SI25289A - Combination of split orthogonal proteases with dimerization domains that enable the assembly - Google Patents

Abstract

The invention relates to a combination of orthogonal graft proteases that recognize a target sequence comprising at least 6 amino acids associated with dimerization domains that allow the formation of split proteases. At least two orthogonal proteases are prepared as split fragments in association with dimerization domains, where dimerization can be inducible by a light, chemical or other input signal. Proteases split one or more target proteins that contain a target sequence for one or more orthogonal proteases and act as further mediators of the signal, the reporting protein, or therapeutic proteins. With appropriately selected target proteins, logical circuits mediated by proteases can be prepared. The invention also relates to cells that contain pronounced cleft proteases to transmit the signal.

Description

A combination of split orthogonal proteases with dimerization domains that allow assembly

Field of the Invention

The invention relates to a combination of two or more orthogonal split proteases with dimerization domains that allow the formation of split proteases and cells containing combinations of orthogonal split proteases and target proteins.

State of the art

The activation of selected cells at a given time and space and the precise control of the cell response to activation with one or more input signals is an important technological problem. Activation can be performed by chemical activators, temperature change, pH, by electrodes or light. Cell activation is also possible with indirect or direct mechanical stimuli such as touch, shear force, fluid flow, hypo- and hyperosmotic stress, and ultrasound. In controlling the cellular response to activation, synthetic biology often consists of artificial signal cascades and logic circuits. Usually, these logical circuits are based on the regulation of transcription and translation of proteins, which is a relatively slow process, since transcription and translation is required, which means that the response has a delay of more than a few dozen minutes. Faster cellular signaling takes place through posttranslational proteins (Olson & Tabor 2012), such as phosphorylation, ubiquitination and proteolytic cleavage.

Up to now, proteolysis has already been described as a mechanism for signal transduction, with three known modes of control of protease activity known: autoinhibitory control, proximity sensor and split protease.

The autoinhibitoma peptide is a short amino acid sequence that binds to the active site of the protease, thereby preventing binding of the target substrate. If such an autoinhibitory peptide is attached to the protease via the cleavage site for the second protease, the activity of the first protease becomes dependent on the activity of the other. For example, a TVMV protease TV activated when thrombin cleavage and HCV protease were activated when cleavage with the TVMV protease (Stein & Alexandrov 2014). With an appropriate selection of linking peptides and inducible dimerization. domains, a protease can also be prepared in which the binding of the autoinhibitom peptide to the active site depends on the presence of the ligand. Thus, the TVMV protease was prepared, either activated or deactivated in the presence of a short peptide ligand (Stein & Alexandrov 2014).

On the other hand, the proximity sensor is a way of controlling the activity of protease, based on the control over the colocation of protease and its substrate. For example, cleavage with TEV protease depends on the external signal via the protease linkage to the membrane receptor (GPCR), while the luciferase is bound to the receptor receptor (isstin) that binds to the membrane receptor only in the presence of an external ligand an example of a neurotransmitter or hormone, wherein the protease bound to the GPCR triggers the proteolytic splitting of the reporter (Eishingdrelo et al., 2011). Similarly, the auto-infected proteins HCV and TVMV described above were coupled to a proximity sensor by adding them to the FKBP and FRB domains (Stein & Alexandrov 2014). These domains are linked in the presence of rapamycin, which also leads to close proximity. If one of the proteases in the binding peptide between the enzyme and the autoinhibitom peptide contains a target cleavage site for expensive protease, then their immediate proximity allows the autoinhibit peptide to be discarded and thus the activation of the system.

The third method of induction of protease with ligand, split protease, has been described so far only for TEV protease (Wehr et al., 2006). The protease sequence was split into the N-terminal and C-terminal fragments attached to the rapamycin-binding domains of FKBP and FRB. In the presence of rapamycin, these domains connect and thus approach the split protease fragments that can only take up the active form. By appropriately allocating target cleavage sites for proteases on the reporting or expensive intermediate proteins, it can also be achieved that the activity of several different proteases is reflected differently on the rapporteur. So far, for example, on the control of genetic circuits with orthogonal proteases, which block the inhibitory domains on transcription factors, or, by cleaving the inhibitory domain to the transcriptional factor of attached degrone, and thereby the transcription factor, are exposed to degradation (Femandez-Rodriguez & Voigt 2016) . Shekhawat and colleagues (Shekhawat et al., 2009) developed a rapporteur consisting of two fragments of split luciferase, each of which is attached to a wrapped helix, and the dimerization of these edged helixes of the luciferase fragment connects to the active form. Each of the wrapped screws contains an auto-inhibitory peptide which protects the dimerization through the cleavage site for the protease. Only when the two auto-inhibitory peptides were split due to the action of two proteases (TEV proteins and caspase 3 were used) dimerization is enabled and the output signal is detected. The rapporteur described above acts as a logical AND function.

Protease TEV belongs to the family of potentiated proteases. Potentials are plant pathogens whose genome is transcribed into a single polyprotein, part of which is also a core inclusion domain (NIa) that splits the viral polyprotein into individual functional subunits. In addition to the TEV protease, PPV, TVMV, SbMV, SuMMV and dear viruses are known and characterized, for example, in the proteins of TEV, and target sequences are also known which of these proteases are effectively cleaved (JM Adams et al., 2005; MJ Adams et al. 2005; Ghabrial et al., 1990; Tozser et al., 2005). For some of these proteases, they have already been shown to be orthogonal (Femandez-Rodriguez & Voigt 2016). Nevertheless, only the TEV protease appears as a widely used synthetic-biological tool and is the only potentiary protease that has been prepared in split form so far.

Literature

Adams, J.M., Antoniw, F.J. & Fauquet, M.C., 2005. Molecular criteria for genus and species discrimination within the family Potyviridae. Archives of Virology, 150 (3), pp.459-479.

Adams, M, J., Antoniw, J.F. & Beaudoin, F., 2005. Overview and analysis of polyprotein cleavage sites in the Potyviridae family. Molecular Plant Pathology, 6 (4), pp.471-487.

Brown, E.J. et al., 1994. A mammalian protein targeted by Gl-arresting rapamycin-reeeptor complex. Nature, 369 (6483), pp.756-758.

Eishingdrelo, H. et al., 2011. A cell-based protein-protein interaction method using a permuted luciferase reporter. Current Chemical genomics, 5, pp.122-128.

Femandez-Rodriguez, J. & Voigt, C. A., 2016. Post-translational control of genetic circuits using Potyvirus proteases. Nucleic Acids Research, 44 (13), pp. 6493-502.

Ghabrial, S.A. et al., 1990. Molecular genetic analysis of the soybean mosaic virus NIa proteinase. The Journal of General Virology, 71 (9), pp. 1921-7.

Kanno, A. et al., 2007. Cyclic luciferase for real-time sensing of caspase-3 activities in living mammals. Angewandte Chemie (International ed. In English), 46 (40), pp.7595-7599.

Kennedy, MJ. et al., 2010. Rapid blue-light-mediated induction of protein interactions in living celis. Nature methods, 7 (12), pp. 973-975.

Olson, EJ. & Tabor, J.J., 2012. Post-translational tools expand the scope of synthetic biology. Current opinion in Chemical biology, 16 (3-4), pp. 300-6.

Sabatini, D.M. et al., 1994. RAFTI: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Celi, 78 (1), pp.35-43.

Sabers, C.J. et al., 1995. Isolation of a protein target of the FKBP12-rapamycin complex in a mammalian celish. The Journal of Biological Chemistry, 270 (2), pp. 815-822.

Shekhawat, S.S. et al., 2009. An Autoinhibited Coiled-Coil Design Strategy for Split-Protein Protease Sensors. Jacs, 131 (42), pp. 15284-15290.

Stein, V. & Alexandrov, K., 2014. Protease-based synthetic sensing and signal amplification. Proceedings of the National Academy of Sciences of the United States of America, 111 (45), pp. 15934-9.

Tozser, J. et al., 2005. Comparison of substrate specificity of two potyvirus proteases. FEBS Journal, 272 (2), pp.514-523.

Wehr, M.C. et al., 2006. Monitoring regulated protein-protein interactions using split TEV. Nature methods, 3 (12), pp. 985-993.

Technical problem

For the precise management and selectivity of biological systems, it is desirable to combine several signals to select different combinations of physiological conditions, cells or signals from the environment. The natural cells do this via signal paths. The problem is to design a new orthogonal signal path, which means that it affects only the selected cell components in a specific way.

For the design of new orthogonal signal paths within human cells, it was found that signaling through proteolysis represents an opportunity for the construction of a system for the rapid transmission of signals that has not yet been utilized. In order to operate within cells, it is best to choose proteases that act on longer target sequences containing at least 6 amino acids, which makes it slightly more prominent in order to disrupt the proteins needed for the cell's functioning, and on the other hand, in target proteins insert specific target sites for cleavage with the selected protease or combinations thereof.

A significant lack of orthogonal proteases was observed in this, which act on well-defined longer different polypeptide sequences, and the operation of which could be directly dependent on the input signal.

For the purposes of more complex control of the cell response to various external signals, we need a larger number of signal molecules and cascades that interact either orthogonally or complement each other and act as logical circuits. It is particularly important that the activity of the transferring molecules in the signal cascade (in the protease described above) is precisely controlled and orthogonal. The selected proteases must therefore: a) be inactive in the absence of a signal, b) facilitate simple reconstitution of the activity in the presence of the signal, c) not affect the endogenous processes in the cell, and d) be orthogonal, therefore the transmission of a signal in one part of the cascade must not be affected to transfer the signal over the second part of the cascade, except when intentionally planned.

It is clear from the state of the art that current solutions can not provide precise, fast, logically-based and selective management of biological systems at several levels coupled with different or identical input signals.

Description of the solution of the problem. The invention solves the above-described problems of the lack of fast orthogonal signaling pathways based on posttranslational modification of proteins, which was achieved by the introduction of a combination of at least two orthogonal split proteases in association with dimerization domains that allow the assembly of the split proteases into cells.

The invention relates to a combination of orthogonal graft proteases that recognize a target sequence comprising at least 6 amino acids associated with dimerization domains that allow the formation of split proteases. At least two orthogonal proteases are prepared as split fragments in association with dimerization domains, where dimerization can be inducible by a light, chemical or other input signal. Proteases split one or more target proteins containing the target sequence for one or more orthogonal protus and act as further mediators of the signal, the reporting protein, or therapeutic proteins. With appropriately selected target proteins, logical circuits mediated by proteases can be prepared.

The invention also relates to cells that contain a combination of orthogonal split proteases in association with dimerization domains and target proteins containing the appropriate cleavage sites identified by individual proteases when they are assembled. A complementary pair of dimerization domains allows the assembly of individual split proteases. The complementary pair can be formed spontaneously or with the aid of an initiator which can be inside cellular or external, such as light, pH, temperature, mechanical stress, chemical signal. Dimerization domains can be different for each type of split protease or are the same for all orthogonal proteases.

The reconstituted protease acts on a target protein that contains a cleavage site for the selected protease and can be an endogenous or transgenic inserted rapporteur or other mediator of the signal.

We have selected a family of potivirus proteases, which is also a TEV protease, and invented new split proteases based on the sequential and functional similarities between the individual proteases of this family. All of the proteases described in this family have a similar amino acid sequence that can be expressed as two fragmented protein fragments, coupled via short moving interconnecting peptides with inducible dimerization domains. Separate protease fragments according to the invention form functional inactive proteins. When adding a ligand or any other signal (e.g., light) that causes the association of dimerization domains, structural and functional reconstitution of the split proteases that cleave the next member of the signaling cascade, comprising the target peptide sequence for cleavage with the selected protease. Such a vaccinated protein may be a direct rapporteur (for example, luciferase or fluorescent protein) or the next mediator of the signal (for example, a transcription factor, kinase, phosphatase, or another protease), and its main feature is that its activity depends on cleavage.

A signaling system based on split proteases contains at least two split proteases. Each of the split proteases in the system may have its target protein (mediator or rapporteur), but two or more proteases may act on the same target protein if it contains various identifiable cleavage sites. The concept of the invention is presented graphically in Figure 1.

Transmission of the signal through split proteases triggers or stops the transcription of selected genes or secretion of selected molecules, which is useful for the treatment of nervous system disorders, hormonal disorders, disorders of the flow and metabolism and other diseases. The invention is useful for regulating the action of human, animal or plant cells, for transmitting the signal to other cells, for secreting peptides, proteins and other molecules, to detect a combination of two or more chemical, light or mechanical signals.

Image description

Figure 1: A schematic diagram of a signal system with orthogonal split proteases associated with dimerization domains that can be activated via an inductoion that may be external or internal-cell. In the presence of the inducer, the inactive split protease is assembled into the active protease and the target protein protein substrate, which leads to a change in the target protein, which may be a rapporteur, a new protease, an inactive enzyme, etc. Each orthogonal split protease can have its own dimerization domains, and thus, various inductors can activate various orthogonal proteases, and thus, by logic operations, we can lead to different cell responses. Proteases break down the target protein which leads to the continuation of the signal pathway (for example, transcriptional regulation) or represents an output signal (for example, a fluorescent protein). If the target protein contains recognizable sites for cleavage with various proteases, the signal transfer with proteases can act as a logic circuit.

Figure 2: Orthogonality of selected proteases. The activity of each protease is shown as a cyclic luciferase activity with a marked cleavage site for the protease. Targeted sequences for cleavage of each protease are shown.

Figure 3: Inducibility of selected proteases. The activity of each protease is shown as cyclic luciferase activity with the appropriate cleavage site for the selected protease. A) Induction of split proteases with rapamycin. B) Induction of split protease TEV with blue light. C) Induction of the split protease PPV with blue light.

Figure 4: Activation of orthogonal signaling pathways mediated by TEV and PPV proteases. Protease TEV cleaves the transcription factor, which increases the expression of the mCitrin rapporteur. Protease PPV by cleavage activates the rapporteur cyclic luciferase.

Figure 5: Logical operation of NOR mediated by TEV and PPV proteases. A) Schematic logic circuit NOR. The target protein in the absence of a signal (input signal 0 0) by dimerization through the wrapped helix P3 and AP4 form an active luciferase rapporteur (output signal 1). In the presence of either or both of the TEV and PPV proteases (input signals 1 0, 0 1 and 1 1), the fragments of the rapporteur break away from the wound hexagons and, therefore, no longer merge into the working rapporteur (output signal 0). B) Reported activity of the NOR logical function with coexpression of TEV and PPV proteases. Addition of any of the proteases or both proteases simultaneously reduces the activity of the rapporteur.

Figure 6: Logic function A NIMPLY B mediated by split TEV proteins with light induction and PPV by chemical induction. A) Schematic of A NIMPLY B logic circuit. The peptide P3mS prevents the formation of a wound heel between AP4 and P3 (input signal 0 0). When cleaved with TEVp protease, P3mS is cleaved and reconstitution of luciferase occurs (input signal 1 0). Protease PPV cleaves the C-terminal luciferase fragment from P3 peptide, thereby preventing the reconstitution of the enzyme (input signals 0 1 and 1 1). B) The measured activity of the reporting logic function A NIMPLY B with different input signals. The activity of the rapporteur is high only with stimulation with light that activates TEV protease, but not with stimulation with rapamycin that activates PPV protease or with rapamycin and light at the same time.

Detailed description of the invention and embodiments

The invention relates to a combination of two or more orthogonal split proteases that recognize a target sequence comprising at least 6 amino acids with dimerization domains that allow the functional reconstitution of protease activity and target proteins with a target sequence recognized by proteases.

The combination of orthogonal split proteases with the dimerization domains of the invention includes: • at least two split proteases, each expressed as at least two split protein fragments, and selected preferably from the NIa family of potivirus proteases, preferably proteins SuMMV, SbMV, PPV and TEV; preferably, at least one of the split proteases consists of two proteins with the protein sequence of SEQ ID 4 and SEQ ID 6, SEQ ID. 10 and SEQ ID. 12, SEQ ED. 16 and SEQ ID. 18, SEQ ID. 22 and SEQ ID. 24 or their homologs having at least 30% similarity of the amino acid sequence of the split proteases associated with the dimerization domains that allow their assembly and which are: (i) spontaneously assembled domains and / or (ii) the assemblage thereof is induced by intracellular or external physical, chemical or biological signals • dimerization domains that are spontaneously assembled domains selected from domains that spontaneously form dimers, preferably dimmer proteins, oblique helix, beta structures that have preferably orthogonal properties, • the dimerization domain is triggered by (i) an intracellular signal, such as: change in metabolite concentration, secondary communicator, change in enzyme activity, or with (ii) external signal such as temperature change, pH value, mechanical stress, change in osmotic pressure, ultrasound, light, chemical or biological signal • dimerization domains, wound helix, light inducible domains, preferably CR Y2 and CIBN, chemically inducible domains, preferably FKBP and FRB, or calcium-dependent domains, preferably calmodulin and Ml3, in fusion with split protease fragments that can form homodymers, heterodimers or with their own excision cause the formation of a covalent bond (intein); and wherein the dimerization is dependent on the input signal, the input signal being a mechanical stimulus, preferably an ultrasound or a touch, a light signal, a chemical ligand, preferably rapamycin, or another physiologically relevant signal, preferably a proteolytic cleavage of the dimerization domain, which spontaneously assembled domains are selected from ortogonal obstructed helixs • a target protein with a recognizable sequence for the proteases of a native, recombinant or artificially generated protein, and the recognizable sequence is at least 6 amino acid residues for at least one protein comprising at least one recognizable cleavage site with at least one of the split proteases and may form the next section of the signal path, pre or a therapeutic target, a therapeutic protein or peptide or a reporting protein, preferably luciferase, SEAP, or a fluorescence protein; • sufficiently long unstructured binding peptides between the individual protein domains that allow for the correct functional reconstitution of protease fragments; • optionally any number of copies of the localization signals , preferably a core localization signal, a signal sequence for transport to the ER or transmembrane domains, and optionally any marker sequences for protein detection or affinity chromatography (e.g. HIS and AU1 markers).

The invention relates to cells that contain the above described orthogonal signaling pathways and in which the signal pathway results in a response that can be expressed in several ways, such as (i) release of endogenous cell metabolites, peptides or proteins (e.g., hormones), ( ii) releasing exogenous metabolites, peptides or proteins, preferably therapeutic proteins, (iii) modifying the activity of endogenous or exogenous proteins (preferably enzymes) in the cell, or (iv) regulating the expression of genes.

The invention relates to cells selected from bacterial or eukaryotic cells, plant cells or human cell lines, preferably the invention relates to mammalian cells and human cell lines, for example to neurons or other nervous system cells, T lymphocytes or other cells immune response or pancreatic beta cell.

Definitions

The term "split protease" refers to two or more polypeptides ("fragments") derived from the protease sequence, each of them being equal to the protease. The fragments themselves are inseparably inactive. The formation of a proteolytically active complex requires the interaction of protease fragments, which is referred to by the term "reconstitution". Protease fragments are selected so as to avoid reconstitution between them without the aid of additional dimerization domains, expressed in fusion with protease fragments in the form of a hymy protein. The term "chimeric protein" means a protein or polypeptide consisting of sequences derived from non-native proteins and formed upon the translation of a nucleic acid hymen which combines the records for the individual domains of non-protein proteins composed in such a way that they form a single open reading frame.

The term "dimerization domain" refers to protein domains that connect independently or in the presence of a ligand to one another through covalent or non-covalent interactions. The term "homodimerization" refers to domains that connect to other domains of the same type, and the term "heterodimerization" refers to domains that connect to other domains of a different type. The term "constitutive dimerization domains" refers to dimerization domains that interconnect independently, for example, wrapped helices, and the term "inducible dimerization domain" refers to dimerization domains that merge only in the presence of a dimerization signal.

The term "signal" refers to a measurable change within a cell or in its environment. The term "input signal" refers to a change that triggers a signal path, and the term "output signal" refers to a change that occurs as a result of the signal path. The input signal may be part of an endogenous path signal, or it is caused exogenously and causes a physiological response of the cell, for example, a change in the concentration of a secondary communicator, such as calcium, or a dimerization signal that affects the dimerization of endogenous or exogenous dimerization domains.

The term "dimerization signal" refers to Uganda, light and mechanical signals, pH changes, post-translational modification of dimerization domains, alteration of the secondary message concentration, or alteration of the transmembrane potential, which causes the dimerization domains that do not have an intrinsic affinity to the connection, can not connect independently in the absence of a dimerization Uganda or a signal.

The term "mechanical signal" used herein refers to all kinds of mechanical disturbances / forces: such as ultrasound, touch, osmotic stress, friction due to the flow of liquid that acts on cells or to the cell membrane. The mechanical signal can be generated by the pressure of a particular solid object, liquid, or other cells on the cell membranes due to a gravitational, centrifugal, shear, or other direct force, or due to indirect forces that induce action on the cell membrane, such as, for example, osmosis, stretching or shrinkage due to temperature or other factors.

The term "ultrasound" refers to acoustic waves with a frequency between about 20 kHz to about 15 MHz generated by the device in which the strength is controlled, sound amplitude, frequency in combination with a suitable converter and a time dependency regime for ultrasonic pulses.

The term "chemical signal" used herein refers to a change in the concentration of Uganda. The term " ligand " used herein refers to short biopolymers or organic or inorganic molecules or ions that can bind to proteins, preferably to dimerization domains.

The term "light signal" refers to electromagnetic waves in the visible range (wavelengths between 400 and 700 nm), the nearby infrared range (wavelengths between 700 nm and 4 pm) or ultraviolet (wavelengths between 10 nm and 400 nm), which may cause conformational or chemical changes in biological molecules, preferably dimerization domains or their ligands.

The term "signal path" used herein refers to one or more events in a cell that may comprise the binding of Uganda, dimerization of proteins or peptides, intrusion of secondary messengers, alteration of transmembrane potential, enzyme-catalyzed reaction, or other changes in the cell, and are caused by an input signal, and their output is an output signal.

The term " orthogonal " used herein refers to the characteristic of the signal paths to take place separately, i.e., that the individual parts of one signal path do not interact with parts of other endogenous or exogenous signal paths. The main feature of the orthogonal signaling paths is that the input signal of each path leads to the output signal independent of the presence or absence of other signal paths or their input and output signals.

The term " orthogonal proteases " means two or more proteases that differ in the order of the target substrate so that none of the orthogonal proteases do not split the target substrate of the second orthogonal protease.

The term " inducible protease " refers to the property of the protease, so that its enzymatic activity significantly changes in the presence of an input signal, which can at the same time be the output signal of the second signal path.

The term "binding peptide" refers to amino acid sequences whose role is to separate the individual domains of the assembled protein and to enable their proper spatial orientation. The role of the binding peptide in the fusion protein, the inclusion of which is optional, may include the insertion of the cleavage site, the posttranslational modification site, the marking sequence, or the localization signal.

The term " cleavage site " refers to the amino acid sequence to which a specific protease can bind and within this sequence a protein is cleaved by peptide binding hydrolysis. The term " labeling sequences " refers to the amino acid sequences added to the protein for easier purification, isolation, or detection of the protein. The term " localization signal " refers to an amino acid sequence that directs the protein to a particular localization in the cell. Localization signals differ according to the host organism in which the protein is expressed. The amino acid sequences of localization signals are well known to those skilled in the art, and it is also known which signal sequence operates in which organism.

The position of connecting peptides, marker sequences, cleavage sites and localization signals is arbitrary, but such that it allows functional expression of the protein and preserves the functions due to which these amino acid sequences have been selected, which is known to the experts of the region.

The term " cell " used herein refers to the eukaryotic cell, on a cellular or multicellular organism (cell line) cultured as a single cell, which is more closely used as a recipient of nucleic acid, and includes offspring of the original cell that has been genetically modified with nucleic acid . The term refers primarily to cells of higher developed eukaryotic organisms, preferably vertebrates, preferably mammals. The term " cells " also refers to human cell lines and plant cells. Of course, the descendants of one cell are not necessarily completely identical to the parents in morphological form and in the whole DNA complement, due to the consequences of natural, random or planned mutations. "Genetically modified host cell" (also "recombinant host cell") is a host cell into which the nucleic acid has been introduced. An eukaryotic genetically modified host cell is formed such that a suitable nucleic acid or recombinant nucleic acid is introduced into the appropriate eukaryotic host cell. The invention hereinafter includes host cells and organisms comprising a nucleic acid according to the invention (transient or stable) bearing the record for operons according to the invention. Suitable host cells are known in the art and include eukaryotic cells. It is known that the protein can be expressed in cells of the following organisms: human, rodent, cattle, pork, poultry, rabbits and the like. Host cells may be grown cell lines of primary or immortalized cell lines.

The term " nucleic acids " used herein refers to a polymeric form of nucleotides of any length, ribonucleotides or deoxyribonucleotides and is not limited to one, two or more chain DNA or RNA, genomic DNA, cDNA, DNA-RNA hybrids, or phosphorothioate polymers spine, from purine and pyrimidine bases or other natural, chemical or biochemical modified, non-derivative or derivatized nucleotide bases.

The term " polypeptide ", " protein ", " peptide ", used herein refers to the polymeric form of amino acids of any length. The term " functional polypeptide " used herein refers to a polypeptide form of any length of amino acids expressing any function, such as: formation of a structure, targeting to a specific location, targeting organelles, facilitating and triggering chemical reactions, binding to other functional polypeptides.

The term "heterologous" used herein refers to the context of genetically modified host cells and refers to a polypeptide for which at least one of the following claims applies: (a) the polypeptide is foreign ("exogenous") for the host cell (in nature it is not present in найдем); (b) the polypeptide is naturally present ("endogenous") in a given host microorganism or host cell, but is produced in an unnatural (more than expected or in greater quantities than found in nature) amounts in a cell or differentiated in a nucleotide sequence from endogenous nucleotide sequences, so that the same protein (having the same or substantially similar amino acid sequence) as the endogen is produced in the unnatural (more than expected and more than found in nature) amounts in the cell.

The term " homologous " used herein refers to proteins or nucleic acids with a well-preserved amino acid or nucleotide sequence, preferably with at least 50% conservation and at least 20% conservation determined by protein or nucleic acid priming techniques known to those skilled in the art . Homologous nucleic acids are encoding for homologous proteins.

The term "recombinant" used herein means that a particular nucleic acid (DNA or RNA) is a product of various combinations of cloning, restriction and / or ligation leading to a construct having structurally encoding or non-coding sequences different from endogenous nucleic acids in the natural host system . In general, a DNA sequence encoding a structurally coding sequence may be aggregated from the cDNA fragments or from short oligonucleotide linkers or from synthetic oligonucleotides from which a synthetic nucleic acid is obtained which can be expressed from the recombinant transcription unit in cellular or in the cell-free transcription and trasnlation system. Such a sequence can be used in the form of an open reading frame and there is no interference due to internal unmanned sequences, introns, which are usually present in eukaryotic genes. Genomic DNA containing important sequences can also be used to form a recombinant gene or transcription unit. Sequences of untranslated DNA may be present at the 5'- or 3'-end of an open reading frame, where such sequences do not affect the manipulation or expression of the coding regions, and can act as modulators for the production of the desired products through various mechanisms.

The input of vectors into host cells is carried out by conventional methods known from the prior art, and the methods relate to transformation or transfection and include: chemical input, electroporation, micro-injection, DNA lipofection, cellular sonication, gene bombardment, viral DNA input, and the like. The entry of DNA may be of transient character or stable. The introduction of a transitory character refers to the insertion of a DNA with a vector that does not incorporate the DNA of the invention into the cell genome. A stable entry is achieved by incorporating DNA according to the invention into the host genome. The insertion of a DNA according to the invention, in particular, for the preparation of a host organism having stable DNA incorporation according to the invention, can be controlled by the presence of markers. The DNA marker marker refers to resistance to antibiotics or chemicals and may be included on a DNA vector according to the invention or on a separate vector.

Implementation examples, which will be described in more detail, are designed to best describe the invention. These descriptions have no intention of limiting the scope of the invention and its applicability, but are merely intended to provide a better understanding of the invention and its use.

Implementation examples

Example 1: Preparation of cells comprising a signal pathway mediated by split proteases

Preparation of DNA records for orthogonal split proteases and their targets

In order to prepare DNA constructs, inventors used molecular biology methods such as: chemical transformation of competent cells of E. coli, plasmid DNA isolation, polymerase polymerase (PCR), reverse transcription - PCR, PCR bonding, nucleic acid concentration determination, DNA electrophoresis agarose gel, isolation of fragments of DNA from agarose gels, chemical synthesis of DNA, DNA cutting with restriction enzymes, plasmid vectors cutting, ligation of DNA fragments, purification of plasmid DNA in large quantities. The exact course of experimental techniques and methods are well known to the experts in the field and are described in the manuals of molecular biology.

For all work we used sterile techniques of work, which are also well known to the experts in the field. All plasmids, completed constructs and partial constructs were transformed into Escherichia coli bacteria by chemical transformation. Plasmids for transfection into cell lines (animal, plant or human) have been isolated using a DNA isolation kit that removes endotoxins. In the described cases, the proteases were selected from the proteases of the NIa family of potivirus proteins, specifically the SuMMV, SbMV, PPV and TEV proteases. Identified fission sequences with each of the described proteases are known to those of skill in the art. Depending on the similarity of the amino acid sequence between these proteases and the already known split protease TEV, nucleotide records for split proteases in fusion with dimerization domains have been prepared. In the described cases, the light-inducing domains of CRY2 and CIBN (Kennedy et al., 2010) and the rapamycin inducible domains of FKBP and FRB were selected as dimerization domains (Sabatini et al., 1994; Brown et al., 1994; Sabers et al., 1995).

The sequences of split protease fragments according to the invention are listed in Table 1. These fragments do not in themselves form active enzymes. The final gene constructs of split proteases in fusion with dimerization domains that allow reconstitution into the working enzyme are listed in Table 2. The remaining sequences used to illustrate the invention are listed in Table 3. All operons were prepared by techniques according to methods known to those skilled in the art. The operones were stopped in suitable plasmids suitable for eukaryotic systems. The suitability of the nucleotide sequence was confirmed by the inventors by sequencing and restriction analyzes.

Table 1: A list of the split proteases sequences that were used to illustrate the invention and their recognizable cleavage sites.

Table 2: Splitted proteases with dimerization domains that were used to illustrate the invention.

Table 3: Fusion proteins and operones, with the exception of the split proteases that were used to illustrate the invention.

Cell culturing methods and techniques are well known to those skilled in the art, and are therefore briefly described in order to illustrate the embodiment. Cell lines of HEK293T cells were grown at 37 ° C and 5% CO2. For cultivation, DMEM medium containing 10% FBS was used, containing all necessary nutrients and growth factors. When the cell culture reached the density, the cells were grafted into a new breeding vessel and / or diluted. For the use of cells in experiments, the number of cells was determined by the hemocytometer and washed by 2.5x104 per hole in the microtiter plate with 96 holes 18-24 hours before the transfection. The glued plates were incubated at 37 ° C and 5% CO2 until the cells were 50-70% confluently transfected for transfection by transfection reagent. The transfection was carried out according to the instructions of the transfection reagent manufacturer (e.g., JetPei, Lipofectamine 2000) adapted for the microtiter plate used.

Example 2: Activity of split proteases in mammalian cells induced by different signals and the orthogonality of cleavage with individual proteases

For the detection of protease activity, a reporting system based on the cyclic luciferase Fluc cyclic luciferase (Kanno et al., 2007) was used. The cyclic luciferase is prepared in such a way that the sequence of the amino acids 4-233 is transferred from the N-terminus to the C-terminus of the protein, wherein a connecting peptide with a recognizable cleavage site with one of the proteases is inserted between the previous C-terminus of the protein and the transferred protein sequence TEV, PPV, SuMMV or SbMV. The C-fragment of the intein DnaE from the organism Nostoc punctiforme is attached to the N-terminus of the sequence thus prepared, via the short linking peptide. The N-fragment of the intein DnaE and the organism N. punctiforme is attached to the C-terminus of the luciferase sequence transmitted, followed by the amino acid sequence for rapid decomposition of PEST-CL1, known to area experts. Such prepared luciferase forms inactive cyclic proteins that, when cleaved with the target protease, break down and acquire the ability to catalyze.

The HEK293T cells in the 96-hole plates were transfected with plasmids one day before the experiment, bearing the record for one of the selected proteases or the two protease-forming split proteases and the plasmids bearing the record for the above-described reporting system and record for the luciferase of Renilla Reniformis Rluc (GenBank AF362545.1). Cells were stimulated by the addition of rapamycin to a final concentration of 1 μM 1 day before measurement or with a light wavelength of 455 nm in a specially prepared device 30 minutes before the measurement.

