFASGSSVLSLWVPDLSKLASLTGSNSNSAY
    207 The amino acid sequence of SEQ ID MHRVGSTGNTSNSSRPRREKRLTYVLNDANDSRHCSGIN
    476. The conserved G-protein beta CLVISKLSLLGGNDYLFSGSRDGTLKRWELADDSAVCSA
    WD-40 repeat domains are TFESHVDWVNDAVLTGETLVSCSSDTTLKTWRPFSDGVC
    underlined. TRTLRQHSDYVTCLAAASKNSNIVASGGLGREVFIWDIE
    AAMAPVSRTSEAMDDDTSNGVLSSGNSVLSTTVRSTNAT
    NSASLHTSQLQGYTPIAAKGHKESVYALAMNDVGTLLVS
    GGTEKVVRVWDPRSGAKQMKLRGHTDNVRALILDSTGRF
    CLSGSSDSIIRLWDLGQQRCVHSYAVHTDSVWALASTPN
    FSHVYSGGRDLSLYLTDLTTRESLLLCMEKHPLLRLTLQ
    DDSIWVATTDSSLHRWPAEGQNPPKMFQRGGSFLAGNLS
    FTRARACLEGSAPVPVNTQPSFVIPGSPGIVQHEILNNR
    RHVLTKDAEGTVKLWEITRGAVLDDYGKVSFEEKKEELF
    EMVSIPAWFTMDTRLGSMSVHLDTPQCFTAEMYAVDLNV
    PDAPEEQKINLAQETLRGLLAHWLSRRRQRLATQASANG
    DFPAGQENALRNHISSRIDVHDDAETHIAGILPAFDFST
    TSPPSIITEGSQGGPWRKKITDLDGTEDEKDFPWWCLEC
    VLHGRLSPRESLKCSFYLHPYEGTTVQVLTQGKLSAPRI
    LRIQKVINYVLEKMVLDRPLDSSNSETTFTPGLSGNQSH
    AAVVGDGSLRSGARVWQQKAKPLVEILCNNQVLSPDMSL
    ATVRTYIWKKPDDLYLYYRLVQNR
    208 The amino acid sequence of SEQ ID MMKGKTIQMQAAHQNHDGETSVACVLWDWHAKHLITAGA
    477. The conserved G-protein beta DNTILIHSYPSSSSSKPITLRHHKNAVTALAINSNVRSL
    WD-40 repeat domains are ASGSVDHSVKLYSYPGGEFQSNVTRFTLPIRSLAFNKSG
    underlined. ELLAAAGDDEGIKLISTIDNSIARVLKGHNGPVTSISFD
    PKNEFLASSDSDGTVIYWELSTGKPVHTLKKIAPNTTSN
    PTSLNQISWRPDGEMLAVPGRKSEVSMYDRDTAEKLFSL
    KGGHSDTICSLAWSPNGKYIATAGTDRQVMVWDADRRQD
    IDKQRFDNPICSVAWKPSDNALAVIDVLGRFGVWESPIA
    SHMKSPADGAERYDNMEDEEPLMARYEEELEDSVSGSLN
    EIINDDDDDDEMGKIPRKILQKKPSVKVEKGKEESNAKA
    FKSGQDSFKLKSAMQEAFQPGATQRQSGKRNFLAYNMLG
    SVITFDNDGFSHIEVDFHDIGKGCRVPSMTDYFGFTMAS
    LSESGSVFGSPQKGEKNPSTLMYRPFSSWANNSEWSMRF
    PMGEEVKAVALGSGWVAAVTSLNFLRVFSEGGLQKFVLS
    MDGPVVTAAGYENLLVVVSHASNPLLSGDQVLSFTVYDI
    SQKTCPLSGRLPLSPGSHLTWLGFSEEGLLSSYDSEGNL
    RVFTNDYNGCWVPIFSAARERKSETESIWMVGLNSTQVF
    CVVCKLPDTYPQVAPKPVLSVLNLSLPLACSDLGADDLE
    NEYLRGSLLLSQMQKKAEDAVACGRESNMEEDSIFKMEA
    ALDRCLLRLIANCCKGDKLVRATELARLLSLEKSLQGAI
    KLVSAMKLPMLAERFNTILEEKILQENMETISCRRLTSE
    AQDMDTPISISVKQVSYGANLGDSPFLPNRQVEPKHSTP
    VFSKPDTKIEVDTSEAIAKGCDAQNGNIKSGDAEVQPAS
    HNDSIQKPSNPFAKASNTSANQAVQRNASLLSSIKQMKT
    ATENEGKRKERARSGSLPQKPAKQSKIS
    209 The amino acid Sequence of SEQ ID MKQKRKGHQVDDPKYSVQTPQEDDTPNESGPASEEVESS
    478. The conserved G-protein beta DEEGGNSSNIEDDIIYSSSEEDPVVSSDYEEDEDAESDA
    WD-40 repeat domains are EGVTAEQELEGDIDNALQNYMGTLTVLSNFHGENLKNAE
    underlined. GEDTSGDDDDEEEMPKRAEESDSPEDENDERPKRAEESD
    FSEDEDEERPKRAEESDSSEDEVPSRNTVGDVPLRWYKD
    EQHIGYDIKGKKIKKQPKKDQLDSFLASTDDSSDWRKVY
    DEYNDEEVELTKDEIKFISRLRKGTIPHADVNPYEPYVD
    WFDWKDKGHPLSNAPEPKRRFIPSKWEAKKVVKLVRAIR
    KGWITFQKAEEKPRFYLMWGDDLKPSEKMANGLSYIPAP
    KPKLPGHEESYNPPPEYIPTQEEINSYQLMYEEDRPKFI
    PKRFDSLRNVPAYDRFLSEIFERCLDLYLCPRTRKKRIN
    IDPESLIPKLPKPKDLQPFPSICFLEYKGHTGAVSCISP
    ESSGQWLASGSKDGTVRIWEVETARCLKVWDIGRPIQHI
    AWNPVSQLSILAVAVDEEVLVLNTGLGSEDSQEKVAELL
    HVKSKPVSADDLGDNTSLTKWIKHEKFDGIKLTHLKPVH
    LISWHHKGDYFATVAPDGNTRAVLVHQLSKQQTQNPFKK
    MQGRVVHVLFHPSRAIFFVATKTHVRVYDLVKQQLVKRL
    VTGLHEVSSMAVHHKGDNLLVGSKEGKVCWFDMDLSTQP
    YKTLKNHSKDIHSVAFHDSYPLFASCSDDCKAYVFYGLV
    YSDLLQNPLIVPLKVLQGHQSVNGMGVLDCQFHPKQPWL
    FTAGADSVVKLYCN
    210 The amino acid sequence of SEQ ID MMSLKRGFEESLVPAKRQKTELSTVTYGDGPRRTSSLES
    479. The conserved G-protein beta PIMLLTGHHAAIYTMKFNPTGTVIASGSHEREIFLWNVH
    WD-40 repeat domains are GDCKNFMVLKGHKNAVLDLHWTTDGCQIISASPDKTLRA
    underlined. WDVETGKQIKKMAEHSSFVNSCCPSRRGPPLVVSGSDDG
    TAKLWDLRHRGAIQTFPDKYQITAVGFSDAADKIYSGGI
    DNEIKVWDLRRGEVTMRLQGHTDTITGMQLSSDGSYLLT
    NSMDCSLRIWDMRPYAPQNRCVKILTGHQHNFEKNLLKC
    SWSSDGSKVTAGSADRMVYIWDTTTRRILYKLPGHTGSV
    NETGFHPTQPIIGSCSSDKQIYLGEIEPNVGYQAVI
    211 The amino acid sequence of SEQ ID MEFSDTYKHTGPCCFSPDARYLAIAVDYRLVIRDVVTLK
    480. The conserved G-protein beta VVQLYSCMDKISNIEWALDSEYILCGLYKRAMVQAWSLS
    WD-40 repeat domains are QPEWTCKIDEGPAGIAHARWSPDSRHIITTSDFQLRLTV
    underlined. WSLVNTACIHIQWPKHASKGVSETQDSKfAAIATRRDCK
    DYVNLLSCHTWEVMGTFTVDTIDLADLEWSPNDSAIVVW
    DSPLEYKVLIYSPDGRCLFKYQAYDSWLGVKTVAWSPCS
    QFLAVGSYDQTLRTLNHLTWKPFAEFVHVSTVRGPASAV
    VFKEVEEPWNLDVSGLHLNDDNAHDIQDGKPAEGHSRVR
    YKVVEFPVNVSSQKHPVDKPNPKQGIGLLAWSRDSQYLF
    TRNDNMPTALWIWDICRLELAALLIQKEPIRAAAWDPVY
    PRVALCTGSSHLYMWTPSGACCVNIPLPQFVVSDLKWNP
    DGTSMLLKDRESFCCTFVPMLPEFNDDETNEE
    212 The amino acid sequence of SEQ ID MAKLIETHSCVPSTERGRGILIAGDAKTNSIIYCNGRSV
    481. The conserved G-protein beta IMRNLDNPLEASVYGEHSYPATVARFSPNGEWVASGDTS
    WD-40 repeat domains are GTVRIWGRGSDHTLKYEYKALAGRIDDLEWSADGQRIVV
    underlined. CGDSKGKSMVRAFMWDSGTNVGEFDGHSRRVLSCSFKPT
    RPFRVATCGEDFLVNFYEGPPFRFKTSHRDHSNYVNCVR
    FAPDGSKFITVGSDRKGVIFDGKMGEKIGELSKEGGHTG
    SIYAASWSPDSKQVLTVSADKSAKIWEISETGNGTVKKT
    LTFGSQGGADDMLVGCLWLNDYLITVSLGGIVSLLSAVD
    PDKPPKTISGHMKSINAIALSLQSGQSEVCSSSYDGVIV
    RWILGVGYAGRVERKDSTQIKCLATIEGELVTCGFDNKV
    RRVPLLSEQHKESEPIDIGAQPKDLDVAVGCPELTFVST
    DAGIIIIRASKIVSTTNVGYAVTAAAISPDGTEAVVGGQ
    DGKLRVYSIKGDTLLEESVLERHRGPINAIRFSPDGSMF
    ASGDLNREAVVWDRITREVKLKNMVYHTARINCIAWSPD
    SSKVATGSLDTCILIYEVGKPASSRITIKGAHLGGVYGL
    AFSDQSTVISAGEDACVRVWSLP
    213 The amino acid sequence of SEQ ID MPQPSVILATAGYDHTVRFWEATSGRCYRTLQYPDSQVN
    482. The conserved G-protein beta HLEITPDKQYLAAAGNPHIRLFEVNSNNPQPVISYDSHT
    WD-40 repeat domains are NNVTAVGFQCDGKWMYSGSEDGTVKIWDLRAPGFQREYE
    underlined and the Trp-Asp (WD) SRAAVNTVVLHPNQTELISGDQNGNIRVWDLNANSCSCE
    repeats signature is in bold. LVPEDTAVRSLTVMWDGSLVVAANNHGTCYVWRLMRGTQ
    TMTNFEPLHKLQAHNSYILKCLLSPEFCEHHRYLATTSS
    DQTVKIWN VDGFTLERTLTGHQRWVWDCVFSVDGAFLVT
    ASSDSTARLWDLSTGEAIRTYQGHHKATVCCALHDGTDG
    ASC
    214 The amino acid sequence of SEQ ID MLTKFETKSNRVKGLSFHPKRPWILASLHSGVIQLWDYR
    483. The conserved G-protein beta MGTLIDKFDEHDGPVRGVHFHKTQPLFVSGGDDYKIKVW
    WD-40 repeat domains are NYKMRQCLFTFVGHLDYIRTVHFHNEYPWIVSASDDQTI
    underlined and the Trp-Asp (WD) RLWNWQSRVCISVLTGHNHYVMSASFHPKEDLVVSASLD
    repeats signature is in bold. The QTVRVWD ISGLRKKTVSPADDLSRLAQMNTDLFGGGDVV
    coatomer WD associated region is VKYVLEGHDRGVNWAAFHTSLPLIVSGADDRQVKLWRMN
    in bold/italics. DTKAWEVDTLRGHTNNVSCVIFHARQDIIVSNSEDKSIR
    VWDMSKRTSVQTFRREHDRFWILAAHPEMNLLAAGHDSG
    MIVFKLERERPAYVVYGGSLLYVK
    Figure US20100122382A1-20100513-P00038
    Figure US20100122382A1-20100513-P00039
    Figure US20100122382A1-20100513-P00040
    Figure US20100122382A1-20100513-P00041
    Figure US20100122382A1-20100513-P00042
    Figure US20100122382A1-20100513-P00043
    Figure US20100122382A1-20100513-P00044
    Figure US20100122382A1-20100513-P00045
    Figure US20100122382A1-20100513-P00046
    Figure US20100122382A1-20100513-P00047
    Figure US20100122382A1-20100513-P00048
    Figure US20100122382A1-20100513-P00049
    Figure US20100122382A1-20100513-P00050
    Figure US20100122382A1-20100513-P00051
    Figure US20100122382A1-20100513-P00052
    Figure US20100122382A1-20100513-P00053
    Figure US20100122382A1-20100513-P00054
    Figure US20100122382A1-20100513-P00055
    Figure US20100122382A1-20100513-P00056
    Figure US20100122382A1-20100513-P00057
    Figure US20100122382A1-20100513-P00058
    Figure US20100122382A1-20100513-P00059
    Figure US20100122382A1-20100513-P00060
    Figure US20100122382A1-20100513-P00061
    IPVLPPGKKSSLLMPPAPILHGGDWPLLRVTKGIFE
    GGLENSTSAAYEEEDEEAAADWGEDIDIENIEGENGEAT
    VLDDQEVKGGEDDEGGWDMEDLELPPDVAAANVGTNQKT
    LFVAPTLGMPVSQIWMQKSSLAGEHAAAGNFETALRLLT
    RQLGIKNFSPLKPLFLELYMGSHTFLPSFASVPAFSLAL
    QRGWSESASPNIRGPPALVYRLSVLEEKLTVAYRATTEG
    RFSEALRLFL
    215 The amino acid sequence of SEQ ID MDLLQNYQDDSEDSNPELRNHPPLEDATATSAPAGVENE
    484. The conserved G-protein beta TSSSPDSSPLRLALPAKSCAPDVDETLMALGVPGSEKKN
    WD-40 repeat domains are NHNKPIDPTQHSVTFNPSYDQLWAPLYGPAHPYAKDGIA
    underlined. QGMRNHKLGFVEDSAIEPFMFDEQYNTFHRYGYAADPSA
    SLGSHIVGDLESLKKNDGASVYNLPKREHKRQKLEKKMI
    QKDENEEEEKEVGEEVDNPSTEEWLKKNRKSPWAGKKEG
    LQTELTEEQKKYAQEHAEKKGDREKGEKVEIVDKTTFHG
    KEERDYQGRSWIDPPKDAKATNDHCYIPKRWVHTWSGHT
    KGVSAIRFFPKYGHLLLSAGMDTKVKIWDVFNSGKCMRT
    YMGHSKAVRDISFSNDGSRFLSAGYDRNIKLWDTETGKV
    ISTFSTGKIPYVVKLHPDEDKQNVLLAGMSDKKIVQWDM
    NSGEITQEYDQHLGAVNTITFVDNNRRFVTSSDDKSLRV
    WEFGIPVVIKYISEPHMHSMPSISLHPNTNWLAAQSLDN
    QILIYSTRERFQLNKKKRFAGHIAAGYACQVNFSPDGRF
    VMSGDGEGRCWFWDWKTCKVFRTLKCHDNVCIGCEWHPL
    EQSKVATCGWDGMIKYWD
    216 The amino acid sequence of SEQ ID MARKGLGTDPAIGSLMSSKKRKEYKVTNRFQEGKRPLYA
    485. The conserved G-protein beta IAFNFIDARYHNIFATAGGTRVTIYQCLEGGAISVLQAY
    WD-40 repeat domains are VDDDKDESFYTLSWACDVNGSPLLVAGGHNGIIRVLDVA
    underlined and the Trp-Asp (WD) NEKVHKSFVGHGDSVNEIRTQALKPSLILSASKDESVRL
    repeats signature is in bold. WN VQTGICILIFAGAGGHRNEVLSVDFHPSDVYRIASCG
    MDNTVKIWSMKEFWTYVEKSFTWTDLPSKFPTKYVQFPV
    FIAAVHSNYVDCTRWLGNFILSKSVDNEVVLWEPYSKEQ
    STSDGVVDILQKYPVPECDIWFIKFSCDFHYNSMAVGNR
    EGKVYVWELQSSPPNLIARLSHAHCKNPIRQTAISHDGS
    TILCCCDDGSMWRWDVVQ
    217 The amino acid sequence of SEQ ID MESGAGGSVGARVPSAKPEMLQQPPYSNGDDDNDMERGT
    486. The conserved G-protein beta APVPSSNPNTVSKWELDKDFLCPICMQTMKDAFLTACGH
    WD-40 repeat domains are SFCYMCIMTHLNNKSNCPCCSLYLTNNQLFPNFLLNKLL
    underlined and the Trp-Asp (WD) KKTSACQMASTASPVENLCLSLQQGAEVSVKELDFLLTL
    repeats signature is in bold. LAEKKRKMEQEEAETNMEILLDFLQRLRQQKQAELNEVQ
    ADLHYIKDDILALEKRRLELSRARERYSRKLHMLLDDPM
    DTTLGHAAIDDGNNVRTAFVRGGQGDAISGKFQQKKAEI
    KAQASSQGMQKRANFCHSDSQVLPTLSGLTIARKRRVLA
    QFDDLQECYLQKRRRWATQLRKQCDGGLRKERDGNSISR
    EGYHAGLEEFQSILTTFTRYSRLRVISELRHGDLFHSAN
    IVSSIEFDRDDELFATAGVSRRIKVFDFATVVNEPADVH
    CPVVEMSTRSKLSCLSWNKCIKSQIASSDYEGIVTVWDV
    NTRQSVMMYEEHEKRAWSVDFSRTEPTRLISGSDDGKVK
    VWCTRQETSVLNIDMKANICCVKYNPGSSYYVAVGSADH
    HIHYYDLRNPSVPLYEFNGHRKTVSYVKFISTNELASAS
    TDSTLRLWD VRDNCLVRTFKGHTNEKNFVGLTVNSEYIA
    CGSETNGVFVYHKAISKPAAWHQFGSPDLDDSDDDTSHF
    ISAVCWKSESPTMLAANSQGTIKVLVLAP
    218 The amino acid sequence of SEQ ID MANYVDSKKNFKCVPALQQFYTGGPFRLSSDGSFLVCAC
    487. The conserved G-protein beta NDEVKVVDLATGSVKNTLEGDSELIVALALTPDNKYLFS
    WD-40 repeat domains are ASRSTQIKFWDLSSATCKRTWKAHNGPVADMACDASGGL
    underlined. LATAGADRSILVWDVDGGYCTHSFRGHQGVVTTVIFHPD
    PHCLLLFSGSDDATVRIWDLVAKKCISVLEKHFSTVTSL
    AISENGWNLLSAGRDKVVNIWDLRDYHCRATIPTYEPLE
    AVCVLPTGSRLVSVMNQSRALPENRKKSGAAPVYFLTVG
    ERGIVRIWYSEGALCLYEQKSSDAIISSDKDELKGGFVS
    AVLLPLTQGVMCVTADQRFLFYNLDESDEGKCDLKVSKR
    LIGYNEEIVDLKFLGDEEKFLAVATNLEQVRMYDLSSMT
    CVYELSGHTDIVLCLDTVVFSGHSLLASGSKDHTVRIWD
    TESKSCICVAAGHMGAVGAVAFSKKAKNFFVSGSSDRTI
    KVWSFASVLDFGGISKSIKLSSQAAVAAHDKDINSVAVA
    PNDSLICTGSQDRTARIWRLPDLVPVLVLRGHKRGVWCV
    EFSPVDQCVMTASGDKTIKIWALSDGSCLKTFEGHTASV
    LRASFLTRGTQFVSSGADGLLKLWTIKSNECIATFDQHE
    DKIWAMAVGKKTEMLATGGSDSLVNLWHDCTTTDEEEAL
    LKEEEAALKDQELLNALADTDYVKAIQLAFELRRPYKLL
    NVFTELYSKGHAQDQIQKVIRELGNEELRLLLEYVREWN
    TKPKFAHVAQFVLFQLFNVLPPKEIIEVQGISELLEGLI
    PYAQRHYSRIDRLMRSTFLLDYTLSSMSVLSPTETDLSS
    SNLLARTADPLHAQIDQFHPTHFPEPNLTPIQSLLDSGN
    TDSVEVTARRAKKKRVSGNDSEKTTVAEVKIGDMENAFD
    EPDVADQGSSRKHKPASSKKRKSIAVGNASIKRIASGNA
    VTIALQV
    219 The amino acid sequence of SEQ ID MESSCSSMNSNRHSTEKRCLRPLQKQGASMNKHSSDRFI
    488. The conserved G-protein beta PARGSIDLDVARFMVTQKQKDNNDIHALSPSPSPSKKAY
    WD-40 repeat domains are QKEMADTLLKNAGAADNNCRILSFNGKSSTVSQGSQENV
    underlined. LANLSISRRARRYIPQSADRTLDAPDLLDDYYLNLLDWS
    STNVLSTALGNTVYLWDASNSSISELLIADEEEGPVTSV
    SWAPDGSQIAVGLNNSVVQLWDSQSNKKLRALKGHHDRV
    GALSWNGPILTTGGLDGIIINHDVRTRDHIVQTYKGHTQ
    EVCGLKWSPSGQQLASGGNDNLLYIWDKSMASHNPSSQY
    FHQLDEHCAAVKALAWCPFQTNLLASGGGTSDGSIKFWN
    TQTGACLNTVDTHSQVCSLLWNRHERELLSSHGLNQNQL
    TLWKYPSMVKITELTGHTARVLHMAQSPDGYTVASAAAD
    ETLKFWQVFGAPDASKKTKDTKGAFNMFHMHIR
    220 The amino acid sequence of SEQ ID MLDEIVADEEEEFNIWKKNTPLLYDVVITHALEWPSLTV
    489. The conserved G-protein beta QWLPDRHQSPTKDYSLQKMIVGTHTSGDEPNYLMIAEVQ
    WD-40 repeat domains are MPLQYSEDGNVGGFESTEAKVHIIQQINHEGEVNRAQYM
    underlined. PQNSFIIATKTVSSDVYVFDYTKHSSNAPQERVCNPELI
    LKGHTNEGYSLSWSPLKEGQLLSGSNDAQICFWDINAAS
    GRKVVEAKQIFKVHEGAVEDVSWHLKHEYLFGSVGDDCH
    LLIWDTRTAAPNKPQHSVVAHESEVNSLAFNPFNEWLLA
    TGSADKTVKLFDLRKLSCSLHTFSNHTEEVFQIEWSPMN
    ETILASSGGDRRLMVWDLRRIGDEQTSEDAEDGPPRLIF
    IHGGHTSKISDFSWNLHDDWLIASVAEDNILQIWQMAEN
    IYHDDADIL
    221 The amino acid sequence of SEQ ID MTKEDHGESRDEMGERMVNEEYKLWKKNTPFLYDLVITH
    490. The conserved G-protein beta ALEWPSLTVQWLPPSCKQQQDIIKDDDIDHPNTQMVILG
    WD-40 repeat domains are THTSDNEPNYLILAEVQLHDGTEDEDGDGDVKRPQDKMK
    underlined. PGTSGGAMGKVRILQQINHQKEVNRARYMPQKPTIIATK
    TVNADVYVFDYSKHPSKPPQEGRCNPELRLQGHESEGYG
    LSWSPLKEGHLLSASDDAQICLWDITAATKAPKVVEANQ
    IFRYHDGPVEDVAWHAIHDHLFGSVGDDHHLLLWDIRND
    SEKPLHIVEAHQAEVNCLAFNPFNEWIVATGSADRTVAL
    HDIRKLDKVLHTCAHHMEEVFQIGWSPQNGAILASCGSD
    RRLMVWDLSRIGDEQNPEDAEEAPPELLFIHGGHTSKIS
    DFSWNPAEEWVIASVAEDNILQVWQMSEHIYNDDNDSPTA
    222 The amino acid sequence of SEQ ID MAMAMGDENAADPVEEFNIWKKNTPFLYDLVITHALEWP
    491. The conserved G-protein beta SLTVQWLPDRHQSSTADYSLQKMIVGTHTSEDEPNYLMI
    WD-40 repeat domains are AEVQIPLQNSEDNIIGGFESTEAKVQIIQKINHEGEVNK
    underlined. ARYMPQNSFVIATKTVSSDVYVFDYSKHPSKAPQERVCN
    PELILKGHSNEGYGLSWSPLKEGYLLSGSNDAQICLWDI
    NAAFGKKVLEANQIFKVHEGAVGDVSWHLKHEYLFGSVG
    DDCHLLIWDMRTAAPNKPQQSVIAHQSEVNSLAFNPFNE
    WLLATGSMDKTVKLFDLRKLSCSLHTFSNHTDQVFQIEW
    SPMNETILASSGADRRLMVWDLARIGETPEDEEDGPPEL
    LFVHGGHTSKISDFSWNLNDDRVIASVAEDNILQIWQMA
    ENIYHDDEDML
    223 The amino acid sequence of SEQ ID MGLFEPFRALGYITDGVPFAVQRRGIETFVTLSVGKAWQ
    492. The conserved G-protein beta IYNCAKLIPVLVGPQMDKKIRALACWRDFTFAATGHDIA
    WD-40 repeat domains are VFRRAHQVATWSGHKAKVTLLLSFGQHVLSVDLEGCLFI
    underlined and the Trp-Asp (WD) WAVAEVNQNKPPIGQIQLGEKFSPSCIMHPDTYLNKVLI
    repeats signature is in bold. GSEEGTLQLWNVNTRKKLYEFKGWGSSIRCCVSSPALDV
    VGIGCSDGKIHVHNLRYDEEIVTFMHSTRGAVTALSFRT
    DGQPLLAAGGSSGVISIWNLEKKKLQSVIKDAHDSSVCS
    LHFFANEPVLMSSATDNSIKMWIFDTTDGEARLLKYRSG
    HSAPPMCIRYYGKGRHILSAGQDRAFRIFSVIQDQQSRE
    LSQGHVGKRAKKLKVKDEEIKLPPVIAFDAAEIRERDWC
    NVVTCHLDDPCAYTWRLQNFVIGEHILKPCLEDPTPVKS
    CSISACGNFAVLGTEGGWLERFNLQSGISRGTYIDIGEK
    RQCAHNGAVVGLACDATNTLLISGGYNGDIKVWDFKGRE
    LKFRWEIEVPLIKIVYHPGNGILATAADDMILRLFDVTA
    MRLVRIFVGHMDRVTDLCFSGDGKWLLSSSMDGTIRVWD
    IISSRQLNAMHMDSAVTALSLSPGMDMLATTHVGHNGIY
    LWANRMIYSKATDIEPFISGKQVVKVSMPTVSSKRESEE
    GDEKRTIVAESNVNKSDVSGSLIGDSYSAQLTPELVTLA
    LLPKAQWQSLVNLDIIKMRNKPIEPPKKPEKAPFFLPSL
    PTLSGERIFIPSSMNGDGDQDETRNDKTVFEARGKKLGG
    ESLSFMQLLQSCAKIKDFTTFTNYLKGLSPSAVDMELRL
    LQIVDNENISETEHSVELQGIGMLLDYFVNEVSCNNNFE
    FVQALIRLFLKIHGETIRCQVSLQEKARKLLEIQSSTWE
    RLDTSFQNARCMITFLSSSQF
    224 The amino acid sequence of SEQ ID MIAAVCWVPKGVAKVLPDSAEPPTQEEIQELLKCNVVAE
    493. The conserved G-protein beta SDDNEDSDEESEEMDTETDKNTDAVAKALAAANALGSQS
    WD-40 repeat domains are SDFQRQHKVDDIANGLKELDMDHYDDEDEGIDIFGSGSL
    underlined and the Trp-Asp (WD) GNCYYPANDMDPYLVEQDDDDEDEIEDMTIKPSDLIILS
    repeats signature is in bold. ARNEDDVSHLEVWIYEEETEEGGSNMYVHHDIILPAFPL
    SLAWLDCNLKGGEKGNFVAVGTMQPEIELWDLDVLDEVE
    PAVVLGGAVKDEASGKTTKLKKKKKNKQAVNFKEGSHTD
    AVLGLAWNMEYRNVLASASADKSVKIWD IVAEKCEHTMQ
    PHTDKVQAVAWNPNQATVLLSGSFDRSVIMMDMRAPTHS
    GIRWPVPADVESLAWDPHTDHSFMVSAEDGTVRGFDIRA
    AASTADFDGKPMFILHAHDKAVCAISYNPAAPSLLTTGS
    TDKMVKLWDITNNQPSCIASTNPNVGAVFSAAFSKNSPF
    LLATGGSKGILHVWDTLDNSEVARRFGKFRPQN
    225 The amino acid sequence of SEQ ID MIMDENEFCDIFSLRKRLCLLSSQEGEEEEELEAMSQLD
    494. The conserved eukaryotic AGEFTVTGNEEVVAIAEDDVNTGILSQDLFSSQDYCTPS
    protein kinase domain is QPQDSTDLDSKDKAPCPLSPVKSTIQRKRCRPELLSNPP
    underlined. DSIQFSFQRLERVRSEESIQSSSQQLARVRSEVSSSDDF
    KTPKITASGQKNYVSQSALALRARVMSPPCIKNPYLDEN
    EELNEKIQRSTRRSPACVTPIQSGACLSRYRADFHELEE
    IGRGNFSRVYKALNRLDGCCYAVKCSQSELRLDTERKVA
    LMEVQSLAALGPHKNIVGYHTAWFENDHLYIQMELCDHN
    LTTANDRGILRTDTDFLEAVYQIAQALEFIHGRGVAHLD
    VKPENIYVRDGTYKLGDFGRATLINGTLHVEEGDARYMS
    REILNDNYEHLDKVDMFSLGATFFELLMRKQYPGSGKRI
    DRDTEIKIPILPGFSIYFQKLLQDLVSNDPGKRPSAKDV
    LKNPIFNKVRGAKEV
    226 The amino acid sequence of SEQ ID MLAPALEMEPVEPQSLKKLSFKSLKRALDLFSPVHGQIA
    495. The conserved G-protein beta PPDPESKKMRISYKLNFEYGGGSGSEDQVPKRKESGAAQ
    WD-40 repeat domains are NQGQQAAGASNALALPGPEGSKIPPMEKSQNALTVGPSL
    underlined and the Trp-Asp (WD) RPQGLNDVGLHGKGTAIISASGSSDRNLSTSAIMERLPS
    repeats signature is in bold. RWPRPVWHPPWKNYRVISGHLGWVRSIAFDPSNQWFCTG
    SADRTIKIWDLASGRLKLTLTGHIEQIRGLAVSSKHTYM
    FSAGDDKQVKCWDLEQNKVIRSYHGHLSGVYCLALHPTI
    DILLTGGRDSVCRVWDIRSKMQIFALSGHDNTVCSVFAR
    PTDPQVVTGSHDTTIKFWD LRHGKTMTTLTNHKKSVRAM
    AQHPKENCFASASADNIKKFQLPRGEFLHNMLSQQKTII
    NTMAVNEEGVMATGGDNGSLWFWDWKSGHNFQQAHTIVQ
    PGSLESEAGIYALSYDLTGSRLVSCEADKTIKMWKEDEL
    ATPETHPLNFKPPKDIRRF
    227 The amino acid sequence of SEQ ID MEEAAKEQSAGSGKPKLLRYGLRSAAKPKEDKKEEQLHQ
    496. The conserved G-protein beta PPPPPPPQQQAAPAPAPAATRSSTSGSAGGRDRRPQQQH
    WD-40 repeat domains are AVDEKYARWKSLVPVLYDWLANHNLLWPSLSCRWGPQLE
    underlined. QATYKNRQRLYISEQTDGSVPNTLVIANCEVVKPRVAAA
    EHVSQFNEEARSPFIRKYKTIIHPGEVNRIRELPQNPNI
    VATHTDSPDVLIWDVESQPNRHAVYGATASRPNLILTGH
    QENAEFALAMCPAEPFVLSGGKDKTVVLWSIQDHITASA
    TDQTTNKSPGSGGSIIKKTGEGNEETGNGPSVGPRGIYC
    GHEDTVEDVAFCPSTAQEFCSVGDDSCLILWDARIGTNP
    VAKVEKAHNGDLHCVDWNPHDNNLILTGSADNSVNMFDR
    RNLTSNGVGSPVYKFEGHKAAVLCVQWSPDKPSVFGSSA
    EDGLLNIWDYERVDKKVDRAPNAPAGLFFQHAGHRDKIV
    DFHWNTADPWTMVSVSDDCDTAGGGGTLQIWRMSDLIYR
    PEEEVLAELENFKAHVLECSKA
    228 The amino acid sequence of SEQ ID MAKDEEEFRGEMEERLVNEEYKIWKKNTPFLYDLVITHA
    497. The conserved G-protein beta LEWPSLTVQWLPDREEPPGKDYSVQKMILGTHTSDNEPN
    WD-40 repeat domains are YLMLAQVQLPLEDAENDARQYDDERGEIGGFGCANGKVQ
    underlined. VIQQINHDGEVNRARYMPQNPFIIATKTVSAEVYVFDYS
    KHPSKPPQDGGCHPDLRLRGHNTEGYGLSWSPFKHGHLL
    SGSDDAQICLWDINVPAKNKVLEAQQIFKVHEGVVEDVA
    WHLRHEYLFGSVGDDRHLLIWDLRTSATNKPLHSVVAHQ
    GEVNCLAFNPFNEWVLATGSADRTVKLFDLRKISSALHT
    FSCHKEEVFQIGWSPKNETILASCSADRRLMVWDLSRID
    EFQTPEDALDGPPELLFIHGGHTSKISDFSWNPCEDWVI
    ASVAEDNILQIWQMAENIYHDEEDDMPPEEVV
    229 The amino acid sequence of SEQ ID MGKYMRKGKGVGEVAVMEVSQGSLGVRTRARTLAAASSQ
    498. The conserved cyclin- KDHRRLGASKSVTTKHQSSAPPASPCVESSMHTCYLELR
    dependent kinase inhibitor domain SRKLEKFSRCYHSAHGATSHGESKRSLSLSEPSRLAVSE
    is underined. EARVASDKSSHRVLQQQSSVAHSRNNSATFSHNAKPAKA
    AQRKERRDDDHTSARPSEAPHEDEDGMEVEASFGENVMD
    LDSRERRTRETTPSSYTRDVETMETPGSTTRPPSNAGRR
    RFQTEGGHGTRNQFHVPTTNEIEEFFAGAEQQEQRRFTD
    RYNYDPVSDSPLPGRFEWVRLRP
    230 The amino acid sequence of SEQ ID MQNMEENVQSSWSLHGNKEICARYEILKRVSSGTYLDVY
    499. The conserved RGRRKEDGLIVALKEVHDYQSSWREIEALQRLCGCPNVV
    serine/threonine protein kinase RLYEVILEFLTSDLYSVIKSAKNKGENGIPEAEVKAWMI
    domain is underlined, and the QILQGLANCHANWVIHRDLKPSNMLISAYGILKLADFGS
    serine/threonine protein kinase MSFLKRAIYEVEYELPQEDILADAPGERLMDEDDSVKGV
    active-site signature is in bold. WNEGEEDSSTAVETNFDDMAETANLDLSWKNEGDMVMQG
    FTSGVGTRWYRAPDFLYGATIYGKEIDLWSLGCILGELL
    ILEPLFSGTSNIDQLSRLVKVLGLQQKKNWPGCSNLPDY
    RKLCFPGDGSPVGLKNHVPNCSDNMFSILERLVCYDPAA
    RLNAKEIVENKYFVEDPYPVLTHELRVPSPLREENNFSE
    DWAKWKDMEVDSDLENIDEFNVVHSSDGFCIKFS
    231 The amino acid sequence of SEQ ID MADVPESLQQEKDEQGTDKNCCDGKFQKEIDIDDMEEEY
    502. The conserved histone NESSIDDEEENLSDNVATNNMGTTPQGQACMAVTVEGIE
    deacetylase family domain is HANSVGCGRNGREGSEEVTAAEDMGHVSIENIREQGRNR
    underlined KSSEQLLALYEQEGLLEDDEDDDDVDWEPFEGVTVQMKW
    YCTNCTMANSDDSVHCDSCGEHRNSDILRQGFLASPYLP
    AESPSSSDVPDERLEESKCVMTTLTPSISPMIGVCCSSL
    QSERRTVVGFDERMLLHSEIQMETYPHPERPDRLRAIAA
    SLRAAGLFPGKCFSIPAREATCEELQTIHSLEHVNAVES
    TSCGMLSHLSPDTYANEHSSLAARLAAGLCADLAKAIMT
    GQAQNGFALVRPPGHHAGVKDSMGFCLHNNAAIAVSASR
    VVGAKKVLIVDWDVHHGNGTQEIFEADQSVLYISLHRHG
    EGFYPGSGAVTEVGSSKGEGYSVNIPWKCGGVGDNDYIF
    AFQHAVLPIAEQFEPDLTIISAGFDAAKGDPLGRCEVTP
    DGFAHMAQMLSCLSKGKMLVILEGGYNLRSISASATAVI
    KVLLGDNPKALPIDIQPSKGGLQTLLEVFEIQSKYWSSL
    KGHDQKLRSQWEAQYGSKKRKVIRKRHMHIVGGPVWWKW
    GRKRVVYYHWFARVSSRKHL
    232 The amino acid sequence of SEQ ID MASGAGAAGVVEWHQKPPNPKNPVVFFDVTIGTIPAGRI
    503. The conserved cyclophilin- KMELFADIVPRTAENFRQFCTGEYRKAGIPIGYKGCHFH
    type peptidyl-prolyl cis-trans RVIKDFMIQAGDFVKGDGSGCISIYGSKFEDENFIAKHT
    isomerase family domain is GPGLLSMANSGPNTNGCQFFLTCAKCDWLDNKHVVFGRV
    underlined and the cyclophilin- LGEGLLVLRKIENVQTGQHNRPKLPCVIAECGEM
    type peptidyl-prolyl cis-trans
    isomerase signature is in bold.
    233 The amino acid sequence of SEQ ID MDHYYQDDFDYLVDDEMVDFADDVEDDVRTRRRSDIDSD
    505. The conserved G-protein beta SENDFDSNNKSPDTTALQAKRGKDIQGIPWNRLNFTREK
    WD-40 repeat domain is underlined. YRETRLQQYKNYENLPRPRRSRNLDKECTNFERGSSFYD
    FRHNTRSVKATIVHFQLRNLVWATSKHNVYLMQNYSIMH
    WSSLKQKGEEVLNVAGPIIPSVKHPGSSPQGLTRVQVSA
    MSVKDNLVVAGGFQGELICKYLDKPGVSFCTKISHDENG
    ITNAVEIYNDASGATRLMTANNDLAVRVFDTEKFTVLER
    FSFPWSVNHTSVSPDGKLVAVLGDNADCLLADCKTGKTV
    GTLRGHLDYSFAAAWHPDGYILATGNQDTTCRLWDVRKL
    SSSLAVLKGRMGAIRSIRFSSDGRFMAMAEPADFVHLYD
    TRQNYTKSQEIDLFGEIAGISFSPDTEAFFVGVADRTYG
    SLLEFNRRRMNYYLDSIL
    234 The amino acid sequence of SEQ ID MDCSGDEEEEQFFESLEEMLSPSDSGSEAADNETGCRNA
    506. The conserved G-protein beta DARSKYEIWKRAPSSIQERRQRFLVRMGLANPSELGNQV
    WD-40 repeat domains are NSTSAESTCSTETANIPNGIERLRENSGAVLRTAGSSGR
    underlined. KTHCKNVINIGLREGSVRSSSSSNGTPDVGEDNGEFGGT
    IFSRSGGTWECMCKIKNLDSGKEFVVDELGQDGLWNKLR
    EVGTDRQLTMDEFERSLGLSPLVQELMRRESGVAQADCN
    GVHHHDAEISSSKRRSWLKALKSAAYSMRRPKEDQSNYD
    SERSGRRSGSFDVPWGKPQWTKVRHYRKRYKEFTALYMG
    QEIEAHEGSIWTMKFSLDGRYLASAGQDCVIHVREVIES
    MRTFGADTPDLYASSAYFSMNGLQELVPLSIEDHANKMK
    RGKIIGSKKSSNSDCIVLPNKVFQLSEEPVCSFHGHLLD
    VFDLSWSPSQYLLSSSMDKTVRLWKLGHESCLKVFSHND
    IVTCIQFNPVDERYFISGSLDGKARIWSIPDRQVVDWSD
    LREMVTAVCYTPDGQGGLVGSIKGSCRFYNTSGNKLQLE
    NQLNVRSKKKKSSGKKITGFQFAPGGDSQKVLITSADSR
    VRVYNGSELVCKYKGFRNTCSQISASFAPNGQHFVCASE
    DSRVYIWNHESPRGSGARHEKSSWSHEHFLSQGVSVAIP
    WSGMKLQPPVWNSPEFMLGQRHNLLSLQGGKDVGCQNGL
    LSREAGEGQESETPLHYISQVSHSCGSQNMVDRDGQDDL
    SRYSACISDSRLSSFMAFPESPGNPDDLNSKVFFSDSSS
    KGSATWPEEKLPPTRKQSRSNSTSSHYDTLKTHLGNTIQ
    GQSGASAAVAWGLVIVTAGHGGEIRSFQNYGLPVRL
    235 The amino acid sequence of SEQ ID MPSIPAIGEFTVCEINRELLTTKDESDTQAKDAYAKILG
    507. The conserved G-protein beta LVFPPISFQIEEGFGSASRQQFDQDLDREDTIVTPSTSE
    WD-40 repeat domain is underlined. GTNALQEGGLLLKGVSVLKNILASSFGPIFSPNDTKVLK
    KVELLQGISWHRHKHILAFISGSNQVTVHDFQDPEWRES
    SLLVSESQRGIEALEWRPNGGTTLSVACRGGICIWSASY
    PGSVAPVRSGVASFLGTSTRGSSVRWTLVDFLQIPGGKA
    VTALSWSPTGRLLASASREDSSFTIWDVAQGVGTPLRRG
    LGGISLLKWSPTGDYLFSAKPNGTFYLWETNTWTLEQWS
    SSGGCVISATWGPDGRMLFMAFSESTTLGSLHFAGRPPS
    LDAHLLPMELPEIGSITGGFGNIEKMAWDGCGERLAVSY
    TGGDLMYVGLIAIYDTRRTPFISASLVGFIRGPGEQVKP
    LAFAFHDKFKQGPLLSVCWSSGLCCTYPLIFRAH
    236 The amino acid sequence of SEQ ID MEEENAKHTEETRQVQVRFTTKLQPALRVPTTSIAIPAH
    508. The conserved G-protein beta LTRYGLSDIVNTLLGNDKPQPFDFLVESELVRTSLEKLL
    WD-40 repeat domains are LIKGISAEKILNIEYILAVVPPKQEEPSLHDDWVSVVDG
    underlined. SYPNFIFSGSFDSIGRIWKGEGLCTHVLEGHRDAITSAA
    FIMPSDSSDSFINLATASKDRTLRLWQFKPNEHMTNGKM
    VRPYKLLKGHTSSVQTVSACPRRNLICSGSWDCSIKIWQ
    TAGEMDIESNAGSVKKRKLEDSTEQIISQIEASRTLEGH
    SQCVSSVVWLEKDTIYSASWDHSVRSWDVETGVNSLTVG
    CRKALHCLSIGGEGSALIAAGGADSVLRIWDPRMPGTFT
    PILQLSSHKSWITACKWHPKSRHHLISASHDGTLKLWDV
    RSKVPLTTLEAHKDKVLCADWWKEDCVISGGADSTLQIF
    SNLNLT
    237 The amino acid sequence of SEQ ID MNRLRSKRNHILELRLGQSEPEKEATLASNRSRGTNAPI
    509. The conserved RING-type zinc VVEDDDDVVVSSPRSFALARSSVSQRSSRIPIVNEEDLE
    finger is underlined. LRLGLAVTGRTSAEHNPRRRHGRVPPNKPIVLCDDAGEA
    DQSSSKKRRTGQQLSSDVQSDESKEVKLTCAICISTMEE
    ETSTICGHIFCKKCITNAIHRWKRCPTCRKKLAINNIIHR
    IYISSSTG
    238 The amino acid sequence of SEQ TD MEEPPPPAVLPSSEDTSIVSSHSFVNAPPTVPVGLDASI
    510. The conserved G-protein beta PQISTPGINQPGLTIPVPPEAAPLTASLVAASAGMPPAV
    WD-40 repeat domains are VPSFVRPAIVAHPSVMPPPSMPLAALPMPVASAVPVAAP
    underlined and the splicing factor HFPPSTPNDNSITPSMPVPTPIVASSSVPPSVTIPGIAP
    motif is in bold. LPFIAPIPVPSSRPVAPSPFMPPARPLGASVSVAMDVDN
    TDEQDQDADNKGESPSSSPDHPEDPSAAEYEITEESRKV
    RERQEQAIQELLLRRRAYALAVPTNDSSVRARLRRLNEP
    ITLFGEREMERRDRLRALMAKLDAEGQLEKLMKVQEEEE
    AAANVDAEEVQEMEGPQVYPFYTEGSQELLKARTEITKF
    SLPRAVSRLQRARRKREDPDEDEDEELKCVLQQSAQINM
    DCSEIGDDRPLSGCAFSSDGTLLATSAWSGVTKLWSVPN
    INKVATLKGHTERVTDVAFSPTNCHLATACADRTAMLWN
    SEGVLMKTYEGHLDRLARLAFHPSGLYLGTASFDKTWRL
    WDVNTGIELLLQEGHSRSVYGIAFQCDGSLAATCGLDGL
    ARIWDLRTGRSILALEGHVKPVLGIDFSPNGYHLATGSE
    DHTCRIWDLRKRQSVYIIPAHSHLVSQVKFEPQEGYFLV
    TASYDSTAKVWSARDFKSIKVLAGHEAKVTSVDITADGQ
    YIATVSHDRTIKLWSSKNSTNDMNIG
    239 The amino acid sequence of SEQ ID MKRAYKLQEFVAHASNVNCLKIGKKSSRVLVTGGEDHKV
    511. The conserved G-protein beta NMWAIGKPNAILSLSGHSSAVESVTFDSAEALVVAGAAS
    WD-40 repeat domains are GTIKLWDLEEAKIVRTLTGHRSNCISVDFHPFGEFFASG
    underlined and the Trp-Asp (WD) SLDTNLKIWDIRRKGCIHTYKGHTRGVNSIRFSPDGRWV
    repeats signature is in bold. VSGGEDNIVKLWDLTAGKLMHDFKCHEGQIQCMDFHPQE
    FLLATGSADRTVKFWD LETFELIGSAGPETTGVRAMIFN
    PDGRTLLTGLHESLKVFSWEPLRCYDAVDVGWSKLADLN
    IHEGKLLGCSYNQSCVGVWVVDISRVGPYAAGNVSRTNG
    HNEAKLASSGHPSVQQLDNNLKTNMARLSLSHSTESGIK
    EPKTTTSLTTTEGLSSTPQRAGIAFSSKNLPASSGPPSY
    VSTPKKNSTSRVQPTTNFQTLSRPDIVPVIVPRSNSLRP
    ETTSDAKKEMNNFGRVVPSTVSTKSTDVIKSGSNRDESD
    KIDSINQKRMTGNDKTDLNIARAEQHVSSRLDNTNTSSV
    VCDGNQPAARWIGAAKFRRNSPVDPVVSPHDRSPTFPWS
    ATDDGVTCQPDRQVTAPELSKRVVEPGRARALVASWETR
    EKALTADTPVLVSGRPPTSPGVDMNSFIPRGSHGTSESD
    LTVSDDNSAIEELMQQHNAFTSILQARLTKLQVIRRFWQ
    RNDLKGAIDATGKMGDHSVSADVISVLIERSEIFTLDIC
    TVILPLLTRLLQSETDRHLTVAMETLLVLVKTFGDVIRA
    TISATPTIGVDLQAEQRLERCNLCYVELENIKQILVPLI
    RRGGAVAKSAQELSLALQEV
    240 The amino acid sequence of SEQ ID MAGSDENNPGVVGGAHVQEGLRVGAGKMGAGNVQQRRAL
    512. The conserved cyclin N- and SNINSNIIGAPPYPCAVNKRVLSEKNVNSENDLLNAAHR
    C-terminal family domains are PITRQFAAQMAYKQQLRPEENKRTTQSVSNPSKSEDCAI
    underlined. LDVDDDKMADDFPVPMFVQHTEAMLEEIDRMEEVEMEDV
    AEEPVTDIDSGDKENQLAVVEYIDDLYMFYQKAEASSCV
    PPNYMDRQQDINERMRGILIDWLIEVHYKFELMDETLYL
    TVNLIDRFLAVQPVVKKKLQLVGVTAMLLACKYEEVSVP
    VVEDLILISDRAYSRKEVLEMERLMVNTLHFNMSVPTPY
    VFMRRFLKAAQSDKKLELLSFFIIELSLVEYDMLKFPPS
    LLAASAIYTALSTITRTKQWSTTCEWHTSYSEEQLLECA
    RLMVTFHQRAGSGKLTGVHRKYSTSKFGHAARTEPANFL
    LDFRL
    241 The amino acid sequence of SEQ ID MQAPREGKSAAAIVGMGKYMKKSKAIPRDVSLLEASPRS
    513. The conserved cyclin- PSATGVRTRAKTLASRRLRRASQRRPPPPAAAAAAAAPS
    dependent kinase inhibitor domain LDASPCPFSYLQLRSRRLRRPRLAPSPEARIDEGPAGSG
    is underlined. SRGSRDASCSARTASSSGGVEGEGACVGRGDRGNGGECV
    RDAAVDASYGENDLEIEDRDRSTRESTPCSLIRDSNANT
    PPGSTTRQQSSCTAHRTQMSILRSIPTSDEMEEFFAYAE
    QRQQRSFIEKYNFDIVKDRPLPGRFEWVQVIP
    242 The amino acid sequence of SEQ ID MDGHSSHLAAQNRSRGSQTPSPSHSAASASATSSIHLKR
    514. The conserved GCN5-related N- KLSAANASAASAAAAAAAAAAAADDHAPPFPPSSISADT
    acetyltransferase family domain is RDGALTSNDDLESISARGGGAGDDSDDDSDDEEEDDGDN
    underlined and the bromodomain is DGGSSLRTFTAARLENVGPAAARNRKIKAESNATVKVEK
    in bold. EDSAKDGGNGAGVGALGPAATSGAGSGSGTVPKEDAVKI
    FTENLQASGAYSAREENLKREEEAGRLKFECLSNDGVDD
    HMVWLIGLKNIFARQLPNMPKEYIVRLVMDRNHKSVMVI
    RRNLVVGGITYRPYASQKFGEIAFCAIKADEQVKGYGTR
    LMNHLKQHARDVDGLTHFLTYADNNAVGYFIKQGFTKEI
    YLDKDRWHGYIKDYDGGILMECKIDPKLPYTDLSTMVRR
    QRQAIDEKIRELSNCHIVYQGIDFQKRDAGVPQNTIKME
    DIPGLREAGWTPDQWGYSRFRGLSDQKRLTFFIRQLLKV
    LNDHSDAWPFKEPVDAREVPDYYDIIKDPMDLKTMTKRV
    ESEQYYVTLEMFIADVKRMFANARTYNSPDTIYFKIATR
    LEAHFQSKVQSNLQSGAGKIQQ
    243 The amino acid sequence of SEQ ID MFNGMMDPELFKLAQEQMNRMSPAELAKIQQQMMSNPEL
    515. The conserved TPR repeat MRMASESMKNMRPEDLRQAAEQLKHVRPEEMAEIGEKMA
    domain is underlined NASPEEIAAVRARADAQMTYEINAAKILKKEGNELHSQG
    RFKDASQKYLRAKNNLKGIPSSEGKNLLLACSLNLMSCY
    LKTRQYEECIKEGSEALACEEKNLKAFYRRGQAYRELGQ
    LKDAVSDLRKAHEISPDDETIAQVLRDTEESLTKEGGSA
    PRGVVIEEITEEDETLASVNHESPSEYSEKRHQESEDAH
    KGPINGDIMGQMTNSESLKALKGDPDAIRSFQNFISNAD
    PTTLAAMGAGNAGEVSPDLIKTASSMIGKMSAEELQKMI
    QLASSFPGENPYVTRNSDSNSNSFGNGSIPNVSPDMLKT
    ASDMMSKMSPDDLQRMFEMASSSRGKDPSLDANHASSSS
    GANLAANLNHILGESEPSSSYHIPSSSRNISSSPLSNFP
    SSPGDMQEQIRNQMKDPAMRQMFTSMMKNMSPEMMANMG
    KQFGLELSPEDAAKAQEAMSSLSPEMLDKMMRWADRAQR
    GVETAKKTKNWLLGRPGMILAICMLLLAVILHRLGFIGS
    244 The amino acid sequence of SEQ ID MIAAISWVPRGASKAVPEVAEPPSKEEIEEILKSGVVER
    516. The conserved G-protein beta SGDSDGEEDDENMDAVASEKADEVSTALSAADALGRISK
    WD-40 repeat domains are VTKAGSGFEDIADGLRELDMDNYDEEDEDVKLFSTGLGD
    underlined. LYYPSNDMDPYLKDKDDDDDTEEIEDLSIKPMDSLIVCA
    RTDDEVNLLEVYLLEPSLSDESNMYVHHEVVISEFPLCT
    AWLDCPIKGGDKGNFIAVGSMEPAIEIWDLDIIDAVEPC
    LVLGGQEELKKKKKKGKKASIKYKEGSHTDSVLGLAWNK
    EFRNILASASADRQVKIWDVAAGKCNITMEHHTDKVQAV
    AWNHHAPQVLLSGSFDHSVVMKDGRIPSHSGYRWSVTAD
    VESLAWDPHSEHFFVVSLEDGTVRGFDVRAAISNSASQS
    LPSFTLHAHEKAVSTISYNPAAPNLLATGSTDKMVKLWD
    LSNNQPSCIASRNPKAGAVFSVSFSEDSPLLLAIGGSKG
    RLEVWDTSSDAAVSRRFGKHGKPKTAEPGS
    245 The amino acid sequence of SEQ ID MKFCKKYQEYMQGQEGKKLPGLGFKKLKKILKRCRRRDS
    517. The conserved Zn-finger, RING LHSQKALQAVQNPRTCPAHCSVCDGSFFPSLLEEMSAVL
    domain is underlined, and the SPX, GCFNKQAQKLLELHLASGFQKYLMWFKGKLRGNHVALIQ
    N-terminal is in bold EGKDLVTYALINAIAIRKILKKYDKIHLSTQGQAFKSQV
    QRMHMEILQSPWLCELIAFHINVRETKANSGKGHALFEG
    CSLVVDDGKPSLSCELFDSIKLDIDLTCSICLDTVFDSV
    SLTCGHIYCYMCACSAASVTIVDGLKAAEPKEKCPLCRE
    ARVFEGAVHLDELNILLSRSCPEYWAERLQTERVERVRQ
    AKEHWESQCRAFMGVE
    246 The amino acid sequence of SEQ ID MVSTQSTRENPSIFFPPPLKPWLLPVVLSLSLSRQLGMA
    518. The conserved G-protein beta AAAAASLPFKKNYRSSQALQQFYAGGPFAVSSDGSFIAC
    WD-40 repeat domains are NCGDSIKIVDSSNASLRPSIDCGSDTITALSLSPDGKLL
    underlined. FSAGHSRQIRVWDLSTSTCLRSWKGHDGPVMSMACPVSG
    GLLATGGADRKVMVWDVDGGFCTHFFKGHDGVVSTVLFH
    PDSNRSLLFSGSDDGTIRVWDLLAKKCASTLRGHDSTVT
    SLAFSEDGLTLLAAGRDKVVSLWDLHNYACKKTIPMYEV
    LESVCVIHSGTVLASQLGLDDQLKVTKESAQNIHFITVG
    ERGILRIWKSEGSVCLFKQEHSDVTVISDEDDSRSGFTA
    AVMLPLDQGLLCVTADQQFLFYYPEKHPEGIFSLTLCRR
    LVGYNEEIVDMKFLGEEENFLAVATNLEQVRVYELASMS
    CSYVLAGHTETVLCLDTCISSSGRTLIVTGSKDNSVRLW
    DSESRHCIGVGVGHMGAVGAVAFSRKRQDFFVSGSSDRT
    LKVWSLDGISEDGVDSTNLKAKAVVAAHDKDINSVAVAP
    NDSLVCSGSQDRTACVWRLPDLVSVVVLKGHKRGIWSVE
    FSPVDQCVLTASGDKTVKIWAISDGSCLKTFEGHVSSVL
    RASFLTRGTQFVSCGADGLVKLWTVRTNECIATYDQHSD
    KVWALAVGKKTEMLATGGSDAVVNLWYDSTASDKEDAFR
    KEEEGVLKGQELENAVSDADYTKAIELALELRRPHKLFE
    LFSELCRTREVGDRVERILSALSGEEVCLLLEYIREWNA
    KPKLCHVAQSVLSQVFRILSPTEIVEIKGIGELLEGLIP
    YSQRHFSRIDRLVRSTYLLDYTLTGMSVIEPEADRSAVN
    DGSPDKSGLEKLEDGLLGENVGEEKIQNKEELESSAYKK
    RKLPRSKDRSKKKSKNVVYADAAAISFRA
    247 The amino acid sequence of SEQ ID MDSAPRRKSGGINLPSGMSETSLRLDGFSGSSSSFRAIS
    519. The conserved G-protein beta NLTSPSKSSSISDRFIPCRSSSRLHTFGLVERGSPVKEG
    WD-40 repeat domains are GNEAYSRLLKAELFGSDFGSLSPAGQGSPMSPSKNMLRF
    underlined. KTESSGPNSPFSPSILRQDSGFSSEASTPPKPPRKVPKT
    PHKVLDAPSLQDDFYLNLVDWSSQNTLAVGLGTCVYLWS
    ASNSKVTKLCDLGPNDGVCAVQWTREGSYISIGTSLGQV
    QIWDGTQCKRVRTMGGHQTRTGVLAWNSRILASGSRDRV
    ILQHDLRVPNEFIGKLVGHKSEVCGLKWSHDDRELASGG
    NDNQLLVWNQHSQQPVLKLTEHTAAVKAIAWSPHQNGLL
    ASGGGTADRCIRFWNTTNGHQTSSVDTGSQVCNLAWSKN
    VNELVSTHGYSQNQIMVWKYPSMAKVATLTGHSLRVLYL
    AMSPDGQTIVTGAGDETLRFWNVFPSAKAPAPVKDTGLW
    SLGRTHIR
    248 The amino acid sequence of SEQ ID MEDEAEIYDGVRAQFPLTFGKQSKPQTSLESVHSATRRG
    520. The conserved G-protein beta GPAPAPAPASSSSLPSTTSPSAAGGAGKSSGLPSLSSSS
    WD-40 repeat domains are TAWLEGLRAGNPRAGREAGIGSRGGDGEDGGRAMIGPPR
    underlined. PPPGFSANDDGGGEDDDDDGDGVMVGPPPPPPGNLGDGD
    DDEEEEEAMIGPPRPPVVDSDEEEEEEEEENRYRLPLSN
    EIVLKGHNKIVSALAVDPTGSRVLSGSYDYTVRMFDFQG
    MNSRLSSFRDFEPVEGHQVRNLSWSPTADRFLCVTGSAQ
    AKIYDRDGLTLGEFVKGDMYIRDLKNTKGHITGLTWGEW
    HPKTKETILTSSEDGSLRIWDVNDFKSQKQVIKPKLARP
    GRVPVTTCTWDREGKCIAGGIGDGSIQIWNLKPGWGSRP
    DIHVEQAHADDITGLKFSSDGKILLTRSFDDSLKVWDLR
    LMKNPLKVFEDLPNHYAQTNIACSPDEQLFLTGTSVERE
    STIGGLLCFFDRSKLELVSRIGISPTCSVVQCAWHPRLN
    QIFATSGDKSQGGTHVLYDPTLSERGALVCVARAPRKKS
    VDDFELKPVIHNPHALPLFRDQPSRKRQREKILKDPLKS
    HKPELPMNGPGHGGRVGASKGSLLTQYLLKQGGMIKETW
    MDEDPREAILKHADAAEKNPKFTRAYAETQPDPVFAKSD
    SEDEDK
  • TABLE 12
    Eucalyptus in silico Data.