For analysis of the activity of the reporting proteins, the cells were lysed with buffer according to the manufacturer's instructions (Promega). We first measured the activity of Fluc followed by Rluc activity. Rluc is expressed independently of the input signals, and therefore its activity tells us the proportion of transfected cells, while Fluc activity shows activation of cyclic luciferase after cleavage with protease. The Fluc / Rluc ratio (RLA - relative luciferase activity) therefore tells us the normalized value of stimulated cells with respect to transfected cells.

Results:

From Figure 2, it is shown that each of the TEV, PPV, SuMMV and SbMV proteases efficiently cleans cyclic luciferase with an appropriate recognition site, while the activity of proteases on cyclic luciferases with an inadequate recognizable site is negligible. In this experiment, the entire protease sequence was used.

Protease TEV, PPV, SbMV and SuMMV were split into two fragments and linked to the ligand-binding domains of FKBP and FRB. From Fig. 3A, the split proteins TEV, PPV, SuMMV and SbMV with dimerization domains FKBP and FRB are cleaved by luciferase with the appropriate recognition site with the addition of rapamycin.

TEV and PPV protease fragments were also prepared in fusion with the proteins CRY2 and CIBN, which are known to be dimerised with blue-light stimulation. From Figures 3B and 3C it is shown that the split proteins TEV and PPV in fusion with the dimerization domains CRY2 and CIBN split cyclic luciferase with a suitable recognizable site upon stimulation with blue light.

Example 3: Control of orthogonal signal pathways with raceed proteases and various input signals

To detect the activity of two orthogonal signaling pathways, in addition to cyclic luciferase, the TAL (N) -VP16-TEVs-KRAB transcription factor has been prepared since cleavage with the protease-dependent transcription factor. The transcription factor was prepared in such a way that at the C-terminus of the TAL DNA binding domain, which is well known to the field experts, the sequence for the activation domain VP16 was followed, followed by a binding peptide with a recognizable sequence for cleaving the TEV protease and the repression domain KRAB. VP16 and KRAB are also well-known to the field experts. During the cleavage, the transcription factor changes the mode of action from repression to the activation of the transcription of genes. To determine the activity of the transcription factor, a gene for the yellow fluorescence protein mCitrine was inserted into the plasmid for minimal promotios with binding sites for the DNA-binding domain TAL.

The HEK293T cells, implanted in 96-hole plates, were transfected one day before the experiment with plasmids bearing cyclic luciferase records with a recognizable cleavage site with PPV protease, a transcription factor TAL (N) -VP16-TEVs-KRAB, mCitrin under the appropriate promotional and a record for luciferase Rluc and a labeled plasmid with a TEV or PPV protease record.

To analyze the activity of the mCitrin reporting protein, the cells were removed from the media and then flushed by fluorescence at the SynergyMX plate reader (manufactured by BioTek) with excitation at a wavelength of 512 nm and emission at a wavelength of 532 nm. The fluorescence of untransfected cells was subtracted from the value obtained. For the analysis of the activity of the reporting protein cyclic luciferase, the cells were lysed with buffer according to the manufacturer's instructions (Promega) and then shifted the activity of FLuc and Rluc as in the above experiment.

Result:

From Figure 4 it can be seen that in the presence of TEV protease only activity of the luciferase rapporteur increases, and in the presence of PPV protease only the activity of the fluorescence reporter increases. In the presence of both orthogonal proteases, the activity of both reporters is increased. This confirms that signal paths are orthogonal.

Example 4: Logical functions by transmitting a signal with proteases

Logical functions NOR and A NIMPLY B have been developed as examples of the logical circuit with signal transfer with proteases, the latter being the equivalent composite logic function A AND NOT B.

For the NOR function (FIG. 5A), a rapeseed split luciferase was used, comprised of an N-terminal luciferase fragment linked via a cleavage site for the TEV protease with an AP4 peptide and a C-terminal luciferase fragment, which is linked via a cleavage site for the PPV protease with the peptide P3 . Peptides P3 and AP4 form a wound helix, which allows the reconstitution of luciferase fragments in the active enzyme. The splitting of this rapporteur with the protease TEV cleaves the N-terminals of the luciferase fragment from the AP4 peptide, thereby preventing the formation of a functional reporting enzyme. Similar cleavage with the PPV protease clears the C-terminal luciferase fragment from P3 peptide, thereby preventing the formation of a functional reporting enzyme. Therefore, the output signal (activity of luciferase) can be detected only in the absence of input signals.

Cells of HEK293T, implanted in 96-hole plates, were transfected with plasmids that were recorded with Rluc luciferase, nLuc-TEVs-AP4 and P3-PPVs-cLuc luciferase, and as marked plasmidoma with TEV protease and PPV protease, one day before the experiment. The activity of the reporting proteins Fluc and Rluc was measured as described above.

Result:

From Figure 5B it can be seen that a decrease in the activity of the reporter was observed when coexpression of any of the selected proteases. This is in line with the expected function of the NOR function.

For the function A NIMPLY B (Fig. 6A), the rapeseed split protease was also used, but in this case it consists of an N-terminal luciferase associated with the peptide AP4, which is further linked to the P4mS peptide by the cleavage site for the TEV protease. The system is added to the C-terminal luciferase fragment bound to the P3 peptide via the cleavage site for PPV protease. The AP4 and P3mS peptides form a wrapped helix, which prevents the formation of a wrapped helix between AP4 and P3 and thus the reconstitution of the functional enzyme of luciferase. When the TEV protector is vaccinated, the formation of the wrapped helix between ΑΡ4 and P3mS destabilizes, since it cleaves the connecting peptide between them. Since the P3 peptide forms a more stable, wound helix with AP4, there is now a reconstitution of luciferase, but only in the absence of PPV protease, since it cleaves the C-terminal fragment of luciferase from the peptide P3. The output signal (activity of luciferase) can therefore be detected only when cleavage with TEV protease and absence of cleavage with PPV protease.

Cells of HEK293T, implanted in 96-hole plates, were transfected one day before the experiment with plasmids bearing the Rluc luciferase, the nLuc-AP4-TEVs-P3mS and P3-PPVs-cLuc reporting protein, and plasmid TEV with inducible CRY2 and CIBN domains, and plasmids bearing split PPV proteases with inducible FKBP and FRB domains. Cells were stimulated by the addition of rapamycin to a final concentration of 1 μM or with a light wavelength of 455 nm in a specially prepared device 15 minutes before the measurement. The activity of the reporting proteins Fluc and Rluc was measured as described above.

Result:

From Figure 6B it can be seen that an increased activity of the reporter was observed only when the cells were stimulated with light that induces the activation of the TEV protease in the absence of rapamycin, which otherwise induces the activation of the PPV protease. This is consistent with the expected function of A N1MPLY B function, where the input signals A and B are light and rapamycin.

List of sequences

SEQ0ENCE LISTING <110> EN-FIST Chemistry Institute of Excellence <120> Combination of split orthogonal proteases with dimerization domains that allow assembly <130> - <160> 84 <170> Patent version 3.5 <210> 1 <211> 732

<212> DNA <213> Tobacco etch virus <220> <221> CDS <222> (1) .. (732) <400> 1 atg gga gaa agc ttg ttt aag gga cca cgt gat tac aac ccg ata tcg 48

Met Gly Glu Ser Leu Phe Lys Gly Pro Arg Asp Tyr Asn Pro Ile Ser 15 10 15 agc acc att tgt cac ttg acg aat gaa tet gat ggg cac aca aca tcg 96

Ser Thr Ile Cys His Leu Thr Asn Glu Ser Asp Gly His Thr Thr Ser 20 25 30 ttg tat ggt att gga ttt ggt ccc ttc ate att aca aac aag cac ttg 144

Leu Tyr Gly Ile Gly Phe Gly Pro Phe Ile Ile Thr Asn Lys His Leu 35 40 45 ttt aga aga aat aat gga aca ctg ttg gtc caa tca cta cat ggt gta 192

Phe Arg Arg Asn Gly Thr Leu Leu Val Gin Ser Leu His Gly Val 50 55 60 ttc aag gtc aag aac acc acg act ttg caa caa cac ete att gat ggg 240

Phe Lys Val Lys Asn Thr Thr Thr Leu Gin Gin His Leu Ile Asp Gly 65 70 75 80 agg gac atg ata att att ege atg cct aag gat ttc cca cca ttt cct 288

Arg Asp Met Ile Ile Arg Met Pro Lys Asp Phe Pro Pro Phe Pro 85 90 95 caa aag ctg aaa ttt aga gag cca caa agg gaa gag ege ata tgt ctt 336

Gin Lys Leu Lys Phe Arg Glu Pro Gin Arg Glu Glu Arg Ile Cys Leu 100 105 110 gtg aca acc aac ttc caa act aag agc atg tet agc atg gtg tca gac 384

Val Thr Thr Asr Phe Gin Thr Lys Ser Met Ser Ser Met Serp Asp 115 120 125 acc agt tgc aca ttc cct tca tet gat ggc ata ttc tgg aag cat tgg 432

Thr Ser Cys Thr Phe Pro Ser Ser Asp Gly Ile Phe Trp Lys His Trp 130 135 140 att caa acc aag gat ggg cag tgt ggc agt cca thta gta tca act aga 480

Ile Gin Thr Lys Asp Gly Gin Cys Gly Ser Pro Leu Val Ser Thr Arg 145 150 155 160 gat ggg ttc att gtt ggt ata cac tca gca tcg aat ttc acc aac aca 528

Asp Gly Phe Ile Val Gly Ile His Ser Ala Ser Asn Phe Thr Asn Thr 165 170 175 aac aat tat ttc aca agc gtg ccg aaa aac ttc atg gaa ttg ttg aca 576

Asn Asn Tyr Phe Thr Ser Val Pro Lys Asn Phe Met Glu Leu Leu Thr 180 185 190 aat cag gag gcg cag cag tgg gtt agt ggt tgg ega tta aat get gac 624

Asn Gin Glu Ala Gin Gin Trp Val Ser Gly Trp Arg Leu Asn Ala Asp 195 200 205 tta gta ttg tgg ggg ggc cat aaa gtt ttc atg agc aaa cct gaa gag 672

Ser Val Leu Trp Gly Gly His Lys Val Phe Met Ser Lys Pro Glu Glu 210 215 220 cct ttt cag cca gtt aag gaa gcg act caa ete atg agt gaa ttg gtg 720

Pro Phe Gin Pro Val Lys Glu Ala Thr Gin Leu Met Ser Glu Leu Val 225 230 235 240 tac tcg caa taa 732

Tyr Ser Gin <210> 2 <211> 243

<212> PRT <213> Tobacco etch virus <400> 2

Met Gly Glu Ser Leu Phe Lys Gly Pro Arg Asp Tyr Asn Pro Ile Ser 15 10 15

Ser Thr Ile Cys His Leu Thr Asn Glu Ser Asp Gly His Thr Thr Ser 20 25 30

Leu Tyr Gly Ile Gly Phe Gly Pro Phe Ile Ile Thr Asn Lys His Leu 35 40 45

Phe Arg Arg Asn Asn Gly Thr Leu Leu Val Gin Ser Leu His Gly Val 50 55 60

Phe Lys Val Lys Asn Thr Thr Thr Leu Gin Gin His Leu Ile Asp Gly 65 70 75 80

Arg Asp Met Ile Ile Arg Met Pro Lys Asp Phe Pro Pro Phe Pro 85 90 95

Gin Lys Leu Lys Phe Arg Glu Pro Gin Arg Glu Glu Arg Ile Cys Leu 100 105 110

Val Thr Thr Asr Phe Gin Thr Lys Ser Met Ser Ser Met Serp Asp 115 120 125

Thr Ser Cys Thr Phe Pro Ser Ser Asp Gly Ile Phe Trp Lys His Trp 130 135 140

Ile Gin Thr Lys Asp Gly Gin Cys Gly Ser Pro Leu Val Ser Thr Arg 145 150 155 160

Asp Gly Phe Ile Val Gly Ile His Ser Ala Ser Asn Phe Thr Asn Thr 165 170 175

Asn Asn Tyr Phe Thr Ser Val Pro Lys Asn Phe Met Glu Leu Leu Thr 180 185 190

Asn Gin Glu Ala Gin Gin Trp Val Ser Gly Trp Arg Leu Asn Ala Asp 195 200 205

Ser Val Leu Trp Gly Gly His Lys Val Phe Met Ser Lys Pro Glu Glu 210 215 220

Pro Phe Gin Pro Val Lys Glu Ala Thr Gin Leu Met Ser Glu Leu Val 225 230 235 240

Tyr Ser Gin <210> 3 <211> 354

<212> DNA <213> Tobacco etch virus <220> <221> CDS <222> (1) .. (354) <400> 3 gga gaa agc ttg ttt aag gga cca cgt gat tac aac ccg ata tcg agc 48

Gly Glu Ser Leu Phe Lys Gly Pro Arg Asp Tyr Asn Pro Ile Ser Ser 15 10 15 acc att tgt cac ttg acg aat gaa tet gat ggg cae aca aca tcg ttg 96

Thr Ile Cys His Leu Thr Asn Glu Ser Asp Gly His Thr Thr Ser Leu 20 25 30 tat ggt att gga ttt ggt ccc ttc ate att aca aac aag cac ttg ttt 144

Tyr Gly Ile Gly Phe Gly Pro Phe Ile Ile Thr Asn Lys His Leu Phe 35 40 45 aga aga aat aat gga aca ctg ttg gtc caa tca cta cat ggt gta ttc 192

Arg Arg Asn Asn Gly Thr Leu Leu Val Gin Ser Leu His Gly Val Phe 50 55 60 aag gtc aag aac acc acg act ttg caa caa cac ete att gat ggg agg 240

Lys Val Lys Asn Thr Thr Thr Leu Gin Gin His Leu Ile Asp Gly Arg 65 70 75 80 gac atg atta ege atg cct aag gat ttc cca cca ttt cct caa 288

Asp Met Ile Ile Ile Arg Met Pro Lys Asp Phe Pro Pro Phe Pro Gin 85 90 95 aag ctg aaa ttt aga gag cca caa agg gaa gag cgc ata tgt ctt gtg 336

Lys Leu Lys Phe Arg Glu Pro Gin Arg Glu Glu Arg Ile Cys Leu Val 100 105 110 aca acc aac ttc caa act 354

Thr Thr Asn Phe Gin Thr 115 <210> 4

<211> 118 <212> PRT <213> Tobacco etch virus <400> 4

Gly Glu Ser Leu Phe Lys Gly Pro Arg Asp Tyr Asn Pro Ile Ser Ser 15 10 15

Thr Ile Cys His Leu Thr Asn Glu Ser Asp Gly His Thr Thr Ser Leu 20 25 30

Tyr Gly Ile Gly Phe Gly Pro Phe Ile Ile Thr Asn Lys His Leu Phe 35 40 45

Arg Arg Asn Asn Gly Thr Leu Leu Val Gin Ser Leu His Gly Val Phe 50 55 60

Lys Val Lys Asn Thr Thr Thr Leu Gin Gin His Leu Ile Asp Gly Arg 65 70 75 80

Asp Met Ile Ile Ile Arg Met Pro Lys Asp Phe Pro Pro Phe Pro Gin 85 90 95

Lys Leu Lys Phe Arg Glu Pro Gin Arg Glu Glu Arg Ile Cys Leu Val 100 105 110

Thr Thr Asr Phe Gin Thr 115 <210> 5 <211> 372

<212> DNA <213> Tobacco etch virus <220> <221> CDS <222> (1) .. (372) <400> 5 aag agc atg tet agc atg gtg tca gac acc agt tgc aca ttc cct tca 48

Lys Ser Met Ser Ser Met Serp Asp Thr Ser Cys Thr Phe Pro Ser 15 10 15 tet gat ggc ata ttc tgg aag cat tgg att caa acc aag gat ggg cag 96

Ser Asp Gly Ile Phe Trp Lys His Trp Ile Gin Thr Lys Asp Gly Gin 20 25 30 tgt ggc agt cca tta gta tca act aga gat ggg ttc att gtt ggt ata 144

Cys Gly Ser Pro Leu Val Ser Thr Arg Asp Gly Phe Ile Val Gly Ile 35 40 45 cac tca gta teg aat ttc acc aac aca aac aat tat tc aca agc gtg 192

His Ser Ala Ser Asn Phe Thr Asn Thr Asn Asn Tyr Phe Thr Ser Val 50 55 60 ccg aaa aac ttc atg gaa ttg ttg aca aat cag gag gcg cag cag tgg 240

Pro Lys Asn Phe Met Glu Leu Leu Thr Asn Gin Glu Ala Gin Gin Trp 65 70 75 80 gtt agt ggt tgg ega tta aat get gac tca gta ttg tgg ggg ggc cat 288

Val Ser Gly Trp Arg Leu Asn Ala Asp Ser Val Leu Trp Gly Gly His 85 90 95 aaa gtt ttc atg agc aaa cct gaa gag cct ttt cag cca gtt aag gaa 336

Lys Val Phe Met Ser Lys Pro Glu Glu Pro Phe Gin Pro Val Lys Glu 100 105 110 gcg act caa ete atg agt gaa ttg gtg tac teg caa 372

Ala Thr Gin Leu Met Ser Glu Leu Val Tyr Ser Gin 115 120 <210> 6 <211> 124

<212> PRT <213> Tobacco etch virus <40Q> 6

Lys Ser Met Ser Ser Met Ser Ser Ser Asp Thr Ser Cys Thr Phe Pro Ser 15 10 15

Ser Asp Gly Ile Phe Trp Lys His Trp Ile Gin Thr Lys Asp Gly Gin 20 25 30

Cys Gly Ser Pro Leu Val Ser Thr Arg Asp Gly Phe Ile Val Gly Ile 35 40 45

His Ser Ala Ser Asn Phe Thr Asn Thr Asn Asn Tyr Phe Thr Ser Val 50 55 60

Pro Lys Asn Phe Met Glu Leu Leu Thr Asn Gin Glu Ala Gin Gin Trp 65 70 75 80

Val Ser Gly Trp Arg Leu Asn Ala Asp Ser Val Leu Trp Gly Gly His 85 90 95

Lys Val Phe Met Ser Lys Pro Glu Glu Pro Phe Gin Pro Val Lys Glu 100 105 110

Ala Thr Gin Leu Met Ser Glu Leu Val Tyr Ser Gin 115 120 <210> 7 <211> 735

<212> DNA <213> Plum pox virus <220> <221> CDS <222> (1) .. (735) <400> 7 atg agc aag agc ctg ttc cgc ggc ctg cgc gac tac aac ccc ate gcc 48

Met Ser Lys Ser Leu Phe Arg Gly Leu Arg Asp Tyr Asn Pro Ile Ala 15 10 15 agc agc ate tgc cag ctg aac aac agc agc ggc gcc cgc cag agc gag 96

Ser Ser Ile Cys Gin Leu Asn Asn Ser Ser Gly Ala Arg Gin Ser Glu 20 25 30 atg ttc ggc ctg ggc ttc ggc ggc ctg ate gtg acc aac cag cac ctg 144

Met Phe Gly Le Gly Le Gle Le Gle Gle Le Thé Asle Gin His Leu 35 40 45 ttc aag cgc aac gac ggc gag ctg acc ate cgc agc cac cac ggc gag 192

Phe Lys Arg Asn Asp Gly Glu Leu Thr Ile Arg Ser His His Gly Glu 50 55 60 ttc gtg gtg aag gac acc aag acc ctg aag ctg ctg ccc tgc aag ggc 240

Phe Val Val Lys Asp Thr Lys Thr Leu Lys Leu Leu Leu Leys Pro Cys Lys Gly 65 70 75 80 cgc gac ate gtg ate ate cgc ctg ccc aag gac ttc ccc ccc ttc ccc 288

Arg Asp Ile Val Ile Ile Arg Leu Pro Lys Asp Phe Pro Pro Phe Pro 85 90 95 aag cgc ctg caa ttc cgc acc ccc acc acc gag cgc gtg tgc ctg 336

Lys Arg Leu Gin Phe Arg Thr Thr Thr Thr Thr Glu Asp Arg Val Cys Leu 100 105 110 ate ggc agc aac ttc cag acc aag agc ate agc agc acc atg agc gag 384

Ile Gly Ser Asn Phe Gin Thr Lys Ser Ile Ser Ser Thr Met Ser Glu 115 120 125 acc agc gcc acc tac ccc gtg gac aac agc cac ttc tgg aag cac tgg 432

Thr Ser Ala Thr Tyr Pro Val Asp Asn Ser His Phe Trp Lys His Trp 130 135 140 ate agc acc aag gac ggc cac tgc ggc ctg ccc ate gtg agc acc cgc 480

Ile Ser Thr Lys Asp Gly His Cys Gly Leu Pro Ile Val Ser Thr Arg 145 150 155 160 gac ggc agc ate ctg ggc ctg cac agc ctg gcc aac agc acc aac acc 52 8

Asp Gly Ser Ile Leu Gly Leu His Ser Leu Ala Asn Ser Thr Asn Thr 165 170 175 cag aac ttc tac gcc gcc tcc ccc gac aac ttc gag acc acc tac ctg 576

Gin Asn Phe Tyr Ala Ala Phe Pro Asp Asn Phe Glu Thr Thr Tyr Leu 180 185 190 agc aac cag gac aac gac aac tgg ate aag cag tgg cgc tac aac ccc 624

Ser Asn Gin Asp Asn Asp Asp Trp Ile Lys Gin Trp Arg Tyr Asn Pro 195 200 205 gac gag gtg tgc tgg ggc agc ctg caa ctg aag cgc gac ate ccc cag 672

Asp Glu Val Cys Trp Gly Ser Leu Gin Leu Lys Arg Asp Ile Pro Gin 210 215 220 agc ccc ttc acc ate tgc aag ctg acc gac ctg gac ggc gag ttc 720

Ser Pro Phe Thr Ile Cys Lys Leu Leu Thr Asp Leu Asp Gly Plu 225 230 235 240 gtg tac acc cag taa 735

Val Tyr Thr Gin <210> 8 <211> 244

<212> PRT <213> Plum pox virus <400> 8

Met Ser Lys Ser Leu Phe Arg Gly Leu Arg Asp Tyr Asn Pro Ile Ala 15 10 15

Ser Ser Ile Cys Gin Leu Asn Asn Ser Ser Gly Ala Arg Gin Ser Glu 20 25 30

Met Phe Gly Le Gly Gly Gly Gly Leu Ile Val Thr Asn Gin His Leu 35 40 45

Phe Lys Arg Asn Asp Gly Glu Leu Thr Ile Arg Ser His His Gly Glu 50 55 60

Phe Val Val Lys Asp Thr Lys Thr Leu Lys Leu Leu Pro Cys Lys Gly 65 70 75 80

Arg Asp Ile Val Ile Ile Arg Leu Pro Lys Asp Phe Pro Pro Phe Pro 85 90 95

Lys Arg Leu Gin Phe Arg Thr Pro Thr Thr Glu Asp Arg Val Cys Leu 100 105 110

Ile Gly Ser Asn Phe Gin Thr Lys Ser Ile Ser Ser Thr Met Ser Glu 115 120 125

Thr Ser Ala Thr Tyr Pro Val Asp Asn Ser His Phe Trp Lys His Trp 130 135 140

Ile Ser Thr Lys Asp Gly His Cys Gly Leu Pro Ile Val Ser Thr Arg 145 150 155 160

Asp Gly Ser Ile Leu Gly Leu His Ser Leu Ala Asn Ser Thr Asn Thr 165 170 175

Gin Asn Phe Tyr Ala Ala Phe Pro Asp Asn Phe Glu Thr Thr Tyr Leu 180 185 190

Ser Asn Gin Asp Asn Asp Asp Trp Ile Lys Gin Trp Arg Tyr Asn Pro 195 200 205

Asp Glu Val Cys Trp Gly Ser Leu Gin Leu Lys Arg Asp Ile Pro Gin 210 215 220

Ser Pro Phe Thr Ile Cys Lys Leu Leu Thr Asp Leu Asp Gly Glu Phe 225 230 235 240

Val Tyr Thr Gin <210> 9 <211> 354

<212> DNA <213> Plum pox virus <220> <221> CDS <222> (1) .. (354) <400> 9 agc aag agc ctg ttc ege ggc ctg ege gac tac aac ccc ate gcc agc 48

Ser Lys Ser Leu Phe Arg Gly Leu Arg Asp Tyr Asn Pro Ile Ala Ser 15 10 15 agc ate tgc cag ctg aac aac agc agc ggc gcc ege cag agc gag atg 96

Ser Ile Cys Gin Leu Asn Asn Ser Ser Gly Ala Arg Gin Ser Glu Met 20 25 30 ttc ggc ctg ggc ttc ggc ggc ctg ate gtg acc aac cag cac ctg ttc 144

Phe Gly Lei Gly Ply Gly Gly Leu Ile Val Thr Asn Gin His Leu Phe 35 40 45 aag ege aac gac ggc gag ctg acc ate ege agc cac cac ggc gag ttc 192

Lys Arg Asn Asp Gly Glu Leu Thr Ile Arg Ser His His Gly Glu Phe 50 55 60 gtg gtg aag gac acc aag acc ctg aag ctg ctg ccc tgc aag ggc ege 240

Val Val Lys Asp Thr Lys Thr Leu Lys Leu Leu Leu Pro Cys Lys Gly Arg 65 70 75 80 gac ate gtg ate ate ege ctg ccc aag gac ttc ccc ccc ttc ccc aag 288

Asp Ile Val Ile Ile Arg Leu Pro Lys Asp Phe Pro Pro Phe Pro Lys 85 90 95 ege ctg caa ttc ege acc ccc acc acc gag gac ege gtg tgc ctg ate 336

Arg Leu Gin Phe Arg Thr Pro Thr Thr Glu Asp Arg Val Cys Leu Ile 100 105 110 ggc agc aac ttc cag acc 354

Gly Ser Asn Phe Gin Thr 115

<210> 10 <211> 118 <212> PRT <213> Plum pox virus <400> 10

Ser Lys Ser Leu Phe Arg Gly Leu Arg Asp Tyr Asn Pro Ile Ala Ser 15 10 15

Ser Ile Cys Gin Leu Asn Asn Ser Ser Gly Ala Arg Gin Ser Glu Met 20 25 30

Phe Gly Leu Gly Ply Gly Gly Leu Ile Val Thr Asn Gin His Leu Phe 35 40 45

Lys Arg Asn Asp Gly Glu Leu Thr Ile Arg Ser His His Gly Glu Phe 50 55 60

Val Val Lys Asp Thr Lys Thr Leu Lys Leu Leu Pro Cys Lys Gly Arg 65 70 75 80

Asp Ile Val Ile Ile Arg Leu Pro Lys Asp Phe Pro Pro Phe Pro Lys 85 90 95

Arg Leu Gin Phe Arg Thr Pro Thr Thr Glu Asp Arg Val Cys Leu Ile 100 105 110

Gly Ser Asn Phe Gin Thr 115 <210> 11 <211> 375

<212> DNA <213> Plum pox virus <220> <221> CDS <222> (1) .. (375) <400> 11 aag agc ate agc agc acc atg agc gag acc agc gcc acc tac ccc gtg 48

Lys Ser Ile Ser Ser Thr Met Ser Glu Thr Ser Ala Thr Tyr Pro Val 15 10 15 gac aac agc cac ttc tgg aag cac tgg ate agc acc aag gac ggc cac 96

Asp Asn Ser His Phe Trp Lys His Trp Ile Ser Thr Lys Asp Gly His 20 25 30 tgc ggc ctg ccc ate gtg agc acc ege gac ggc agc ate ctg ggc ctg 144

Cys Gly Leu Pro Ile Val Ser Thr Arg Asp Gly Ser Ile Leu Gly Leu 35 40 45 cac agc ctg gcc aac agc acc aac acc cag aac ttc tac gcc gcc ttc 192

His Ser Leu Ala Asn Ser Thr Asr Thr Gin Asn Phe Tyr Ala Ala Phe 50 55 60 ccc gac aac ttc gag acc acc tac ctg agc aac cag gac aac gac aac 240

Pro Asp Asn Phe Glu Thr Thr Thir Leu Ser Asn Asn Asn Asn Asn Asn 65 70 75 80 tgg aate cag tgg ege tac aac ccc gac gag gtg tgc tgg ggc agc 288

Trp Ile Lys Gin Trp Arg Tyr Asn Pro Asp Glu Val Cys Trp Gly Ser 85 90 95 ctg caa ctg aag cgc gac ate ccc cag agc ccc ttc acc ate tgc aag 336

Leu Gin Leu Lys Arg Asp Ile Pro Gin Ser Pro Phe Thr Ile Cys Lys 100 105 110 ctg acc gac ctg gac ggc gag ttc gtg tac acc cag 375

Leu Leu Thr Asp Leu Asp Gly Glu Phe Val Tyr Thr Gin 115 120 125 <210> 12 <211> 125

<212> PRT <213> Plum pox virus <400> 12

Lys Ser Ile Ser Ser Thr Met Ser Glu Thr Ser Ala Thr Tyr Pro Val 15 10 15

Asp Asn Ser His Phe Trp Lys His Trp Ile Ser Thr Lys Asp Gly His 20 25 30

Cys Gly Leu Pro Ile Val Ser Thr Arg Asp Gly Ser Ile Leu Gly Leu 35 40 45

His Ser Leu Ala Asn Ser Thr Asr Thr Gin Asn Phe Tyr Ala Ala Phe 50 55 60

Pro Asp Asn Phe Glu Thr Thr Tyr Leu Ser Asn Gin Asp Asn Asp Asn 65 70 75 80

Trp Ile Lys Gin Trp Arg Tyr Asn Pro Asp Glu Val Cys Trp Gly Ser 85 90 95

Leu Gin Leu Lys Arg Asp Ile Pro Gin Ser Pro Phe Thr Ile Cys Lys 100 105 110

Leu Leu Thr Asp Leu Asp Gly Glu Phe Val Tyr Thr Gin 115 120 125 <210> 13

<211> 806 <212> DNA <213> Sunflower mild mosaic virus <220> <221> CDS <222> (1) .. (804) <400> 13 atg gta acg gcc gcc agt gtg ctg gaa ttc gcg gcc get cta gag cca 48

Met Val Thr Ala Ala Ser Val Leu Glu Phe Ala Ala Ala Leu Glu Pro 15 10 15 cca tgg gcg tga gcc tga gcc gcg gcg tgc gcg act aca acg cca tca 96

Pro Trp Ala Ala Ala Ala Ala Ala Tha Thr Thr Pro Ser 20 25 30 gca gggg gg gg gg gg gg gg gg gg gg gg gc gca gca gcg

Ala Ala Trp Cys Ala Ala Pro Thr Thr Ala Ala Ala Ala Ala Pro 35 40 45 cca tgt acg gca teg get acg get get aca tca tca cca aca agc acc 192

Pro Cys Thr Ala Ser Ala Thr Ala Ala Thr Ser Ser Pro Thr Ser Thr 50 55 60 tgt tcc gcg aga aca acg gcc gcc tgc tga tca cca gcc acc acg gcg 240

Cys Ser Ala Arg Thr Thr Ala Ala Cys Ser Pro Ala Thr Thr Ala 65 70 75 agt aca tet gca aga aca gcg cca gcc tga agc tga gcc tgg tgc ccg 288

Ser Thr Ser Ala Arg Thr Ala Pro Ala Ser Ala Trp Cys Pro 80 85 90 gcc gcg aca tgc tgc tga gcc tgc cca agg act gcc ccc cct tcc 336

Ala Ala Thr Cys Cys Ser Ala Cys Pro Arg Thr Ala Pro Pro Ser 95 100 105 cca gca agc tga agt ttc gag agc cca cta gcg aag aaa agg ccg tgc 384

Pro Ala Ser Ser Phe Glu Ser Pro Leu Ala Lys Lys Arg Pro Cys 110 115 120 ttg tag tca caa act tcc agg aga agc ate ttt cca gca tgg tga gcg 432

Leu Ser Gin Thr Ser Arg Arg Ser Ile Phe Pro Ala Trp Ala 125 130 aga gca get gcg tgg tgc agc gcg agg aca gcc cca tet ggc gcc act 480

Arg Ala Ala Ala Trp Cys Ser Ala Arg Thr Ala Pro Ser Gly Ala Thr 135 140 145 150 gga tca gca cca agg acg gcc act gcg gcg ccc cca tcg tga gca tcc 528

Gly Ser Ala Pro Arg Thr Ala Thr Ala Ala Pro Pro Ser Ala Ser 155 160 165 gcg acg gct aca tca tcg gca gcc act gcg gcg aga acc cca tga cca 576

Ala Thr Ala Thr Ser Ser Ala Ala Thr Ala Ala Arg Thr Pro Pro 170 175 180 gca act tet tca cca gca tcc cca agg act tcc aga acc tgc tga acg 624

Ala Thr Ser Ser Pro Ala Ser Pro Arg Thr Ser Arg Thr Cys Thr 185 190 195 gca agg agg cca acg agt ggg tga gcg gct gga agt aca aca tcg acg 672

Ala Arg Arg Pro Thr Ser Gly Ala Ala Gly Ser Thr Thr Ser Thr 200 205 210 ccg tgt gct ggg gcg gcc tga gcg tgg tga acg acg ccc cca gcg agc 720

Pro Cys Ala Gly Ala Ala Ala Trp Thr Pro Pro Ala Ser 215 220 cct tca tca ccg cca agg tgg tga gcg ccc tgg aca ccg agg gca tca 768

Pro Ser Ser Pro Pro Arg Trp Ala Pro Trp Thr Pro Arg Ala Ser 225 230 235 agg tgc agt acc cat acg atg ttc cag att acg ctt aa 806

Arg Cys Ser Thr His Thr Met Phe Gin Ile Thr Leu 240 245 250 <210> 14 <211> 19

<212> PRT <213> Sunflower mild mosaic virus <400> 14

Met Val Thr Ala Ala Ser Val Leu Glu Phe Ala Ala Ala Leu Glu Pro 15 10 15

Pro Trp Ala <210> 15

<211> 16 <212> PRT <213> Sunflower mild mosaic virus <400> 15

Ala Ala Ala Cys Ala Thr Thr Pro Ala Ala Ala Ala Ala 15 10 15 <210> 16 <211> 34

<212> PRT <213> Sunflower mild mosaic virus <400> 16

Pro Thr Thr Ala Ala Ala Ala Pro Pro Cys Thr Ala Ser Ala Thr 15 10 15

Ala Ala Thr Ser Ser Pro Thr Ser Thr Cys Ser Ala Arg Thr Thr Ala 20 25 30

Ala Cys <210> 17 <211> 15

<212> PRT <213> Sunflower mild mosaic virus <400> 17

Ser Pro Ala Thr Thr Ala Ser Thr Ser Ala Arg Thr Ala Pro Ala 15 10 15 <210> 18 <211> 9

<212> PRT <213> Sunflower mild mosaic virus <400> 18

Ala Trp Cys Pro Ala Ala Thr Cys Cys 1 5 <210> 19 <211> 13

<212> PRT <213> Sunflower mild mosaic virus <400> 19

Ser Ala Cys Pro Arg Thr Ala Pro Pro Ser Pro Ala Ser 15 10 <210> 20 <211> 13

<212> PRT <213> Sunflower mild mosaic virus <400> 20

Ser Phe Glu Ser Pro Leu Ala Lys Lys Arg Pro Cys Leu 15 10

<210> 21 <211> 12 <212> PRT <213> Sunflower mild mosaic virus <400> 21

Ser Gin Thr Ser Arg Arg Ser Ile Phe Pro Ala Trp 15 10 <210> 22 <211> 30

<212> PRT <213> Sunflower mild mosaic virus <400> 22

Ala Arg Ala Ala Ala Trp Cys Ser Ala Arg Thr Ala Pro Ser Gly Ala 15 10 15

Thr Gly Ser Ala Pro Arg Thr Ala Thr Ala Ala Pro Pro Ser 20 25 30 <210> 23

<211> 16 <212> PRT <213> Sunflower mild mosaic virus <400> 23

Ala Ser Ala Thr Ala Thr Ser Ser Ala Ala Thr Ala Ala Arg Thr Pro 15 10 15 <210> 24 <211> 15

<212> PRT <213> Sunflower mild mosaic virus <400> 24

Pro Ala Thr Ser Ser Pro Ala Ser Pro Arg Thr Ser Arg Thr Cys 15 10 15 <210> 25

<211> 8 <212> PRT <213> Sunflower mild mosaic virus <400> 25

Thr Ala Arg Arg Pro Thr Ser Gly 1 5 <210> 26 <211> 14

<212> PRT <213> Sunflower mild mosaic virus <400> 26

Ala Ala Gly Ser Thr Thr Thr Thr Pro Cys Ala Gly Ala Ala 15 10 <210> 27 <211> 13

<212> PRT <213> Sunflower mild mosaic virus <400> 27

Thr Pro Pro Pro Ala Ser Pro Ser Ser Pro Pro Arg Trp 15 10 <210> 28 <211> 20

<212> PRT <213> Sunflower mild mosaic virus <400> 28

Ala Pro Trp Thr Pro Arg Ala Ser Arg Cys Ser Thr His Thr Met Phe 15 10 15

Gin Ile Thr Leu 20 <210> 29 <211> 354

<212> DNA <213> Sunflower mild mosaic virus <220> <221> CDS <222> (1) .. (354) <400> 29 ggc gtg agc ctg agc cgc ggc gtg cgc gac tac aac gcc ate agc agc 48

Gly Val Ser Leu Ser Arg Gly Val Arg Asp Tyr Asn Ala Ile Ser Ser 15 10 15 atg gtg tgc cgc gtg acc aac gac agc ggc agc agc agc acc acc atg 96

Met Val Cys Arg Val Thr Asn Asp Ser Gly Ser Ser Ser Thr Thr Met 20 25 30 tac ggc ate ggc tac ggc tgc tac ate ate acc aac aag cac ctg ttc 144

Tyr Gly Ile Gly Tyr Gly Cys Tyr Ile Ile Thr Asn Lys His Leu Phe 35 40 45 cgc gag aac aac ggc cgc ctg ctg ate acc agc cac cac ggc gag tac 192

Arg Glu Asn Asg Gly Arg Leu Leu Ile Thr Ser His His Gly Glu Tyr 50 55 60 ate tgc aag aac agc gcc agc ctg aag ctg agc ctg gtg ccc ggc cgc 240

Ile Cys Lys Asn Ser Ala Ser Leu Lys Leu Ser Leu Val Pro Gly Arg 65 70 75 80 gac atg ctg ctg ate cgc ctg ccc aag gac tgc ccc ccc ttc ccc agc 288

Asp Met Leu Leu Ile Arg Leu Pro Lys Asp Cys Pro Pro Phe Pro Ser 85 90 95 aag ctg aag ttt Cga gag ccc act agc gaa gaag aag gcc gtg ctt gta 336

Lys Leu Lys Phe Arg Glu Pro Thr Ser Glu Glu Lys Ala Val Leu Val 100 105 110 gtc aca aac ttc cag gag 354

Val Thr Asn Phe Gin Glu 115 <210> 30

<211> 118 <212> PRT <213> Sunflower mild mosaic virus <400> 30

Gly Val Ser Leu Ser Arg Gly Val Arg Asp Tyr Asn Ala Ile Ser Ser 15 10 15

Met Val Cys Arg Val Thr Asn Asp Ser Gly Ser Ser Ser Thr Thr Met 20 25 30

Tyr Gly Ile Gly Tyr Gly Cys Tyr Ile Ile Thr Asn Lys His Leu Phe 35 40 45

Arg Glu Asn Asn Gly Arg Leu Leu Ile Thr Ser His His Gly Glu Tyr 50 55 60

Ile Cys Lys Asn Ser Ala Ser Leu Lys Leu Ser Leu Val Pro Gly Arg 65 70 75 80

Asp Met Leu Leu Ile Arg Leu Pro Lys Asp Cys Pro Pro Phe Pro Ser 85 90 95

Lys Leu Lys Phe Arg Glu Pro Thr Ser Glu Glu Lys Ala Val Leu Val 100 105 110

Val Thr Asn Phe Gin Glu 115 <210> 31 <211> 369

<212> DNA <213> Sunflower mild mosaic virus <220> <221> CDS <222> (1) .. (369) <400> 31 aag cat ctt tcc agc atg gtg agc gag agc agc tgc gtg gtg cag cgc 48

Lys His Leu Ser Ser Met Val Ser Glu Ser Ser Cys Val Val Gin Arg 15 10 15 gag gac agc ccc ate tgg cgc cac tgg ate agc acc aag gac ggc cac 96

Glu Asp Ser Pro Ile Trp Arg His Trp Ile Ser Thr Lys Asp Gly His 20 25 30 tgc ggc gcc ccc ate gtg agc ate cgc gac ggc tac ate ate ggc agc 144

Cys Gly Ala Pro Ile Val Ser Ile Arg Asp Gly Tyr Ile Ile Gly Ser 35 40 45 cac tgc ggc gag aac ccc atg acc agc aac ttc ttc acc agc ate ccc 192

His Cys Gly Glu Asn Pro Met Thr Ser Asn Phe Phe Thr Ser Ile Pro 50 55 60 aag gac ttc cag aac ctg ctg aac ggc aag gag gcc aac gag tgg gtg 240

Lys Asp Phe Gin Asn Leu Leu Asn Gly Lys Glu Ala Asn Glu Trp Val 65 70 75 80 agc ggc tgg aag tac aac ate gac gcc gtg tgc tgg ggc ggc ctg agc 288

Ser Gly Trp Lys Tyr Asn Ile Asp Ala Val Cys Trp Gly Gly Leu Ser 85 90 95 gtg gtg aac gac gcc ccc agc gag ccc ttc ate acc gcc aag gtg gtg 336

Val Val Asn Asp Ala Pro Ser Glu Pro Phe Ile Thr Ala Lys Val Val 100 105 110 agc gcc ctg gac acc gag ggc ate aag gtg cag 369

Ser Ala Leu Asp Thr Glu Gly Ile Lys Val Gin 115 120 <210> 32 <211> 123

<212> PRT <213> Sunflower mild mosaic virus <400> 32

Lys His Leu Ser Ser Met Val Ser Glu Ser Ser Cys Val Val Gin Arg 15 10 15

Glu Asp Ser Pro Ile Trp Arg His Trp Ile Ser Thr Lys Asp Gly His 20 25 30

Cys Gly Ala Pro Ile Val Ser Ile Arg Asp Gly Tyr Ile Ile Gly Ser 35 40 45

His Cys Gly Glu Asn Pro Met Thr Ser Asn Phe Phe Thr Ser Ile Pro 50 55 60

Lys Asp Phe Gin Asn Leu Leu Asn Gly Lys Glu Ala Asn Glu Trp Val 65 70 75 80

Ser Gly Trp Lys Tyr Asn Ile Asp Ala Val Cys Trp Gly Gly Leu Ser 85 90 95

Val Val Asn Asp Ala Pro Ser Glu Pro Phe Ile Thr Ala Lys Val Val 100 105 110

Ser Ala Leu Asp Thr Glu Gly Ile Lys Val Gin 115 120 <210> 33 <211> 762

<212> DNA <213> Soybean mosaic virus <220> <221> CDS <222> (1). . (759) <400> 33 atg agc aag agc gtg tac aag ggc ctg cgc gac tac agc ggc ate agc 48

Met Ser Lys Ser Val Tyr Lys Gly Leu Arg Asp Tyr Ser Gly Ile Ser 15 10 15 acc ctg ate tgc cag ctg acc aac agc agc gac ggc cac aag gag acc 96

Thr Leu Ile Cys Gin Leu Thr Asn Ser Ser Asp Gly His Lys Glu Thr 20 25 30 atg ttc ggc gtg ggc tac ggc agc ttc ate ate acc aac ggc cac ctg 144

Met Phe Gly Val Gly Tyr Gly Ser Phe Ile Ile Thr Asn Gly His Leu 35 40 45 ttc ege ege aac aac ggc atg ctg acc gtg aag acc tgg cac ggc gag 192

Phe Arg Arg Asn Asn Gly Met Leu Thr Val Lys Thr Trp His Gly Glu 50 55 60 ttc gtg ate cac aac acc cag ctg aag ate cac ttc ate cag ggc 240

Phe Val Ile His Asn Thr Thr Gin Leu Lys Ile His Phe Ile Gin Gly 65 70 75 80 ege gac gtg ate ctg ate ege atg ccc aag gac ttc ccc ccc ttc ggc 288

Arg Asp Val Ile Leu Ile Arg Met Pro Lys Asp Phe Pro Pro Phe Gly 85 90 95 aag ege aac ctg ttc ege cag ccc aag ege gag gag ege gtg tgc atg 336

Lys Arg Asn Leu Phe Arg Gin Pro Lys Arg Glu Glu Arg Val Cys Met 100 105 110 gtg ggc acc aac ttc cag gag aag agc ctg ege gcc acc gtg agc gag 384

Val Gly Thr Asn Phe Gin Glu Lys Ser Leu Arg Ala Thr Val Ser Glu 115 120 125 agc agc atg ate ctg ccc gag ggc aag ggc agc ttc tgg ata cac tgg 432

Ser Ser Met Ile Leu Pro Glu Gly Lys Gly Ser Phe Trp Ile His Trp 130 135 140 ate acc acc cag gac ggc ttc tgc ggc ctg ccc ctg gtg agc gtg aac 480

Ile Thr Thr Gin Asp Gly Phe Cys Gly Leu Pro Leu Val Ser Val Asn 145 150 155 160 gac ggc cac ate gtg ggc ate cac ggc ctg acc agac aac gac agc gag 528

Asp Gly His Ile Val Gly Ile His Gly Leu Thr Ser Asn Asp Ser Glu 165 170 175 aag aac ttc ttc gtg ccc ctg acc gac ggc ttc gag aag gag tac ctg 576

Lys Asn Phe Phe Val Pro Leu Thr Asp Gly Phe Glu Lys Glu Tyr Leu 180 185 190 gag aac gcc gac aac ctg agc tgg gac aag cac tgg ttc tgg gag ccc 624

Glu Asn Ala Asp Asn Leu Ser Trp Asp Lys His Trp Phe Trp Glu Pro 195 200 205 agc aag ate gcc tgg ggc agc ctg aac ctg gtg gag gag cag ccc aag 672

Ser Lys Ile Ala Trp Gly Ser Leu Asn Leu Val Glu Glu Gin Pro Lys 210 215 220 gag gag ttc aag ate agc aag ctg gtg agc gac ctg ttc ggc aac acc 720

Glu Glu Phe Lys Ile Ser Lys Leu Val Ser Asp Leu Phe Gly Asn Thr 225 230 235 240 gtg acc gtg cag tac cca tac gat gtt cca gat tac get taa 762

Val Thr Val Gin Tyr Pro Tyr Asp Val Pro Asp Tyr Ala 245 250 <210> 34 <211> 253

<212> PRT <213> Soybean mosaic virus <400> 34

Met Ser Lys Ser Val Tyr Lys Gly Leu Arg Asp Tyr Ser Gly Ile Ser 15 10 15

Thr Leu Ile Cys Gin Leu Thr Asn Ser Ser Asp Gly His Lys Glu Thr 20 25 30

Met Phe Gly Val Gly Tyr Gly Ser Phe Ile Ile Thr Asn Gly His Leu 35 40 45

Phe Arg Arg Asn Asn Gly Met Leu Thr Val Lys Thr Trp His Gly Glu 50 55 60

Phe Val Ile His Asn Thr Thr Gin Leu Lys Ile His Phe Ile Gin Gly 65 70 75 80

Arg Asp Val Ile Leu Ile Arg Met Pro Lys Asp Phe Pro Pro Phe Gly 85 90 95

Lys Arg Asn Leu Phe Arg Gin Pro Lys Arg Glu Glu Arg Val Cys Met 100 105 110

Val Gly Thr Asn Phe Gin Glu Lys Ser Leu Arg Ala Thr Val Ser Glu 115 120 125

Ser Ser Met Ile Leu Pro Glu Gly Lys Gly Ser Phe Trp Ile His Trp 130 135 140

Ile Thr Thr Gin Asp Gly Phe Cys Gly Leu Pro Leu Val Ser Val Asn 145 150 155 160

Asp Gly His Ile Val Gly Ile His Gly Leu Thr Ser Asn Asp Ser Glu 165 170 175

Lys Asn Phe Phe Val Pro Leu Thr Asp Gly Phe Glu Lys Glu Tyr Leu 180 185 190

Glu Asn Ala Asp Asn Leu Ser Trp Asp Lys His Trp Phe Trp Glu Pro 195 200 205

Ser Lys Ile Ala Trp Gly Ser Leu Asn Leu Val Glu Glu Gin Pro Lys 210 215 220

Glu Glu Phe Lys Ile Ser Lys Leu Val Ser Asp Leu Phe Gly Asn Thr 225 230 235 240

Val Thr Val Gin Tyr Pro Tyr Asp Val Pro Asp Tyr Ala 245 250 <210> 35 <211> 354

<212> DNA <213> Soybean mosaic virus <220> <221> CDS <222> (1) .. (354) <400> 35 agc aag agc gtg tac aag ggc ctg cgc gac tac agc ggc ate agc acc 48

Ser Lys Ser Val Tyr Lys Gly Leu Arg Asp Tyr Ser Gly Ile Ser Thr 15 10 15 ctg ate tgc cag ctg acc aac agc agc gac ggc cac aag gag acc atg 96

Leu Ile Cys Gin Leu Thr Asn Ser Ser Asp Gly His Lys Glu Thr Met 20 25 30 ttc ggc gtg ggc tac ggc agc ttc ate ate acc aac ggc cac ctg ttc 144

Phe Gly Val Gly Tyr Gly Ser Phe Ile Ile Thr Asn Gly His Leu Phe 35 40 45 cgc cgc aac aac ggc atg ctg acc gtg aag acc tgg cac ggc gag ttc 192

Arg Arg Asn Asn Gly Met Leu Thr Val Lys Thr Trp His Gly Glu Phe 50 55 60 gtg ate cac aac acc acc cag ctg aag ate cac ttc ate cag ggc cgc 240

Val Ile His Asn Thr Thr Gin Leu Lys Ile His Phe Ile Gin Gly Arg 65 70 75 80 gac gtg ate ctg ate cgc atg ccc aag gac ttc ccc ccc ttc ggc aag 288

Asp Val Ile Leu Ile Arg Met Pro Lys Asp Phe Pro Pro Phe Gly Lys 85 90 95 cgc aac ctg ttc cgc cag ccc aag cgc gag gg cgc gtg tgc atg gtg 336

Arg Asn Leu Phe Arg Gin Pro Lys Arg Glu Glu Arg Val Cys Met Val 100 105 110 ggc acc aac ttc cag gag 354

Gly Thr Asn Phe Gin Glu 115 <210> 36

<211> 118 <212> PRT <213> Soybean mosaic virus <400> 36

Ser Lys Ser Val Tyr Lys Gly Leu Arg Asp Tyr Ser Gly Ile Ser Thr 15 10 15

Leu Ile Cys Gin Leu Thr Asn Ser Ser Asp Gly His Lys Glu Thr Met 20 25 30

Phe Gly Val Gly Tyr Gly Ser Phe Ile Ile Thr Asn Gly His Leu Phe 35 40 45

Arg Arg Asn Asn Gly Met Leu Thr Val Lys Thr Trp His Gly Glu Phe 50 55 60

Val Ile His Asn Thr Thr Gin Leu Lys Ile His Phe Ile Gin Gly Arg 65 70 75 80

Asp Val Ile Leu Ile Arg Met Pro Lys Asp Phe Pro Pro Phe Gly Lys 85 90 95

Arg Asn Leu Phe Arg Gin Pro Lys Arg Glu Glu Arg Val Cys Met Val 100 105 110

Gly Thr Asn Phe Gin Glu 115 <210> 37 <211> 375

<212> DNA <213> Soybean mosaic virus <220> <221> CDS <222> (1) .. (375) <400> 37 aag agc ctg cgc gcc agc gg agc atg ate ctg ccc gag 48

Lys Ser Leu Arg Ala Thr Val Ser Glu Ser Ser Met Ile Leu Pro Glu 15 10 15 ggc aag ggc agc ttc tgg ata cac tgg ate acc acc cag gac ggc ttc 96

Gly Lys Gly Ser Phe Trp Ile His Trp Ile Thr Thr Gin Asp Gly Phe 20 25 30 tgc ggc ctg ccc ctg gtg agc gtg aac gac ggc cac ate gtg ggc ate 144

Cys Gly Leu Pro Leu Val Ser Val Asn Asp Gly His Ile Val Gly Ile 35 40 45 cac ggc ctg acc agc aac gac agc gag aag aac ttc ttc gtg ccc ctg 192

His Gly Leu Thr Ser Asn Asp Ser Glu Lys Asn Phe Phe Val Pro Leu 50 55 60 acc gac ggc ttc gag aag gag tac ctg gag aac gcc gac aac ctg agc 240

Thr Asp Gly Phe Glu Lys Glu Tyr Leu Glu Asn Ala Asp Asn Leu Ser 65 70 75 80 tgg gac aag cac tgg tgg ggg ccc agc aag ate gcc tgg ggc agc 288

Trp Asp Lys His Trp Phe Trp Glu Pro Ser Lys Ile Ala Trp Gly Ser 85 90 95 ctg aac ctg gtg gag cag ccc aag gag gag ttc aag ate agc aag 336

Leu Asn Leu Val Glu Glu Gin Pro Lys Glu Glu Phe Lys Ile Ser Lys 100 105 110 ctg gtg agc gac ctg ttc ggc aac acc gtg acc gtg cag 375

Leu Val Ser Asp Leu Phe Gly Asn Thr Val Thr Val Gin 115 120 125 <210> 38 <211> 125

<212> PRT <213> Soybean mosaic virus <400> 38

Lys Ser Leu Arg Ala Thr Val Ser Glu Ser Ser Met Ile Leu Pro Glu 15 10 15

Gly Lys Gly Ser Phe Trp Ile His Trp Ile Thr Thr Gin Asp Gly Phe 20 25 30

Cys Gly Leu Pro Leu Val Ser Val Asn Asp Gly His Ile Val Gly Ile 35 40 45

His Gly Leu Thr Ser Asn Asp Ser Glu Lys Asn Phe Phe Val Pro Leu 50 55 60

Thr Asp Gly Phe Glu Lys Glu Tyr Leu Glu Asn Ala Asp Asn Leu Ser 65 70 75 80

Trp Asp Lys His Trp Phe Trp Glu Pro Ser Lys Ile Ala Trp Gly Ser 85 90 95

Leu Asn Leu Val Glu Glu Gin Pro Lys Glu Glu Phe Lys Ile Ser Lys 100 105 110

Leu Val Ser Asp Leu Phe Gly Asn Thr Val Thr Val Gin 115 120 125 <210> 39 <211> 711

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (708) <400> 39 atg gga gtg caa gtg gaa acc ate tcc ccg gga gac ggg ege acc ttc 48

Met Gly Val Gin Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe 15 10 15 ccc aag ege ggc cag acc tgc gtg gtg cac tac acc ggg atg ctt gaa 96

Pro Lys Arg Gly Gin Thr Cys Val Val His Tyr Thr Gly Met Leu Glu 20 25 30 gat gga aag aaa ttt gat tcc tcc cgg gac aga aac aag ccc ttt aag 144

Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys 35 40 45 ttt atg cta ggc aag cag gag gtg ate ega ggc tgg gaa gaa ggg gtt 192

Phe Met Leu Gly Lys Gin Glu Val Ile Arg Gly Trp Glu Glu Gly Val 50 55 60 gcc cag atg agt gtg ggt cag aga gcc aaa ctg act ata tet cca gat 240

Ala Gin Met Ser Val Gly Gin Arg Ala Lys Leu Thr Ile Ser Pro Asp 65 70 75 80 tat gcc tat ggt gcc act ggg cac cca ggc ate ate cca cca cat gcc 288

Tyr Ala Tyr Gly Ally Thr Gly His Pro Gly Ile Pro Pro His Ala 85 90 95 act ete gtc ttc gat gtg gag ctt cta aaa ctg gaa gga tcc gga agt 336

Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Gly Ser Gly Ser 100 105 110 aag agc atg tet agc atg gtg tca gac acc agt tgc aca ttc cct tca 384

Lys Ser Met Ser Ser Met Serp Asp Thr Ser Cys Thr Phe Pro Ser 115 120 125 tet gat ggc ata ttc tgg aag cat tgg att caa acc aag gat ggg cag 432

Ser Asp Gly Ile Phe Trp Lys His Trp Ile Gin Thr Lys Asp Gly Gin 130 135 140 tgt ggc agt cca tta gta tca act aga gat ggg ttc att gtt ggt ata 480

Cys Gly Ser Pro Leu Val Ser Thr Arg Asp Gly Phe Ile Val Gly Ile 145 150 155 160 cac tca gca teg aat ttc acc aac aca aac aat tat tc aca agc gtg 528

His Ser Ala Ser Asn Phe Thr Asn Thr Asn Asn Tyr Phe Thr Ser Val 165 170 175 ccg aaa aac ttc atg gaa ttg ttg aca aat cag gag gcg cag cag tgg 576

Pro Lys Asn Phe Met Glu Leu Leu Thr Asn Gin Glu Ala Gin Gin Trp 180 185 190 gtt agt ggt tgg ega tta aat get gac tca gta ttg tgg ggg ggc cat 624

Val Ser Gly Trp Arg Leu Asn Ala Asp Ser Val Leu Trp Gly Gly His 195 200 205 aaa gtt ttc atg agc aaa cct gaa gag cct ttt cag cca gtt aag gaa 672

Lys Val Phe Met Ser Lys Pro Glu Glu Pro Phe Gin Pro Val Lys Glu 210 215 220 gcg act caa ete atg agt gaa ttg gtg tac teg caa taa 711

Ala Thr Gin Leu Met Ser Glu Leu Val Tyr Ser Gin 225 230 235 <210> 40 <211> 236

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 40

Met Gly Val Gin Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe 15 10 15

Pro Lys Arg Gly Gin Thr Cys Val Val His Tyr Thr Gly Met Leu Glu 20 25 30

Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys 35 40 45

Phe Met Leu Gly Lys Gin Glu Val Ile Arg Gly Trp Glu Glu Gly Val 50 55 60

Ala Gin Met Ser Val Gly Gin Arg Ala Lys Leu Thr Ile Ser Pro Asp 65 70 75 80

Tyr Ala Tyr Gly Ally Thr Gly His Pro Gly Ile Pro Pro His Ala 85 90 95

Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Gly Ser Gly Set 100 105 110

Lys Ser Met Ser Ser Ser Ser Ser Asp Thr Ser Cys Thr Phe Pro Ser 115 120 125

Ser Asp Gly Ile Phe Trp Lys His Trp Ile Gin Thr Lys Asp Gly Gin 130 135 140

Cys Gly Ser Pro Leu Val Ser Thr Arg Asp Gly Ile Val Gly Ile 145 150 155 160

His Ser Ala Ser Asn Phe Thr Asn Thr Asn Asr Tyr Phe Thr Ser Val 165 170 175

Pro Lys Asn Phe Met Glu Leu Leu Thr Asn Gin Glu Ala Gin Gin Trp 180 185 190

Val Ser Gly Trp Arg Leu Asn Ala Asp Ser Val Leu Trp Gly Gly His 195 200 205

Lys Val Phe Met Ser Lys Pro Glu Glu Pro Phe Gin Pro Val Lys Glu 210 215 220

Ala Thr Gin Leu Met Ser Glu Leu Val Tyr Ser Gin 225 230 235 <210> 41 <211> 651

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (648) <400> 41 atg ate ete tgg cat gag atg tgg cat gaa ggc ctg gaa gag gca tet 48

Met Ile Leu Trp His Glu Met Trp His Glu Gly Leu Glu Glu Ala Ser 15 10 15 cgt ttg tac ttt ggg gaa agg aac gtg aaa ggc atg ttt gag gtg ctg 96

Arg Leu Tyr Phe Gly Glu Arg Asn Val Lys Gly Met Phe Glu Val Leu 20 25 30 gag ccc ttg cat get atg atg gaa cgg ggc ccc cag act ctg aag gaa 144

Glu Pro Leu His Ala Met Met Glu Arg Gly Pro Gin Thr Leu Lys Glu 35 40 45 aca tcc ttt aat cag gcc tat ggt ega gat tta atg gag gcc caa gag 192

Thr Ser Phe Asn Gin Ala Tyr Gly Arg Asp Leu Met Glu Ala Gin Glu 50 55 60 tgg tgc agg aag tac atg aaa tca ggg aat gtc aag gac ete ete caa 240

Trp Cys Arg Lys Tyr Met Lys Ser Gly Asn Val Lys Asp Leu Leu Gin 65 70 75 80 gcc tgg gac ete tat tat cat gtg ttc ega ega ate tca aag gga tcc 288

Ala Trp Asp Leu Tyr Tyr His Val Phe Arg Arg Ile Ser Lys Gly Ser 85 90 95 gga agt gga gaa agc ttg ttt aag gga cca cgt gat tac aac ccg ata 336

Gly Ser Gly Glu Ser Leu Phe Lys Gly Pro Arg Asp Tyr Asn Pro Ile 100 105 110 teg agc acc att tgt cac ttg acg aat gaa tet gat ggg cac aca aca 384

Ser Ser Thr Ile Cys His Leu Thr Asn Glu Ser Asp Gly His Thr Thr 115 120 125 teg ttg tat ggt att gga ttt ggt ccc ttc ate att aca aac aag cac 432

Ser Leu Tyr Gly Ile Gly Phe Gly Pro Phe Ile Ile Thr Asn Lys His 130 135 140 ttg ttt aga aga aat aat gga aca ctg ttg gtc caa tca cta cat ggt 480

Leu Phe Arg Arg Asn Asn Gly Thr Leu Leu Val Gin Ser Leu His Gly 145 150 155 160 gta ttc aag gtc aag aac acc acg act ttg caa caa cac ete att gat 528

Val Phe Lys Val Lys Asn Thr Thr Thr Leu Gin Gin His Leu Ile Asp 165 170 175 ggg agg gac atg ata att att cgc atg cct aag gat ttc cca cca ttt 576

Gly Arg Asp Met Ile Ile Arg Met Pro Lys Asp Phe Pro Pro Phe 180 185 190 cct caa aag Ctg aaa ttt aga gag cca caa agg gaa gag cgc ata tgt 624

Pro Gin Lys Leu Lys Phe Arg Glu Pro Gin Arg Glu Glu Arg Ile Cys 195 200 205 ctt gtg aca acc aac ttc caa act taa 651

Leu Val Thr Thr Asn Phe Gin Thr 210 215 <210> 42

<211> 216 <212> PRT <213> Artificial Seguence <220> <223> Synthetic Construct <400> 42

Met Ile Leu Trp His Glu Met Trp His Glu Gly Leu Glu Glu Ala Ser 15 10 15

Arg Leu Tyr Phe Gly Glu Arg Asn Val Lys Gly Met Phe Glu Val Leu 20 25 30

Glu Pro Leu His Ala Met Met Glu Arg Gly Pro Gin Thr Leu Lys Glu 35 40 45

Thr Ser Phe Asn Gin Ala Tyr Gly Arg Asp Leu Met Glu Ala Gin Glu 50 55 60

Trp Cys Arg Lys Tyr Met Lys Ser Gly Asn Val Lys Asp Leu Leu Gin 65 70 75 80

Ala Trp Asp Leu Tyr Tyr His Val Phe Arg Arg Ile Ser Lys Gly Ser 85 90 95

Gly Ser Gly Glu Ser Leu Phe Lys Gly Pro Arg Asp Tyr Asn Pro Ile 100 105 110

Ser Ser Thr Ile Cys His Leu Thr Asn Glu Ser Asp Gly His Thr Thr 115 120 125

Ser Leu Tyr Gly Ile Gly Phe Gly Pro Phe Ile Ile Thr Asn Lys His 130 135 140

Leu Phe Arg Arg Asn Gly Thr Leu Leu Val Gin Ser Leu His Gly 145 150 155 160

Val Phe Lys Val Lys Asn Thr Thr Thr Leu Gin Gin His Leu Ile Asp 165 170 175

Gly Arg Asp Met Ile Ile Ile Atg Met Pro Lys Asp Phe Pro Pro Phe 180 185 190

Pro Gin Lys Leu Lys Phe Arg Glu Pro Gin Arg Glu Glu Arg Ile Cys 195 200 205

Leu Val Thr Thr Asn Phe Gin Thr 210 215 <210> 43 <211> 759

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (756) <400> 43 atg gga gtg caa gtg gaa acc ate tcc ccg gga gac ggg cgc acc ttc 4g