    SEQ ConsID
    ID eucSpp Family 1 2 3 4 5 6 7 8 9 10 11 12
    1 3910 Cyclin- 0.25 0.11 0.20 0.73
    dependant
    protein
    kinase
    2 19213 Cyclin- 0.59 0.64
    dependant
    protein
    kinase
    3 36800 Cyclin- 0.11 0.36
    dependant
    protein
    kinase
    4 40260 Cyclin- 0.85
    dependant
    protein
    kinase
    5 41965 Cyclin- 0.35 0.86
    dependant
    protein
    kinase
    6 2906 Cyclin- 0.93 0.81
    dependant
    protein
    kinase
    7 1518 Cyclin- 0.08 0.28 0.08 0.06 0.11
    dependant
    protein
    kinase
    8 8078 Cyclin- 0.17 3.20
    dependant
    protein
    kinase
    9 9826 Cyclin- 0.36 0.23 0.15 0.04 0.24 0.43
    dependant
    protein
    kinase
    10 10364 Cyclin- 0.11 1.52 0.13
    dependant
    protein
    kinase
    11 11523 Cyclin- 0.15 0.06 0.15 2.40
    dependant
    protein
    kinase
    12 24358 Cyclin- 0.76 0.07 0.04 0.24
    dependant
    protein
    kinase
    13 39125 Cyclin- 0.23
    dependant
    protein
    kinase
    14 5362 Cyclin- 0.68 0.06 0.08 1.17
    dependant
    protein
    kinase
    15 44857 Cyclin- 0.68 0.06 0.08 1.17
    dependant
    protein
    kinase
    16 1743 Cyclin A 0.19 2.10 0.06 0.15
    17 12405 Cyclin A 0.06 0.59 2.84
    18 3739 Cyclin B 0.42 1.99 0.08 2.33
    19 22338 Cyclin B 0.86
    20 28605 Cyclin B 0.39 0.04 0.47
    21 41006 Cyclin B 0.71
    22 6643 Cyclin D 0.85 0.83 0.06 1.06 0.08 0.26
    23 45338 Cyclin D 2.03
    24 46486 Cyclin D 0.30
    25 12070 Cyclin- 0.24 0.82 0.06 0.26 0.92
    dependent
    kinase
    regulatory
    subunit
    26 6617 Histone 0.08 0.06 0.04 0.55 0.51 0.26
    acetyltransferase
    27 7827 Histone 2.27 0.11 0.04
    acetyltransferase
    28 8036 Histone 1.16
    acetyltransferase
    30 1596 Histone 0.17 0.16 0.08 2.98 0.88 0.26 0.98 0.71
    deacetylase
    31 5870 Histone 0.19 0.17 0.12 5.43
    deacetylase
    32 6901 Histone 1.21 0.08 2.01 1.16 0.08
    deacetylase
    33 6902 Histone 0.08 0.11 1.21 0.47
    deacetylase
    34 7440 Histone 0.48 1.23 0.15 0.22 0.48 0.20 2.02
    deacetylase
    35 8994 Histone 0.09 0.15
    deacetylase
    36 24580 Histone 0.42 1.22
    deacetylase
    37 37831 Histone 0.08 0.22 0.40 1.19 0.12
    deacetylase
    38 34958 MAT1 CDK- 0.15 0.23
    activating
    kinase
    assembly
    factor
    39 22967 Peptidyl- 0.72 0.69
    prolyl cis-
    trans
    isomerase
    40 8599 Peptidyl- 0.46 0.08 0.50 0.17 0.51 0.28 3.01
    prolyl cis-
    trans
    isomerase
    41 9919 Peptidyl- 0.51 0.35 0.06 0.15 0.43 4.24
    prolyl cis-
    trans
    isomerase
    42 15820 Peptidyl- 0.04 6.78
    prolyl cis-
    trans
    isomerase
    43 8327 Peptidyl- 0.06 0.04 6.86
    prolyl cis-
    trans
    isomerase
    44 4604 Peptidyl- 0.68
    prolyl cis-
    trans
    isomerase
    45 966 Peptidyl- 0.59 1.02 0.54 0.69 0.50 0.93 0.59 0.95 18.65
    prolyl cis-
    trans
    isomerase
    46 1037 Peptidyl- 0.59
    prolyl cis-
    trans
    isomerase
    47 4603 Peptidyl- 0.17 0.17 1.24 0.04 0.34
    prolyl cis-
    trans
    isomerase
    48 5465 Peptidyl- 1.21 0.08 0.66 0.11 0.29 0.16 6.99
    prolyl cis-
    trans
    isomerase
    49 6571 Peptidyl- 0.51 0.08 0.41 0.08 1.14
    prolyl cis-
    trans
    isomerase
    50 6786 Peptidyl- 0.42 0.33 0.06 0.41 0.04
    prolyl cis-
    trans
    isomerase
    51 7057 Peptidyl- 0.42 0.11 0.04
    prolyl cis-
    trans
    isomerase
    52 8670 Peptidyl- 1.56 0.39 0.20 0.12
    prolyl cis-
    trans
    isomerase
    53 9137 Peptidyl- 0.04 0.59
    prolyl cis-
    trans
    isomerase
    54 10285 Peptidyl- 0.60 1.16 0.04 0.04 0.45
    prolyl cis-
    trans
    isomerase
    55 10600 Peptidyl- 0.16 0.17 0.06 0.46
    prolyl cis-
    trans
    isomerase
    56 11551 Peptidyl- 0.08 0.06 0.04 0.08 1.89
    prolyl cis-
    trans
    isomerase
    57 20743 Peptidyl- 0.76
    prolyl cis-
    trans
    isomerase
    58 23739 Peptidyl- 0.59
    prolyl cis-
    trans
    isomerase
    60 31985 Peptidyl- 1.99
    prolyl cis-
    trans
    isomerase
    61 32025 Peptidyl- 0.99
    prolyl cis-
    trans
    isomerase
    62 32173 Peptidyl- 1.99
    prolyl cis-
    trans
    isomerase
    64 9143 Retinoblastoma 0.90 0.15
    related
    protein
    65 349 WD40 repeat 0.24 0.34 0.08 0.17 0.22 0.33 0.08 0.25 2.24
    protein
    66 575 WD40 repeat 0.25 0.94 0.31 0.34 0.11 0.16 0.47 1.87
    protein
    67 804 WD40 repeat 0.15 0.34 0.39 0.33 0.39 1.82
    protein
    68 805 WD40 repeat 0.97 0.51 4.66 0.23 0.17 0.77 0.33 1.07 0.24 4.43
    protein
    69 806 WD40 repeat 0.83 0.04
    protein
    70 2248 WD40 repeat 0.08 0.08 1.92 0.06 0.08 0.91
    protein
    71 3203 WD40 repeat 0.34 0.18 0.15 0.17 0.11 0.30 0.04 0.72
    protein
    72 3209 WD40 repeat 0.08 0.15 0.17 0.12 0.61
    protein
    73 4429 WD40 repeat 0.08 1.16 0.08 0.13
    protein
    74 4607 WD40 repeat 0.76 0.54 0.06 0.07
    protein
    75 4682 WD40 repeat 0.08 0.28 0.23 1.13 0.08 0.12
    protein
    76 5786 WD40 repeat 0.08 0.06 0.46 0.08 0.13
    protein
    77 5887 WD40 repeat 1.61 1.23 0.08 0.06 0.15 0.28 1.41
    protein
    78 5981 WD40 repeat 0.08 0.37
    protein
    79 6766 WD40 repeat 0.24 0.08 1.31 0.51 0.06 0.74 0.51 0.28
    protein
    80 6769 WD40 repeat 0.93 0.17 0.12 2.28
    protein
    81 6907 WD40 repeat 0.25 0.17 0.06 0.45 0.32 0.47 1.67
    protein
    82 7518 WD40 repeat 0.91 0.28 0.15 0.55 0.59
    protein
    83 7717 WD40 repeat 0.47 0.38
    protein
    84 7718 WD40 repeat 0.24 1.88 0.08 0.22 0.04 0.92
    protein
    85 7741 WD40 repeat 1.42 0.11 0.47
    protein
    86 7884 WD40 repeat 1.33 0.15 0.24
    protein
    87 8258 WD40 repeat 0.72 0.19 0.23 0.87 0.15 0.08 0.08
    protein
    88 8465 WD40 repeat 0.47 0.08 1.75
    protein
    89 8616 WD40 repeat 0.57 0.08 0.69 0.16 0.13
    protein
    90 8690 WD40 repeat 0.26 0.08 0.35 1.39 0.34 0.32 2.13 0.80
    protein
    91 8708 WD40 repeat 0.57 0.04
    protein
    92 8850 WD40 repeat 0.09 0.06 0.27 2.03
    protein
    93 9072 WD40 repeat 1.21 0.17 0.48
    protein
    94 9465 WD40 repeat 0.24 0.72 0.33 0.15
    protein
    95 9472 WD40 repeat 0.36 1.99 0.11 0.61 6.90
    protein
    96 9550 WD40 repeat 0.90 0.11 1.78
    protein
    97 10284 WD40 repeat 0.24 0.08 1.82 1.22 0.16 0.47 0.28
    protein
    98 10595 WD40 repeat 0.16 0.17 0.11 6.52 0.85
    protein
    99 10657 WD40 repeat 0.06 0.12
    protein
    100 12636 WD40 repeat 0.06 0.65
    protein
    101 12748 WD40 repeat 1.50 0.08 0.06 1.67 0.04 0.38
    protein
    102 12879 WD40 repeat 0.08 0.33 0.06 0.04 0.08 2.00
    protein
    103 15515 WD40 repeat 0.35 0.30
    protein
    104 15724 WD40 repeat 0.25 0.33 0.15 0.47 0.04 0.39
    protein
    105 16167 WD40 repeat 0.24 0.52
    protein
    106 16633 WD40 repeat 1.96 0.12 0.42
    protein
    107 17485 WD40 repeat 0.65
    protein
    108 18007 WD40 repeat 0.12
    protein
    109 20775 WD40 repeat 0.17 0.08
    protein
    110 23132 WD40 repeat 2.42
    protein
    111 23569 WD40 repeat 0.91 0.91
    protein
    112 23611 WD40 repeat 4.15
    protein
    113 24934 WD40 repeat 0.34 0.04
    protein
    114 25546 WD40 repeat 0.09
    protein
    115 30134 WD40 repeat 0.07
    protein
    116 31787 WD40 repeat 0.19 1.19
    protein
    117 34435 WD40 repeat 0.35 0.08
    protein
    118 34452 WD40 repeat 1.44 0.20 0.25
    protein
    119 35789 WD40 repeat 0.20
    protein
    120 35804 WD40 repeat 0.19 0.27 0.08
    protein
    121 43057 WD40 repeat 0.30 0.57
    protein
    122 46741 WD40 repeat 0.46
    protein
    123 47161 WD40 repeat 1.78
    protein
    235 6366 WD40 repeat 0.08 0.68 0.23 0.93 0.11 0.36 0.83 0.24 0.94
    protein
    236 17378 WD40 repeat 0.65 0.12 0.08
    protein
    252 45414 Cyclin B 3.13
    253 44328 Cyclin- 0.38
    dependant
    kinase
    inhibitor
    254 15615 Histone 0.22 0.04
    acetyltransferase
    255 17239 Peptidyl- 0.08 0.50 0.08
    prolyl cis-
    trans
    isomerase
    256 18643 WD40 repeat 0.04 0.90
    protein
    257 19127 WD40 repeat 0.04 0.89
    protein
    258 22624 WD40 repeat 1.16
    protein
    259 32424 WD40 repeat 0.50
    protein
    260 37472 WD40 repeat 0.08 0.17
    protein
    In Table 12, the following numbers 1-12 represent the following tissues:
    1 is bud reproductive;
    2 is bud vegetative;
    3 is cambium;
    4 is fruit;
    5 is leaf 6 is phloem;
    7 is reproductive;
    8 is root;
    9 is sap vegetative;
    10 is stem;
    11 is whole; and
    12 is xylem.
  • TABLE 13
    Pine in silico data.
    ConsID
    SEQ pinus
    ID Radiata Family 1 2 3 4 5 6 7 8 9 10 11 12
    124 1766 Cyclin- 1.02 0.05 1.58 0.15 0.22 0.22 0.18 2.16 4.91
    dependant
    protein
    kinase
    125 2927 Cyclin- 0.16 0.19 0.11 0.14 0.04 0.36 0.38 0.17
    dependant
    protein
    kinase
    126 7642 Cyclin- 0.22 0.21 0.05 0.07
    dependant
    protein
    kinase
    127 13714 Cyclin- 0.11 0.11
    dependant
    protein
    kinase
    128 16332 Cyclin- 0.54 0.26 0.14 0.04 0.91
    dependant
    protein
    kinase
    129 21677 Cyclin- 0.05 0.14 0.17
    dependant
    protein
    kinase
    130 27562 Cyclin- 0.41
    dependant
    protein
    kinase
    131 1504 Cyclin- 0.16 0.36 0.35 0.21 0.54 0.09 0.65
    dependant
    protein
    kinase
    132 15211 Cyclin- 0.13 0.15 0.19 0.19
    dependant
    protein
    kinase
    133 20421 Cyclin- 0.04 0.05 0.95
    dependant
    protein
    kinase
    134 3187 Cyclin- 0.34 0.15 0.04 0.18 0.38
    dependant
    protein
    kinase
    135 15661 Cyclin- 0.04 0.13
    dependant
    protein
    kinase
    136 13874 Cyclin A 0.31 0.27 0.15 0.05
    137 14615 Cyclin A 0.16 0.15
    138 4578 Cyclin B 0.47 0.14 0.13 0.22 0.74 0.38
    139 23387 Cyclin B 0.29 0.26 0.17
    140 6970 Cyclin D 0.14 0.27 0.04
    141 10322 Cyclin D 0.16 0.19 0.06 0.14 1.12 1.36
    142 22721 Cyclin D 0.27 0.36
    143 23407 Cyclin D 0.15 0.26 0.31
    144 1945 Cyclin- 0.28 0.55 0.41 0.16 1.62 5.02 0.22 0.72 0.39 3.06
    dependent
    kinase
    regulatory
    subunit
    145 8233 Cyclin- 0.21
    dependent
    kinase
    regulatory
    subunit
    146 8234 Cyclin- 0.16 0.11
    dependent
    kinase
    regulatory
    subunit
    147 22054 Cyclin- 0.05 0.22 0.18
    dependent
    kinase
    regulatory
    subunit
    148 12137 Histone 0.06 1.51 0.19
    acetyltransferase
    149 12582 Histone 0.64 0.15 1.09 0.33 0.63
    acetyltransferase
    150 15285 Histone 0.21 0.12 0.70 0.14
    acetyltransferase
    151 17229 Histone 0.94 0.16
    acetyltransferase
    152 20724 Histone 0.04 0.19 0.19
    acetyltransferase
    153 4555 Histone 0.16 0.14 0.97 0.14 0.89 0.89
    deacetylase
    154 4556 Histone 0.14
    deacetylase
    155 5729 Histone 0.31 0.28 0.22 0.58 0.22 2.00 0.48 0.07 0.04 2.73 1.46
    deacetylase
    156 7395 Histone 0.14 0.14 0.19 0.93 0.04 0.14 1.33
    deacetylase
    157 9503 Histone 0.11 0.14
    deacetylase
    158 11283 Histone 0.19 0.15 0.96 1.35
    deacetylase
    159 12322 Histone 0.16 0.06 0.11 0.04 0.05 0.29
    deacetylase
    161 23236 Histone 0.13 0.11
    deacetylase
    162 171 Peptidyl- 0.07 0.46
    prolyl
    cis-trans
    isomerase
    163 172 Peptidyl- 0.19 0.11 0.18 0.11 0.46
    prolyl
    cis-trans
    isomerase
    164 1480 Peptidyl- 2.51 4.20 0.88 2.97 1.58 3.53 7.36 1.33 2.74 0.72 6.62 10.14
    prolyl
    cis-trans
    isomerase
    168 1692 Peptidyl- 0.16 0.22 0.65 0.61 0.26 0.29 0.18 1.28 0.34
    prolyl
    cis-trans
    isomerase
    169 5313 Peptidyl- 0.14 0.07 0.37 0.17
    prolyl
    cis-trans
    isomerase
    170 6362 Peptidyl- 0.14 0.33 0.05 0.06 0.60 0.04 2.92 0.68
    prolyl
    cis-trans
    isomerase
    171 6493 Peptidyl- 0.42 0.11 0.21 0.11 0.04 0.25 0.32
    prolyl
    cis-trans
    isomerase
    172 6983 Peptidyl- 0.61 0.13 0.04
    prolyl
    cis-trans
    isomerase
    174 7665 Peptidyl- 0.11 0.39 0.05 0.62 0.25
    prolyl
    cis-trans
    isomerase
    175 12196 Peptidyl- 0.19 0.15 0.14 0.16
    prolyl
    cis-trans
    isomerase
    176 13382 Peptidyl- 0.25 0.06 0.07 0.04 0.87 0.15
    prolyl
    cis-trans
    isomerase
    177 16461 Peptidyl- 0.19 0.15 0.15 0.04 0.04 0.74
    prolyl
    cis-trans
    isomerase
    178 17611 Peptidyl- 0.24 0.11 0.27 0.41 0.99
    prolyl
    cis-trans
    isomerase
    179 19776 Peptidyl- 0.13 0.07 0.16 0.05 0.61
    prolyl
    cis-trans
    isomerase
    180 20659 Peptidyl- 0.15 0.19
    prolyl
    cis-trans
    isomerase
    181 22559 Peptidyl- 0.11 0.14 0.20
    prolyl
    cis-trans
    isomerase
    182 24188 Peptidyl- 0.23
    prolyl
    cis-trans
    isomerase
    183 27973 Peptidyl- 1.01
    prolyl
    cis-trans
    isomerase
    184 1353 WD40 0.44 0.05 0.73 0.11 1.07 0.70 1.32
    repeat
    protein
    185 1978 WD40 0.14 0.05 0.44 0.11 0.21 0.27 0.36 1.46 0.82
    repeat
    protein
    186 2810 WD40 0.42 0.79 0.11 0.39 0.27 0.36 1.69 1.03
    repeat
    protein
    187 2811 WD40 0.14 0.09 0.14
    repeat
    protein
    188 2812 WD40 0.15 0.18 0.04 0.16
    repeat
    protein
    189 3514 WD40 0.63 0.06 0.14 0.18 0.48 0.56
    repeat
    protein
    190 4104 WD40 0.14 0.25 0.27 0.37 0.36 0.19 0.18 0.39 0.53
    repeat
    protein
    191 5595 WD40 0.14 0.25 0.15 0.14 0.07 0.23
    repeat
    protein
    192 5754 WD40 0.31 0.14 0.06 0.07 0.16 0.10 0.16
    repeat
    protein
    193 6463 WD40 0.16 0.56 0.22 0.43 0.81 0.53 0.21 0.08 1.00 0.70
    repeat
    protein
    194 6665 WD40 0.31 0.28 0.45 0.44 0.96 0.07 3.37 2.68
    repeat
    protein
    195 6750 WD40 0.14 0.59 0.05 0.37 0.42 0.04 0.18 0.52
    repeat
    protein
    196 7030 WD40 0.31 0.40 0.54 0.45 0.37 0.07 1.58 3.41
    repeat
    protein
    197 7854 WD40 0.11 0.14 0.05
    repeat
    protein
    198 7917 WD40 0.22 0.39 0.13 0.15 0.18 0.56
    repeat
    protein
    199 7989 WD40 0.11 0.04 0.11
    repeat
    protein
    200 8506 WD40 0.47 0.33 0.11 0.86 0.19 1.28 0.04 1.23 3.12
    repeat
    protein
    201 8692 WD40 0.21 0.06 0.11 0.15 0.10 0.87
    repeat
    protein
    202 8693 WD40 0.11 0.80 0.25 0.14 0.18 0.53 0.31
    repeat
    protein
    203 9170 WD40 0.16 0.11 0.05 0.05
    repeat
    protein
    204 9408 WD40 0.33 0.05 0.41 0.15 0.14 0.41 0.33
    repeat
    protein
    205 9522 WD40 0.11 0.18
    repeat
    protein
    206 9734 WD40 0.11 0.05 0.11 0.15 0.07 0.25 0.11
    repeat
    protein
    207 9815 WD40 0.11 0.18 0.14
    repeat
    protein
    208 10670 WD40 0.40 0.16 0.11 0.16 0.34 0.31
    repeat
    protein
    209 11297 WD40 0.53 0.15 0.16 0.05
    repeat
    protein
    210 13098 WD40 0.19 0.11 0.54 0.31 0.14 0.26 1.85 0.14
    repeat
    protein
    211 13172 WD40 0.04
    repeat
    protein
    212 13589 WD40 0.11 0.06 0.21 0.05 0.37
    repeat
    protein
    213 13608 WD40 0.11 0.04 0.59 0.33
    repeat
    protein
    214 14299 WD40 0.16 0.05 1.09 0.38
    repeat
    protein
    215 14498 WD40 0.21 0.44 0.30
    repeat
    protein
    216 14548 WD40 0.16 0.11 0.11 0.82
    repeat
    protein
    217 14610 WD40 0.16 0.27
    repeat
    protein
    218 16090 WD40 0.43 0.04 0.37 0.85
    repeat
    protein
    219 16722 WD40 0.10
    repeat
    protein
    220 16785 WD40 0.05 0.13 0.38 0.50
    repeat
    protein
    221 17094 WD40 0.29 0.15 0.24 0.81
    repeat
    protein
    222 17527 WD40 0.04 0.10
    repeat
    protein
    223 17591 WD40 0.14 0.10
    repeat
    protein
    224 17769 WD40 0.39
    repeat
    protein
    225 18047 WD40 0.05 0.22 0.98 0.15 2.68 0.07 0.19 0.80
    repeat
    protein
    226 18414 WD40 0.16 0.15 0.34 0.23 0.19
    repeat
    protein
    227 18986 WD40 0.41 0.15
    repeat
    protein
    228 19479 WD40 0.05 0.28 0.32
    repeat
    protein
    229 20144 WD40 0.43 0.29 0.05
    repeat
    protein
    230 22480 WD40 0.15 0.27
    repeat
    protein
    231 23079 WD40 0.13 0.04
    repeat
    protein
    232 26739 WD40 0.15 0.18
    repeat
    protein
    233 26951 WD40 0.21 0.20
    repeat
    protein
    234 26529 WEE1-like 0.04 0.18
    protein
    237 888 WD40 0.11 0.18
    repeat
    protein
    238 14166 Cyclin- 0.16 0.05 0.05
    dependant
    kinase
    inhibitor
    239 3189 Cyclin- 0.06
    dependant
    protein
    kinase
    240 9356 Histone 0.11 0.22 0.46
    acetyltransferase
    241 65 Histone 0.16 0.22 0.27 0.22 0.24 0.34
    deacetylase
    242 14197 Histone 0.16 0.33 0.05
    deacetylase
    243 9081 Peptidyl- 0.11 0.05 0.29 0.26 0.69
    prolyl
    cis-trans
    isomerase
    244 13417 Peptidyl- 0.06 0.59
    prolyl
    cis-trans
    isomerase
    245 5755 WD40 0.16
    repeat
    protein
    246 6670 WD40 0.14 0.05
    repeat
    protein
    247 7027 WD40 0.14 0.15 1.30 0.15
    repeat
    protein
    248 7276 WD40 0.14 0.11 0.05
    repeat
    protein
    249 7390 WD40 0.31 0.14 0.11 0.44 1.29 0.38
    repeat
    protein
    250 12648 WD40 0.05 0.06 0.05 0.94
    repeat
    protein
    251 13171 WD40 0.19 0.63 0.19 0.34
    repeat
    protein
    Table 13, the following numbers 1-12 represent the following tissues:
    1 is bud reproductive;
    2 is bud vegetative;
    3 is callus;
    4 is cambium;
    5 is meristem vegetative;
    6 is phloem;
    7 is reproductive female;
    8 is reproductive male;
    9 is root;
    10 is vascular;
    11 is whole; and
    12 is xylem.
  • TABLE 14
    Oligo Table.
    Oligo
    SEQ
    ID Oligo ID Microarray Oligo Seq
    521 Euc_003910_O_4 GATTTTAAGTAACTCAATTAGCAGTTCCAACATTAAACCATTATTATTACCCCTTTTATC
    522 Euc_019213_O_1 CTCAAAAAGTACTTGGATGCGTGCGGTGACAACGGACTCGAACCGTACACTGTCAAATCT
    523 Euc_036800_O_4 TTGTCAAGTTGCAGGACGTAGTGCACAGTGAGAGGCGTCTATATCTAGTTTTTGAGTACT
    524 Euc_040260_O_1 GAAGAAATTATATAACTAGATACAAGGTTAGCTAGGTATATAATAGCGGTACAAGTCTTT
    525 Euc_041965_O_1 GGACAAATCAAGTAGAACTTCTCTCGGCAGCATCAGTTTTTCTAATCCATGCCTTGTTGC
    526 Euc_002906_O_1 CTCAGTTCTGATAATGCCTCGGATATATGGCCGAGTGTTCGCTGGACGGCCTCTTATGTT
    527 Euc_001518_O_3 GGAGATTCTGAACTGCAACAGCTCCTACACATTTTCAGACTGTTGGGTACTCCAAATGAA
    528 Euc_008078_O_2 GACTGGTAAAATCGTTGCACTAAAAAAGGTCCGGTTTGACAACTTGGAACCTGAAAGCGT
    529 Euc_009826_O_4 AAACACCAATCTATCAACACTGTCGAGTTTAGTCACTAGTAGAACCGGAGATAACAAACA
    530 Euc_010364_O_1 CTATGATCCTGAGCGCAAGCAAGTTATGACCAATAGAGTCGTTACACTATGGTACCGAGC
    531 Euc_011523_O_1 TGTTGTGAAGGTAGTTATAGCCATCGATTAGACAGTGATTAAAGTAGTACCCGTGCCAAT
    532 Euc_024358_O_2 CCACATACAAGAGTTGTTACGCTACACATCCTATACCATCAAAGGAACGTTGGAATGCCA
    533 Euc_039125_O_3 TATGATCGACACAAGCATTTTGTGTTGGAGCCTCAGCTAATTGTATGTCATCGAGTACTT
    534 Euc_005362_O_3 AAAATTTTTGCTACGGATAATGTTGTGAGGCGAGGCAGTCGAAATTACGGAGGTTGACTT
    535 Euc_044857_O_1 ATGCAGGGATCAAATTTGTGAGTACTACGTAAAATTTTGCTACGGAGGCGAGGCAGTCGA
    536 Euc_001743_O_1 GAAGAATACAGGCTCGTACCTGATACACTGTACCTGACTGTTAACTACATAGATCGGTAT
    537 Euc_012405_O_1 TCCACCCTAAATGCGATACGTGAAAAGTATAGACAACAGAAGGTAAACTATTCATTACTG
    538 Euc_003739_O_2 AGGCTTCTAGTTGCGTTCCCCCAAACTACATGGATCGGCAGCAGGATATTAATGAGCGGA
    539 Euc_022338_O_2 GAGAAAAATGACAGATTGATATCGATGATGATGACTGTCGTGTCATCAGTAGTGTGCTTT
    540 Euc_028605_O_5 TTTCCAATTGTAGTTCGTCTTTTATTGTAACAATAAATTGATAGATACTGATTCGAAATA
    541 Euc_041006_O_1 ACATTTATGCTAACTATAGGAGAACGGAGAATTGTAGCTGCGTCTCTGCTAACTACATGG
    542 Euc_006643_O_1 TTCTGGCTTAAAGGCTATTCTTTGTGCACAATGACCTGAGGGAGGTCTCGACAGACCACT
    543 Euc_045338_O_1 TTCATCCGGGTCCTGGTTATCATACTCTTATATATGTTGGGGAATAACGGTTCATATGTT
    544 Euc_046486_O_3 GGGTGTGCTTAATAGTTCTTATTAGTCTTAGCTTATTATCTTTGATTGGACATGCTATAA
    545 Euc_012070_O_2 CTTGCTAAGTAGACATGTTATATTTCTAATGCTTTGAGAACAATATTACAGTATAATTAG
    546 Euc_006617_O_2 AATCATCGACTAGACCGATGGTCAAAGTGGTAATCATGTAATTAAACGCGTTTGTCATTG
    547 Euc_007827_O_2 ATGGAAAAATCTATGGATATGAAGGATTGAAGATATCCGTCTGGGTAAGCTGTGTATCAT
    548 Euc_008036_O_3 TTATGATTTGAGAAAACCCTTGCAGGCTGCGATTTGCGGATCATGACAGCATAGTTTTGC
    549 Euc_001596_O_2 GTTTTGTTGTGAGGGCTTGGTAGGTTTTCATTATATTGTAATGTCGACGACAGAGATTTT
    550 Euc_005870_O_3 CCAATTAATGTTACTGCTCAAGCTGACGTACCTGCGAAAAAAGCACCAGTGACTGCTAAT
    551 Euc_006901_O_3 TGATGTCAAAACGTAGCTCTTTTTTGTGTGAGCTATCCTGCTAAATTAAACCTCAGCAAA
    552 Euc_006902_O_1 ACATGAGTATTATGAATACTTCGGTCCTGACTATACACTTCATGTTGCTCCGAGTAACAT
    553 Euc_007440_O_2 GAATTGGCGATCACAATCTACTGTAGTCAATACTCAAGTGGGAGGTGTAAATAGATTCCA
    554 Euc_008994_O_1 GATCATGTGTAATCAGTATATCAGGTTAGAAACAGTACTCTTGAGCTTAGCGGGCACTGT
    555 Euc_024580_O_2 TCCTGTGAAGGTGGTCGACTCAATCAAAAGGTACCTTGTAGATAAGGTACCTTTTCTCAA
    556 Euc_037831_O_5 GCATTTTATACGACGGATAGAGTCATGACCGTATCTTTCCATAAGTTTGGGGACTTCTTC
    557 Euc_034958_O_3 CCTCGTTTCTTTGCGGTTCGGACGCATCATGGATGTATCTCCAAAGAGTAATCTGTCGAT
    558 Euc_022967_O_2 AATTCAGATCTATTAGTGAAAGTTGGCATGAGTCTCAATCTTAGGGGAATACAGTACGGA
    559 Euc_008599_O_3 TGATATGAGTATCATAACTCGGATGGTGACAACTTTGTACTACGGTCGGCACCGGTAGAT
    560 Euc_009919_O_1 CATATACAATCTTAGTGGATTAGCTGAGGTCGAAACTGACAAGAGTGATCGCCCGTTGGA
    561 Euc_015820_O_2 CATGGCTAACGCTGGCCCTAGCACTAATGGGAGCCAATTTTTCATATGCACTGTAAAGAC
    562 Euc_008327_O_2 AACAAAGTCTACCTTGACATTAGCATCGGTAACCCTGTCGGGAAACTAGTCGGAAGAATT
    563 Euc_004604_O_2 TGTGCTTGGATATACTGTATAAGCATTCTATATTATGCTTGTTGGCTTCGTTTTGAGGGA
    564 Euc_000966_O_1 TTAACGTCGACCGCTTCTCTGCCCCTTGAATTTTCCCGAGAAAACCAGGAACCTGCCAAA
    565 Euc_001037_O_1 TGTTGAATACGATGTATTATAATGTTGGTGTCTTGGTGAAATACAGAATTATGCTTGCGT
    566 Euc_004603_O_2 ATCGCTGTGGCTGATCTCGTCGCTCCGGCTTTTCATAAAAATCATGGCTGAGGCAATCGA
    567 Euc_005465_O_2 CTCGCAACCCTATATCTCGCTCAGGCGAAGAAGTCTGAGGATTTGAAAGAGGTGACTCAC
    568 Euc_006571_O_1 TGTTTTTGGGTACACGCAGTTAGGATAACTAGCATGAAAGCCCGATCCCGCATATACAGG
    569 Euc_006786_O_2 GAGGACTAGCCGGAACTTCATCGAACTCTCTCGGAGGGGTTACTACGATAACGTCAAGTT
    570 Euc_007057_O_1 GATGGCTAGCACTGTGTAGAAAGGTGAATTTAAAGTACTTGTCTACACTGCTTATTAAAT
    571 Euc_008670_O_2 TGAGACTGTCTTGGCGTGTATTTTGGAATAAACTATTATCACGTTTTGTTAAATATAATA
    572 Euc_009137_O_3 TTACAAAATGGCTCTCAGAAAGTATCGAAAGGCCCTGCGCTATCTGGATATCTGCTGGGA
    573 Euc_010285_O_2 AATTTTATGTTTGCTACTGCTTAGTGCTTAATGGACTTGCGTAGGTATTCAAATTACAGA
    574 Euc_010600_O_1 TGGAACCGTGGTATCGGCTGACGTTATCCGTGATTTTAAGACTGGAGATAGTTTATGCTA
    575 Euc_011551_O_2 CTTTGATGTATCCTCAGTGTACTGCTTTTAGCTATGTATAGATCGAGTCAACTCATTGAA
    576 Euc_020743_O_3 TTTTTATTATTTACCTTCGCCTTTACGCTGCATACGTTAATAGGTTATTATTTCCTTCAA
    577 Euc_023739_O_1 ATTTGTCCATGACAATCGTAGTCGAAGACACGATACGCTCTTAGATGGTACGGAAATCTG
    578 Euc_031985_O_2 TGAATAGAGATAACTTTTCTGAGTGTGAATTGGATATTACGTTGCAAATAGCCGAATGAA
    579 Euc_032025_O_2 GCTTTAGGTTAGGGATCCCTGTAAGCTGATGATAGATATTGGAGATGGTACTTGTAAGAT
    580 Euc_032173_O_1 TGTTGTGTTTGGAAAGGTGCTGTCTGGGATGGATGTTGTCCACAAGATTGAGGCTGAAGG
    581 Euc_009143_O_1 GGAAAGCGGGGAATGAGCATGTGGATATTATCTCTTTCTACAATGAAATATTCATTCCTT
    582 Euc_000349_O_1 CATCAGGACGTTGACTCTAATTAAGACATATGTGACAGAGCGCCCTGTTAATGCGGTTAC
    583 Euc_000575_O_2 CTTTAGGTTTGATCTGTCTGTTTTGTCTATCCTGCGAGTTTCGAGCATGTGCGTGTGTGA
    584 Euc_000804_O_1 CAGCCCCAATAGATACTGGCTCTGTGCCGCTACTGAGAACAGTATTAAAATCTGGGACCT
    585 Euc_000805_O_2 AAGAATGAAGCTGATATGAGTGATGGAACTACGGGGGCCATGAGCTCAAATAAGAAGGTC
    586 Euc_000806_O_1 TGACTACAATTAGCACCTCACCATTATCGAACTGTATAATTGTGCTTGCCTGCTATTATT
    587 Euc_002248_O_4 TTGAAGCGGAAATATATATTTATGCTACTACATAAGTAATGTACTACTTGACAAGATGAG
    588 Euc_003203_O_1 TACTCGATGTGGTATAGAATTTATCCAATGTACTCCTAAATGTAGATACATCGTGTATTG
    589 Euc_003209_O_2 GCTTCGTCTGATACCACTATCAAGATAATAGGCGTGAGCAATAGCTCTGGATCACAGCAC
    590 Euc_004429_O_4 GGTCGGCTTGCTAGTGTATCTGATGACAAGAGCATATCACTCTATGATTACTCATGAAGG
    591 Euc_004607_O_3 GAAAGGAGAAAAGCATGGAGATCGATCTCGGAAACCTCGCATTCGACGTCGATTTTCATC
    592 Euc_004682_O_1 GATTCAGTACCCGGATTCGCAAGTCAACCGGTTGGAGATAACTCCACATAAGCGGTACCT
    593 Euc_005786_O_1 TTCCATGTATCAAGCCGCATCAATGTTTGTCGCTGCAATTAACATGTGTGCAGTCGATCC
    594 Euc_005887_O_2 TTCAGCGCATTGTGTAAATGTAGATAGGTGATATATTTCTCGTTGCAATGTAGGGTAAGA
    595 Euc_005981_O_2 TCCAATAATCACATTTACCATCAACAGGCATCAGCAACATACTGTTGTAGTGTAATTAAT
    596 Euc_006766_O_1 GGGCATTCTGACTACCTGCACTGTATAGCTGCACGGAACTCTTCTAGTCAGATTATAACA
    597 Euc_006769_O_1 AATCGTCTGGTAGATTGTCAAAAACTAATAAACCTGTGATTGATCCGGATTCTAGTAATG
    598 Euc_006907_O_2 AGTTGAGGATTCTCCACTATGACAGCTCTCATGGCTTGAATCTAAAGTCATCTGGTTTTC
    599 Euc_007518_O_1 GAACAATCATTCTGTAGAACACTAGAGTCTATATGCTTGACTGTATCGGTTAATTAATTC
    600 Euc_007717_O_1 AGATAGCGATAGAGTTATACTGCATGTACTGAGGTAAATGTTTTGATTACTCCACCCAAT
    601 Euc_007718_O_1 AAGAATTGTTAGGAGGTGTATACTTTCTGTAACTGTATTCAATGAGCATACACCTGACGG
    602 Euc_007741_O_2 CAACTCATATAATGACTGGATTCTGGCAACCGCGTCTTCAGACACAACAGTTGGACTATT
    603 Euc_007884_O_1 AGTGTAAAAGGATGCCCCTAATAGATTATATGCCAAGTGTAGTATATATAATAGTGCTTT
    604 Euc_008258_O_2 AAGAATCTACAGTTGTCTTATGCTACTCTATTACTCAATTATGCTGTGCTATTGATTGAG
    605 Euc_008465_O_4 TCTGAATACATACTTTGTGGTCTCTATAAAAGACCAATGATACAGGCATGGTCATTAATT
    606 Euc_008616_O_5 TAAATCTTCTCATGTGCCTGGCGTAAATTTTGCAGTTATTACTAGACCAAGATAGTTTCA
    607 Euc_008690_O_4 ACATGGATTCGATCAATCGCCACATGACAACTAAAACAAGCGGTTCACGTGATTGTAATT
    608 Euc_008708_O_4 AGATGAGTATGCTCGGGTGTATGATATTCGCAATTACAAGTGGAATGGATCGCATAATTT
    609 Euc_008850_O_5 TCTTTGATTCTGTTGTATGGTGTATCTTATTGTATCTTCTATCTGCCCCCCATGTAATTC
    610 Euc_009072_O_1 TTCGTTGTGTAGTACTGGGAGTTACTACTTGTATGTATGTAAATCATGTGGCGTCTGTCC
    611 Euc_009465_O_1 GGAGATGTGTAATATGTCTGAGCGGTCACACTCTAGCTGTTACATGCGTAAAGTGGGGAG
    612 Euc_009472_O_3 CCACCGTTGCGTAACTCGAATAGCCGGATTTTCGTTTTCGTTTTTATTTCCCCGTTAATT
    613 Euc_009550_O_1 TGAGATGCTCTGTGTGAGGACTTTTACGAAACTTGAATGGCCCGTAAGGACAATAAGCTT
    614 Euc_010284_O_3 TGGGTTGTTGCGACGGGTTCTACAGATAAGACTGTTAAGTTATTTGATCTACGCAAGATC
    615 Euc_010595_O_1 GCAGAGGTGCCTACATATGCTTTAGAATGCTAGTAGCTTGGAAGTGCAACACGCTCGTGA
    616 Euc_010657_O_1 AGTAAAGTTTAACGACTATGCATCTGTCGTAGTATCAGCCGGCTATGATCGTTCAGTGCG
    617 Euc_012636_O_2 CGTTAGGATAGTCTTTAAAGGAGTTGGTGATTATTGATTTCCACCCAATATATGTAGCGT
    618 Euc_012748_O_2 GAGCAAGCTACTTACAAAAATCGACAGCGTCTTTACCTATCTGAACAGACAGATGGCAGT
    619 Euc_012879_O_2 TCCTTCCGACAAGTACCGTATTGCAAGTTGTGGTATGGACAATACGGTTAAAATCTGGTC
    620 Euc_015515_O_1 TTTCACTCGATGACGGTTGGCCGGATAAATAATCGCTTATATAGTCCTAATAAGTTCCAT
    621 Euc_015724_O_3 ATATGTAGGTGGTAGAGGTGTGGATATTGCATAGACCGAACCTCCGCAGGTCCGCATTCT
    622 Euc_016167_O_1 CCATTGAACTACTTATGGATTACTTTATACATGAAATATCATGCCGGAGTAATTTTGAGT
    623 Euc_016633_O_3 AGCATTAGAGACCTGGATTTTAGTCTAGATTCAGAGTTTTTGGCTACGACATCTACTGAT
    624 Euc_017485_O_3 AAAGGTTTATCCCTCATTGGATTTGATATATAAACTGAGAGTGTTTTGCCCCCCATTAAA
    625 Euc_018007_O_1 GTACAGCGTGTATTTCTTGTTACGATACTTGAGGGGTTAGAGGCACCTACGAATTAGGAA
    626 Euc_020775_O_3 ATATCCTTATGAATGAAGTTTGGATGATAAGTGGCGCCAGACTTTCTACTCACCCTTTTT
    627 Euc_023132_O_3 TGATCACATCGTTGTTTGCAATAAGACGTCATCAATTTATATCATGACTCTACAGGGACA
    628 Euc_023569_O_2 TTTTCCCAGTGTACTGCGAGAGTGATGCTACATAAGTTTACTCTTGTGTCTAACTTTTCC
    629 Euc_023611_O_1 AGATTCTACAGATGGCGCTATACGAGCTGTTATACGGACATTTTATGACCATACACATCC
    630 Euc_024934_O_3 TGCTACGGGAAACCAGGACAAAACTTGTAGGATTTGGGACATACGAAACTTATCTAAGTC
    631 Euc_025546_O_1 CAAGTCATATAGTTACAGTGTCGCATGACAGAACAATTAAGCTCTGGACTAGTAACGACG
    632 Euc_030134_O_2 TGCCACATCGTAACCATCATAGCACTTATCATCTAATTATGGTGAAAGGGAGTTATATAT
    633 Euc_031787_O_5 GTTTATACTTATAAACAACAGAGAGACAACTGTACAGGTGTTGTAAACACTCCCAGTGTG
    634 Euc_034435_O_1 CTGTGTTTTAGCCCGAGGGCCAATCACTTAGTTGCTACTTCGTGGGATAATCAGGTACGG
    635 Euc_034452_O_3 GCAAAGTAGAGTTTAAGTTTCGTTGTGCTTGGACCGGAAAACTCACATGCTTAGAGTTTA
    636 Euc_035789_O_5 AAGATTTGGGCATAACTTGTATGAACTTTTTCTGTTGTCGACACTGTAATTACACGAGCT
    637 Euc_035804_O_4 AAACAGATGCATGTATGCTTCATAACTCTATAGATATGGAAATGTCACTGTACACTGATC
    638 Euc_043057_O_2 TTATTGGTGCACAGGACGGAAAATTGCGCATATATTCTATTTCAGGTGATACATTAACAG
    639 Euc_046741_O_1 AGGCACAGACACTTGCCTAAACCAATATACAAGGCAGGTATTCTAAGGCGCACCGTGAAT
    640 Euc_047161_O_4 CATGCGAAGGTTTCTGGGAATTTTCAGTAGAAAATTCGGTCGTGGCGGCCATCCTCGATA
    641 Pra_001766_O_1 TTAAGCTGATAGCTTTAGTTCCTACGTGGAATGTATAAATGCACCATTGTCCATAAGGCA
    642 Pra_002927_O_2 GGATGCTCTGGTTACATGACTACTCCTTAGGGAATCAGTCAGACATTTTAAATAACTTCC
    643 Pra_007642_O_2 TCATTAAGCGGTACTGGCAGAGGACATGTCTATTTATACAAGCAAATGGTCCTATTGGCT
    644 Pra_013714_O_1 ATGTTGGTCAGACCTCAAATATTGTACTCCCCACACTAGGGAGCATTTACGGTGAATATA
    645 Pra_016332_O_1 TCCTCTCGACCCTTAGAGTCCTCTGCGAATCTTGTTGTTAGTTACTGTGTACGCTGTAAC
    646 Pra_021677_O_3 AAGCATGTTTTGAATTTATGGTGGTGGCATGTGGATATTTGAACTTGGTTGAGAAAAATT
    647 Pra_027562_O_2 CATTCCTATTGAAGGGTCAACCTTTAATTTTGGCTAGCAGGACTGTATAGGATTATATGC
    648 Pra_001504_O_2 TTATTGTATTTTAGATTCTTGATGGCCATCTAAACTTCTGGCTGCTTGGTGCAACATTGA
    649 Pra_015211_O_2 ATAGCTAATGATTCCATGCTATCCATGGTATCTACTTCACGATAATAAAGGTCTTAGTCC
    650 Pra_020421_O_2 CACCTAATAGGCCTGAGTATTGCTCACCACTATGCTGATATGGGGAGCAATAACGTTAGT
    651 Pra_003187_O_2 TTTCTTTTCACTTTGTACTAATGATCATTGTGACCACAAAATCTTTATACACAATACAGA
    652 Pra_015661_O_1 CTTGTCACTATCCTCATATTGATATCACCTCGTGTATGTTGTGGGGTGGCAAAATTACTT
    653 Pra_013874_O_1 TATTTTAACTCAGCGACTTACCAGCCTAGTAAGCAATGGGGAGCTTGCATGTATTAGTTT
    654 Pra_014615_O_1 ATTCGTCCTGGTCCTTTAGGACATGTACTTATGTCCATGCAAGTGCTTCTTGCCTAAGCT
    655 Pra_004578_O_2 TTCTAGGCGATATATATCGCCGTAACTTTGGATGTGTTAAGAATATAGGGGATCATTAGC
    656 Pra_023387_O_3 AGTTGCAGAGTGTGTAGCAACTGATGAGCATAGTTGTTATGTTTCTCAACTCAGTTGCAC
    657 Pra_006970_O_1 AAGAAACTCATACACTGGACAGGCCAACCTTCCAAATATGTGTTTAGAAAACCTTTGTCT
    658 Pra_010322_O_1 AAGGGGTGCTATCCATATCTAGAATCTACCATGCTCAATGAGGTATCTTCATTAGTATAC
    659 Pra_022721_O_1 ATCTAATGCTAGTTTATTGATTTCTATGATCCAAGACCTCGTCATAGATCAAGTGCCTAG
    660 Pra_023407_O_1 TTGTTATTAAATACCATTCAATATGCTTATGATTCATGAATGCTTAAGAGATTCTGCTGC
    661 Pra_001945_O_2 GCTTCTAAACTGTAGAAGCCTGTTATCTTTAGACTCGTGGTTATGTGAACTACTTTTACA
    662 Pra_008233_O_1 GGCTGTGGGGATTCGAGCCTGATGGTTATGCACTGTGGCCAGCAAGATGTTGAAGTTTTA
    663 Pra_008234_O_4 GCCTGATGGTTATGCACTGTAAGTGATCTGATTTGATTAACTATTTTATCAATTAATTTT
    664 Pra_022054_O_2 ATGGTCATTATCCGAGATAGTGCGCTTTGTCATGGGAAAATGACTATTGAATGTGAGTTT
    665 Pra_012137_O_2 TTTTCTGGTGCATCCTTAACACAGCTTGGTTACATGGTGAATTACAGTATTTGAAGGAGT
    666 Pra_012582_O_2 AGATTTAATGCCACTTAGGTGATCGGTGACCCACTTGTACATATAGATGTTGGCGATGTT
    667 Pra_015285_O_2 AAGAAATTCATCAATTCTTTGAAATTATTGTTCCCTTTTGATGCGGCCCCTTTCTGGAGG
    668 Pra_017229_O_1 TAAAGTATATTTTAGCCGCTGTTGTTGTAAATTTATGTTTTTCATTGCTATCAACATTTA
    669 Pra_020724_O_2 GGTTTTCCTATAAGATGTATGAATTCGCACTGTGGTGCAATTTTATGAATTAAACTCAAA
    670 Pra_004555_O_1 TTTACTATTCCGTCTGGGCTTAGAGATGTACGTTAATTGGTCATTTAAGACGACTCAGTT
    671 Pra_004556_O_5 TCAAATCTAGTCAATATCCGTGTTGAGCTAAACAAGCGCTGAAAGTTTGCTCGAATCAGC
    672 Pra_005729_O_2 AGAAAGTTGTGTACTAATTTGTATTGTAACGTCCATTTATCCAACGAGTCCTCCATTCAT
    673 Pra_007395_O_3 CAGTACTGTATTCGAAGATCCTGAAAATTTACTAAAACAAATGGAATATCAACAACCTAG
    674 Pra_009503_O_1 TTGCTCTATATAATTTGTGCTCGTGTGTGTACTTGAAGATCCATCCTCACATAGTCCAAT
    675 Pra_011283_O_1 GTGTGTATAGTTTTATAACACTCTATGGTATCACTACCACTATGGGCCTGTTTAGTCCAA
    676 Pra_012322_O_3 GAAGCAGAATCAGCTTTGACCAGTATTTAGTGTCTTGTATACAATTCTTGTTTCAGTGAA
    677 Pra_023236_O_3 AAATCAAGATTAAAATCCGAAACCAAGGCTAACCAGCAAACTGTGAGGTGTACATTGTTG
    678 Pra_000171_O_2 TTCCAAGCAGAAGGGCACATGTTGTGACATCAAGTAGTAGATTGTTCTGCAGATTCTGGT
    679 Pra_000172_O_1 GTTAATGTAATACATTTAGTTTTTAGATAACTGTTAATGTGTAGTAAAGCACTAGGAAGA
    680 Pra_001480_O_3 GAGGCTTCAAAGGTTTTTGTGTCTTTTCTAGTTATTATAAACGCTTCATAGGTTCCTAGG
    681 Pra_001692_O_2 GAAGATTGTAAGTTGGGTGAACTTTTTTACCACGCTAGGTTGATCTATTTTAAGACTCTT
    682 Pra_005313_ORF_O1 AAAATAGCTGCGCGTACCACAAAGGTGACAAACGCCGGATTTCTCTTATCAGACTTGTCA
    683 Pra_006362_O_1 TTTAATTATCATAGTTTTATTCCGGCTATCTTGATCATTCACGGAAGTCCCGAGAGTCAA
    684 Pra_006493_O_3 GTGGAGTGAACGTGGTTACTTCAATGGATTACCCTTCTATCGTGTCATTAAACACTTTGT
    685 Pra_006983_O_1 GCTAACTCTTCTAGTTGAGATCTCCATCAATTAATGGATACAAACATTGAGTTTCACTTT
    686 Pra_007665_O_1 GGATCACTACTGGATTCCGTTACATTAGTTATTGCAAGTTGGTTATTATGTACGTTTATA
    687 Pra_012196_O_1 ATGAACAAATGCAATTACCCTGTTTTATTCTATCCCGCTTTAATTAATATTGGTCATGTT
    688 Pra_013382_O_1 TTTGCTTGTGGATTGTACTGTGGTACATGGTATAAATCTATAGGCTATGTCGATTATTTT
    689 Pra_016461_O_1 ATATAAGATATAAGATATTGCCAGCAAACTATTTGACAGGTTATTTAATAAAGTGTGCTA
    690 Pra_017611_O_1 TTTTAAATGTGGACAGAGGCACTATAAGAATGCGAAATATCGTCGGAGCACGACTAATTG
    691 Pra_019776_O_1 ATAGACTAGTTCTACAAAGCCCTAGGATGATGGACTTCATTTCTTTTGCATTAAGATGAA
    692 Pra_020659_O_1 GATTTCTTATGGGGTTGGAACATTCCTCGCTGCCTTCTGGTAATATTAGGTTATGCGTTT
    693 Pra_022559_O_3 AATTGAGGTTGACTGTGTACTTCTCCAGTGGACAGGAGAAAGCGATAAAATTCAAACGTT
    694 Pra_024188_O_5 AAGGAAGGGCAAATAGAGCTCGCGCTCAAGAAATACCTTAAATCGATACGGTATTTGGAT
    695 Pra_027973_O_2 TAATTTAAGAGCTATGAAACAACTACCTTTTGGAATGGTTTTGTTTTTAGCATCCCAATT
    696 Pra_001353_O_1 TTGTAAATTATGCTGGTTCCATATGGGGGTTAATCAGTATCCTGGTTATTTGTGACACCA
    697 Pra_001978_O_3 GTTGTGAACTATCAATAGACGGGGATGGTCCTTTTTAGCTGCTCCTTAAGCAGCTCAAAT
    698 Pra_002810_O_2 TCAATTCCGGTCATATGTAGACGACTATAATGTTGTTTGTGTCCTATAACTATAGTGTTG
    699 Pra_002811_O_1 CATTTTACACCCTATAACAAAATATAGTGTCATAAGTTTACACCAGGTAACAACTCTATA
    700 Pra_002812_O_3 ATGGAGAGTTTTATTCATTACATGAAAGAGTATGTCACCTTTCGTGCTCCATCTATTGAT
    701 Pra_003514_O_1 TTTCACGTCCTGTATACTCACTCAAGCAACTTTAGGATGAAGAGCTAAAGTATATCAAAG
    702 Pra_004104_O_2 AATGCACTCTTTATAAAGTGGGATGAGGTATGTGTTTCCTTCCTATTGGCTAACCTGAAT
    703 Pra_005595_O_1 ATTGGGCAATCGTTATTGATTTTACCTATCGCTATCTCACTGTCCGCCAATTTAGTGTAA
    704 Pra_005754_O_1 TTTCAGCGGATATAAAGTCTTCCAACTTGTAAACCGGTGCTGTGAAGATTAAAAGTCCTT
    705 Pra_006463_O_1 GCTTTAGAGGCAATGGTAGATTATGAAGTCAACACCAGGGAGTTTGACCGTTTGGGACAT
    706 Pra_006665_O_1 CATTCAATTTGACATTGGAGTTTCAAGGCATTCCAAGGATAGCATGTACACAAGTTGAAT
    707 Pra_006750_O_1 CATAAAATTACTATGGAAGTTGGATCATTATCTATGCCATAGTGGAGTAGAACTAGATTT
    708 Pra_007030_O_1 CTCTTGATTCTAGAATCTAAACTACTACCTTGCGGACATGACTGAGCATCTCTCTAACAG
    709 Pra_007854_O_1 CAGGGTTGTGCTAGTTTAACATTTTAACTTAATGTAATCATGTAAGCTTTAGAGAGGTGG
    710 Pra_007917_O_1 GTAAATGTTTACATTGAGGTCATGCATGAGTGTTAATTACGCTTTCACTACTGTTCACTT
    711 Pra_007989_ORF_O2 AATTAAAGCTTGGTTGTATGATCATTTGGGATCGAGAGTAGATTATGATGCTCCTGGGCA
    712 Pra_008506_O_1 TTATCTAGCTAGAAGTTGTGAAATTAAGAGGGATGTGAGGATTGGGTTATAACTAGTGTA
    713 Pra_008692_ORF_O2 AATGAATCAGGCATTAAAGCGGGAATCATTTATGACTTGGCAACCTGAAAATTCTATTAA
    714 Pra_008693_O_2 TTCTTGACGTTTTAATATGGTATGGTATTAAATTTGGAAGGCCTATTCGATTGTTTGCAA
    715 Pra_009170_O_1 TTCTTATAACCTGTACGATTGCCGATATATCACCAATTTTGCTGATTTTAATCTGAGTTT
    716 Pra_009408_O_1 CAATTTCATATTCGGGTTCAATGTAGTGCCTCTCATTTTAGGGTGATAGCATGAGTTTTT
    717 Pra_009522_O_1 TCCACAAGTTAACATAGGTAACTATCGACTGAAGTGAACTGGGGGGCAGAAGCTAACTAT
    718 Pra_009734_O_2 TTTAGATAGCCATTTACATTTTACTTATTATTGGACTTGTAAAGATTTTTGTACCCTTGT
    719 Pra_009815_O_4 TTGCTGAAATATTTCAAGCTGAAAGTTATGATTCTGGCCAAGAAGTCTACTGAAAATTTG
    720 Pra_010670_O_2 AAACATAAGTTTGGCCCAGATTCGGTTTATCATAAAATCTGGCTGCATATAAGGTGTCAG
    721 Pra_011297_O_1 ATGTTCTAGAATTTGTCTAAGCTAGCTACTGGTGTTTAACTGATATGGAAAACTTTTGCC
    722 Pra_013098_O_2 TTTGGGGAGTACTTTAGTCAATAAAAGTGAAGTGAATCATGATATAAAGGGTTTAAGTAA
    723 Pra_013172_O_2 AGAAGTTACTAATTTGTAGATAAATTCTAACGAAGGTGATGATAGCATACACGTAATGAA
    724 Pra_013589_O_2 GAATTTTGATGGTAGCGTATGGTTGAAGGAAAACTTGGATATATCATGTAAACATTTTTC
    725 Pra_013608_O_1 TTAATGAACCGCTTTTTCCTTGAGAGGCTATGAATGCCTGTAGAACTAATCCTTTAAGTA
    726 Pra_014299_O_2 TTTCTCTAACACTATATTTTCTGGTATGACCGCTCTACATTGTATATTAACCCTTGCAAA
    727 Pra_014498_O_1 TATATTCACTGTGCTGGGATTATCCTCTCCCCTTTTTGACCCACTGTTGTGTGTATTTGA
    728 Pra_014548_O_1 GAGCATACAGCGTTATCTTTGAGACGAGTCATCAATGATAATATCCTCGTAAAAGGTTAC
    729 Pra_014610_O_2 TTTATTCAATTACGACGGATTCAGTTGGCCTTTTGTAACATTCAAGTATCCATCTATCAC
    730 Pra_016090_O_2 ATGTTCAGGGGTATTAAAAATTCAGAGGATAAATTTCCTCACTCTCAAGTGTTAGATGGT
    731 Pra_016722_O_2 CAAAGTCTAGACGTTAATGTTTTGGAACTCTTTTTTCGAATTTGTGCCTATTGAATCACT
    732 Pra_016785_O_3 TATAAATATATTGTACTGGGGATCCAAGACATGGCAATATATGTCGAGATTTTCATTTTC
    733 Pra_017094_O_3 CTTTTGCATGAGTTCAAATGTCTTTGTGACATATTGTCTTGAACCACCGAGGATATATCA
    734 Pra_017527_O_2 GTTTGTATGTCCAATAGATTATAACCTATTTACTGTGACACTATTCTTCACACCCATGTC
    735 Pra_017591_ORF_O2 AGATCTAGTTGTTTCAGCATCGTTGGACCAAACTGTTCGTGTATGGGATATAAGTGGCCT
    736 Pra_017769_O_2 TGCCGTATCAAAAGATTGGTACTTCCTTATGGACACACAAGATCGTAAGCATGGCTGAAT
    737 Pra_018047_O_2 TTGATGGCCACATGAGTTGTTTATACAAGTCGTTGTTTTATGAGAGAACCTTCTTCAGAT
    738 Pra_018414_O_1 ATTTCTATAGTGCCATATGCTTGTCGGTTGTCATTGACCTCTAATAGAATAGCCAGAGTA
    739 Pra_018986_O_1 TTCACGGCAGTTGAACTAGTCATAGTGGAATATTATTTAAATGGTGTATTCTAGTCACAT
    740 Pra_019479_ORF_O1 TGCAGGCGCTCTATAGTTCTGTTCTCTAGCATGAAGTGTGTATTTTATCTATTGTGGACC
    741 Pra_020144_O_1 TGTCTTTAATCTTCAGGGTTCGTTACTAACAATTGAGCTCAAATCTCTATTCTGACCAGC
    742 Pra_022480_O_1 CATTTATAGAGTTGTGCAAAATCACCCATAATGCTATGAATTGACAGGTGACTGTAATCT
    743 Pra_023079_O_2 GGAGAAAATTTCCTATCCCTTTGTGGGTGTGTGAAAAACGAAATATAGAGGAACAATGTG
    744 Pra_026739_O_2 ACCAATCATTTATTTGCAGTGTAGTTGATATGAAGGGAGAAATATGACAGTTGGTTTCAA
    745 Pra_026951_O_2 AAGTTAATGTTCTCATAGGTTATTCATTGGAGTTGTCTCGTATGTACGCTGTGCCGTAGT
    746 Pra_026529_O_2 CTCATAAATTGAGGCTTGCCTACGTTAATTGTTATATATGGAGAGCCATGCTAATTGTTA
    747 Euc_006366_O_2 GCAGATCATGTAATTGTATCTCAAATTATAGTATCCGTATTCTGTACAAATGCTCCGGAA
    748 Euc_017378_O_1 TCTTTACGCAGATGGTGACTGAAGCTGGTTCCGAGATCGGCATATGTAGCTGGTAGAGGT
    749 Pra_000888_O_1 TTCACATTGAGGGTTGCCGTCGGTATTCGCCGATGATATCCTGTTTTACGCGCAACAGTT
    750 Pra_014166_O_1 TCATTATTTAGGGTGCAGGCTGTATAAAATGTTGTAAATTGTAGTATCAATGTGTACAAT
    751 Pra_003189_O_1 GCATTCACCACGACAGTAAAGTAATCATTATGATTACTAATGTATTGCTTTCATGGGGTG
    752 Pra_009356_O_4 AAAGGGTATATTTTGTCTCATGTTGGGGTGATAATTCTCCCTGAAAGTCTCCAAAATATA
    753 Pra_000065_ORF_O_2 AAATTTCCGGTTGCCATAGTCTAGTGGGGTGAGGGTTCATTCTAGGGGATTTATTGTGTT
    754 Pra_014197_ORF_O1 GCAGTGATAAAGGTACTTCTTGGTGATAATCCTAAAGCCTTACCCATGGATATCCAGCCT
    755 Pra_009081_O_2 TTCTTTAACAAGGTAAAAATCCCCCCCTTGGCATGTAGCTCAATTAGTTGTAATGGAACT
    756 Pra_013417_O_1 AGTTGTAAACAGTGTAATAAGGAGCAGAAGTTGTGATAGCTTTTAGGAACGATAGACTTT
    757 Pra_005755_O_1 TGAACCAATTCTTGTATATTAGATATGTAACATGTATGAATGTCCATAGAGCAGAGCTTT
    758 Pra_006670_O_2 AGCCAGGCACGCTTAACTAAATTTCGTTTAGTTCACCATGACTATTCGTTGAACTTAATG
    759 Pra_007027_O_1 CAAAACCCCTTGTAGGGTGGACTTCTGTTGTATCCAATTTTTATGGCATAATTAGCTAGT
    760 Pra_007276_O_1 AATTTGGTGATTATTCCTTACCATATCGTACTGTACAGATACGGTAAGGTCGAAATATAT
    761 Pra_007390_ORF_O1 CATGCCGTGATCGGTCGATTGCATTAAGTGCTGCAAGGATCAAATAGTGGCACTGTCATG
    762 Pra_012648_ORF_O1 CAAACATAAATAAGGTTGCTACTTTAAAGGGACATACGGAACGAGTTACTGATGTGGCAT
    763 Pra_013171_O_2 ATTTATGGATGAGGTACTCCTTATGAATATCTTCAAACTAAGAAATAACTATATATGCAA
    764 Euc_045414_O_2 CTTGGTTTTTGTTGAGCTTTCTATTTCAAGCAATTTGTGATTGGGGGGTTCTGCATTCTT
    765 Euc_044328_O_2 ATGTCTAAAGAGCCGTGATCTATGAGTAGATTAGAAACCGCCTTTTTAGTTGCAAACGCC
    766 Euc_015615_O_2 TTGCAACAAGGTATACTTAGTCAGTCCTTGTTATGTATGTCTTTTGTCAACCCTTCAGGG
    767 Euc_017239_O_3 GGCGGAATCCCTTTGTTCTTTCGAGCTTTACGTGACAAGTCGGCCAGAAAGCAGTAGCAT
    768 Euc_018643_O_3 TTGATGTACGAGCCGCTATATCTAATTCTGCCTCCCAGTCACTGCCAAGTTTTACTCTTC
    769 Euc_019127_O_5 GTCTTGCATGTCAGCTATTATACAGTCCTGTTTATAGTCCTGTGATGTAATAAAAAGCTG
    770 Euc_022624_O_3 AAGTAGGAGATCGTGTAGAGAGAATACTTTCTGCTCTCAGCGGCGAAGAGGTTTGTCTGC
    771 Euc_032424_O_1 AATTGTGAGTAGAATAGGAGAAACTTTTGTACAAGATTAATACGTGTGGCATAATAAGAT
    772 Euc_037472_O_1 TGATGTGCAGTTTACATTATTATGGTTCGAGTATTATTTAGCTGCCCTATCTTAAGTCAT
  • TABLE 15
    Peptide Table.