Met Gly Val Gin Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe 15 10 15 ccc aag cgc ggc cag acc tgc gtg gtg cac tac acc ggg atg ctt gaa 96

Pro Lys Arg Gly Gin Thr Cys Val Val His Tyr Thr Gly Met Leu Glu 20 25 30 gat gga aag aaa ttt gat tcc tcc cgg gac aga aac aag ccc ttt aag 144

Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys 35 40 45 ttt atg cta ggc aag cag gag gtg ate ega ggc tgg gaa gaa ggg gtt 192

Phe Met Leu Gly Lys Gin Glu Val Ile Arg Gly Trp Glu Glu Gly Val 50 55 60 gcc cag atg agt gtg ggt cag aga gcc aaa ctg act ata tet cca gat 240

Ala Gin Met Ser Val Gly Gin Arg Ala Lys Leu Thr Ile Ser Pro Asp 65 70 75 80 tat gcc tat ggt gcc act ggg cac cca ggc ate ate cca cca cat gcc 288

Tyr Ala Tyr Gly Ala Thr Gly His Pro Gly Ile Pro Pro His Ala 85 90 95 act ete gtc ttc gat gtg gag ctt cta aaa ctg gaa gat act tat aga 336

Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Asp Thr Tyr Arg 100 105 110 tat att gat act tat aga tat att aag agc atg tet agc atg gtg tca 384

Tyr Ile Asp Thr Tyr Arg Tyr Ile Lys Ser Met Ser Ser Met Val Ser 115 120 125 gac acc agt tgc aca ttc cct tca tet gat ggc ata ttc tgg aag cat 432

Asp Thr Ser Cys Thr Phe Pro Ser Ser Asp Gly Ile Phe Trp Lys His 130 135 140 tgg att caa acc aag gat ggg cag tgt ggc agt cca tta gta tca act 480

Trp Ile Gin Thr Lys Asp Gly Gin Cys Gly Ser Pro Leu Val Ser Thr 145 150 155 160 aga gat ggg ttc att gtt ggt ata cac tca gca teg aat ttc acc aac 528

Arg Asp Gly Phe Ile Val Gly Ile His Ser Ala Ser Asn Phe Thr Asn 165 170 175 aca aac aat tat ttc aca agc gtg ccg aaa aac ttc atg gaa ttg ttg 576

Thr Asn Asn Tyr Phe Thr Ser Val Pro Lys Asn Phe Met Glu Leu Leu 180 185 190 aca aat cag gag gcg cag cag tgg gtt agt ggt tgg ega tta aat get 624

Thr Asn Gin Glu Ala Gin Gin Trp Val Ser Gly Trp Arg Leu Asn Ala 195 200 205 gac tca gta ttg tgg ggg ggc cat aaa gtt ttc atg agc aaa cct gaa 672

Asp Ser Val Leu Trp Gly Gly His Lys Val Phe Met Ser Lys Pro Glu 210 215 220 gag cct ttt cag cca gtt aag gaa gcg act caa ete atg agt gaa ttg 720

Glu Pro Phe Gin Pro Val Lys Glu Ala Thr Gin Leu Met Ser Glu Leu 225 230 235 240 gtg tac teg caa gat cct aaa aag aag aga aag gta taa 759

Val Tyr Ser Gin Asp Pro Lys Lys Lys Arg Lys Val 245 250 <210> 44 <211> 252

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 44

Met Gly Val Gin Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe 15 10 15

Pro Lys Arg Gly Gin Thr Cys Val Val His Tyr Thr Gly Met Leu Glu 20 25 30

Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys 35 40 45

Phe Met Leu Gly Lys Gin Glu Val Ile Arg Gly Trp Glu Glu Gly Val 50 55 60

Ala Gin Met Ser Val Gly Gin Arg Ala Lys Leu Thr Ile Ser Pro Asp 65 70 75 80

Tyr Ala Tyr Gly Ally Thr Gly His Pro Gly Ile Pro Pro His Ala 85 90 95

Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Asp Thr Tyr Arg 100 105 110

Tyr Ile Asp Thr Tyr Arg Tyr Ile Lys Ser Met Ser Ser Met Val Ser 115 120 125

Asp Thr Ser Cys Thr Phe Pro Ser Ser Asp Gly Ile Phe Trp Lys His 130 135 140

Trp Ile Gin Thr Lys Asp Gly Gin Cys Gly Ser Pro Leu Val Ser Thr 145 150 155 160

Arg Asp Gly Phe Ile Val Gly Ile His Ser Ala Ser Asn Phe Thr Asn 165 170 175

Thr Asn ASn Tyr Phe Thr Ser Val Pro Lys Asn Phe Met Glu Leu Leu 180 185 190

Thr Asn Gin Glu Ala Gin Gin Trp Val Ser Gly Trp Arg Leu Asn Ala 195 200 205

Asp Ser Val Leu Trp Gly Gly His Lys Val Phe Met Ser Lys Pro Glu 210 215 220

Glu Pro Phe Gin Pro Val Lys Glu Ala Thr Gin Leu Met Ser Glu Leu 225 230 235 240

Val Tyr Ser Gin Asp Pro Lys Lys Lys Arg Lys Val 245 250 <210> 45 <211> 699

<212> DNA <213> Artificial SequenCe <220> <223> - <220> <221> CDS <222> {1) .. (696) <400> 45 atg gac ccg aaa aag aag aga aag gta ate ete tgg cat gag atg tgg 48

Met Asp Pro Lys Lys Lys Arg Lys Val Ile Leu Trp His Glu Met Trp 15 10 15 cat gaa ggc ctg gaa gag gca tet cgt ttg tac ttt ggg gaa agg aac 96

His Glu Gly Leu Glu Glu Ala Ser Arg Leu Tyr Phe Gly Glu Arg Asn 20 25 30 gtg aaa ggc atg ttt gag gtg ctg gag ccc ttg cat get atg atg gaa 144

Val Lys Gly Met Phe Glu Val Leu Glu Pro Leu His Ala Met Met Glu 35 40 45 cgg 99c ccc cag act ctg aag gaa aca tcc ttt aat cag gcc tat ggt 192

Arg Gly Pro Gin Thr Leu Lys Glu Thr Ser Phe Asn Gin Ala Tyr Gly 50 55 60 ega gat tta atg gag gcc caa gag tgg tgc agg aag tac atg aaa tca 240

Arg Asp Leu Met Glu Ala Gin Glu Trp Cys Arg Lys Tyr Met Lys Ser 65 70 75 80 ggg aat gtc aag gac ete ete caa gcc tgg gac ete tat tat cat gtg 288

Gly Asn Val Lys Asp Leu Leu Gin Ala Trp Asp Leu Tyr Tyr His Val 85 90 95 ttc ega ega ate tca aag gat act tat aga tat att gat act tat aga 336

Phe Arg Arg Ile Ser Lys Asp Thr Tyr Arg Tyr Ile Asp Thr Tyr Arg 100 105 110 tat att gga gaa agc ttg ttt aag gga cca cgt gat tac aac ccg ata 384

Tyr Ile Gly Glu Ser Leu Phe Lys Gly Pro Arg Asp Tyr Asn Pro Ile 115 120 125 teg agc acc att tgt cac ttg acg aat gaa tet gat ggg cac aca aca 432

Ser Ser Thr Ile Cys His Leu Thr Asn Glu Ser Asp Gly His Thr Thr 130 135 140 teg ttg tat ggt att gga ttt ggt ccc ttc ate att aca aac aag cac 480

Ser Leu Tyr Gly Ile Gly Phe Gly Pro Phe Ile Ile Thr Asn Lys His 145 150 155 160 ttg ttt aga aga aat aat gga aca ctg ttg gtc caa tca cta cat ggt 528

Leu Phe Arg Arg Asn Asn Gly Thr Leu Leu Val Gin Ser Leu His Gly 165 170 175 gta ttc aag gtc aag aac acc acg act ttg caa caa cac ete att gat 576

Val Phe Lys Val Lys Asn Thr Thr Thr Leu Gin Gin His Leu Ile Asp 180 185 190 ggg agg gac atg ata att att ege atg cct aag gat ttc cca cca ttt 624

Gly Arg Asp Met Ile Ile Arg Met Pro Lys Asp Phe Pro Pro Phe 195 200 205 cct caa aag ctg aaa ttt aga gag cca caa agg gaa gag ege ata tgt 672

Pro Gin Lys Leu Lys Phe Arg Glu Pro Gin Arg Glu Glu Arg Ile Cys 210 215 220 ctt gtg aca acc aac ttc caa act taa 699

Leu Val Thr Thr Asn Phe Gin Thr 225 230 <210> 46 <211> 232

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 46

Met Asp Pro Lys Lys Lys Arg Lys Val Ile Leu Trp His Glu Met Trp 15 10 15

His Glu Gly Leu Glu Glu Ala Ser Arg Leu Tyr Phe Gly Glu Arg Asn 20 25 30

Val Lys Gly Met Phe Glu Val Leu Glu Pro Leu His Ala Met Met Glu 35 40 45

Arg Gly Pro Gin Thr Leu Lys Glu Thr Ser Phe Asn Gin Ala Tyr Gly 50 55 60

Arg Asp Leu Met Glu Ala Gin Glu Trp Cys Arg Lys Tyr Met Lys Ser 65 70 75 80

Gly Asn Val Lys Asp Leu Leu Gin Ala Trp Asp Leu Tyr Tyr His Val 85 90 95

Phe Arg Arg Ile Ser Lys Asp Thr Tyr Arg Tyr Ile Asp Thr Tyr Arg 100 105 110

Tyr Ile Gly Glu Ser Leu Phe Lys Gly Pro Arg Asp Tyr Asn Pro Ile 115 120 125

Ser Ser Thr Ile Cys His Leu Thr Asn Glu Ser Asp Gly His Thr Thr 130 135 140

Ser Leu Tyr Gly Ile Gly Phe Gly Pro Phe Ile Ile Thr ASn Lys His 145 150 155 160

Leu Phe Arg Arg Asn Gly Thr Leu Leu Val Gin Ser Leu His Gly 165 170 175

Val Phe Lys Val Lys Asn Thr Thr Thr Leu Gin Gin His Leu Ile Asp 180 185 190

Gly Arg Asp Met Ile Ile Arg Met Pro Lys Asp Phe Pro Pro Phe 195 200 205

Pro Gin Lys Leu Lys Phe Arg Glu Pro Gin Arg Glu Glu Arg Ile Cys 210 215 220

Leu Val Thr Thr Asn Phe Gin Thr 225 230 <210> 47 <211> 714

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (711) <400> 47 atg gga gtg caa gtg gaa acc ate tcc ccg gga gac ggg ege acc ttc 48

Met Gly Val Gin Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe 15 10 15 ccc aag ege ggc cag acc tgc gtg gtg cac tac acc ggg atg ctt gaa 96

Pro Lys Arg Gly Gin Thr Cys Val Val His Tyr Thr Gly Met Leu Glu 20 25 30 gat gga aag aaa ttt gat tcc tcc ggg aga aac aag ccc ttt aag 144

Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys 35 40 45 ttt atg cta ggc aag cag gag gtg ate ega ggc tgg gaa gaa ggg gtt 192

Phe Met Leu Gly Lys Gin Glu Val Ile Arg Gly Trp Glu Glu Gly Val 50 55 60 gcc cag atg agt gtg ggt cag aga gcc aaa ctg act ata tet cca gat 240

Ala Gin Met Ser Val Gly Gin Arg Ala Lys Leu Thr Ile Ser Pro Asp 65 70 75 80 tat gcc tat ggt gcc act ggg cac cca ggc ate ate cca cca cat gcc 288

Tyr Ala Tyr Gly Ally Thr Gly His Pro Gly Ile Pro Pro His Ala 85 90 95 act ete gtc ttc gat gtg gag ctt cta aaa ctg gaa gga tcc gga agt 336

Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Gly Ser Gly Ser 100 105 110 aag agc ate agc agc acc atg agc gag acc agc gcc acc tac ccc gtg 384

Lys Ser Ile Ser Ser Thr Met Ser Glu Thr Ser Ala Thr Tyr Pro Val 115 120 125 gac aac agc cac ttc tgg aag cac tgg ate agc acc aag gac ggc cac 432

Asp Asn Ser His Phe Trp Lys His Trp Ile Ser Thr Lys Asp Gly His 130 135 140 tgc ggc ctg ccc ate gtg agc acc ege gac ggc agc ate ctg ggc ctg 480

Cys Gly Leu Pro Ile Val Ser Thr Arg Asp Gly Ser Ile Leu Gly Leu 145 150 155 160 cac agc ctg gcc aac agc aac acc cag aac ttc tac gcc gcc ttc 528

His Ser Leu Ala Asn Ser Thr Asr Thr Gin Asn Phe Tyr Ala Ala Phe 165 170 175 ccc gac aac ttc gag acc acc tac ctg agc aac cag gac aac gac aac 576

Pro Asp Asn Phe Glu Thr Thr Tyr Leu Ser Asn Gin Asp Asn Asn Asn 180 185 190 tgg aate cag tgg ege tac aac ccc gac gag gtg tgc tgg ggc agc 624

Trp Ile Lys Gin Trp Arg Tyr Asn Pro Asp Glu Val Cys Trp Gly Ser 195 200 205 ctg caa ctg aag ege gac ate ccc cag agc ccc ttc acc ate tgc aag 672

Leu Gin Leu Lys Arg Asp Ile Pro Gin Ser Pro Phe Thr Ile Cys Lys 210 215 220 ctg acc gac ctg gac ggc gag ttc gtg tac acc cag taa 714

Leu Leu Thr Asp Leu Asp Gly Glu Phe Val Tyr Thr Gin 225 230 235 <210> 48 <211> 237

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 48

Met Gly Val Gin Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe 15 10 15

Pro Lys Arg Gly Gin Thr Cys Val Val His Tyr Thr Gly Met Leu Glu 20 25 30

Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys 35 40 45

Phe Met Leu Gly Lys Gin Glu Val Ile Arg Gly Trp Glu Glu Gly Val 50 55 60

Ala Gin Met Ser Val Gly Gin Arg Ala Lys Leu Thr Ile Ser Pro Asp 65 70 75 80

Tyr Ala Tyr Gly Ally Thr Gly His Pro Gly Ile Pro Pro His Ala 85 90 95

Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Gly Ser Gly Ser 100 105 110

Lys Ser Ile Ser Ser Thr Met Ser Glu Thr Ser Ala Thr Tyr Pro Val 115 120 125

Asp Asn Ser His Phe Trp Lys His Trp Ile Ser Thr Lys Asp Gly His 130 135 140

Cys Gly Leu Pro Ile Val Ser Thr Arg Asp Gly Ser Ile Leu Gly Leu 145 150 155 160

His Ser Leu Ala Asn Ser Thr Asr Thr Gin Asn Phe Tyr Ala Ala Phe 165 170 175

Pro Asp Asn Phe Glu Thr Thr Tyr Leu Ser Asn Gin Asp Asn Asn Asn 180 185 190

Trp Ile Lys Gin Trp Arg Tyr Asn Pro Asp Glu Val Cys Trp Gly Ser 195 200 205

Leu Gin Leu Lys Arg Asp Ile Pro Gin Ser Pro Phe Thr Ile Cys Lys 210 215 220

Leu Leu Thr Asp Leu Asp Gly Glu Phe Val Tyr Thr Gin 225 230 235 <210> 49 <211> 651

<212> DNA <213> Artificial Seguence <220> <223> - <220> <221> CDS <222> (1) .. (648) <400> 49 atg ate ete tgg cat gag atg tgg cat gaa ggc ctg gaa gag gca tet 48

Met Ile Leu Trp His Glu Met Trp His Glu Gly Leu Glu Glu Ala Ser 15 10 15 cgt ttg tac ttt ggg gaa agg aac gtg aaa ggc atg ttt gag gtg ctg 96

Arg Leu Tyr Phe Gly Glu Arg Asn Val Lys Gly Met Phe Glu Val Leu 20 25 30 gag ccc ttg cat get atg atg gaa cgg ggc ccc cag act ctg aag gaa 144

Glu Pro Leu His Ala Met Met Glu Arg Gly Pro Gin Thr Leu Lys Glu 35 40 45 aca tcc ttt aat cag gcc tat ggt ega gat tta atg gag gcc caa gag 192

Thr Ser Phe Asn Gin Ala Tyr Gly Arg Asp Leu Met Glu Ala Gin Glu 50 55 60 tgg tgc agg aag tae atg aaa tca ggg aat gtc aag gac ete ete caa 240

Trp Cys Arg Lys Tyr Met Lys Ser Gly Asn Val Lys Asp Leu Leu Gin 65 70 75 80 gcc tgg gac ete tat tat cat gtg ttc ega ega ate tca aag gga tcc 288

Ala Trp Asp Leu Tyr Tyr His Val Phe Arg Arg Ile Ser Lys Gly Ser 85 90 95 gga agt agc aag agc ctg ttc ege ggc ctg ege gac tac aac ccc ate 336

Gly Ser Ser Lys Ser Leu Phe Arg Gly Leu Arg Asp Tyr Asn Pro Ile 100 105 110 gcc agc agc ate tgc cag ctg aac aac agc agc ggc gcc ege cag agc 384

Ala Ser Ser Ile Cys Gin Leu Asn Ser Ser Gly Ala Arg Gin Ser 115 120 125 gag atg ttc ggc ctg ggc ttc ggc ggc ctg ate gtg acc aac cag cac 432

Glu Met Phe Gly Lei Gly Ply Gly Gly Leu Ile Val Thr Asn Gin His 130 135 140 ctg ttc aag ege aac gac ggc gag ctg acc ate ege agc cac cac ggc 480

Leu Phe Lys Arg Asn Asp Gly Glu Leu Thr Ile Arg Ser His His Gly 145 150 155 160 gag ttc gtg gtg aag gac acc aag acc Ctg aag ctg ctg ccc tgc aag 528

Glu Phe Val Val Lys Asp Thr Lys Thr Leu Lys Leu Leu Pro Cys Lys 165 170 175 ggc ege gac ate gtg ate ate ege ctg ccc aag gac ttc ccc ccc ttc 576

Gly Arg Asp Ile Val Ile Ile Arg Leu Pro Lys Asp Phe Pro Pro Phe 180 185 190 ccc aag ege ctg caa ttc ege acc ccc acc acc gag gac ege gtg tgc 624

Pro Lys Arg Leu Gin Phe Arg Thr Pro Thr Thr Glu Asp Arg Val Cys 195 200 205 ctg ate ggc agc aac ttc cag acc taa 651

Leu Ile Gly Ser Asn Phe Gin Thr 210 215 <210> 50

<211> 216 <212> PRT <213> Artificial Seguence <220> <223> Synthetic Construct <400> 50

Met Ile Leu Trp His Glu Met Trp His Glu Gly Leu Glu Glu Ala Ser 15 10 15

Arg Leu Tyr Phe Gly Glu Arg Asn Val Lys Gly Met Phe Glu Val Leu 20 25 30

Glu Pro Leu His Ala Met Met Glu Arg Gly Pro Gin Thr Leu Lys Glu 35 40 45

Thr Ser Phe Asn Gin Ala Tyr Gly Arg Asp Leu Met Glu Ala Gin Glu 50 55 60

Trp Cys Arg Lys Tyr Met Lys Ser Gly Asn Val Lys Asp Leu Leu Gin 65 70 75 80

Ala Trp Asp Leu Tyr Tyr His Val Phe Arg Arg Ile Ser Lys Gly Ser 85 90 95

Gly Ser Ser Lys Ser Leu Phe Arg Gly Leu Arg Asp Tyr Asn Pro Ile 100 105 110

Ala Ser Ser Ile Cys Gin Leu Asn Asn Ser Ser Gly Ala Arg Gin Ser 115 120 125

Glu Met Phe Gly Le Gly Ply Gly Gly Leu Ile Val Thr Asn Gin His 130 135 140

Leu Phe Lys Arg Asn Asp Gly Glu Leu Thr Ile Arg Ser His His Gly 145 150 155 160

Glu Phe Val Lys Asp Thr Lys Thr Leu Lys Leu Leu Pro Cys Lys 165 170 175

Gly Arg Asp Ile Val Ile Ile Arg Leu Pro Lys Asp Phe Pro Pro Phe 180 185 190

Pro Lys Arg Leu Gin Phe Arg Thr Pro Thr Thr Glu Asp Arg Val Cys 195 200 205

Leu Ile Gly Ser Asn Phe Gin Thr 210 215 <210> 51 <211> 735

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (732) <400> 51 atg gga gtg caa gtg gaa acc ate tcc ccg gga gac ggg ege acc ttc 48

Met Gly Val Gin Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe 15 10 15 ccc aag ege ggc cag acc tgc gtg gtg cac tac acc ggg atg ctt gaa 96

Pro Lys Arg Gly Gin Thr Cys Val Val His Tyr Thr Gly Met Leu Glu 20 25 30 gat gga aag aaa ttt gat tcc tcc cgg gac aga aac aag ccc ttt aag 144

Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys 35 40 45 ttt atg cta ggc aag cag gag gtg ate ega ggc tgg gaa gaa ggg gtt 192

Phe Met Leu Gly Lys Gin Glu Val Ile Arg Gly Trp Glu Glu Gly Val 50 55 60 gcc cag atg agt gtg ggt cag aga gcc aaa ctg act ata tet cca gat 240

Ala Gin Met Ser Val Gly Gin Arg Ala Lys Leu Thr Ile Ser Pro Asp 65 70 75 80 tat gcc tat ggt gcc act ggg cac cca ggc ate ate cca cca cat gcc 288

Tyr Ala Tyr Gly Ally Thr Gly His Pro Gly Ile Pro Pro His Ala 85 90 95 act ete gtc ttc gat gtg gag ctt cta aaa ctg gaa gga tcc gga agt 336

Thr Leu Val Phe Asp Val Glu Leu Leu Lyche Leu Glu Gly Ser Gly Ser 100 105 110 aag cat ctt tcc agc atg gtg agc gag agc agc tgc gtg gtg cag cgc 384

Lys His Leu Ser Ser Met Val Ser Glu Ser Ser Cys Val Val Gin Arg 115 120 125 gag gac agc Ccc ate tgg cgc cac tgg ate agc acc aag gaC ggc cac 432

Glu Asp Ser Pro Ile Trp Arg His Trp Ile Ser Thr Lys Asp Gly His 130 135 140 tgc ggc gcc ccc ate gtg agc ate cgc gac ggc tac ate ate ggc agc 480

Cys Gly Ala Pro Ile Val Ser Ile Arg Asp Gly Tyr Ile Ile Gly Ser 145 150 155 160 cac tgc ggc gag aac ccc atg acc agc aac ttc ttc acc agc ate ccc 528

His Cys Gly Glu Asn Pro Met Thr Ser Asn Phe Phe Thr Ser Ile Pro 165 170 175 aag gac ttc cag aac ctg ctg aac ggc aag gag gcc aac gag tgg gtg 576

Lys Asp Phe Gin Asn Leu Leu Asn Gly Lys Glu Ala Asn Glu Trp Val 180 185 190 agc ggc tgg aag tac aac ate gac gcc gtg tgc tgg ggc ggc ctg agc 624

Ser Gly Trp Lys Tyr Asn Ile Asp Ala Val Cys Trp Gly Gly Leu Ser 195 200 205 gtg gtg aac gac gcc ccc agc gag ccc ttc ate acc gcc aag gtg gtg 672

Val Val Asn Asp Ala Pro Ser Glu Pro Phe Ile Thr Ala Lys Val Val 210 215 220 agc gcc ctg gac acc gag ggc ate aag gtg cag tac cca tac gat gtt 720

Ser Ala Leu Asp Thr Glu Gly Ile Lys Val Gin Tyr Pro Tyr Asp Val 225 230 235 240 cca gat tac get taa 735

Pro Asp Tyr Ala <210> 52 <211> 244

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 52

Met Gly Val Gin Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe 15 10 15

Pro Lys Arg Gly Gin Thr Cys Val Val His Tyr Thr Gly Met Leu Glu 20 25 30

Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys 35 40 45

Phe Met Leu Gly Lys Gin Glu Val Ile Arg Gly Trp Glu Glu Gly Val 50 55 60

Ala Gin Met Ser Val Gly Gin Arg Ala Lys Leu Thr Ile Ser Pro Asp 65 70 75 80

Tyr Ala Tyr Gly Ally Thr Gly His Pro Gly Ile Pro Pro His Ala 85 90 95

Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Gly Ser Gly Ser 100 105 110

Lys His Leu Ser Ser Met Val Ser Glu Ser Ser Cys Val Val Gin Arg 115 120 125

Glu Asp Ser Pro Ile Trp Arg His Trp Ile Ser Thr Lys Asp Gly His 130 135 140

Cys Gly Ala Pro Ile Val Ser Ile Arg Asp Gly Tyr Ile Ile Gly Ser 145 150 155 160

His Cys Gly Glu Asn Pro Met Thr Ser Asn Phe Phe Thr Ser Ile Pro 165 170 175

Lys Asp Phe Gin Asn Leu Leu Asn Gly Lys Glu Ala Asn Glu Trp Val 180 185 190

Ser Gly Trp Lys Tyr Asn Ile Asp Ala Val Cys Trp Gly Gly Leu Ser 195 200 205

Val Val Asn Asp Ala Pro Ser Glu Pro Phe Ile Thr Ala Lys Val Val 210 215 220

Ser Ala Leu Asp Thr Glu Gly Ile Lys Val Gin Tyr Pro Tyr Asp Val 225 230 235 240

Pro Asp Tyr Ala <210> 53

<211> 681 <212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (678) <400> 53 atg gag cag aag ctg ate agc gag gag gat ctg ate ete tgg eat gag 48

Met Glu Gin Lys Leu Ile Ser Glu Glu Asp Leu Ile Leu Trp His Glu 15 10 15 atg tgg eat gaa ggc ctg gaa gag gca tet cgt ttg tac ttt ggg gaa 96

Met Trp His Glu Gly Leu Glu Glu Ala Ser Arg Leu Tyr Phe Gly Glu 20 25 30 agg aac gtg aaa ggc atg ttt gag gtg ctg gag ccc ttg eat get atg 144

Arg Asn Val Lys Gly Met Phe Glu Val Leu Glu Pro Leu His Ala Met 35 40 45 atg gaa cgg ggc ccc cag act ctg aag gaa aca tcc ttt aat cag gcc 192

Met Glu Arg Gly Pro Gin Thr Leu Lys Glu Thr Ser Phe Asn Gin Ala 50 55 60 tat ggt ega gat tta atg gag gcc caa gag tgg tgc agg aag tac atg 240

Tyr Gly Arg Asp Leu Met Glu Ala Gin Glu Trp Cys Arg Lys Tyr Met 65 70 75 80 aaa tca ggg aat gtc aag gac ete ete caa gcc tgg gac ete tat tat 288

Lys Ser Gly Asn Val Lys Asp Leu Leu Gin Ala Trp Asp Leu Tyr Tyr 85 90 95 eat gtg ttc ega ega ate tca aag gga tcc gga agt ggc gtg agc ctg 336

His Val Phe Arg Arg Ile Ser Lys Gly Ser Gly Ser Gly Val Ser 100 100 110 agc ege ggc gtg ege gac tac aac gcc ate agc agc atg gtg tgc ege 384

Ser Arg Gly Val Arg Asp Tyr Asn Ala Ile Ser Ser Met Val Cys Arg 115 120 125 gtg acc aac gac agc ggc agc agc agc acc acc atg tac ggc ate ggc 432

Val Thr Asn Asp Ser Gly Ser Ser Ser Thr Thr Met Tyr Gly Ile Gly 130 135 140 tac ggc tgc tac ate ate acc aac aag cac ctg ttc ege gag aac aac 480

Tyr Gly Cys Tyr Ile Ile Thr Asn Lys His Leu Phe Arg Glu Asn Asn 145 150 155 160 ggc ege ctg ctg ate acc agc cac cac ggc gag tac ate tgc aag aac 528

Gly Arg Leu Leu Ile Thr Ser His His Gly Glu Tyr Ile Cys Lys Asn 165 170 175 agc gcc agc ctg aag ctg agc ctg gtg ccc ggc ege gac atg ctg ctg 576

Ser Ala Ser Leu Lys Leu Ser Leu Val Pro Gly Arg Asp Met Leu Leu 180 185 190 ate ege ctg ccc aag gac tgc ccc ccc ttc ccc agc aag ctg aag ttt 624

Ile Arg Leu Pro Lys Asp Cys Pro Pro Phe Pro Ser Lys Leu Lys Phe 195 200 205 ega gag ccc act agc gaa gaa aag gcc gtg ctt gta gtc aca aac ttc 672

Arg Glu Pro Thr Ser Glu Glu Lys Ala Val Leu Val Val Thr Asn Phe 210 215 220 cag gag taa 681

Gin Glu 225 <210> 54

<211> 226 <212> PRT <213> Artificial Seguence <220> <223> Synthetic Construct <400> 54

Met Glu Gin Lys Leu Ile Ser Glu Glu Asp Leu Ile Leu Trp His Glu 15 10 15

Met Trp His Glu Gly Leu Glu Glu Ala Ser Arg Leu Tyr Phe Gly Glu 20 25 30

Arg Asn Val Lys Gly Met Phe Glu Val Leu Glu Pro Leu His Ala Met 35 40 45

Met Glu Arg Gly Pro Gin Thr Leu Lys Glu Thr Ser Phe Asn Gin Ala 50 55 60

Tyr Gly Arg Asp Leu Met Glu Ala Gin Glu Trp Cys Arg Lys Tyr Met 65 70 75 80

Lys Ser Gly Asn Val Lys Asp Leu Leu Gin Ala Trp Asp Leu Tyr Tyr 85 90 95

His Val Phe Arg Arg Ile Ser Lys Gly Ser Gly Ser Gly Val Ser Leu 100 105 110

Ser Arg Gly Val Arg Asp Tyr Asn Ala Ile Ser Ser Met Val Cys Arg 115 120 125

Val Thr Asn Asp Ser Gly Ser Ser Ser Thr Thr Met Tyr Gly Ile Gly 130 135 140

Tyr Gly Cys Tyr Ile Ile Thr Asn Lys His Leu Phe Arg Glu Asn Asn 145 150 155 160

Gly Arg Leu Leu Ile Thr Ser His His Gly Glu Tyr Ile Cys Lys Asn 165 170 175

Ser Ala Ser Leu Lys Leu Ser Leu Val Pro Gly Arg Asp Met Leu Leu 180 185 190

Ile Arg Leu Pro Lys Asp Cys Pro Pro Phe Pro Lys Leu Lys Phe 195 200 205

Arg Glu Pro Thr Ser Glu Glu Lys Ala Val Leu Val Val Thr Asn Phe 210 215 220

Gin Glu 225 <210> 55 <211> 741

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (738) <400> 55 atg gga gtg caa gtg gaa acc ate tcc ccg gga gac ggg ege acc ttc 48

Met Gly Val Gin Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe 15 10 15 ccc aag ege ggc cag acc tgc gtg gtg cac tac acc ggg atg ctt gaa 96

Pro Lys Arg Gly Gin Thr Cys Val Val His Tyr Thr Gly Met Leu Glu 20 25 30 gat gga aag aaa ttt gat tcc tcc cgg gac aga aac aag ccc ttt aag 144

Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys 35 40 45 ttt atg cta ggc aag cag gag gtg ate ega ggc tgg gaa gaa ggg gtt 192

Phe Met Leu Gly Lys Gin Glu Val Ile Arg Gly Trp Glu Glu Gly Val 50 55 60 gcc cag atg agt gtg ggt cag aga gcc aaa ctg act ata tet cca gat 240

Ala Gin Met Ser Val Gly Gin Arg Ala Lys Leu Thr Ile Ser Pro Asp 65 70 75 80 tat gcc tat ggt gcc act ggg cac cca ggc ate ate cca cca cat gcc 288

Tyr Ala Tyr Gly Ally Thr Gly His Pro Gly Ile Pro Pro His Ala 85 90 95 act ete gtc ttc gat gtg gag ctt cta aaa ctg gaa gga tcc gga agt 336

Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Gly Ser Gly Ser 100 105 110 aag agc ctg cgc gcc acc gtg agc gag agc agc atg ate ctg ccc gag 384

Lys Ser Leu Arg Ala Thr Val Ser Glu Ser Ser Met Ile Leu Pro Glu 115 120 125 ggc aag ggc agc ttc tgg ata cae tgg ate acc acc cag gac ggc ttc 432

Gly Lys Gly Ser Phe Trp Ile His Trp Ile Thr Thr Gin Asp Gly Phe 130 135 140 tgc ggc ctg ccc ctg gtg agc gtg aac gac ggc cac ate gtg ggc ate 480

Cys Gly Leu Pro Leu Val Ser Val Asn Asp Gly His Ile Val Gly Ile 145 150 155 160 cac ggc ctg acc agc aac gac agc gag aag aac ttc ttc gtg ccc ctg 528

His Gly Leu Thr Ser Asn Asp Ser Glu Lys Asn Phe Phe Val Pro Leu 165 170 175 acc gac ggc ttc gag aag gag tac ctg gag aac gcc gac aac ctg agc 576

Thr Asp Gly Phe Glu Lys Glu Tyr Leu Glu Asn Ala Asp Asn Leu Ser 180 185 190 tgg gac aag cac tgg tgg ggg ccc agc aag ate gcc tgg ggc agc 624

Trp Asp Lys His Trp Phe Trp Glu Pro Ser Lys Ile Ala Trp Gly Ser 195 200 205 ctg aac ctg gtg gag cag ccc aag gag gag ttc aag ate agc aag 672

Leu Asn Leu Val Glu Glu Gin Pro Lys Glu Glu Phe Lys Ile Ser Lys 210 215 220 ctg gtc agc gac ctg ttc ggc aac acc gtg acc gtg cag tac cca tac 720

Leu Val Ser Asp Leu Phe Gly Asn Thr Val Thr Val Gin Tyr Pro Tyr 225 230 235 240 gat gtt cca gat tac get taa 741

Asp Val Pro Asp Tyr Ala 245 <210> 56 <211> 246

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 56

Met Gly Val Gin Val Glu Thr Ile Ser Pro Gly Asp Gly Arg Thr Phe 15 10 15

Pro Lys Arg Gly Gin Thr Cys Val Val His Tyr Thr Gly Met Leu Glu 20 25 30

Asp Gly Lys Lys Phe Asp Ser Ser Arg Asp Arg Asn Lys Pro Phe Lys 35 40 45

Phe Met Leu Gly Lys Gin Glu Val Ile Arg Gly Trp Glu Glu Gly Val 50 55 60

Ala Gin Met Ser Val Gly Gin Arg Ala Lys Leu Thr Ile Ser Pro Asp 65 70 75 80

Tyr Ala Tyr Gly Ally Thr Gly His Pro Gly Ile Pro Pro His Ala 85 90 95

Thr Leu Val Phe Asp Val Glu Leu Leu Lys Leu Glu Gly Ser Gly Ser 100 105 110

Lys Ser Leu Arg Ala Thr Val Ser Glu Ser Ser Met Ile Leu Pro Glu 115 120 125

Gly Lys Gly Ser Phe Trp Ile His Trp Ile Thr Thr Gin Asp Gly Phe 130 135 140

Cys Gly Leu Pro Leu Val Ser Val Asn Asp Gly His Ile Val Gly Ile 145 150 155 160

His Gly Leu Thr Ser Asn Asp Ser Glu Lys Asn Phe Phe Val Pro Leu 165 170 175

Thr Asp Gly Phe Glu Lys Glu Tyr Leu Glu Asn Ala Asp Asn Leu Ser 180 185 190

Trp Asp Lys His Trp Phe Trp Glu Pro Ser Lys Ile Ala Trp Gly Ser 195 200 205

Leu Asn Leu Val Glu Glu Gin Pro Lys Glu Glu Phe Lys Ile Ser Lys 210 215 220

Leu Val Ser Asp Leu Phe Gly Asn Thr Val Thr Val Gin Tyr Pro Tyr 225 230 235 240

Asp Val Pro Asp Tyr Ala 245 <210> 57

<211> 681 <212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (678) <400> 57 atg gag cag aag ctg ate agc gag gag gat ctg ate ete tgg cat gag 48

Met Glu Gin Lys Leu Ile Ser Glu Glu Asp Leu Ile Leu Trp His Glu 15 10 15 atg tgg cat gaa ggc ctg gaa gag gca tet cgt ttg tac ttt ggg gaa 96

Met Trp His Glu Gly Leu Glu Glu Ala Ser Arg Leu Tyr Phe Gly Glu 20 25 30 agg aac gtg aaa ggc atg ttt gag gtg ctg gag ccc ttg cat get atg 144

Arg Asn Val Lys Gly Met Phe Glu Val Leu Glu Pro Leu His Ala Met 35 40 45 atg gaa cgg ggc ccc cag act ctg aag gaa aca tcc ttt aat cag gcc 192

Met Glu Arg Gly Pro Gin Thr Leu Lys Glu Thr Ser Phe Asn Gin Ala 50 55 60 tat ggt ega gat tta atg gag gcc caa gag tgg tgc agg aag tac atg 240

Tyr Gly Arg Asp Leu Met Glu Ala Gin Glu Trp Cys Arg Lys Tyr Met 65 70 75 80 aaa tca ggg aat gtc aag gac ete ete caa gcc tgg gac ete tat tat 288

Lys Ser Gly Asn Val Lys Asp Leu Leu Gin Ala Trp Asp Leu Tyr Tyr 85 90 95 cat gtg ttc ega ega ate tca aag gga tcc gga agt agc aag agc gtg 336

His Val Phe Arg Arg Ile Ser Lys Ser Gly Ser Ser Lys Ser Val 100 105 110 tac aag ggc ctg ege gac tac agc ggc ate agc acc ctg ate tgc cag 384

Tyr Lys Gly Leu Arg Asp Tyr Ser Gly Ile Ser Thr Leu Ile Cys Gin 115 120 125 ctg acc aac agc agc gac ggc cac aag gag acc atg ttc ggc gtg ggc 432

Leu Thr Asn Ser Ser Asp Gly His Lys Glu Thr Met Phe Gly Val Gly 130 135 140 tac ggc agc ttc ate ate acc aac ggc cac ctg ttc ege ege aac aac 480

Tyr Gly Ser Phe Ile Ile Thr Asn Gly His Leu Phe Arg Arg Asn Asn 145 150 155 160 ggc atg ctg acc gtg aag acc tgg cac ggc gag ttc gtg ate cac aac 528

Gly Met Leu Thr Val Lys Thr Trp His Gly Glu Phe Val Ile His Asn 165 170 175 acc acc cag ctg aag ate cac ttc ate cag ggc ege gac gtg ate ctg 576

Thr Thr Gin Leu Lys Ile His Phe Ile Gin Gly Arg Asp Val Ile Leu 180 185 190 ate ege atg ccc aag gac ttc ccc ccc ttc ggc aag ege aac ctg ttc 624

Ile Arg Met Pro Lys Asp Pro Pro Phe Gly Lys Arg Asn Leu Phe 195 200 205 ege cag ccc aag ege gag gag ege gtg tgc atg gtg ggc acc aac ttc 672

Arg Gin Pro Lys Arg Glu Glu Atg Val Cys Met Val Gly Thr Asn Phe 210 215 220 cag gag taa 681

Gin Glu 225 <210> 58

<211> 226 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 58

Met Glu Gin Lys Leu Ile Ser Glu Glu Asp Leu Ile Leu Trp His Glu 15 10 15

Met Ttp His Glu Gly Leu Glu Glu Ala Ser Arg Leu Tyr Phe Gly Glu 20 25 30

Arg Asn Val Lys Gly Met Phe Glu Val Leu Glu Pro Leu His Ala Met 35 40 45

Met Glu Arg Gly Pro Gin Thr Leu Lys Glu Thr Ser Phe Asn Gin Ala 50 55 60

Tyr Gly Arg Asp Leu Met Glu Ala Gin Glu Trp Cys Arg Lys Tyr Met 65 70 75 80

Lys Ser Gly Asn Val Lys Asp Leu Leu Gin Ala Trp Asp Leu Tyr Tyr 85 90 95

His Val Phe Arg Arg Ile Ser Lys Gly Ser Gly Ser Ser Lys Ser Val 100 105 110

Tyr Lys Gly Leu Arg Asp Tyr Ser Gly Ile Ser Thr Leu Ile Cys Gin 115 120 125

Leu Thr Asn Ser Ser Asp Gly His Lys Glu Thr Met Phe Gly Val Gly 130 135 140

Tyr Gly Ser Phe Ile Ile Thr Asn Gly His Leu Phe Arg Arg Asn Asn 145 150 155 160

Gly Met Leu Thr Val Lys Thr Trp His Gly Glu Phe Val Ile His Asn 165 170 175

Thr Thr Gin Leu Lys Ile His Phe Ile Gin Gly Arg Asp Val Ile Leu 180 185 190

Ile Arg Met Pro Lys Asp Phe Pro Phe Gly Lys Arg Asn Leu Phe 195 200 205

Arg Gin Pro Lys Arg Glu Glu Arg Val Cys Met Val Gly Thr Asn Phe 210 215 220

Gin Glu 225 <210> 59 <211> 1929

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (1926) <400> 59 atg cac cac cac aac atg gac aaa aag act ata gtt tgg 48

Met His His His His His Lys Met Asp Lys Lys Thr Ile Val Trp 15 10 15 ttt aga aga gac cta agg att gag gat aat cct gca tta gca gca gct 96

Phe Arg Arg Asp Leu Arg Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala 20 25 30 gct cac gaa gga tet gtt ttt cct gtc ttc att tgg tgt cct gaa gaa 144

Ala His Glu Gly Ser Val Phe Pro Val Phe Ile Trp Cys Pro Glu Glu 35 40 45 gaa gga cag ttt tat cct gga aga gct tca aga tgg tgg atg aaa caa 192

Glu Gly Gin Phe Tyr Pro Gly Arg Ala Ser Arg Trp Trp Met Lys Gin 50 55 60 tca ctt gct cac tta tet caa tcc ttg aag gct ctt gga tet gac ete 240

Ser Leu Ala His Leu Ser Gin Ser Leu Lys Ala Leu Gly Ser Asp Leu 65 70 75 80 act tta ate aaa acc cac aac acg att tca gcg ate ttg gat tgt ate 288

Thr Leu Ile Lys Thr His Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile 85 90 95 ege gtt acc ggt gct aca aaa gtc gtc ttt aac cac ete tat gat cct 336

Arg Val Thr Gly Ala Thr Lys Val Val Phe Asn His Leu Tyr Asp Pro 100 105 110 gtt tcg tta gtt cgg gac cat acc gta aag gag aag ctg gtg gaa cgt 384

Val Ser Leu Val Arg Asp His Thr Val Lys Glu Lys Leu Val Glu Arg 115 120 125 ggg ate tet gtg caa agc tac aat gga gat cta ttg tat gaa ccg tgg 432

Gly Ile Ser Val Gin Ser Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp 130 135 140 gag ata tac tgc gaa aag ggc aaa cct ttt acg agt ttc aat tet tac 480

Glu Ile Tyr Cys Glu Lys Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr 145 150 155 160 tgg aag aaa tgc tta gat atg tcg att gaa tcc gtt atg ctt cct cct 528

Trp Lys Lys Cys Leu Asp Met Ser Ile Glu Ser Val Met Leu Pro Pro 165 170 175 cct tgg cgg ttg atg cca ata act gca gcg get gaa gcg att tgg gcg 576

Pro Trp Arg Leu Met Pro Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala 180 185 190 tgt tcg att gaa gaa cta ggg ctg gag aat gag gcc gag aaa ccg agc 624

Cys Ser Ile Glu Glu Leu Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser 195 200 205 aat gcg ttg tta act aga get tgg tet cca gga tgg agc aat get gat 672

Asn Ala Leu Leu Thr Arg Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp 210 215 220 aag tta cta aat gag ttc ate gag aag cag ttg ata gat tat gca aag 720

Lys Leu Leu Asn Glu Phe Ile Glu Lys Gin Leu Ile Asp Tyr Ala Lys 225 230 235 240 aac agc aag aaa gtt gtt ggg aat tet act tca cta ctt tet ccg tat 768

Asn Ser Lys Val Val Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr 245 250 255 ete cat ttc ggg gaa ata agc gtc aga cae gtt ttc cag tgt gcc cgg 816

Leu His Phe Gly Glu Ile Ser Val Arg His Val Phe Gin Cys Ala Arg 260 265 270 atg aaa caa att ata tgg gca aga gat aag aac agt gaa gga gaa gaa 864

Met Lys Gin Ile Ile Trp Ala Arg Asp Lys Asn Ser Glu Gly Glu Glu 275 280 285 agt gca gat ctt ttt ctt agg gga ate ggt tta aga gag tat tet cgg 912

Ser Ala Asp Leu Phe Leu Arg Gly Ile Gly Leu Arg Glu Tyr Ser Arg 290 295 300 tat ata tgt ttc aac ttc ccg ttt act cac gag caa tcg ttg ttg agt 960

Tyr Ile Cys Phe Asn Phe Pro Phe Thr His Glu Gin Ser Leu Leu Ser 305 310 315 320 cat ctt ctt tttc cct tgg gat get gat gtt gat aag ttc aag gcc 1008

His Leu Arg Phe Phe Pro Trp Asp Ala Asp Val Asp Lys Phe Lys Ala 325 330 335 tgg aga caa ggc agg acc ggt tat ccg ttg gtg gat gcc gga atg aga 1056

Trp Arg Gin Gly Arg Thr Gly Tyr Pro Leu Val Asp Ala Gly Met Arg 340 345 350 gag ctt tgg get acc gga tgg atg cat aac aga ata aga gtg att gtt 1104

Glu Leu Trp Ala Thr Gly Trp Met His Asn Arg Ile Arg Val Ile Val 355 360 365 tca agt ttt get gtg aag ttt ctt ete ctt cga tgg aaa tgg gga atg 1152

Ser Ser Phe Ala Val Lys Phe Leu Leu Leu Pro Trp Lys Trp Gly Met 370 375 380 aag tat ttc tgg gat aca ctt ttg gat get gat ttg gaa tgt gac ate 1200

Lys Tyr Phe Trp Asp Thr Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile 385 390 395 400 ctt ggc tgg cag tat ate tet ggg agt ate ccc gat ggc cac gag ctt 1248

Leu Gly Trp Gin Tyr Ile Ser Gly Ser Ile Pro Asp Gly His Glu Leu 405 410 415 gat ege ttg gac aat ccc gcg tta caa ggc gcc aaa tat gac cca gaa 1296

Asp Arg Leu Asp Asn Pro Ala Leu Gin Gly Ala Lys Tyr Asp Pro Glu 420 425 430 ggt gag tac ata agg caa tgg ctt ccc gag ctt gcg aga ttg cca act 1344

Gly Glu Tyr Ile Arg Gin Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr 435 440 445 gaa tgg ate cat cat cca tgg gac get cct tta acc gta ete aaa get 1392

Glu Trp Ile His His Pro Trp Asp Ala Pro Leu Thr Val Leu Lys Ala 450 455 460 tet ggt gtg gaa ete gga aca aac tat gcg aaa ccc att gta gac ate 1440

Ser Gly Val Glu Leu Gly Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile 465 470 475 480 gac aca get cgt gag cta cta get aaa get att tca aga acc cgt gaa 1488

Asp Thr Ala Arg Glu Leu Leu Ala Lys Ala Ile Ser Arg Thr Arg Glu 485 490 495 gca cag ate atg ate gga gca gca ggc ggc tet ggc ggc ggc tcc gga 1536

Ala Gin Ile Met Ile Gly Gly Gly Gly Gly Gly Gly Gly Ser Gly 500 505 510 ggc gag cag aag ctg ate agc gag gag gac ctg gga gaa agc ttg 1584

Gly Ser Glu Gin Lys Leu Ile Ser Glu Glu Asp Leu Gly Glu Ser Leu 515 520 525 ttt aag gga cca cgt gat tac aac ccg ata teg agc acc att tgt cac 1632

Phe Lys Gly Pro Arg Asp Tyr Asn Pro Ile Ser Ser Thr Ile Cys His 530 535 540 ttg acg aat gaa tet gat ggg cac aca aca teg ttg tat ggt att gga 1680

Leu Thr Asn Glu Ser Asp Gly His Thr Thr Ser Leu Tyr Gly Ile Gly 545 550 555 560 ttt ggt ccc ttc ate att aca aac aag cac ttg ttt aga aga aat aat 1728

Phe Gly Pro Phe Ile Ile Thr Asn Lys His Leu Phe Arg Arg Asn Asn 565 570 575 gga aca ctg ttg gtc caa tca cta cat ggt gta ttc aag gtc aag aac 1776

Gly Thr Leu Leu Val Gin Ser Leu His Gly Val Phe Lys Val Lys Asn 580 585 590 acc acg act ttg caa caa cac ete att gat ggg agg gac atg ata att 1824

Thr Thr Thr Leu Gin Gin His Leu Ile Asp Gly Arg Asp Met Ile Ile 595 600 605 att ege atg cct aag gat ttc ca cca ctt cct caa aag ctg aaa ttt 1872

Ile Arg Met Pro Lys Asp Phe Pro Pro Phe Pro Gin Lys Leu Lys Phe 610 615 620 aga gag cca caa agg gaa gag ege ata tgt ctt gtg aca acc aac ttc 1920

Arg Glu Pro Gin Arg Glu Glu Arg Ile Cys Leu Val Thr Thr Thr Asn Phe 625 630 635 640 caa act taa 1929

Gin Thr <210> 60 <211> 642

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 60

Met His Lies Lys Thr Ile Val Trp 15 10 15

Phe Arg Arg Asp Leu Arg Ile Glu Asp Asn Pro Ala Leu Ala Ala Ala 20 25 30

Ala His Glu Gly Ser Val Phe Pro Val Phe Ile Trp Cys Pro Glu Glu 35 40 45

Glu Gly Gin Phe Tyr Pro Gly Arg Ala Ser Arg Trp Met Lys Gin 50 55 60

Ser Leu Ala His Leu Ser Gin Ser Leu Lys Ala Leu Gly Ser Asp Leu 65 70 75 80

Thr Leu Ile Lys Thr His Asn Thr Ile Ser Ala Ile Leu Asp Cys Ile 85 90 95

Arg Val Thr Gly Ala Thr Lys Val Val Phe Asn His Leu Tyr Asp Pro 100 105 110

Val Ser Leu Val Arg Asp His Thr Val Lys Glu Lys Leu Val Glu Arg 115 120 125

Gly Ile Ser Val Gin Ser Tyr Asn Gly Asp Leu Leu Tyr Glu Pro Trp 130 135 140

Glu Ile Tyr Cys Glu Lys Gly Lys Pro Phe Thr Ser Phe Asn Ser Tyr 145 150 155 160

Trp Lys Lys Cys Leu Asp Met Ser Ile Glu Ser Val Leu Pro Pro 165 170 175

Pro Trp Arg Leu Met Pro Ile Thr Ala Ala Ala Glu Ala Ile Trp Ala 180 185 190

Cys Ser Ile Glu Glu Leu Gly Leu Glu Asn Glu Ala Glu Lys Pro Ser 195 200 205

Asn Ala Leu Leu Thr Arg Ala Trp Ser Pro Gly Trp Ser Asn Ala Asp 210 215 220

Lys Leu Leu Asn Glu Phe Ile Glu Lys Gin Leu Ile Asp Tyr Ala Lys 225 230 235 240

Asn Ser Lys Val Val Gly Asn Ser Thr Ser Leu Leu Ser Pro Tyr 245 250 255

Leu His Phe Gly Glu Ile Ser Val Arg His Val Phe Gin Cys Ala Arg 260 265 270

Met Lys Gin Ile Ile Trp Ala Arg Asp Lys Asn Ser G1U Gly Glu Glu 275 280 285

Ser Ala Asp Leu Phe Leu Atg Gly Ile Gly Leu Arg Glu Tyr Ser Arg 290 295 300

Tyr Ile Cys Phe Asn Phe Pro Phe Thr His Glu Gin Ser Leu Leu Ser 305 310 315 320

His Leu Arg Phe Phe Pro Trp Asp Ala Asp Val Asp Lys Phe Lys Ala 325 330 335

Trp Arg Gin Gly Arg Thr Gly Tyr Pro Leu Val Asp Ala Gly Met Arg 340 345 350

Glu Leu Trp Ala Thr Gly Trp Met His Asn Arg Ile Arg Val Ile Val 355 360 365

Ser Ser Phe Ala Val Lys Phe Leu Leu Leu Pro Trp Lys Trp Gly Met 370 375 380

Lys Tyr Phe Trp Asp Thr Leu Leu Asp Ala Asp Leu Glu Cys Asp Ile 385 390 395 400

Leu Gly Trp Gin Tyr Ile Ser Gly Ser Ile Pro Asp Gly His Glu Leu 405 410 415

Asp Arg Leu Asp Asn Pro Ala Leu Gin Gly Ala Lys Tyr Asp Pro Glu 420 425 430

Gly Glu Tyr Ile Arg Gin Trp Leu Pro Glu Leu Ala Arg Leu Pro Thr 435 440 445

Glu Trp Ile His His Pro Trp Asp Ala Pro Leu Thr Val Leu Lys Ala 450 455 460

Ser Gly Val Glu Leu Gly Thr Asn Tyr Ala Lys Pro Ile Val Asp Ile 465 470 475 480

Asp Thr Ala Arg Glu Leu Leu Ala Lys Ala Ile Ser Arg Thr Arg Glu 485 490 495

Ala Gin Ile Met Ile Gly Gly Gly Gly Gly Ser Gly 500 505 510

Gly Ser Glu Gin Lys Leu Ile Ser Glu Glu Asp Leu Gly Glu Ser Leu 515 520 525

Phe Lys Gly Pro Arg Asp Tyr Asn Pro Ile Ser Ser Thr Ile Cys His 530 535 540

Leu Thr Asn Glu Ser Asp Gly His Thr Thr Ser Leu Tyr Gly Ile Gly 545 550 555 560

Phe Gly Pro Phe Ile Ile Thr Asn Lys His Leu Phe Arg Arg Asn Asn 565 570 575

Gly Thr Leu Leu Val Gin Ser Leu His Gly Val Phe Lys Val Lys Asn 580 585 590

Thr Thr Thr Leu Gin Gin His Leu Ile Asp Gly Arg Asp Met Ile Ile 595 600 605

Ile Arg Met Pro Lys Asp Pro Pro Phe Pro Gin Lys Leu Lys Phe 610 615 620

Arg Glu Pro Gin Arg Glt Glu Arg Ile Cys Leu val Thr Thr Asr Phe 625 630 635 640

Gin Thr <210> 61 <211> 960

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (930) <400> 61 atg cac cac cac cac cac cac aat gga gct ata gga ggt gac ctt ttg 48

Met His His His His His As Gly Gly As Leu Leu 15 10 15 ctc aat ttt cct gac atg tcg gtc cta gag cgc caa agg gct cac ctc 96

Leu Asn Phe Pro Asp Met Ser Val Leu Glu Arg Gin Arg Ala His Leu 20 25 30 aag tac ctc aat ccc acc ttt gat tet cct ctc gcc ggc ttc ttt gcc 144

Lys Tyr Leu Asn Pro Thr Phe Asp Ser Pro Leu Ala Gly Phe Phe Ala 35 40 45 gat tet tca atg att acc ggc ggc gag atg gac agc tat ctt tcg act 192

Asp Ser Ser Met Ile Thr Gly Gly Glu Met Asp Ser Tyr Leu Ser Thr 50 55 60 gcc ggt ttg aat ctt ccg atg atg tac ggt gag acg acg gtg gaa ggt 240

Ala Gly Leu Asn Leu Pro Met Met Tyr Gly Glu Thr Thr Val Glu Gly 65 70 75 80 gat tca aga ctc tca att tcg ccg gaa acg acg ctt ggg act gga aat 288

Asp Ser Arg Leu Ser Ile Ser Pro Glu Thr Thr Leu Gly Thr Gly Asn 85 90 95 ttc aag gca gcg aag ttt gat aca gag act aag gat tgt aat gag gcg 336

Phe Lys Ala Ala Lys Phe Asp Thr Glu Thr Lys Asp Cys Asn Glu Ala 100 105 110 gcg aag aag atg acg atg aac aga gat gac cta gta gaa gaa gga gaa 384

Ala Lys Lys Met Thr Met Asn Arg Asp Asp Leu Val Glu Glu Gly 115 120 125 gaa gag aag tcg aaa ata aca gag caa aac aat ggg agc aca aaa agc 432

Glu Glu Lys Ser Lys Ile Thr Glu Gin Asn Asn Gly Ser Thr Lys Ser 130 135 140 ate aag aag atg aaa cac aaa gcc aag aaa gaa gag aac aat ttc tet 480

Ile Lys Lys Met Lys His Lys Ala Lys Lys Glu Glu Asn Asn Phe Ser 145 150 155 160 aat gat tca tet aaa gtg acg aag gaa ttg gag aaa acg gat tat att 528

Asn Asp Ser Ser Lys Val Thr Lys Glu Leu Glu Lys Thr Asp Tyr Ile 165 170 175 ggc ggc tet ggc ggc ggc tcc gga ggc tet aag agc atg tet agc atg 576

Gly Gly Ser Gly Gly Gly Ser Gly Gly Ser Lys Ser Met Ser Ser Met 180 185 190 gtg tca gac acc agt tgc aca ttc cct tca tet gat ggc ata ttc tgg 624

Val Ser Asp Thr Ser Cys Thr Phe Pro Ser Ser Asp Gly Ile Phe Trp 195 200 205 aag cat tgg att caa acc aag gat ggg cag tgt ggc agt cca tta gta 672

Lys His Trp Ile Gin Thr Lys Asp Gly Gin Cys Gly Ser Pro Leu Val 210 215 220 tca act aga gat ggg ttc att gtt ggt ata cac tca gca tcg aat ttc 720

Ser Thr Arg Asp Gly Phe Ile Val Gly Ile His Ser Ala Ser Asn Phe 225 230 235 240 acc aac aca aac aat tat tc aca agc gtg ccg aaa aac ttc atg gaa 768

Thr Asn Thr Asn Asn Tyr Phe Thr Ser Val Pro Lys Asn Phe Met Glu 245 250 255 ttg ttg aca aat cag gag gcg cag cag tgg gtt agt ggt tgg ega tta 816

Leu Leu Thr Asn Gin Glu Ala Gin Gin Trp Val Ser Gly Trp Arg Leu 260 265 270 aat gct gac tca gta ttg tgg ggg ggc cat aaa gtt ttc atg agc aaa 864

Asn Ala Asp Ser Val Leu Trp Gly Gly His Lys Val Phe Met Ser Lys 275 280 285 cct gaa gag cct ttt cag cca gtt aag gaa gcg act caa ctc atg agt 912

Pro Glu Glu Pro Phe Gin Pro Val Lys Glu Ala Thr Gin Leu Met Ser 290 295 300 gaa ttg gtg tac tchg caa tacccatacg atgttccaga ttacgcttaa 960

Glu Leu Val Tyr Ser Gin 305 310 <210> 62 <211> 310

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 62

Met His He 's His His His Asn Gly As Leu Leu 15 10 15

Leu Asn Phe Pro Asp Met Ser Val Leu Glu Arg Gin Arg Ala His Leu 20 25 30

Lys Tyr Leu Asn Pro Thr Phe Asp Ser Pro Leu Ala Gly Phe Phe Ala 35 40 45

Asp Ser Ser Met Ile Thr Gly Gly Glu Met Asp Ser Tyr Leu Ser Thr 50 55 60

Ala Gly Leu Asn Leu Pro Met Met Tyr Gly Glu Thr Thr Val Glu Gly 65 70 75 80

Asp Ser Arg Leu Ser Ile Ser Pro Glu Thr Thr Leu Gly Thr Gly Asn 85 90 95

Phe Lys Ala Ala Lys Phe Asp Thr Glu Thr Lys Asp Cys Asn Glu Ala 100 105 110

Ala Lys Lys Met Thr Met Asn Arg Asp Asp Leu Val Glu Glu Gly 115 120 125

Glu Glu Lys Ser Lys Ile Thr Glu Gin Asn Gly Ser Thr Lys Ser 130 135 140

Ile Lys Lys Met Lys His Lys Ala Lys Lys Glu Glu Asn Asn Phe Ser 145 150 155 160

Asn Asp Ser Ser Lys Val Thr Lys Glu Leu Glu Lys Thr Asp Tyr Ile 165 170 175

Gly Gly Ser Gly Gly Gly Ser Gly Gly Ser Lys Ser Met Ser Ser Met 180 185 190

Val Ser Asp Thr Ser Cys Thr Phe Pro Ser Ser Asp Gly Ile Phe Trp 195 200 205

Lys His Trp Ile Gin Thr Lys Asp Gly Gin Cys Gly Ser Pro Leu Val 210 215 220

Ser Thr Arg Asp Gly Phe Ile Val Gly Ile His Ser Ala Ser Asn Phe 225 230 235 240

Thr Asn Thr Asn Asn Tyr Phe Thr Ser Val Pro Lys Asn Phe Met Glu 245 250 255

Leu Leu Thr Asn Gin Glu Ala Gin Gin Trp Val Ser Gly Trp Arg Leu 260 265 270

Asn Ala Asp Ser Val Leu Trp Gly Gly His Lys Val Phe Met Ser LyS 275 280 285

Pro Glu Glu Pro Phe Gin Pro Val Lys Glu Ala Thr Gin Leu Met Ser 290 295 300

Glu Leu Val Tyr Ser Gin 305 310 <210> 63 <211> 1938

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (1935) <400> 63 atg cac cac cac cac cac cac ggc tet ggc aag atg gac aaa aag act 48

Met His His His His Gly Ser Gly Lys Met Asp Lys Lys Thr 1 5 10 15 ata gtt tgg ttt aga aga gac cta agg att gag gat aat cct gca tta 96

Ile Val Trp Phe Arg Arg Asp Leu Arg Ile Glu Asp Asn Pro Ala Leu 20 25 30 gca gca get get cac gaa gga tet gtt ttt cct gtc ttc att tgg tgt 144

Ala Ala Ala Ala His Glu Gly Ser Val Phe Pro Val Phe Ile Trp Cys 35 40 45 cct gaa gaa gaa gaga cag ttt tat cct gga aga get tca aga tgg tgg 192

Pro Glu Glu Gly Gly Phe Tyr Pro Gly Arg Ala Ser Arg Trp Trp 50 55 60 atg aaa caa tca ctt get cac tta tet caa tcc ttg aag get ctt gga 240

Met Lys Gin Ser Leu Ala His Leu Ser Gin Ser Leu Lys Ala Leu Gly 65 70 75 80 tet gac ete act tta ate aaa acc cac aac acg att tca gcg ate ttg 288

Ser Asp Leu Thr Leu Ile Lys Thr His Asn Thr Ile Ser Ala Ile Leu 85 90 95 gat tgt ate ege gtt acc ggt get aca aaa gtc gtc ttt aac cac ete 336

Asp Cys Ile Arg Val Thr Gly Ala Thr Lys Val Val Phe Asn His Leu 100 105 110 tat gat cct gtt teg tta gtt cgg gac cat acc gta aag gag aag ctg 384

Tyr Asp Pro Val Ser Leu Val Arg Asp His Thr Val Lys Glu Lys Leu 115 120 125 gtg gaa cgt ggg ate tet gtg caa agc tac aat gga gat cta ttg tat 432

Val Glu Arg Gly Ile Ser Val Gin Ser Tyr Asn Gly Asp Leu Leu Tyr 130 135 140 gaa ccg tgg gag ata tac tgc gaa aag ggc aaa cct ttt acg agt ttc 480

Glu Pro Trp Glu Ile Tyr Cys Glu Lys Gly Lys Pro Phe Thr Ser Phe 145 150 155 160 aat tet tac tgg aag aaa tgc tta gat atg teg att gaa tcc gtt atg 528

Asn Ser Tyr Trp Lys Lys Cys Leu Asp Met Ser Ile Glu Ser Val Met 165 170 175 ctt cct cct cct cgg ttg atg cca ata act gca gcg get gaa gcg 576

Leu Pro Pro Pro Trp Arg Leu Met Pro Ile Thr Ala Ala Ala Glu Ala 180 185 190 att tgg gcg tgt teg att gaa gaa cta ggg ctg gag aat gag gcc gag 624

Ile Trp Ala Cys Ser Ile Glu Glu Leu Gly Leu Glu Asn Glu Ala Glu 195 200 205 aaa ccg agc aat gcg ttg tta act aga get tgg tet cca gga tgg agc 672

Lys Pro Ser Asn Ala Leu Leu Thr Arg Ala Trp Ser Pro Gly Trp Ser 210 215 220 aat get gat aag tta cta aat gag ttc ate gag aag cag ttg ata gat 720

Asn Ala Asp Lys Leu Leu Asn Glu Phe Ile Glu Lys Gin Leu Ile Asp 225 230 235 240 tat gca aag aac agc aag aaa gtt gtt ggg aat tet act tca cta ctt 768

Tyr Ala Lys Asn Ser Lys Lys Val Val Gly Asn Ser Thr Ser Leu Leu 245 250 255 tet ccg tat ete cat ttc ggg gaa ata agc gtc aga cac gtt ttc cag 816

Ser Pro Tyr Leu His Phe Gly Glu Ile Ser Val Arg His Val Phe Gin 260 265 270 tgt gcc cgg atg aaa caa att ata tgg gca aga gat aag aac agt gaa 864

Cys Ala Arg Met Lys Gin Ile Ile Trp Ala Arg Asp Lys Asn Ser Glu 275 280 285 gga gaa gaa agt gca gat ctt ttt ctt agg gga ate ggt tta aga gag 912

Gly Glu Glu Ser Ala Asp Leu Phe Leu Arg Gly Ile Gly Leu Arg Glu 290 295 300 tat tet cgg tat ata tgt ttc aac ttc ccg ttt act cac gag caa teg 960

Tyr Ser Arg Tyr Ile Cys Phe Asn Phe Pro Phe Thr His Glu Gin Ser 305 310 315 320 ttg ttg agt cat ctt ttt ttc cct tgg gat get gat gtt gat aag 1008

Leu Leu Ser His Leu Arg Phe Phe Pro Trp Asp Ala Asp Val Asp Lys 325 330 335 ttc aag gcc tgg aga caa ggc agg acc ggt tat ccg ttg gtg gat gcc 1056

Phe Lys Ala Trp Arg Gin Gly Arg Thr Gly Tyr Pro Leu Val Asp Ala 340 345 350 gga atg agg gag ctt tgg get acc gga tgg atg cat aac aga ata aga 1104

Gly Met Arg Glu Leu Trp Ala Thr Gly Trp Met His Asn Arg ile Arg 355 360 365 gtg att gtt tta agc ttt gct gtg aag ttt ctt ctt ctt cgg aaa 1152

Val Ile Val Ser Ser Phe Ala Val Lys Phe Leu Leu Leu Pro Trp Lys 370 375 380 tgg gga atg aag tat ttc tgg gat aca ctt ttg gat gct gat ttg gaa 1200

Trp Gly Met Lys Tyr Phe Trp Asp Thr Leu Leu Asp Ala Asp Leu Glu 385 390 395 400 tgt gac ate ctt ggc tgg cag tat ate tet ggg agt ate ccc gat ggc 1248

Cys Asp Ile Leu Gly Trp Gin Tyr Ile Ser Gly Ser Ile Pro Asp Gly 405 410 415 cac gag ctt gat ege ttg gac aat ccc gcg tta caa ggc gcc aaa tat 1296

His Glu Leu Asp Arg Leu Asp Asn Pro Ala Leu Gin Gly Ala Lys Tyr 420 425 430 gac cca gaa ggt gag tac ata agg caa tgg ctt ccc gag ctt gcg aga 1344

Asp Pro Glu Gly Glu Tyr Ile Arg Gin Trp Leu Pro Glu Leu Ala Arg 435 440 445 ttg cca act gaa tgg ate cat cat cca tgg gac gct cct tta acc gta 1392

Leu Pro Thr Glu Trp Ile His His Pro Trp Asp Ala Pro Leu Thr Val 450 455 460 ctc aaa gct tet ggt gtg gaa ctc gga aca aac tat gcg aaa ccc att 1440

Leu Lys Ala Ser Gly Val Glu Leu Gly Thr Asr Tyr Ala Lys Pro Ile 465 470 475 480 gta gac gac cgt gag cta cta gct aaa gct att tca aga 1488

Val Asp Ile Asp Thr Ala Arg Glu Leu Leu Ala Lys Ala Ile Ser Arg 485 490 495 acc cgt gaa gca cag ate atg ate gga gca gca ggc ggc tet ggc ggc 1536

Thr Arg Glu Ala Gin Ile Met Ile Gly Ala Gly Gly Gly Gly Gly 500 505 510 ggc tcc gga ggc tet gag cag aag ctg ate agc gag gag gac ctg agc 1584

Gly Ser Gly Gly Ser Glu Gin Lys Leu Ile Ser Glu Glu Asp Leu Ser 515 520 525 aag agc ctg ttc ege ggc ctg ege gac tac aac ccc ate gcc agc agc 1632

Lys Ser Leu Phe Arg Gly Leu Arg Asp Tyr Asn Pro Ile Ala Ser Ser 530 535 540 ate tgc cag ctg aac aac agc agc ggc gcc ege cag agc gag atg ttc 1680

Ile Cys Gin Leu Asn Asn Ser Ser Gly Ala Arg Gin Ser Glu Met Phe 545 550 555 560 ggc ctg ggc ttc ggc ggc ctg ate gtg acc aac cag cac ctg ttc aag 1728

Gly Leu Gly Ply Gly Gly Leu Ile Val Thr Asn Gin His Leu Phe Lys 565 570 575 ege aac gac ggc gag ctg acc ate ege agc cac cac ggc gag ttc gtg 1776

Arg Asn Asp Gly Glu Leu Thr Ile Arg Ser His His Gly Glu Phe Val 580 585 590 gtg aag gac acc aag acc ctg aag ctg ctg ccc tgc aag ggc ege gac 1824

Val Lys Asp Thr Lys Thr Leu Lys Leu Leu Lys Leu Pro Cys Lys Gly Arg Asp 595 600 605 ate gtg ate ate ege ctg ccc aag gac ttc ccc ccc ttc ccc aag ege 1872

Ile Val Ile Ile Arg Leu Pro Lys Asp Pro Pro Phe Pro Lys Arg 610 615 620 ctg caa ttc ege acc ccc acc acc gag gac ege gtg tgc ctg ate ggc 1920

Leu Gin Phe Arg Thr Pro Thr Thr Glu Asp Arg Val Cys Leu Ile Gly 625 630 635 640 agc aac ttc cag acc taa 1938

Ser Asn Phe Gin Thr 645 <210> 64 <211> 645

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 64

Met His Lily Lys Thr 15 10 15

Ile Val Trp Phe Arg Arg Asp Leu Arg Ile Glu Asp Asn Pro Ala Leu 20 25 30

Ala Ala Ala His Glu Gly Ser Val Phe Pro Val Phe Ile Trp Cys 35 40 45

Pro Glu Glu Gly Gly Phe Tyr Pro Gly Arg Ala Ser Arg Trp Trp 50 55 60

Met Lys Gin Ser Leu Ala His Leu Ser Gin Ser Leu Lys Ala Leu Gly 65 70 75 80

Ser Asp Leu Thr Leu Ile Lys Thr His Asn Thr Ile Ser Ala Ile Leu 85 90 95

Asp Cys Ile Arg Val Thr Gly Ala Thr Lys Val Val Phe Asn His Leu 100 105 110

Tyr Asp Pro Val Ser Leu Val Arg Asp His Thr Val Lys Glu Lys Leu 115 120 125

Val Glu Arg Gly Ile Ser Val Gin Ser Tyr Asn Gly Asp Leu Leu Tyr 130 135 140

Glu Pro Trp Glu Ile Tyr Cys Glu Lys Gly Lys Pro Phe Thr Ser Phe 145 150 155 160

Asn Ser Tyr Trp Lys Lys Cys Leu Asp Met Ser ile Glu Ser Val Met 165 170 175

Leu Pro Pro Pro Trp Arg Leu Met Pro Ile Thr Ala Ala Ala Glu Ala 180 185 190

Ile Trp Ala Cys Ser Ile Glu Glu Leu Glu Leu Glu Asn Glu Ala Glu 195 200 205

Lys Pro Ser Asn Ala Leu Leu Thr Arg Ala Trp Ser Pro Gly Trp Ser 210 215 220

Asn Ala Asp Lys Leu Leu Asn Glu Phe Ile Glu Lys Gin Leu Ile Asp 225 230 235 240

Tyr Ala Lys Asn Ser Lys Lys Val Val Gly Asn Ser Thr Ser Leu Leu 245 250 255

Ser Pro Tyr Leu His Phe Gly Glu Ile Ser Val Arg His Val Phe Gin 260 265 270

Cys Ala Arg Met Lys Gin ile Ile Trp Ala Arg Asp Lys Asn Ser Glu 275 280 285

Gly Glu Glu Ser Ala Asp Leu Phe Leu Arg Gly Ile Gly Leu Arg Glu 290 295 300

Tyr Ser Arg Tyr Ile Cys Phe Asn Phe Pro Phe Thr His Glu Gin Ser 305 310 315 320

Leu Leu Ser His Leu Arg Phe Phe Pro Trp Asp Ala Asp Val Asp Lys 325 330 335

Phe Lys Ala Trp Arg Gin Gly Arg Thr Gly Tyr Pro Leu Val Asp Ala 340 345 350

Gly Met Arg Glu Leu Trp Ala Thr Gly Trp Met His Asn Arg Ile Arg 355 360 365

Val Ile Val Ser Ser Phe Ala Val Lys Phe Leu Leu Leu Pro Trp Lys 370 375 380

Trp Gly Met Lys Tyr Phe Trp Asp Thr Leu Leu Asp Ala Asp Leu Glu 385 390 395 400

Cys Asp Ile Leu Gly Trp Gin Tyr Ile Ser Gly Ser Ile Pro Asp Gly 405 410 415

His Glu Leu Asp Arg Leu Asp Asn Pro Ala Leu Gin Gly Ala Lys Tyr 420 425 430

Asp Pro Glu Gly Glu Tyr Ile Arg Gin Trp Leu Pro Glu Leu Ala Arg 435 440 445

Leu Pro Thr Glu Trp Ile His Pro Pro Asp Ala Pro Leu Thr Val 450 455 460

Leu Lys Ala Ser Gly Val Glu Leu Gly Thr Asn Tyr Ala Lys Pro Ile 465 470 475 480

Val Asp Ile Asp Thr Ala Arg Glu Leu Leu Ala Lys Ala Ile Ser Arg 485 490 495 fhr Arg Glu Ala Gin Ile Met Ile Gly Ala Gly Gly Ser Gly Gly 500 505 510

Gly Ser Gly Gly Ser Glu Gin Lys Leu Ile Ser Glu Glu Asp Leu Ser 515 520 525

Lys Ser Leu Phe Arg Gly Leu Arg Asp Tyr Asn Pro Ile Ala Ser Ser 530 535 540

Ile Cys Gin Leu Asn Asn Ser Ser Gly Ala Arg Gin Ser Glu Met Phe 545 550 555 560

Gly Leu Gly Ply Gly Gly Leu Ile Val Thr Asn Gin His Leu Phe Lys 565 570 575

Arg Asn Asp Gly Glu Leu Thr Ile Arg Ser His His Gly Glu Phe Val 580 585 590

Val Lys Asp Thr Lys Thr Leu Lys Leu Leu Pro Cys Lys Gly Arg Asp 595 600 605

Ile Val Ile Ile Arg Leu Pro Lys Asp Phe Pro Pro Phe Pro Lys Arg 610 615 620

Leu Gin Phe Arg Thr Pro Thr Thr Glu Asp Arg Val Cys Leu Ile Gly 625 630 635 640

Ser Asn Phe Gin Thr 645 <210> 65 <211> 951

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (948) <400> 65 atg gag cag aag ctg ate agc gag gag gat ctg aat gga get ata gga 48

Met Glu Gin Lys Leu Ile Ser Glu Glu Asp Leu Asn Gly Ala Ile Gly 15 10 15 ggt gac ctt ttg ete aat ttt cct gac atg teg gtc cta gag ege caa 96

Gly Asp Leu Leu Leu Asn Phe Pro Asp Met Ser Val Leu Glu Arg Gin 20 25 30 agg get cac ete aag tac ete aat ccc acc ttt gat tet cct ete gcc 144

Arg Ala His Leu Lys Tyr Leu Asn Pro Thr Phe Asp Ser Pro Leu Ala 35 40 45 ggc ttc ttt gcc gat tet tca atg att acc ggc ggc gag atg gac agc 192

Gly Phe Phe Ala Asp Ser Ser Met Ile Thr Gly Gly Glu Met Asp Ser 50 55 60 tat ctt teg act gcc ggt ttg aat ctt ccg atg atg tac ggt gag acg 240

Tyr Leu Ser Thr Ala Gly Leu Asn Leu Pro Met Met Tyr Gly Glu Thr 65 70 75 80 acg gtg gaa ggt gat tca aga ete tca att teg ccg gaa acg acg ctt 288

Thr Val Glu Gly Asp Ser Arg Leu Ser Ile Ser Pro Glu Thr Thr Leu 85 90 95 ggg act gga aat ttc aag gca gcg aag ttt gat aca gag act aag gat 336

Gly Thr Gly Asn Phe Lys Ala Ala Lys Phe Asp Thr Glu Thr Lys Asp 100 105 110 tgt aat gag gcg gcg aag aag atg acg atg aac aga gat gac cta gta 384

Cys Asn Glu Ala Lys Lys Met Thr Met Asn Arg Asp Asp Leu Val 115 120 125 gaa gaa gga gaa gaa gag aag teg aaa ata aca gag caa aac aat ggg 432

Glu Glu Gly Glu Glu Lys Ser Lys Ile Thr Glu Gin Asn Asn Gly 130 135 140 agc aca aaa agc ate aag aag atg aaa cac aaa gec aag aaa gaa gag 480

Ser Thr Lys Ser Ile Lys Lys Met Lys His Lys Ala Lys Lys Glu Glu 145 150 155 160 aac aat ttc tet aat gat tca tet aaa gtg acg aag gaa ttg gag aaa 528

Asn Asn Phe Ser Asn Ser Ser Lys Val Thr Lys Glu Leu Glu Lys 165 170 175 acg gat tat att ggc ggc ggc ggc ggc ggc gga tcc ggc tec gga ggc aag 576

Thr Asp Tyr Ile Gly Gly Ser Gly Gly Gly Ser Gly Ser Gly Gly Lys 180 185 190 agc ate agc agc acc atg agc gag acc agc gcc acc tac ccc gtg gac 624

Ser Ile Ser Ser Thr Met Ser Glu Thr Ser Ala Thr Tyr Pro Val Asp 195 200 205 aac agc cac ttc tgg aag cac tgg ate agc acc aag gac ggc cac tgc 672

Asn Ser His Phe Trp Lys His Trp Ile Ser Thr Lys Asp Gly His Cys 210 215 220 ggc ctg ccc ate gtg agc acc ege gac ggc agc ate ctg ggc ctg cac 720

Gly Leu Pro Ile Val Ser Thr Arg Asp Gly Ser Ile Leu Gly Leu His 225 230 235 240 agc ctg gcc aac agc aac acc cag aac ttc gcc gcc ttc ccc 768

Ser Leu Ala Asn Ser Thr Asr Thr Gin Asn Phe Tyr Ala Ala Phe Pro 245 250 255 gac aac ttc gag acc acc tac ctg agc aac cag gac aac gac aac tgg 816

Asp Asn Phe Glu Thr Thr Tyr Leu Ser Asn Gin Asp Asn Asp Asn Trp 260 265 270 ate aag cag tgg ege tac aac ccc gac gag gtg tgc tgg ggc agc ctg 864

Ile Lys Gin Trp Arg Tyr Asn Pro Asp Glu Val Cys Trp Gly Ser Leu 275 280 285 caa ctg aag ege gac ate ccc cag agc ccc ttc acc ate tgc aag ctg 912

Gin Leu Lys Arg Asp Ile Pro Gin Ser Pro Phe Thr Ile Cys Lys Leu 290 295 300 ctg acc gac ctg gac ggc gag ttc gtg tac acc cag taa 951

Leu Thr Asp Leu Asp Gly Glu Phe Val Tyr Thr Gin 305 310 315 <210> 66 <211> 316

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 66

Met Glu Gin Lys Leu Ile Ser Glu Glu Asp Leu Asn Gly Ala Ile Gly 15 10 15

Gly Asp Leu Leu Leu Asn Phe Pro Asp Met Ser Val Leu Glu Arg Gin 20 25 30

Arg Ala His Leu Lys Tyr Leu Asn Pro Thr Phe Asp Ser Pro Leu Ala 35 40 45

Gly Phe Phe Ala Asp Ser Ser Met Ile Thr Gly Gly Glu Met Asp Ser 50 55 60

Tyr Leu Ser Thr Ala Gly Leu Asn Leu Pro Met Met Tyr Gly Glu Thr 65 70 75 80

Thr Val Glu Gly Asp Ser Arg Leu Ser Ile Ser Pro Glu Thr Thr Leu 85 90 95

Gly Thr Gly Asn Phe Lys Ala Ala Lys Phe Asp Thr Glu Thr Lys Asp 100 105 110

Cys Asn Glu Ala Ala Lys Lys Met Thr Met Asn Arg Asp Asp Leu Val 115 120 125

Glu Glu Gly Glu Glu Lys Ser Lys Ile Thr Glu Gin Asn Asn Gly 130 135 140

Ser Thr Lys Ser Ile Lys Lys Met Lys His Lys Ala Lys Lys Glu Glu 145 150 155 160

Asn Asn Phe Ser Asn Asp Ser Ser Lys Val Thr Lys Glu Leu Glu Lys 165 170 175

Thr Asp Tyr Ile Gly Gly Ser Gly Gly Gly Ser Gly Ser Gly Gly Lys 180 185 190

Ser Ile Ser Ser Thr Met Ser Glu Thr Ser Ria Thr Tyr Pro Val Rsp 195 200 205

Asn Ser His Phe Trp Lys His Trp Ile Ser Thr Lys Asp Gly His Cys 210 215 220

Gly Leu Pro Ile Val Ser Thr Arg Asp Gly Ser Ile Leu Gly Leu His 225 230 235 240

Ser Leu Ala Asn Ser Thr Asr Thr Gin Asn Phe Tyr Ala Ala Phe Pro 245 250 255

Asp Asn Phe Glu Thr Thr Tyr Leu Ser Asn Gin Asp Asn Asp Asn Trp 260 265 270

Ile Lys Gin Trp Arg Tyr Asn Pro Asp Glu Val Cys Trp Gly Ser Leu 275 280 285

Gin Leu Lys Arg Asp Ile Pro Gin Ser Pro Phe Thr Ile Cys Lys Leu 290 295 300

Leu Thr Asp Leu Asp Gly Glu Phe Val Tyr Thr Gin 305 310 315 <210> 67 <211> 2304

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (2301) <400> 67 atg gac aca cgt aaa tat tta ggc aaa caa aat gtc tat 48

Met Ile Lys Ile Ala Thr Arg Lys Tyr Leu Gly Lys Gin Asn Val Tyr 15 10 15 gac att gga gtt gag ege gac cat aat ttt gca ete aaa aat ggc ttc 96

Asp Ile Gly Val Glu Arg Asp His Asn Phe Ala Leu Lys Asn Gly Phe 20 25 30 ata get tet aat tgt ttc aat gat act tat aga tat att gac acc get 144

Ile Ala Ser Asn Cys Phe Asn Asp Thr Tyr Arg Tyr Ile Asp Thr Ala 35 40 45 ate ete agc gtg gtg cca ttt cac cac ggc ttc ggc atg ttc acc acg 192

Ile Leu Ser Val Val Phe His Gly Phe Gly Met Phe Thr Thr 50 55 60 ctg ggc tac ttg ate tgc ggc ttt cgg gtc gtg ete atg tac ege ttc 240

Leu Gly Tyr Leu Ile Cys Gly Phe Arg Val Val Leu Met Tyr Arg Phe 65 70 75 80 gag gag gag cta ttc ttg ege agc ttg caa gac tat aag att caa tet 288

Glu Glu Glu Leu Phe Leu Arg Ser Leu Gin Asp Tyr Lys Ile Gin Ser 85 90 95 gcc ctg ctg gtg ccc aca cta ttt agc ttc ttc get aag agc act ete 336

Ala Leu Leu Val Pro Thr Leu Phe Ser Phe Phe Ala Lys Ser Thr Leu 100 105 110 ate gac aag tac gac cta agc aac ttg cac gag ate gcc agc ggc ggg 384

Ile Asp Lys Tyr Asp Leu Ser Asn Leu His Glu Ile Ala Ser Gly Gly 115 120 125 gcg ccg ete agc aag gag gta ggt gag gcc gtg gcc aaa ege ttc cac 432

Ala Pro Leu Ser Lys Glu Val Gly Glu Ala Val Ala Lys Arg Phe His 130 135 140 cta cg ggc cate ggc cg ggc ac acc ac ac acc ac gc 480

Leu Pro Gly Ile Arg Gin Gly Tyr Gly Leu Thr Glu Thr Thr Ser Ala 145 150 155 160 att ctg ate acc ccc gaa ggg gac gac aag cct ggc gca gta ggc aag 528

Ile Leu Ile Thr Pro Glu Gly Asp Asp Lys Pro Gly Ala Val Gly Lys 165 170 175 gtg ccc ttc ttc gag get aag gtg gtg gac ttg gac acc ggt aag 576

Val Val Pro Phe Phe Glu Ala Lys Val Val Asp Leu Asp Thr Gly Lys 180 185 190 aca ctg ggt gtg aac cag ege ggc gag ctg tgc gtc cgt ggc ccc atg 624

Thr Leu Gly Val Asn Gin Arg Gly Glu Leu Cys Val Arg Gly Pro Met 195 200 205 ate atg agc ggc tac gtt aac aac ccc gag get aca aac get ete ate 672

Ile Met Ser Gly Tyr Val Asn Asn Pro Glu Ala Thr Asn Ala Leu Ile 210 215 220 gac aag gac ggg ctg cac agc ggc gac gac gac gac gac 720

Asp Lys Asp Gly Trp Leu His Ser Gly Asp Ile Ala Tyr Trp Asp Glu 225 230 235 240 gac gag cac ttc ttc ate gtg gac cgg ctg aag agc ctg ate aaa tac 768

Asp Glu His Phe Phe Ile Val Asp Arg Leu Lys Ser Leu Ile Lys Tyr 245 250 255 aag ggc tac cag gta gcc cca gcc gaa ctg gag agc ate ctg ctg caa 816

Lys Gly Tyr Gin Val Ala Pro Ala Glu Leu Glu Ser Ile Leu Leu Gin 260 265 '270 cac ccc aac ate tc gac gcc ggg gtc gcc gcc ctg ccc gac gac gat 864

His Pro Asn Ile Phe Asp Ala Gly Val Ala Gly Leu Pro Asp Asp Asp Asp Asp Asp Asp 275 280 285 gcc ggc gag ctg ccc gcc gtca

Ala Gly Glu Leu Pro Ala Val Val Val Leu Glu His Gly Lys Thr 290 295 300 atg acc gag aag gag ate gtg gac tat gtg gcc agc cag gtt aca acc 960

Met Thr Glu Lys Glu Ile Val Asp Tyr Val Ala Ser Gin Val Thr Thr 305 310 315 320 gcc aag aag ctg ege ggt ggt gtt gtg ttc gtg gac gag gtg cct aaa 1008

Ala Lys Lys Leu Arg Gly Gly Val Val Phe Val Asp Glu Val Pro Lys 325 330 335 gga ctg acc ggc aag ttg gac gcc ege aag ate ege gag att ete att 1056

Gly Leu Thr Gly Lys Leu Asp Ala Arg Lys Ile Arg Glu Ile Leu Ile 340 345 350 aag gcc aag aag gga tcc gaa aat ete tat ttc cag agc ggc ggt gcc 1104

Lys Ala Lys Lys Gly Ser Glu Asn Leu Tyr Phe Gin Ser Gly Gly Ala 355 360 365 aaa aac att aag aag ggc cca gcg cca ttc tac cca ete gaa gac ggg 1152

Lys Asn Ile Lys Lys Gly Pro Ala Pro Phe Tyr Pro Leu Glu Asp Gly 370 375 380 acc gcc cg gag gag cag gag cag gag atg aag ege tac gcc ctg gtg 1200

Thr Ala Gly Glu Gin Leu His Lys Ala Met Lys Arg Tyr Ala Leu Val 385 390 395 400 ccc ggc acc ate gcc ttt acc gac gca cat ate gag gtg gac att acc 1248

Pro Gly Thr Ile Ala Phe Thr Asp Ala His Ile Glu Val Asp Ile Thr 405 410 415 tac gcc gag tac ttc gag atg agc gtt cgg ctg gca gaa get atg aag 1296

Tyr Ala Glu Tyr Phe Glu Met Ser Val Arg Leu Ala Glu Ala Met Lys 420 425 430 ege tat ggg ctg aat aca aac cat cgg ate gtg gtg tgc agc gag aat 1344

Arg Tyr Gly Leu Asn Thr Asn His Arg Ile Val Val Cys Ser Glu Asn 435 440 445 agc ttg cag ttc ttc atg ccc gtg ttg ggt gcc ctg ttc ate ggt gtg 1392

Ser Leu Gin Phe Phe Met Pro Val Leu Gly Ala Leu Phe Ile Gly Val 450 455 460 get gtg gcc cca get aac gac ate tac aac gag ege gag ctg ctg aac 1440

Ala Val Ala Pro Ala Asn Asp Ile Tyr Asn Glu Arg Glu Leu Leu Asn 465 470 475 480 agc atg ggc ate agc cag ccc acc gtc gta ttc gtg agc aag aaa ggg 1488

Ser Met Gly Ile Ser Gin Pro Thr Val Val Phe Val Ser Lys Lys Gly 485 490 495 ctg caa aag ate ete aac gtg caa aag aag cta ccg ate ata caa aag 1536

Leu Gin Lys Ile Leu Asn Val Gin Lys Leu Pro Ile Ile Gin Lys 500 505 510 ate ate ate atg gat agc aag acc gac tac cag ggc ttc caa agc atg 1584

Ile Ile Ile Met Asp Ser Lys Thr Asp Tyr Gin Gly Phe Gin Ser Met 515 520 525 tac acc ttc gtg act tcc cat ttg cca ccc ggc ttc aac gag tac gac 1632

Tyr Thr Phe Val Thr Ser His Leu Pro Pro Gly Phe Asn Glu Tyr Asp 530 535 540 ttc gtg ccc gag agc ttc gac cgg gac aaa acc ate gcc ctg ate atg 1680

Phe Val Pro Glu Ser Phe Asp Arg Asp Lys Thr Ile Ala Leu Ile Met 545 550 555 560 aac agt agt ggc agt acc gga ttg ccc aag ggc gta gcc cta ccg cac 1728

Asn Ser Ser Gly Ser Thr Gly Leu Pro Lys Gly Val Ala Leu Pro His 565 570 575 ege acc get tgt gtc ega ttc agt cat gcc ege gac ccc ate ttc ggc 1776

Arg Thr Ala Cys Val Arg Phe Ser His Ala Arg Asp Pro Ile Phe Gly 580 585 590 aac cag ate ate ccc gcc gag tac tgt tta agc tat gaa acg gaa ata 1824

Asn Gin Ile Ile Pro Ala Glu Tyr Cys Leu Ser Tyr Glu Thr Glu Ile 595 600 605 ttg aca gta gaa tat gga tta tta ccg att ggt aaa att gta gaa aag 1872

Leu Thr Val Glu Tyr Gly Leu Leu Pro Ile Gly Lys Ile Val Glu Lys 610 615 620 cgc ate gaa tgt act gtt tat agc gtt gat aat aat gga aat att tat 1920

Arg Ile Glu Cys Thr Val Tyr Ser Val Asp Asn Asn Gly Asn Ile Tyr 625 630 635 640 aca caa cct gta gca caa tgg cac gat cgc gga gaa caa gag gtg ttt 1968

Thr Gin Pro Val Ala Gin Trp His Asp Arg Gly Glu Gin Glu Val Phe 645 650 655 gag tat tgt ttg gaa gat ggt tca ttg att cgg gca aca aaa gac cat 2016

Glu Tyr Cys Leu Glu Asp Gly Ser Leu Ile Arg Ala Thr Lys Asp His 660 665 670 aag ttt atg act gtt gat ggt caa atg ttg eca att gat gaa ata ttt 2064

Lys Phe Met Thr Val Asp Gly Gin Met Leu Pro Ile Asp Glu Ile Phe 675 680 685 gaa cgt gaa ttg gat ttg atg cgg gtt gat aat ttg ccg aac ggc ggc 2112

Glu Arg Glu Leu Asp Leu Met Arg Val Asp Asn Leu Pro Asn Gly Gly 690 695 700 aag ate gcc gtc aat tet get tgc aag aac tgg agt agc tta agc 2160

Lys Ile Ala Val Asn Ser Ala Cys Lys Asn Trp Phe Ser Ser Leu Ser 705 710 715 720 cac ttt gtg ate cac ctt aac agc cac ggc ttc cct ccc gag gtg gag 2208

His Phe wave Ile His Leu Asn Ser His Gly Phe Pro Pro Glu Val Glu 725 730 735 gag ccc gcc gcc ggc acc ctg ccc atg agc tgc gcc cag gag agc ggc 2256

Glu Gin Ala Ala Gly Thr Leu Pro Met Ser Cys Ala Gin Glu Ser Gly 740 745 750 atg gat aga cac cct get get tgc gcc agc gcc agg ate aac gtc taa 2304

Met Asp Arg His Pro Ala Ala Cys Ala Ser Ala Arg Ile Asn Val 755 760 765 <210> 68 <211> 767