    Patent Patent
    Protein ORF ORF
    SEQ ID Target Patent PEPTIDE Sequence start stop
    261 CDK type A MGDGSLGSGGRGNSGGGGGGGSRPEWLQQYDLIGKIGEGTYGLVFLARIKHPST 387 1820
    NRGKYIAIKKFKQSKDGDGVSPTAIREIMLLREISHENVVKLVNVHINPVDMSL
    YLAFDYADHDLYEIIRHHRDKVNQAINPYTVKSLLWQLLNGLNYLHSNWIIHRD
    LKPSNILVMGEGEEQGVVKIADFGLARVYQAPLKPLSDNGVVVTIWYRAPELLL
    GAKHYTSAVDMWAVGCIFAELLTLKPLFQGQEVKANPNPFQLDQLDKIFKVLGH
    PTQEKWPMLVNLPHWQSDVQHIQRHKYDDNALGNVVRLSSKNATFDLLSKMLEY
    DPQKRITAAQALEHEYFRMEPLPGRNALVPSSPGDKVNYPTRPVDTTTDIEGTT
    SLQPSQSASSGNAVPGNMPGPHVVTNRPMPRPMHMVGMQRVPASGMAGYNLNPS
    GMGGGMNPSGIPMQRGVANQAQQSRRKDPGMGMGGYPPQQKQRRF
    262 CDK type A MEKYQQLAKIGEGTYGIVYKAKDKKSGELLALKKIRLEAEDEGIPSTAIREISL 99 1007
    LKQLQHPNIVRLYDVVHTEKKLTLVFEFLDQDLKKYLDACGDNGLEPYTVKSFL
    YQLLQGIAFCHEHRVLHRDLKPQNLLINMEGELKLADFGLARAFGIPVRNYTHE
    VVTLWYRAPDVLMGSRKYSTQVDIWSVGCIFAEMVNGRPLFPGSSEQDQLLRIF
    KTLGTPSLKTWPGMAELPDFKDNFPKYVVQSFKKICPKKLDKTGLDLLSRMLQY
    DPAKRISAEQAMGHPYFKDLKLRKPKAAGPGP
    263 CDK type A MDQYEKIEKIGEGTYGVVYKAIDRSTNKTIALKKIRLEQEDEGVPSTAIREISL 120 1004
    LKEMQHGNIVKLQDVVHSERRLYLVFEYLDLDLKKHMDSCPEFSKDTHTIKMFL
    YQILRGISYCHSHRVLHRDLKPQNLLLDRRTNSLKLADFGLARAFGIPVRTFTH
    EVVTLWYRAPEILLGSRHYSTPVDVWSVGCIFAEMVNRRPLFPGDSEIDELFKI
    FRIMGTPNEDSWPGVTSLPDFKSTFPKWASQDLKTVTPTVDPAGIDLLSKMLCM
    DPRRRITAKVALEHEYFKDVGVIP
    264 CDK type A MVMKSKLDKYEKLEKLGEGTYGVVYKAQDKTTKEIYALKKIRLESEDEGIPSTA 23 937
    IREIALLKELQHPNVVRIHDVIHTNKKLILVFEFVDYDLKKFLHNFDKGIDPKI
    VKSLLYQLVRGVAHCHQQKVLHRDLKPQNLLVSQEGILKLGDFGLARAFGIPVK
    NYTNEVVTLWYRAPDILLGSKNYSTSVDIWSIGCIFVEMLNQKPLFPGSSEQDQ
    LKKIFKIMGTPDATKWPGIAELPDWKPENFEKYPGEPLNKVCPKMDPDGLDLLD
    KMLKCNPSERIAAKNAMSHPYFKDIPDNLKKLYN
    265 CDK type A MDQYEKVEKIGEGTYGVVYKAIDRLTNETIALKKIRLEQEDEGVPSTAIREISL 149 1033
    LKEMQHGNIVRLQDVVHSENRLYLVFEYLDLDLKKHMDSSPDFAKDPRLVKIFL
    YQILRGIAYCHSHRVLHRDLKPQNLLIDRRTNALKLADFGLARAFGIPVRTFTH
    EVVTLWYRAPEILLGSRHYSTPVDVWSVGCIFAEMVNQRPLFPGDSEIDELFKI
    FRILGTPNEDTWPGVTALPDFKSAFPKWPAKNLQDMVPGLNSAGIDLLSKMLCL
    DPSKRITARSALEHEYFKDIGFVP
    266 CDK type B-1 MEKYEKLEKVGEGTYGKVYKAKDKATGQLVALKKTRLEMDEEGVPPTALREVSL 199 1116
    LQLLSQSLYVVRLLSVEHVDGGSKRKPMLYLVFEYLDTDLKKFIDSHRKGPNPR
    PVPAATVQNFLYQLLKGVAHCHSHGVLHRDLKPQNLLVDKEKGILKIADLGLGR
    AFTVPLKSYTHEVVTLWYRAPEVLLGSAHYSIGVDMWSVGCIFAEMVRRQALFP
    GDSEFQQLLHIFRLLGTPTEKQWPGVTTLRDWHVYPQWEPQNLARAVPSLGPDG
    VDLLSKMLKYDPAERISAKAALDHPFFDSLDKSQF
    267 CDK type B-2 MERPATAAVSAMEAFEKLEKVGEGTYGKVYRAREKATGKIVALKKTRLHEDEEG 41 982
    VPPTTLREISILRMLSRDPHIVRLMDVKQGQNKEGKTVLYLVFEYMETDLKKYI
    RGFRSSGESIPVNIVKSLMYQLCKGVAFCHGHGVLHRDLKPHNLLMDKKTLTLK
    IADLGLARAFTVPIKKYTHEILTLWYRAPEVLLGATHYSTAVDMWSVGCIFAEL
    VTKQALFPGDSELQQLLHIFRLLGTPNEKMWPGVSSLMNWHEYPQWKPQSLSTA
    VPNLDKDGLDLLSQMLHYEPSRRISAKAAMEHPYFDDVNKTCL
    268 CDK type C MGCVLGREVSSGIVTESKGRDSSEVETSKRDDSVAAKVEGEGKAEEVRTEETQK 291 2042
    KEKVEDDQQSREQRRRSKPSTKLGNLPKHIRGEQVAAGWPSWLSDICGEALNGW
    IPRRANTFEKIDKIGQGTYSNVYKAKDLLTGKIVALKKVRFDNLEPESVRFMAR
    EILILRHLDHPNVVKLEGLVTSRMSCSLYLVFEYMEHDLAGLAASPAIKFTEPQ
    VKCYMHQLLSGLEHCHNRRVLHRDIKGSNLLIDNGGVLKIGDFGLASFYDPDHK
    HRMTSRVVTLWYRPPELLLGANDYGVGIDLWSAGCILAELLAGKPIMPGRTEVE
    QLHKIYKLCGSPSEEYWKKYKLPNATLFKPREPYRRCIRETFKDFPPSSLPLIE
    TLLAIDPAERGTATDALQSEFFRTEPYACEPSSLPQYPPSKEMDAKKRDDEARR
    LRAASKGQADGSKKERTRDRRVRAVPAPEANAELQHNIDRRRLISHANAKSKSE
    KFPPPHQDGALGFPLGASHRFDPAVVPPDVPFTSTSFTSSKEHDQTWSGPLVDP
    PGAPRRKKHSAGGQRESSKLSMGTNKGRRADSHLKAYESKSIA
    269 CDK type C MYSKSSAVDDSRESPKDRVSSSRRLSEVKTSRLDSSRRENGFRARDKVGDVSVM 107 2236
    LIDKKVNGSARFCDDQIEKKSDRLQKQRRERAEAAAAADHPGAGRVPKAVEGEQ
    VAAGWPVWLSAVAGEAIKGWLPRRADTFEKLDKIGQGTYSSVYKARDVTNNKIV
    ALKRVRFDNLDTESVKFMAREIHILRMLDHPNVIKLEGLITSRMSCSLYLVFEY
    MEHDLTGLASRPDVKFSEPQIKCYMKQLLSGLDHCHKHGVLHRDIKGSNLLIDN
    NGILKIADFGLASVFDPHQTAPLTSRVVTLWYRPPELLLGASRYGVEVDLWSTG
    CILGELYTGKPILPGKTEVEQLHKIFKLCGSPSDDYWRRLHLPHAAVFKPPQPY
    RRCVAEIFKELPPVALGLLETLISVDPSQRGTAAFALRSEFFTASPLPCDPSSL
    PKYPPSKEIDMKLREEEARRRGAAGGKNELEKRGTKDSRTNSAYYPNAGQLQVK
    QCHSNANGRSEIFGPYQEKTVSGFLVAPPKQARVSKETRKDYAEQPDRASFSGP
    LVPGPGFSKAGKELGHSITVSRNTNLSTLSSLVTSRTGDNKQKSGPLVSESANQ
    ASRYSGPIREMEPARKQDRRSHVRTNIDYRSREDGNSSTKEPALYGRGSAGNKI
    YVSGPLLVSSNNVDQMLKEHDRRIQEHARRARFDKARVGNNHPQAAVDSKLVSV
    HDAG
    270 CDK type C MGCIPTIISDGRRRSAAPDKRRPRPRRSSSEGEAPPHATAAGSEGGESARGAPG 82 1749
    KERPEPAPRFVVRSPQGWPPWLVAAVGHAIGEFVPRCADSFRKLAKIGEGTYSN
    VYKARDLVTGKTVALKKVRFDNLEAESIKFMAREILVLTRLNHPNVIKLEGPVT
    SRMSSGLYLAFEYMEHDLSGIAARQNGKFTEPQVKCFMRQLLSGLEHCHNHDVL
    HRDIKCSNLLIDNEGNLKIADFGLATFYDPERKQVMTNRVVTLWYRAPELLLGA
    TSYGIGIDLWSAGCILAELLYGKPIMPGRTEVEQLHKIFKLCGSPSEAYWNKFK
    LPNANIFKPPQPYARCIAETFKDFPPSALPLLETLLSIDPDERGTATTALNSEF
    FAAEPHACEPSSLPKYPPSKEMDLKLIKEKTRRDSSKRPSAIHGSRRDGIHDRA
    GRVIPAPEATAENQATLHRPRAMKKANPMSRSEKFPPAHMDGVVGSSANAWLSG
    PASNAAPDSRRHRSLNQNPSSSVGKASTGSSTTQETLKVAPELLQVGSSSLHPC
    HRMLVYGSNLTIRSK
    271 CDK type C MGCICAKQADRGPASPGSGILTGAGTGTGTRSSKIPSGLFEFEKSGVKEHGGRS 151 1560
    GELRKLEEKGSLSKRLRLELGFSHRYVEAEQAAAGWPSWLTAVAGDAIQGLVPL
    KADSFEKLEKIGQGTYSSVFRARELANGRMVALKKVRFDNFQPESIQFMAREIS
    ILRRLDHPNIMKLEGIITSRMSNSIYLVFEYMEHDLYGLISSPQVKFSDAQVKC
    YMKQLLSGIEHCHQHGVIHRDVKSSNILVNNEGILRIGDFGLANILNPKDRQQL
    TSHVVTLWYRPPELLMGSTSYGVTVDLWSVGCVFAELMFRKPILRGRTEVEQLH
    KIFKLCGSPPDGYWKMCKVPQATMFRPRHAYECTLRERCKGIATSAMKLMETFL
    SIEPHKRGTASSALISEYFRTVPYACDPSSLPKYPPNKEIDAKHREEARRKKAR
    SRVREAEVGKRPTRIHRASQEQGFSSNIAPKEKRSYA
    272 CDK type C MAVAAPGHLNVNESPSWGSRSVDCFEKLEQIGEGTYGQVYMAKEKKTGEIVALK 82 1644
    KIRMDNEREGFPITAIREIKILKKLHHENVIKLKEIVTSPGPEKDEQGRPEGNK
    YKGGIYMVFEYMDHDLTGLADRPGMRFSVPQIKCYMRQLLTGLHYCHINQVLHR
    DIKGSNLLIDNEGNLKLADFGLARSFSNDHNANLTNRVITLWYRPPELLLGATK
    YGPAVDMWSVGCIFAELLHGKPIFPGKDEPEQLNKIFELCGAPDEINWPGVSKI
    PWYNNFKPTRPMKRRLREVFRHFDRHALELLERMLTLDPSQRISAKDALDAEYF
    WADPLPCDPKSLPKYESSHEFQTKKKRQQQRQHEETAKRQKLQHPPQHPRLPPV
    QQSGQAHAQMRPGPNQLMHGSQPPVATGPPGHHYGKPRGPSGGAGRYPSSGNPG
    GGYNHPSRGGQGGSGGYNSGPYPPQGRAPPYGSSGMPGAGPRGGGGNNYGVGPS
    NYPQGGGGPYGGSGAGRGSNMMGGNRNQQYGWQQ
    273 CDK type C MGCICTKGILPAHYRIKDGGLKLSKSSKRSVGSLRRDELAVSANGGGNDAADRL 626 2782
    ISSPHEVENEVEDRKNVDFNEKLSKSLQRRATMDVASGGHTQAQLKVGKVGGFP
    LGERGAQVVAGWPSWLTAVAGEAINGWVPRRADSFEKLEKIGQGTYSSVYRARD
    LETNTIVALKKVRFANMDPESVRFMAREIIIMRKLDHPNVMKLEGLITSRVSGS
    LYLVFEYMDHDLAGLAATPSIKLTESQIKCYMQQLLRGLEYCHSHGVLHRDIKG
    SNLLVDNNGNLKIGDFGLATFFRTNQKQPLTSRVVTLWYRPPELLLGSSDYGAS
    VDLWSSGCILAELFAGKPIMPGRTEVEQLHKIFKLCGSPSEEYWKKSKLPHATI
    FKPQQPYKRCLLETFKDFPSSALGLLDVLLAVEPECRGTASSALQNEFFTSNPL
    PSDPSSLPKYPSSKEFDARLRDEEARKHKATAGKARGLESIRKGSKESKVVPTS
    NANADLKASIQKRQEQSNPRSTGEKPGGTTQNNFILSGQSAKPSLNGSTQIGNA
    NEVEALIVPDRELDSPRGGAELRRQRSFMQRRASQLSRFSNSVAVGGDSHLDCS
    REKGANTQWRDEGFVARCSHPDGGELAGKHDWSHHLLHRPISLFKKGGEHSRRD
    SIASYSPKKGRIHYSGPLLPSGDNLDEMLKEHERQIQNAVRKARLDKVKTKREY
    ADHGQTESLLCWANGR
    274 CDK type D MDPDPSPDPDPPKSWSIHTRREIIARYEILERVGSGAYSDVYRGRRLSDGLAVA 13 1467
    LKEVHDYQSAFREIEALQILRGSPHVVLLHEYFWREDEDAVLVLEFLRSDLAAV
    IADASRRPRDGGGGGAAALRAGEVKRWMLQVLEGVDACHRNSIVHRDLKPGNLL
    ISEEGVLKIADFGQARILLDDGNVAPDYEPESFEERSSEQADILQQPETMEADT
    TCPEGQEQGAITREAYLREVDEFKAKNPRHEIDKETSIFDGDTSCLATCTTSDI
    GEDPFKGSYVYGAEEAGEDAQGCLTSCVGTRWFRAPELLYGSTDYGLEVDLWSL
    GCIFAELLTLEPLFPGISDIDQLSRIFNVLGNLSEEVWPGCTKLPDYRTISFCK
    IENPIGLESCLPNCSSDEVSLVRRLLCYDPAARATPMELLQDKYFTEEPLPVPI
    SALQVPQSKNSHDEDSAGGWYDYNDMDSDSDFEDFGPLKFTPTSTGFSIQFP
    275 CDK type D MDPDPSPSPDPPKSWSIHTRREIIARYEILERVGSGAYSDVYRGRRLSDGLAVA 113 1558
    LKEVHDYQSAFREIEALQILRGSPHVVLLHEYFWREDEDAVLVLEFLRSDLAAV
    IADASRRPRGGGVAPLRAGEGKRWMLQVLEGVDACHRNSIVHRDLKPGNLLISE
    EGVLKIADFGQARILLDDGNVAPDYEPESFEERSSEQADILQQPETMEADTTCP
    EGQEQGAITREAYLREVDEFKAKNPRHEIDKETSIYDGDTSCLATCTTSDIGED
    PFKGSYVYGAEEAGEDAQGSLTSCVGTRWFRAPELLYGSTDYGLEVDLWSLGCI
    FAELLTLEPLFPGISDIDQLSRIFNVLGNLSEEVWPGCTKLPDYRTISFCKIEN
    PIGLESCLPNCSSDEVSLVRRLLCYDPAARATPMELLQDKYFTEEPLPVPISAL
    QVPQSKNSHDEDSAGGWYDYNDMDSDSDFEDFGPLKFTPTSTGFSIQFP
    276 Cyclin A MSNQHRRSSFSSSTTSSLAKRHASSSSSSLENAGKAFAAAAVPSHLAKKRAPLG 187 1686
    NLTNLKAGDGNSRSSSAPSTLVANATKLAKTRKGSSTSSSIMGLSGSALPRYAS
    TKPSGVLPSVNPSIPRIEIAVDPMSCSMVVSPSRSDMQSVSLDESMSTCESFKS
    PDVEYIDNEDVSAVDSIDRKTFSNLYISDAAAKTAVNICERDVLMEMETDEKIV
    NVDDNYSDPQLCATIACDIYQHLRASEAKKRPSTDFMDRVQKDITASMRAILID
    WLVEVAEEYRLVPDTLYLTVNYIDRYLSGNVMNRQRLQLLGVACMMIAAKYEEI
    CAPQVEEFCYITDNTYFKEEVLQMESSVLNYLKFEMTAPTVKCFLRRFVRAAQG
    VNEVPSLQLECMANYIAELSLLEYDMLCYAPSLVAASAIFLAKFVITPSKRPWD
    PTLQHYTLYQPSDLGNCVKDLHRLCFNNHGSTLPAIREKYSQHKYKYVAKKYCP
    PSIPPEFFHNLVY
    277 Cyclin A MNKENAVGTKSEAPTIRITRSRSKALGTSTGMLPSSRPSFKQEQKRTVRANAKR 238 1653
    SASDENKGTMVGNASKQHKKRTVLNDVTNIFCENSYSNCLNAAKAQTSRQGRKW
    SMKKDRDVHQSGAVQIMQEDVQAQFVEESSKIKVAESMEITIPDKWAKRENSEH
    SISMKDTVAESSRKPQEFICGEKSAALVQPSIVDIDSKLEDPQACTPYALDIYN
    YKRSTELERRPSTIYMETLQKDVTPNMRGILVDWLVEVSEEYKLVPDTLYLTVN
    LIDRSLSQKFIEKQRLQLLGVTCMLIASKYEEICPPRVEEFCFITDNTYTSLEV
    LKMESRVLNLLHFQLSVPTVKTFLRRFVQAAQVSSEVPSVELEYLANYLAELTL
    VEYSFLKELPSLMAASAVLLARWTLNQSDNPWNLTLEHYTKYKASELKAAVLAL
    EDLQLNTSGSTLNAIREKYRQQKVNYSLLIHSKANHEIL
    278 Cyclin B MAGSDENNPGVVGGAHVQEGLRVGAGKMGAGNVQQRRALSNINSNIIGAPPYPC 235 1539
    AVNKRVLSEKNVNSENDLLNAAHRPITRQFAAQMAYKQQLRPEENKRTTQSVSN
    PSKSEDCAILDVDDDKMADDFPVPMFVQHTEAMLEEIDRMEEVEMEDVAEEPVT
    DIDSGDKENQLAVVEYIDDLYMFYQKAEASSCVPPNYMDRQQDINERMRGILID
    WLIEVHYKFELMDETLYLTVNLIDRFLAVQPVVKKKLQLVGVTAMLLACKYEEV
    SVPVVEDLILISDRAYSRKEVLEMERLMVNTLHFNMSVPTPYVFMRRFLKAAQS
    DKKLELLSFFIIELSLVEYDMLKFPPSLLAASAIYTALSTITRTKQWSTTCEWH
    TSYSEEQLLECARLMVTFHQRAGSGKLTGVHRKYSTSKFGHAARTEPANFLLDF
    RL
    279 Cyclin B MASRPIVPVQARGEAAIGGGAGKAAIGGGAGKQQKKNGAAEGRNRKALGDIGNL 158 1618
    VTVRGIEGKVQPHRPITRSFCAQLLANAQAAAAAENNKKQAVVNVNGAPSILDV
    PGAGKRAEPAAAAAAAVAKAAQKKVVKPKQKAEVIDLTSDSERAIEAKKKQQHH
    EPTKKEGEKSSRRNMPTLTSVLTARSKAACGMTKKPKEKVVDIDAGDAHNELAA
    FEYIEDIYTYYKEAENESLPRNYMSSQPEINEKMRAILVDWLIEIHNKFDLMPE
    TLYLTINIIDRFLSVKAVPRRELQLLGMGALFTASKYEEIWAPEVNDLVCIADR
    AYSHEQVLAMEKTILGKLEWTLTVPTHYVFLVRFIKASLGDRKLENMVYFLAEL
    GVMNYATLTYCPSMVAASAVYAARCTLGLTPLWNDTLKLHTGFSESQLMDCARL
    LVGYHAKAKENKLQVVYKKYSSSQREGVALIPPAKALLCEGGGLSSSSSLASSS
    280 Cyclin B MGLPDENNAALSKPTNLQVGGLEIGGRKFGQEIRQTRRALSVINQNLVGDRAYP 205 1530
    CHVVNKRGHSKRDAVCGKDQVDPVHRPLTRKFAAQTASTQQHCIEEAKKPRTAV
    QERNEFGDCIFVDVEDCQPSSENQPVPMFLEIPESRLDDDMEEVEMEDIVEEEE
    EEPIMDIDGRDKKNPLAVVDYIEDIYANYRRTENCSCVSANYMAQQADINEKMR
    SILIDWLIEVHDKFDLMHETLFLTVNLIDRFLARQSVVRKKLQLVGLVAMLLAC
    KYEEVSVPVVGDLILISDKAYTRKEVLEMESLMLNSLQFNMSVPTPYVFMRRFL
    KAAESDKKLEVLSFFLIELSLVEYEMVKFPPSLLAAAAIFTAQCTLYGFKQWTK
    TCEWHSNYTEDQLLECARMMVGFHQKAATGKLTGVHRKYGTSKFGYTSKCEPAN
    FLLGEMKNP
    281 Cyclin B MGLPDENNAALSKPTNLQVGGLEIGGRKFGQEIRQTRRALSVINQNLVGDRAYP 174 1499
    CHVVNKRGHSKRDAVCGKDQVDPVHRPLTRKFAAQTASTQQHCIEEAKKPRTAV
    QERNEFGDCIFVDVEDCQPSSENQPVPMFLEIPESRLDDDMEEVEMEDIVEEEE
    EEPIMDIDGRDKKNPLAVVDYIEDIYANYRRTENCSCVSANYMAQQADINEKMR
    SILIDWLIEVHDKFDLMHETLFLTVNLIDRFLARQSVVRKKLQLVGLVAMLLAC
    KYEEVSVPVVGDLILISDKAYTRKEVLEMEKLMLNSLQFNMSVPTPYVFMRRFL
    KAAESDKKLEVLSFFLIELSLVEYEMVKFPPSLLAAAAIFTAQCTLYGFKQWTK
    TCEWHSNYTEDQLLECARMMVGFHQKAATGKLTGVHRKYGTSKFGYTSKCEAAN
    FLLGEMKNP
    282 Cyclin D MAMVQRQGHDPSSPQEQEDGPSSFLSDDALYCEEGRFEEDDGGGGGQVDGIPLF 94 1332
    PSQPADRQQDSPWADEDGEEKEEEEAELQSLFSKERGARPELAKDDGGAVAARR
    EAVEWMLMVRGVYGFSALTAVLAVDYLDRFLAGFRLQRDNRPWMTQLVAVACLA
    LAAKVEETDVPLLVELQEVGDARYVFEAKTVQRMELLVLSTLGWEMHPVTPLSF
    VHHVARRLGASPHHGEFTHWAFLRRCERLLVAAVSDARSLKHLPSVLAAAAMLR
    VIEEVEPFRSSEYKAQLLSALHMSQEMVEDCCRFILGIAETAGDAVTSSLDSFL
    KRKRRCGHLSPRSPSGVIDASFSCDDESNDSWATDPPSDPDDNDDLNPLPKKSR
    SSSPSSSPSSVPDKVLDLPFMNRIFEGIVNGSPI
    283 Cyclin D MEASYQPHHHGHLRQHDPSSSQQEEQVPFDALYCSEEHWGEEDEEEGLASDGLL 176 1342
    SEERDHRLLSPRALLDQDLLWEDEELASLFSKEEPGGMRLNLENDPSLADARRE
    AVEWIMRVHAHYAFSALTALLAVNYWDRFTCSFALQEDKPWMTQLSAVACLSLA
    AKVEETQVPLLIDFQVEDSSPVFEAKNIQRMELLVLSSLEWKMNPVTPLSFLDY
    MTRRLGLTGHLCWEFLRRCENVLLSVISDCRFTCYLPSVIAASTMLHVINGLKP
    RLDVEDQTQLLGILAMGMDKIDACYKLIDDDHALRSQRYSHNKRKFGSVPGSPR
    GVMELCFSSDGSNDSWSVAASVSSSPEPHSKKSRAGEEAEDRLLRGLEGEEDDP
    ASADIFSFPH
    284 Cyclin D MALQEEDTRRHYPTAPPFSPDGLYCEDETFGEDLADNACEYAGGGARDGLCEIK 150 1283
    DPTLPPSLLGQDLFWEDGELASLVSRETGTHPCWDELISDGSVALARKDAVGWI
    LRVHGHYGFRPLTAMLAVNYLDRFFLSRSYQRDRPWISQLVAVACLSVAAKVEE
    TQVPILLDLQVANAKFVFESRTIQRMELLLMSTLDWRMNSVTPISFFDHILRRF
    GLTTNLHRQFFWMCERLLLSVVADVRLASFLPSVVATAAMLYVNKEIEPCICSE
    FLDQLLSLLKINEDRVNECYELILELSIDHPEILNYKHKRKRGSVPSSPSGVID
    TSFSCDSSNDSWGVASSVSSSLEPRFKRSRFQDQQMGLPSVNVSSMGVLNSSY
    285 Cyclin- MGQIQYSEKYFDDTYEYRHVVLPPDVAKLLPKNRLLSENEWRAIGVQQSRGWVH 101 367
    dependent YAIHRPEPHIMLFRRPLNYQQQQENQAQQNMLAK
    kinase
    regulatory
    subunit
    286 Histone MGSIDPPKAEQNGTAAAAVADPGQKPGAGDAMPPPPPVKHSNGTAAEPDVATKR 9 1352
    acetyltransferase RRMSVLPLEVGTRVMCRWRDGKYHPVKVIERRKLNPGDPNDYEYYVHYTEFNRR
    LDEWVKLEQLDLNSVETVVDEKVEDKVTGLKMTRHQKRKIDETHVEGHEELDAA
    SLREHEEFTKVKNIATIELGRYEIETWYFSPFPPEYNDCSKLYFCEFCLNFMKR
    KEQLQRHMKKCDLKHPPGDEIYRSGTLSMFEVDGKKNKVYGQNLCYLAKLFLDH
    KTLYYDVDLFLFYVLCECDDRGCHMVGYFSKEKHSEESYNLACILTLPPYQRKG
    YGKFLIAFSYELSKKEGKVGTPERPLSDLGLLSYKGYWTRVLLDILKKHKANIS
    IKELSDMTAIKADDILNTLQSLDLIQYRKGQHVICADPKVLDRHLKAAGRGGLE
    VDVSKLIWTPYREQG
    287 Histone MAQKHSTAPDPAAEPKKRRRVGFSGIDAGVDPNGCFKVYLVSREEEVGAPDSFC 89 1486
    acetyltransferase LDPVDLSHFFEEEDGKIYGYEGLKISVWVSCVSFHSYAEIAFESKSDGGKGITD
    LNTALKNMFGETLVDNKDDFLQTFSKETQFIRSTVSAGEILKHKHSDDHVNDSV
    SNLKVGSDVEAVRMLMGDMTAGHLYSRLVPLVLLLVDGSSPIDVTDSSWELYLL
    IQKTSDQQGNFHDRLLGFAAVYRFYHYPDSSRLRLGQILVLPLYQRKGYGRYLL
    EVLNNVAIADDVYDFTIEEPVDNLQHLRTCIDVQRLLSFDKVQQAVNSTVSQLK
    QGKLSKKTYIPRLLPPPSVVEDARKRFKINKKQFLQCWEILVYLGLDPADKSIQ
    DYFSVISNRVRADILGKDSETAGKKVIEVPSDFDPEMSFVMHRAKAGGEANGIQ
    VEDNQNKQEEQLQQLIDERLKDIKLIAEKVTQK
    288 Histone MAQKHSTAPDPAAEPKKRRRVGFSGIDAGVDPNGCFKVYLVSREEEVGAPDSFC 89 1477
    acetyltransferase LDPVDLSHFFEEEDGKIYGYEGLKISVWVSCVSFHSYAEIAFESKSDGGKGITD
    LNTALKNMFGETLVDNKDDFLQTFSKETQFIRSTVSAGEILKHKHSDGHVNDSV
    SNLKVGSDVEAVRMLMGDMTAGHLYSRLVPLVLLLVDGSNPIDVTDSSWELYLL
    IQKTSDQQGNFHDRLLGFAAVYRFYHYPDSLRLRLGQILVLPLYQRKGYGHYLL
    EVLNNVAIADDVYDFTIEEPVDNLQHLRTCIDVQRLLSFDKVQQAVNSTVSQLK
    QGKLSKKTYIPRLLPPPSVVEDARKRFKINKKQFLQCWEILVYLGLDPADKSIQ
    DYFSVISNRVRADILGKDSETAGKKVIEVPSDFDPEMSFVLHRAKAGGETNGIQ
    VEDNQNKQEEQLQQLIDERLKDIKLIAQKVSRK
    289 Histone MALPMEFWGVEVKAGQPLKVNPGNAKILHLSQASLGECKSSKGNESVPLHVKFG 160 1062
    deacetylase DQKLVLGTLSTENFPQLAFDLVFEKEFELSHNWKSGSVYFCGYKSVVHDDDDEF
    SDLESDSEEEDLPMIGVENGKVAAQASAKTATASANASKVESSGKQKARIPQPM
    KVDEDDSDEDDDDEDEDESDEEGVDGEADSDEEEDESDEEETPKKAEIGKKRAA
    DSATKTPVPAKKSKLPTPQKTDGKKGGHTATPHPAKQAGKNPANSANKSQSPKS
    AGQVSCKSCSKTFNSDGALQSHSKAKHGGK;
    290 Histone MEFWGVEVKAGQPLKVNPGNAKILHLSQASLGECKSSKGNESVPLHVKFGDQKL 172 1077
    deacetylase VLGTLSTENFPQLAFDLVFEKEFELSHNWKSGSVYFCGYKSVVHDDDDEFSDLE
    SDSEEEDLPMIGVENGKVAAQASAKTATASANASKVESSGKQKASIPQPMKVDE
    DDSDEDDDEDDDDEDESDEGVDGEADSDEEEDESDEEETPKKAEIGKKRAADSA
    TKTPVPAKKSKLPTPQKTDGKKGGHTATPHPAKQAGKNPANSANKSQSPKSAGQ
    VSCKSCSKTFNSDGALQSHSKAKHGGK
    291 Histone MEFWGVEVKSGEPLNVEPGAETVVHLSQACLGETKEKTKESVLLYVHIGVQKLV 66 989
    deacetylase LGTLSADKFPQIPFDLVFEKSFKLSHNWKNGSVFFSGYKTLLPCGSDADSPYSD
    SDTDEGLPINVTAQADVPAKKAPVTANANAAKPNLASAKQKVKIVESNEDGKNE
    GDDDEDADVSSDDDAEDDSGDEDMVDGGDESSDEDDDDSEEGESSEEEEPKAQP
    SKKRPADSVLKTPASDKKSKLETPQKTDGKKASEHVATPYPSKQAGKAIASKGQ
    AKQQTPNSNEFSCKPCNRSFKSDQALQSHNKAKHGGS
    292 Histone MDTGGNSLPSGPDGVKRKVCYFYDPEVGNYYLLQHMQVLKPVPARDRDLCRFHA 111 1541
    deacetylase DDYVAFLRSITPETQQDQLRQLKRFNVGEDCPVFDGLHSFCQTYAGGSVGGAVK
    LNHGLCDIAINWAGGLHHAKKCEASGFCYVNDIVLGILELLKQHERVLYVDIDI
    HHGDGVEEAFYTTDRVMTVSFHKFGDYFPGTGDIRDIGYGKGKYYSLNVPLDDG
    IDDESYHSLFKPIIGKVMEVFKPGAVVLQCGADSLSGDRLGCFNLSIKGHAECV
    RYMRSFNVPVLLLGGGGYTIRNVARCWCYETGVALGLEVDDKMPQHEYYEYFGP
    DYTLHVAPSNMENKNSRQLLEEIRSKLLENLSKLQHAPSVPFQERPPDTELPEA
    DEDQEDPDERWDPDSDMDVDEDRKPLPSRVKRELIVEPEVKDQDSQKASIDHGR
    GLDTTQEDNASIKVSDMNSMITDEQSVKMEQDNVNKPSEQIFPK
    293 Histone MDTGGNSLPSGPDGVKRKVCYFYDPEVGNYYYGQGHPMKPHRIRMTHALLAHYG 116 1615
    deacetylase LLQHMQVLKPVPARDRDLCRFHADDYVAFLRSITPETQQDQLRQLKRFNVGEDC
    PVFDGLHSFCQTYAGGSVGGAVKLNHGLCDIAINWAGGLHHAKKCEASGFCYVN
    DIVLGILELLKQHERVLYVDIDIHHGDGVEEAFYTTDRVMTVSFHKFGDYFPGT
    GDIRDIGYGKGKYYSLNVPLDDGIDDESYHSLFKPIIGKVMEVFKPGAVVLQCG
    ADSLSGDRLGCFNLSIKGHAECVRYMRSFNVPVLLLGGGGYTIRNVARCWCYET
    GVALGLEVDDKMPQHEYYEYFGPDYTLHVAPSNMENKNSRQLLEDIRSKLLENL
    SKLQHAPSVPFQERPPDTELPEADEDQEDPDERWDPDSDMDVDEDRKPLPSRVK
    RELIVEPEVKDQDSQKASIDHGRGLDTTQEDNASIKVSDMNSMITDEQSVKMEQ
    DNVNKPSEQIFPK
    294 Histone MRPKDRISYFYDGDVGSVYFGPNHPMKPHRLCMTHHLVLSYELHTKMEIYRPHK 155 1453
    deacetylase AYPAELAQFHSPDYVEFLHRITPDTQHLFPNDLAKYNLGEDCPVFENLFEFCQI
    YAGGTIDAARRLNNQLCDIAINWAGGLHHAKKCEASGFCYINDLVLGILELLKY
    HARVLYIDIDVHHGDGVEEAFYFTDRVMTVSFHKFGDMFFPGTGDVKEIGGKEG
    KFYAINVPLKDGIDDTSFTRLFKAIISKVVETYQPGAIVLQCGADSLAGDRLGC
    FNLSIDGHSECVRFVKKFNLPLLVTGGGGYTKENVARCWVVETGVLLDTELPNE
    IPENEYFKYFAPDYSLKIPRGNIVLENLNSKSYLSAIKVQVLENLENIQHAPSV
    QMQEVPPDFYIPDFDEDEQNPDERMDQHTQDKQIQRDDEYYDGDNDNDHNMDDS
    295 Histone MTVAEDFHVNNRSKMVSQATPESRLTGGEDDNSLHNQVDELLCQELPERQVILE 228 2033
    deacetylase FEGTRPKPYFSDHNGGENSALGVRATEDDLNSDVEAEEKQKEMITLEDMYKNDGT
    LYDDDEDDSDWEPVKRQVELMRWFCTNCTMVNVEDVFLCDICGEHRDSGILRHG
    FYASPFMQDVGAPSVEAEVQESREDHARSSPPSSSTVVGFDEKMLLHSEVEMKS
    HPHPERADRLQAIAASLATAGIFPGRCRSLPVREITKEELQMVHSSEHVDAVEM
    TSHMFSSYFTPDTYANEHSARAARIAAGLCADLASTIISGRSKNGFALVRPPGH
    HAGIKHAMGFCLHNNAAVAALAAQGAGAKKVLIVDWDVHHGNGTQEIFDGNKSV
    LYISLHRHEGGNFYPGTGAAHEVGTMGAEGYCVNIPWSRRGVGDNDYVFAFHHI
    VLPIASAFAPDFTIISAGFDAARGDPLGCCDVTPAGYAQMTHMLSALSGGKLLV
    ILEGGYNLRSISSSAVAVIKVLLGDSPISEIADAVPSKAGLRTVLEVLKIQRSY
    WPSLESIFWELQSQWGIFLVDNRRKQIRKRRRVLVPIWWKWGRKSVLYHLLNGH
    LHVKTKR
    296 Histone MAAAPSSPPTNRVDVFWHDGMLSHDTGRGVFDTGSDPGFLDVLEKHPENPDRVR 110 1258
    deacetylase NMVSILKRGPISPFISWHTATPALISQLLSFHSPEYINELVEADKNGGKVLCAG
    TFLNPGSWDAALLAAGNTLSAMKYVLDGKGKIAYALVRPPGHHAQPSQADGYCF
    LNNAGLAVRLALDSGCKRVVVVDIDVHYGNGTAEGFYQSSDVLTISLHMNHGSW
    GPSHPQSGSVDELGEDEGYGYNMNIPLPNGTGDRGYEYAVTELVVPAVESFKPE
    MVVLVVGQDSSAFDPNGRQCLTMDGYRAIGRTIRGLADRHSGGRILIVQEGGYH
    VTYSAYCLHATVEGILDLPDPLLADPIAYYPEDEAFPVKVVDSIKRYLVDKVPF
    LKEH
    297 Histone MVESSGGASLPSVGQDARKRRVSYFYEPTIGDYYYGQGHPMKPHRIRMAHNLIV 50 1462
    deacetylase HYYLHRRMEISRPFPAATTDIRRFHSEDYVTFISSVTPETVSDPAFSRQLKRFN
    VGEDCPVFDGIFGFCQASAGGSMGAAVKLNRGDSDIALNWAGGLHHAKKSEASG
    FCYVNDIVLGILELLKVHKRVLYVDIDVHHGDGVEEAFYTTDRVMTVSFHKFGD
    FFPGSGHIKDTGAGPGKNYALNVPLNDGIDDESFRGMFRPIIQKVMEVYQPDAV
    VLQCGADSLSGDRLGCFNLSVKGHADCLRFLRSFNVPLMVLGGGGYTMRNVARC
    WCYETAVAVGVEPENDLPYNEYYEYFGPDYTLHVEPCSMENLNAPKDLERIRNM
    LLEQLSRIPHAPSVPFQMTPPITQEPEEAEEDMDERPKPRIWNGEDYESDAEED
    KSQHRSSNADALHDENVEMRDSVGENSGDKTREDRSPS
    298 MAT1 CDK- MVVPSSNPHNREMAIRRRMASTFNKREDDFPSLREYNDYLEEVEEMTFNLIEGV 176 739
    activating DVPTIEAKIAKYQEENAEQIMINRAKKAEEFAAALAASKGLPPQTDPDGALNSQ
    kinase assembly AGLSVGTQGQYAPAIAGGQPRPTGMAPQPVPLGTGLDTHGYDDEEMIKLRAERG
    factor GRAGGWSIELSKKRALEEAFGSLWL
    299 Peptidylprolyl MAAIISCHHYHSCCSSLIASKWVGARIPTSCFGRSSTQSNNAASVRQFVTRCSS 150 1529
    isomerase SPSSRGQWQPHQNGEKGRSFSLRECAISIALAVGLVTGVPSLDMSTGNAYAASP
    ALPDLSVLISGPPIKDPEALLRYALPINNKAIREVQKPLEDITDSLKVAGLRAL
    DSVERNVRQASRVLKQGKNLIVSGLAESKKDHGVELLDKLEAGMDELQQIVEDG
    NRDAVAGKQRELLNYVGGVEEDMVDGFPYEVPEEYKNMPLLKGRAAVDMKVKVK
    DNPNLEECVFRIVLDGYNAPVTAGNFVDLVERHFYDGMEIQRADGFVVQTGDPE
    GPAESFIDPSTEKPRTIPLEIMVDGEKAPVYGATLEELGLYKAQTKLPFNAFGT
    MAMARDEFEDNSASSQIFWLLKESELTPSNANILDGRYAVFGYVTENQDFLADL
    KVGDVIESVQVVSGLDNLANPSYKIAG;
    300 Peptidylprolyl MAGEDFDIPPADEMNEDFDLPDDDDDAPVMKAGDEKEIGKQGLKKKLVKEGDAW 247 1971
    isomerase ETPDNGDEVEVHYTGTLLDGTQFDSSRDRGTPFKFTLGQGQVIKGWDQGIKTMK
    KGENAIFTIPPELAYGEAGSPPTIPPNATLQFDVELLSWTSVKDICKDGGIFKK
    ILVEGEKWENPKDLDEVLVKYEFQLEDGTTIARSDGVEFTVKEGHFCPAVAKAV
    KTMKKGEKVLLTVKPQYGFGEKGKPASGDEGAVPPNATLQITLELVSWKTVSEV
    TDDKKVIKKILKEGEGYERPNEGAVVEVKLIGKLQDGTVFVKKGHDDCEELFKF
    KIDEEQVVDGLDKAVMNMKKGEVALLTVAPEYAFGSSESKQDLAVVPPSSTVYY
    EVELVSFVKDKESWDMNTEEKIEAAGKKKEEGNVIFKAGKYAKASKRYEKAVKY
    IEYDTSFSEDEKKQAKALKVACNLNDAACKLKLKDYNQAEKLCTKVLELDSRNV
    KALYRRAQAYIELSDLDLAEFDIKKALEIDPHNRDVKLEYKVLKEKVKEFNKKD
    AKFYGNMFAKMSKLEPVEKTAAKEPEPMSIDSKA;
    301 Peptidylprolyl MSTVYVLEPPTKGKVVLNTTHGPLDVELWPKEAPKAVRNFVQLCLEGYYDNTIF 136 1644
    isomerase HRIIKDFLVQGGDPTGSGTGGESIYGDAFSDEFHSRLRFKHRGLVACANAGSPH
    SNGSQFFITLDRCDWLDRKNTIFGKITGDSIYNLSGLAEVETDKSDRPLDPPPK
    IISVEVLWNPFEDIVPRAPVRSLVPTVPDVQNKEPKKKAVKKLNLLSFGEEAEE
    EEKALVVVKQKIKSSHDVLDDPRLLKEHIPSKQVDSYDSKTARDVQSVREALSS
    KKQELQKESGAEFSNSFREIADDEDDDDDDASFDARMRRQILQKRKELGDLPPK
    PKPKSRDGISARKERETSISRDKDDDDDDDQPRVEKLSLKKKGIGSEARGERMA
    NADADLQLLNDAERGRQLQKQKKHRLRGREDEVLTKLETFKASVFGKPLASSAK
    VGDGDGDLSDWRSVKLKFAPEPGKDRMTRNEDPNDYVVVDPLLEKGKEKFNRMQ
    AKEKRRGREWAGKSLT;
    302 Peptidylprolyl MASAISMHSSGLLLLQGTNGKDVTEMGKAPASSRVANMQQRKYGATCCVARGLT 48 836
    isomerase SRSHYASSLAFKQFSKTPSIKYDRMVEIKAMATDLGLQAKVTNKCFFDVEIGGE
    PAGRIVIGLFGDDVPKTVENFRALCTGEKGFGYKGCSFHRIIKDFMIQGGDFTR
    GNGTGGKSIYGSTFEDENFALKHVGPGVLSMANAGPSTNGSQFFICTVKTPWLD
    NRHVVFGQVVDGMDVVQKLESQETSRSDVPRQPCRIVNCGELPLDG;
    303 Peptidylprolyl MAASFTALSNVGSLSSPRNGSEIRRFRPSCNVAASVRPPPLKAGLSASSSSSFS 49 822
    isomerase GSLRLIPLSSSPQRKSRPCSVRASAEAAAAQSKVTNKVYLDISIGNPVGKLVGR
    IVIGLYGDDVPQTAENFRALCTGEKGFGYKGSTVHRVIKDFMIQGGDFDKGNGT
    GGKSIYGRTFKDENFKLSHVGPGVVSMANAGPNTNGSQFFICTVKTPWLDQRHV
    VFGQVLEGMDIVRLIESQETDRGDRPRKRVVVSDCGELPVV;
    304 Peptidylprolyl MAEAIDLTGDGGVMKTIVRRAKPDAVSPSETLPLVDVRYEGVLAETGEVFDSTH 185 751
    isomerase EDNTLFSFEIGKGSVISAWDTALRTMKVGEVAKITCKPEYAYGSTGSPPDIPPD
    ATLIFEVELVACKPCKGFSVTSVTEDKARLEELKKQREIAAATKEEEKKRREEA
    KAAAAARVQAKLDAKKGHGKGKGKAK;
    305 Peptidylprolyl MGNPKVFFDMSIGGQPAGRIVMELYADVVPRTAENFRALCTGEKGAGRSGKPLH 103 621
    isomerase YKGSSFHRVIPGFMCQGGDFTAGNGTGGESIYGSKFADENFVKKHTGPGVLSMA
    NAGPGTNGSQFFVCTAKTEWLDGKHVVFGQIVDGMDVVKAIEKVGSSSGRTSKP
    VVVADCGQLS
    306 Peptidylprolyl MPNPKVFFDMTIGGAAAGRVVMELYADTTPRTAENFRALCTGEKGVGRSKKPLH 41 559
    isomerase YKGSKFHRVIPSFMCQGGDFTAGNGTGGESIYGVKFADENFIKKHTGPGILSMA
    NAGPGTNGSQFFICTTKTEWLDGKHVVFGKVVEGMEVVKAIEKVGSSSGRTSKP
    VVVADCGQLP
    307 Peptidylprolyl MAEAIDLTGDGGVMKTIVRRAKPDAVSPSETLPLVDVRYEGVLAETGEVFDSTH 127 693
    isomerase EDNTLFSFEIGKGSVISAWDTALRTMKVGEVAKITCKPEYAYGSTGSPPDIPPD
    ATLIFEVELVACKPCKGFSVTSVTEDKARLEELKKQREIAAATKEEEKKRREEA
    KAAAAARVQAKLDAKKGHGKGKGKAK
    308 Peptidylprolyl MATARSFFLCALLLLATLYLAQAKKSEDLKEVTHKVYFDVEIAGKPAGRIVMGL 28 639
    isomerase YGKAVPKTAENFRALCTGEKGTGKSGKPLHYKGSSFHRIIPSFMLQGGDFTLGD
    GRGGESIYGEKFADENFKLKHTGPGLLSMANAGPDTNGSQFFITTVTTSWLDGR
    HVVFGKVLSGMDVVYKVEAEGRQSGTPKSKVVIADSGELPL
    309 Peptidylprolyl MMRREISVLLQPRFVLAFLALAVLLLVFAFPFSRQRGDQVEEEPEITHRVYLDV 135 812
    isomerase DIDGQHLGRIVIGLYGEVVPRTVENFRALCTGEKGKSANGKKLHYKGTPFHRII
    SGFMIQGGDVIYGDGKGYESIYGGTFADENFRIKHSHAGIISMVNSGPDSNGSQ
    FFITTVKASWLDGEHVVFGRVIQGMDTVYAIEGGAGTYNGKPRKKVIIADSGEI
    PKSKWDEER
    310 Peptidylprolyl MWATAEGGPPEVTLETSMGSFTVELYFKHAPRTSRNFIELSRRGYYDNVKFHRI 119 613
    isomerase IKDFIVQGGDPTGTGRGGESIYGKKFEDEIKPELKHTGAGILSMANAGPNTNGS
    QFFITLAPCPSLDGKHTIFGRVCRGMEIIKRLGSVQTDNNDRPIHDVKILRTSV
    KD
    311 Peptidylprolyl MSNPKVFFDILIGKMKAGRVVMELFADVTPKTAENFRALCTGEKGIGRSGKPLH 38 562
    isomerase YKGSTFHRIIPNFMCQGGDFTRGNGTGGESIYGMKFADENFKIKHTGLGVLSMA
    NAGPDTNGSQFFICTEKTPWLDGKHVVFGKVIDGYNVVKEMESVGSDSGSTRET
    VAIEDCGQLSEN
    312 Peptidylprolyl MDDDFEFPASSNVENDDDDGMDMDDMGGDVPEEEDPVASPAVLKVGEEREIGKA 109 1872
    isomerase GFKKKLVKEGEGWETPSSGDEVEVHYTGTLLDGTKFDSSRDRGTPFKFKLGRGQ
    VIKGWDEGIKTMKKGENAIFTIPPELAYGESGSPPTIPPNATLQFDVELLSWSS
    VKDICKDGGILKKVLVEGEKWDNPKDLDEVFVKYEASLEDGTLISKSDGVEFTV
    GDGYFCAALAKAVKTMKKGEKVLLTVMPQYAFGETGRPASGDEAAVPPDASLQI
    MLELVSWKTVSDVTKDKKVLKKTLKEGEGYERPNDGAAVQVRLCGKLQDGTVFV
    KKDDEEPFEFKIDEEQVIDGLDRAVKNMKKGEVALVTIQPEYAFGPTESQQDLA
    VVPANSTVYYEVELLSFVKEKESWEMNNQEKIEAAARKKEEGNAAFKAGKYVRA
    SKRYEKAVRFIEYDSSFSDEEKQQAKTLKNTCNLNDAACKLKLKDFKEAEKLCT
    KVLEGDGKNVKALYRRAQAYIQLVDLDLAEQDIKKALEIDPNNRDVKLEYKILK
    EKVREYNKRDAQFYGNMFAKMNKLEHSRTAGMGAKHEAAPMTIDSKA
    313 Peptidylprolyl MAKPRCFMDISIGGELEGRIVGELYTDVAPKTAENFRALCTGEKGIGPHTGAPL 74 1159
    isomerase HYKGVRFHRVIKGFMVQGGDISAGDGTGGESIYGLKFEDENFDLKHERKGMLSM
    ANSGPNTNGSQFFITTTRTSHLDGKHVVFGRVVKGMGVVRSVEHVTTAAGDCPT
    VDVVIADCGEIPAGADDGIRNFFKDGDTYPDWPADLDESPAELSWWMDAVDSIK
    AFGNGSYKKQDYKMALRKYRKALRYLDICWEKEGIDEVESSSLRKTKSQIFTNS
    SACKLKLCDLKGALLDAEFAVRDGENNAKAYFRQGQAHMELNDIDAAAESFSKA
    LELEPNDVGIKKELNAAKKKIFERREQEKRAYRKMFL
    314 Peptidylprolyl MTKRKNPLVFLDVSIDGDPVERIVIELFADTVPRTAENFRSLCTGEKGVGKTTG 54 2045
    isomerase KPLHYKGSYFHRIIKGFMAQGGDFSNGNGTGGESIYGGKFADENFKLAHDGPGL
    LSMANGGPNTNGSQFFIIFKRQPHLDGKHVVFGKVMRGMEVVKKIEQVGSANGK
    PLQPVKIVDCGETSETGTQDAVVEEKSKSATLKAKKKRSARDSSSESRGKRRQR
    KSRKERTRKRRRYSSSDSYSSESSDSDSESYSSDTESESKSHSESSVSDSSSSD
    GRRRKRKSTKREKLRRQRGKDSRGEQKSARYDKKSRHKSADSSSDSESESSSRS
    RSRDDKKKSSRRESARSVSKLKDAEANSPENLESPRDREIKKVEDNSSHEEGEF
    SPKNDVQHNGHGTDAKFGKYDDQRPRSDGSKKSSGSMRDSPKRLANSVPQGSPS
    SSPAHKASEPSSSIRARNPSRSPAPDGNSKRIRKGRGFTERFSYARRYRTPSPE
    DVTYRPYHYGRRNFHDRRNDRYSNYRSYSERSPHRRYRSPPRGRSPPRYQRRRS
    RSRSVSRSPGGNKGRYRGRDQSRSRSRSRSRSPRRGSSPANKQLPLSERLKSRL
    GTRVDEHSPRRRRSSSRSHDSSRSRSPDEVPDKHEGKAAPVSPARSRSSSPSGR
    GLVSYGDASPDSGIN
    315 Peptidylprolyl MSVLLVTSLGDIVVDLHADRCPLTCKNFLKLCRIKYYNGCVFHTVQKDFTAQTG 53 1879
    isomerase DPTGTGTGGDSVYKFLYGDQARFFMDEIHLDLKHSKTGTVAMASGGENLNASQF
    YFTLRDDLDYLDGKHTVFGEVAEGLETLTRINEAYVDEKGRPYKNIRIRHTYIL
    DDPFDDPPQLAELIPDASPEGKPKDEVVDDVRLEDDWVPLDEQLGPAQLEEAIR
    AKEAHSRAVVLESIGDIPDAEIKPPDNVLFVCKLNPVTEDEDLHTIFSRFGTVV
    SADVIRDFKTGDSLCYAFIEFENKDSCEQAYFKMDNALIDDRRIKVDFSQSVAK
    LWSQFKRKDSQAAKGKGCFKCGAPDHMARECPGSSTRQPLSKYILKEDNAQRGG
    DDSRYEMVFDEDAPESPSHGKKRRGRDDRDDRHKMSRQSVEETKFNDREGGHSV
    DKHRQSERSKHREDEMSRDSKASEAGRRRIDRDFPEEERDGEKYTESHRDRDGK
    RGDYRDYRKGEADVQTHGDRRGDENYRRKSAAYDDGHEGAGAARRKDSNDDHHA
    YRRGYGDSRKGTRDEDDDGRGRRDDPSYRRSSGHKDSSNGGREEQKYRSGETDG
    KSHPERSHRGDRRR
    316 Peptidylprolyl MRPFNGGSSIACLVLVIAAGALAESQGPHLGSARVVFQTNYGDIEFGFFPGVAP 7 690
    isomerase RTVDHIFKLVRLGCYNTNHFFRVDKGFVAQVADVANGRTAPMNDEQRTEAEKTI
    VGEFSNVKHVRGILSMGRYDDPDSAQSSFSILLGDAPHLDGKYAIFGRVTKGDE
    TLKKLEQLPTRREGMFVMPTERITILSSYYYDTGAESCEEENSTLRRRLAASAV
    EVERQRMKCFP
    317 Peptidylprolyl MPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRALCTGEKGTGRSGKPLH 83 601
    isomerase FKGSSFHRVIPGFMCQGGDFTRGNGTGGESIYGEKFADENFVKKHTGPGILSMA
    NAGPNTNGSQFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGSGRTSKP
    VVIADSGQLA
    318 Peptidylprolyl MRFTSITSAIALFAAAASALDKPLDIKVDKAVECSRKTKAGDKIQVHYRGTLEA 125 535
    isomerase DGSEFDASYKRGQPLSFHVGKGQVIKGWDQGLLDMCPGEKRTLTIQPDWGYGSR
    GMGPIPANSVLIFETELVEIAGVAREEL
    319 Peptidylprolyl MGNPKVFFDMSIGGQPAGRIVMELYADVVPRTAENFRALCTGEKGAGRSGKPLH 55 573
    isomerase YKGSSFHRVIPGFMCQGGDFTAGNGTGGESIYGSKFADENFVKKHTGPGVLSMA
    NAGPGTNGSQFFVCTAKTEWLDGKHVVFGQIVDGMDVVKAIEKVGSSSGRTSKP
    VVVADCGQLS
    320 Peptidylprolyl MAVATRSRWVAMSVAWILVLFGTLALIQNRLSDTGASSDPKLVHRKVGEEKKKP 147 842
    isomerase DDLEEVTHKVFFDVEIGGKPAGRIVMGLFGKTVPKTVENFRALCTGEKGIGKSG
    KPLNYKGSQFHRIIPKFMIQGGDFTLGDGRGGESIYGNKFSDENFKLKHTDAGR
    LSMTNAGPDTNGSQFFITTVTTSWLDGRHVVFGKVLSGMDVVHKIEAEGGQSGQ
    PKSIVVISDSGELDL