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 68

Met Ile Lys Ile Ala Thr Arg Lys Tyr Leu Gly Lys Gin Asn Val Tyr 15 10 15

Asp Ile Gly Val Glu Arg Asp His Asn Phe Ala Leu Lys Asn Gly Phe 20 25 30

Ile Ala Ser Asn Cys Phe Asn Asp Thr Tyr Arg Tyr Ile Asp Thr Ala 35 40 45

Ile Leu Ser Val Val Phe His Gly Phe Gly Met Phe Thr Thr 50 55 60

Leu Gly Tyr Leu Ile Cys Gly Phe Arg Val Val Leu Met Tyr Arg Phe 65 70 75 80

Glu Glu Glu Leu Phe Leu Arg Ser Leu Gin Asp Tyr Lys Ile Gin Ser 85 90 95

Ala Leu Leu Val Pro Thr Leu Phe Ser Phe Phe Ala Lys Ser Thr Leu 100 105 110

Ile Asp Lys Tyr Asp Leu Ser Asn Leu His Glu Ile Ala Ser Gly Gly 115 120 125

Ala Pro Leu Ser Lys Glu Val Gly Glu Ala Val Ala Lys Arg Phe His 130 135 140

Leu Pro Gly Ile Arg Gin Gly Tyr Gly Leu Thr Glu Thr Thr Ser Ala 145 150 155 160

Ile Leu Ile Thr Pro Glu Gly Asp Asp Lys Pro Gly Ala Val Gly Lys 165 170 175

Val Val Pro Phe Phe Glu Ala Lys Val Val Asp Leu Asp Thr Gly Lys 180 185 190

Thr Leu Gly Val Asn Gin Arg Gly Glu Leu Cys Val Arg Gly Pro Met 195 200 205

Ile Met Ser Gly Tyr Val Asn Asn Pro Glu Ala Thr Asn Ala Leu Ile 210 215 220

Asp Lys Asp Gly Trp Leu His Ser Gly Asp Ile Ala Tyr Trp Asp Glu 225 230 235 240

Asp Glu His Phe Phe Ile Val Asp Arg Leu Lys Ser Leu Ile Lys Tyr 245 250 255

Lys Gly Tyr Gin Val Ala Pro Ala Glu Leu Glu Ser Ile Leu Leu Gin 260 265 270

His Pro Asn Ile Phe Asp Ala Gly Val Ala Gly Leu Pro Asp Asp Asp 275 280 285

Ala Gly Glu Leu Pro Ala Ala Val Val Leu Glu His Gly Lys Thr 290 295 300

Met Thr Glu Lys Glu Ile Val Asp Tyr Val Ala Ser Gin Val Thr Thr 305 310 315 320

Ala Lys Lys Leu Arg Gly Gly Val Val Phe Val Asp Glu Val Pro Lys 325 330 335

Gly Leu Thr Gly Lys Leu Asp Ala Arg Lys Ile Arg Glu Ile Leu Ile 340 345 350

Lys Ala Lys Lys Gly Ser Glu Asn Leu Tyr Phe Gin Ser Gly Gly Ala 355 360 365

Lys Asn Ile Lys Lys Gly Pro Ala Pro Phe Tyr Pro Leu Glu Asp Gly 370 375 380

Thr Ala Gly Glu Gin Leu His Lys Ala Met Lys Arg Tyr Ala Leu Val 385 390 395 400

Pro Gly Thr Ile Ala Phe Thr Asp Ala His Ile Glu Val Asp Ile Thr 405 410 415

Tyr Ala Glu Tyr Phe Glu Met Ser Val Arg Leu Ala Glu Ala Met Lys 420 425 430

Arg Tyr Gly Leu Asn Thr Asn His Arg Ile Val Val Cys Ser Glu Asn 435 440 445

Ser Leu Gin Phe Phe Met Pro Val Leu Gly Ala Leu Phe Ile Gly Val 450 455 460

Ala Val Ala Pro Ala Asn Asp Ile Tyr Asn Glu Arg Glu Leu Leu Asn 465 470 475 480

Ser Met Gly Ile Ser Gin Pro Thr Val Val Phe Val Ser Lys Lys Gly 485 490 495

Leu Gin Lys Ile Leu Asn Val Gin Lys Leu Pt Ile Ile Gin Lys 500 505 510

Ile Ile Ile Met Asp Ser Lys Thr Asp Tyr Gin Gly Phe Gin Ser Met 515 520 525

Tyr Thr Phe Val Thr Ser His Leu Pro Pro Gly Phe Asn Glu Tyr Asp 530 535 540

Phe Val Pro Glu Ser Phe Asp Arg Asp Lys Thr Ile Ala Leu Ile Met 545 550 555 560

Asn Ser Ser Gly Ser Thr Gly Leu Pro Lys Gly Val Ala Leu Pro His 565 570 575

Arg Thr Ala Cys Val Arg Phe Ser His Ala Arg Asp Pro Ile Phe Gly 580 585 590

Asn Gin Ile Ile Pro Ala Glu Tyr Cys Leu Ser Tyr Glu Thr Glu Ile 595 600 605

Leu Thr Val Glu Tyr Gly Leu Leu Pro Ile Gly Lys Ile Val Glu Lys 610 615 620

Arg Ile Glu Cys Thr Val Tyr Ser Val Asp Asn Asn Gly Asn Ile Tyr 625 630 635 640

Thr Gin Pro Val Ala Gin Trp His Asp Arg Gly Glu Gin Glu Val Phe 645 650 655

Glu Tyr Cys Leu Glu Asp Gly Ser Leu Ile Arg Ala Thr Lys Asp His 660 665 670

Lys Phe Met Thr Val Asp Gly Gin Met Leu Pro Ile Asp Glu Ile Phe 675 680 685

Glu Arg Glu Leu Asp Leu Met Arg Val Asp Asn Leu Pro Asn Gly Gly 690 695 700

Lys Ile Ala Val Asn Ser Ala Cys Lys Asn Trp Phe Ser Ser Leu Ser 705 710 715 720

His Phe Val Ile His Leu Asn Ser His Gly Phe Pro Pro Glu Val Glu 725 730 735

Glu Gin Ala Ala Gly Thr Leu Pro Met Ser Cys Ala Gin Glu Ser Gly 740 745 750

Met Asp Arg His Pro Ala Ala Cys Ala Ser Ala Arg Ile Asn Val 755 760 765 <210> 69 <211> 2304

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (1791) <400> 69 atg gac aca cgt aaa tat tta ggc aaa caa aat gtc tat 48

Met Ile Lys Ile Ala Thr Arg Lys Tyr Leu Gly Lys Gin Asn Val Tyr 15 10 15 gac att gga gtt gag ege gac cat aat ttt gca ete aaa aat ggc ttc 96

Asp Ile Gly Val Glu Arg Asp His Asn Phe Ala Leu Lys Asn Gly Phe 20 25 30 ata get tet aat tgt ttc aat gat act tat aga tat att gac acc get 144

Ile Ala Ser Asn Cys Phe Asn Asp Thr Tyr Arg Tyr Ile Asp Thr Ala 35 40 45 ate ete agc gtg gtg cca ttt cac cac ggc ttc ggc atg ttc acc acg 192

Ile Leu Ser Val Val Phe His Gly Phe Gly Met Phe Thr Thr 50 55 60 ctg ggc tac ttg ate tgc ggc ttt cgg gtc gtg ete atg tac ege ttc 240

Leu Gly Tyr Leu Ile Cys Gly Phe Arg Val Val Leu Met Tyr Arg Phe 65 70 75 80 gag gag gag cta ttc ttg ege agc ttg caa gac tat aag att caa tet 288

Glu Glu Glu Leu Phe Leu Arg Ser Leu Gin Asp Tyr Lys Ile Gin Ser 85 90 95 gcc ctg ctg gtg cec aca cta ttt agc ttc ttc get aag agc act ete 336

Ala Leu Leu Val Pro Thr Leu Phe Ser Phe Phe Ala Lys Ser Thr Leu 100 105 110 ate gac aag tac gac cta agc aac ttg cac gag ate gcc agc ggc ggg 384

Ile Asp Lys Tyr Asp Leu Ser Asn Leu His Glu Ile Ala Ser Gly Gly 115 120 125 gcg ccg ete agc aag gag gta ggt gag gcc gtg gcc aaa ege ttc cac 432

Ala Pro Leu Ser Lys Glu Val Gly Glu Ala Val Ala Lys Arg Phe His 130 135 140 cta cg ggc cate ggc cg ggc ac acc ac ac acc ac gc 480

Leu Pro Gly Ile Arg Gin Gly Tyr Gly Leu Thr Glu Thr Thr Ser Ala 145 150 155 160 att ctg ate acc ccc gaa ggg gac gac aag cct ggc gca gta ggc aag 528

Ile Leu Ile Thr Pro Glu Gly Asp Asp Lys Pro Gly Ala Val Gly Lys 165 170 175 gtg gtc ccc ttc ttc gag gct aag gtg gtg gac ttg gac acc ggt aag 576

Val val Pro Phe Phe Glu Ala Lys Val Val Asp Leu Asp Thr Gly Lys 180 185 190 aca ctg ggt gtg aac cag cgc ggc gag ctg tgc gtc cgt ggc ccc atg 624

Thr Leu Gly Val Asn Gin Arg Gly Glu Leu Cys Val Arg Gly Pro Met 195 200 205 ate atg agc ggc tac gtt aac aac ccc gag gct aca aac gct ete ate 672

Ile Met Ser Gly Tyr Val Asn Asn Pro Glu Ala Thr Asn Ala Leu Ile 210 215 220 gac aag gac ggg ctg cac agc ggc gac gac gac gac gac 720

Asp Lys Asp Gly Trp Leu His Ser Gly Asp Ile Ala Tyr Trp Asp Glu 225 230 235 240 gac gag cac ttc ttc ate gtg gac cgg ctg aag agc ctg ate aaa tac 768

Asp Glu His Phe Phe Ile Val Asp Arg Leu Lys Ser Leu Ile Lys Tyr 245 250 255 aag ggc tac cag gta gcc cca gcc gaa ctg gag agc ate ctg ctg caa 816

Lys Gly Tyr Gin Val Ala Pro Ala Glu Leu Glu Ser Ile Leu Leu Gin 260 265 270 cac ccc aac ate tc gac gcc ggg gtc gcc gcc ctg ccc gac gac gat 864

His Pro Asn Ile Phe Asp Ala Gly Val Ala Gly Leu Pro Asp Asp Asp Asp Asp Asp Asp 275 280 285 gcc ggc gag ctg ccc gcc gtca

Ala Gly Glu Leu Pro Ala Val Val Val Leu Glu His Gly Lys Thr 290 295 300 atg acc gag aag gag ate gtg gac tat gtg gcc agc cag gtt aca acc 960

Met Thr Glu Lys Glu Ile Val Asp Tyr Val Ala Ser Gin Val Thr Thr 305 310 315 320 gcc aag aag ctg cgc ggt gpt gtg ttc gtg gac gag gtg cct aaa 1008

Ala Lys Lys Leu Arg Gly Gly Val Val Phe Val Asp Glu Val Pro Lys 325 330 335 gga ctg acc ggc aag ttg gac gcc cgc aag ate cgc gag att ete att 1056

Gly Leu Thr Gly Lys Leu Asp Ala Arg Lys Ile Arg Glu Ile Leu Ile 340 345 350 aag gcc aag aag gaga tcc aac gtg gtg gtg cac cag gcc ggc gcc 1104

Lys Ala Lys Lys Gly Ser Asn Val Val Val His Gin Ala Gly Gly Ala 355 360 365 aaa aac att aag aag ggc cca gcg cca ttc tac cca ete gaa gac ggg 1152

Lys Asn Ile Lys Lys Gly Pro Ala Pro Phe Tyr Pro Leu Glu Asp Gly 370 375 380 acc gcc cg gag gag cag gag cag gag atg aag cgc tac gcc ctg gtg 1200

Thr Ala Gly Glu Gin Leu His Lys Ala Met Lys Arg Tyr Ala Leu Val 385 390 395 400 ccc ggc acc ate gcc ttt acc gac gca cat ate gag gtg gac att acc 1248

Pro Gly Thr Ile Ala Phe Thr Asp Ala His Ile Glu Val Asp Ile Thr 405 410 415 tac gcc gag tac ttc gag atg agc gtt cgg ctg gca gaa gct atg aag 1296

Tyr Ala Glu Tyr Phe Glu Met Ser Val Arg Leu Ala Glu Ala Met Lys 420 425 430 cgc tat ggg ctg aat aca aac cat cgg ate gtg gtg tgc agc gag aat 1344

Arg Tyr Gly Leu Asn Thr Asn His Arg Ile Val Val Cys Ser Glu Asn 435 440 445 agc ttg cag ttc ttc atg ccc gtg ttg ggt gcc ctg ttc ate ggt gtg 1392

Ser Leu Gin Phe Phe Met Pro Val Leu Gly Ala Leu Phe Ile Gly Val 450 455 460 gct gtc gcc cca gct aac gac ate tac aac gag cgc gag ctg ctg aac 1440

Ala Val Ala Pro Ala Asn Asp Ile Tyr Asn Glu Arg Glu Leu Leu Asn 465 470 475 480 agc atg ggc ate agc cag ccc acc gtc gta ttc gtg agc aag aaa ggg 1488

Ser Met Gly Ile Ser Gin Pro Thr Val Val Phe Val Ser Lys Lys Gly 485 490 495 ctg caa aag ate ete aac gtg caa aag aag cta ccg ate ata caa aag 1536

Leu Gin Lys Ile Leu Asn Val Gin Lys Leu Pro Ile Ile Gin Lys 500 505 510 ate ate ate atg gat agc aag acc gac tac cag ggc ttc caa agc atg 1584

Ile Ile Ile Met Asp Ser Lys Thr Asp Tyr Gin Gly Phe Gin Ser Met 515 520 525 tac acc ttc gtg act tcc cat ttg cca ccc ggc ttc aac gag tac gac 1632

Tyr Thr Phe Val Thr Ser His Leu Pro Pro Gly Phe Asn Glu Tyr Asp 530 535 540 ttc gtg ccc gag agc ttc gac cgg gac aaa acc ate gcc ctg ate atg 1680

Phe Val Pro Glu Ser Phe Asp Arg Asp Lys Thr Ile Ala Leu Ile Met 545 550 555 560 aac agt agt ggc agt acc gga ttg ccc aag ggc gta gcc cta ccg cac 1728

Asn Ser Ser Gly Ser Thr Gly Leu Pro Lys Gly Val Ala Leu Pro His 565 570 575 ege acc get tgt gtc ega ttc agt cat gcc ege gac ccc ate ttc ggc 1776

Arg Thr Ala Cys Val Arg Phe Ser His Ala Arg Asp Pro Ile Phe Gly 580 585 590 aac cag ate ate ccc gccgagtact gtttaagcta tgaaacggaa atattgacag 1831

Asn Gln Ile Ile Pro 595 tagaatatgg attattaccg attggtaaaa ttgtagaaaa gcgcatcgaa tgtactgttt 1891 atagcgttga taataatgga aatatttata cacaacctgt agcacaatgg cacgatcgcg 1951 gagaacaaga ggtgtttgag tattgtttgg aagatggttc attgattegg gcaacaaaag 2011 accataagtt tatgactgtt gatggtcaaa tgttgccaat tgatgaaata tttgaacgtg 2071 aattggattt gatgegggtt gataatttgc cgaaeggcgg caagatcgcc gtcaattctg 2131 cttgcaagaa ctggttcagt agcttaagcc actttgtgat ccaccttaac agccacggct 2191 tccctcccga ggtggaggag caggccgccg gcaccctgcc catgagctgc gcccaggaga 2251 gcggcatgga tagacaccct gctgcttgcg ccagcgccag gatcaacgtc taa 2304 <210> 70 <211> 597

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 70

Met Ile Lys Ile Ala Thr Arg Lys Tyr Leu Gly Lys Gin Asn Val Tyr 15 10 15

Asp Ile Gly Val Glu Arg Asp His Asn Phe Ala Leu Lys Asn Gly Phe 20 25 30

Ile Ala Ser Asn Cys Phe Asn Asp Thr Tyr Arg Tyr Ile Asp Thr Ala 35 40 45

Ile Leu Ser Val Val Phe His Gly Phe Gly Met Phe Thr Thr 50 55 60

Leu Gly Tyr Leu Ile Cys Gly Phe Arg Val Val Leu Met Tyr Arg Phe 65 70 75 80

Glu Glu Glu Leu Phe Leu Arg Ser Leu Gin Asp Tyr Lys Ile Gin Ser 85 90 95

Ala Leu Leu Val Pro Thr Leu Phe Ser Phe Phe Ala Lys Ser Thr Leu 100 105 110

Ile Asp Lys Tyr Asp Leu Ser Asn Leu His Glu Ile Ala Ser Gly Gly 115 120 125

Ala Pro Leu Ser Lys Glu Val Gly Glu Ala Val Ala Lys Arg Phe His 130 135 140

Leu Pro Gly Ile Arg Gin Gly Tyr Gly Leu Thr Glu Thr Thr Ser Ala 145 150 155 160

Ile Leu Ile Thr Pro Glu Gly Asp Asp Lys Pro Gly Ala Val Gly Lys 165 170 175

Val Val Pro Phe Phe Glu Ala Lys Val Val Asp Leu Asp Thr Gly Lys 180 185 190

Thr Leu Gly Val Asn Gin Arg Gly Glu Leu Cys Val Arg Gly Pro Met 195 200 205

Ile Met Ser Gly Tyr Val Asn Asn Pro Glu Ala Thr Asn Ala Leu Ile 210 215 220

Asp Lys Asp Gly Trp Leu His Ser Gly Asp Ile Ala Tyr Trp Asp Glu 225 230 235 240

Asp Glu His Phe Phe Ile Val Asp Arg Leu Lys Ser Leu Ile Lys Tyr 245 250 255

Lys Gly Tyr Gin Val Ala Pro Ala Glu Leu Glu Ser Ile Leu Leu Gin 260 265 270

His Pro Asn Ile Phe Asp Ala Gly Val Ala Gly Leu Pro Asp Asp Asp 275 280 285

Ala Gly Glu Leu Pro Ala Ala Val Val Leu Glu His Gly Lys Thr 290 295 300

Met Thr Glu Lys Glu Ile Val Asp Tyr Val Ala Ser Gin Val Thr Thr 305 310 315 320

Ala Lys Lys Leu Arg Gly Gly Val Val Phe Val Asp Glu Val Pro Lys 325 330 335

Gly Leu Thr Gly Lys Leu Asp Ala Arg Lys Ile Arg Glu Ile Leu Ile 340 345 350

Lys Ala Lys Lys Gly Ser Asn Val Val Val His Gin Ala Gly Gly Ala 355 360 365

Lys Asn Ile Lys Lys Gly Pro Ala Pro Phe Tyr Pro Leu Glu Asp Gly 370 375 380

Thr Ala Gly Glu Gin Leu His Lys Ala Met Lys Arg Tyr Ala Leu Val 385 390 395 400

Pro Gly Thr Ile Ala Phe Thr Asp Ala His Ile Glu Val Asp Ile Thr 405 410 415

Tyr Ala Glu Tyr Phe Glu Met Ser Val Arg Leu Ala Glu Ala Met Lys 420 425 430

Arg Tyr Gly Leu Asn Thr Asn His Arg Ile Val Val Cys Ser Glu Asn 435 440 445

Ser Leu Gin Phe Phe Met Pro Val Leu Gly Ala Leu Phe Ile Gly Val 450 455 460

Ala Val Ala Pro Ala Asn Asp Ile Tyr Asn Glu Arg Glu Leu Leu Asn 465 470 475 480

Ser Met Gly Ile Ser Gin Pro Thr Val Val Phe Val Ser Lys Lys Gly 485 490 495

Leu Gin Lys Ile Leu Asn Val Gin Lys Leu Pro Ile Ile Gin Lys 500 505 510

Ile Ile Ile Met Asp Ser Lys Thr Asp Tyr Gin Gly Phe Gin Ser Met 515 520 525

Tyr Thr Phe Val Thr Ser His Leu Pro Pro Gly Phe Asn Glu Tyr ASp 530 535 540

Phe Val Pro Glu Ser Phe Asp Arg Asp Lys Thr Ile Ala Leu Ile Met 545 550 555 560

Asn Ser Ser Gly Ser Thr Gly Leu Pro Lys Gly Val Ala Leu Pro His 565 570 575

Arg Thr Ala Cys Val Arg Phe Ser His Ala Arg Asp Pro Ile Phe Gly 580 585 590

Asn Gin Ile Pro 595 <210> 71 <211> 2313

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (2310) <400> 71 atg gac aca cgt aaa tat tta ggc aaa caa aat gtc tat 48

Met Ile Lys Ile Ala Thr Arg Lys Tyr Leu Gly Lys Gin Asn Val Tyr 15 10 15 gac att gga gtt gag cgc gac cat aat ttt gca ctc aaa aat ggc ttc 96

Asp Ile Gly Val Glu Arg Asp His Asn Phe Ala Leu Lys Asn Gly Phe 20 25 30 ata gct tet aat tgt ttc aat gat act tat aga tat att gac acc get 144

Ile Ala Ser Asn Cys Phe Asn Asp Thr Tyr Arg Tyr Ile Asp Thr Ala 35 40 45 ate ctc agc gtg gtg cca ttt cac cac ggc ttc ggc atg ttc acc acg 192

Ile Leu Ser Val Val Pro Phe His Gly Phe Gly Met Phe Thr Thr 50 55 60 ctg ggc tac ttg ate tgc ggc ttt cgg gtc gtg ctc atg tac cgc ttc 240

Leu Gly Tyr Leu Ile Cys Gly Phe Arg Val Val Leu Met Tyr Arg Phe 65 70 75 80 gag gag gag cta ttc ttg cgc agc ttg caa gac tat aag att caa tet 288

Glu Glu Glu Leu Phe Leu Arg Ser Leu Gin Asp Tyr Lys Ile Gin Ser 85 90 95 gcc ctg ctg gtg ccc aca cta ttt agc ttc ttc gct aag agc act ctc 336

Ala Leu Leu Val Pro Thr Leu Phe Ser Phe Phe Ala Lys Ser Thr Leu 100 105 110 ate gac aag tac gac cta agc aac ttg cac gag ate gcc agc ggc ggg 384

Ile Asp Lys Tyr Asp Leu Ser Asn Leu His Glu Ile Ala Ser Gly Gly 115 120 125 gcg ccg ctc agc aag gag gta ggt gag gcc gtg gcc aaa cgc ttc cac 432

Ala Pro Leu Ser Lys Glu Val Gly Glu Ala Val Ala Lys Arg Phe His 130 135 140 cta cg ggc cate ggc cg ggc tc ggc ctg aca gaa aca acc agc gcc 480

Leu Pro Gly Ile Arg Gin Gly Tyr Gly Leu Thr Glu Thr Thr Ser Ala 145 150 155 160 att ctg ate acc ccc gaa ggg gac gac aag cct ggc gca gta ggc aag 528

Ile Leu Ile Thr Pro Glu Gly Asp Asp Lys Pro Gly Ala Val Gly Lys 165 170 175 gtg gtc ccc ttc ttc gag gct aag gtg gtg gac ttg gac acc ggt aag 576

Val Val Pro Phe Phe Glu Ala Lys Val Val Asp Leu Asp Thr Gly Lys 180 185 190 aca ctg ggt gtg aac cag cgc ggc gag ctg tgc gtc cgt ggc ccc atg 624

Thr Leu Gly Val Asn Gin Arg Gly Glu Leu Cys Val Arg Gly Pro Met 195 200 205 ate atg agc ggc tac gtt aac aac ccc gag gct aca aac gct ctc ate 672

Ile Met Ser Gly Tyr Val Asn Asn Pro Glu Ala Thr Asn Ala Leu Ile 210 215 220 gac aag gac ggg ctg cac agc ggc gac gac gac gac gac 720

Asp Lys Asp Gly Trp Leu His Ser Gly Asp Ile Ala Tyr Trp Asp Glu 225 230 235 240 gac gag cac ttc ttc ate gtg gac cgg ctg aag agc ctg ate aaa tac 768

Asp Glu His Phe Phe Ile Val Asp Arg Leu Lys Ser Leu Ile Lys Tyr 245 250 255 aag ggc tac cag gta gcc cca gcc gaa ctg gag agc ate ctg ctg caa 816

Lys Gly Tyr Gin Val Ala Pro Ala Glu Leu Glu Ser Ile Leu Leu Gin 260 265 270 cac ccc aac ate tc gac gcc ggg gtc gcc gcc ctg ccc gac gac gat 864

His Pro Asn Ile Phe Asp Ala Gly Val Ala Gly Leu Pro Asp Asp Asp Asp Asp Asp Asp 275 280 285 gcc ggc gag ctg ccc gcc gtca

Ala Gly Glu Leu Pro Ala Val Val Val Leu Glu His Gly Lys Thr 290 295 300 atg acc gag aag gag ate gtg gac tat gtg gcc agc cag gtt aca acc 960

Met Thr Glu Lys Glu Ile Val Asp Tyr Val Ala Ser Gin Val Thr Thr 305 310 315 320 gcc aag aag ctg cgc ggt gpt gtg ttc gtg gac gag gtg cct aaa 1008

Ala Lys Lys Leu Arg Gly Gly Val Val Phe Val Asp Glu Val Pro Lys 325 330 335 gga ctg acc ggc aag ttg gac gcc cgc aag ate cgc gag att ctc att 1056

Gly Leu Thr Gly Lys Leu Asp Ala Arg Lys Ile Arg Gle Ile Leu Ile 340 345 350 aag gcc aag aag gaga tcc gag tcc gtc agc ctg caa agc ggc tca ggt 1104

Lys Ala Lys Lys Gly Ser Glu Ser Val Ser Leu Gin Ser Gly Ser Gly 355 360 365 ggc ggt gcc aaa aac att aag aag ggc cca gcg cca ttc tac cca ctc 1152

Gly Gly Ally Lys Asn Ile Lys Lys Gly Pro Ala Pro Phe Tyr Pro Leu 370 375 380 gag gag gag gag cag cg cac aaa gcc atg aag cgc tac 1200

Glu Asp Gly Thr Ala Gly Glu Gin Leu His Lys Ala Met Lys Arg Tyr 385 390 395 400 gcc ctg gtg ccc ggc acc ate gcc ttt acc gac gca cat ate gag gtg 1248

Ala Leu Val Pro Gly Thr Ile Ala Phe Thr Asp Ala His Ile Glu Val 405 410 415 gac att acc tac gcc gag tac ttc gag atg agc gtt cgg ctg gca gaa 1296

Asp Ile Thr Tyr Ala Glu Tyr Phe Glu Met Ser Val Arg Leu Ala Glu 420 425 430 gct atg aag cgc tat ggg ctg aat aca aac cat cgg ate gtg gtg tgc 1344

Ala Met Lys Arg Tyr Gly Leu Asn Thr Asn His Arg Ile Val Val Cys 435 440 445 agc gag aat agc ttg cag ttc ttc atg ccc gtg ttg ggt gcc ctg ttc 1392

Ser Glu Asn Ser Leu Gin Phe Phe Met Pro Val Leu Gly Ala Leu Phe 450 455 460 ate ggt gtg gct gtc gcc cca gct aac gac ate tac aac gag cgc gag 1440

Ile Gly Val Ala Val Ala Pro Ala Asn Asp Asle Ile Tyr Asn Glu Arg Glu 465 470 475 480 ctg ctg aac agc atg ggc ate agc cag ccc acc gtc gta ttc gtg agc 1488

Leu Leu Asn Ser Met Gly Ile Ser Gin Pro Thr Val Val Phe Val Ser 485 490 495 aag aaa ggg ctg caa aag ate ete aac gtg caa aag aag cta ccg ate 1536

Lys Lys Gly Leu Gin Lys Ile Leu Asn Val Gin Lys Lys Leu Pro Ile 500 505 510 ata caa aag ate ate ate atg gat agc aag acc gac tac cag ggc ttc 1584

Ile Gin Lys Ile Ile Ile Met Asp Ser Lys Thr Asp Tyr Gin Ghe Phe 515 520 525 caa agc atg tac acc ttc gtg act tcc cat ttg cca ccc ggc ttc aac 1632

Gin Ser Met Tyr Thr Phe Val Thr Ser He Leu Pro Pro Gly Phe Asn 530 535 540 gag tac gac ttc gtg ccc gag agc ttc gac cgg gac aaa acc ate gcc 1680

Glu Tyr Asp Phe Val Pro Glu Ser Phe Asp Arg Asp Lys Thr Ile Ala 545 550 555 560 ctg ate atg aac agt agt ggc agt acc gga ttg ccc aag ggc gta gcc 1728

Leu Ile Met Asn Ser Ser Gly Ser Thr Gly Leu Pro Lys Gly Val Ala 565 570 575 cta cc cc cgc acc gct tgt gtc ega ttc agt cat gcc cgc gac ccc 1776

Leu Pro His Arg Thr Ala Cys Val Arg Phe Ser His Ala Arg Asp Pro 580 585 590 ate ttc ggc aac cag ate ate ccc gcc gag tac tgt tta agc tat gaa 1824

Ile Phe Gly Asn Gin Ile Ile Pro Ala Glu Tyr Cys Leu Ser Tyr Glu 595 600 605 acg gaa ata ttg aca gta gaa tat gga tta tta ccg att ggt aaa att 1872

Thr Glu Ile Leu Thr Val Glu Tyr Gly Leu Leu Pro Ile Gly Lys Ile 610 615 620 gta gaa aag cgc ate gaa tgt act gtt tat agc gtt gat aat aat gga 1920

Val Glu Lys Arg Ile Glu Cys Thr Val Tyr Ser Val Asp Asn Asn Gly 625 630 635 640 aat att tat aca caa cct gta gca caa tgg cac gat cgc gga gaa caa 1968

Asn Ile Tyr Thr Gin Pro Val Ala Gin Trp His Asp Arg Gly Glu Gin 645 650 655 gag gtg ttt gag tat tgt ttg gaa gat ggt tta ttg att cgg gca aca 2016

Glu Val Phe Glu Tyr Cys Leu Glu Asp Gly Ser Leu Ile Arg Ala Thr 660 665 670 aaa gac cat aag ttt atg act gtt gat ggt caa atg ttg cca att gat 2064

Lys Asp His Lys Phe Met Thr Val Asp Gly Gin Met Leu Pro Ile Asp 675 680 685 gaa ata ttt gaa cgt gaa ttg gat ttg atg cgg gtt gat aat ttg ccg 2112

Glu Ile Phe Glu Arg Glu Leu Asp Leu Met Arg Val Asp Asn Leu Pro 690 695 700 aac ggc ggc aag ate gcc gtc aat tet gct tgc aag aac tgg ttc agt 2160

Asn Gly Gly Lys Ile Ala Val Asn Ser Ala Cys Lys Asn Trp Phe Ser 705 710 715 720 agc tta agc cac ttt gtg ate cac ctt aac agc cac ggc ttc cct ccc 2208

Ser Leu Ser His Phe Val Ile His Leu Asn Ser His Gly Phe Pro Pro 725 730 735 gag gag gag gag gcc gcc cg ccc atg agc tgc gcc cag 2256

Glu Val Glu Glu Gin Ala Ala Gly Thr Leu Pro Met Ser Cys Ala Gin 740 745 750 gg agc ggc atg gat aga cac cct gct gct tgc gcc agc gcc agg ate 2304

Glu Ser Gly Met Asp Arg His Pro Ala Ala Cys Ala Ser Ala Arg Ile 755 760 765 aac gtc taa 2313