    321 Peptidylprolyl MAVTLHTNLGDIKCEIFCDEVPKAAEHNARGILSMANSGPNTNGSQFFIAYAKQ 167 487
    isomerase PHLNGLYTIFGRVIHGFEVLDIMEKTQTGPGDRPLAEIRLNRVTIHANPLAG
    322 Peptidylprolyl MAVATRSRWVAMSVAWILVLFGTLALIQNRLSDTGASSDPKLVHRKVGEEKKKP 195 890
    isomerase DDLEEVTHKVFFDVEIGGKPAGRIVMGLFGKTVPKTVENFRALCTGEKGIGKSG
    KPLNYKGSQFHRIIPKFMIQGGDFTLGDGRGGESIYGNKFSDENFKLKHTDAGR
    LSMANAGPDTNGSQFFITTVTTSWLDGRHVVFGKVLSGMDVVHKIEAEGGQSGQ
    PKSIVVISDSGELDL
    323 Peptidylprolyl MGNPKVFFDMSIGGQPAGRIVMELYADVVPRTAENFRALCTGEKGAGRSGKPLH 68 586
    isomerase YKGSSFHRVIPGFMCQGGDFTAGNGTGGESIYGSKFADENFVKKHTGPGVLSMA
    NAGPGTNGSQFFVCTAKTEWLDGKHVVFGQIVDGMDVVKAIEKVGSSSGRTSKP
    VVVADCGQLS
    324 Retinoblastoma MSPVAANAMEEAAEPEVPAPVTPSKDDADTDAAVSRFLGFCKSKLGLAEGNCVQ 182 3265
    related protein SSTLLRKTAHVLRSSGTVIGTGTAEEAERYWFAFVLYTVRRVGERKAEDEQNGS
    DETEVPLSRILKASVLNLIDFFKEIPQFVIKAGAIVSGIYGANWDSRLEAREMQ
    TNYVHLCILCKFYKRICGEFFILNDAKDDMKSADSSTSDPVIMYQPFGWLLFLA
    LRIHALSRFKDLVSSTNALVSVLAILIIHLPTRFRKFSISDSSQLVKRSEKGVD
    LVGSLAYRYDTSEDEIKRTLEKANNVIAEILGITPPPASECKAENLENVDTDGL
    IYFGNLMEETSLSSILSTLEKIYEDATRNDSEFDERVFINDDDSLLVSGSLSGA
    AINLTGAKRKYDSFASPAKTITRPLSPSRSPASHINGIIGGTNLRITATPVATA
    MTTAKWLRTFVSPLPSKPSTDLQGFLASCDRDVTSDVIRRANIILEAIFPNSPI
    GERTVTGGLQNANLMDNMWAEQRRLEALKLYYRVLEAMCRAEAQILHSNNLTSL
    LTNERFHRCMLACSAELVLATHKTVTMLFPAVLERTGITAFDLSKVIESFVRHE
    ETLPRELRRHLNTLEERLLENMVWERGSSMYNSLVVARPALAPEINRLGLLPEP
    MPSLDAIALLINFSSSGLPQSPVQKHEASPGQNGDIRSPKRISTEYRSVLVERN
    FTSPVKDRLLALSNIKSKLPPPPLQSAFASPTRPHPGGGGETCAETAIHIFFSK
    ITKLAAVRINAMLERLQLSQQIKEGVYCLFQQILSQRTNLFFNRHIDQVILCCF
    YGVAKINQINLTFREIIYNYRKQPQCKPQVFRNVFVDWSTRRNGKAGNEHVDII
    SFYNEIFIPSVKPLLVELGPTGATTRTNRTSEVGNKNDAQCPGSPKISSFPTLP
    DMSPKKVSASHNVYVSPLRSSKMDASISHSSKSYYACVGESTHAYQSPSKDLVA
    INSRLNGNRKVRGTLNFDDVDAGLVSDSMVANSLYLQNGSSMSSSTAKSSEKPES
    325 WD40 repeat MRPILMKGHERPLTFLKYNREGDLLFSCAKDHTPTVWFADNGERLGTYRGHNGA 165 1145
    protein VWCCDVSRDSMRLITGSADTTAKLWSVQNGTQLFTFNFDSPARSVDFSIGDKLA
    VITTDPFMELPSAIHVKRIARDPADQASESVLVLRGHQGRIARAVWGPLNKTII
    SAGEDAVIRIWDSETGKLLRESDKETGHKKAVTSLMKSVDGSHFVTGSQDKSAK
    LWDIRTLTLIKTYVTERPVNAVTMSPLLDHVVLGGGQDASAVTMTDHRAGKFEA
    KFFDKILQEEIGGVKGHFGPINALAFNPDGKSFSSGGEDGYVRLHHFDPDYFNI
    KI
    326 WD40 repeat MDKKRTVVPLVCHGHSRPVVDLFYSPITPDGFFLISASKDSSPMLRNGETGDWI 529 1569
    protein GTFEGHKGAVWSCCLDTNALRAASGSADFSAKLWDALSGDELHSFEHKHIVRSC
    AFSEDTHLLLTGGVEKILRIFDLNRPDAPPREVDNSPGSIRTVAWLHSDQTILS
    SCTDIGGVRLWDVRSGKIVQTLETKSPVTSSEVSQDGRYITTADGSTVKFWDAN
    HFGLVKSYNMPCNIESASLEPKLGNKFIAGGEDMWVHIFDFHTGEEIGCNKGHH
    GPVHCVRFSPGGESYASGSEDGTIRIWQTGPANNVEGDANPSNGPVTGKAKVGA
    DEVTRKVEDLQIGKEGKDWREG
    327 WD40 repeat MAEGLILKGTMRAHTDMVTAIAIPIDNSDMVVTSSRDKSIILWHLTKEEKVYGV 156 1136
    protein PRRRLTGHSHFVQDVVLSSDGQFALSGSWDGELRLWDLATGVSARRFVGHTKDV
    LSVAFSIDNRQIVSASRDRTIKLWNTLGECKYTIQEGEAHTDWVSCVRFSPNTL
    QPTIVSASWDRTIKVWNLTNCKLRNTLAGHNGYVNTVAVSPDGSLCASGGKDGV
    ILLWDLAEGKRLYNLEAGAIIHSLCFSPNRYWLCAATENSIKIWDLESKSIVED
    LRVDLKNEADKTDGTTTAASNKKVIYCTSLNWSADGSTLFSGYNDGVIRVWGTG
    RY
    328 WD40 repeat MAEGLHLKGTMKAHTDMVTAIAVPIDNADMIVTSSRDKSIILWHLTKEDKVYGV 90 1073
    protein PRRRLTGHSHFVQDVVLSSDGQFALSGSWDGELRLWDLATGVSARRFVGHTKDV
    LSVAFSIDNRQIVSASRDRTIKLWNTLGECKYTIQEGEAHNDWVSCVRFSPNTL
    QPTIVSASWDRTVKVWNLTNCKLRNTLQGHSGYVNTVAVSPDGSLCASGGKDGV
    ILLWDLAEGKKLYSLEAGAIIHSLCFSPNRYWLCAATENSIKIWDLESKSIVED
    LRVDLKNEADMSDGTTGAMSSNKKVIYCTSLNWSADGSTLFSGYNDGVIRVWGI
    GRY
    329 WD40 repeat MAEGLHLKGTMKAHTDMVTAIAVPIDNADMIVTSSRDKSIILWHLTKEDKVYGV 66 1049
    protein PRRRLTGHSHFVQDVVLSSDGQFALSGSWDGELRLWDLATGVSARRFVGHTKDV
    LSVAFSIDNRQIVSASRDRTIKLWNTLGECKYTIQEGEAHNDWVSCVRFSPNTL
    QPTIVSASWDRTVKVWNLTNCKLRNTLQGHSGYVNTVAVSPDGSLCASGGKDGV
    ILLWDLAEGKKLYSLEAGAIIHSLCFSPNRYWLCAATENSIKIWDLESKSIVED
    LRVDLKNEADMSDGTTGAMSSNKKVIYCTSLNWSADGSTLFSGYNDGVIRVWGI
    GRY
    330 WD40 repeat MSGVPAPPFATTTPENGTMSSNSPAFHRDSDDDDDQGEVFLDDSDIIHEVAVDD 227 1512
    protein EDLPDADDEADEAEEADDSLHIFTGHNGEVYSLACSPTDATLVATGAGDDKGFL
    WRIGHGDWAVELQGHKDSISSLAFSLDGQLLASGSLDGVIQIWDVPSGNLKGTL
    DGPGGGIEWIRWHPKGHIILAGSEDSTVWMWNADKMAYLNMFSGHGNSVTCGDF
    TPDGKTICTGSDDATLRIWNPKSGENIHVVKGHPYHAEGLTSMAISSDSGLAIT
    GAKDGSVRIVNISSGRVVSSLDAHADSVEFVGLALSSPWAATGSLDQKLIIWDL
    QHSSPRATCDHEDGVTCLSWVGASRFLASGCVDGKVRVWDSLSGDCVRTFHGHS
    DAIQSLSVSANEEFLVSVSIDGTARVFEIAEFH
    331 WD40 repeat MGTSQHQLSSCLQLLPRRRGNKNLIFRRTMASGGAAAVAPPPGYKPYRHLKTLT 33 1076
    protein GHVAAVSCVKFSNDGTLLASASLDKTLIIWSSAALSLLHRLVGHSEGVSDLAWS
    SDSHYICSASDDRTLRIWSSRSPFDCLKTLRGHTDFVFCVNFNPQSSLIVSGSF
    DETIRIWEVKTGRCLNVIRAHSMPVTSVHFNRDGSLIVSGSHDGSCKIWDTKNG
    ACLKTLIDDTVPAVSFAKFSPNGKFILVATLNDTLKLWNYATGKFLKIYTGHKN
    SVYCLTSTFSVTNGKYIVSGSEDRCICIWDLQGKNLIQKLEGHSDTVISVTCHP
    SENKIASAGLDSDRTVRIWLQDA
    332 WD40 repeat MPSQKIETGHQDIVHDVAMDYYGKRVATASSDTTIKIIGVSNSSGSQHLASLSG 65 973
    protein HKGPVWQVAWAHPKFGSILASCSYDGQVILWKEGNQNDWAQAHVFNDHKSSVNS
    IAWAPHELGLCLACGSSDGNISVFTARPDGGWDTTRIEQAHPVGVTSVSWAPSM
    APGALVGSGLLDPVQKLASGGCDNTVKVWKLYNGTWKMDCFPALQMHSDWVRDV
    AWAPNLGLPKSTIASASQDGTVVIWTVAKEGEQWQGKVLKDFKTPVWRVSWSLT
    GNLLAVADGNNNVTLWNEAVDGEWQQVTTVEP
    333 WD40 repeat MKIAGLKSVENAHDESVWAAAWVPATESRPALLLTGSLDETVKLWRPDELALER 82 1047
    protein TNAGHFLGVVSVAAHPSGVIAASASIDSFVRVFDVDTNATIATLEAPPSEVWQM
    QFDPKGTTLAVAGGGSASIKLWDTATWELNATLSIPRPEQPKPSEKGNKKFVLS
    VAWSPDGRRLACGSMDGTISIFDVARAKFLHHLEGHFMPVRSLVFSPVEPRLLF
    SASDDAHVHMYDSEGKSLVGSMSGHASWVLSVDVSPDGAALATGSSDRTVRLWD
    LSMRAAVQTMSNHSDQVWGVAFRPMAGAGVRAGGRLASVSDDKSISLYDYS
    334 WD40 repeat MEIDLGNLAFDVDFHPSEQLVASGLITGDLLLYRYGDGSSPEKLLEVRAHGESC 43 1101
    protein RAVRFINDGKAILTGSPDCSILATDVETGSVVARVENAHEAAVNRLVNLTESTI
    ATGDDNGCIKVWDTRQRSCCNTFSAHEDFISDMTFASDSMKLVVTSGDGTLSVC
    NLRSNKVQTRSEFSEDELLSVVIMKNGRKVVCGTQSGTLLLYSWGFFKDCSDRF
    VDLSPSSVDALLKLDEDRIIAGTENGLISLIGILPNRIIQPIAEHSDHPIERLA
    FSHDKKFLGSISHDQTLKLWDLNDILGSEDSPSSQAAIDDSDSDEMDVDANPPD
    SSKGNKKKHSGKGNDVGNANNFFADLGD
    335 WD40 repeat MSQQPSVILATASYDHTIRFWEAKSGRCYRTIQYPDSQVNRLEITPHKRYLAVA 142 1095
    protein GNPSIRLFDVNSNTPQPVMSFDSHTNNVMAVGFQYDGNWMYSGSEDGTVRTWDL
    RARGCQREYESRGAVNTVVLHPNQTELISGDQNGNIRVWDLTANSCSCELVPEV
    DTAVRSLTVMWDGSLVVAANNNGTCYVWRLLRGSQTMTNFEPLHKLQAHNGYIL
    KCLLSPEFCEPHRYLATASSDHTVKIWNVEGFTLEKTLIGHQRWVWDCVFSVDG
    AYLITASSDTTARLWSMSTGQDIRVYQGHHKATTCCALHDGAEGSPG
    336 WD40 repeat MEDAMDMEVEVEVEAEEHSPSSSNPSGSSFRRFGLKNSIQTNFGSDYVFEITPK 61 1257
    protein FDWSLMGVSLSSNAVKLYSPTTGQYCGECRGHSDTVNGISFSGPSSPHVLHSCS
    SDGTIRAWDTRSFKEVSCISAGPSQEIFSFSFGGSSDSLLSAGCKSQILFWDWR
    NKKQVACLEDSHVDDVTQVCFVPHHQNKLISASVDGLICIFDTAGDINDDEHME
    SVINVGTSIGKVGIFGQTFEKLWCLTHIETLSVWDWKEGTNEANFEDARKLASD
    SWSLDHIDYFVDCHSAEEGEGLWVIGGTNAGTLGYFPVKYKGGAAIGSPEAVLG
    GGHSDVVRSVLPMSGMAGTTSKTRGIFGWTGGEDGRLCCWLSDDSSATSRSWMS
    SNLVLKSSRSHHKKNRHQPY
    337 WD40 repeat MSQHQEYPMEYAADDYDVGEVEDDMYFHERVMGDSDTDEDEEYDHLDNKITDTS 193 1527
    protein AADARRGKDIQGIPWERLSVTREKYRRTRIEQYKNYENVPQSGESSEKDCKPTR
    KGGNYYEFWRNTRSVKSTILHFQLRNLVWSTTKHDVYLMSHFSIIHWSSLTCKK
    TEVLDVYGHVAPREKHPGSLLEGFTQTQVSTLAVRDKLLIAGGFQGELICKNLD
    RPGVSYCCRTTYDDNAITNAVEIYDYPSGAVHFMASNNDCGVRDFDMEKFELSR
    HFTFPWPVNHTSLSPDGKLLVIVGDNPEGIVVDSQRGKTIRPLQGHLDFSFASA
    WHPDGHIFATGNQDKTCRIWDIRNLSKSVAVLKGNLGAIRSIRFTSDGRFMAMA
    EPADFVHVYDVKSGYEKEQEIDFFGEISGVSFSPDTESLFVGVWDRTYGSLLQY
    NRCRNYSYLDSM
    338 WD40 repeat MGASSDPNPDVSDEHQKRSEIYTYEAPWHIYAMNWSVRRDKKYRLAIASLLDHP 109 1155
    protein AAAAAVPNRVEIVQLDDSTGEIRADPNLSFDHPYPATKAAFVPDKDCQRADLLA
    TSSDFLRIWRIADDSSRVDLRSFLNGNKNSEFCRPLTSFDWNEAEPKRIGTSSI
    DTTCTIWDIERETVDTQLIAHDKEVYDIAWGGVSVFASVSADGSVRVFDLRDKE
    HSTIIYESSEPDTPLVRLGWNKQDPRYMATIIMDSAKVVVLDIRYPTMPVVELQ
    RHQASVNAIAWAPHSSCHICTAGDDSQALIWDLSSMAQPVEGGLDPILAYTAGA
    EIEQLQWSSSQPDWVAIAFSLKLQ
    339 WD40 repeat MRGGGGGGDATGWDEDAYRESVLKEREVQTRTVFRAAFAPSPSPSPSPDAVVVA 71 1213
    protein SSDGSVASYSISACLSDHRLQSLRFADAKSQNVLEAEPACFLQGHDGPAYDVKF
    YGEGEDSLLLSCGDDGRIRGWMWRDITSSEAHDHSQGNSAKPVLDLVNPQSRGP
    WGALSPIPENNALAVDVKRGSIYAAAGDSCAYCWDVECGKIKTVFKGHSDYLHC
    IAARNSSSQIITGSEDGTARIWDCRSGKCVQVIDPDKDHKKGFFASVSCLALDA
    SESWLVCGRGRDLSVWSISASDCIAKISTNAPAQDVLFDDNQILLVGAEPLISR
    LDMNGAVLSQIHCAPQSVFSVSLHQSGVTAVGGYGGLVDVISQFGSHLCTFRCK
    CI
    340 WD40 repeat MEAPIIDPLQGDFPEVIEEYLEHGIMKCIAFNRRGTLLAAGCTDGSCIIWDFET 109 1785
    protein RGVAKELRDKECTAAITSVCWSKYGHRILVSASDKSLILWDVLSGEKIAHTTLQ
    HTVLQACLHPGSSTPSICLACPFSSAPMIVDLNTGSTTALPVLTADVSNGATPL
    SRNKTSDTSVTYSPCNACFNKHGDLVYAGTSKGEILIIDHKNVRVCAIVLVSGG
    AVIKNVVFSRNGQYMLTNSNDRLIRIYKNLLPPKDGLKMLDELNESFNESDDVE
    KLKAIGSKCLELLHEFQDSITRVQWKAPCFSGDGEWVIGGAASRGEHKIYIWDR
    AGHLVKILEGPKEALMDLAWHPVHPIIISVSLTGLVYIWAKDYTENWSAFAPDF
    KELEENEEYVEREDEFDLVPETEKVKGLDVHEDDEVDVLTVERDSVFSDSDMSQ
    EELCFLPAVPCLDIPEQQDKCVGSCSKLPDGNHSGSPLSVEAGQNGNASNHNSS
    PLEPMENSTADDTDGVRLKRKRKPSEKGLELQAEKVKKPVKPLKSSGRLSKTNK
    PVIDPDSSNGVYGDDGSD
    341 WD40 repeat MRGVSWPEDGNNPSTSSSSQRNQQQAHAPRAVSGHAASHPSASNIFKLLVQREV 364 2685
    protein SPRSKHSSKKLWREASKCQPYPFQQSCEAVRDVRQGLISWVESASLRHLSAKYC
    PLVPPPRSTIAAAFSPDGKILASTHGDHTVKLIDSQTGSCLKVLRGHRRTPWVV
    RFHPLYPEILASGSLDHEVRLWDANTAECIGSRNFYRPIASIAFHARGELLAVA
    SGHKLYIWHYNRRGETSSPTIVLRTQRSLRAVHFHPHAAPFLLTAEVNDLDSAD
    SAMTLATSPGYLHYPPPTVYFADAHSHERSRLADELPLMPLPLLMWPSFTRDDG
    RVPLQRIDGDVGLNGQQRVDSSSSVRLWTYSTPSGQYELLLSPVESGNSPSMPE
    ETGNNAFSSAVEAEVSQSAMDTVEDMEVQPEERNTQFFSFSDPRFWELPLLHGW
    LVGQTQAGPRSVRQSSPGDIETQSAFGEVASVSPITSGVMPVSMDPSRFGGRSG
    SRYRSPGSRGVHVTGPNNDGPRDENDPQSVVSKLRSELAASLAAAASTELPCTV
    KLRIWPHDVKDPCAQLDLESCRLTIPHAVLCSEMGAHFSPCGRFLAACVACVLP
    HLESDPGLHGQVNQDVTGVATSPTRHPISAHQIMYELRIYSLEEATFGIVLASR
    PVRAAHCLTSIQFSPTSEHLLLAYGRRHSSLLKSIVIDGENTVPIYTILEVYRV
    SDMELVRVLPSAEDEVNVACFHPSVGGGLIYGTKEGKLRILHYDSSHGLNLKSS
    GFLDENVPEVQTYALEC
    342 WD40 repeat MDSAVAIAALSLVVGAAIALLFFGNYFRKRRSEVVAMAEADLQPHPKNPSRPPP 96 1412
    protein QPAAKKVHAKSHAHGADKDKNKRHHPLDLNTLKGHGDSVTGLCFASDGRSLATA
    CADGVVRVFKLDDASNKSFKFLRINLPAGGHPTAVAFGDGVSSVIVASQHLSGC
    SLYMYGEEKPTNLDSNKQQTKLPMPEIKWEHHKVHEQKAILTLSGAAANYDSGD
    GSTIIASCSEGTDIIIWHAKTGKILGNVDTNQLKNTMSAISPNGRFIAAAAFTA
    DVKVWEIVYSKDGSVKGVTKVMQLKGHKSAVTWLCFTPNSEQIVTASKDGSIRI
    WNINVRYHLDEDTKTLKVFPIPLQDSSGTTLHYERLSLSPDGKILAATHGSMLQ
    WLCIETGKVLDTAEKAHDGDITCMSWAPQSIPTGDKKVNVLATASGDKKVKLWA
    APPLPS
    343 WD40 repeat MEVEPKKASKTFPVKPKLKPKPRTPSGKTPESKYWSSFKTTHPLDNLSFSVPSL 116 1702
    protein AFSPSPPHLLAAAHSATVSLFSPHRTTISSFSDVVSSLSFRSDGQLLAASDLSG
    LIQVFDVRSRTPLRRLRSHARPVRFVRYPVLDKLHLVSGGDDALVKYWDVAGES
    VVSELRGHKDYVRCGDCSPADANCFVTGSYDHVVKLWDVRVRDGNRAATEVNHG
    SPVQDVIFLPSGSLVATAGGNSVKIWDLIGGGRMVYSMESHNKTVTSICVGTMG
    AQQSGEEGVQLRILSVGLDGYMKVFDYSRMKVTHSMRFPAPLLSIGFSPDSNVR
    AIGTSNGILYVGKRKAKENAEGGANGILGLGSVEEPRRRVLKPSFYRYFHRGQS
    EKPSEGDYLVMRPKKVKLAEHDKLLKKFQHKNALISVLGGNDPEKVVAVMEELV
    ARRALLKCVLNLDADELGLILTFLHKNSTVPRYSSLLLGLAKKVIDLRLEDIRA
    SDALKGHIRNLKRSVDEEIRIQEGLQEIQGMVSPLLRIAGRR
    344 WD40 repeat MQGGSSGVGYGLKYQARCISDVKADTDHTSFLTGTLSLKEENEVHLLRLSSGGT 46 1101
    protein ELICEGLFSHPSEIWDLSSCPFDQRIFSTVFSTGESYGAAVWQIPELYGQLNSP
    QLEKIASLDAHSRKISCVLWWPSGRHDKLVSIDEENIFLWGLDCSKKSAQVQSQ
    ESAGMLHNLSGGAWDPHDVNTVAATCESSIQFWDLRTMKKANSLESVHARDLDY
    DMRKKHLLVTSEDESGVRVWDLRMPKAPIQEFPGHTHWTWAVRCNPDYEGLILS
    AGTDSAVNLWWSSTASSDELISERLIDSPTRKLDPLLHSYNDYEDSVYGLAWSS
    REPWIFASLSYDGRVVVESVKPFLSRK
    345 WD40 repeat MAEEEGSAELEQQLEEEFAVWKKNTPILYDLLISHALEWPSLTVHWAPLLPQPS 23 1258
    protein SSAAAAAGDPSLAAHRLVLGTHTSDGAPNFLILADALLPSSESDHCGDDAVLPK
    VEISQKIRVDGEVNRARFMPQNHNIVGAKTNGCEVYVFDCSKQAAKQHDGGFDP
    DLRLTGHDGEGYGLSWSPLKENYLLSASHDKKICLWDISAAAQDKVLGAMHVFE
    AHEGAVGDASWHSKNDNLFGSAGDDCQLMIWDLRTNKAQQCVKAHEKEVNSVSF
    NSYNDWILATASSDTTVGLFDMRKLTTPLHVFSSHEGEVLQVEWDPNHEAVLAS
    SSEDRRVMVWDLNRIGDEQQEGDASDGPAELLFSHGGHKAKISDFSWNKNEPWV
    ISSVAEDNSVQVWQMAESICGDDDDMQAMEGYI
    346 WD40 repeat MGNYGEEDEDQYFDALEETASVSDRGSNSSDCCSSGSGLDENVLDSLGFEFWTK 404 2644
    protein FPESVRARRNRFLMLTGLGIEANSVDKEDAFPPSCNEIEVYTCKVTRDDGAVQR
    SLDSYNCISLLQSSTSIRSNQEVESLRGDSLLSSFRGRSKESDDLTELCGMGCP
    ESKRNAVSEFGSVSQGSIEELRRIVASSPLVHPLLHRKLEYERELIETKQKMGA
    GWLRKFGSATCISGRQGDTWSDPDDLEITAGMKMRRVRAHSSKKKYKELSSLYA
    AQEFLAHEGSISTMKFSMDGQYLASAGEDTVVRVWKVTEEDRSERVNVTVDPSC
    LYFALNESTQLASLNTNKEHIGKAKTFQRSSDSSCVILPLKVFQITEKPWHEFK
    GHNGEVLDLSWSSKGYLLSSSTDKTVRLWRVGCDRCQRVYSHNDYVTCISFNPV
    NENFFISGSIDGKVRIWNVFGGQVVAYIDCREIVSAVCYRSDGKGAIVGTMTGN
    CLFYSIKDNHLQMDAQVYLHGKKKSPGKRITGFQFPPNDPGKLMITSADSVIRV
    LSGLDVVCKLKGPRNSGGPMIATFTSDGKHVISASEDSNVYIWNYAGQDKTSSR
    VKKIWSCESFWSSNASVALPWCGIRTVPEALAPPSRSEERRASCAENGENHHML
    EEYFQKMPPYSPDCFSLSRGFFLELLPKGSATWPEEKLSDTSPPTVSSQAISKL
    EYKFLKSACHSVLSSAHMWGLVIVTAGWDGRIRTYHNYGLPVRS
    347 WD40 repeat MDIDFKEYRLRCELRGHEDDVRGVCVCGDGSIGTSSRDRTVRLWAPSAGERRKY 107 2383
    protein EVARVLLGHKSFVGPLAWVPPSEELPEGGIVSGGMDTLVMAWDLRNGEAQTLKG
    HQLQVTGIVLDGGDIVSASVDCTLIRWKNGQLTEHWEAHKAPIQAVIRLPSGEL
    VTGSSDTTLKLWRGKTCTQTFVGHTDTVRGLAVMPDLGILSASHDGSIRLWAVS
    GECLMEMVDHTSIVYSVDSHASGLIVSGSEDRFAKIWKDGVCFQSIEHPGCVWD
    VKFLEDGDIVTACSDGTIRIWTNQEDRMANSTELELFDLELSSYKRSRKRVGGL
    KLEELPGLEALQVPGTSDGQTKVIREGDNGVAYAWNSTELKWDKIGEVVDGPED
    SMNRPALDGVQYDYVFDVDIGDGEPTRKLPYNRSDNPYDTADKWLLKENLPLSY
    RQQIVEFILANSGQRDFNLDPSFRDPYTGSSAYVPGAPSQLAAKQARPTFKHIP
    KKGMLVFDAAQFDGILKKINEFNNTLLSNQEKKNLSLTDIEISRLGAVVKILKD
    TSHYHSSKFADADFDLMLKLLESWPYEMMFPVIDIFRMVILHPDGADGLLRHQE
    DKKDVLMESIKRATGNPSVPANFLTSIRAVTNLFKNSAYYSWLQKHRSEMLDAF
    SSCSSSSNKNLQLSYATLLLNYAVLLIEKKDEEGQSQVLSAALELAENESLEVD
    ARYRALVAIGSLMLDGLVKRIALDFDVEHIAKAARTSKEAKIAEVGADIELLIK
    QS
    348 WD40 repeat MEFTEAYKQSGPCCFSPNARFIAVAVDYRLVIRDTLSLKVVQLFSCLDKISYIE 243 1625
    protein WALDSEYILCGLYKRPMIQAWSLIQPEWTCKIDEGPAGIAYARWSPDSRHILTT
    SDFQLRLTVWSLVNTACVHVQWPKHASKGVSFTRDGKFAAICTRHDCKDYINLL
    SCHNWEIMGVFAVDTLDLADIQWSPDDSAIVIWDSPLEYKVLVYSPDGRCLFKY
    QAYESGLGVKSVSWSPCGQFLAVGSYDQMLRVLSHLTWKTFAEFTHLSNVRAPC
    CAAIFKEVDEPLQIDMSELSLSDDYMQGNSGDAPEGHYRVRYDVTEVPITLPCQ
    KPPADRPNPKQGIGLMSWSNDSQYICTRNDSMPTILWIWDMRHLELAAILVQKD
    PIRAAVWDPTGTRLVLCTGSSHLYMWTPSGAYCVSVPLSQFNITDLKWNSDGSC
    LLLKDKESFCCAAAPLPPDESSDYSSDD
    349 WD40 repeat MATIAALDDDMVRSMSIGAVFSDFVGKLNSLDFHRKDDILVTAGEDDSVRLYDI 126 1127
    protein ANARLLKTTFHKKHGTDRVCFTHHPNSLICSSTKNLDTGESLRYISMYDNRSLR
    YFKGHKQRVVSLCMSPINDSFMSGSLDHSVRMWDLRVNACQGILRLRGRPTVAY
    DQQGLVFAVAMEGGAIKLFDSRSYDKGPFDAFLVGGDTSEVCDIKFSNDGKSVL
    LSTTNNNIYVLDAYAGDKQCGFNLEPSPSTPIEASFSPDGQYVVSGSGDGTLHA
    WNISRRNEVACWNSHIGVASCLKWAPRRAMFVAASTVLTFWIPNSEPELASAKG
    EAGVPPEQV
    350 WD40 repeat MSVAELKERHRAATETVNSLRERLKQKRVQLLDTDVAGYARTQGKTPVTFGATD 257 1390
    protein LVCCRTLQGHTGKVYSLDWTPERNRIVSVSQDGRFIVWNALTSQKTHAIRLPCA
    WVMTCAFAPNGQSVACGGLDSVCSIFNLNSPVDRDSNLPVSRMLSGHKGYVSSC
    QYVPDGDAHLITGSGDQTCVLWDITTGLRTSVFGGEFQSGHTADVLSVSTNGSS
    PRIFVSGSCDSTARMWDTRVASRAVHTYHGHESGVNAVKFFPDGNRFGTGSDDG
    TCRLFDIRTGHELQVYYQQRGIDEIPHVTSIAFSISGRLLIAGYSNGDCFVWDT
    LLAQVVLNLGSLQNSHEGRISCLGVSADGSALCTGSWDTNLKIWAFGGIRRVT
    351 WD40 repeat MKKRPRGASLDQAVVDIRRREVGGLSGLSFARRLAASEGLVLRLDIYNKLKGHR 178 1632
    protein GCVNTVGFNLDGDIVISGSDDRHVKLWDWQTGKVKLSFDSGHLSNVFQAKIMPY
    TDDRSIVTCAADGQARHAQILEGGQVQTMLLAKHRGRAHKLAIDPGSPHIVYTC
    GEDGLVQRLDLRSNTARELFTCREVYGTHVEVVHLNAIAIDPRNPNLFVIGGSD
    EYARVYDIRNYKWNGSHNFGRSANYFCPSHLIGEAHVGITGLAFSGQSELLVSY
    NDESIYLFTQEMGLGPDPLSASTKSVDSNSSEVTSPTAVNVDDNVTPQVYKGHR
    NCETVKGVGFFGPKCEYVVSGSDCGRIFIWKKKGGQLIRVMAADKHVVNCIEPH
    PHIPALASSGIENDIKIWTPKAIERATLPMNVEQLKPKARGWMNRISSPRQLLL
    QLYSLERWPEHGGETSSGLAAGQEELTELFFALSANGNGSPDGGGDPSGPLL
    352 WD40 repeat MSKRGYKLQEFVAHSSNVNCLSIGKKACRLFLTGGDDCKVNLWAIGKPNSLMSL 290 2917
    protein CGHTNAVESVAFDSAEVLVLAGASSGVIKLWDVEEAKMVRGLTGHRSNCTAMEF
    HPFGEFFASGSTDTNLKIWDIRKKGCIHTYKGHTRGISTIRFSPDGRWVVSGGN
    DNVVKVWDLTAGKLLHDFKFHENHIRSIDFHPLEFLLATGSADRTVKFWDLETF
    ELIGSSRPEAAGVRAIAFHPDGRTLFCGLEDSLKVYSWEPVICHDGVDMGWSTL
    ADLCIHDGKLLGCSYYQSSVGVWVADASLIEPYGTNVKPQQKDSGDDEIEHQES
    RPSAKVGTTIRSTSIMRCASPDYETKDIKNIYVDTASGNPVSSQRVGTTNFAKV
    TQPLDFNDTPNLTLRRQGLVTETPDGLSGHVPSKSITQPKVVSRDSPDGKDSSR
    RESITFSRTKPGMLLRPAHSRRPSSTKYDVDRLSACAEIGVLSSAKSGSESLVD
    SFLNIKVAPEDGARNGCEDNHSSVKNVSVESEKVLPLQTPKTEKCDQTVGFKEE
    INSVKFVNGVAVVPGRTRTLVEKFEKREKLNSTEDQTINTPENPTLDKTPPPSL
    AENEEKSDRLNIVERKATRMSSHMVTAEDRTPVTLVGSPEDQSTVMAPQRELPA
    DESSKTPPLPVEDLEIHHGSNVSEDKATILSSQTVSEEDSKRSTLIRNFRRRDR
    FKSTEGRSPVMATQRKLPTDESGKTSSLPMEDLEIKGGLNVSEDKATSFSSRAP
    PREDRAHSALVRNVRKRDKFKSTNDTITVMVHQRGLSTDEASTVSVERVERRQL
    SNNVENPLNNLPPHSVPPTTTRGEPQYVGSESDSVNHEDVTELLLGNHEVFLST
    LRSRLTKLQVV
    353 WD40 repeat MSTFLTGTALSNPNPNKSYEVVQPPNDSVSSLSFNPKANFLVATSWDNQVRCWE 148 1197
    protein IVRSGTSLGTTPKASISHDQPVLCSTWKDDGTTVFSGGCDKQVKMWPLSGGQPM
    TVAMHDAPIKEISWIPEMNLLVTGSWDKTLRYWDTRQANPVHIQQLPERCYALT
    VRHPLMVVGTADRNLIIYNLQSPQTEFKRISSPLKYQTRCLAAFPDQQGFLVGS
    IEGRVGVHHLDDSQQSKNFTFKCHREGSEIYSVNSLNFHPVHHTFATAGSDGAF
    NFWDKDSKQRLKAMSRCSQPIPCSTFNNDGSIFAYSACYDWSKGAENHNPATAK
    TYIFLHLPQESEVKGKPRLGTTGRK
    354 WD40 repeat MEVEAQQRDVNNVMCQLVDPEGTTLGPPMYLPQDVGPQQLQQMVNKLLSNEDKL 140 1567
    protein PYTFYISDQELVVPLESYLQKNKVSVEKVLSIVYQPQAIFRIRPVNRCSATIAG
    HSEAVLSVAFSPDGKQLASGSGDTTVRLWDLSTQTPMFTCKGHKNWVLSIAWSP
    DGKHLVSGSKAGEIQCWDPLTGQPSGNPLVGHKKWITGISWEPVHLSSPCRRFV
    SSSKDGDARIWDVTLRRCVICLSGHTLAVTCVKWGGDGVIYTGSQDCTIKVWET
    SQGKLIRELKGHGHWVNSLALSTEYVLRTGAFDHTGKQYSSAEEMKQVALERYK
    KMKGNAPERLVSGSDDFTMFLWEPSVSKHPKTRMTGHQQLVNHVYFSPDGQWVA
    SASFDKSVKLWNGITGKFVAAFRGHVGPVYQISWSADSRLLLSGSKDSTLKIWD
    IRTKKLKRDLPGHADEVFAVDWSPDGEKVVSGGKDKVLKLWMG
    355 WD40 repeat MDAGSAHSSSNMKTQSRSPLQEQFLQRRNSRENLDRFIPNRSAMDFDYAHYMLT 376 1737
    protein EGRKGKENPAVSSPSREAYRKQLAETLNMNRTRILAFKNKPPTPVELIPHELTS
    AQPAKPTKTRRYIPQTSERTLDAPDLLDDYYLNLLDWGSSNVLSIALGNTVYLW
    NASDGSTSELVTIDDETGPVTSVSWAPDGRHIAVGLNNSDVQLWDSADNRLLRT
    LRGGHRSRVGSLAWNNHILTTGGMDGLIVNNDVRVRSHIVDTYRGHTQEVCGLK
    WSASGQQLASGGNDNILHIWDRSTASSNSPTQWLHRLEEHTAAVKALAWCPFQG
    NLLASGGGGGDRTIKFWNTHTGACLNSVDTGSQVCALLWNKNERELLSSHGFTQ
    NQLTLWKYPSMVKIAELTGHTSRVLFMAQSPDGCTVASAAGDETLRFWNVFGVP
    EVAKPAPKANPEPFAHLNRIR
    356 WD40 repeat MEEAIPFKNLPSREYQGHKKKVHSVAWNCTGTKLASGSVDQTARVWHIEPHGHG 69 1010
    protein KVKDIELKGHTDSVDQLCWDPKHADLIATASGDKTVRLWDARSGKCSQQAELSG
    ENINITYKPDGTHVAVGNRDDELTILDVRKFKPIHKRKFNYEVNEIAWNMSGEM
    FFLTTGNGTVEVLAYPSLRPVDTLMAHTAGCYCIAIDPVGRYFAVGSADSLVSL
    WDISEMLCVRTFTKLEWPVRTISFNHTGDYVASASEDLFIDISNVQTGRTVHQI
    PCRAAMNSVEWNPKYNLLAYAGDDKNKYQADEGVFRIFGFESA
    357 WD40 repeat MGKDEEEMRGEIEERLINEEYKVWKKNTPFLYDLVITHALEWPSLTVEWLPDRE 149 1423
    protein EPPGKDYSVQKLVLGTHTSENEPNYLMLAQVQLPLEDAENDARHYDDDRADVGG
    FGCANGKVQIIQQINHDGEVNRARYMPQNSFIIATKTVSAEVYVFDYSKHPSKP
    PLDGACSPDLRLRGHSTEGYGLSWSKFKQGHLLSGSDDAQICLWDINATPKNKS
    LDAMQIFKVHEGVVEDVAWHLRHEYLFGSVGDDQYLLIWDLRTPSVTKPVQSVV
    AHQSEVNCLAFNPFNEWVVATGSTDKTVKLFDLRKISTALHTFDAHKEEVFQVG
    WNPKNETILASCCLGRRLMVWDLSRIDEEQTPEDAEDGPPELLFIHGGHTSKIS
    DFSWNTCEDWVVASVAEDNILQIWQMAENIYHDEDDVPGEESNKGS
    358 WD40 repeat MMRGFSCTEDGDAPSTSSTSPPPPPPPPHRQQMQAPRASSSSSGQPTSRRSTGN 365 2677
    protein VFKLLARREVSPRSKHSLKKFWGEASECQLCPFQQSYEAVRDVRRSLISWVEAF
    SLQHLSAKYCPLMPPPRSTIAAAFSPDGKILASTHGDHTVKLIDSQTGSCLKVL
    RGHRRTPWVVRFHPLYPEILASGSLDHEVHLWDANTAECIGSRNFYRPIASIAF
    HAQGDLLAVASGHKLYIWHYNRSGETSSPTIVLRTPRSLRAVHFHPHAAPFLLT
    AEVNDLDLTDSAMTLATSPGYLHYPPPTIYLADAHSNERSRLEDELPLMPSPLL
    MWPSFTRDDGRATLPHIGGDVGLSGQQRVDSLSSSQYEFHPSPIEPSSSTSMHE
    EMGTDPFSSVRESEVTQSAMNIVDNTEVQPEERSTYSFSFSDPRFWELPSVYGW
    LVGQTQAAPRTAPSPGALETASALGEVASVSPVRSEFMPGGMDQPRLGGRSGSG
    CRSSGSRMMRTAGLNDHPHDENYPQSVVSKLRSELEASLAAAASTELPCTVKLR
    VWPYDMKDPCALFRSESCRLTIPHAVLCSEMGAHFSPCGRFFAACVACVLPQLE
    ADPVLHGQVDPDVTGVATSPTRHPVSAYQIMYELRIYSLEEATFGMVLASRSIR
    AAHCLTSIQFSPTSEHLLLAYGRRHNSLLKSIVIDGENTVPIYSILEVYRVSDM
    ELVRVLPSAEDEVNVACFHPSVGGGLVYGTKEGKLRILQIDSSGGLNPKSTGFL
    DENMAEVPTYALEC
    359 WD40 repeat MGEGDLPRTEAGVLRGHEGAVLAARFNGDGNYCLSCGKDRTIRLWNPHRGIHIK 24 923
    protein TYKSHGREVRDVHCTSDNSKLISCGGDRQIFYWDVSTGRVIRRFRGHDSEVNAV
    KFNDYASVVVSAGYDRSVRAWDCRSHSTEPIQIINTFQDSVMSVCLTKTEIIGG
    SVDGTVRTFDIRIGREISDDLGQPVNCISMSNDGNCILASCLDSTLRLVDRSAG
    ELLQEYKGHTCKSYKLDCCLTNTDAHVAGGSEDGYVFFWDLVDASVISKFRAHS
    SVVTSVSYHPKEDCMITASVDGTIKVWKT
    360 WD40 repeat MACIKGVGRSASVAMAPDGGYLATGTMAGTVDLSFSSSASLEIFGLDFQSDDRD 221 3598
    protein LPLIAESPSSERFNRLSWGKNGSGSDEFSLGLIAGGLVDGTIGLWNPLSLIRSE
    AGDKAIVGHLSRHKGPVRGLEFNVIAPNLLASGADDGEICIWDLAAPREPSHFP
    PLRGSGSAAQGEISFLSWNSKVQHILASTSYNGTTVVWDLKKQKPVISFSDSVR
    RRCSVLQWNPDLATQLVVASDEDSSPTLRLWDMRNIMSPVKEFAGHTRGVIAMS
    WCPNDSSYLVTCAKDNRTICWDTVTGEIVCELPAGSNWNFDVHWYPKIPGVISA
    SSFDGKIGIYNVEGCSRYGVRENEFGAATLRAPKWFKRPVGASFGFGGKVVSFH
    TRSTGGPSVNSSEVFVHDIITEQTLVSRSSEFEAAIQSGDRPSLRALCEKKSQH
    CESTDDQETWGFLKVLLEDDGTARSKLLAHLGFDIPTETNDGSQEDLSQQVNAL
    GLEDVTADKVVQEDNNESMVFPTDNGEDFFNNLPSPRADTPVSTSADGFPTVNA
    AVEPSQDEVDGLEESSDPSFDDSVQRALVVGDYKAAVALCMSANKLADALVIAH
    VGGASLWESTRDKYLKMSRLPYLKVVFAMVNNDLQSLVDTRPLKFWKETLAILC
    SFAQGEEWAMLCNSLASKLMAAGNMLAATLCFICAGNIDKTVEIWSRSLATEHD
    GMSYMDLLQDLMEKTIVLALASGQKQFSASVCKLVEKYAEILASQGLLTTAMDY
    LKLLGTDDLSPELAVLRDRIAFSVEAEKGANISAFNGSQDPRGAVYGVDQSNYG
    MVDTSQHYYPEAAQPQVPHTVPGSPYGENYQQPFGSSFGKGYNTPMQYQAPSQA
    SMFVPSEPPQNAQPSFVPTPVTSQPTTRSQFIPAPPLALRNPEQYQQPTLGSHL
    YPGSVNPTFQPLPHAPGPVAPVPPQVSSVPGQNMPQAVAPTQMRGFMPVTNPGV
    VQNPGPISMQPATPIESAAAQPVVSPAAPPPTVQTADTSNVPAPQKPVIATLTR
    LYNETSEALGGSRANPAKKREIEDNSRKIGALFAKLNSGDISKNAADKLVQLCQ
    ALDNGDYSTALQIQVLLTTSEWDECNFWLATLKRMIKTRQNVRLS
    361 WD40 repeat MKERGKGAGRSVDERYTQWKSLVPVLYDWLANHNLVWPSLSCRWGPQLEQATYK 44 1447
    protein NRQRLYLSEQTDGSVPNTLVIANVEVVKPRVAAAEHISQFNEEARSPFVKKFKT
    IIHPGEVNRIRELPQNSKIVATHTDSPDVLIWDVETQPNRHAVLGASTSRPDLI
    LTGHKDNAEFALAMSPTEPFVLSGGKDRYVVLWSIQDHISTLAADPGSAKSPGS
    AGTNNKQSSKAAGGNDKTGDSPSIEPRGVYLGHGDTVEDVTFCPSSAQEFCSVG
    DDSCLILWDARTGSSPAIKVEKAHHADLHCVDWNPHDVNLILTGSADNTVRMFD
    RRNLTSGGVGSPVHTFEGHNAAVLCVQWSPDKSSVFGSSAEDGILNIWDHEKIG
    RKIETVGSKVPNSPPGLFFRHAGHRDKVVDFHWNSSDPWTIVSVSDDGESTGGG
    GTLQIWRMIDLIYRPEEEVLAELDKFKSHILSCTS
    362 WD40 repeat MAKIAPGCEPVAGTLTPSKKREYRVTNRLQEGKRPLYAVVFNFIDSRYFNVFAT 196 1314
    protein VGGNRVTVYQCLEGGVIAVLQSYIDEDKDESFYTVSWACNIDRTPFVVAGGING
    IIRVIDAGNEKIHRSFVGHGDSINEIRTQPLNPSLIVSASKDESVRLWNVHTGI
    CILIFAGAGGHRNEVLSVDFHPSDKYRIASCGMDNTVKIWSMKEFWTYVEKSFT
    WTDLPSKFPTKYVQFPVFIAPVHSNYVDCNRWLGDFVLSKSVDNEIVLWEPKMK
    EQSPGEGSVDILQKYPVPECDIWFIKFSCDFHYHSIAIGNREGKIYVWELQSSP
    PVLIAKLSHPQSKSPIRQTAMSFDGSTILSCCEDGTIWRWDAITASTS
    363 WD40 repeat MNTAMHFGAGWRSIAEMGYTMSRLEIEPESCEDEKSLDGVGNSQGPNELPRCLD 193 1668
    protein HELAHLTNLKSRPHEHLIRDFPGRRALPVSTVKMLAGRECNYSRRGRFSSADCC
    HMLSRYVPVNGPSPLDQMNSRAYVSQFSADGSLFVAGFQGSHIRIYNVDKGWKC
    QKNILTKSLRWTITDTSLSPDQRYLVYASMSPIVHIVDIGSAAMDSLANITEIH
    EGLDFSADSGPYSFGIFSVKFSTDGREVVAGSSDDSIYVYDLVANKLSLRIPAH
    ESDVNTVCFADESGHIIYSGSDDTYCKVWDRRCLSARNKPAGVLMGHLEGITFI
    DSRGDGRYFISNGKDQTIKLWDIRKMGSDICRRGFRNFEWDYRWMDYPPRARDS
    KHPFDLSVATYKGHSVLRTLIRCYFSPVHSTGQKYIYTGSHDSCVYIYDVVTGA
    QVAALKHHKSPVRDCSWHPEYPMIVSSSWDGDIVKWEFFGNGETEIPAMIKKRIR
    RRHLY
    364 WD40 repeat MEPQPQAPKKRGRKPKPKEDKKEEQLHQPPPPPPPQQQAAPAPAPAATRSSTSG 78 1634
    protein SAGGRDRRPQQQHAVDEKYARWKSLVPVLYDWLANHNLLWPSLSCRWGPQLEQA
    TYKNRQRLYISEQTDGSVPNTLVIANCEVVKPRVAAAEHVSQFNEEARSPFIRK
    YKTIIHPGEVNRVRELPQNPNIVATHTDSPDVLIWDVESQPNRHAVYGATASRP
    NLILTGHQENAEFALAMCPAEPFVLSGGKDKTVVLWSIQDHITASATDQTTNKS
    PGSGGSIIKKTGEGNEETGNGPSVGPRGIYCGHEDTVEDVAFCPSTAQEFCSVG
    DDSCLILWDARVGTNPVAKVEKAHNGDLHCVDWNPHDNNLILTGSADNSVNMFD
    RRNLTSNGVGSPVYKFEGHKAAVLCVQWSPDKPSVFGSSAEDGLLNIWDYERVD
    KKVDRAPNAPAGLFFQHAGHRDKIVDFHWNAADPWTMVSVSDDCDTAGGGGTLQ
    IWRMSDLIYRPEEEVLAELENFKAHVLECSKA
    365 WD40 repeat MGIFEPYRAVGYITTGVPFSVQRLGTETFVTVSVGKAFQVYNCAKLSLVLVGPQ 85 2826
    protein LPKKIRALASYREYTFAAYGSDIGIFKRAHQLATWSGHTAKVCLLLLFGEHILS
    VDVDGNAYIWAFKGMNYNLSPVGHILLDSNFTPSCIMHPDTYLNKVILGSQEGP
    LQLWNISTKTKLYEFKGWNSSVSSCVSSPALDVVAVGCADGKIHVHNIRYDEEL
    VTFSHSMRGSVTALSFSTDGQPLLASGSSSGVVSIWNLDKRRLQSVIRDAHDGS
    IISLHFFANEPVLMSSSADNSIKMWIFDTSDGDPRLLRFRSGHSAPPLCIRFYA
    NGRHILSAGQDRAFRLFSVVQDQQSRELSQRHVSKRAKKLKLKEEEIKLKPVIA
    FDVAEIRERDWCNVVTSHMDTPQAYVWRLQNFVIGEHILRPCPNKPTPVKACMI
    SACGNFAILGTAGGWIERFNLQSGISRGSYIDQLEGTNSAHDGEVVGVACDATN
    TLMISAGYAGDIKVWDFKGRELKSRWEIGSSLVKISYHRLNGLLATVADDFIIR
    LFDAVALRMVRKFEGHTDRITDLCFSEDGKWLLSSSMDGSLRIWDIILARQVDA
    VFVDVSITALSLSPNMDILATTHVDQNGVFLWVNQSMFSGDSDINLYASGKEVV
    TVKLPSVSSVEGSQVEESNEPTIRHSESKDVPSFRPSLEQIPDLVTLSLLPKSQ
    WQSLINLDIIKVRNKPVEPPKKPEKAPFFLPSIPSLSGEILFKPSEMSDKGDMK
    ADEDKSKITPEVPSSRFLQLLHSCSEAKNFSPFTTYIKGLSPSTLDLELRMLQI
    IDDDAVDADADDPQDVDKRQELLSIELLMDYFIHEISCRSNFEFVQALVRLFLK
    IHGETIRRQSVLQNKAKVLLETQCSVWQRVDKLFQGARCMVAFLSNSQF
    366 WD40 repeat MEETKVTCGSWIRRPENVNLAVLGRSPRRRGSAALEIFAFDPKSTSLSSSPLVA 74 1246
    protein HVIEEIEGDPLAIAVHPNGEDIVCFASSGSCLSFELSGQESNLKLLTKELPPLR
    GIGPQKCMAFSVDGSRFATGGVDGRLRILEWPSLRIILDEPKAHKSIRDLDFSL
    DSEFLATTSTDGSARIWKAEDGLPCTTLTRRSDEKIELCRFSKDGTKPFLFCTV
    QRGDKAVTGVWDISTWNKIGHKRLLRKPAVVMSISLDGKYLAQGSKDGDMCVVE
    VKKMEVSHWSKRLHLGTSLTSLEFCPIERVVITTSDEWGVLVTKLNVPADWKAW
    QVYLLLLGLFLASLVAFYIFYENSDSFWGFPLGKDQPARPKIGSVLGDPKSADD
    QNMWGEFGPLDM
    367 WD40 repeat MADPVEHQHQQHQQHQLQQQRRRGWRIQGGQYLGEISALCFLHLPPPPLSLSSS 100 4377
    protein PVLSLSSGLDSESRDRPACSFRFPSAGSGSQVSLFDLASGAMVRTFYVFRGIRV
    HGIVLGCADFPGGSSSSSSTLDYVIAVYGERRVKLFRLSVRLGRGAGEGSGTVL
    SADLELVSAAPRLSHWVMDVRFLKENGTSEDELQRCLTVAIGCSDNSIRLWDVD
    KCSFVLAVSSPERCLLYSMRLWGDNLEDLQVASGTIYNEILIWKVVPNHDAPSS
    NELTEEGLTNSCAGNSVHECLRYEAYHICRLVGHEGSIFRIAWSSDGSKLVSVS
    DDRSARIWEVHCKVQYSEDAGEVGLLFGHSARVWDCYISDNLIVTAGEDCSCRV
    WGLDGQQHDVIKEHIGRGIWRCLYDPWSSLLVTGGFDSAIKVHKLDASLAEASA
    KQSNIKDLSDGTELFTTHLPNSSGHSGHMDSKSEYVRCLSFSCEDVMYIATNHG
    YLYHAKLCNDGDLRWTELAQVSNEVQIICMELLPSNPYDPRIDADDWVAVGDGK
    GWTTVVRVVKNSDSPKVSTSFSWAAEMDRQLLGIHWCKSLGHRFIFTADPRGAL
    KLWRFFEVSQSSSLYPENSPRISLIAEFKSDLGARIMCLDVAFESELLICGDLR
    GNLVLFPLLKDLLLDTFVVSAAKISPVNHFKGAHGISAVSSISVAHMSFNHIEL
    RSTGADGCICYMEYDKGLQSLNFVGMKQVKELSMIESVSTENESTGYRTSGSYA
    SGFASTDFIIWNLVTEAKVLQVSCGGWRRPHSYYLGDVPEMKNCFAYVKDDIIY
    IRRHWIKDSKDKILPQNLRLQFHGREVHSLCFVTGDFQLRKNKQSSWIVTGCED
    GTVRLTRYTQCTDNWSSSKLLGEHVGGSAVRSICCVSNIHTTSSGTSVSDVKGI
    ENLPKDIKGTLMEDECNPSLLISVGAKRVLTSWLLRRRKQDGKEDDVTDLQEAE
    NSSLPSSAGSSTFSFQWLSTDMPVKYSVPSKKSGSIKKLIGVSDTNVRCKSLLP
    DSEALQSKVSAVDKNEDDWRYLAVTAFLVRHSGSRLIVCFIIVACSDATLAIRA
    LVLPYRLWFDVALMVPLSSPVLSLQHVIIGRCQLPDENVQIGNVYVVISGATDG
    SIAFWDLTESVEAFMRRLSNIHLEKFMDCQKRPRTGRGSQGGRWWRSLSKIACK
    EQPINDPVTAKAIKELNRKLTGGVACGSSSSMLDASPELDSNAANSSFEIIEVN
    PFHVLNGVHQSGVNCLHVCETKHGQSSDGRFLYQLVSGGDDQALHLLKFEVLVQ
    PPVQVPDVPNSDIRNSILVEEFLLDEQNQKTKCTIEFISQEKIASAHNSAVKGV
    WTDGTWVFSTGLDQRVRCWISKDRGTPTELAHFIISVPEPEALDARSICWDQYQ
    IAVAGRGMQMIEFHVPSSEIR
    368 WD40 repeat MPYKLSATLSNHSSDVRAVASPSDDLILSASRDSTAISWFRQSPSSFTPASVIR 58 2439
    protein AGSRFVNAIAYLPPTPRAPQGYAVVGGQDTVVNVFALGPGDKEEPEYTLVGHTD
    NVCALSVNSDDTIISGSWDKTAKVWKDFALVYDLKGHQQSVWAVLAMNEKEFLT
    ASADRTIKYWVQHKTMQTYEGHRDAVRGLALIPDIGFASCSNDSEIRVWTMGGD
    VVYTLSGHTSFVYSLSVLPNGDLVSAGEDRSVRVWRDGECSQVIVHPAISVWAV
    STMPNGDIISGSSDGVVRVFSESEKRWATASELKALEDQIASQSLPSQQVGDVK
    KTDLPGPEALSVPGKKAGEVKMIRSGDVVEAHQWDSLASSWQKIGEVVDAIGSG
    RKQLHDGKEYDYVFDVDIQEGAPPLKLPYNVSENPYTAAQRFLEQNDLPTGYLD
    QVVKFIEQNTAGVKLGNDGYVDPFTGASRYQPATQSTSNTASSSYMDPFTGGSR
    HIAESAPSNVPQGSHATGIIPFSKPIFFKLANVSAMQAKMFQFDEVLRNEISTA
    TLAMRPDEVIMVNETFTYLSKVVTSTSSARTSLGWIHIETIMQILDRWPVPQRF
    PVIDLGRLVTAYCMNAFSGPGDLEKFFSCLFRTSEWTSITSGSKALTKAQETNV
    LLLFRTIANSLDGAPLNDMEWIKQIFRELAQTPQLVLNKSHRLALASVLFNFSC
    IGLKGPVPADVRTLHLTIILQVLRSPNDDPEVAYRTCVALGNMLYSDKTRGTPR
    DAQSPSPTELKSAVAAIKGGFSDPRINDVHREIMSLI
    369 WD40 repeat MPPQKIESGHKDTVHDLAMDYYGKRLATASSDHTINVVGVSSSGSQHLATLIGH 159 1064
    protein QGPVWQISWAHPKFGSLLASCSYDGRVIIWREGNPNEWTQAQVFEEHKSSVNSV
    AWAPHELGLCLACGSSDGNISVFTARQDGGWDTSRIDQAHPVGVTSVSWAPSTA
    PGALVGSGMMEPVQKLCSGGCDNTVKVWKLYNRVWKLDCFPVLQMHTDWVRDVA
    WAPNLGLPKSTIASASQDGRVIIWTLAKEGDQWQGKVLYDFRTPVWRVSWSLTG
    NILAVADGNNNVSLWNEAVDGEWIQVSTVEP
    370 WD40 repeat MSAPMLEIEARDVVKIVLQFCKENSLHQTFQTLQSECQVSLNTVDSIETFVADI 118 1665
    protein NSGRWDAILPQVAQLKLPRNTLEDLYEQIVLEMIELRELDTARAILRQTQAMGV
    MKQEQPERYLRLEHLLVRTYFDPNEAYQDSTKEKRRAQIAQALAAEVTVVPPSR
    LMALVGQALKWQQHQGLLPPGTQFDLFRGTAAMKQDVDDMYPTTLSHTIKFGTK
    SHAECARFSPDGQFLVSCSVDGFIEVWDYMSGKLKKDLQYQADETFMMHDDPVL
    CVDFSRDSEMLASGSQDGKIKVWRIRTGQCLRRLERAHSQGVTSVLFSRDGSQL
    LSTSFDGSARIHGLKSGKQLKEFRGHSSYVNDAIFSNDGSRVITASSDCTVKVW
    DVKTSDCLQTFKPPPPLRGGDASVNSVHLFPKNADHIVVCNKTSSIYIMTLQGQ
    VVKSLSSGKREGGDFVAACVSPKGEWIYCVGEDRNLYCFSCQSGKLEHLMKVHE
    KDVIGVTHHPHRNLVATYSEDSTMKLWKP
    371 WD40 repeat MDLLQSYAEDNDGDLGRHSSPEPSPPRLLPSKSAAPKVDDTTLALTVAQTNQTL 57 16828
    protein ARPIDPSQHAVAFNPTYDQLWAPICGPAHPYAKDGIAQGMRNHKLGFVEDAAIG
    SFLFDEQYNTFQRYGYAADPCASTGNEYVGDLDALKQNDGISVYNIRQQEQKKY
    AEEYAKKKGEERGEGGREKAEVVSDKSTFHGKEERDYQGRSWIAPPKDAKATND
    HCYIPKRLVHTWSGHTKGVSAIRFFPKHGHLILSAGMDTKVKIWDVFNSGKCMR
    TYMGHSKAVRDISFCNDGTKFLTAGYDKNIKYWDTETGKVISTFSTGKIPYVVK
    LHPDDEKQNILLAGMSDKKIVQWDMNTGQITQEYDQHLGAVNTITFVDDNRRFV
    TSSDDKSLRVWEFGIPVVIKYISEPHMHSMPSISLHPNTNWLAAQSLDNQILIY
    STRERFQLNKKKRFAGHIVAGYACQVNFSPDGRFVMSGDGEGRCWFWDWKSCKV
    FRTLKCHEGVCIGCEWHPLEQSKVATCGWDGLIKYWD
    372 WD40 repeat MESNGNLEQTLQDGRIYRQLNSLIVAHLRDHNFPQAASAVALATMTPLNVEAPR 250 1566
    protein NRLLELVAKGLAVEKGELLRGVSHAGTNDLGGSIPASYGLVPAPWTAIDFSSLR
    DTKGMSKSFTKHETRHLSDHKNVARCARFSTDGRFFATGSADTSIKLFEVSKIK
    QMMLPDSTDGAIRAVIRTFYDHTHPVNDLDFHPQNTVLISAAKDHTVKFFDYSK
    ATAKRAFRVIQDTHNVRSVAFHPSGDFLLAGTDHPIPHLYDVNTFQCYLSANVP
    EFAVNAAINQVRYSSSGGMYVTASKDGTIRFWDGASANCVRSIAGAHGAAEVTS
    ANFTKDQRYVLSCGKDSTVKLWEVGTGRLVKQYLGATHMQLRCQAVFNNTEEFV
    LSIDEPSNEIVVWDAMTAEKVARWPSNHNGPPRWIEHSPTEAAFVSCGTDRSIR
    FWKETH
    373 WD40 repeat MSNFQGEDGEYVADDFEAEDGDEELHGRESADPESDVDEIDTPSNRFTDTTADQ 106 1434
    protein ARRGRDIQGIPWERLSITREKYRRTRLEQYKNYENVPQSGEKSGKDCTVTEKGN
    SFYEFRRNSRSVKSTILHFQLRNLVWATSKHDVYLMSNYSVVHWSSLTGKKSEV
    LNLAGHVAPNEKHPGSLLEGFTQTQVSTLAVKDRFLVAGGFQGELICKFLDRPG
    ISFCSRTTYDDNAITNAVEIYVSPSGGIHFIASNNDCGVRDFDMENFELSKHFR
    FPWPVNHTSLSPDGKLLVIVGDDPEGILVDAKTGKTIMPLRGHLDFSFASEWHP
    DGVTFATGNQDKTCRIWDIRNLSKSIAVLKGNLGAIRSIRYTSDGRYMAIAEPA
    DFVHVYDTKTGYKKEQEIDFFGEISGMSFSPDTESLFIGVWDRTYGSLLEYGRR
    RNFSYLDCLV
    374 WD40 repeat MGVEEDLEDLNALAESTDAAVDGQAALASAVDSVTLQPAPPILPPVIPPPAVPV 190 1917
    protein VAPVPTIPPVLRPLAPLPIRPPVLRPPAPKRDEAGSSDSDSDHDGTAAGSTAEY
    EITEESRLVRERHEKAMQDLMMKRRGAALAVPTNDKAVRARLRRLGEPMTLFGE
    REMERRDRLRMLMAKLDAEGQLEKLMKAHEDEEAAASAAPEDVEEEMLQYPFYT
    EGSKALFNARIDIAKFSITRAALRLERARRRRDDPDEDVDAEIDWALKKAESLS
    LHCSEIGDDRPLSGCSFSHDGKLLATCSMSGVAKLWDTCRMPQVNRVLTLKGHT
    ERATDVAFSPVQNHIATASADRTAKLWNTEGTILKTFEGHLDRLGRIAFHPSGK
    YLGTTSFDKTWRLWDIESGEELLLQEGHSRSIYGIDFHRDGSLVASCGLDALAR
    VWDLRTGRSILALEGHVKPVLGVSFSPNGYHLATGGEDNTCRIWDLRKKKSLYT
    IPAHANLISEVKFEPQEGYFLVTASYDTTAKVWSARDFKPVKTLSVHEAKITSV
    DITADASHIVTVSHDRTIKLWTSNDDVKEQAMDVD
    375 WD40 repeat MVKAYLRYEPAAAFGVIASVESNIAYDASGKHLLAPALEKVGVWHVRQGVCTKA 102 2942
    protein LAPSASSAAGPSLAVTAIASSPSSLIASGYADGSIRIWDFEKGSCETTLNGHKG
    AVSVLRYGKLGSLLASGSKDNDIILWDVVGETGLYRLRGHRDQVTDLVFLDSDK
    KLVSSSKDKYLRVWDLETQHCMQIVGGHHSEIWSLDTDPEERYLVTGSADPELR
    FYTVKNDSSDERSEADASGGVGNGDLASHNKWDVLKQFGEIQRQSKDRVATVRF
    NKNGNLLACQAAGKLVEVFRVLDEAEAKRKAKRRLHRKREKKGADVNENGDSSR
    GIGEGHDTMVTVADVFKLLQTIRASKKICSISFCPVAPKSSLATLALSLNNNLL
    EFHSIEADKTSKMLTIELQGHRSDVRSVTLSSDNTLLMSTSHNSVKIWNPSTGS
    CLRTIDSGYGLCGLIVPQNKHALIGTKDGAIEIFDVGSGTCIEVVEAHGGSIRS
    IVAIPNQNGFVTGSADHDIKFWEYGMKQKPGDNSKHLTVSNVRTLKMNDDVLVV
    AVSPDAQKIAVALLDCTVKVFFMDSLKLMHSLYGHRLPVLCLDISSDGDLIVTG
    SADKNLMIWGLDFGDRHKSIFAHGDSIMAVQFVGNTHYMFSVGKDRLVKYWDAD
    KFELLLTLEGHHADIWCLAISNRGDFLVTGSHDRSIRRWDRTEEPFFIEEEKEK
    RLEEMFESDLDNAFGNKYVPKEEIPEEGAVALAGKKTQETLSATDSIIEALDIA
    EVELKRIAEHEEEKNNGKTAEFHPNYVMLGLSPSDFILRALSNVQTNDLEQTLL
    ALPFSDALKLLSYLKDWTTYPDKVELVSRIATVLLQTHYNQLVSTPAARPLLTT
    LKDILHKKVKECKDTIGFNLAAMDHLKQLMALRSDALFQDAKVKLLEIRSQLSK
    RLEERTDPREAKRRKKKQKKSTNMHAWP
    376 WD40 repeat MGGVQAEREDKDKVSLELTEEILQSMEVGMTFRDYSGRISSMDFHRASSYLVTA 75 1079
    protein SDDESIRLYDVASATCLKTINSKKYGVDLVSFTSHPMTVIYSSKNGWDESLRLL
    SLHDNKYLRYFKGHHDRVVSLSLCPRNECFISGSLDRTVLLWDQRAEKCQGLLR
    VQGRPATAYDDPGLVFAIAFGGCVRMFDARKYEKGPFEIFSVGGDVSDANVVKF
    SNDGRLMLLTTTDGHIHVLDSFRGTLLYTFNVKPTSSKSTLEASFSPEGMFVIS
    GSGDGSVYAWSVRGGKEVASWLSTDTEPPVIKWAPGNLMFATGSSELSFWIPDL
    SKLGAYVGRK
    377 WD40 repeat MAAFGAAPAGNHNPNKSSEVIQPPSDSVSSLCFSPRANHLVATSWDNQVRCWEL 99 1148
    protein TKNGASVTSVPKASMSHDQPVLCSAWKDDGTTVFSGGCDKQAKMWSLMSGGQPV
    TVAMHDAPIKEIAWIPEMNVLVTGSWDKTLKYWDTRQSNPVHTQQLPERCYAMT
    VRYPLMVVGTADRNLIVFNLQNPQAEFKRFSSPLKYQTRCVAAFPDQQGFLVGS
    IEGRVGVHHLDDSQISKNFTFKCHRDNNDIYSVNSLNFHPVHHTFATAGSDGTF
    NFWDKDSKQRLKAMSRCSQPIPCSTFNNDGTIYAYSVCYDWSKGAENHNPATAK
    TYIFLHLPQESEVKAKPRVGTTNRK
    378 WD40 repeat MNCSISGEVPEEPVVSTKSGHVFERRLIERYVSDYGKCPVSGEPLTMDDVLPVK 232 1806
    protein MGKIVKPRPLQAASIPGLLSIFQNEWDSLMLSNFALEQQLHTARQELSHALYQH
    DAACRVIARLKKERDEARSLLALAERQIPMTASSDIAVNAPAMSNGRKASLDEE
    PGYAGKKMRPGISASIIAEITDCNLALSQQRKKRQIPSTLAPVEDLERYTQLSS
    YPLHKTGKPGITSLDICHSKDIIATGGIDTSAVLFDRSSGQIMSTLSGHSKKVT
    SVNFDAQGDMVLTGSADKTVRIWQGSEDGSYNCRHILKDHTAEVQAITVHATNN
    YFATASLDNTWCFYEFSTGLCLTQVEGASGSEGYTSAAFHPDGLILGTGTSNAD
    VKIWDVKTQANVTTFSGHTGAITAISFSENGYFLATAAQDGVKLWDLRKLKNFR
    TFSAYDKDTGTNSVEFDHSGCYLGLAGSDIRVYQVASVKSEWNCVKTFPDLSGT
    GKVTCVKFGPDSKYIAVGSMDHNLRIFGLPSEDGAMES
    379 WD40 repeat MAAPGVETLKKEIKELKEKIAQHRLDTDGEQPLPAAAKSKSVPEVSAALKQRRI 72 1124
    protein LKGHFGKIYALHWSADSRHLVSASQDGKLIIWNGFTTNKVHAIPLRSSWVMTCA
    YSPSGNLVACGGLDNLCSVYKVPHGGNKESSSAQKTYGELAQHEGYLSCCRFIK
    DNEIVTSSGDSTCILWDVETKTPKAIFNDHTGDVMSLAVFDDKGVFVSGSCDAT
    AKLWDHRVHKQCVMTFQGHESDINSVQFFPDGDAFGTGSDDSSCRLFDIRAYQQ
    INKYSSDKILCGITSVAFSKTGKSLFAGYDDYNTYVWDTLSGNQVEVLTGHENR
    VSCLGVSEDGKALATGSWDTLLKIWA
    380 WD40 repeat MGGVEDESEPASKRMKLSSRVLRGLANGSSRTEPAAGSSLDLMARPLPIEGDEE 315 2069
    protein VIGSKGVIKRVEFVRLIAKALYSLGYEKSGARLEEESGIPLQSSVVNLFMQQIS
    DGLWDESVVTLHKIGLSDENLVKSASFLILEQKFLELLDQEKAMDALKTLRTEI
    TPLCIKNSRVRELSSCIISPSSCGLLNQNKRNSTRARSRSELLEELQKLLPPAV
    IIPERRLEHLVEQALVLQTDACMLHNSIDMEMSLYTDHQCGKEHIPCRTLQILQ
    SHNDEVWLVQFSHNGKYLASASNDRSAIIWEVDENGSVSLKHKLTGHQKPISSV
    CWSPDDRQLLTCGVGETVRRWDVSSGECLRVYEKAGHGLISCAWFPDGKWICYG
    VSDRSICMCDLEGKEIECWKGQRTLSISDLEITSDGKQIISICRETAILLLDRE
    AKYERMIEENQTITSFSLSKDNRYLLVNLLNQEIHLWDIKGDFRLVAKYKGLKR
    SRFVIRSCFGGLKQAFVASGSEDSQVYIWHKGSGELIEPLPGHSGAVNCVSWNP
    ANHHMLASASDDRTIRIWGLNELNTRHKGARPNGVHYCNGNGTS
    381 WD40 repeat MTQLAETYACMPSTERGRGILIAGNPKPGSNSVLYTNGRSVVILNLDNPLDISV 145 1968
    protein YAEHAYPATVARFSPNGEWVASADSSGAVRIWGAYNDHVLKKEFKVLSGRIDDL
    QWSPDGLRIVASGDGKGKSLVRAFMWDSGTNVGEFDGHSRRVLSCAFKPTRPFR
    IVTCGEDFLVNFYEGPPFKFKLSRRDHSNFVNCLRFSPDGNRFISVSSDKKGII
    YDGKTGEKIGELSSDGGHTGSIYAVSWSPDSKQVITVSADKSAKIWDISEDGSG
    NLRKTLTSSGSGGVDDMLVGCLWQNNHLVTVSLGGTISIYTAGDLDKAPVSFSG
    HMKNVSSLSVLKGDPKVILSSSYDGLIIKWIQGIGFSGRVQRKESTQIKCLAAV
    DEEIVTSGYDNKVCRVSGSGDAEFIDIGCQPKDLSLALQCPEFALVSTDTGVVL
    LRGAKIVSTINLGFAVTASTVAPDGTEAIIGAQDGKLRIYSISGDTLTEEAVLE
    KHRGAISVIHYSPDLSMFASGDLNREAVVWDRASREVRLKNILYHTARINCLAW
    SPDSSTVATGSLDTCVIIYEVDKPASNRLTIKGAHLGGVYGLAFTDDFSVVSSG
    EDACIRVWKINRQ
    382 WD40 repeat MKVKVISRSTDEFTRERSQDLQRVFRNFDPNLRTQEKAVEYVRALNAAKLDKVF 130 1488
    protein ARPFVGAMDGHVDSVSCMAKNPNYLKGIFSGSMDGDIRLWDIASRRTVCQFPGH
    QGPVRGLAASTDGQILVSCGIDSTVRLWNVPVATLGESDGTHENLAKPLAVYVW
    KNAFWAVDHQWDGELFATAGAQVDIWNQNRSQPISSFEWGTDTVISVRFNPGEP
    NVLATSGSDRSITLYDLRMSSPTRKVIMRTKTNAISWNPMEPMNFTAANEDCNC
    YSYDARKLEEAKCVHKDHVSAVMDIDYSPTGREFVTGSYDRTVRIFQYNGGHSR
    EVYHTKRMQRVFCVKFSCDASYVISGSDDTNLRLWKAKASEQLGVVLPRERRKH
    EYHEAVKSRYKHLPEVKRIVRHRHLPKPIYKAGILRRTVNEADRRKEERRKAHS
    APGSSSAEPLRKRRIIKEIE
    383 WD40 repeat MVRSIKNPKKAKRKNKGSKNGDGSSSSSSIPSMPTKVWQPGVDKLEEGEELQCD 269 1693
    protein PSAYNSLHAFHIGWPCLSFDIVRDTLGLVRTEFPHQVYFVAGTQAEKPTWNSIG
    IFKVSNITGKRRELVPSKPTDDADEESDSSDSDEDSDDEVGGSGTPILQLRKVG
    HEGCVNRIRAMNQNPHICASWGDSGHVQIWDFSSHLNALAESEADVSQGASSVF
    NQAPLVKFGGHKDEGYALDWSPLVPGRLVSGDCKNSIHLWEPTSGSTWNVDSTP
    FIGHAASVEDLQWSPTEENVFASCSVDGTIAIWDTRLGKTPAASFKAHDADVNV
    ISWNRLATCMLASGCDDGTFSIHDLRLLKEGDSVVAHFEYHKHPVTSIEWSPHE
    ASTLAVSSADCQLTIWDLSLEKDEEEEAEFKAKTKEQVNAPEDLPPQLLFVHQG
    QKDLKELHWHAQIPGMIVSTAADGFNILMPSNIQSTLPSDGA
    384 CDK type A MERYKVIKELGDGTYGSVWKALNQQTHEIVAIKKMKRKYYIWEECINLREVKSL 1163 2545
    RKLNHPNIIKLKEVIRENNELFFIFEYMECNLYQIMKERSTPFSETAIIKFCYQ
    ILQGLSYMHRNGYFHRDLKPENLLVTSDLIKIADFGLAREVLTSPPYTDYVSTR
    WYRAPEVLLQSPTYTTAIDMWAVGAILAELFTLHPLFPGESELDEIYKICGVLG
    TPDYETWPDGMQLAAFRNFIFPQFLPVNLSVLIPHASPEAIDLITRLCSWDPQK
    RPTAEQALHHPFFRIGMSIPLSLGGHFQDNTCAAEVDTNFHSKKACKGRGMGEK
    ESSLECFLGLSLGLKPSLGHLGAMGSQGVGAVKQEVGSSPGCQSNPKQSLFQVL
    NSRAILPLFSSSPNLNVVPVKSSLPSAYTVNSQVMWPTIAGPPAAAVTVSTLQP
    SILGDFKIFGKSMGLASQYAGKEASPFS
    385 CDK type A MGEMGRGINNSSNNNNSNRPAWLQHYDLVGKIGEGTYGLVFLARSKLPNNRGLR 152 1582
    IAIKKFKQSKDGDGVSPTAIREIMLLREFSHENVVKLVNVHINHVDMSLYLAFD
    YAEHDLYEIIRHHREKLNHHNINQYTVKSLLWQLLNGLNYLHSNWIVHRDLKPS
    NILVMGEGEEHGVVKIADFGLARIYQAPLKPLSDNGVVVTIWYRAPELLLGAKH
    YTSAVDMWAVGCIFAELITLKPLFQGVEVKASPNPFQLDQLDKIFKVLGHPTIE
    KWPTLMNLPHWSKNLQQIQQHKYDNAGLHIGPIPAKSPAYDLLSKMLEYDPRKR
    ITAAQALEHEYFRIDPQPGRNALVPSQPGEKAINYPPRLVDANTDFDGTIAPQP
    SQVSSGNAPSGSIASAAVPAVRPLPQQMQLMGMQRMQNPGMAAFNLGAQASMSG
    LNHNNIALQRGSSQQQAHQQVRRKEPNSGFPNTGYPPPPKSRRL
    386 CDK type B-1 MDKYEKLEKVGEGTYGKVYKARDKMTGQLVALKKTRLEMDEEGVPPSSLREISL 389 1297
    LQMLSQSIYVVRLLCVEHVTKKGKPLLYLVFEYLDTDLKKFIDYRRSVNAGPLP
    QNVIQSFMYQLLKGVAHCHSHGVLHRDLKPQNLLVDKSKGLLKVGDLGLGRAFT
    VPLKCYTHEVVTLWYRAPEVLLGSTHYSTPVDIWSVGCIFAEMVRRQPLFPGDC
    EIQQLLHIFTLLGTPTEEMWPGVKRLRDWHEYPQWKPENLARAVPNLSPTGLDL
    ISKMLQCDPAKRISAKAAMNHPYFDDLDKSQF;
    387 CDK type B-1 MDGYEKMDKVGEGTYGKVYMARDKKTGQLVALKKTRLENDGEGIPPTALREISL 38 946
    LQMLSQDIYIVRLLDVKHTENKLGKPLLYLVFEYMESDLKKYIDSYRRSHTKMP
    PSMIKSFMYQLCRGVAYCHSRGVMHRDLKPHNLLVDKEKGVLKIADLGLSRAFT
    VPVKKYTHEIVTLWYRAPEVLLGATHYSLPVDIWSVGCIFAEMSRMQALFTGDS
    EVQQLMNIFRFLGTPNEEVWPGVTKLKDWHIYPEWKPQDISHAVPDLEPSGLDL
    LSQMLVYEPSKRISAKKALEHPYFDDLDKSQF
    388 CDK type B-1 MDAYEKLEKVGEGTYGKVYKAKDKNTGQLVALKKTRLESDDEGIPPTALREISL 180 1088
    LQMLSQDIHIVRLLDVEHTENKNGKPLLYLVFEYMDSDLKKYIDGYRRSHTKVP
    PNIIKSFMYQLCQGVAYCHSRGVMHRDLKPHNLLVDKQRGVVKIADLGLGRAFT
    IPIKKYTHEIVTLWYRAPEVLLGATHYSTPVDIWSVGCIFAEMVRLQALFIGDS
    EVQQLFKIFSFLGTPNEEIWPGVTKFRDWHIYPQWKPQDISSAVPDLEPSGVDL
    LSKMLVYEPSKRISAKKALEHPYFDDLDKSQF
    389 CDK type B-1 MDSYEKLEKVGEGTYGKVYKAKDKKTGKLVALKKTRLENDGEGIPPTALREISL 40 948
    LQMLSQDMNIVRLLDVEHTENKNGKPLLYLVFEYMDSDLKKYVDGYRRSHTKMP
    PKIIKSFMYQLCQGVAYCHSRGVMHRDLKPHNLLVDKQRGVLKIADLGLGRAFT
    VPIKKYTHEIVTLWYRAPEVLLGATHYSTPVDIWSVGCIFAEMSRMHALFCGDS
    EVQQLMSIFKFLGTPNEGVWPGVTKLKDWHIYPEWRPQDLSRAVPDLEPSGVDL
    LTKMLVYEPSKRISAKKALQHPYFDDLDKSQF
    390 CDK type B-1 MEKYEKLEKVGEGTYGKVYKGRDKRTGRLVALKKTPFHQEEGIPPTAIREISLL 299 1134
    KSLSQCIYIVKLLDVKASFNGKGKHVLFMVFEYADSDLKKHIDAHRQCNTKLSP
    RSIQSYMFQLCKGIAYCHSHGVLHRDLKPQNILVDQKIGLLKIADLGLGRACTV
    PIKSYTFEVVTLWYRAPEVLLGAKRYSMALDIWSLGCIFAELCNLQALFAGDSQ
    IQQLINIFRLLGTPNEQLWPGVTQLSDWHEFPQWRPQDLSKVVFNLDPNGVDLL
    SKMLQYDPAKRISAKEALDHPYFDSLDKSQF
    391 CDK type C MGCVCGKPSARAADYVESPAEKGASSNSRSSSMASRRLVAPAVMDQGIDAENGH 105 2642
    EGDYRTKLRGKQSNGADPVSLLSDDAEKQRHSRHHQHQQHHPIRPHHLRPQGEF
    VPNANSNPRFGNPPRHIEGEQVAAGWPAWLTAVAGEAIKGWIPRRADSFEKLDK
    IGQGTYSNVYKARDLDTGKIVALKKVRFDNLEPESVRFMAREIQVLRRLDHPNV
    VKLEGLVTSRMSCSLYLVFEYMDHDLAGLAACPGIKFTEPQVKCYMQQLLRGLD
    HCHSRGVLHRDIKGSNLLIDNGGILKIADFGLATFFHPDQRQPLTSRVVTLWYR
    PPELLLGATEYGVAVDLWSTGCILAELLAGKPIMPGRTEVEQLHKIFKLCGSPS
    EDYWKKSKLPHATIFKPQQPYKRCVAETFKDFPPSALALMEVLLAIEPADRGTA
    TSALKSDFFTTKPLACDPSSLPKYPPSKEFDAKIRDEEARRQRAAGGRGRDAAR
    RPSRESRAIPAPEANAELAISIQKRRLSSQGPSKSKSEKFNPQQEDGAVGFPIE
    PPRPMHIGIDAGATSRMYSQQFGPSHSGPLSNQISSSIWGKNQKEDEIQMAPGR
    PSRSSKATISDFRKPGACAPQPGADLSHLSSLVATARSNAGIDTHKDRSGMWQH
    NRIDAIDGVHNNGKHEFLEVPEHPNRQDWTRFQQPESFKGLDNYHLQDLPATHH
    RKDERVASKEATMNWQGYGGQGGDKIHYSGPLLPPSGNIDEILKEHERHIQHAV
    RRARQDKGRPQRSNLSQNERKAFEHRSFVSGVNGNAGYSDLVNELPISVGSNRL
    KVSKTRGTEEIVELRELEREPLSSVMEKYEREHEM
    392 CDK type C MGCVCAKQSDILGEPESPKVKGSNLASSRWSVSSETKQLPQHSDSGILHHQHYY 187 2580
    HPRDESDEAKLKESNYGGSKRRTRQGRDPADLDMGIFVRTPSSQSEAELVAAGW
    PAWMAAFAGEAIHGWIPRRAESFEKLYKIGQGTYSNVYKARDLDNGKIVALKKV
    RFDSLDAESVRFMAREILVLRKLDHPNIVKLEGLVTSEVSSSLYLVFEYMEHDL
    AGLAACPGIKFTEPQVKCYMQQLLQGLDHCHRHGVLHRDIKGSNLLIDNGGILK
    IADFGLATFFYPDQKQLLTSRVVTLWYRPPELLLGATDYGVAVDIWSAGCILAE
    LLAGKPILPGRTEVEQLHKTFKLCGSPSEDYWKESKLPHATIFKPQHPYKSCIA
    EAFKDFSPSALALLETLLAIEPGHRGEASGALKSEFFTTEPLSCDPSSLPKYPP
    SKEFDAKLRAQETRRQRDVGVRGHGSEAARRTSRLSRAGPTPNEGAELTALTQK
    QHSTSHATSNIGSEKPSTKKEDYTAGLHIDPPRPVNHSYETTGVSRAYDAIRGV
    AYSGPLSQTHVSGSTSGKKPKRDHVKGLSGQSSLQPSKPFIVSDSRSERIYEKS
    HVTDLSNHSRLAVGRNRDTTDPHKSLSTLMQQIQDGTLDGIDIGTHEYARAPVS
    STKQKSAQLQRPSALKYVDNVQLQNTRVGSRQSDERPANKESDMVSHRQGQRIH
    CSGPLLHPSANIEDLLQKHEQQIQQAVRRAHHGKREALSNKSSLPGKKPVDHRA
    WVSSGKGNKESPYFKGKGNKELSDLKGGPTAKVTNFRQKVM
    393 CDK type C MAVANPGQLNLQEAPSWGSRSVNCFEKLEQIGEGTYGQVYMAKEIETGEIVALK 220 1749
    KIRMDNEREGFPITAIREIKLLKKLQHENVIKLKEIVTSPGPEKDEQGKSDGNK
    YNGSIYMVFEYMDHDLTGLAERPGMRFSVPQIKCYMKQLLIGLHYCHINQVLHR
    DIKGSNLLIDNNGILKLADFGLARSFCSDQNGNLTNRVITLWYRPPELLLGSTK
    YGPAVDMWSVGCIFAELLYGKPILPGKNEPEQLTKIFELCGSPDESNWPGVSKL
    PWYSNFKPQRQMKRRVRESFKNFDRHALDLVEKMLTLDPSQRISAKDALDAEYF
    WTDPVPCAPSSLPRYEPSHDFQTKRKRQQQRQHDEMTKRQKISQHPPQQHVRLP
    PIQNAGQGHLPLRPGPNPTMHNPPPQFPVGPSHYTGGPRGAGGQNRHPQNIRPL
    HAAQGGGYNANRGYGGPPQQQGGGYPPHGMGNQGPRGGQFGGRGAGYSQGGPYG
    GPVGGRGPNVGGGNRGPQFWSEQ
    394 CDK type D MQNMEDNVQSSWSLHGNKEICARYEILERVGSGTYSDVYRGRRKADGLIVALKE 438 1748
    VHDYQSSWREIEALQRLCGCPNVVRLYEWFWRENEDAVLVLEFLPSDLYSVIKS
    GKNKGENGIPEAEVKAWMIQILQGLADCHANWVIHRDLKPSNLLISADGILKLA
    DFGQARILEEPEAIYEVEYELPQEDIVADAPGERLMEEDDSVKGVRNEGEEDSS
    TAVETNFGDMAETANLDLSWKNEGDMVMQGFTSGVGTRWYRAPELLYGATIYGK
    EIDLWSLGCILGELLILEPLFSGTSDIDQLSRLVKVLGTPTEENWPGCSNLPDY
    RKLCFPGDGSPVGLKNHVPSCSDSVFSILERLVCYDPAARLNAKEVLENKYFVE
    DPYPVLTHELRVPSPLREENNFSEDWAKWKDMEADSDLENIDEFNVVHSSDGFC
    IKFS
    395 CDK type D MDLNQYPEDLNPELPEGTDNVDNPDNNKGSPVPSPHPPLKPLDPSERYRKGITL 240 1631
    GQGTYGIVYKAFDTVTNKTVAVKKIHLGKAKEGVNVTALREIKLLKELSHPNII
    QLIDAYPHKQNLHIVFEFMETDLEAVIKDRNLVFSPADIKSYLQMTLKGLAVCH
    KKWVLHRDMKPNNLLIAADGQLKLGDFGLARLFGSPDRKFTHQVFAVWYRAPEL
    LFGAKQYGPAVDIWATGCIFAELLLRKPFLQGVSDLDQIGKIFAAFGTPRQSQW
    PDVASLPDFVEFQFVPAPSLRSLFPMASEDALDLLSKMFTLDPKNRITAQQALE
    HRYFSSVPAPTRPDLLPKPSKVDSSRPPKHASPDGPVVLSPSKARRVMLFPNNL
    AGILPKQVSQSTTGGTPIEFDMPTQKLREVCPRSRITESGKKHLKRKTMDMSAA
    LDECAREQEGQEGKTILDPDHQRSAKKEKHM
    396 Cyclin A MAGGQENCVRITRARAACVSKASAPVIQSQVDEKKSRKRAPKRAAVDDLAANAS 252 1604
    GSQPKRRAVLGDVTNLHAAATDCLSTAEDQVDAPNPSIKGRARNKKKEARTSTK
    VVKDEIHPESNPLADHSSNLSECQKPPAAKLAEQRSLRGVPSKAKQGGSSNSQS
    CSKHTDIDKDHTDPQMCTTYVEDIYEYLRNAELKNRPSANFMETAQNDITPNMR
    AILVDWLVEVSEEYKLVPDTLYLTVSYIDRYLSANPTSRHKLQLLGVSCMLIAS
    KYEEVCPPHVEEFCYITDNTYTRDEMLSMERKILIFLNFEMTKPTTKSFLRRFV
    RASQAGNKAPSLHMEFLANYLAELTLMECSFLQYLPSLIAASTVFLSRLTLDFL
    TNPWNPTLAHYTGYKASQLKDCVMAIYNVQMNRKGSTLVAIREKYQQHKFKCVA
    SLPPPPFIAERFFEDTPN
    397 Cyclin A MTGTQASNVRITRARAAKSTLNNALPPLPPAQGKPRGKRAATESNISGFSVAAE 261 1817
    PLKRRAVLSDVSNICKEAAAVDCLKKPKAVKVVSQNANAKGRGRGIPRNNKKIT
    QEAEIKKETSPAICNVDDASAGNAIGDDKQNNNVNPLKEVQDNPKELNPIAEQI
    SVHPHCKQSVEKPNEKEIVVSDNKAAIASLKQQSTLQSLRIPKQPKYSLKQGNP
    VPLANLHEDVGRSSCSDFIDIDSEYKDPQMCTAYVTDIYANMRVVELKRRPLPN
    FMETTQRDINANMRSVLIDWLVEVSEEYKLVPDTLYLTVSYIDRFLSANVVNRQ
    RLQLLGVSCMLVASKYEEICAPPVEEFCYITDNTYKKEEVLEMEISVLNRLQYD
    LTTPTTKTFLRRFIRAAQASCKVSSLHLEFMGNYLAELTLVEYDFLKYLPSLIA
    AAAVFVARMTLDPMVHPWNSTLQHYTGYKVSDMRDCICAIHDLQLNRKGCTLAA
    IREKYNQPKFKCVANLFPPPIISPQFLIDNEV
    398 Cyclin B MAAPNQNALLINNNNRRPLVDIGNLVGALNAQCNISKNGARKRAFGDIGNLVED 167 1576
    LDAKCTISKYWVRKRPRTNFGVNANKGASSSTQGQGIVVRGEQKAWDRIVWGNK
    QSCAIKMNAQHVTATQRGTAISISDIIDSSVQDGGIKAPSQLKARKQTVRTVTA
    TLTARSEDSLRDVLEVPPGIDDGDRDNPLAVVEYVEDIYHFYRKIEVRSCVPPD
    YMTRQLEIKDSMRGVIIDWLIEVHRTFLLMPETLYLTVNIIDRYLSIQSVTRNE
    LQLMGITAMFIASKYEEISPPKINDLVYITKDAYTSKQIVNMEHTILNRLKFKL
    TVPTPYVFLVRFLKAAGPDKVMKNLAFFLVDLCLLHYKMIKYSPSMLAAAAVYT
    AQCTLKKHPYWNKTLILHIGYSEAHLRECAHLMADLHLKAEGSNLKSVYKKYSY
    PIFGSVAFLSPAKIPAGTVAAPAIDKCAHQIYLRNLR
    399 Cyclin B MFPNKQTQGLVQNKKMASKAAQPKAMVPPQRVPPAANNRRALGDIGNIVADVGG 183 1598
    KCNVTKDGVNGKPLAQVSRPITRSFGAQLLAQAAANKGISAANNQTQVPVVIPK
    ADVRGNKQRRTSKSKDIPPTTVVTNESDDCVIIEQAQRIKPTCNHNVGAVGNKE
    KPQLLTAKPKSLTASLTSRSAVALRGFRFDDEMTEAEEDPLPNIDVGDRDNQLA
    VVEYVEDIYKFYRRTEQMSCVPDYMPRQQEINPKMRAVLINWLIEVHYRFGLMP
    ETLYLTTNLIDRYLATQLVSRSNYQLVGATAMLLASKYEEIWAPEMNDFLDILE
    NKFERKHVLVMEKAMLNKLKFHLTVPTPYVFLVRFLKAAASDEEMENLVFFLME
    LSLMQYVMIKFPPSMLAAAAVYTAQITLKKTTVWNDVLKRHTGYSEIDLKECTR
    LMVAFHQSSEESKLNVVFKKYSMPEYDSVALIKPAKLPA
    400 Cyclin D MAPSFDCVANAYIESCEDQEKLRQNAQILAQSGENDVDEPVSMLVQRETHYMLP 98 1126
    EDYLQRLRNRTLDVNVRREAVGWILKVHSFYNFGAPTAYLAVNYLDRFLSRHRM
    PQGVKAWMIQLMAVACLSLAAKMEETQVPLPSDLQREDARFIFDARTIQRMELL
    ILSTLQWGMRSITPFSFIDYFAYRAVQGHGHGHDATPKAVMSRAIELILSTTEE
    IDFMEYRPSAIAAAALLCAAEEVVPLQAVHYKRALSSSITDVDKDKMFGCYNLI
    QETIIEGGCYWTPMSLQSTEKTPVGVLDAAACLSNTPTSSYSVKPYASVTAAKR
    RKLNEICSALLVSQAHPC
    401 Cyclin D MAANFWTSSHCKELLDAEKVGIVHPLDKDQGLTQEDVKIIKINMSNCIRTLAQY 148 894
    VKLRQRVVATAITYCRRVYTRKSFTEYDPQLVAPTCLYLASKAEESTVQAKLVI
    FYMKKYSKHRYEIKDMLEMEMKLLEALDYYLVIYHPYRPLIQFLQDAGLNDLKV
    TAWALVNDTYRTDLILTYPPYMIALACIYFACIMEEKDAQAWFEELRVDMNEIK
    NISMEIVDYYDNYRVIPDEKMNSALNKLPHRF
    402 Cyclin D MAPALSSSYECLSHLLCAEDASNVVGCWDEDESKIFCEEEEGFGIQHFPDFPVP 287 1363
    DDDEIRVLVRKESQYMPGKSYVQSYQNLGLDFTARQNAIGWILKVHGSYNFGPL
    TAYLSINYLDRFLSRNPLPKAKVWMLQLLSVACLSLAAKMEETQVPLLLDLQAE
    EPDFLFEPRTIQRMELLVLSTLEWRMLSVTPFSFVDYFLQGGGGRKPPPRAMVA
    RANELIFNTHTVLDFLEHRPSAIAAAAVICAAEEVLPLEAAQYKETILSCSLVD
    KEWVFGSYNLIQEVLIEKFSTPKKAKSASSSIPQSPVGVLDAFCLSNNSNNTSL
    EASLSVNLYASVAAKRRKLNDYCNTWRMFQHSTC
    403 Cyclin D MAPNCIDCAPSDLFCAEDAFGVVEWGDAETGSLYGDEDQLHYNLDICDQHDEHL 251 1348
    WDDGELVAFAEKETLYVPNPVEKNSAEAKARQDAVDWILKVHAHYGFGPVTAVL
    SINYLDRFLSANQLQQDKPWMTQLAAVACLSLAAKMDETEVPLLLDFQVEEAKY
    IFESRTIQRMELLVLSTLEWRMSPVTPLSYIDHASRMIGLENHHCWIFTMRCKE
    ILLNTLRDAKFLGLLPSVVAAAIMLHVIKETELVNPCEYENRLLSAMKVNKDMC
    ERCIGLLIAPESSSLGSFSLGLKRKSSTINIPVPGSPDGVLDATFSCSSSSCGS
    GQSTPGSYDSNNSSILCISPAVIKKRKLNYEFCSDLHCLED
    404 Cyclin- MPQIQYSEKYTDDTYEYRHVVLPPETAKLLPKNRLLNENEWRAIGVQQSRGWVH 229 510
    dependent YAIHRPEPHIMLFRRPLNYQQNQQQQAGAQSQPMGLKAQ
    kinase
    regulatory
    subunit
    405 Cyclin- MDQIEYSEKYYDDTYEYRHVELPPDVARLLPKNRLLTENEWRGIGVQQSRGWVH 92 409
    dependent YAIHCSEPHIMLFRRPLNYEQNHQHPEPHIMLFRRPLNCQPNHQPQAHHPT
    kinase
    regulatory
    subunit
    406 Cyclin- MDQIEYSEKYYDDTYEYRHVELPPDVARLLPKNRLLTENEWRGIGVQQSRGWVH 64 381
    dependent YAIHCSEPHIMLFRRPLNYEQNHQHPEPHIMLFRRPLNCQPNHQPQAHHPT
    kinase
    regulatory
    subunit
    407 Cyclin- MPQIQYSEKYYDDTYEYRHVVLPPDVARLLPKNRLLNENEWRGIGVQQSRGWVH 68 349
    dependent YAIHRPEPHIMLFRRHLNYQQNQQQQAQQQPAQAMGLQA
    kinase
    regulatory
    subunit
    408 Histone MALVETEPVTLIHPEEPKKFKKKPTPGRGGVISHGLTEEEARVKAIAEIVGAMV 125 1849
    acetyltransferase EGCRKGEDVDLNALKAAACRRYGLSRAPKLVEMIAALPDGERAAVLPKLKAKPV
    RTASGIAVVAVMSKPHRCPHIATTGNICVYCPGGPDSDFEYSTQSYTGYEPTSM
    RAIRARYNPYVQTRSRIDQLKRLGHTVDKVEFILMGGTFMSLPADYRDYFIRNL
    HDALSGHTSSNVEEAVCYSEHSATKCTGLTIETRPDYCLGPHLRQMLSYGCTRL
    EIGVQSTYEDVARDTNRGHTVAAVADCFCLAKDAGFKVVAHMMPDLPNVGVERD
    MESFREFFENPAFRADGLKIYPTLVIRGTGLYELWKTGRYRNYPPEQLVDIIAR
    VLALVPPWTRVYRVQRDIPMPLVTSGVEKGNLRELALARMDDLGLKCRDVRTRE
    AGIQDIHHKIRPEVVELVRRDYCANEGWETFLSYEDTRQDILVGLLRLRKCGHN
    TTCPELKGRCSIVRELHVYGTAVPVHGRDADKLQHQGYGTLLMEQAERIAWKEH
    RSIKIAVISGVGTRHYYRKLGYELEGPYMMKYLN
    409 Histone MLGFRDLYTSICEHLQRASGRLPIIAAATSLISTPEIAAVEKENKAPNSVDKMG 70 1602
    acetyltransferase MGSADESGRFSTSNGQFMNMNNGVVKEEWKGGVPVVPSAPTTVPVITNVKLETP
    SSPDHDMARKRKLGFLPLEVGTRVLCKWRDGKFHPVKIIERRKLPNGATNDYEY
    YVHYTEFNRRLDEWVKLEQLELDSVETDADEKVDDKAGSLKMTRHQKRKIDETH
    VEGNEELDAASLREHEEFTKVKNITKIELGRYEIETWYFSPFPSEYNNCEKLYF
    CEFCLNFMKRKEQLQRHMRKCDLKHPPGDEIYRSGTLSMFEVDGKKNKVYAQNL
    CYLAKLFLDHKTLYYDVDLFLFYILCECDERGCHMVGYFSKEKHSEESYNLACI
    LTLPPYQRKGYGKFLISFSYELSKKEGKVGTPERPLSDLGLLSYRGYWTRVLLD
    ILKKHKSNISIKELSDMTAIKADDVLSTLQGLDLIQYRKGQHAICADPKVLDRH
    LKAVGRGGLEVDVCKLIWTPYKEQ
    410 Histone MGSLDESTCSEEIRDEGKDSIRTKFKVESTVNNAQNGGNDNSKKKRAAGLPLEV 140 1465
    acetyltransferase GIRLLCKWRDSKLHPVKIIERRKLPNGFPQDYEYYVHYTEFNRRLDEWVKLEQF
    ELDSVETDADEKIEDKGGSLKMTRHQKRKIDEIHVEEGQGHEDFDPASLREHEE
    FTKVKNIAKVELGRYEIETWYFSPFPPEYSHCEKLFFCEFCLNFMKRKEQLQRH
    MRKCDLKHPPGDEIYRNGTLSMFEVDGKKNKIYGQNLCYLAKLFLDHKTLYYDV
    DLFLFYVLCECDDRGCHVVGYFSKEKHSDEAYNLACILTLPPYQRKGYGKFLIA
    FSYELSKKEGKVGTPERPLSDLGLLSYRGYWTRILLDILKKQRGNISIKELSDM
    TAIKVEDVISTLQVLDLIQYRKGQHVICADPKVLDRHLKAAGIAGLEVDVSKLI
    WTPYKEQCG
    411 Histone MASAPMVGCDDSRDKHRWVESKVYMRKGHGKGSKGNAGFNAQNSTAQVRRENDN 628 2565
    acetyltransferase MGNSIADNGKSEAASEGLSSLSRKQITVNQDHPPNETSSMPAVGGLQNIDTHVT
    FKLEGCSKQEIWELRKKLTNELEQVRGTFKKLEARELQLRGYSVSAGVNTSYSA
    SQFSGNDMRNNGGKEVTSEVASGGAITPKQAQRESNPPRQLSISLMENNQAASD
    MGEKGKRTPKANQYYRNSEFVLGKDKFPPAESKKSKSTGNKKISQSKVFSKETM
    QVGKEFMPQKSVNEVFKQCSLLLTKLMKHKYGWVFNLPVDAQALGLHDYHTIIK
    RPMDLGTVKSKLEKNLYNSPASFAEDVKLTFSNAMTYNPKGHEVHTMAEQLLQL
    FEERWKTIYEEHLDGKMRFGSGQGLGASSSTKKLPFQDSKKNIKKSEPAGGPSP
    PKPKSTNHHASRTPSAKKPKAKDPHKRDMTYEEKQKLSTNLQNLPQERLELIVQ
    IIKKRNPSLCQHDEEIEVDIDSFDTETLWELDRFVTNYKKSLSKNKKKALLADQ
    AKRASEHGSARNKHPMIGRELPMNNKKGEQGEKVVEIDHMPPVNPPVVEVEKDG
    VYAKRSSSSSSSSSDSGSSSSDSDSGSSSGSESDAYAATSPPAGSNTSARG
    412 Histone MEGHSGALGFGQGFSRSSQSPNLSPSPSHSASASVTSSGQKRKRNEVEHAGVAS 55 1818
    acetyltransferase NSTGMFAVPPSHIYSHLHPMSMSMPMPMHNSHPSSLSESRDGALTSNDDDDNLT
    GGNQSQLDSMSAGNTDGREDFDDEDDDDDDEEDDDEVEGDEEDQDHDPDADDDS
    DDGHDSMRTFTAARLDNGAPNSRNLKPKADAAGVAIAPTVKTEPILDTVKEEKV
    SGNNNNNSVSANNAQVAPSGSAVLLSAVKEEANKPTSTDHIQTSGAYCAREESL
    KREEDADRLKFVCFGNDGIDQHMIWLIGLKNIFARQLPNMPKEYIVRLVMDRSH
    KSVMIIKQNQVVGGITYRPYLSQKFGEIAFCAITADEQVKGYGTRLMNHLKQHA
    RDVDGLTHFLTYADNNAVGYFIKQDFTKEIKLEKERWHGYIKDYDGGILMECKI
    DPKLPYTDLPAMIRWQRQTIDEKIRELSNCHIVYSGIDIQKKEAGIPRKPIKVE
    DIPGLKEAGWTTDQWGHSRFRLLNSPSEGLPNRQVLHAFMRSLHKAMVEHADAW
    PFKEPVDPRDVPDYYDIIKDPMDVKRMFTNARTYNTHETIYYKCANR
    413 Histone MEESGNSLTSGPDGSKRRVSYFYDSDIGNYYYSQGHPMKPHRIRMAHSLIVHYA 259 1710
    deacetylase LDEKMEVCRPNLLQSRELRVFHADDYISFLQSVTPETQHEQLRQLKRFNVGEDC
    PVFDGLYNFCQTYAGGSVGAAIKLNNKEADIAINWSGGLHHAKKCEASGFCYVN
    DIVLAILELLKVHQRVLYIDIDIHHGDGVEEAFYSTDRVMSVSFHKFGDYFPGT
    GHLKDVGYGKGKYYSLNVPLNDGIDDESYKNLFRPIIQKVMEIYQPEAVVLQCG
    ADSLSGDRLGCFNLSVKGHADCVRFLRSFNVPLVLVGGGGYTIRNVARCWCYET
    AVAVGVEPQDKLPYNEYYEYFGPDYTLHVAPSNMENQNSAKELAKIRNTLLEQL
    KRIQHVPSVPFQERPPDTKFPEEDEEDYEKRPKGHKWGGEYFGSESDEEQKPQN
    RDIDISDKPGIRRQSPPNVEAAKKIKVEEEDGDIGIVNENDGAKWPLGEAG
    414 Histone MEESGNSLTSGPDGSKRRVSYFYDSDIGNYYYSQGHPMKPHRIRMAHSLIVHYA 356 1807
    deacetylase LDEKMEVCRPNLLQSRELRVFHADDYISFLQSVTPETQHEQLRQLKRFNVGEDC
    PVFDGLYNFCQTYAGGSVGAAIKLNNKEADIAINWSGGLHHAKKCEASGFCYVN
    DIVLAILELLKVHQRVLYIDIDIHHGDGVEEAFYSTDRVMSVSFHKFGDYFPGT
    GHLKDVGYGKGKYYSLNVPLNDGIDDESYKNLFRPIIQKVMEIYQPEAVVLQCG
    ADSLSGDRLGCFNLSVKGHADCVRFLRSFNVPLVLVGGGGYTIRNVARCWCYET
    AVAVGVEPQDKLPYNEYYEYFGPDYTLHVAPSNMENQNSAKELAKIRNTLLEQL
    KRIQHVPSVPFQERPPDTKFPEEDEEDYEKRPKGHKWGGEYFGSESDEEQKPQN
    RDIDISDKPGIRRQSPPNVEAAKKIKVEEEDGDIGIVNENDGAKWPLGEAG
    415 Histone MEFWGVEVKPGEALTCDPGDERYLHMSQAAIGDKEGAKENERVSLYVHVDGKKF 261 1298
    deacetylase VLGTLSRGKCDQIGLDLVFEKEFKLSHTSQTGSVFVSGYTTVDHEALDGFPDDE
    DLESSEDEEEELAQITTLTAKENGGKTGAKPVKPESKSSVTDKAAAKGKPEVKP
    PVKKQEDDSDSDEDEDEDEDEDEDDDDEDDEDMKDASASDDGDEEDDSDEESDD
    DEEEDEETPKPAAGKKRPMPASDNKSPATDKKAKITTPAGGQKPGADKGKKTEH
    IATPYPKHGAKGPASGVKGKETPLGSKQTPGSKVKNSSTPESGKKSGQFKCQSC
    SRDFATEGALSSHNAAKHGGK
    416 Histone MMETGGNSLPSGPDGVKRKVAYFYDPEVGNYYYGQGHPMKPHRIRMTHALLVQY 365 2251
    deacetylase GLHKEMQILKPYPARDRDLCRFHADDYVAFLRGITPETIQDQVKALKRFNVGDD
    CPVFDGLYQYCQTYAGGSVGGAVKLNHKLCDIAINWAGGLHHAKKCEASGFCYV
    NDIVLAILELLKYHKRVLYVDIDIHHGDGVEEAFYTTDRVMTVSFHKFGDYFPG
    TGDIRDIGCGKGKYYAVNVPLDDGIDDESFQSLFKPIIQQVMLVYNPEAIVLQC
    GADSLSGDRLGCFNLSVKGHAECVRYMRSFNVPLLMVGGGGYTVRNVARCWCYE
    TGVAVGVEIDDKMPQHEYYEYFGPDYTVHVAPSNMENKNTKQYLDKIRSKILEN
    INSLPCAPSAQFQVQPPDTDFPELEEEDYDERTRSHKWDGASCDSDSENGDLKH
    RNHDVEESAFPRHNLANISYNTKIKLEGVGTGGLDMAAGTDTKKNDESFEAMDY
    ESGEELRQDHFASTINASQPCDPALLTGVQNQLQSTDTVKPIEQSGNAPGIPPP
    SVATVSTGTRPSSISRTSSLNSMSSVKQGSILGPNPPQGLNASGLQFPVPTSNS
    PIRQGGSYSITVQAPDKQGLQNHMKGPQNMPGNS
    417 Histone MPPKDRVAYFYDGDVGSVYFGPNHPMKPHRLCMTHHLVLSYELHKKMEIYRPHK 156 1454
    deacetylase AYPVELAQFHSADYVEFLHRITPDTQHLFTKELVKYNMGEDCPVFENLFEFCQI
    YAGGTIDAAHRLNNQICDIAINWSGGLHHAKKCEASGFCYINDLVLGILELLKH
    HARVLYVDIDVHHGDGVEEAFYFTDRVMTVSFHKYGDMFFPGTGDVKEVGEREG
    KYYAINVPLKDGIDDASFTRLFKTIITKVVDIYQPGAIVLQCGADSLAGDRLGC
    FNLSIDGHAQCVRIVKKFNLPLLVTGGGGYTKENVARCWSVETGVLLDTELPNE
    IPDNDYIKYFAPDYSLKINTAGNMENLNSKTYLSAIKVQVMENLRAIQHAPSVQ
    MHEVPPDFYIPDIDEDELNPDERMDQHTQDRQIQRDDEYYDGDNDIDHDMEEAS
    418 Histone MDSSKSEEANILHVFWHEGMLNHDLGTGVFDTLEDPGFLEVLEKHPENADRVRN 203 1348
    deacetylase MLSILRKGPIAPYTEWHTGRAAYLSELYSFHRPDYVDMLAKTSTAGGKTLCHGT
    RLNPGSWEAALLAAGTTLEAMRYILDGHGKLSYALVRPPGHHAQPTQADGYCFL
    NNAGLAVELAVASGCKRVAVVDIDVHYGNGTAEGFYERDDVLTISLHMNHGSWG
    PSHPQTGFHDEVGRGKGLGFNLNVPLPNGTGDKGYEHAMHELVVPAISKFMPEM
    IVLVIGQDSSAFDPNGRECLTMEGYRKIGQIMRQQADQFSGGRLVVVQEGGYHI
    TYAAYCLHATLEGVLCLPHPLLSDPIAYYPEHDIYSERVTFIKNYWQGIISTTD
    KRN
    419 Histone MEESGNALVSGPDGSKRRVTYFYDADIGNYYYGQGHPMKPHRMRMAHNLIVHYG 229 1644
    deacetylase LHQRMEVCRPHLAQSKDIRAFHTDDYIHFLSSVAPDTQQEQLRQLKRFNVGEDC
    PVFDGLFNFCQSSAGGSIGAALKLNRKDADIAINWAGGLHHAKKCEASGFCYVN
    DIVLGILELLKVHQRVLYIDIDIHHGDGVEEAFYTTDRVMTVSFHKFGDYFPGT
    GHIKDVGYGKGKYYALNVPLNDGIDDESYKHLFRPIIQKVMEVYQPEAVVLQCG
    ADSLSGDRLGCFNLSVKGHADCVRFVRSFNIPLMLVGGGGYTIRNVARCWCYET
    AVAVGVEPQDKLPYNEYYEYFGPDYTLYVAPSNMENLNTEKDLEKMRNVLLEQL
    SKIQHTPSVPFQERPPDTEFNDEEEEDMEKRSKCRIWDGEYVGSEPEEDGKLPR
    FDADTYERSVLKHENKRLVPVSNVEPLKRIKQEEDGAAV
    420 Histone MPPKDRVAYFYDGDVGSVYFGPNHPMKPHRLCMTHHLVLSYELHKKMEIYRPHK 156 1454
    deacetylase AYPVELAQFHSADYVEFLHRITPDTQHLFTKELVKYNMGEDCPVFENLFEFCQI
    YAGGTIDAAHRLNNQICDIAINWSGGLHHAKKCEASGFCYINDLVLGILELLKH
    HARVLYVDIDVHHGDGVEEAFYFTDRVMTVSFHKYGDMFFPGTGDVKEVGEREG
    KYYAINVPLKDGIDDASFTRLFKTIITKVVDIYQPGAIVLQCGADSLAGDRLGC
    FNLSIDGHAQCVRIVKKFNLPLLVTGGGGYTKENVARCWSVETGVLLDTELPNE
    IPDNDYIKYFAPDYSLKINTAGNMENLNSKTYLSAIKVQVMENLRAIQHAPSVQ
    MHEVPPDFYIPDIDEDELNPDERMDQHTQDRQIQRDDEYYDGDNDIDHDMEEAS
    421 Histone MDLNLVSHGEEEEGVRRRKVGIVYDERMCKHATPEDQPHPEQPDRIRVIWDKLN 27 2222
    deacetylase SAGVLHKCVMVEAKEASEEQLAGVHSRKHIEVMKSIGTARYNKKKRDKLAASYS
    SIYFSQGSSEAALLAAGSVVEISEKVASGELDAGVAIVRPPGHHAEADKAMGFC
    LFNNIAIAAKHLVHERPELGVQEVLIVDWDVHHGNGTQHMFWTDPHVLYFSVHR
    FDAGTFYPGGDDGFYDKIGEGKGAGYNINVPWEQGKCGDADYLAVWDHVLVPVA
    KSYDPDMVLISGGFDAALGDPLGGCRLTPYGYSLMTKKLMEFAGGKIVLALEGG
    YNLKSLADSFLACVEALLKDGPSRSSVLTHPFGSTWRVIQAVRKELSSFWPALN
    EELQLPRLLKDASESFDKLSSSSSDESSASEDEKKIAEVTSIMEVSPDPSSILA
    LTAEDIAQPLAGLKIEEAGTDSQRSSDHTLLDLTNDDTQKLKQFEGEIFVMIGD
    EESVPSASSSKDQNESTVVLSKSNIKAHSWRLTFSSIYVWYASYGSNMWNPRFL
    CYIEGGQVEGMAKRCCGSEDKTPPQRIQWKVVPHRMFFGRSYTNTWGSGGVSFL
    DPNCSDTSEAHVCLYKITLAQFNDLLLQENNLNCGTEHPLVDLSSIDAIRNGNS
    ILELIKDSWYGTLIYLGMEGGLPIVTFTCSVCDVEKFKHGQLPLCPPSSRYENI
    LIRGLVQGKKLSEDDATAYIRAASTSPLL
    422 Peptidylprolyl MADEDLDLSDVGEVEDEPGEEIESTPPLAVGQEKEINSLALKKKLLKVGTRWET 71 1759
    isomerase PENGDEVTVHYTGTLPDGTKFDSSRDRGEPFTFKLGQGQVIKGWDQGIVTMKKG
    ERALFTIPPELAYGSSGVRPTIPPNATLQFDVELLSWTNIVDVCNDGGILKRII
    SEGEKYERPKDPDEVTVKYEAKLEDGTLVAKSPEEGVEFYVNDGHFCPAIAKAV
    KTMKRGESVILTIKPTYAFGERGKDAEEGFAAIPPNATLTTSLELVSFKAVIAV
    TEDKKVIKKILKEADGYDKPSDGTVVQIRYTAKLQDGTIFEKKGYEGEEPFQFV
    VDEEQVIAGLDKAVETMKTGEIALITIGAEYGFGNFETQRDLAVIPPNSTLIYE
    VEMISFTKEKESWDMDTTEKIEASKQKKEQGNSLFKVGKYQRAAKKYEKAAKYI
    EHDSSFSAEEKKQSKVLKVSCNLNHAACRLKLKDFKEAVKLCSKVLELESQNVK
    ALYRRAQAYIETADLDLAEFDIKKALEIEPQNREVQLEYKILKQKQIEYNKKDA
    KLYGNMFAKLNKLEAFEGKVLS
    423 Peptidylprolyl MADEGLELSDVAEVEDEPGEEFESAPPLVVGQEKELNSSGLKKKLLKAGTRCET 358 2040
    isomerase PENGDEVTVHYTGTLLDGTKFDSSRDRGEPFTFNIGQGQVIKGWDQGIVTMKKR
    EHALFTIPPELAYGASGMPPTIPPNATLQFDVELLSWTNIVDVCKDGGILKRII
    SDGEKYERPKDPDEVTVKYEAKLEDGMLVAKSPEEGVEFYVNDGNFCPAIVKAV
    KTMKKGENVTLTIKPAYAFGEQGKDAEEGFAAIPPNATITINLQLVSFKAVKEV
    TEDKKVIKKILKEADGYDKPSDGTVVQIRYTAKLQDGTIFEKKGYAGEEPFQFV
    VDEEQVIAGLDKAVETMKTGEVALITIGPEYGFGNIETQRDLAVIPPYSTLIYE
    VEMVSFTKEKESWDMNTTENIEASKQKKEQGNSLFKVGKYLRAAKKYDKAAKYI
    EHDNSFSAEEKKQSKVLKVSCNLNHAACCLKLKDFKKAVKLCSKVLELESQNVK
    ALYRRAQAYIETADLDLAEFDIKKALEIEPQNREVRLEYLILKQKQIEYNKKDA
    KLYGNMFARQNKLEAIEGKD
    424 Peptidylprolyl MPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRALCTGEKGTGRSGKPLH 238 756
    isomerase FKGSSFHRVIPGFMCQGGDFTRGNGTGGESIYGEKFADENFVKKHTGPGILSMA
    NAGPNTNGSQFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGSGRTSKP
    VVIADSGQLA
    425 Peptidylprolyl MPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRALCTGEKGNGRSGKPLH 238 756
    isomerase FKGSSFHRVIPGFMCQGGDFTRGNGTGGESIYGEKFADENFVKKHTGPGILSMA
    NAGPNTNGSQFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGSGRTSKP
    VVIADSGQLA
    426 Peptidylprolyl MPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRALCTGEKGTGRSGKPLH 238 756
    isomerase FKGSSFHRVIPGFMCQGGDFTRGNGTGGESIYGEKFADENFVKKHTGPGILSMA
    NAGPNTNGSQFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGSGRTSKP
    VVIADSGQLA
    427 Peptidylprolyl MPNPKVFFDMQVGGAPAGRIVMELYADVVPKTAENFRALCTGEKGTGRSGKPLH 238 756
    isomerase FKGSSFHRVIPGFMCQGGDFTRGNGTGGESIYGEKFADENFVKKHTGPGILSMA
    NAGPNTNGSQFFICTAQTSWLDGKHVVFGQVVEGLEVVRDIEKVGSGSGRTSKP
    VVIADSGQLA
    428 Peptidylprolyl MADDFELPESAGMMENEDFGDTVFKVGEEKEIGKQGLKKLLVKEGGSWETPETG 176 1912
    isomerase DEVEVHYTGTLLDGTKFDSSRDRGTPFKFKLGQGQVIKGWDQGIATMKKGENAV
    FTIPPDLAYGESGSQPTIPPNATLKFDVELLSWASVKDICKDGGIFKKIIKEGE
    KWEHPKEADEVLVKYEARLEDGTVVSKSEEGVEFYVKDGYFCPAFAIAVKTMKK
    GEKVLLTVKPQYGFGHQGREAIGNDVARSTNATLLVDLELVSWKVVDEVTDDKK
    VLKKILKQGEGYERPNDGAVVKVKYTGKLEDGTIFEEKGSDEEPFEFMAGEEQV
    VDGLDRAVMTMKKGEVALVSVAAEYGYQTEIKTDLAVVPPKSTLIYEVELVSFV
    KEKESWDMNTAEKIEAAGKKKEEGNALFKVGKYFRASKKYEKATKYIEYDTSFS
    EEEKKQSKPLKVTCNLNNAACKLKLKDYTQAEKLCTKVLEVESQNVKALYRRAQ
    AYIQTADLELAELDIKKALEIDPNNRDVKLEYRALKEKQKEYNKKEAKFYGNMF
    ARMSKLEELESRKSGSQKVETANKEEGSDAMAVDGESA
    429 Peptidylprolyl MAASLTPLGAGLAYATIYDQAKVRKLEPTKRSLIALCQHSDSQHRRFITRKYHV 64 765
    isomerase NVQILNRRDAIRLIGLAAGLCIDLSLMYDARGAGLPPQENAKLCDTTCEKELEN
    APMITTESGLQYKDIKIGNGPSPPIGFQVAANYVAMVPSGQVFDSSLDKGQPYI
    FRVGSGQVIKGLDEGLLSMKVGGKRRLYIPGPLAFPKGLNSAPGRPRVAPSSPV
    IFDVSLEFIPGLESEEE
    430 Peptidylprolyl MSAASLSADMAIRGTILGKTALHVLGPQVVSQCRQPVMFKCPPHTLRKMRFSAQ 93 881
    isomerase DLQSKNFYSGFTPFKSVFISTSKRSWQAGSARAMSQDAAFQSKVTTKCFLDIEI
    GGDPAGRIVLGLFGEDVPKTAENFRALCTGEKGFGYKGSSFHRIIKDFMLQGGD
    FDRGDGTGGKSIYGRTFEDENFKLAHVGPGVLSMANAGPNTNGSQFFICTVKTP
    WLDKRHVVFGQVIEGMEIVKKLESEETNRTDRPKRPCRIVDCGELP
    431 Peptidylprolyl MGRIKPQTLLQQSKKKKVPGRISVSTIIVCNLIIIFLMFSLVGIYRQRAKRNRA 372 1070
    isomerase TSRSDGDEEMENFGRSKINSVPHQAIVNTTKGLITLELFGKSSAHTVEKFVEWS
    ERGYFNGLPFYRVIKHFVIQVGDPKFAGNREDWTVGGQLNVQLEFSPKHEAFML
    GTSKLEDQGDGFELFITTAPIPDLNDKLNVFGRVIKGQDVVQEIEEVDTDEHFQ
    PKSPIIINDVRLKDEL
    432 Peptidylprolyl MARQSTLLLFWSLVFLGAIVFTQAKHEELEEVTHKVYFDVDIAGKPAGRVVIGL 28 594
    isomerase FGKAVPKTVENFRALCTGEKGVGKSGKPLHYKGSFFHRIIPSFMIQGGDFTLGD
    GRGGESIYGTKFADENFKLKHTGPVFITTVTTDWLDGRHVVFGKIISGMDVVYK
    VEAEGRQSGQPKRKVKIADSGELSMD
    433 Peptidylprolyl MARQSTLLLFWSLVFLGAIVFTQAKHEELEEVTHKVYFDVDIAGKPAGRVVIGL 34 648
    isomerase FGKAVPKTVENFRALCTGEKGVGKSGKPLHYKGSFFHRIIPSFMIQGGDFTLGD
    GRGGESIYGTKFADENFKLKHTGPGFLSMANAGPDTNGSQFFITTVTTDWLDGR
    HVVFGKIISGMDVVYKVEAEGRQSGQPKRKVKIADSGELSMD
    434 Peptidylprolyl MEMDEIQEQSQPQSSEKQDISQESDTGNDKTINAEKITSENAEVEEDDMLPPKV 481 1611
    isomerase NTEVEVLHDKVTKQIIKEGSGNKPSRNSTCFLHYRAWAESTMHKFQDTWQEQQP
    LELVLGREKKELSGFAIGVAGMKAGERALLHVDWQLGYGEEGNFSFPNVPPRAN
    LIYEAELIGFEEAKEGKARSDMTVEERIEAADRRRQQGNELFKEDKLAEAMQQY
    EMALAYMGDDFMFQLFGKYKDMANAVKNPCHLNMAQCLLKLNRYEEAIGQCNMV
    LAEDEKNIKALFRRGKARATLGQTDDAREDFQKVRKFSPEDKAVIRELRLLAEH
    DKQVYQKQKEMFKGLFGQKPEQKPKKLHWFVVFWQWLLSMIRTIFRMRSKTD
    435 Peptidylprolyl MAGAGEGTPEVTLETSMGPITVELYHKHAPKTCRNFLELSRRGYYNNVKFHRVI 93 584
    isomerase KDFMVQGGDPTGTGRGGESIYGPRFEDEITRDLKHTGAGILSMANAGPNTNGSQ
    FFISLAPTPWLDEKHTIFGRVCKGMDVVKRLGNVQTDKNDRPIHDVKILRTTVKD
    436 Peptidylprolyl MMDPELMRLAQEQMSKISPDELMKMQRQIMANPDLMRMASENMKNLKPEDIRFA 250 1869
    isomerase AEQMKNVRKEEMAEISERISRASPEEIEAMKARANLQSAYQLQVAQNLKDQGNQ
    LHARMKYSEAAEKYLQARNNLTGIPFSEAKSLLLASSSNLMSCYLKTGQYEECV
    QTGSEVLAYDAMNVKALYRRGQAYKQIGKLELAVADLRKAVEVSPEDETIAQAL
    REASTELMEKGGTQDQNGPRIEEIIEEEAVQPTAEKYPQSAPMVTSVTEDVSDD
    EQGSEDQNGFSRDSFQATNAPDGQMYAESLRNLTENPDMLRTMQSLMKNVDPDS
    LVALSGGKLSPDMVKTVSGMFGRMSPEEIQNMMKMSSTLSRQNPSTSSRFDDIT
    RGHSNMDSSPQSVSVDNDLFEENQNRVGESSTNLSSSAAFSGMPNFSAEMQEQV
    RNQMNDPATRQMFTSMIQNMSPEMMASMSEQFGVKLSPEDAVKAQNAMASLSPN
    DLDRLMNWATRLQTAIDYARKIKNWILGRPGLIFAISMLLLAIILHRFGYIGD
    437 Peptidylprolyl MGVEKEILRPGNGPKPRPGQSVTVHCTGYGKNEDLSQKFWSTKDPGQKPFTFTI 84 422
    isomerase GQGRVIKGWDEGVLDMQLGEIFKLRCSPDYGYGSNGFPAWGIRPNSVLVFEIEV
    LSVN
    438 Peptidylprolyl MPNPRCYLDITIGEELEGRILVELYSDVVPKTAENFRALCTGEKGIGPHTGVPL 128 1213
    isomerase HYKGLPFHRVIKGFMIQGGDISAQNGTGGESIYGLKFDDENFQLKHERRGMLSM
    ANSGPNTNGSQFFITTTRTSHLDGKHVVFGKVIKGMGVVRGIEHTPTESNDRPS
    LDVVISDCGEIPEGSDDGIANFFKDGDLYPDWPADLDEKSAEISWWMNAVDSAK
    CFGNENYKKGDYKMALRKYRKALRYLDICWEKEEIDEEKSNHLRKTKSQIFTNS
    SACKLKLGDLKGALLDTEFAMRDGEDNVKALFRQGQAYMALKDVDSAVASFKKA
    LQLEPNDAGIRKELAVATKMINDRRDQERRAYARMFQ
    439 Peptidylprolyl MGDVIDLNGDGGVLKTIIRSAKPGAMQPTEDLPNVDVHYEGTLADTGEVFDTTR 265 837
    isomerase EDNTLFSFELGKGTVIKAWDIAVKTMKVGEVARITCKPEYAYGSAGSPPDIPEN
    ATLIFEVELVACKPRKGSTFGSVSDEKARLEELKKQREIAAASKEEEKKRREEA
    KATAAARVQAKLEAKKGQGRGKGKSKGK
    440 Peptidylprolyl MGLGLKIASASFLPIFNIMATRSLCILLVCFIPVLAHVLSLQDPELGTVRVYFQ 38 781
    isomerase TTYGDIEFGFFPHVAPKTVEHIYKLVRLGCYNSNHFFRVDKGFVAQVADVVGGR
    EVPLNSEQRKEGEKTIVGEFSEVKHVRGILSMGRYSDPDSASSSFSILLGNAPH
    LDGQYAVFGKVTKGDDTLKRLEEVPTRQEGIFVMPLERIRILSTYYYDTNERES
    NLTCDHEVSILKRRLVESAYEIEYQRRKCLP
    441 Peptidylprolyl MASKRSLRTMNVWPTLPPLVLLLLLCFSSMSSSVVAKKSDVSELQIGVKHKPKS 38 526
    isomerase CDIQAHKGDRIKVHYRGSLTDGTVFDSSFERGDPIEFELGSGQVIKGWDQGLLG
    MCVGEKRKLRIPSKLGYGAQGSPPKIPGGATLIFDTELVAVNGKGISNDGDSDL
    442 Peptidylprolyl MSGAPAERPISYFDITIGGKPIGRIVFSLYADLVPKTAENFRALCTGEKGIGKS 37 1158
    isomerase GKPLCYAGSGFHRVIKGFMCQGGDFTAGNGTGGESIYGEKFEDEAFPVKHTKPF
    LLSMANAGKDTNGSQFFITVSQTPHLDDKHVVFGEVIKGKSIVRAIENYPTASG
    DVPTSPIIISACGVLSPDDPSLAASEETIGDSYEDYPEDDDSDVQNPEVALDIA
    RKIRELGNKLFKEGQIELALKKYLKSIRYLDVHPVLPDDSPPELKDSYDALLAP
    LLLNSALAALRTQPADAQTAVKNATRALERLELSDADKAKALYREASAHVILKQ
    EDEAEEDLVAASQLSPEDMAISSKLKEVKDEKKKKREKEKKAFKKMFSS
    443 Peptidylprolyl MASSLRSSLFSSWALDSKSVCSLFNLNPGKMGLPSISTPLNWRTCCCSHSSELL 61 768
    isomerase ELNEGLQSSRRKTVMGLSTVIALSLVYCDEVGAVSTSKRALRSQKVPEDEYTTL
    PNGLKYYDLKVGSGTEAVKGSRVAVHYVAKWKGITFMTSRQGMGITGGTPYGFD
    VGASERGAVLKGLDLGVQGMRVGGQRILIVPPELAYGNTGIQEIPPNATLEFDV
    ELISIKQSPEGSSVKIVEG
    444 WD40 repeat MGAIEDEEPPLKRLKVSSPGLRRGLEEEAPSLSVGSVSILMAKSLSLEEGETVG 421 2172
    protein SKGLIRRVEFVRIITQALYSLGYQKAGALLEEESGILLQSSNVALFRKQILDGK
    WDESVVTLRGIDQVEVEGNTLKAASFLILQQKFFELLDKGNIPEAMKTLRLEIS
    PMQLNTKRVHELASCIVFPSRCEELGYSKQGNPKSSQRMKVLQEIQQLLPPSIM
    IPEKRLERLVEQALNVQREACIFHNSLDPALSLYTDHQCGRDQIPTTTLQVLES
    HKNEVWFLQFSNNGKYLASASKDCSAIIWEITEGDSFSMKHRLSAHQKPVSFVA
    WSPDDKLLLTCGIEEVVKLWNVETGECKLTYDKANSGFTSCGWFPDGERFISGG
    VDKCIYIWDLEGKELDSWKGQGMPKISDLAVTSDGKEIISICGDNAIVMYNLDT
    KTERLIEEESGITSLCVSKDSRFLLLNLANQEIHLWDIGARSKLLLKYKGHRQG
    RYVIRSCFGGSDLAFVVSGSEDSQVYIWHRGNGELLAVLPGHSGTVNCVSWNPV
    NPHVFASASDDYTIRIWGVNRNTFRSKNASSSNGVVHLANGGP
    445 WD40 repeat MPGTTAGAGIEPIEPQSLKKLSLKSLKRSFDLFASLHGEPQPPDQRSQRIRIAC 163 1647
    protein KVRAEYEVVKNLPTLPQREVGSSVSNSNVGETHSSLTTNQAQGFPTDTSGDLSK
    DEGKEITSIAVHLQPQTGLIDGKAGAIAGTSTAISSVGSSDRYQPSAAIMKRLP
    SKWPRPIWHPPWKNYRVISGHLGWVRSVAFDPGNEWFCTGSADRTIKIWEVATG
    KLKLTLTGHIEQIRGLAVSSRHPYLFSAGDDKQVKCWDLEYNKAIRSYHGHLSG
    VYCLALHPTLDILCTGGRDSVCRVWDIRTKAQIFALSGHENTVCSVFTQAIDPQ
    VVTGSHDTTIKLWDLAAGKTMSTLTYHKKSVRAIAKHPFEHTFASASADNIKKF
    KLPKGEFLHNMLSQQKTIVNAMAINEDNVLVSAGDNGSLWFWDWKSGHNFQQAQ
    TIVQPGSLDSEAGIYALQYDITGSRLVSCEADKTIKMWKEDETATPESHPINFK
    APKDIRRF
    446 WD40 repeat MRPILMKGHERPLTFLKYNRDGDLLFSCAKDHTPTVWYGHNGERLGTYRGHNGA 192 1172
    protein VWCCDVSRDSTRLITSSADQTAKLWNVETGAQLFSFNFESPARAVDLAIGDKLV
    VITTDPFMELPSAIHIKRIEKDLSKQTADSVLTITGIKGRINRAVWGPLNSTII
    SGGEDSVVRIWDSETGKLLRESDKETGHQKPITSLCKSADGSHFLTGSLDKSAR
    LWDIRTLTLIKTYVTERPVNAVAISPLLDHVVIGGGQEASHVTTTDRRAGKFEA
    KFFHKILEEEIGGVKGHFGPINSLAFNPDGRSFASGGEDGYVRLHHFDPDYFHI
    KM
    447 WD40 repeat MRPILMKGHERPLTFLKYNRDGDLLFSCAKDHTPTVWYGHNGERLGTYRGHNGA 131 1111
    protein VWCCDVSRDSTRLITSSADQTAKLWNVETGNQLFSFNFESPARAVDLAIGDKLV
    VITTDPFMELPSAIHIKRIEKDLSKQTADSVLTITGIKGRINRAVWGPLNSTII
    SGGEDSVVRIWDSETGKLLRESDKETGHQKAITSLCKSADGSHFLTGSLDKSAR
    LWDIRTLTLIKTYVTERPVNAVAISPLLDHVVIGGGQEASHVTTTDRRAGKFEA
    KFFHKILEEEIGGVKGHFGPINSLAFNPDGRSFASGGEDGYVRLHHFDPDYFHI
    KM
    448 WD40 repeat MAENNVGDFIPLDRQEYPSKPAPGAVDSSFWKSFKKKEVSRQIAGVTCINFCPE 149 1726
    protein PPHDFAVTSSTRVHIYDGKSCELKKTITKFKDVAYSGVFRSDSQIIAAGGETGV
    IQVFNAKSQMVLRQLKGHGRPVRVVRYSPQDKLHLLSGGDDSMVKWWDITTQEE
    LLNLEGHKDYVRCGAASPSSVNLWATGSYDHTVRLWDLRNSKTVLQLKHGKPLE
    DVLFFPSGGLLATAGGNVVKVWDILGGGRPIHTMETHQKTVMAMCISKVPRSGQ
    ALGDAPSRLVTASLDGYMKVFDLDHFKVTHSARYPAPILSMGISSLCRTMAVGT
    SSGLLFIRQRKGQIEDKIHSDSSGLQVNPVNDEKDSAVLKPNQYRYYLRGRSEK
    PSEGDYVVKRMAKVYFQEYDKDLRHFNHSKALVSALKAADSKGTVAVIEELVAR
    KRLIQTLSILNLDELELLINFLSRFILVPKYSRFLISLTDRVLDARAVDLGKSE
    NLKKQIADLKGIVVQELRVQQSMQELQGIIEPLIRASAR
    449 WD40 repeat MDVETSGKPTGNKRTYTRLPRQVCVFWQEGRCTRESCNFLHVDEPGSVKRGGAT 948 2228
    protein NGFAPKRSYNGSDERDTLAAGPPGGSRRNISARWGRGRGGIFISDERQKIRNKV
    CNYWLAGNCQRGEECKYLHSFVMGSDVKFLTQLSGHVKAIRGIAFPSDSGKLYS
    GGQDKKVIVWDCQTGQGTDIPLNDEVGCLMSEGPWIFVGLPNAVKAWNILTSTE
    LSLVGPRGQVHALAVGNGMLFAGTHDGSILAWKFSPASNTFEPAASLVGHTQAV
    VSLVSGADRLYSGSMDKTIRVWDLGTFQCLQTLRDHTSVVMSLLCWDQFLLSCS
    LDNTVKVWVATSSGALEVTYTHNEEHGVLALCGMNDEQAKPVLLCSCNDNTVRL
    YDLPSFSERGRIFSRNEVRTFQIAPGGLFFTGDATGELKVWNWATQKS
    450 WD40 repeat MSVQELRERHAAATAKVNALRERIKAKRLQLLDTDVATYASSNGRTPISFSFTD 332 1465
    protein LVCCRTLQGHTGKVYSLDWTSEKNRIVSASQDGRLIVWNALTSQKTHAIKLPCA
    WVMTCAFSPSGQAVACGGLDSVCSIFQLNNQLDRDGHLPVSRILSGHRSYVSSC
    QYVPDGDTHVITGSGDRTCIQWDVTTGQRIAIFGGEFPLGHTADVMSVSISAAN
    PKEFVSGSCDTTTRLWDTRIASRAIRTFHGHEADVNTVKFFPDGLRFGSGSDDG
    TCRLFDIRTGHQLQVYRQPPRENQSPTVTAIAFSFSGRLLFAGYSNGDCFVWDT
    ILEKVVLNLGELQNTHNGRISCLGLSADGSALCTGSWDKNLKIWAFGGHRKIV
    451 WD40 repeat MKVKIISRSTDEFTRERSNDLQRVFRNFDPNLHTQARAQEYVRALNAAKLDKIF 232 1590
    protein AKPFLAAMSGHIDGISAMAKSPRHLKSIFSGSVDGDIRLWDIAARRTVQQFPGH
    RGAVRGLTVSTEGGRLISCGDDCTVRLWDIPVAGIGESSYGSENVQKPLATYVG
    KNSFRAVDYQWDSNVFATGGAQVDIWDHDRSEPTNSFAWGSDTVISVRFNPAEK
    DIFATTASDRSIVLYDLRMASPLNKLIMQTRNNAIAWNPREPMNFTAANEDCNC
    YSYDMRRMNISTCVHQDHVSAVMDIDYSPSGREFVTGSYDRTVRIFPYNAGHSR
    EIYHTKRMQRVFCVKFSGDATYVVSGSDDANIRLWKAKASEQLGVLLPRERKRH
    EYLDAVKERFKHLPEIKRIERHRHLPKPIYKAALLRHTVNAAAKRKEERKRAHS
    APGSVVTNPLRKKRIVAQLE
    452 WD40 repeat MDHYYQDDFDYLVDDEMVDFADDVEDDVRTRRRSDIDSDSENDFDLNNKSPDTT 207 1550
    protein ALQAKRGKDIQGIPWNRLNFTREKYRETRLQQYKNYENLPRPRRSRNLDKECTN
    FERGSSFYDFRHNTRSVKATIVHFQLRNLVWATSKHNVYLMQNYSIMHWSSLKQ
    KGEEVLNVAGPIVPSVKHPGSSPQGLTRVQVSAMSVKDNLVVAGGFQGELICKY
    LDKPGVSFCTKISHDENGITNAVEIYNDASGATRLMTANNDLAVRVFDTEKFTV
    LERFSFPWSVNHTSVSPDGKLVAVLGDNADCLLADCKTGKTVGTLRGHLDYSFA
    AAWHPDGYILATGNQDTTCRLWDVRKLSSSLAVLKGRMGAIRSIRFSSDGRFMA
    MAEPADFVHLYDTRQNYTKSQEIDLFGEIAGISFSPDTEAFFVGVADRTYGSLL
    EFNRRRMNYYLDSIL
    453 WD40 repeat MAEALVLRGTMEGHTDAVTAIATPIDNSDMIVSSSRDKSILLWNLTKEPEKYGV 221 1171
    protein PRRRLTGHSHFVQDVVISSDGQFALSGSWDSELRLWDLNTGLTTRRFVGHTKDV
    LSVAFSIDNRQIVSASRDRTIKLWNTLGECKYTIQPDAEGHSNWISCVRFSPSA
    TNPTIVSCSWDRTVKVWNLTNCKLRNTLVGHGGYVNTAAVSPDGSLCASGGKDG
    VTMLWDLAEGKRLYSLDAGDIIYALCFSPNRYWLCAATQQCVKIWDLESKSIVA
    DLRPDFIPNKKAQIPYCTSLSWSADGSTLFSGYTDGKIRVWGIGHV
    454 WD40 repeat MAAIKSTSRSASVAFAPDAPLLAAGTMAGAIDLSFSSLANLEIFKLDFQSDDPE 221 3679
    protein LPVVGECPSNERLNRLSWGSAGGSFGIIAGGLVDGTINIWNPATLINSEDNGDA
    LIARLEQHTGPVRGLEFNTISTNLLASGAEDGELCIWDLANPTAPTHFPPLKGV
    GSGAQGEISFLAWNRKVQHILASTSYSGTTVVWDLRRQKPIISFPDATRRRCSV
    LQWNPDASTQLIVASDDDNSPTLRAWDLRNTISPYKEFVGHSRGVIAMSWCPSD
    SLFLLTCAKDNRTLCWDTGSGEIVCELPAGANWNFDVQWSPKIPGILSTSSFDG
    KIGIHNIEACSRNVSGEVEFGGAIVRGGPSALLKAPKWLERPAGVSFGFGGKLA
    SFRPSTVAQAADHRHSEVFIHNLVTEDNLVIRSTEFEAAIADGEKVSLRALCDR
    KAEESQSDEEKETWNFLRVMFEDEGTARTKLLEHLGFKVQSEENGDLQETHSSK
    IDDIGSEIGKTLTLDDKTEEDVLPQLKGGQDAAIPQDNGEDFFDNLHSPKEEVS
    LSHVGNDFVGEKDKDMVVNGAEIEHETEDLTEYSDWNEAIQHSLVVGDYKGAVL
    QCLSANRMADALIIAHLGGNSLWEKTRDEYLKKAKSSYLKVVSAMVNNDLTGLV
    NSRPLKSWKETLAMLCTYSQREEWTVLCDMLASRLIAAGNVMAATLCYICAGNI
    EKTVEIWSRSLKYDYDGRSFVDHLQDVMEKTVVLALATGQKRVSPSLSKLVENY
    AELLASQGLLTTAMEYLKLLGTEESSHELSILRDRLYLSGTDNKVEASSFPFET
    RQDLTESQYNMHQTGFGAPETQKNYQENVHQVLPSGSYTDNYQPTANTHYIAGY
    QPAPQQQPSFQNYFTPASYQPAPSPNVFYPSQVSQAEQSNFAPPVNQPPMKTFV
    PSTPPILRNVDQYQTPSLNPQLYQGVSSATVETHPYQTGAPASVSVGTTPGQPS
    VVPNFMVPGPVTAPTVTPRGFMPVTTPTQHPLGSANPPVQPQSPQSSQVQSVTA
    ATTPPPTIQNVDTSNVAAEIRPVIGTLRRLYDETSEALGGARANPAKRREIEDN
    SRKIGSLFAKLNSGDISSNAASKLVHLCQALESRDYATAFQIQVGLTTSDWDEC
    SFWLAALKRMIKVKQNMR
    455 WD40 repeat MAGAADSQLQTLSERDSTPNFKNLHTREYAAHKKKVHSVAWNCTGTKLASGSVD 269 1252
    protein QTARVWNIEPHGHSKTKDLELKGHADSVDQLCWDPKHSELLATASGDRTVRLWD
    ARSGKCSQQVELSGENINITFKPDGTHIAVGNRDDELTIIDVRKFKPLHKRKFS
    YEVNEIAWNTTGELFFLTTGNGTVEVLSYPSLQVLHTLVAHTAGCYCIAIDPIG
    RYFAVGSADALVSLWDLSEMLCVRTFTKLEWPVRTISFNHDGQYIASASEDLFI
    DIADVQTGRTVHQISCRAAMNSVEWNPKYNLLAFAGDDKNKYMQDEGVFRVFGF
    ETP
    456 WD40 repeat MAATSPVGAGSGRELANPPTDGISNLRFSNHSDHLLVSSWDRKVRLYDASANSL 214 1242
    protein KGQFVHGGPVLDCCFHDDASGFSGSADNTVRRYDFSTRKEDILGRHEAPVRCVE
    YSYAAGQVITGSWDKTLKCWDPRGASGQEKTLVGTYSQLERVYSMSLVGHRLVV
    ATAGRHINVYDLRNMSQPEQRRESSLKYQTRCVRCYPNGTGFALSSVEGRVAME
    FFDLSEAGQAKKYAFKCHRKSEAGRDTVYPVNAIAFHPIYGTFATGGCDGYVNV
    WDGNNKKRLYQYSKYPTSIAALSFSRDGRLLAVASSYTFEEGEKPHEPDAVFVR
    SVNEAEVKPKPKVYAAPP
    457 WD40 repeat MASDDEEGFKNEEAPGVVDEAEVQEGLRACFPLSFGKQEKKQAPLESIHSATKR 119 2065
    protein PEDPRPRRQLGPPRPPPSILAEQEDSDRFVGPPRPPQFVRDDNDDGEAEIMIGP
    PRPPAQYSDDHDNEETIGPPKPSYLEKGEETDQMVGPSKRGSDDETSGDSDDGD
    DAVDFRVPLSNEIVLRGHTKVVSALAIDQTGSRVLTGSYDYSVRMYDFQGMTSQ
    LKSFRQLEPAEGHQVRSLSWSPTSDRFLCVTGSAQAKIFDRDGLTLGEFVKGDM
    YLRDLKNTKGHISGLTCGEWHPKEKQTILTCSEDGSLRIWDVNDFNTQKQVIKP
    KLAKPGRVPVTACAWGRDGKCIAGGVGDGSIQVWNLKPGWGSRPDLYVAKGHDD
    DITGLQFSADGNILLTRSTDETLKVWDLRKAITPLQVFRDLPNNYAQTNVAFSP
    DERLIFTGTSVERDGNSGGLLCFYDRQTLELVLRIGVSPVHSVVRCTWHPRHNQ
    VFATVGDKKEGGAHILYDPALSERGALVCVARAPRKKSLDDFEAKPVIHNPHAL
    PLFRDEPSRKRQREKARMDPMKSQRPDLPVTGPGFGGRVGSTKGSLLTQYLLKE
    GGLIKETWMEEDPREAILKYADVAAKDPKFIAPAYAQTQPETVFAETDSEEEQK
    458 WD40 repeat MKERGQSHAGQPSVDERYTQWKSLVPVLYDWLANHNLVWPSLSCRWGPQMHQAT 186 1550
    protein YKNSQRLYLSEQTDGTVPNTLVIATCEVVKPRVAAAEHISQFNEEARSPFVKKF
    KTIIHPGEVNRIRELPQNSKIVATHTDGPDVLIWDVDTQPNRQATLGAADSRPD
    LVLTGHKDNAEFALAMSPSAPFVLSGGKDKCVLLWSIQDHISAATEPSSAKASK
    TPSSAHGEKVPKIPSIGPRGVYKGHKDTVEDVQFCPSNAQEFCSVGDDSALILW
    DARNGNEPVIKVEKAHNADLHCVDWNPHDENLILTGSADNSVRMFDRRNLTSSG
    VGSPVHKFEGHSAPVLCVQWCPDKASVFGSAAEDSYLNVWDYEKVGKNVGKKTP
    PGLFFQHAGHRDKVVDFHWNSFDPWTIVSVSDDGESTGGGGTLQIWRMSDLIYR
    PEDEVLAELERFRAHILSCQNK
    459 WD40 repeat MSSLSRELVFLILQFLDEEKFKESVHKLEQESGFFFNMKYFDEKAQAGEWDEVE 244 3671
    protein RYLSGFTKVDDNRYSMKIFFEIRKQKYLEALDRQDRAKAVDILVKDLKVFSTFN
    EELYKEITQLLTLDNFRENEQLSKYGDTKSARTIMMSELKKLIEANPLFREKLI
    YPNLKASRLRTLINQSLNWQHQLCKNPRPNPDIKTLFTDHACGPPNGARTPTQP
    TASLGVLPKATTFTPIGPHGPFPSSSTATSGLASWMSNPNMVTSPQAPVAVGPS
    VPVPPNQATLLKRPRTPPGSSSVVDYQTADSEQLIKRLRPVSQSIDEATYPGPT
    LRVPWSTDDLPKTLARALNEPYPVTSIDFHPSQQTFLLVGTKNGEITLWEVGSR
    EKLATRSFKIWDNANCSNHLEAAFVKDSSVSINRVLWSPDGTLIGIAFTKHLVH
    TYTFQGLDLRQHLEIDAHVGGVNDLAFSHPNKQLCVVTCGDDKMIKVWDAVTGR
    KLYNFEGHDAPVYSVCPHHKENIQFIFSTAVDGKIKAWLYDHLGSRVDYDAPGH
    SCTTMMYSADGTRLFSCGTSKEGESFLVEWNESEGAIKRTYSGLRKKGSGVVQF
    DTTQNHFLAVGDEHLIKFWDMDSTNMLTSCDAEGGLLNLPRLRFNKEGSLLAVT
    TVNGIKILANADGQKLLKTMENRTFDLPSRAHIDAASATSSPATGRMERIERTS
    SANTVSGINGVDPAQSSEKLRLSDDLSEKTKIWKLTEITDSIQCRCITLPENAA
    EPASKVSRLLYTNSGVGLLALGSNAVHKLWKWNRSEQNPSGKATASVHPQRWQP
    TSGLLMTNDITDINPEEAVPCIALSKNDSYVMSASGGKVSLFNMMTFKVMTTFM
    PPPPASTFLAFHPQDNNIIAIGMEDSTIHIYNVRVDEVKTKLKGHQKRITGLAF
    SSTQNILVSSGADAQLCVWNTETWEKRKSKTIQMPVGKTVSGDTRVQFHSDQLH
    ILVVHETQLAIYDAYKLERQYQWVPQDALSAPILYATYSCNRQLIYATFSDGNI
    GVYDAEILRPRCRIAPTTYLSSGTSSSTSLPLVVAAHPHEPNQFAIGLSDGAVQ
    VLEPSESEGKWGVSPPPENGVVPAVVAGPSTSNQGSEQAPR
    460 WD40 repeat MAKDEEEFRGEMEERLVNEEYKIWKKNTPFLYDLVITHALEWPSLTVQWLPDRE 163 1431
    protein EPPGKDYSVQKMILGTHTSDNEPNYLMLAQVQLPLEDAENDARQYDDERGEIGG
    FGCANGKVQVIQQINHDGEVNRARYMPQNPFIIATKTVSAEVYVFDYSKHPSKP
    PQDGGCHPDLRLRGHNTEGYGLSWSPFKHGHLLSGSDDAQICLWDINVPAKNKV
    LEAQQIFKVHEGVVEDVAWHLRHEYLFGSVGDDRHLLIWDLRTSATNKPLHSVV
    AHQGEVNCLAFNPFNEWVLATGSADRTVKLFDLRKISSALHTFSCHKEEVFQIG
    WSPKNETILASCSADRRLMVWDLSRIDEFQTPEDALDGPPELLFIHGGHTSKIS
    DFSWNPCEDWVIASVAEDNILQIWQMAENIYHDEEDDMPPEEVV
    461 WD40 repeat MSPGVKQTGSQKFESGHQDVVHDVTMDYYGKRIATCSADRTIKLFGLNASDTPS 155 1081
    protein LLASLTGHEGPVWQVAWAHPKFGSMLASCSYDGRVIIWREGQQENEWSQVQVFK
    EHEASVNSISWAPNELGLCLACGSSDGSITVFTCREDGSWDKTKIDQAHQVGVT
    AVSWAPASAPGSLVGQPSDPIQKLVSGGCDNTAKVWKFYNGSWKLDCFPPLQMH
    TDWVRDVAWAPNLGLPKSTIASCSQDGKVVIWTQGKEGDKWEGRILNDFKIPVW
    RVNWSLTGNILAVADGNNSVTLWKEAVDGDWNQVTTVQ
    462 WD40 repeat MSSGVKQTGSQKFESGHQDVVHDVTMDYYGKRIATCSADRTIKLFGMNTSDTPT 537 1463
    protein LLASLTGHEGPVWQVAWAHPKFGSMLASCSYDRRVIIWREGQQENEWSQVQVFK
    EHEASVNSISWAPHELGLCLACGSSDGSITVFTGREDGSWDKTKIDQAHQVGVT
    AVSWAPASAPGSLVGQPSDPVQKLVSGGCDNTAKVWKFYNGSWKLDCFPPLQMH
    TDWVRDVAWAPNLGLPKSTIASCSQDGRVVIWTQGKEGDKWEGKILNDFKTPVW
    RISWSLTGNILAVADGNNNVTLWKEAVDGEWNQVTTVQ
    463 WD40 repeat MKKRSRPSNGHLSTAAKNKSRKTAPITKDPFFDSAHNRNKSKGKGKSRGKGEEI 284 1909
    protein FSSDEDDDAIGRDAPAEEEEEIAEEERETADEKRLRVAKAYLDKIRAITKANEE
    DNEEEAGEDEETEAERRGKRDSLVAEILQQEQLEESGRVQRQLASRVVTPSKLV
    ECRVVKRHKQSVTAVALTEDDLRGFSASKDGTIIHWDVETGASEKYEWPSQAVS
    VSSSNEVSKTQKGKGSKKQGSKHVLSMAVSSDGRYLATGGLDRYIHLWDTRTQK
    HIQAFRGHRGAVSCLAFRQGTQQLISGSFDRTIKLWSAEDRAYMDTLYGHQSEI
    LAVDCLRKERVLSVGRDHTLRLWKVPEETQLVFRGHAASLECCCFINNEDFLSG
    SDDGSIELWSMLRKKPVFMAKNAHGHAIVENLSEDTSTREEPDEEVTTRQLPNG
    NSIGNGMTNQMGITPSVESWVGAVTVCRGTDLAASGAGNGVVRLWAIENSSKSL
    RALHDIPLTGFVNSLTFARSGRFLIAGVGQEPRLGRWGRIQAARNGVTLCPIELS
    464 WD40 repeat MAATFGTINTATSPHNPNKSFEIVQPPNDSISSLSFSPKANYLVATSWDNQVRC 610 1659
    protein WEVLQTGASMPKAAMSHDQPVLCSTWKDDGTAVFSAGCDKQAKMWPLLTGGQPV
    TVAMHDAPIKDIAWIPEMNLLATGSWDKTLKYWDTRQSNPVHTQQLPERCFALS
    VRHPLMVVGTADRNLIIFNLQNPQTEFKRISSPLKYQTRCVAAFPDKQGFLVGS
    IEGRVGVHHVEEAQQSKNFTFKCHRDSNDIYAVNSLNFHPVHQTFATAGSDGAF
    NFWDKDSKQRLKAMARSNQPTPCSTFNSDGSLYAYAVSYDWSKGAENHNPATAK
    HHILLHVPQESEIKGKPRVTTSGRK
    465 WD40 repeat MVVMDKGTHQTNEDESESEFIDEDDVIDEISIDEEDLPDADVEGEDVQEDNKRS 241 1452
    protein EPDENSSSLDDAIHTFEGHEDTLFAVACSPVDATWVASGGGDDKAFMWRIGHAT
    PFFELKGHTDSVVALSFSNDGLLLASGGLDGVVRIWDASTGNLIHVLDGPGGGI
    EWVRWHPKGHLVLAGSEDYSTWMWNADLGKCLSVYTGHCESVTCGDFTPDGKAI
    CTGSADGSLRVWNPQTQESKLTVKGYPYHTEGLTCLSISSDSTLVVSGSTDGSV
    HVVNIKNGKVVASLVGHSGSIECVRFSPSLTWVATGGMDKKLMIWELQSSSLRC
    TCQHEEGVMRLSWSLSSQHIITSSLDGIVRLWDSRSGVCERVFEGHNDSIQDMV
    VTVDQRFILTGSDDTTAKVFEIGAF
    466 WD40 repeat MPVFRTAFNGYAVKFSPFVETRLAVATAQNFGIIGNGRQHVLELTPNGIVEVCA 223 1173
    protein FDSSDGLYDCTWSEANENLVVSASGDGSVKIWDIALPPVANPIRSLEEHAREVY
    SVDWNLVRKDCFLSASWDDTIRLWTIDRPQSMRLFKEHTYCIYAAVWNPRHADV
    FASASGDCTVRIWDVREPNATIIIPAHEHEILSCDWNKYNDCMLVTGSVDKLIK
    VWDIRTYRTPMTVLEGHTYAIRRVKFSPHQESLIASCSYDMTTCMWDYRAPEDA
    LLARYDHHTEFAVGIDISVLVEGLLASTGWDETVYVWQHGMDPRAC
    467 WD40 repeat MDSRNRRSRLNLPPGMSPSSLHLETTAGSPGLSRVNSSPSTPSPSRTTTYSDRF 251 1777
    protein IPSRTGSRLNGFALIDKQPQPLPSPTRSAAEGRDDASSSSASAYSTLLRNELFG
    EDVVGPATPATPEKSTGLYGGSRDSIKSPMSPSRNLFRFKNDHGGNSPGSPYSA
    STVGSEGLFSSNVGTPPKPARKITRSPYKVLDAPALQDDFYLNLVDWSSNNVLA
    VGLGTCVYLWSACTSKVTKLCDLGVNDSVCSVGWTPQGTHLAVGTNIGEVQIWD
    TSRCKKVRTMGGHCTRAGALAWSSYILSSGSRDRNILHRDIRVQDDFIRKLVGH
    KSEVCGLKWSYDDRELASGGNDNQLLVWNQQSAQPLLRFNEHTAAVKAIAWSPH
    QHGILASGGGTADRCLRFWNTATDTRLNCVDTGSQVCNLVWCKNVNELVSTHGY
    SQNQIMVWRYPSMSKLATLTGHTLRVLYLAISPDGQTIVTGAGDETLRFWSIFP
    SPKSQSAVHDSGLWSLGRTHIR
    468 WD40 repeat MEKKKVVVPIVCHGHSRPIVDLFYSPVTPDGLFLISASKDSSTMLRNGETGDWI 367 1419
    protein GTFEGHKGAVWSCCLDNRALRAASGSADFSAKIWDALTGDELHCFVHKHIVRAC
    AFSESTSLLLTGGHEKILRIFDLNRPDAPPKEVDNSPGSIRTVAWLHSDQTILS
    SNSDAGGVRLWDLRTEKIVRVLETKSPVTSAEVSQDGRYITTADGNSVKFWDAN
    HFGMVKSYTMPCMVESASLEPTMGNMFVAGGEDMWVRLFDFHTGEEIACNKGHH
    GPVHCVRFAPGGESYSSGSEDGTIRIWQTLNMNSEENESYGVNGLSGKVRVGVD
    DVVQKVEGFQITADGHLNDKPEKPNP
    469 WD40 repeat MERYSQGTQKKSEIYTYEAPWQIYGMNWSVRKDKKFRLGIGSFLEEYNNRVEII 284 1303
    protein ELDEESGEFKSDPRLAFDHPYPTTKIMFVPDKECQRPDLLATTGDYLRIWQVCE
    DRVEPKSLLNNNKNSEFCAPLTSFDWNDADPKRIGTSSIDTTCTIWDIEKEVVD
    TQLIAHDKEVYDIAWGEVGVFASVSADGSVRVFDLRDKEHSTIIYESSQPETPL
    LRLGWNKQDPRFIATILMDSCKVVILDIRFPTLPVAELQRHQASVNTIAWAPHS
    PCHICTAGDDSQALIWELSSVSQPLVEGGGLDPILAYTAAAEINQLQWSSMQPD
    WVAIAFSNEVQILRV
    470 WD40 repeat MQSENNLDESLHLREVQELQGHTDTVWAVAWNPVTGIDGAPSMLASCSGDKTVR 684 1784
    protein IWENTHTLNSTSPSWACKAVLEETHTRTVRSCAWSPNGKLLATASFDATTAIWE
    NVGGEFECIASLEGHENEVKSVSWSASGMLLATCGRDKSVWIWDVQPGNEFECV
    SVLQGHTQDVKMVQWHPNRDILVSASYDNSIKVWAEDGDGDDWACMQTLGNSVS
    GHTSTVWAVSFNSSGDRMVSCSDDLTLMVWDTSINPAERSGNAGPWKHLCTISG
    YHDRTIFSVHWSRSGLIASGASDDCIRLFSESTDDSVTPVDGTSYKLILKKEKA
    HSMDVNSVQWHPSEPQLLASASDDGRIKIWEVTRINGLANSH
    471 WD40 repeat MKRAYKLQEFVAHASNVNCLKIGKKSSRVLVTGGEDHKVNMWAIGKPNAILSLS 336 2738
    protein GHSSAVESVTFDSAEALVVAGAASGTIKLWDLEEAKIVRTLTGHRSNCISVDFH
    PFGEFFASGSLDTNLKIWDIRRKGCIHTYKGHTRGVNSIRFSPDGRWVVSGGED
    NIVKLWDLTAGKLMHDFKCHEGQIQCMDFHPQEFLLATGSADRTVKFWDLETFE
    LIGSAGPETTGVRAMIFNPDGRTLLTGLHESLKVFSWEPLRCYDAVDVGWSKLA
    DLNIHEGKLLGCSYNQSCVGVWVVDISRVGPYAAGNVSRTNGHNEAKLASSGHP
    SVQQLDNNLKTNMARLSLSHSTESGIKEPKTTTSLTTTEGLSSTPQRAGIAFSS
    KNLPASSGPPSYVSTPKKNSTSRVQPTTNFQTLSRPDIVPVIVPRSNSLRPETT
    SDVKKEMNNFGRVVPSTVSTKSTDVIKSGSNRDESDKIDSINQKRMTGNDKTDL
    NIARAEQHVSSRLDNTNTSSVVCDGNQPAARWIGAAKFRRNSPVDPVVSPHDRS
    PTFPWSATDDGVTCQPDRQVTAPELSKRVVEPGRARALVASWETREKALTADTP
    VLVSGRPPTSPGVDMNSFIPRGSHGTSESDLTVSDDNSAIEELMQQHNAFTSIL
    QARLTKLQVIRRFWQRNDLKGAIDATGKMGDHSVSADVISVLIERSEIFTLDIC
    TVILPLLTRLLQSETDRHLTVAMETLLVLVKTFGDVIRATISATPTIGVDLQAE
    QRLERCNLCYVELENIKQILVPLIRRGGAVAKSAQELSLALQEV
    472 WD40 repeat MSTLEIEARDVIKIVLQFCKENSLHQTFQTLQNECQVSLNTVDSLETFVADINS 81 1622
    protein GRWDVILPQVAQLKLPRKKLEDLYEQIVLEMIELRELDTARAILRQTQAMGFMK
    QEQPERYLRLEHLLVRTYFDPREAYHESSKEKRRSQIAQALASEVTVVPPSRLM
    ALIGQSLKWQQHQGLLPPGTQFDLFRGTAAVKADEEEMYPTTLAHTIKFGKQSH
    PECARFSPDGQYLVSCSVDGFIEVWDYISGKLKKDLQYQADDSFMMHDDAVLCV
    DFSRDSEMLASGSQDGKIKVWRIRTGQCLRRLERAHSQGVTSLSFSRDGSQLLS
    TSFDSTARIHGLKSGKALKEFRGHTSYVNDAIFTSDGGRVITASSDCTVKVWDV
    KTTDCIQTFKPPPPLKGGDVSVNSVHLFPKNSEHIVVCNKASSIYIMTLQGQVV
    KSFSSGKREGGDFVAACISPKGEWIYCVGEDRNIYCFSQQSGKLEHLMKAHDKD
    IIGVTPHPHRNLLVTYSEDSTMKIWKP
    473 WD40 repeat MDIELEDQPFDLDFHPSAPIVAVALITGRLQLFRYVDISSEPERLWTVTAHTES 399 1460
    protein CRAARFINAGSSVLTASPDCSILATNVETGQPVARLDNAHGAAINCLTNLTEST
    IASGDENGIIKVWDTRQNSCCNKFKAHEDYISDMEFVPDTMQLLGTSGDGTLSV
    CNLRKNKVHARSEFSEDELLSVALMKNGKKVVCGSQEGVLLLYSWGYFKDCSDR
    FVGHPHSVDALLKLDEDTVLTGSSDGIIRVVSILPNKMIGVIGEHSSYPIERLA
    FSHDRNVLGSASHDQILKLWDIHYLHEDDEPETNKQEAVNDENVDMDLDVDTEK
    RPRGSKRKKRAEKGQTSSQKQSSDFFADI
    474 WD40 repeat MDRIQQIPHTCVARKINLPLGMSKESLALNLPANLAPTMSPPSITYSDRFIPSR 207 1673
    protein KASNFEEFALPDKTSPSPNSAGGQSSSTNGEGRDDACAAYSALLRTELFPATPD
    KTEGCRRPVIGSPSGNVFRFKSQQCKSQSPFSLCPVGEDGDLSETGAVARKTTR
    KIPRSPFKVLDAPALQDDFYLNLVDWSSHNILAVGLSACVYLWSASSSKVTKLC
    DLGLDDNVCSVAWTQRGTYLAVGTNNGGVQIWDAAHCKQVRTMEGHCTRVGTLA
    WNSHILSSGGRDRNILQRDIRAQDDFVSKFSGHKSEVCGLKWSYDNRELASGGN
    DNQLFVWNQQSQQPVLKYNEHTAAVKAIAWSPHQHGLLASGGGTADRCIRFWNT
    ATNTSLNCVDTGSQVCNLVWSKNVNELVSTHGYSQNQIIVWRYPTMSKLATLTG
    HTLRVLYLAISPDGQTIVTGAGDETLRFWNVFPSSKTQQNTIRDMGVWSSGRTH
    IR
    475 WD40 repeat MAGGQGEGEEKVDKLSMELTEDVMKSMEIGAVFKDYNGKINSLDFHRTNNYLVT 263 1309
    protein ASDDEAIRLFDTASATWQKTSYSKKYGVDLICFTNHQTSVLYSSKNGWDESLRH
    LSLMDNKYLRYFKGHHDRVVSLCMSPKGECFMSGSLDRTVLLWDLRIDKCQGLI
    RVRGRPAVAYDEQGLVFAISNEGGLIKMFDARLYDKGPFDTFVVEGDKSEASGI
    KFSNDGKLILLSTMDSNIHVLDAYQGTTVHSFSVEAVPNGGEAVPNGGTLEASF
    SPDGKFVISGSGNGNIHAWSVNSGKEVACWTTEGVIPAVVKWAPRRLMFASGSS
    VLSLWVPDLSKLASLTGSNSNSAY
    476 WD40 repeat MHRVGSTGNTSNSSRPRREKRLTYVLNDANDSRHCSGINCLVISKLSLLGGNDY 232 2529
    protein LFSGSRDGTLKRWELADDSAVCSATFESHVDWVNDAVLTGETLVSCSSDTTLKT
    WRPFSDGVCTRTLRQHSDYVTCLAAASKNSNIVASGGLGREVFIWDIEAAMAPV
    SRTSEAMDDDTSNGVLSSGNSVLSTTVRSTNATNSASLHTSQLQGYTPIAAKGH
    KESVYALAMNDVGTLLVSGGTEKVVRVWDPRSGAKQMKLRGHTDNVRALILDST
    GRFCLSGSSDSIIRLWDLGQQRCVHSYAVHTDSVWALASTPNFSHVYSGGRDLS
    LYLTDLTTRESLLLCMEKHPLLRLTLQDDSIWVATTDSSLHRWPAEGQNPPKMF
    QRGGSFLAGNLSFTRARACLEGSAPVPVNTQPSFVIPGSPGIVQHEILNNRRHV
    LTKDAEGTVKLWEITRGAVLDDYGKVSFEEKKEELFEMVSIPAWFTMDTRLGSM
    SVHLDTPQCFTAEMYAVDLNVPDAPEEQKINLAQETLRGLLAHWLSRRRQRLAT
    QASANGDFPAGQENALRNHISSRIDVHDDAETHIAGILPAFDFSTTSPPSIITE
    GSQGGPWRKKITDLDGTEDEKDFPWWCLECVLHGRLSPRESLKCSFYLHPYEGT
    TVQVLTQGKLSAPRILRIQKVINYVLEKMVLDRPLDSSNSETTFTPGLSGNQSH
    AAVVGDGSLRSGARVWQQKAKPLVEILCNNQVLSPDMSLATVRTYIWKKPDDLY
    LYYRLVQNR
    477 WD40 repeat MMKGKTIQMQAAHQNHDGETSVACVLWDWHAKHLITAGADNTILIHSYPSSSSS 56 2950
    protein KPITLRHHKNAVTALAINSNVRSLASGSVDHSVKLYSYPGGEFQSNVTRFTLPI
    RSLAFNKSGELLAAAGDDEGIKLISTIDNSIARVLKGHNGPVTSISFDPKNEFL
    ASSDSDGTVIYWELSTGKPVHTLKKIAPNTTSNPTSLNQISWRPDGEMLAVPGR
    KSEVSMYDRDTAEKLFSLKGGHSDTICSLAWSPNGKYIATAGTDRQVMVWDADR
    RQDIDKQRFDNPICSVAWKPSDNALAVIDVLGRFGVWESPIASHMKSPADGAER
    YDNMEDEEPLMARYEEELEDSVSGSLNEIINDDDDDDEMGKIPRKILQKKPSVK
    VEKGKEESNAKAFKSGQDSFKLKSAMQEAFQPGATQRQSGKRNFLAYNMLGSVI
    TFDNDGFSHIEVDFHDIGKGCRVPSMTDYFGFTMASLSESGSVFGSPQKGEKNP
    STLMYRPFSSWANNSEWSMRFPMGEEVKAVALGSGWVAAVTSLNFLRVFSEGGL
    QKFVLSMDGPVVTAAGYENLLVVVSHASNPLLSGDQVLSFTVYDISQKTCPLSG
    RLPLSPGSHLTWLGFSEEGLLSSYDSEGNLRVFTNDYNGCWVPIFSAARERKSE
    TESIWMVGLNSTQVFCVVCKLPDTYPQVAPKPVLSVLNLSLPLACSDLGADDLE
    NEYLRGSLLLSQMQKKAEDAVACGRESNMEEDSIFKMEAALDRCLLRLIANCCK
    GDKLVRATELARLLSLEKSLQGAIKLVSAMKLPMLAERFNTILEEKILQENMET
    ISCRRLTSEAQDMDTPISISVKQVSYGANLGDSPFLPNRQVEPKHSTPVFSKPD
    TKIEVDTSEAIAKGCDAQNGNIKSGDAEVQPASHNDSIQKPSNPFAKASNTSAN
    QAVQRNASLLSSIKQMKTATENEGKRKERARSGSLPQKPAKQSKIS
    478 WD40 repeat MKQKRKGHQVDDPKYSVQTPQEDDTPNESGPASEEVESSDEEGGNSSNIEDDII 193 2577
    protein YSSSEEDPVVSSDYEEDEDAESDAEGVTAEQELEGDIDNALQNYMGTLTVLSNF
    HGENLKNAEGEDTSGDDDDEEEMPKRAEESDSPEDENDERPKRAEESDFSEDED
    EERPKRAEESDSSEDEVPSRNTVGDVPLRWYKDEQHIGYDIKGKKIKKQPKKDQ
    LDSFLASTDDSSDWRKVYDEYNDEEVELTKDEIKFISRLRKGTIPHADVNPYEP
    YVDWFDWKDKGHPLSNAPEPKRRFIPSKWEAKKVVKLVRAIRKGWITFQKAEEK
    PRFYLMWGDDLKPSEKMANGLSYIPAPKPKLPGHEESYNPPPEYIPTQEEINSY
    QLMYEEDRPKFIPKRFDSLRNVPAYDRFLSEIFERCLDLYLCPRTRKKRINIDP
    ESLIPKLPKPKDLQPFPSICFLEYKGHTGAVSCISPESSGQWLASGSKDGTVRI
    WEVETARCLKVWDIGRPIQHIAWNPVSQLSILAVAVDEEVLVLNTGLGSEDSQE
    KVAELLHVKSKPVSADDLGDNTSLTKWIKHEKFDGIKLTHLKPVHLISWHHKGD
    YFATVAPDGNTRAVLVHQLSKQQTQNPFKKMQGRVVHVLFHPSRAIFFVATKTH
    VRVYDLVKQQLVKRLVTGLHEVSSMAVHHKGDNLLVGSKEGKVCWFDMDLSTQP
    YKTLKNHSKDIHSVAFHDSYPLFASCSDDCKAYVFYGLVYSDLLQNPLIVPLKV
    LQGHQSVNGMGVLDCQFHPKQPWLFTAGADSVVKLYCN
    479 WD40 repeat MMSLKRGFEESLVPAKRQKTELSTVTYGDGPRRTSSLESPIMLLTGHHAAIYTM 187 1233
    protein KFNPTGTVIASGSHEREIFLWNVHGDCKNFMVLKGHKNAVLDLHWTTDGCQIIS
    ASPDKTLRAWDVETGKQIKKMAEHSSFVNSCCPSRRGPPLVVSGSDDGTAKLWD
    LRHRGAIQTFPDKYQITAVGFSDAADKIYSGGIDNEIKVWDLRRGEVTMRLQGH
    TDTITGMQLSSDGSYLLTNSMDCSLRIWDMRPYAPQNRCVKILTGHQHNFEKNL
    LKCSWSSDGSKVTAGSADRMVYIWDTTTRRILYKLPGHTGSVNETGFHPTQPII
    GSCSSDKQIYLGEIEPNVGYQAVI
    480 WD40 repeat MEFSDTYKHTGPCCFSPDARYLAIAVDYRLVIRDVVTLKVVQLYSCMDKISNIE 51 1436
    protein WALDSEYILCGLYKRAMVQAWSLSQPEWTCKIDEGPAGIAHARWSPDSRHIITT
    SDFQLRLTVWSLVNTACIHIQWPKHASKGVSFTQDGKFAAIATRRDCKDYVNLL
    SCHTWEVMGTFTVDTIDLADLEWSPNDSAIVVWDSPLEYKVLIYSPDGRCLFKY
    QAYDSWLGVKTVAWSPCSQFLAVGSYDQTLRTLNHLTWKPFAEFVHVSTVRGPA
    SAVVFKEVEEPWNLDVSGLHLNDDNAHDIQDGKPAEGHSRVRYKVVEFPVNVSS
    QKHPVDKPNPKQGIGLLAWSRDSQYLFTRNDNMPTALWIWDICRLELAALLIQK
    EPIRAAAWDPVYPRVALCTGSSHLYMWTPSGACCVNIPLPQFVVSDLKWNPDGT
    SMLLKDRESFCCTFVPMLPEFNDDETNEE
    481 WD40 repeat MAKLIETHSCVPSTERGRGILIAGDAKTNSIIYCNGRSVIMRNLDNPLEASVYG 525 2351
    protein EHSYPATVARFSPNGEWVASGDTSGTVRIWGRGSDHTLKYEYKALAGRIDDLEW
    SADGQRIVVCGDSKGKSMVRAFMWDSGTNVGEFDGHSRRVLSCSFKPTRPFRVA
    TCGEDFLVNFYEGPPFRFKTSHRDHSNYVNCVRFAPDGSKFITVGSDRKGVIFD
    GKMGEKIGELSKEGGHTGSIYAASWSPDSKQVLTVSADKSAKIWEISETGNGTV
    KKTLTFGSQGGADDMLVGCLWLNDYLITVSLGGIVSLLSAVDPDKPPKTISGHM
    KSINAIALSLQSGQSEVCSSSYDGVIVRWILGVGYAGRVERKDSTQIKCLATIE
    GELVTCGFDNKVRRVPLLSEQHKESEPIDIGAQPKDLDVAVGCPELTFVSTDAG
    IIIIRASKIVSTTNVGYAVTAAAISPDGTEAVVGGQDGKLRVYSIKGDTLLEES
    VLERHRGPINAIRFSPDGSMFASGDLNREAVVWDRITREVKLKNMVYHTARINC
    IAWSPDSSKVATGSLDTCILIYEVGKPASSRITIKGAHLGGVYGLAFSDQSTVI
    SAGEDACVRVWSLP
    482 WD40 repeat MPQPSVILATAGYDHTVRFWEATSGRCYRTLQYPDSQVNHLEITPDKQYLAAAG 152 1099
    protein NPHIRLFEVNSNNPQPVISYDSHTNNVTAVGFQCDGKWMYSGSEDGTVKIWDLR
    APGFQREYESRAAVNTVVLHPNQTELISGDQNGNIRVWDLNANSCSCELVPEDT
    AVRSLTVMWDGSLVVAANNHGTCYVWRLMRGTQTMTNFEPLHKLQAHNSYILKC
    LLSPEFCEHHRYLATTSSDQTVKIWNVDGFTLERTLTGHQRWVWDCVFSVDGAF
    LVTASSDSTARLWDLSTGEAIRTYQGHHKATVCCALHDGTDGASC
    483 WD40 repeat MLTKFETKSNRVKGLSFHPKRPWILASLHSGVIQLWDYRMGTLIDKFDEHDGPV 470 4114
    protein RGVHFHKTQPLFVSGGDDYKIKVWNYKMRQCLFTFVGHLDYIRTVHFHNEYPWI
    VSASDDQTIRLWNWQSRVCISVLTGHNHYVMSASFHPKEDLVVSASLDQTVRVW
    DISGLRKKTVSPADDLSRLAQMNTDLFGGGDVVVKYVLEGHDRGVNWAAFGTSL
    PLIVSGADRQVGKLWRMNDTKAWEVDTLRGHTNNVSCVIFHARQDIIVSNSEDK
    SIRVWDMSKRTSVQTFRREHDRFWILAAHPEMNLLAAGHDSGMIVFKLERERPA
    YVVYGGSLLYVKDRYLRTYEFATQKDNPLIPIRKPGSIGPNQGPRSLSYSPTEN
    AILICSDADGGAYELYAVPKDSHGRSDTVQEAKKGLGGSAVGVARNRFAVLDKN
    HNQVTIKNLKNEVTKKFDLPVTADALFYAGTGNLLCRSEDSVFLFDMQQRTVLG
    EIQTPNVRYVVWSNDMENVALLSKHTIIIASKKLSSTCSLHETIRVKSGAWDDN
    GIFMYSTLNHIKYCLPNGDSGIIKTLDVPVYITKVSGKSLYCLDRDGKNRVIQI
    DITECLFKLALSKKKYDYVINMIRNSQLCGQAIIAYLQQKGFPEVALHFVRDER
    TRFNLAVESGNIEIAVASAKEIDEKDHWYRLGVEALRQGNAGIVEYAYQRTKNF
    ERLSFLYLITGNLDKLSKMLRIAEMKNDVMGQFHNALYLGDIQERIKILEESGH
    LHLAYATASLHGLADIADRLAADLGGNIPVLPPGKKSSLLMPPAPILHGGDWPL
    LRVTKGIFEGGLENSTSAAYEEEDEEAAADWGEDIDIENIEGENGEATVLDDQE
    VKGGEDDEGGWDMEDLELPPDVAAANVGTNQKTLFVAPTLGMPVSQIWMQKSSL
    AGEHAAAGNFETALRLLTRQLGIKNFSPLKPLFLELYMGSHTFLPSFASVPAFS
    LALQRGWSESASPNIRGPPALVYRLSVLEEKLTVAYRATTEGRFSEALRLFLNI
    LHTIPVIVVDSRKEIDEVKELIGIAKEYVLGLRMEVKRKEIRDDAVRQQELAAY
    FTHCNLQKAHLKLALLNAMGISYRCKNYNTAANFARRLLETDPSSNHATKARQV
    LQVCERNLQDATQLNYDFRNPFVVCGATFTPIYRGQKEVSCPYCMARFVPDIAG
    KLCSICDLAIVGSDASGLFCFATQTR
    484 WD40 repeat MDLLQNYQDDSEDSNPELRNHPPLEDATATSAPAGVENETSSSPDSSPLRLALP 196 2007
    protein AKSCAPDVDETLMALGVPGSEKKNNHNKPIDPTQHSVTFNPSYDQLWAPLYGPA
    HPYAKDGIAQGMRNHKLGFVEDSAIEPFMFDEQYNTFHRYGYAADPSASLGSHI
    VGDLESLKKNDGASVYNLPKREHKRQKLEKKMIQKDENEEEEKEVGEEVDNPST
    EEWLKKNRKSPWAGKKEGLQTELTEEQKKYAQEHAEKKGDREKGEKVEIVDKTT
    FHGKEERDYQGRSWIDPPKDAKATNDHCYIPKRWVHTWSGHTKGVSAIRFFPKY
    GHLLLSAGMDTKVKIWDVFNSGKCMRTYMGHSKAVRDISFSNDGSRFLSAGYDR
    NIKLWDTETGKVISTFSTGKIPYVVKLHPDEDKQNVLLAGMSDKKIVQWDMNSG
    EITQEYDQHLGAVNTITFVDNNRRFVTSSDDKSLRVWEFGIPVVIKYISEPHMH
    SMPSISLHPNTNWLAAQSLDNQILIYSTRERFQLNKKKRFAGHIAAGYACQVNF
    SPDGRFVMSGDGEGRCWFWDWKTCKVFRTLKCHDNVCIGCEWHPLEQSKVATCG
    WDGMIKYWD
    485 WD40 repeat MARKGLGTDPAIGSLMSSKKRKEYKVTNRFQEGKRPLYAIAFNFIDARYHNIFA 214 1323
    protein TAGGTRVTIYQCLEGGAISVLQAYVDDDKDESFYTLSWACDVNGSPLLVAGGHN
    GIIRVLDVANEKVHKSFVGHGDSVNEIRTQALKPSLILSASKDESVRLWNVQTG
    ICILIFAGAGGHRNEVLSVDFHPSDVYRIASCGMDNTVKIWSMKEFWTYVEKSF
    TWTDLPSKFPTKYVQFPVFIAAVHSNYVDCTRWLGNFILSKSVDNEVVLWEPYS
    KEQSTSDGVVDILQKYPVPECDIWFIKFSCDFHYNSMAVGNREGKVYVWELQSS
    PPNLIARLSHAHCKNPIRQTAISHDGSTILCCCDDGSMWRWDVVQ
    486 WD40 repeat MESGAGGSVGARVPSAKPEMLQQPPYSNGDDDNDMERGTAPVPSSNPNTVSKWE 68 2146
    protein LDKDFLCPICMQTMKDAFLTACGHSFCYMCIMTHLNNKSNCPCCSLYLTNNQLF
    PNFLLNKLLKKTSACQMASTASPVENLCLSLQQGAEVSVKELDFLLTLLAEKKR
    KMEQEEAETNMEILLDFLQRLRQQKQAELNEVQADLHYIKDDILALEKRRLELS
    RARERYSRKLHMLLDDPMDTTLGHAAIDDGNNVRTAFVRGGQGDAISGKFQQKK
    AEIKAQASSQGMQKRANFCHSDSQVLPTLSGLTIARKRRVLAQFDDLQECYLQK
    RRRWATQLRKQCDGGLRKERDGNSISREGYHAGLEEFQSILTTFTRYSRLRVIS
    ELRHGDLFHSANIVSSIEFDRDDELFATAGVSRRIKVFDFATVVNEPADVHCPV
    VEMSTRSKLSCLSWNKCIKSQIASSDYEGIVTVWDVNTRQSVMMYEEHEKRAWS
    VDFSRTEPTRLISGSDDGKVKVWCTRQETSVLNIDMKANICCVKYNPGSSYYVA
    VGSADHHIHYYDLRNPSVPLYEFNGHRKTVSYVKFISTNELASASTDSTLRLWD
    VRDNCLVRTFKGHTNEKNFVGLTVNSEYIACGSETNGVFVYHKAISKPAAWHQF
    GSPDLDDSDDDTSHFISAVCWKSESPTMLAANSQGTIKVLVLAP
    487 WD40 repeat MANYVDSKKNFKCVPALQQFYTGGPFRLSSDGSFLVCACNDEVKVVDLATGSVK 874 3705
    protein NTLEGDSELIVALALTPDNKYLFSASRSTQIKRWDLSSATCKRTWKAHNGPVAD
    MACDASGGLLATAGADRSILVWDVDGGYCTHSFRGHQGVVTTVIFHPDPHCLLL
    FSGSDDATVRIWDLVAKKCISVLEKHFSTVTSLAISENGWNLLSAGRDKVVNIW
    DLRDYHCRATIPTYEPLEAVCVLPTGSRLVSVMNQSRALPENRKKSGAAPVYFL
    TVGERGIVRIWYSEGALCLYEQKSSDAIISSDKDELKGGFVSAVLLPLTQGVMC
    VTADQRFLFYNLDESDEGKCDLKVSKRLIGYNEEIVDLKFLGDEEKFLAVATNL
    EQVRMYDLSSMTCVYELSGHTDIVLCLDTVVFSGHSLLASGSKDHTVRIWDTES
    KSCICVAAGHMGAVGAVAFSKKAKNFFVSGSSDRTIKVWSFASVLDFGGISKSI
    KLSSQAAVAAHDKDINSVAVAPNDSLICTGSQDRTARIWRLPDLVPVLVLRGHK
    RGVWCVEFSPVDQCVMTASGDKTIKIWALSDGSCLKTFEGHTASVLRASFLTRG
    TQFVSSGADGLLKLWTIKSNECIATFDQHEDKIWAMAVGKKTEMLATGGSDSLV
    NLWHDCTTTDEEEALLKEEEAALKDQELLNALADTDYVKAIQLAFELRRPYKLL
    NVFTELYSKGHAQDQIQKVIRELGNEELRLLLEYVREWNTKPKFAHVAQFVLFQ
    LFNVLPPKEIIEVQGISELLEGLIPYAQRHYSRIDRLMRSTFLLDYTLSSMSVL
    SPTETDLSSSNLLARTADPLHAQIDQFHPTHFPEPNLTPIQSLLDSGNTDSVEV
    TARRAKKKRVSGNDSEKTTVAEVKIGDMENAFDEPDVADQGSSRKHKPASSKKR
    KSIAVGNASIKRIASGNAVTIALQV
    488 WD40 repeat MESSCSSMNSNRHSTEKRCLRPLQKQGASMNKHSSDRFIPARGSIDLDVARFMV 360 1754
    protein TQKQKDNNDIHALSPSPSPSKKAYQKEMADTLLKNAGAADNNCRILSFNGKSST
    VSQGSQENVLANLSISRRARRYIPQSADRTLDAPDLLDDYYLNLLDWSSTNVLS
    TALGNTVYLWDASNSSISELLIADEEEGPVTSVSWAPDGSQIAVGLNNSVVQLW
    DSQSNKKLRALKGHHDRVGALSWNGPILTTGGLDGIIINHDVRTRDHIVQTYKG
    HTQEVCGLKWSPSGQQLASGGNDNLLYIWDKSMASHNPSSQYFHQLDEHCAAVK
    ALAWCPFQTNLLASGGGTSDGSIKFWNTQTGACLNTVDTHSQVCSLLWNRHERE
    LLSSHGLNQNQLTLWKYPSMVKITELTGHTARVLHMAQSPDGYTVASAAADETL
    KFWQVFGAPDASKKTKTKDTKGAFNMFHMHIR
    489 WD40 repeat MLDEIVADEEEEFNIWKKNTPLLYDVVITHALEWPSLTVQWLPDRHQSPTKDYS 185 1384
    protein LQKMIVGTHTSGDEPNYLMIAEVQMPLQYSEDGNVGGFESTEAKVHIIQQINHE
    GEVNRAQYMPQNSFIIATKTVSSDVYVFDYTKHSSNAPQERVCNPELILKGHTN
    EGYSLSWSPLKEGQLLSGSNDAQICFWDINAASGRKVVEAKQIFKVHEGAVEDV
    SWHLKHEYLFGSVGDDCHLLIWDTRTAAPNKPQHSVVAHESEVNSLAFNPFNEW
    LLATGSADKTVKLFKLRKLSCSLFTFSNHTEEVFQIEWSPMNETILASSGGDRR
    LMVWDLRRIGDEQTSEDAEDGPPELIFIHGGHTSKISDFSWNLHDDWLIASSAE
    DNILQIWQMAENIYHDDADIL
    490 WD40 repeat MTKEDHGESRDEMGERMVNEEYKLWKKNTPFLYDLVITHALEWPSLTVQWLPPS 241 1533
    protein CKQQQDIIKDDDIDHPNTQMVILGTHTSDNEPNYLILAEVQLHDGTEDEDGDGD
    VKRPQDKMKPGTSGGAMGKVRILQQINHQKEVNRARYMPQKPTIIATKTVNADV
    YVFDYSKHPSKPPQEGRCNPELRLQGHESEGYGLSWSPLKEGHLLSASDDAQIC
    LWDITAATKAPKVVEANQIFRYHDGPVEDVAWHAIHDHLFGSVGDDHHLLLWDI
    RNDSEKPLHIVEAHQAEVNCLAFNPFNEWIVATGSADRTVALHDIRKLDKVLHT
    CAHHMEEVFQIGWSPQNGAILASCGSDRRLMVWDLSRIGDEQNPEDAEEAPPEL
    LFIHGGHTSKISDFSWNPAEEWVIASVAEDNILQVWQMSEHIYNDDNDSPTA
    491 WD40 repeat MAMAMGDENAADPVEEFNIWKKNTPFLYDLVITHALEWPSLTVQWLPDRHQSST 230 1435
    protein ADYSLQKMIVGTHTSEDEPNYLMIAEVQIPLQNSSEDNIIGGFESTEAKVQIIQK
    INHEGEVNKARYMPQNSFVIATKTVSSDVYVFDYSKHPSKAPQERVCNPELILK
    GHSNEGYGLSWSPLKEGYLLSGSNDAQICLWDINAAFGKKVLEANQIFKVHEGA
    VGDVSWHLKHEYLFGSVGDDCHLLIWDMRTAAPNKPQQSVIAHQSEVNSLAFNP
    FNEWLLATGSMDKTVKLFDLRKLSCSLHTFSNHSTDQVFQIEWSPMNETILASSG
    ADRRLMVWDLARIGETPEDEEDGPPELLFVHGGHTSKISDFSWNLNDDRVIASV
    AEDNILQIWQMAENIYHDDEDML
    492 WD40 repeat MGLFEPFRALGYITDGVPFAVQRRGIETFVTLSVGKAWQIYNCAKLIPVLVGPQ 101 2857
    protein MDKKIRALACWRDFTFAATGHDIAVFRRAHQVATWSGHKAKVTLLLSFGQHVLS
    VDLEGCLFIWAVAEVNQNKPPIGQIQLGEKFSPSCIMHPDTYLNKVLIGSEEGT
    LQLWNVNTRKKLYEFKGWGSSIRCCVSSPALDVVGIGCSDGKIHVHNLRYDEEI
    VTFMHSTRGAVTALSFRTDGQPLLAAGGSSGVISIWNLEKKKLQSVIKDAHDSS
    VCSLHFFANEPVLMSSATDNSIKMWIFDTTDGEARLLKYRSGHSAPPMCIRYYG
    KGRHILSAGQDRAFRIFSVIQDQQSRELSQGHVGKRAKKLKVKDEEIKLPPVIA
    FDAAEIRERDWCNVVTCHLDDPCAYTWRLQNFVIGEHILKPCLEDPTPVKSCSI
    SACGNFAVLGTEGGWLERFNLQSGISRGTYIDIGEKRQCAHNGAVVGLACDATN
    TLLISGGYNGDIKVWDFKGRELKFRWEIEVPLIKIVYHPGNGILATAADDMILR
    LFDVTAMRLVRIFVGHMDRVTDLCFSGDGKWLLSSSMDGTIRVWDIISSRQLNA
    MHMDSAVTALSLSPGMDMLATTHVGHNGIYLWANRMIYSKATDIEPFISGKQVV
    KVSMPTVSSKRESEEGDEKRTIVAESNVNKSDVSGSLIGDSYSAQLTPELVTLA
    LLPKAQWQSLVNLDIIKMRNKPIEPPKKPEKAPFFLPSLPTLSGERIFIPSSMN
    GDGDQDETRNDKTVFEARGKKLGGESLSFMQLLQSCAKIKDFTTFTNYLKGLSP
    SAVDMELRLLQIVDNENISETEHSVELQGIGMLLDYFVNEVSCNNNFEFVQALI
    RLFLKIHGETIRCQVSLQEKARKLLEIQSSTWERLDTSFQNARCMITFLSSSQF
    493 WD40 repeat MIAAVCWVPKGVAKVLPDSAEPPTQEEIQELLKCNVVAESDDNEDSDEESEEMD 43 1548
    protein TETDKNTDAVAKALAAANALGSQSSDFQRQHKVDDIANGLKELDMDHYDDEDEG
    IDIFGSGSLGNCYYPANDMDPYLVEQDDDDEDEIEDMTIKPSDLIILSARNEDD
    VSHLEVWIYEEETEEGGSNMYVHHDIILPAFPLSLAWLDCNLKGGEKGNFVAVG
    TMQPEIELWDLDVLDEVEPAVVLGGAVKDEASGKTTKLKKKKKNKQAVNFKEGS
    HTDAVLGLAWNMEYRNVLASASADKSVKIWDIVAEKCEHTMQPHTDKVQAVAWN
    PNQATVLLSGSFDRSVIMMDMRAPTHSGIRWPVPADVESLAWDPHTDHSFMVSA
    EDGTVRGFDIRAAASTADFDGKPMFILHAHDKAVCAISYNPAAPSLLTTGSTDK
    MVKLWDITNNQPSCIASTNPNVGAVFSAAFSKNSPFLLATGGSKGILHVWDTLD
    NSEVARRFGKFRPQN
    494 WEE1-like MIMDENEFCDIFSLRKRLCLLSSQEGEEEEELEAMSQLDAGEFTVTGNEEVVAI 206 1657
    protein AEDDVNTGILSQDLFSSQDYCTPSQPQDSTDLDSKDKAPCPLSPVKSTIQRKRC
    RPELLSNPPDSIQFSFQRLERVRSEESIQSSSQQLARVRSEVSSSDDFKTPKIT
    ASGQKNYVSQSALALRARVMSPPCIKNPYLDENEELNEKIQRSTRRSPACVTPI
    QSGACLSRYRADFHELEEIGRGNFSRVYKALNRLDGCCYAVKCSQSELRLDTER
    KVALMEVQSLAALGPHKNIVGYHTAWFENDHLYIQMELCDHNLTTANDRGILRT
    DTDFLEAVYQIAQALEFIHGRGVAHLDVKPENIYVRDGTYKLGDFGRATLINGT
    LHVEEGDARYMSREILNDNYEHLDKVDMFSLGATFFELLMRKQYPGSGKRIDRD
    TEIKIPILPGFSIYFQKLLQDLVSNDPGKRPSAKDVLKNPIFNKVRGAKEV
    495 WD40 repeat MLAPALEMEPVEPQSLKKLSFKSLKRALDLFSPVHGQIAPPDPESKKMRISYSL 117 1580
    protein NFEYGGGSGSEDQVPKRKESGAAQNQGQQAAGASNALALPGPEGSKIPPMEKSQ
    NALTVGPSLRPQGLNDVGLHGKGTAIISASGSSDRNLSTASAIMERLPSRWPRPV
    WHPPWKNYRVISGHLGWVRSIAFDPSNQWFCTGSADRTIKIWDLASGRLKLTLT
    GHIEQIRGLAVSSKHTYMFSAGDDKQVKCWDLEQNKVIRSYHGHLSGRLKLTLT
    PTIDILLTGGRDSVCRVWDIRSKMQIFALSGHDNTVCSVFARPTDPQVVTGSHD
    TTIKFWDLRHGKTMTTLTNHKKSVRAMAQHPKENCFASASADNIKKFQLPRGEF
    LHNMLSQQKTIINTMAVNEEGVMATGGDNGSLWFWDWKSGHNGQQAHTIVQPGS
    LESEAGIYALSYDLTGSRLVSCEADKTIKMWKEDELATPETHPLNFKPPKDIRRF
    496 WD40 repeat MEEAAKEQSAGSGKPKLLRYGLRSAAKPKEDKKEEQLHQPPPPPPPQQQAAPAP 111 1700
    protein APAATRSSTSGSAGGRDRRPQQQHAVDEKYARWKSLVPVLYDWLANHNLLWPSL
    SCRWGPQLEQATYKNRQRLYISEQTDGSVPNTLVIANCEVVKPRVAAAEHVSQF
    NEEARSPFIRKYKTIIHPGEVNRIRELPQNPNIVATHTDSPDVLIWDVESQPNR
    HAVYGATASRPNLILTGHQENAEFALAMCPAEPFVLSGGKDKTVVLWSIQDHIT
    ASATDQTTNKSPGSGGSIIKKTGEGNEETGNGPSVGPRGIYCGHEDTVEDVAFC
    PSTAQEFCSVGDDSCLILWDARIGTNPVAKVEKAHNGDLHCVDWNPHDNNLILT
    GSADNSVNMFDRRNLTSNGVGSPVYKFEGHKAAVLCVQWSPDKPSVFGSSAEDG
    LLNIWDYERVDKKVDRAPNAPAGLFFQHAGHRDKIVDFHWNTADPWTMVSVSDD
    CDTAGGGGTLQIWRMSDLIYRPEEEVLAELENGKAHVLECSKA
    497 WD40 repeat MAKDEEEFRGEMEERLVNEEYKIWKKNTPFLYDLVITHALEWPSLTVQWLPDRE 144 1412
    protein EPPGKDYSVQKMILGTHTSDNEPNYLMLAQVQKOKEDAENDARQYDDERGEIGG
    EGCANGKVQVTQQTNHDGEVNEARYYIPQNPETTATKTVSAEVYVEDYSKHPSKP
    PQDGGCHPDLRLRGHNTEGYGLSWSPFKHGHLLSGSDDAQICLWDINVPAKNKV
    LEAQQIFKVHEGVVEDVAWHLRHEYLFGSVGDDRHLLIWDLRTSATNKPLHSVV
    AHQGEVNCLAFNPFNEWVLATGSADRTVKLFDLRKISSALHTFSCHKEEVFQIG
    WSPKNETILASCSADRRLMVWDLSRIDEFQTPEDALDGPPELLFIHGGHTSKIS
    DFSWNPCEDWVIASVAEDNILQIWQMAENIYHDEEDDMPPEEVV
    498 Cyclin- MGKYMRKGKGVGEVAVMEVSQGSLGVRTRARTLAAASSQKDHRRLGASKSVTTK 793 1683
    dependant HQSSAPPASPCVESSMHTCYLELRSRKLEKFSRCYHSAHGATSHGESKRSLSLS
    kinase EPSRLAVSEEARVASDKSSHRVLQQQSSVAHSRNNASATFSHNAKPAKAAQRKER
    inhibitor RDDDHTSARPSEAPHEDEDGMEVEASFGENVMDLDSRERRTRETTPSSYTRDVE
    TMETPGSTTRPPSNAGRRRFQTEGGHGTRNQFHVPTTNEIEEFFAGAEQQEQRR
    FTDRYNYDPVSDSPLPGRFEWVRLRP
    499 CDK type D MQNMEENVQSSWSLHGNKEICARYEILKRVSSGTYLDVYRGRRKEDGLIVALKE 415 2196
    VHDYQSSWREIEALQRLCGCPNVVRLYEVILEFLTSDLYSVIKSAKKNKGENGIP
    EAEVKAWMIQILQGLANCHANWVIHRDLKPSNMLISAYGILKLADFGSMSFLKR
    AIYEVEYELPQEDILADAPGERLMDEDDSVKGVWNEGEEDSSTAVETNFDDMAE
    TANLDLSWKNEGDMVMQGFTSGVGTRWYRAPDFLYGATIYGKEIDLWSLGCILG
    ELLILEPLFSGTSNIDOLSRLVKVLGLQQKKNWPGCSNLPDYRKLCFPGDGSPV
    GLKNHVPNCSDNMFSILERLVCYDPAARLNAKEIVENKYFVEDPYPVLTHELRV
    PSPLREENNFSEDWAKWKDMEVDSDLENIDEFNVVHSSDGFCIKFS
    500 Histone MAPVKRIEPEKTKANEGKPKRRKVAFAIDTGIEANDCISLHLVSTPEEMRDAEG 109 1653
    acetyltransferase VEDQSLSFNPEYMQHFVGEHGKIYGYKGLKIDVWLNALSFHAYVDIQYESKVEE
    GKSEKEATDLTDIMKRIFGRGLVEDRNAFIQSFSSNSQSIESMIHNEGERIATR
    EILTDKGLSAQGDSERLGVSNEIFRLELSDPQIREWHARLEPLVLLFVEGSQPI
    EQDDPKWEMYIRVQRESLSGGSAVCRLLGFCTVYRFYHYPDTTRLRISQILVFP
    PYQGKGHGLLLLEAVNKTAVSRDSYDVTVEEPSESLQELRDCMDTIRISQILVFP
    MPAVKSAVQKLKEANPSDKGAADHCLEGNVNNETVTTSSTKPKNKSGWFPPPGL
    VEEVRKHLKISKKQFKRCWEILLYLNLDRSDSQCEDKYHISLMEQIMSELFDKS
    SEKSAKGKRVIDIDNEYDNSKTFIMVRTRNPGNGEGFLPEALEGGMEVSQEDQL
    KSLFEERLEEIAQIAEKVPSLCKALQMP
    501 Histone MPEDRKKILEALAAKRKAEAESGEKKPRQKSSLNPAKPVSKPVSKPVGGIGSKG 343 1023
    deacetylase KSTSAPISSTKAKSKHKEEVKAKRVTKMDRYETDEDDESEEEEDLDSESDDDEL
    SDEDSEDDIKSKSVKKLPPQSKGKAPVKGISSSNGKGRDEKGKGIMKDKGKAKA
    KVEESSSDAEGDSDDDGGDLSDDPLQEVDPSNILPSKTRREASQPTNYQFANMS
    GDDDDDDDSD
    502 Histone MADVPESLQQEKDEQGTDKNCCDGKFQKEIDIDDMEEEYNESSIDDEEENLSDN 417 2351
    deacetylase VATNNMGTIPQGQACMAVTVEGIEHANSVGCGRNGREGSEEVTAAEDMGHVSIE
    NIREQGRNRKSSEQLLALYEQEGLLEDDEDDDDVDWEPFEGVTVQMKWYCTNCT
    MANSDDSVHCDSCGEHRNSDILRQGFLASPYLPAESPSSSDVPDERLEESKCVM
    TTLTPSISPMIGVCCSSLQSERRTVVGFDERMLLHSEIQMETYPHPERPDRLRA
    IAASLRAAGLFPGKCFSIPAREATCEELQTIHSLEHVNAVESTSCGMLSHLSPD
    TYANEHSSLAARLAAGLCADLAKAIMTGQAQNGFALVRPPGHHAGVKDSMGFCL
    HNNAAIAVSASRVVGAKKVLIVDWDVHHGNGTQEIFEADQSVLYISLHRHGEGF
    YPGSGAVTEVGSSKGEGYSVNIPWKCGGVGDNDYIFAFQHAVLPIAEQFEPDLT
    IISAGFDAAKGDPLGRCEVTPDGFAHMAQMLSCLSKGKMLVILEGGYNLRSISA
    SATAVIKVLLGDNPKALPIDIQPSKGGLQTLLEVFEIQSKYWSSLKGHDQKLRS
    QWEAQYGSKKRKVIRKRHMHIVGGPVWWKWGRKRVVYYHWFARVSSRKHL
    503 Peptidylprolyl MASGAGAAGVVEWHQKPPNPKNPVVFFDVTIGTIPAGRIKMELFADIVPRTAEN 69 641
    isomerase FRQFCTGEYRKAGIPIGYKGCHFHRVIKDFMIQAGDFVKGDGSGCISIYGSKFE
    DENFIAKHTGPGLLSMANSGPNTNGCQFFLTCAKCDWLDNKHVVFGRVLGEGLL
    VLRKIENVQTGQHNRPKLPCVIAECGEM
    504 Peptidylprolyl MAKLVSSVCAFSCQQRHPHSRPRFLSNRDHYNHYHNHSHYHNVCYFPPMMMMQQ 172 1623
    isomerase QLQKQKRMTTKTITSLFKCNSSNHTLLKGLKEFMGFKFRLQAAMLSCEMSILGR
    VFAIFFIVHQAAAPFPFNHFDNWLVPPASAVLYSPNTKVPRTGEVALRKSIPAN
    PAMKSIQDFLEDIYYLLRFPQRKPYGTMEGDVKSALQIAINEKDSILGSVPLDM
    KERGLQLYNFLIDGQGGLQVLIEYIKEKDPDKVSVNLSSSLDTIAQLELLQAPG
    LPYLLPEEYQQYPRLNGRATIEFTMEKGDNSMFSVSSGGGLQKTATIQVVLDGY
    SAPLTAGNFTKLVIDGAYNGLKLKTTEQAVISDNERAEAGFNLPIEILPAGGFE
    PLYRTTLSVQDGELPVLPLSVYGAIAMAHNTISEDYSSPSQFFFYLYDKRNAGL
    GGLSFDEGQFSVFGYTTVGKEILPQLKTGDIIKSAKLVDGFDHLVLPSSST
    505 WD40 repeat MDHYYQDDFDYLVDDEMVDFADDVEDDVRTRRRSDIDSDSENDFDSNNKSPDTT 231 1768
    protein ALQAKRGKDIQGIPWNRLNFTREKYRETRLQQYKNYENLPRPRRSRNLDKECTN
    FERGSSFYDFRHNTRSVKATIVHFQLRNLVWATSKHNVYLMQNYSIMHWSSLKQ
    KGEEVLNVAGPIIPSVKHPGSSPQGLTRVQVSAMSVKDNLVVAGGFQGELICKY
    LDKPGVSFCTKISHDENGITNAVEIYNDASGATRLMTANNDLAVRVFDTEKFTV
    LERFSFPWSVNHTSVSPDGKLVAVLGDNADCLLADCKTGKTVGTLRGHLDYSFA
    AAWHPDGYILATGNQDTTCRLWDVRKLSSSLAVLKGRMGAIRSIRFSSDGRFMA
    MAEPADFVHLYDTRQNYTKSQEIDLFGEIAGISFSPDTEAFFVGVADRTYGSLL
    EFNRRRMNYYLDSIL
    506 WD40 repeat MDCSGDEEEEQFFESLEEMLSPSDSGSEAADNETGCRNADARSKYEIWKRAPSS 376 2943
    protein IQERRQRFLVRMGLANPSELGNQVNSTSAESTCSTETANIPNGIERLRENSGAV
    LRTAGSSGRKTHCKNVINIGLREGSVRSSSSSNGTPDVGEDNGEFGGTIFSRSG
    GTWECMCKIKNLDSGKEFVVDELGQDGLWNKLREVGTDRQLTMDEFERSLGLSP
    LVQELMRRESGVAQADCNGVHHHDAEISSSKRRSWLKALKSAAYSMRRPKEDQS
    NYDSERSGRRSGSFDVPWGKPQWTKVRHYRKRYKEFTALYMGQEIEAHEGSIWT
    MKFSLDGRYLASAGQDCVIHVREVIESMRTFGADTPDLYASSAYFSMNGLQELV
    PLSIEDHANKMKRGKIIGSKKSSNSDCIVLPNKVFQLSEEPVCSFHGHLLDVFD
    LSWSPSQYLLSSSMDKTVRLWKLGHESCLKVFSHNDIVTCIQFNPVDERYFISG
    SLDGKARIWSIPDRQVVDWSDLREMVTAVCYTPDGQGGLVGSIKGSCRFYNTSG
    NKLQLENQLNVRSKKKKSSGKKITGFQFAPGGDSQKVLITSADSRVRVYNGSEL
    VCKYKGFRNTCSQISASFAPNGQHFVCASEDSRVYIWNHESPRGSGARHEKSSW
    SHEHFLSQGVSVAIPWSGMKLQPPVWNSPEFMLGQRHNLLSLQGGKDVGCQNGL
    LSREAGEGQESETPLHYISQVSHSCGSQNMVDRDGQDDLSRYSACISDSRLSSF
    MAFPESPGNPDDLNSKVFFSDSSSKGSATWPEEKLPPTRKQSRSNSTSSHYDTL
    KTHLGNTIQGQSGASAAVAWGLVIVTAGHGGEIRSFQNYGLPVRL
    507 WD40 repeat MPSIPAIGEFTVCEINRELLTTKDESDTQAKDAYAKILGLVFPPISFQIEEGFG 107 1498
    protein SASRQQFDQDLDREDTIVTPSTSEGTNALQEGGLLLKGVSVLKNILASSFGPIF
    SPNDTKVLKKVELLQGISWHRHKHILAFISGSNQVTVHDFQDPEWRESSLLVSE
    SQRGIEALEWRPNGGTTLSVACRGGICIWSASYPGSVAPVRSGVASFLGTSTRG
    SSVRWTLVDFLQIPGGKAVTALSWSPTGRLLASASREDSSFTIWDVAQGVGTPL
    RRGLGGISLLKWSPTGDYLFSAKPNGTFYLWETNTWTLEQWSSSGGCVISATWG
    PDGRMLFMAFSESTTLGSLHFAGRPPSLDAHLLPMELPEIGSITGGFGNIEKMA
    WDGCGERLAVSYTGGDLMYVGLIAIYDTRRTPFISASLVGFIRGPGEQVKPLAF
    AFHDKFKQGPLLSVCWSSGLCCTYPLIFRAH
    508 WD40 repeat MEEENAKHTEETRQVQVRFTTKLQPALRVPTTSIAIPAHLTRYGLSDIVNTLLG 118 1425
    protein NDKPQPFDFLVESELVRTSLEKLLLIKGISAEKILNIEYILAVVPPKQEEPSLH
    DDWVSVVDGSYPNFIFSGSFDSIGRIWKGEGLCTHVLEGHRDAITSAAFIMPSD
    SSDSFINLATASKDRTLRLWQFKPNEHMTNGKMVRPYKLLKGHTSSVQTVSACP
    RRNLICSGSWDCSIKIWQTAGEMDIESNAGSVKKRKLEDSTEQIISQIEASRTL
    EGHSQCVSSVVWLEKDTIYSASWDHSVRSWDVETGVNSLTVGCRKALHCLSIGG
    EGSALIAAGGADSVLRIWDPRMPGTFTPILQLSSHKSWITACKWHPKSRHHLIS
    ASHDGTLKLWDVRSKVPLTTLEAHKDKVLCADWWKEDCVISGGADSTLQIFSNL
    NLT
    509 WD40 repeat MNRLRSKRNHILELRLGQSEPEKEATLASNRSRGTNAPIVVEDDDDVVVSSPRS 186 797
    protein FALARSSVSQRSSRIPIVNEEDLELRLGLAVTGRTSAEHNPRRRHGRVPPNKPI
    VLCDDAGEADQSSSKKRRTGQQLSSDVQSDESKEVKLTCAICISTMEEETSTIC
    GHIFCKKCITNAIHRWKRCPTCRKKLAINNIHRIYISSSTG
    510 WD40 repeat MEEPPPPAVLPSSEDTSIVSSHSFVNAPPTVPVGLDASIPQISTPGINQPGLTI 387 2456
    protein PVPPEAAPLTASLVAASAGMPPAVVPSFVRPAIVAHPSVMPPPSMPLAALPMPV
    ASAVPVAAPHFPPSTPNDNSITPSMPVPTPIVASSSVPPSVTIPGIAPLPFIAP
    IPVPSSRPVAPSPFMPPARPLGASVSVAMDVDNTDEQDQDADNKGESPSSSPDH
    PEDPSAAEYEITEESRKVRERQEQAIQELLLRRRAYALAVPTNDSSVRARLRRL
    NEPITLFGEREMERRDRLRALMAKLDAEGQLEKLMKVQEEEEAAANVDAEEVQE
    MEGPQVYPFYTEGSQELLKARTEITKFSLPRAVSRLQRARRKREDPDEDEDEEL
    KCVLQQSAQINMDCSEIGDDRPLSGCAFSSDGTLLATSAWSGVTKLWSVPNINK
    VATLKGHTERVTDVAFSPTNCHLATACADRTAMLWNSEGVLMKTYEGHLDRLAR
    LAFHPSGLYLGTASFDKTWRLWDVNTGIELLLQEGHSRSVYGIAFQCDGSLAAT
    CGLDGLARIWDLRTGRSILALEGHVKPVLGIDFSPNGYHLATGSEDHTCRIWDL
    RKRQSVYIIPAHSHLVSQVKFEPQEGYFLVTASYDSTAKVWSARDFKSIKVLAG
    HEAKVTSVDITADGQYIATVSHDRTIKLWSSKNSTNDMNIG
    511 WD40 repeat MKRAYKLQEFVAHASNVNCLKIGKKSSRVLVTGGEDHKVNMWAIGKPNAILSLS 359 2761
    protein GHSSAVESVTFDSAEALVVAGAASGTIKLWDLEEAKIVRTLTGHRSNCISVDFH
    PFGEFFASGSLDTNLKIWDIRRKGCIHTYKGHTRGVNSIRFSPDGRWVVSGGED
    NIVKLWDLTAGKLMHDFKCHEGQIQCMDFHPQEFLLATGSADRTVKFWDLETFE
    LIGSAGPETTGVRAMIFNPDGRTLLTGLHESLKVFSWEPLRCYDAVDVGWSKLA
    DLNIHEGKLLGCSYNQSCVGVWVVDISRVGPYAAGNVSRTNGHNEAKLASSGHP
    SVQQLDNNLKTNMARLSLSHSTESGIKEPKTTTSLTTTEGLSSTPQRAGIAFSS
    KNLPASSGPPSYVSTPKKNSTSRVQPTTNFQTLSRPDIVPVIVPRSNSLRPETT
    SDAKKEMNNFGRVVPSTVSTKSTDVIKSGSNRDESDKIDSINQKRMTGNDKTDL
    NIARAEQHVSSRLDNTNTSSVVCDGNQPAARWIGAAKFRRNSPVDPVVSPHDRS
    PTFPWSATDDGVTCQPDRQVTAPELSKRVVEPGRARALVASWETREKALTADTP
    VLVSGRPPTSPGVDMNSFIPRGSHGTSESDLTVSDDNSAIEELMQQHNAFTSIL
    QARLTKLQVIRRFWQRNDLKGAIDATGKMGDHSVSADVISVLIERSEIFTLDIC
    TVILPLLTRLLQSETDRHLTVAMETLLVLVKTFGDVIRATISATPTIGVDLQAE
    QRLERCNLCYVELENIKQILVPLIRRGGAVAKSAQELSLALQEV
    512 Cyclin B MAGSDENNPGVVGGAHVQEGLRVGAGKMGAGNVQQRRALSNINSNIIGAPPYPC 238 1648
    AVNKRVLSEKNVNSENDLLNAAHRPITRQFAAQMAYKQQLRPEENKRTTQSVSN
    PSKSEDCAILDVDDDKMADDFPVPMFVQHTEAMLEEIDRMEEVEMEDVAEEPVT
    DIDSGDKENQLAVVEYIDDLYMFYQKAEASSCVPPNYMDRQQDINERMRGILID
    WLIEVHYKFELMDETLYLTVNLIDRFLAVQPVVKKKLQLVGVTAMLLACKYEEV
    SVPVVEDLILISDRAYSRKEVLEMERLMVNTLHFNMSVPTPYVFMRRFLKAAQS
    DKKLELLSFFIIELSLVEYDMLKFPPSLLAASAIYTALSTITRTKQWSTTCEWH
    TSYSEEQLLECARLMVTFHQRAGSGKLTGVHRKYSTSKFGHAARTEPANFLLDF
    RL
    513 Cyclin- MQAPREGKSAAAIVGMGKYMKKSKAIPRDVSLLEASPRSPSATGVRTRAKTLAS 59 859
    dependant RRLRRASQRRPPPPAAAAAAAAPSLDASPCPFSYLQLRSRRLRRPRLAPSPEAR
    kinase IDEGPAGSGSRGSRDASCSARTASSSGGVEGEGACVGRGDRGNGGECVRDAAVD
    inhibitor ASYGENDLEIEDRDRSTRESTPCSLIRDSNANTPPGSTTRQQSSCTAHRTQMSI
    LRSIPTSDEMEEFFAYAEQRQQRSFIEKYNFDIVKDRPLPGRFEWVQVIP
    514 Histone MDGHSSHLAAQNRSRGSQTPSPSHSAASASATSSIHLKRKLSAANASAASAAAA 44 1829
    acetyltransferase AAAAAAAADDHAPPFPPSSISADTRDGALTSNDDLESISARGGGAGDDSDDDSD
    DEEEDDGDNDGGSSLRTFTAARLENVGPAAARNRKIKAESNATVKVEKEDSAKD
    GGNGAGVGALGPAATSGAGSGSGTVPKEDAVKIFTENLQASGAYSAREENLKRE
    EEAGRLKFECLSNDGVDDHMVWLIGLKNIFARQLPNMPKEYIVRLVMDRNHKSV
    MVIRRNLVVGGITYRPYASQKFGEIAFCAIKADEQVKGYGTRLMNHLKQHARDV
    DGLTHFLTYADNNAVGYFIKQGFTKEIYLDKDRWHGYIKDYDGGILMECKIDPK
    LPYTDLSTMVRRQRQAIDEKIRELSNCHIVYQGIDFQKRDAGVPQNTIKMEDIP
    GLREAGWTPDQWGYSRFRGLSDQKRLTFFIRQLLKVLNDHSDAWPFKEPVDARE
    VPDYYDIIKDPMDLKTMTKRVESEQYYVTLEMFIADVKRMFANARTYNSPDTIY
    FKIATRLEAHFQSKVQSNLQSGAGKIQQ
    515 Peptidylprolyl MFNGMMDPELFKLAQEQMNRMSPAELAKIQQQMMSNPELMRMASESMKNMRPED 109 1866
    isomerase LRQAAEQLKHVRPEEMAEIGEKMANASPEEIAAVRARADAQMTYEINAAKILKK
    EGNELHSQGRFKDASQKYLRAKNNLKGIPSSEGKNLLLACSLNLMSCYLKTRQY
    EECIKEGSEALACEEKNLKAFYRRGQAYRELGQLKDAVSDLRKAHEISPDDETI
    AQVLRDTEESLTKEGGSAPRGVVIEEITEEDETLASVNHESPSEYSEKRHQESE
    DAHKGPINGDIMGQMTNSESLKALKGDPDAIRSFQNFISNADPTTLAAMGAGNA
    GEVSPDLIKTASSMIGKMSAEELQKMIQLASSFPGENPYVTRNSDSNSNSFGNG
    SIPNVSPDMLKTASDMMSKMSPDDLQRMFEMASSSRGKDPSLDANHASSSSGAN
    LAANLNHILGESEPSSSYHIPSSSRNISSSPLSNFPSSPGDMQEQIRNQMKDPA
    MRQMFTSMMKNMSPEMMANMGKQFGLELSPEDAAKAQEAMSSLSPEMLDKMMRW
    ADRAQRGVETAKKTKNWLLGRPGMILAICMLLLAVILHRLGFIGS
    516 WD40 repeat MIAAISWVPRGASKAVPEVAEPPSKEEIEEILKSGVVERSGDSDGEEDDENMDA 212 1815
    protein VASEKADEVSTALSAADALGRISKVTKAGSGFEDIADGLRELDMDNYDEEDEDV
    KLFSTGLGDLYYPSNDMDPYLKDKDDDDDTEEIEDLSIKPMDSLIVCARTDDEV
    NLLEVYLLEPSLSDESNMYVHHEVVISEFPLCTAWLDCPIKGGDKGNFIAVGSM
    EPAIEIWDLDIIDAVEPCLVLGGQEELKKKKKKGKKASIKYKEGSHTDSVLGLA
    WNKEFRNILASASADRQVKIWDVAAGKCNITMEHHTDKVQAVAWNHHAPQVLLS
    GSFDHSVVMKDGRIPSHSGYRWSVTADVESLAWDPHSEHFFVVSLEDGTVRGFD
    VRAAISNSASQSLPSFTLHAHEKAVSTISYNPAAPNLLATGSTDKMVKLWDLSN
    NQPSCIASRNPKAGAVFSVSFSEDSPLLLAIGGSKGRLEVWDTSSDAAVSRRFG
    KHGKPKTAEPGS
    517 WD40 repeat MKFCKKYQEYMQGQEGKKLPGLGFKKLKKILKRCRRRDSLHSQKALQAVQNPRT 207 1193
    protein CPAHCSVCDGSFFPSLLEEMSAVLGCFNKQAQKLLELHLASGFQKYLMWFKGKL
    RGNHVALIQEGKDLVTYALINAIAIRKILKKYDKIHLSTQGQAFKSQVQRMHME
    ILQSPWLCELIAFHINVRETKANSGKGHALFEGCSLVVDDGKPSLSCELFDSIK
    LDIDLTCSICLDTVFDSVSLTCGHIYCYMCACSAASVTIVDGLKAAEPKEKCPL
    CREARVFEGAVHLDELNILLSRSCPEYWAERLQTERVERVRQAKEHWESQCRAF
    MGVE
    518 WD40 repeat MVSTQSTRENPSIFFPPPLKPWLLPVVLSLSLSRQLGMAAAAAASLPFKKNYRS 6 2786
    protein SQALQQFYAGGPFAVSSDGSFIACNCGDSIKIVDSSNASLRPSIDCGSDTITAL
    SLSPDGKLLFSAGHSRQIRVWDLSTSTCLRSWKGHDGPVMSMACPVSGGLLATG
    GADRKVMVWDVDGGFCTHFFKGHDGVVSTVLFHPDSNRSLLFSGSDDGTIRVWD
    LLAKKCASTLRGHDSTVTSLAFSEDGLTLLAAGRDKVVSLWDLHNYACKKTIPM
    YEVLESVCVIHSGTVLASQLGLDDQLKVTKESAQNIHFITVGERGILRIWKSEG
    SVCLFKQEHSDVTVISDEDDSRSGFTAAVMLPLDQGLLCVTADQQFLFYYPEKH
    PEGIFSLTLCRRLVGYNEEIVDMKFLGEEENFLAVATNLEQVRVYELASMSCSY
    VLAGHTETVLCLDTCISSSGRTLIVTGSKDNSVRLWDSESRHCIGVGVGHMGAV
    GAVAFSRKRQDFFVSGSSDRTLKVWSLDGISEDGVDSTNLKAKAVVAAHDKDIN
    SVAVAPNDSLVCSGSQDRTACVWRLPDLVSVVVLKGHKRGIWSVEFSPVDQCVL
    TASGDKTVKIWAISDGSCLKTFEGHVSSVLRASFLTRGTQFVSCGADGLVKLWT
    VRTNECIATYDQHSDKVWALAVGKKTEMLATGGSDAVVNLWYDSTASDKEDAFR
    KEEEGVLKGQELENAVSDADYTKAIELALELRRPHKLFELFSELCRTREVGDRV
    ERILSALSGEEVCLLLEYIREWNAKPKLCHVAQSVLSQVFRILSPTEIVEIKGI
    GELLEGLIPYSQRHFSRIDRLVRSTYLLDYTLTGMSVIEPEADRSAVNDGSPDK
    SGLEKLEDGLLGENVGEEKIQNKEELESSAYKKRKLPRSKDRSKKKSKNVVYAD
    AAAISFRA
    519 WD40 repeat MDSAPRRKSGGINLPSGMSETSLRLDGFSGSSSSFRAISNLTSPSKSSSISDRF 213 1726
    protein IPCRSSSRLHTFGLVERGSPVKEGGNEAYSRLLKAELFGSDFGSLSPAGQGSPM
    SPSKNMLRFKTESSGPNSPFSPSILRQDSGFSSEASTPPKPPRKVPKTPHKVLD
    APSLQDDFYLNLVDWSSQNTLAVGLGTCVYLWSASNSKVTKLCDLGPNDGVCAV
    QWTREGSYISIGTSLGQVQIWDGTQCKRVRTMGGHQTRTGVLAWNSRILASGSR
    DRVILQHDLRVPNEFIGKLVGHKSEVCGLKWSHDDRELASGGNDNQLLVWNQHS
    QQPVLKLTEHTAAVKAIAWSPHQNGLLASGGGTADRCIRFWNTTNGHQTSSVDT
    GSQVCNLAWSKNVNELVSTHGYSQNQIMVWKYPSMAKVATLTGHSLRVLYLAMS
    PDGQTIVTGAGDETLRFWNVFPSAKAPAPVKDTGLWSLGRTHIR
    520 WD40 repeat MEDEAEIYDGVRAQFPLTFGKQSKPQTSLESVHSATRRGGPAPAPAPASSSSLP 101 2110
    protein STTSPSAAGGAGKSSGLPSLSSSSTAWLEGLRAGNPRAGREAGIGSRGGDGEDG
    GRAMIGPPRPPPGFSANDDGGGEDDDDDGDGVMVGPPPPPPGNLGDGDDDEEEE
    EAMIGPPRPPVVDSDEEEEEEEEENRYRLPLSNEIVLKGHNKIVSALAVDPTGS
    RVLSGSYDYTVRMFDFQSMNSRLSSFRDFEPVEGHQVRNLSWSPTADRFLCVTG
    SAQAKIYDRDGLTLGEFVKGDMYIRDLKNTKGHITGLTWGEWHPKTKETILTSS
    EDGSLRIWDVNDFKSQKQVIKPKLARPGRVPVTTCTWDREGKCIAGGIGDGSIQ
    IWNLKPGWGSRPDIHVEQAHADDITGLKFSSDGKILLTRSFDDSLKVWDLRLMK
    NPLKVFEDLPNHYAQTNIACSPDEQLFLTGTSVERESTIGGLLCFFDRSKLELV
    SRIGISPTCSVVQCAWHPRLNQIFATSGDKSQGGTHVLYDPTLSERGALVCVAR
    APRKKSVDDFELKPVIHNPHALPLFRDQPSRKRQREKILKDPLKSHKPELPMNG
    PGHGGRVGASKGSLLTQYLLKQGGMIKETWMDEDPREAILKHADAAEKNPKFTR
    AYAETQPDPVFAKSDSEDEDK
  • TABLE 16
    BLAST Sequence Alignment Table.
    BlastX top BlastX e BlastX BlastX
    SEQ ID Target Patent Identifier hit Gene name value identities overlap
    1 CDK type A eucalyptusSpp_003910 Q9FRN5 PUTATIVE 0 367 492
    SERINE/THREONINE
    KINASE
    2 CDK type A eucalyptusSpp_019213 O44000 CDC2-LIKE e−160 217 290
    PROTEIN
    KINASE TPK2
    3 CDK type A eucalyptusSpp_036800 Q40789 PROTEIN 0 259 294
    KINASE
    P34CDC2
    4 CDK type A eucalyptusSpp_040260 Q27168 CDC2 e−156 208 304
    5 CDK type A eucalyptusSpp_041965 Q43361 CDC2PA mRNA. e−159 274 294
    SPTREMBL
    6 CDK type B-1 eucalyptusSpp_002906 Q9FYT9 Cyclin- e−159 269 305
    dependent
    kinase B1-1
    7 CDK type B-2 eucalyptusSpp_001518 Q9FSH4 B2-TYPE 0 270 315
    CYCLIN
    DEPENDENT
    KINASE
    8 CDK type C eucalyptusSpp_008078 Q9LDC1 CRK1 protein 0 415 558
    9 CDK type C eucalyptusSpp_009826 Q9LNN0 F8L10.9 0 392 716
    protein.
    SPTREMBL
    10 CDK type C eucalyptusSpp_010364 Q8GZA7 Putative e−172 309 499
    cyclin-
    dependent
    protein
    kinase.
    11 CDK type C eucalyptusSpp_011523 Q8W2N0 Cyclin- e−165 273 405
    dependent
    kinase CDC2C
    12 CDK type C eucalyptusSpp_024358 P93320 CDC2MSC 0 448 523
    PROTEIN
    13 CDK type C eucalyptusSpp_039125 O80540 F14J9.26 0 418 743
    protein
    14 CDK type D eucalyptusSpp_005362 O80345 CDK- e−180 305 483
    activating
    kinase 1AT
    (Cdk-
    activating
    kinase
    CAK1At)
    15 CDK type D eucalyptusSpp_044857 O80345 CDK- e−177 302 477
    activating
    kinase 1AT
    (Cdk-
    activating
    kinase
    CAK1At)
    16 Cyclin A eucalyptusSpp_001743 Q39879 MITOTIC 0 360 508
    CYCLIN A2-
    TYPE
    17 Cyclin A eucalyptusSpp_012405 Q39878 MITOTIC e−179 278 470
    CYCLIN A2-
    TYPE
    18 Cyclin B eucalyptusSpp_003739 Q9LDM4 F2D10.10 e−148 288 466
    (F5M15.6)
    19 Cyclin B eucalyptusSpp_022338 P93557 Mitotic e−168 310 476
    cyclin
    20 Cyclin B eucalyptusSpp_028605 Q40337 B-like e−158 300 439
    cyclin.
    SPTREMBL
    21 Cyclin B eucalyptusSpp_041006 Q40337 B-like e−158 300 439
    cyclin
    22 Cyclin D eucalyptusSpp_006643 Q9SXN7 NtcycD3-1 1E−73 177 404
    protein
    23 Cyclin D eucalyptusSpp_045338 Q8LK74 Cyclin D3.1 e−101 190 332
    protein.
    SPTREMBL
    24 Cyclin D eucalyptusSpp_046486 Q9ZRX7 CYCLIN D3.2 e−126 196 373
    PROTEIN
    25 Cyclin- eucalyptusSpp_012070 CAB69358 SEQUENCE 1 8E−64 83 88
    dependent FROM PATENT
    kinase WO9841642
    regulatory
    subunit
    26 Histone eucalyptusSpp_006617 O80378 181 0 371 395
    acetyltransferase (Fragment)
    27 Histone eucalyptusSpp_007827 Q9FJT8 Histone e−148 260 465
    acetyltransferase acetyltransferase
    HAT B
    28 Histone eucalyptusSpp_008036 Q9FJT8 Histone e−149 262 465
    acetyltransferase acetyltransferase
    HAT B.
    SPTREMBL
    30 Histone eucalyptusSpp_001596 Q9M4T5 Putative 7E−76 156 305
    deacetylase histone
    deacetylase
    HD2
    31 Histone eucalyptusSpp_005870 Q9M4T4 Putative 7E−66 144 318
    deacetylase histone
    deacetylase
    HD2c
    (AT5g03740/F17C15_160)
    32 Histone eucalyptusSpp_006901 HDAC_ARATH Histone 0 405 499
    deacetylase deacetylase
    (HD)
    33 Histone eucalyptusSpp_006902 AAM13152 HISTONE 0 427 499
    deacetylase DEACETYLASE
    34 Histone eucalyptusSpp_007440 Q8W508 HISTONE 0 369 428
    deacetylase DEACETYLASE
    35 Histone eucalyptusSpp_008994 Q8LD93 Histone 0 354 536
    deacetylase deacetylase,
    putative
    36 Histone eucalyptusSpp_024580 Q94EJ2 At1g08460/T27G7_7 e−165 274 373
    deacetylase (HDA8).
    SPTREMBL
    37 Histone eucalyptusSpp_037831 Q9FML2 Histone 0 356 464
    deacetylase deacetylase.
    SPTREMBL
    38 MAT1 CDK- eucalyptusSpp_034958 Q8LES8 Hypothetical 4E−47 101 190
    activating protein
    kinase
    assembly
    factor
    39 Peptidylprolyl 001209EGXC004488HT TL40_SPIOL Peptidylprolyl 0 329 392
    isomerase cis-
    trans
    isomerase,
    chloroplast
    precursor
    40 Peptidylprolyl 010310EGXD012820HT Q9FJL3 PEPTIDYLPROLYL 0 453 579
    isomerase ISOMERASE
    41 Peptidylprolyl 010310EGXD013036HT O82646 HYPOTHETICAL 0 302 521
    isomerase 57.1 KDA
    PROTEIN (EC
    5.2.1.8)
    42 Peptidylprolyl 010316EGXF999037HT BAB39983 PUTATIVE e−115 146 172
    isomerase PEPTIDYLPROLYL
    CIS-
    TRANS
    ISOMERASE,
    CHLOROPLAST
    43 Peptidylprolyl 010324EGXF002118HT AAK32894 AT5G13120/T19L5_80 e−122 179 264
    isomerase
    44 Peptidylprolyl 011019EGKA001923HT AAM14253 HYPOTHETICAL e−108 146 188
    isomerase 20.3 KDA
    PROTEIN
    45 Peptidylprolyl eucalyptusSpp_000966 Q8L5T1 Peptidylprolyl 1E−91 155 170
    isomerase isomerase
    (Cyclophilin)
    (EC
    5.2.1.8)
    46 Peptidylprolyl eucalyptusSpp_001037 Q8VX73 CYCLOPHILIN e−120 155 169
    isomerase (EC 5.2.1.8)
    47 Peptidylprolyl eucalyptusSpp_004603 AAM14253 HYPOTHETICAL e−108 146 188
    isomerase 20.3 KDA
    PROTEIN.
    48 Peptidylprolyl eucalyptusSpp_005465 Q9SP02 Cyclophilin 2E−93 172 204
    isomerase ROC7 (EC
    5.2.1.8)
    (AT5g58710/mzn1_160)
    (Pepti . . .
    49 Peptidylprolyl eucalyptusSpp_006571 O49605 EC 5.2.1.8 9E−98 169 224
    isomerase (Cyclophilin-
    like
    protein)
    (Peptidyl-
    prolyl
    50 Peptidylprolyl eucalyptusSpp_006786 Q93VG0 Cyclophilin 5E−82 142 164
    isomerase (EC 5.2.1.8)
    (Peptidyl-
    prolyl cis-
    trans
    51 Peptidylprolyl eucalyptusSpp_007057 Q38901 Cytosolic 3E−84 144 172
    isomerase cyclophilin
    (EC 5.2.1.8)
    (Peptidyl-
    prolyl
    52 Peptidylprolyl eucalyptusSpp_008670 Q9FJL3 PEPTIDYLPROLYL 0 423 596
    isomerase ISOMERASE
    53 Peptidylprolyl eucalyptusSpp_009137 Q9C566 Cyclophilin- e−168 285 361
    isomerase 40 (EC
    5.2.1.8)
    (Expressed
    protein)
    54 Peptidylprolyl eucalyptusSpp_010285 Q9LY75 Cyclophylin- e−160 345 658
    isomerase like protein
    (EC 5.2.1.8)
    (Peptidyl-
    prolyl
    55 Peptidylprolyl eucalyptusSpp_010600 Q93YQ8 HYPOTHETICAL 0 346 475
    isomerase 50.1 KDA
    PROTEIN
    (FRAGMENT)
    56 Peptidylprolyl eucalyptusSpp_011551 Q9ZVG4 T2P11.13 e−115 154 192
    isomerase PROTEIN
    57 Peptidylprolyl eucalyptusSpp_020743 Q8VXA5 PUTATIVE e−125 161 172
    isomerase CYCLOSPORIN
    A-BINDING
    PROTEIN
    58 Peptidylprolyl eucalyptusSpp_023739 FK21_NEUCR FK506- 3E−49 74 112
    isomerase binding
    protein
    precursor
    (FKBP-21)
    60 Peptidylprolyl eucalyptusSpp_031985 Q8L8W5 Cyclophilin- 1E−82 155 229
    isomerase like protein
    (EC 5.2.1.8)
    (Peptidyl-
    prolyl
    61 Peptidylprolyl eucalyptusSpp_032025 Q9LPC7 F22M8.7 1E−45 99 160
    isomerase protein (EC
    5.2.1.8)
    (Peptidyl-
    prolyl cis-
    trans
    62 Peptidylprolyl eucalyptusSpp_032173 Q8L8W5 Cyclophilin- 4E−83 156 229
    isomerase like protein
    (EC 5.2.1.8)
    (Peptidyl-
    prolyl
    64 Retinoblastoma eucalyptusSpp_009143 Q9SLZ4 Retinoblastoma- 0 704 1008
    related related
    protein protein
    65 WD40 repeat eucalyptusSpp_000349 AAK49947 TGF-BETA 0 291 326
    protein RECEPTOR-
    INTERACTING
    PROTEIN
    1
    66 WD40 repeat eucalyptusSpp_000575 Q9LW17 WD-40 repeat e−168 282 341
    protein protein-like
    (Expressed
    protein)
    67 WD40 repeat eucalyptusSpp_000804 GBLP_SOYBN Guanine 0 291 326
    protein nucleotide-
    binding
    protein beta
    subunit-like
    68 WD40 repeat eucalyptusSpp_000805 GBLP_MEDSA Guanine e−171 291 327
    protein nucleotide-
    binding
    protein beta
    69 WD40 repeat eucalyptusSpp_000806 GBLP_MEDSA Guanine e−171 291 327
    protein nucleotide-
    binding
    protein beta
    subunit-like
    70 WD40 repeat eucalyptusSpp_002248 AAL86002 HYPOTHETICAL 0 261 388
    protein 43.8 KDA
    PROTEIN
    71 WD40 repeat eucalyptusSpp_003203 Q9SY00 Putative WD- e−144 236 317
    protein repeat
    protein
    (AT4G02730/T5J8_2)
    72 WD40 repeat eucalyptusSpp_003209 AAM14986 HYPOTHETICAL e−160 259 302
    protein 32.6 KDA
    PROTEIN
    73 WD40 repeat eucalyptusSpp_004429 Q9SZQ5 HYPOTHETICAL 0 260 322
    protein 34.3 KDA
    PROTEIN
    74 WD40 repeat eucalyptusSpp_004607 AAC27402 EXPRESSED 0 253 356
    protein PROTEIN
    75 WD40 repeat eucalyptusSpp_004682 AAK00964 HYPOTHETICAL 0 264 313
    protein 35.3 KDA
    PROTEIN
    76 WD40 repeat eucalyptusSpp_005786 Q944S2 At2g47790/F17A22.18 e−155 264 396
    protein (Expressed
    protein).
    SPTREMBL
    77 WD40 repeat eucalyptusSpp_005887 Q94AB4 AT3g13340/MDC11_13 0 332 446
    protein
    78 WD40 repeat eucalyptusSpp_005981 Q8L4X6 WD-repeat 0 315 348
    protein protein
    GhTTG2.
    SPTREMBL
    79 WD40 repeat eucalyptusSpp_006766 Q8L4M1 Putative WD- e−137 234 369
    protein 40 repeat
    protein
    80 WD40 repeat eucalyptusSpp_006769 Q9LJC6 RETINOBLASTOMA- 0 372 566
    protein BINDING
    PROTEIN-LIKE
    81 WD40 repeat eucalyptusSpp_006907 Q94C94 Hypothetical 0 446 812
    protein protein.
    82 WD40 repeat eucalyptusSpp_007518 Q93ZN5 AT4G00090/F6N15_8 0 311 436
    protein
    83 WD40 repeat eucalyptusSpp_007717 O82266 At2g47990 e−180 327 528
    protein protein
    (Hypothetical
    58.9 kDa
    protein)
    84 WD40 repeat eucalyptusSpp_007718 Q8RWD8 Hypothetical e−173 278 350
    protein protein.
    SPTREMBL
    85 WD40 repeat eucalyptusSpp_007741 Q8LA40 Putative WD- e−158 269 409
    protein 40 repeat
    protein,
    MSI2
    86 WD40 repeat eucalyptusSpp_007884 Q9FHY2 Similarity e−149 316 765
    protein to unknown
    protein
    87 WD40 repeat eucalyptusSpp_008258 Q9LHN3 EMB|CAB63739.1 0 524 758
    protein (AT3G18860/MCB22_3)
    88 WD40 repeat eucalyptusSpp_008465 Q9FLS2 WD-repeat 0 366 460
    protein protein-like
    89 WD40 repeat eucalyptusSpp_008616 Q9LYK6 Hypothetical e−148 252 321
    protein protein
    90 WD40 repeat eucalyptusSpp_008690 Q9SW94 G PROTEIN 0 326 376
    protein BETA SUBUNIT
    91 WD40 repeat eucalyptusSpp_008708 Q8L862 Hypothetical e−167 297 487
    protein protein
    92 WD40 repeat eucalyptusSpp_008850 O22725 F11P17.7 0 402 853
    protein protein.
    SPTREMBL
    93 WD40 repeat eucalyptusSpp_009072 Q9SAJ0 F23A5.2 (form e−176 288 350
    protein 2) (mRNA
    export
    protein,
    putative)
    94 WD40 repeat eucalyptusSpp_009465 Q9FLX9 NOTCHLESS 0 384 475
    protein PROTEIN
    HOMOLOG
    95 WD40 repeat eucalyptusSpp_009472 Q9SZA4 WD-REPEAT 0 374 457
    protein PROTEIN-LIKE
    PROTEIN
    96 WD40 repeat eucalyptusSpp_009550 Q9FKT5 Gb|AAF54217.1 e−167 275 313
    protein (Hypothetical
    protein)
    97 WD40 repeat eucalyptusSpp_010284 O22466 WD-40 repeat 0 397 423
    protein protein MSI1
    98 WD40 repeat eucalyptusSpp_010595 Q94C94 Hypothetical 0 419 789
    protein protein
    99 WD40 repeat eucalyptusSpp_010657 Q94AH2 HYPOTHETICAL 0 243 298
    protein 33.1 KDA
    PROTEIN
    100 WD40 repeat eucalyptusSpp_012636 Q8L611 Hypothetical 0 756 1133
    protein protein
    101 WD40 repeat eucalyptusSpp_012748 AAD10151 PUTATIVE WD- 0 375 469
    protein 40 REPEAT
    PROTEIN,
    MSI4
    102 WD40 repeat eucalyptusSpp_012879 Q8VZY6 FERTILIZATION- 0 291 377
    protein INDEPENDENT
    ENDOSPERM
    PROTEIN
    103 WD40 repeat eucalyptusSpp_015515 Q8LPI5 Putative WD- 0 360 493
    protein repeat
    protein.
    SPTREMBL
    104 WD40 repeat eucalyptusSpp_015724 O22607 WD-40 repeat 0 395 522
    protein protein MSI4
    105 WD40 repeat eucalyptusSpp_016167 Q93YS7 Putative WD- 0 663 917
    protein repeat
    membrane
    protein
    106 WD40 repeat eucalyptusSpp_016633 Q9SUY6 HYPOTHETICAL e−174 240 384
    protein 43.8 KDA
    PROTEIN
    107 WD40 repeat eucalyptusSpp_017485 Q8RXC4 Hypothetical 0 650 1348
    protein 144.7 kDa
    protein
    108 WD40 repeat eucalyptusSpp_018007 O94289 WD repeat- e−129 302 794
    protein containing
    protein
    109 WD40 repeat eucalyptusSpp_020775 Q8W403 Sec13p e−150 242 304
    protein
    110 WD40 repeat eucalyptusSpp_023132 AAK52092 WD-40 REPEAT 0 458 515
    protein PROTEIN
    111 WD40 repeat eucalyptusSpp_023569 Q9XIJ3 T10O24.21. 0 404 576
    protein SPTREMBL
    112 WD40 repeat eucalyptusSpp_023611 Q8L4J2 Cleavage e−174 301 438
    protein stimulation
    factor 50K
    chain
    (Cleavage
    stimulation
    113 WD40 repeat eucalyptusSpp_024934 Q94AB4 AT3g13340/MDC11_13. 0 343 444
    protein WD-
    repeat
    protein-like
    SPTREMBL
    114 WD40 repeat eucalyptusSpp_025546 O22212 Hypothetical 0 352 566
    protein 61.8 kDa
    Trp-Asp
    repeats
    containing
    protein
    115 WD40 repeat eucalyptusSpp_030134 Q9LVF2 Genomic DNA, 0 677 946
    protein chromosome
    3, P1 clone:
    MIL23
    116 WD40 repeat eucalyptusSpp_031787 AAL91206 WD REPEAT 0 264 329
    protein PROTEIN-LIKE
    117 WD40 repeat eucalyptusSpp_034435 Q9SAJ0 F23A5.2(form e−178 290 349
    protein 2) (mRNA
    export
    protein,
    putative).
    SPTREMBL
    118 WD40 repeat eucalyptusSpp_034452 Q94BR4 Hypothetical 0 381 525
    protein protein
    (Putative
    pre-mRNA
    splicing
    factor
    119 WD40 repeat eucalyptusSpp_035789 P93563 Guanine 3E−88 171 356
    protein nucleotide-
    binding
    protein beta
    subunit
    120 WD40 repeat eucalyptusSpp_035804 Q9FNN2 WD-repeat 0 356 589
    protein protein-
    like.
    SPTREMBL
    121 WD40 repeat eucalyptusSpp_043057 Q9LV35 WD40-repeat 0 472 610
    protein protein.
    SPTREMBL
    122 WD40 repeat eucalyptusSpp_046741 Q93VK1 AT4g28450/F20O9_130 0 363 452
    protein
    123 WD40 repeat eucalyptusSpp_047161 Q9ZUN8 Putative WD- 0 350 473
    protein 40 repeat
    protein
    124 CDK type A pinusRadiata_001766 Q9M3W7 PUTATIVE e−128 237 436
    CDC2-RELATED
    PROTEIN
    KINASE CRK2.459
    e−128
    125 CDK type A pinusRadiata_002927 Q9FRN5 PUTATIVE 0 349 470
    SERINE/THREONINE
    KINASE
    126 CDK type B-1 990309PRCA009171HT Q9FYT8 Cyclin- e−145 244 303
    dependent
    kinase B1-2
    127 CDK type B-1 pinusRadiata_013714 Q9FYT8 CYCLIN- e−174 222 304
    DEPENDENT
    KINASE B1-2
    128 CDK type B-1 pinusRadiata_016332 Q9FYT8 CYCLIN- e−178 228 304
    DEPENDENT
    KINASE B1-2
    129 CDK type B-1 pinusRadiata_021677 Q9FYT8 CYCLIN- e−176 229 304
    DEPENDENT
    KINASE B1-2
    130 CDK type B-1 pinusRadiata_027562 Q9FYT8 Cyclin- e−118 211 304
    dependent
    kinase B1-2
    131 CDK type C pinusRadiata_001504 Q9LNN0 F8L10.9 0 434 790
    protein
    132 CDK type C pinusRadiata_015211 Q9LNN0 F8L10.9 0 371 746
    protein
    133 CDK type C pinusRadiata_020421 P93320 Cdc2MsC 0 318 432
    protein
    134 CDK type D pinusRadiata_003187 O80345 CDK- e−137 226 485
    ACTIVATING
    KINASE 1AT
    (CDK-
    ACTIVATING
    KINASE
    CAK1AT)
    135 CDK type D pinusRadiata_015661 Q947K6 CDK- 0 266 407
    ACTIVATING
    KINASE.
    136 Cyclin A pinusRadiata_013874 Q96226 Cyclin e−108 223 474
    137 Cyclin A pinusRadiata_014615 CAC27333 PUTATIVE A- 0 332 390
    LIKE CYCLIN
    (FRAGMENT)
    138 Cyclin B pinusRadiata_004578 O65064 Probable 9E−87 162 217
    G2/mitotic-
    specific
    cyclin
    (Fragment)
    139 Cyclin B pinusRadiata_023387 O04389 B-like 2E−98 220 466
    cyclin
    140 Cyclin D pinusRadiata_006970 P93103 CYCLIN-D 1E−75 135 293
    LIKE PROTEIN
    141 Cyclin D pinusRadiata_010322 CAC17049 SEQUENCE 33 e−131 171 254
    FROM PATENT
    WO0065040
    142 Cyclin D pinusRadiata_022721 P93103 CYCLIN-D 1E−76 137 289
    LIKE PROTEIN
    143 Cyclin D pinusRadiata_023407 Q9SMD5 CYCD3,2 8E−90 139 278
    PROTEIN
    144 Cyclin- pinusRadiata_001945 Q947Y1 PUTATIVE 5E−55 74 86
    dependent CYCLIN-
    kinase DEPENDENT
    regulatory KINASE
    subunit REGULATORY
    SUBUNIT
    145 Cyclin- pinusRadiata_008233 CAB69358 SEQUENCE 1 4E−49 65 86
    dependent FROM PATENT
    kinase WO9841642
    regulatory
    subunit
    146 Cyclin- pinusRadiata_008234 CAB69358 SEQUENCE 1 4E−49 65 86
    dependent FROM PATENT
    kinase WO9841642
    regulatory
    subunit
    147 Cyclin- pinusRadiata_022054 CAB69358 SEQUENCE 1 8E−55 70 82
    dependent FROM PATENT
    kinase WO9841642
    regulatory
    subunit
    148 Histone pinusRadiata_012137 Q9FK40 Histone 0 496 555
    acetyltransferase acetyltransferase
    (AT5g50320/MXI22_3)
    149 Histone pinusRadiata_012582 O80378 181 0 354 402
    acetyltransferase (Fragment)
    SPTREMBL
    150 Histone pinusRadiata_015285 O80378 181 0 342 401
    acetyltransferase (Fragment)
    151 Histone pinusRadiata_017229 Q9LNC4 F9P14.9 e−118 268 585
    acetyltransferase protein
    152 Histone pinusRadiata_020724 Q9AR19 Histone e−177 355 639
    acetyltransferase acetyltransferase
    GCN5
    (Expressed
    protein)
    153 Histone pinusRadiata_004555 AAM13152 HISTONE 0 331 488
    deacetylase DEACETYLASE
    154 Histone pinusRadiata_004556 AAM13152 HISTONE 0 331 488
    deacetylase DEACETYLASE
    155 Histone pinusRadiata_005729 Q9M4U5 Histone 9E−62 154 348
    deacetylase deacetylase
    2 isoform b
    156 Histone pinusRadiata_007395 AAM13152 HISTONE 0 335 426
    deacetylase DEACETYLASE
    157 Histone pinusRadiata_009503 Q8W508 Histone 0 365 427
    deacetylase deacetylase
    158 Histone pinusRadiata_011283 AAM19887 AT1G08460/T27G7_7 0 255 366
    deacetylase
    159 Histone pinusRadiata_012322 Q9FML2 HISTONE 0 327 435
    deacetylase DEACETYLASE
    (PUTATIVE
    HISTONE
    DEACETYLASE)
    161 Histone pinusRadiata_023236 Q8RX28 Putative e−144 238 390
    deacetylase histone
    deacetylase
    162 Peptidylprolyl pinusRadiata_000171 Q9FJL3 PEPTIDYLPROLYL 0 364 549
    isomerase ISOMERASE
    163 Peptidylprolyl pinusRadiata_000172 Q38949 FK506 0 365 552
    isomerase BINDING
    PROTEIN
    FKBP62
    (ROF1)
    164 Peptidylprolyl pinusRadiata_001480 Q8VXA5 PUTATIVE e−125 161 172
    isomerase CYCLOSPORIN
    A-BINDING
    PROTEIN
    168 Peptidylprolyl pinusRadiata_001692 FKB7_WHEAT 70 kDa 0 418 553
    isomerase peptidylprolyl
    isomerase
    (EC 5.2.1.8)
    169 Peptidylprolyl pinusRadiata_005313 AAB64339 FKBP-TYPE 1E−97 135 175
    isomerase PEPTIDYL-
    PROLYL CIS-
    TRANS
    ISOMERASE
    170 Peptidylprolyl pinusRadiata_006362 BAB39983 PUTATIVE 3E−77 129 168
    isomerase PEPTIDYL-
    PROLYL CIS-
    TRANS
    ISOMERASE,
    CHLOROPLA . . .
    290 3e−77
    171 Peptidylprolyl pinusRadiata_006493 Q9C835 Hypothetical 2E−62 128 235
    isomerase 26.4 kDa
    protein (EC
    5.2.1.8)
    (Peptidyl-
    prol . . .
    172 Peptidylprolyl pinusRadiata_006983 AAK96784 CYCLOPHILIN e−103 151 204
    isomerase
    174 Peptidylprolyl pinusRadiata_007665 Q9LDC0 FKBP-like e−138 239 378
    isomerase protein
    (Genomic
    DNA,
    chromosome
    3, P1 clone:
    175 Peptidylprolyl pinusRadiata_012196 Q93VG0 Cyclophilin 4E−74 132 160
    isomerase (EC 5.2.1.8)
    (Peptidyl-
    prolyl cis-
    trans
    176 Peptidylprolyl pinusRadiata_013382 Q9C588 HYPOTHETICAL 0 288 581
    isomerase 60.2 KDA
    PROTEIN
    177 Peptidylprolyl pinusRadiata_016461 O04287 IMMUNOPHILIN 9E−66 88 109
    isomerase
    178 Peptidylprolyl pinusRadiata_017611 Q9C566 Cyclophilin- e−163 276 360
    isomerase 40 (EC
    5.2.1.8)
    (Expressed
    protein)
    179 Peptidylprolyl pinusRadiata_019776 AAM14253 HYPOTHETICAL e−110 146 190
    isomerase 20.3 KDA
    PROTEIN
    180 Peptidylprolyl pinusRadiata_020659 AAO63961 Hypothetical 7E−85 159 227
    isomerase protein
    SPTREMBL
    181 Peptidylprolyl pinusRadiata_022559 AAK43974 PUTATIVE 2E−73 113 153
    isomerase PEPTIDYL-
    PROLYL CIS-
    TRANS
    ISOMERASE
    182 Peptidylprolyl pinusRadiata_024188 Q9P3X9 PEPTIDYL- e−122 210 379
    isomerase PROLYL CIS-
    TRANS
    ISOMERASE
    (EC 5.2.1.8)
    183 Peptidylprolyl pinusRadiata_027973 Q9SR70 T22K18.11 3E−69 125 171
    isomerase protein
    (AT3g10060/T22K18_11)
    184 WD40 repeat pinusRadiata_001353 Q9FNN2 WD-repeat 0 317 590
    protein protein-
    likeSPTREMBL
    185 WD40 repeat pinusRadiata_001978 PRL1_ARATH PP1/PP2A 0 341 502
    protein phosphatases
    pleiotropic
    regulator
    PRL1
    186 WD40 repeat pinusRadiata_002810 AAK49947 TGF-BETA 0 273 326
    protein RECEPTOR-
    INTERACTING
    PROTEIN
    1
    187 WD40 repeat pinusRadiata_002811 AAK49947 TGF-BETA 0 273 326
    protein RECEPTOR-
    INTERACTING
    PROTEIN
    1
    188 WD40 repeat pinusRadiata_002812 AAM15129 HYPOTHETICAL e−127 225 521
    protein 58.9 KDA
    PROTEIN
    189 WD40 repeat pinusRadiata_003514 Q9FJ94 Similarity e−137 242 445
    protein to myosin
    heavy chain
    kinaseSPTREMBL
    190 WD40 repeat pinusRadiata_004104 GBB_ORYSA Guanine 0 294 378
    protein nucleotide-
    binding
    protein beta
    subunit
    191 WD40 repeat pinusRadiata_005595 Q9FTT9 PUTATIVE 0 320 459
    protein DKFZP564O0463
    PROTEIN
    192 WD40 repeat pinusRadiata_005754 Q94JT6 At1g78070/F28K19_28SPTREMBL e−168 294 451
    protein
    193 WD40 repeat pinusRadiata_006463 GBLP_MEDSA Guanine e−152 261 324
    protein nucleotide-
    binding
    protein beta
    subunit-like . . .
    538 e−152
    194 WD40 repeat pinusRadiata_006665 AAM20553 HYPOTHETICAL 0 655 1169
    protein 119.9 KDA
    PROTEIN.
    1229 0.0
    195 WD40 repeat pinusRadiata_006750 AAM13119 HYPOTHETICAL e−158 264 312
    protein 35.4 KDA
    PROTEIN. 560
    e−158
    196 WD40 repeat pinusRadiata_007030 Q9LJN8 MITOTIC e−169 284 335
    protein CHECKPOINT
    PROTEIN. 595
    e−169
    197 WD40 repeat pinusRadiata_007854 Q8H919 Putative WD 0 429 644
    protein domain
    containing
    protein
    198 WD40 repeat pinusRadiata_007917 AAD10151 PUTATIVE WD- 0 353 462
    protein 40 REPEAT
    PROTEIN,
    MSI4
    199 WD40 repeat pinusRadiata_007989 Q9LRZ0 Genomic DNA, 0 480 687
    protein chromosome
    3, TAC
    clone: K20I9
    200 WD40 repeat pinusRadiata_008506 MSI1_LYCES WD-40 repeat 0 364 420
    protein protein MSI1
    201 WD40 repeat pinusRadiata_008692 Q8W403 Sec13p e−134 218 301
    protein
    202 WD40 repeat pinusRadiata_008693 Q8W403 Sec13p e−137 222 301
    protein
    203 WD40 repeat pinusRadiata_009170 Q9M0V4 U3 snoRNP- e−127 244 524
    protein associated-
    like
    protein.
    SPTREMBL
    204 WD40 repeat pinusRadiata_009408 Q9SAJ0 F23A5.2(FORM e−171 282 350
    protein 2). 602 e−171
    205 WD40 repeat pinusRadiata_009522 Q8RXQ4 Hypothetical e−129 231 395
    protein 43.8 kDa
    protein
    206 WD40 repeat pinusRadiata_009734 AAO27452 Peroxisomal e−142 227 317
    protein targeting
    signal type
    2 receptor.
    SPTREMBL
    207 WD40 repeat pinusRadiata_009815 AAM20433 CELL CYCLE 0 326 500
    protein SWITCH
    PROTEIN
    208 WD40 repeat pinusRadiata_010670 AAN72058 Expressed e−157 264 345
    protein protein
    209 WD40 repeat pinusRadiata_011297 AAM13100 WD REPEAT e−157 262 337
    protein PROTEIN
    ATAN11
    210 WD40 repeat pinusRadiata_013098 AAM13153 HYPOTHETICAL e−136 229 352
    protein 39.1 KDA
    PROTEIN. 487
    e−136
    211 WD40 repeat pinusRadiata_013172 Q8H0T9 Hypothetical 0 437 860
    protein protein
    212 WD40 repeat pinusRadiata_013589 AAK52092 WD-40 REPEAT 0 448 512
    protein PROTEIN
    213 WD40 repeat pinusRadiata_013608 AAC27402 EXPRESSED e−141 202 358
    protein PROTEIN
    214 WD40 repeat pinusRadiata_014299 Q9XED5 Cell cycle 0 335 488
    protein switch
    proteinSPTREMBL
    215 WD40 repeat pinusRadiata_014498 Q9FH64 WD REPEAT e−152 206 329
    protein PROTEIN-LIKE
    216 WD40 repeat pinusRadiata_014548 Q93ZS6 HYPOTHETICAL 0 505 763
    protein 82.2 KDA
    PROTEIN
    217 WD40 repeat pinusRadiata_014610 Q9M298 Hypothetical 0 450 922
    protein 104.7 kDa
    protein
    218 WD40 repeat pinusRadiata_016090 Q9SIY9 Putative WD- 0 442 802
    protein 40 repeat
    proteinSPTREMBL
    219 WD40 repeat pinusRadiata_016722 O22826 Putative e−159 257 310
    protein splicing
    factorSPTREMBL
    220 WD40 repeat pinusRadiata_016785 AAG60193 PUTATIVE 0 344 464
    protein WD40 PROTEIN
    221 WD40 repeat pinusRadiata_017094 Q9LV35 WD40-REPEAT 0 406 604
    protein PROTEIN
    222 WD40 repeat pinusRadiata_017527 Q9AYE4 Hypothetical e−154 254 314
    protein 35.3 kDa
    protein
    223 WD40 repeat pinusRadiata_017591 O80706 F8K4.21 0 905 1218
    protein protein
    224 WD40 repeat pinusRadiata_017769 Q9XIJ3 T10O24.21 0 446 607
    protein
    225 WD40 repeat pinusRadiata_018047 Q8VZY6 FERTILIZATION- 0 285 373
    protein INDEPENDENT
    ENDOSPERM
    PROTEIN
    226 WD40 repeat pinusRadiata_018414 Q947M8 COPI 0 455 638
    protein
    227 WD40 repeat pinusRadiata_018986 Q9LFE2 WD40-repeat 0 518 886
    protein protein
    228 WD40 repeat pinusRadiata_019479 Q9SZA4 WD-repeat e−156 276 454
    protein protein-like
    protein
    229 WD40 repeat pinusRadiata_020144 Q8W514 MSI TYPE 0 288 413
    protein NUCLEOSOME/CHROMATIN
    ASSEMBLY
    FACTOR C
    230 WD40 repeat pinusRadiata_022480 Q8W514 MSI type e−167 287 426
    protein nucleosome/chromatin
    assembly
    factor C
    231 WD40 repeat pinusRadiata_023079 Q8W514 MSI type e−169 283 397
    protein nucleosome/chromatin
    assembly
    factor C. SPTREMBL
    232 WD40 repeat pinusRadiata_026739 Q93YS7 Putative WD- 0 591 918
    protein repeat
    membrane
    protein.
    SPTREMBL
    233 WD40 repeat pinusRadiata_026951 Q93VS5 AT4g18900/F13C5_70 e−163 290 503
    protein (Hypothetical
    protein)
    234 WEE1-like pinusRadiata_026529 Q9SRY9 F22D16.3 e−122 209 451
    protein PROTEIN
    235 WD40 repeat eucalyptusSpp_006366 Q8LF96 PRL1 protein 0 374 492
    protein
    236 WD40 repeat eucalyptusSpp_017378 O22607 WD-40 repeat 0 371 453
    protein protein MSI4
    237 WD40 repeat pinusRadiata_000888 O22466 WD-40 repeat 0 364 420
    protein protein MSI1
    238 Cyclin- pinusRadiata_014166 Q9FKB5 GENOMIC DNA, 5E−42 114 304
    dependant CHROMOSOME
    kinase 5, TAC
    inhibitor CLONE: K24G6
    (CYCLIN-
    DEPENDENT
    239 CDK type D pinusRadiata_003189 Q9M5G4 CDK- 8E−21 56 100
    activating
    kinase
    240 Histone pinusRadiata_009356 Q9FJT8 Histone 7E−85 187 510
    acetyltransferase acetyltransferase
    HAT B
    241 Histone pinusRadiata_000065 Q9LPW6 F13K23.8 5E−18 71 209
    deacetylase protein.
    242 Histone pinusRadiata_014197 Q8GXJ1 Putative e−170 308 519
    deacetylase histone
    deacetylase
    243 Peptidylprolyl pinusRadiata_009081 Q9ZRQ9 Cyclophilin e−106 185 190
    isomerase (EC 5.2.1.8)
    (Peptidyl-
    prolyl cis-
    trans
    244 Peptidyprolyl pinusRadiata_013417 Q8H4T0 Putative e−140 235 345
    isomerase peptidyl-
    prolycis-
    trans
    isomerase
    protein
    245 WD40 repeat pinusRadiata_005755 Q9SKW4 F5J5.6. e−143 144 319
    protein
    246 WD40 repeat pinusRadiata_006670 Q9LDG7 WD-40 repeat e−163 393 960
    protein protein-like
    (MJK13.13
    protein)
    247 WD40 repeat pinusRadiata_007027 Q8GWR1 Hypothetical e−157 276 470
    protein protein.
    248 WD40 repeat pinusRadiata_007276 Q9LF27 Hypothetical e−138 235 428
    protein 47.3 kDa
    protein
    249 WD40 repeat pinusRadiata_007390 Q94AH4 PUTATIVE 3E−17 53 158
    protein RING ZINC
    FINGER
    PROTEIN. 91
    3e−17
    250 WD40 repeat pinusRadiata_012648 O22212 Hypothetical 0 324 561
    protein 61.8 kDa
    Trp-Asp
    repeats
    containing
    protein
    251 WD40 repeat pinusRadiata_013171 Q8H0T9 Hypothetical 0 437 860
    protein protein.
    252 Cyclin B eucalyptusSpp_045414 Q9LDM4 F2D10.10 e−142 255 423
    (F5M15.6)
    253 Cyclin- eucalyptusSpp_044328 Q9FKB5 GENOMIC DNA, 1E−54 121 260
    dependant CHROMOSOME
    kinase 5, TAC
    inhibitor CLONE: K24G6
    (CYCLIN-
    DEPENDENT
    254 Histone eucalyptusSpp_015615 Q9AR19 Histone 0 390 563
    acetyltransferase acetyltransferase
    GCN5
    (Expressed
    protein)
    255 Peptidylprolyl eucalyptusSpp_017239 Q8GWM6 Hypothetical 0 364 591
    isomerase protein
    256 WD40 repeat eucalyptusSpp_018643 Q93VS5 AT4g18900/F13C5_70 0 229 327
    protein (Hypothetical
    protein)
    257 WD40 repeat eucalyptusSpp_019127 Q9SRX9 F22D16.14 e−131 232 337
    protein protein.
    SPTREMBL
    258 WD40 repeat eucalyptusSpp_022624 Q9LFE2 WD40-repeat 0 594 868
    protein protein
    259 WD40 repeat eucalyptusSpp_032424 Q8LPL5 Cell cycle 0 255 327
    protein switch
    protein
    260 WD40 repeat eucalyptusSpp_037472 Q9SK69 Putative WD- 0 461 677
    protein 40 repeat
    protein
    (AT2G20330/F11A3.12)

Claims (55)

1. An isolated polynucleotide comprising a nucleic acid sequence that (i) is selected from the group consisting of SEQ ID NOs: 1-260 and variants thereof, (ii) is selected from the group consisting of SEQ ID NOs: 521-772 and variants thereof, or (iii) encodes the catalytic or substrate-binding domain of a polypeptide selected from of any one of SEQ ID NOs: 261-520, wherein the polynucleotide encodes a polypeptide having the activity of said polypeptide selected from any one of SEQ ID NOs: 261-520.
2.-5. (canceled)
6. The isolated polynucleotide of claim 1, wherein the variant has a sequence identity that is greater than or equal to 80% to any one of SEQ ID NOs: 1-260 or encodes a protein with an amino acid sequence having a sequence identity that is greater than 60%, 65%, 70%, 75%, 80%, 85% or 90% to any one of SEQ ID NOs: 261-520, and wherein the protein encoded by the polynucleotide possesses the activity of the protein encoded by said any one of SEQ ID NOs: 1-260.
7.-8. (canceled)
9. A DNA construct comprising at least one polynucleotide of claim 1, operably linked in sense or antisense orientation to a promoter, wherein the promoter is selected from the group consisting of a constitutive promoter, a strong promoter, an inducible promoter, a regulatable promoter, a temporally regulated promoter, and a tissue-preferred promoter.
10.-13. (canceled)
14. The DNA construct of claim 9, wherein an RNA transcript of the polynucleotide is complementary to a nucleic acid sequence selected from the group consisting of 1-260.
15. A plant cell, comprising the DNA construct of claim 9.
16. The plant cell of claim 15, wherein the plant cell is in a transgenic plant, and wherein the phenotype of the plant is different from a plant of the same species which does not comprise the plant cell, wherein the difference in phenotype is in lignin quality, lignin structure, wood composition, wood appearance, wood density, wood strength, wood stiffness, cellulose polymerization, fiber dimensions, lumen size, other plant components, plant cell division, plant cell development, number of cells per unit area, cell size, cell shape, cell wall composition, rate of wood formation, aesthetic appearance of wood, formation of stem defects, average microfibril angle, width of the S2 cell wall layer, rate of growth, rate of root formation, ratio of root to branch vegetative development, leaf area index, and leaf shape.
17.-20. (canceled)
21. The transgenic plant of claim 16, wherein the plant is of a species of Eucalyptus or Pinus.
22. The transgenic plant of claim 16, wherein the plant exhibits one or more traits selected from the group consisting of increased drought tolerance, herbicide resistance, reduced or increased height, reduced or increased branching, enhanced cold and frost tolerance, improved vigor, enhanced color, enhanced health and nutritional characteristics, improved storage, enhanced yield, enhanced salt tolerance, enhanced resistance of the wood to decay, enhanced resistance to fungal diseases, altered attractiveness to insect pests, enhanced heavy metal tolerance, increased disease tolerance, increased insect tolerance, increased water-stress tolerance, enhanced sweetness, improved texture, decreased phosphate content, increased germination, increased micronutrient uptake, improved starch composition, improved flower longevity, production of novel resins, and production of novel proteins or peptides, reduced period of juvenility, an increased period of juvenility, propensity to form reaction wood, self-abscising branches, accelerated reproductive development or delayed reproductive development as compared to a plant of the same species that has not been transformed with the DNA construct.
23.-31. (canceled)
32. A wood obtained from a transgenic tree which has been transformed with the DNA construct of claim 9.
33. A wood pulp obtained from a transgenic tree which has been transformed with the DNA construct of claim 9.
34.-36. (canceled)
37. An isolated polypeptide comprising an amino acid sequence encoded by the isolated polynucleotide of claim 1.
38.-43. (canceled)
44. The isolated polynucleotide of claim 1, wherein the polynucleotide comprises fewer than about 100 nucleotide bases.
45. A method of correlating gene expression in two different samples, comprising: detecting a level of expression of one or more genes encoding a product encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-260 and conservative variants thereof in a first sample; detecting a level of expression of the one or more genes in a second sample; comparing the level of expression of the one or more genes in the first sample to the level of expression of the one or more genes in the second sample; and correlating a difference in expression level of the one or more genes between the first and second samples.
46. The method of claim 45, wherein the first sample and the second sample are plant tissues that are from the same or different plant.
47. The method of claim 4, wherein the first sample and the second sample are (i) from the same plant tissue, (ii) harvested during a different season of the year, and/or (iii) obtained from plants in different stages of development.
48.-50. (canceled)
51. The method of claim 46 wherein the plant tissue is selected from the group consisting of vascular tissue, apical meristem, vascular cambium, xylem, phloem, root, flower, cone, fruit, and seed.
52. The method of claim 51, wherein the plant tissues are obtained from at least one of (i) a different type of tissue, (ii) a different stage of development, or (iii) different stages of the cell cycle.
53.-54. (canceled)
55. The method of claim 51, wherein the plant tissues are from one or more species of Eucalyptus or Pinus.
56. (canceled)
57. The method of claim 45, wherein the step of detecting is effected using one or more polynucleotides capable of hybridizing to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-260 under standard hybridization conditions.
58. (canceled)
59. The method of claim 57, wherein the step of detecting is accomplished by hybridization to a labeled nucleic acid.
60. (canceled)
61. The method of claim 57, wherein at least one of polynucleotides hybridizes to a 3′ untranslated region of the nucleic acid sequence.
62. (canceled)
63. The method of claim 57, wherein the one or more polynucleotides comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 521-772.
64.-66. (canceled)
67. The method of claim 45, further comprising, prior to the detecting steps, the step of amplifying at least one of the genes.
68. The method of claim 45, further comprising, prior to the detecting steps, the step of labeling at least one of the genes with a detectable label.
69. A combination for detecting expression of one or more genes, comprising two or more oligonucleotides, wherein each oligonucleotide is capable of hybridizing to a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-260 or to an RNA transcript of a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-260.
70. (canceled)
71. The combination of claim 69, wherein the oligonucleotides each hybridize to different nucleic acid sequences or to different RNA transcripts.
72. (canceled)
73. The combination of claim 69, wherein at least one of the oligonucleotides hybridizes to a 3′ untranslated region of a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 1-260.
74.-75. (canceled)
76. The combination of claim 69, wherein at least one of the oligonucleotides comprises a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 521-772.
77.-83. (canceled)
84. The combination of claim 69, comprising from about 2 to about 5000 oligonucleotides.
85. The combination of claim 84, wherein each of the oligonucleotides is labeled with a detectable label.
86. A microarray comprising the combination of claim 69 provided on a solid support, wherein each of the oligonucleotides occupies a unique location on said solid support.
87. (canceled)
88. A method for detecting one or more nucleic acid sequences in a sample, comprising contacting the sample with the combination of claim 69.
89.-91. (canceled)
92. The method of claim 88, wherein at least one of the oligonucleotides hybridizes to a 3′ untranslated region of a gene that comprises the nucleic acid sequence of at least any one of SEQ ID NOs 1-260.
93.-103. (canceled)
104. A kit for detecting gene expression comprising the microarray of claim 86 and one or more buffers or reagents for a nucleotide hybridization reaction.
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