Asn Val 770 <210> 72 <211> 770

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 72

Met Ile Lys Ile Ala Thr Arg Lys Tyr Leu Gly Lys Gin Asn Val Tyr 15 10 15

Asp Ile Gly Val Glu Arg Asp His Asn Phe Ala Leu Lys Asn Gly Phe 20 25 30

Ile Ala Ser Asn Cys Phe Asn Asp Thr Tyr Arg Tyr Ile Asp Thr Ala 35 40 45

Ile Leu Ser Val Val Phe His Gly Phe Gly Met Phe Thr Thr 50 55 60

Leu Gly Tyr Leu Ile Cys Gly Phe Arg Val Val Leu Met Tyr Arg Phe 65 70 75 80

Glu Glu Glu Leu Phe Leu Arg Ser Leu Gin Asp Tyr Lys Ile Gin Ser 85 90 95

Ala Leu Leu Val Pro Thr Leu Phe Ser Phe Phe Ala Lys Ser Thr Leu 100 105 110

Ile Asp Lys Tyr Asp Leu Ser Asn Leu His Glu Ile Ala Ser Gly Gly 115 120 125

Ala Pro Leu Ser Lys Glu Val Gly Glu Ala Val Ala Lys Arg Phe His 130 135 140

Leu Pro Gly Ile Arg Gin Gly Tyr Gly Leu Thr Glu Thr Thr Ser Ala 145 150 155 160

Ile Leu Ile Thr Pro Glu Gly Asp Asp Lys Pro Gly Ala Val Gly Lys 165 170 175

Val Val Pro Phe Phe Glu Ala Lys Val Val Asp Leu Asp Thr Gly Lys 180 185 190

Thr Leu Gly Val Asn Gin Arg Gly Glu Leu Cys Val Arg Gly Pro Met 195 200 205

Ile Met Ser Gly Tyr Val Asn Asn Pro Glu Ala Thr Asn Ala Leu Ile 210 215 220

Asp Lys Asp Gly Trp Leu His Ser Gly Asp Ile Ala Tyr Trp Asp Glu 225 230 235 240

Asp Glu His Phe Phe Ile Val Asp Arg Leu Lys Ser Leu Ile Lys Tyr 245 250 255

Lys Gly Tyr Gin Val Ala Pro Ala Glu Leu Glu Ser Ile Leu Leu Gin 260 265 270

His Pro Asn Ile Phe Asp Ala Gly Val Ala Gly Leu Pro Asp Asp Asp 275 280 285

Ala Gly Glu Leu Pro Ala Ala Val Val Leu Glu His Gly Lys Thr 290 295 300

Met Thr Glu Lys Glu Ile Val Asp Tyr Val Ala Ser Gin Val Thr Thr 305 310 315 320

Ala Lys Lys Leu Arg Gly Gly Val Val Phe Val Asp Glu Val Pro Lys 325 330 335

Gly Leu Thr Gly Lys Leu Asp Ala Arg Lys Ile Arg Glu Ile Leu Ile 340 345 350

Lys Ala Lys Lys Gly Ser Glu Ser Val Ser Leu Gin Ser Gly Ser Gly 355 360 365

Gly Gly Ala Lys Asn Ile Lys Gly Pro Ala Pro Phe Tyr Pro Leu 370 375 380

Glu Asp Gly Thr Ala Gly Glu Gin Leu His Lys Ala Met Lys Arg Tyr 385 390 395 400

Ala Leu Val Pro Gly Thr Ile Ala Phe Thr Asp Ala His Ile Glu Val 405 410 415

Asp Ile Thr Tyr Ala Glu Tyr Phe Glu Met Ser Val Arg Leu Ala Glu 420 425 430

Ala Met Lys Arg Tyr Gly Leu Asn Thr Asn His Arg Ile Val Val Cys 435 440 445

Ser Glu Asn Ser Leu Gin Phe Phe Met Pro Val Leu Gly Ala Leu Phe 450 455 460

Ile Gly Val Ala Val Ala Pro Ala Asn Asp Ile Tyr Asn Glu Arg Glu 465 470 475 480

Leu Leu Asn Ser Met Gly Ile Ser Gin Pro Thr Val Val Phe Val Ser 485 490 495

Lys Lys Gly Leu Gin Lys Ile Leu Asn Val Gin Lys Leu Pro Ile 500 505 510

Ile Gin Lys Ile Ile Ile Met Asp Ser Lys Thr Asp Tyr Gin Gly Phe 515 520 525

Gin Ser Met Tyr Thr Phe Val Thr Ser His Leu Pro Pro Gly Phe Asn 530 535 540

Glu Tyr Asp Phe Val Pro Glu Ser Phe Asp Arg Asp Lys Thr Ile Ala 545 550 555 560

Leu Ile Met Asn Ser Ser Gly Ser Thr Gly Leu Pro Lys Gly Val Ala 565 570 575

Leu Pro His Arg Thr Ala Cys Val Arg Phe Ser His Ala Arg Asp Pro 580 585 590

Ile Phe Gly Asn Gin Ile Ile Pro Ala Glu Tyr Cys Leu Ser Tyr Glu 595 600 605

Thr Glu Ile Leu Thr Val Glu Tyr Gly Leu Leu Pro Ile Gly Lys Ile 610 615 620

Val Glu Lys Arg Ile Glu Cys Thr Val Tyr Ser Val Asp Asn Asn Gly 625 630 635 640

Asn Ile Tyr Thr Gin Pro Val Ala Gin Trp His Asp Arg Gly Glu Gin 645 650 655

Glu Val Phe Glu Tyr Cys Leu Glu Asp Gly Ser Leu Ile Arg Ala Thr 660 665 670

Lys Asp His Lys Phe Met Thr val Asp Gly Gin Met Leu Pro Ile Asp 675 680 685

Glu Ile Phe Glu Arg Glu Leu Asp Leu Met Arg Val Asp Asn Leu Pro 690 695 700

Asn Gly Gly Lys Ile Ala Val Asn Ser Ala Cys Lys Asn Trp Phe Ser 705 710 715 720

Ser Leu Ser His Phe Val Ile His Leu Asn Ser His Gly Phe Pro Pro 725 730 735

Glu Val Glu Glu Gin Ala Ala Gly Thr Leu Pro Met Ser Cys Ala Gin 740 745 750

Glu Ser Gly Met Asp Arg His Pro Ala Ala Cys Ala Ser Ala Arg Ile 755 760 765

Asn Val 770 <210> 73 <211> 2313

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (2310) <400> 73 atg ate aaa ata gcc aca cgt aaa tat tta ggc aaa caa aat gtc tat 48

Met Ile Lys Ile Ala Thr Arg Lys Tyr Leu Gly Lys Gin Asn Val Tyr 15 10 15 gac att gga gtt gag ege gac cat aat ttt gca ete aaa aat ggc ttc 96

Asp Ile Gly Val Glu Arg Asp His Asn Phe Ala Leu Lys Asn Gly Phe 20 25 30 ata get tet aat tgt ttc aat gat act tat aga tat att gac acc get 144

Ile Ala Ser Asn Cys Phe Asn Asp Thr Tyr Arg Tyr Ile Asp Thr Ala 35 40 45 ate ete agc gtg gtg cca ttt cac cac ggc ttc ggc atg ttc acc acg 192

Ile Leu Ser Val Val Phe His Gly Phe Gly Met Phe Thr Thr 50 55 60 ctg ggc tac ttg ate tgc ggc ttt cgg gtc gtg ete atg tac ege ttc 240

Leu Gly Tyr Leu Ile Cys Gly Phe Arg Val Val Leu Met Tyr Arg Phe 65 70 75 80 gag gag gag cta ttc ttg ege agc ttg caa gac tat aag att caa tet 288

Glu Glu Glu Leu Phe Leu Arg Ser Leu Gin Asp Tyr Lys Ile Gin Ser 85 90 95 gec ctg ctg gtg ccc aca cta ttt agc ttc ttc get aag agc act ete 336

Ala Leu Leu Val Pro Thr Leu Phe Ser Phe Phe Ala Lys Ser Thr Leu 100 105 110 ate gac aag tac gac cta agc aac ttg cac gag ate gcc agc ggc ggg 384

Ile Asp Lys Tyr Asp Leu Ser Asn Leu His Glu Ile Ala Ser Gly Gly 115 120 125 gcg ccg ete agc aag gag gta ggt gag gcc gtg gcc aaa ege ttc cac 432

Ala Pro Leu Ser Lys Glu Val Gly Glu Ala Val Ala Lys Arg Phe His 130 135 140 cta cg ggc cate ggc cg ggc ac acc ac ac acc ac gc 480

Leu Pro Gly Ile Arg Gin Gly Tyr Gly Leu Thr Glu Thr Thr Ser Ala 145 150 155 160 att ctg ate acc ccc gaa ggg gac gac aag cct ggc gca gta ggc aag 528

Ile Leu Ile Thr Pro Glu Gly Asp Asp Lys Pro Gly Ala Val Gly Lys 165 170 175 gtg ccc ttc ttc gag get aag gtg gtg gac ttg gac acc ggt aag 576

Val Val Pro Phe Phe Glu Ala Lys Val Val Asp Leu Asp Thr Gly Lys 180 185 190 aca ctg ggt gtg aac cag ege ggc gag ctg tgc gtc cgt ggc ccc atg 624

Thr Leu Gly Val Asn Gin Arg Gly Glu Leu Cys Val Arg Gly Pro Met 195 200 205 ate atg agc ggc tac gtt aac aac ccc gag get aca aac get ete ate 672

Ile Met Ser Gly Tyr Val Asn Asn Pro Glu Ala Thr Asn Ala Leu ile 210 215 220 gac aag gac ggc tgg ctg cac agc ggc gac ate gcc tac ggg gag 720

Asp Lys Asp Gly Trp Leu His Ser Gly Asp Ile Ala Tyr Trp Asp Glu 225 230 235 240 gac gag cac ttc ttc ate gtg gac cgg ctg aag agc ctg ate aaa tac 768

Asp Glu His Phe Phe Ile Val Asp Arg Leu Lys Ser Leu Ile Lys Tyr 245 250 255 aag ggc tac cag gta gcc cca gcc gaa ctg gag agc ate ctg ctg caa 816

Lys Gly Tyr Gin Val Ala Pro Ala Glu Leu Glu Ser Ile Leu Leu Gin 260 265 270 cac ccc aac ate tc gac gcc ggg gtc gcc gcc ctg ccc gac gac gat 864

His Pro Asn Ile Phe Asp Ala Gly Val Ala Gly Leu Pro Asp Asp Asp Asp Asp Asp Asp 275 280 285 gcc ggc gag ctg ccc gcc gtca

Ala Gly Glu Leu Pro Ala Val Val Val Leu Glu His Gly Lys Thr 290 295 300 atg acc gag aag gag ate gtg gac tat gtg gcc agc cag gtt aca acc 960

Met Thr Glu Lys Glu Ile Val Asp Tyr Val Ala Ser Gin Val Thr Thr 305 310 315 320 gcc aag aag ctg ege ggt ggt gtt gtg ttc gtg gac gag gtg cct aaa 1008

Ala Lys Lys Leu Arg Gly Gly Val Val Phe Val Asp Glu Val Pro Lys 325 330 335 gga ctg acc ggc aag ttg gac gcc cgc aag ate ege gag att ete att 1056

Gly Leu Thr Gly Lys Leu Asp Ala Arg Lys Ile Arg Glu Ile Leu Ile 340 345 350 aag gcc aag aag gga tcc gag gaa ata cac ctg caa agc ggc tca ggt 1104

Lys Ala Lys Lys Gly Ser Glu Glu Ile His Leu Gin Ser Gly Ser Gly 355 360 365 ggc ggt gcc aaa aac att aag aag ggc cca gcg cca ttc tac cca ete 1152

Gly Gly Ala Lys Asn Ile Lys Lys Gly Pro Ala Pro Phe Tyr Pro Leu 370 375 380 gag gag gag gag gag cag cag gag atg aag ege tac 1200

Glu Asp Gly Thr Ala Gly Glu Gin Leu His Lys Ala Met Lys Arg Tyr 385 390 395 400 gcc ctg gtg ccc ggc acc ate gcc ttt acc gac gca cat ate gag gtg 1248

Ala Leu Val Pro Gly Thr Ile Ala Phe Thr Asp Ala His Ile Glu Val 405 410 415 gac att acc tac gcc gag tac ttc gag atg agc gtt cgg ctg gca gaa 1296

Asp Ile Thr Tyr Ala Glu Tyr Phe Glu Met Ser Val Arg Leu Ala Glu 420 425 430 Get atg aag ege tat ggg ctg aat aca aac cat cgg ate gtg gtg tgc 1344

Ala Met Lys Arg Tyr Gly Leu Asn Thr Asn His Arg Ile Val Val Cys 435 440 445 agc gag aat agc ttg cag ttc ttc atg ccc gtg ttg ggt gcc ctg ttc 1392

Ser Glu Asn Ser Leu Gin Phe Phe Met Pro Val Leu Gly Ala Leu Phe 450 455 460 ate ggt gtg get gtg gcc cca get aac gac ate tac aac gag ege gag 1440

Ile Gly Val Ala Val Ala Pro Ala Asn Asp Asle Ile Tyr Asn Glu Arg Glu 465 470 475 480 ctg ctg aac agc atg ggc ate agc cag ccc acc gtc gta ttc gtg agc 1488

Leu Leu Asn Ser Met Gly Ile Ser Gin Pro Thr Val Val Phe Val Ser 485 490 495 aag aaa ggg ctg caa aag ate ete aac gtg caa aag aag cta ccg ate 1536

Lys Lys Gly Leu Gin Lys Ile Leu Asn Val Gin Lys Lys Leu Pro Ile 500 505 510 ata caa aag ate ate ate atg gat agc aag acc gac tac cag ggc ttc 1584

Ile Gin Lys Ile Ile Ile Met Asp Ser Lys Thr Asp Tyr Gin Ghe Phe 515 520 525 caa agc atg tac acc ttc gtg act tcc cat ttg cca ccc ggc ttc aac 1632

Gin Ser Met Tyr Thr Phe Val Thr Ser He Leu Pro Pro Gly Phe Asn 530 535 540 gag tac gac ttc gtg ccc gag agc ttc gac cgg gac aaa acc ate gcc 1680

Glu Tyr Asp Phe Val Pro Glu Ser Phe Asp Arg Asp Lys Thr Ile Ala 545 550 555 560 ctg ate atg aac agt agt ggc agt acc gga ttg ccc aag ggc gta gcc 1728

Leu Ile Met Asn Ser Ser Gly Ser Thr Gly Leu Pro Lys Gly Val Ala 565 570 575 cta cc cc cgc acc get tgt gtc ega ttc agt cat gcc cgc gac ccc 1776

Leu Pro His Arg Thr Ala Cys Val Arg Phe Ser His Ala Arg Asp Pro 580 585 590 ate ttc ggc aac cag ate ate ccc gcc gag tac tgt tta agc tat gaa 1824

Ile Phe Gly Asn Gin Ile Ile Pro Ala Glu Tyr Cys Leu Ser Tyr Glu 595 600 605 acg gaa ata ttg aca gta gaa tat gga tta tta ccg att ggt aaa att 1872

Thr Glu Ile Leu Thr Val Glu Tyr Gly Leu Leu Pro Ile Gly Lys Ile 610 615 620 gta gaa aag cgc ate gaa tgt act gtt tat agc gtt gat aat aat gga 1920

Val Glu Lys Arg Ile Glu Cys Thr Val Tyr Ser Val Asp Asn Asn Gly 625 630 635 640 aat att tat aca caa cct gta gca caa tgg cac gat cgc gga gaa caa 1968

Asn Ile Tyr Thr Gin Pro Val Ala Gin Trp His Asp Arg Gly Glu Gin 645 650 655 gag gtg ttt gag tat tgt ttg gaa gat ggt tta ttg att cgg gca aca 2016

Glu Val Phe Glu Tyr Cys Leu Glu Asp Gly Ser Leu Ile Arg Ala Thr 660 665 670 aaa gac cat aag ttt atg act gtt gat ggt caa atg ttg cca att gat 2064

Lys Asp His Lys Phe Met Thr Val Asp Gly Gin Met Leu Pro Ile Asp 675 680 685 gaa ata ttt gaa cgt gaa ttg gat ttg atg cgg gtt gat aat ttg ccg 2112

Glu Ile Phe Glu Arg Glu Leu Asp Leu Met Arg Val Asp Asn Leu Pro 690 695 700 aac ggc ggc aag ate gcc gtc aat tet get tgc aag aac tgg ttc agt 2160

Asn Gly Gly Lys Ile Ala Val Asn Ser Ala Cys Lys Asn Trp Phe Ser 705 710 715 720 agc tta agc cac ttt gtg ate cac ctt aac agc cac ggc ttc cct ccc 2208

Ser Leu Ser His Phe Val Ile His Leu Asn Ser His Gly Phe Pro Pro 725 730 735 gag gag gag gag gcc gcc cg ccc atg agc tgc gcc cag 2256

Glu Val Glu Glu Gin Ala Ala Gly Thr Leu Pro Met Ser Cys Ala Gin 740 745 750 gg agc ggc atg gat aga cac cct gct gct tgc gcc agc gcc agg ate 2304

Glu Ser Gly Met Asp Arg His Pro Ala Ala Cys Ala Ser Ala Arg Ile 755 760 765 aac gtc taa 2313

Asn Val 770 <210> 74 <211> 770

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 74

Met Ile Lys Ile Ala Thr Arg Lys Tyr Leu Gly Lys Gin Asn Val Tyr 15 10 15

Asp Ile Gly Val Glu Arg Asp His Asn Phe Ala Leu Lys Asn Gly Phe 20 25 30

Ile Ala Ser Asn Cys Phe Asn Asp Thr Tyr Arg Tyr Ile Asp Thr Ala 35 40 45

Ile Leu Ser Val Val Phe His Gly Phe Gly Met Phe Thr Thr 50 55 60

Leu Gly Tyr Leu Ile Cys Gly Phe Arg Val Val Leu Met Tyr Arg Phe 65 70 75 80

Glu Glu Glu Leu Phe Leu Arg Ser Leu Gin Asp Tyr Lys Ile Gin Ser 85 90 95

Ala Leu Leu Val Pro Thr Leu Phe Ser Phe Phe Ala Lys Ser Thr Leu 100 105 110

Ile Asp Lys Tyr Asp Leu Ser Asn Leu His Glu Ile Ala Ser Gly Gly 115 120 125

Ala Pro Leu Ser Lys Glu Val Gly Glu Ala Val Ala Lys Arg Phe His 130 135 140

Leu Pro Gly Ile Arg Gin Gly Tyr Gly Leu Thr Glu Thr Thr Ser Ala 145 150 155 160

Ile Leu Ile Thr Pro Glu Gly Asp Asp Lys Pro Gly Ala Val Gly Lys 165 170 175

Val Val Pro Phe Phe Glu Ala Lys Val Val Asp Leu Asp Thr Gly Lys 180 185 190

Thr Leu Gly Val ASn Gin Arg Gly Glu Leu Cys Val Arg Gly Pro Met 195 200 205

Ile Met Ser Gly Tyr Val Asn Asn Pro Glu Ala Thr Asn Ala Leu Ile 210 215 220

Asp Lys Asp Gly Trp Leu His Ser Gly Asp Ile Ala Tyr Trp Asp Glu 225 230 235 240

Asp Glu His Phe Phe Ile Val Asp Arg Leu Lys Ser Leu Ile Lys Tyr 245 250 255

Lys Gly Tyr Gin Val Ala Pro Ala Glu Leu Glu Ser Ile Leu Leu Gin 260 265 270

His Pro Asn Ile Phe Asp Ala Gly Val Ala Gly Leu Pro Asp Asp Asp 275 280 285

Ala Gly Glu Leu Pro Ala Ala Val Val Leu Glu His Gly Lys Thr 290 295 300

Met Thr Glu Lys Glu Ile Val Asp Tyr Val Ala Ser Gin Val Thr Thr 305 310 315 320

Ala Lys Lys Leu Arg Gly Gly Val Val Phe Val Asp Glu Val Pro Lys 325 330 335

Gly Leu Thr Gly Lys Leu Asp Ala Arg Lys Ile Arg Glu Ile Leu Ile 340 345 350

Lys Ala Lys Lys Gly Ser Glu Glu Ile His Leu Gin Ser Gly Ser Gly 355 360 365

Gly Gly Ala Lys Astle Ile Lys Lys Gly Pro Ala Pro Phe Tyr Pro Leu 370 375 380

Glu Asp Gly Thr Ala Gly Glu Gin Leu His Lys Ala Met Lys Arg Tyr 385 390 395 400

Ala Leu Val Pro Gly Thr Ile Ala Phe Thr Asp Ala His Ile Glu Val 405 410 415

Asp Ile Thr Tyr Ala Glu Tyr Phe Glu Met Ser Val Arg Leu Ala Glu 420 425 430

Ala Met Lys Arg Tyr Gly Leu Asn Thr Asn His Arg Ile Val Val Cys 435 440 445

Ser Glu Asn Ser Leu Gin Phe Phe Met Pro Val Leu Gly Ala Leu Phe 450 455 460

Ile Gly Val Ala Val Ala Pro Ala Asn Asp Ile Tyr Asn Glu Arg Glu 465 470 475 480

Leu Leu Asn Ser Met Gly Ile Ser Gin Pro Thr Val Val Phe Val Ser 485 490 495

Lys Lys Gly Leu Gin Lys Ile Leu Asn Val Gin Lys Leu Pro Ile 500 505 510

Ile Gin Lys Ile Ile Ile Met Asp Ser Lys Thr Asp Tyr Gin Gly Phe 515 520 525

Gin Ser Met Tyr Thr Phe Val Thr Ser His Leu Pro Pro Gly Phe Asn 530 535 540

Glu Tyr Asp Phe Val Pro Glu Ser Phe Asp Arg Asp Lys Thr Ile Ala 545 550 555 560

Leu Ile Met Asn Ser Ser Gly Ser Thr Gly Leu Pro Lys Gly Val Ala 565 570 575

Leu Pro His Arg Thr Ala Cys Val Arg Phe Ser His Ala Arg Asp Pro 580 585 590

Ile Phe Gly Asn Gin Ile Ile Pro Ala Glu Tyr Cys Leu Ser Tyr Glu 595 600 605

Thr Glu Ile Leu Thr Val Glu Tyr Gly Leu Leu Pro Ile Gly Lys Ile 610 615 620

Val Glu Lys Arg Ile Glu Cys Thr Val Tyr Ser Val Asp Asn Asn Gly 625 630 635 640

Asn Ile Tyr Thr Gin Pro Val Ala Gin Trp His Asp Arg Gly Glu Gin 645 650 655

Glu Val Phe Glu Tyr Cys Leu Glu Asp Gly Ser Leu Ile Arg Ala Thr 660 665 670

Lys Asp His Lys Phe Met Thr Val Asp Gly Gin Met Leu Pro Ile Asp 675 680 685

Glu Ile Phe Glu Arg Glu Leu Asp Leu Met Arg Val Asp Asn Leu Pro 690 695 700

Asn Gly Gly Lys Ile Ala Val Asn Ser Ala Cys Lys Asn Trp Phe Ser 705 710 715 720

Ser Leu Ser His Phe Val Ile His Leu Asn Ser His Gly Phe Pro Pro 725 730 735

Glu Val Glu Glu Gin Ala Ala Gly Thr Leu Pro Met Ser Cys Ala Gin 740 745 750 G1U Ser Gly Met Asp Arg His Pro Ala Ala Cys Ala Ser Ala Arg Ile 755 760 765

Asn Val 770 <210> 75 <211> 1671

<212> DNA <213> Artificial Sequence <220> <223> - <220>

<221> CDS <222> (1) .. (1668) <400> 75 atg gag cag aag ctg ate agc gag gag gac ctg ggt tet gga gaa gat 48

Met Glu Gin Lys Leu Ile Ser Glu Glu Asp Leu Gly Ser Gly Glu Asp 15 10 15 gcc aaa aac att aag aag ggc cca gcg cca ttc tac cca ete gaa gac 96

Ala Lys Asn Ile Lys Lys Gly Pro Ala Pro Phe Tyr Pro Leu Glu Asp 20 25 30 ggg acc gcc gg cag ctg cac aaa gcc atg aag ege tac gcc ctg 144

Gly Thr Ala Gly Glu Gin Leu His Lys Ala Met Lys Arg Tyr Ala Leu 35 40 45 gtg ccc ggc acc ate gcc ttt acc gac gca cat ate gag gtg gac att 192

Val Pro Gly Thr Ile Ala Phe Thr Asp Ala His Ile Glu Val Asp Ile 50 55 60 acc tac gcc gag tac ttc gag atg agc gtt cgg ctg gca gaa get atg 240

Thr Tyr Ala Glu Tyr Phe Glu Met Ser Val Arg Leu Ala Glu Ala Met 65 70 75 80 aag ege tat ggg ctg aat aca aac cat cgg ate gtg gtg tgc agc gag 288

Lys Arg Tyr Gly Leu Asn Thr Asn His Arg Ile Val Val Cys Ser Glu 85 90 95 aat agc ttg cag ttc ttc atg ccc gtg ttg ggt gcc ctg ttc ate ggt 336

Asn Ser Leu Gin Phe Phe Met Pro Val Leu Gly Ala Leu Phe Ile Gly 100 105 110 gtg get gtg gcc cca get aac gac ate tac aac gag ege gag ctg ctg 384

Val Ala Val Ala Pro Ala Asn Asp Asle Ile Tyr Asn Glu Arg Glu Leu Leu 115 120 125 aac agc atg ggc ate agc cag ccc acc gtc gta ttc gtg agc aag aaa 432

Asn Ser Met Gly Ile Ser Gin Pro Thr Val Val Phe Val Ser Lys Lys 130 135 140 ggg ctg caa aag ate ete aac gtg caa aag aag cta ccg ate ata caa 480

Gly Leu Gin Lys Ile Leu Asn Val Gin Lys Leu Pro Ile Ile Gin 145 150 155 160 aag ate ate ate atg gat agc aag acc gac tac cag ggc ttc caa agc 528

Lys Ile Ile Ile Met Asp Ser Lys Thr Asp Tyr Gin Gly Phe Gin Ser 165 170 175 atg tac acc ttc ct ccc tc ct ccc gc ttc aac gag tac 576

Met Tyr Thr Phe Val Thr Ser His Leu Pro Pro Gly Phe Asn Glu Tyr 180 185 190 gac ttc gtg ccc gag agc ttc gac cgg gac aaa acc ate gcc ctg ate 624

Asp Phe Val Pro Glu Ser Phe Asp Arg Asp Lys Thr Ile Ala Leu Ile 195 200 205 atg aac agt agt ggc agt acc gga ttg ccc aag ggc gta gcc cta ccg 672

Met Asn Ser Ser Gly Ser Ther Gly Leu Pro Lys Gly Val Ala Leu Pro 210 215 220 cac ege acc ttc gtc ega ttc agt cat gcc ege gac ccc ate ttc 720

His Arg Thr Ala Cys Val Arg Phe Ser His Ala Arg Asp Pro Ile Phe 225 230 235 240 ggc aac cag ate ate ccc gac acc get ate ete agc gtg gtg cca ttt 768

Gly Asn Gin Ile Pro Asp Thr Ala Ile Leu Ser Val Val Pro Phe 245 250 255 cac cac ggc ttc ggc atg ttc acc acg ctg ggc tac ttg ate tgc ggc 816

His His Gly Phe Gly Met Phe Thr Thr Leu Gly Tyr Leu Ile Cys Gly 260 265 270 ttt cgg gtc gtg ctc tg ctc cgc

Phe Arg Val Val Leu Met Tyr Arg Phe Glu Glu Glu Leu Phe Leu Arg 275 280 285 agc ttg caa gac tat aag att caa tet gcc ctg ctg gtg ccc aca cta 912

Ser Leu Gin Asp Tyr Lys Ile Gin Ser Ala Leu Leu Val Pro Thr Leu 290 295 300 ttt agt ttc ttc get aag agc act ctc ate gac aag tac gac cta agc 960

Phe Ser Phe Phe Ala Lys Ser Thr Leu Ile Asp Lys Tyr Asp Leu Ser 305 310 315 320 aac ttg cac gag ate gcc agc ggc ggg gcg ccc cc agc aag gag gta 1008

Asn Leu His Glu Ile Ala Ser Gly Gly Ala Pro Leu Ser Lys Glu Val 325 330 335 ggt gag gcc gtg gcc aaa cgc ttc cac cta cca ggc ate cgc cag ggc 1056

Gly Glu Ala Val Ala Lys Arg Phe His Leu Pro Gly Ile Arg Gin Gly 340 345 350 tac ggc ctg aca gaa aca acc agc gcc att ctg ate acc ccc gaa ggg 1104

Tyr Gly Leu Thr Glu Thr Thr Ser Ala Ile Leu Ile Thr Pro Glu Gly 355 360 365 gac gac aag cct ggc gca gta ggc aag gtg gtg ccc ttc ttc gag get 1152

Asp Asp Lys Pro Gly Ala Val Gly Lys Val Val Pro Phe Phe Glu Ala 370 375 380 aag gtg gtg gac ttg gac acc ggt aag aca ctg ggt gtg aq cag cgc 1200

Lys Val Val Asp Leu Asp Thr Gly Lys Thr Leu Gly Val Asn Gin Arg 385 390 395 400 ggc gg ctg tgc gtc cgt ggc ccc atg ate atg agc ggc tac gtt aac 1248

Gly Glu Leu Cys Val Arg Gly Pro Met Ile Met Ser Gly Tyr Val Asn 405 410 415 aac ccc gag get aca aac get ctc ate gac aag gac ggc tgg ctg cac 1296

Asn Pro Glu Ala Thr Asn Ala Leu Ile Asp Lys Asp Gly Trp Leu His 420 425 430 agc ggc gac gac gac gac gac gac gac gac gac cac ttc ttc ate gtg 1344

Ser Gly Asp Ile Ala Tyr Trp Asp Glu Asp Glu His Phe Phe Ile Val 435 440 445 gac cgg ctg aag agc ctg ate aaa tac aag ggc tac cag gta gcc cca 1392

Asp Arg Leu Lys Ser Leu Ile Lys Tyr Lys Gly Tyr Gin Val Ala Pro 450 455 460 gcc aga ate ctg ctg caa cac ccc aac ate ttc gac gcc 1440

Ala Glu Leu Glu Ser Ile Leu Gin His Pro Asn Ile Phe Asp Ala 465 470 475 480 ggg gc gcc ggc ccc gcc gac gac gac gcc ggc gag ctg ccc gcc gca 1488

Gly Val Ala Gly Leu Pro Asp Asp Ala Gly Glu Leu Pro Ala Ala 485 490 495 gtc gtc gtg ctg gaa cac ggt aaa ggc ggc tet ggc ggc tet gaa aat 1536

Val Val Val Leu Glu His Gly Lys Gly Gly Ser Gly Gly Ser Glu Asn 500 505 510 ttg tat ttc cag agt ggc ggc tet ggc ggc tet tca ccc gag gac gag 1584

Leu Tyr Phe Gin Ser Gly Gly Ser Gly Gly Ser Ser Pro Glu Asp Glu 515 520 525 ctt get get aat gaa gag gag ttg cag caa aat gaa caa aag ttg get 1632

Leu Ala Ala Asn Glu Glu Glu Leu Gin Gin Asn Glu Gin Lys Leu Ala 530 535 540 caa att aag caa aaa ctt caa get ate aaa tac ggt taa 1671

Gin Ile Lys Gin Lys Leu Gin Alla Ile Lys Tyr Gly 545 550 555 <210> 76 <211> 556

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 76

Met Glu Gin Lys Leu Ile Ser Glu Glu Asp Leu Gly Ser Gly Glu Asp 15 10 15

Ala Lys Asn Ile Lys Lys Gly Pro Ala Pro Phe Tyr Pro Leu Glu Asp 20 25 30

Gly Thr Ala Gly Glu Gin Leu His Lys Ala Met Lys Arg Tyr Ala Leu 35 40 45

Val Pro Gly Thr Ile Ala Phe Thr Asp Ala His Ile Glu Val Asp Ile 50 55 60

Thr Tyr Ala Glu Tyr Phe Glu Met Ser Val Arg Leu Ala Glu Ala Met 65 70 75 80

Lys Arg Tyr Gly Leu Asn Thr Ash His Arg Ile Val Val Cys Ser Glu 85 90 95

Asn Ser Leu Gin Phe Phe Met Pro Val Leu Gly Ala Leu Phe Ile Gly 100 105 110

Val Ala Val Ala Pro Ala Asn Asp Ile Tyr Asn Glu Arg Glu Leu Leu 115 120 125

Asn Ser Met Gly Ile Ser Gin Pro Thr Val Val Phe Val Ser Lys Lys 130 135 140

Gly Leu Gin Lys Ile Leu Asn Val Gin Lys Leu Pro Ile Ile Gin 145 150 155 160

Lys Ile Ile Ile Met Asp Ser Lys Thr Asp Tyr Gin Gly Phe Gin Ser 165 170 175

Met Tyr Thr Phe Val Thr Ser His Leu Pro Pro Gly Phe Asn Glu Tyr 180 185 190

Asp Phe Val Pro Glu Ser Phe Asp Arg Asp Lys Thr Ile Ala Leu Ile 195 200 205

Met Asn Ser Ser Gly Ser Thr Gly Leu Pro Lys Gly Val Ala Leu Pro 210 215 220

His Arg Thr Ala Cys Val Arg Phe Ser His Ala Arg Asp Pro Ile Phe 225 230 235 240

Gly Asn Gin Ile Pro Asp Thr Ala Ile Leu Ser Val Val Pro Phe 245 250 255

His Gly Phe Gly Met Phe Thr Thr Leu Gly Tyr Leu Ile Cys Gly 260 265 270

Phe Arg Val Val Leu Met Tyr Arg Phe Glu Glu GlU Leu Phe Leu Arg 275 280 285

Ser Leu Gin Asp Tyr Lys Ile Gin Ser Ala Leu Leu Val Pro Thr Leu 290 295 300

Phe Ser Phe Phe Ala Lys Ser Thr Leu Ile Asp Lys Tyr Asp Leu Ser 305 310 315 320

Asn Leu His Glu Ile Ala Ser Gly Gly Ala Pro Leu Ser Lys Glu Val 325 330 335

Gly Glu Ala Val Ala Lys Arg Phe His Leu Pro Gly Ile Arg Gin Gly 340 345 350

Tyr Gly Leu Thr Glu Thr Thr Ser Ala Ile Leu Ile Thr Pro Glu Gly 355 360 365

Asp Asp Lys Pro Gly Ala Val Gly Lys Val Val Pro Phe Phe Glu Ala 370 375 380

Lys Val Val Asp Leu Asp Thr Gly Lys Thr Leu Gly Val Asn Gin Arg 385 390 395 400

Gly Glu Leu Cys Val Arg Gly Pro Met Ile Met Ser Gly Tyr Val Asn 405 410 415

Asn Pro Glu Ala Thr Asn Ala Leu Ile Asp Lys Asp Gly Trp Leu His 420 425 430

Ser Gly Asp Ile Ala Tyr Trp Asp Glu Asp Glu His Phe Phe Ile Val 435 440 445

Asp Arg Leu Lys Ser Leu Ile Lys Tyr Lys Gly Tyr Gin Val Ala Pro 450 455 460

Ala Glu Leu Glu Ser Ile Leu Leu Gin His Pro Asn Ile Phe Asp Ala 465 470 475 480

Gly Val Ala Gly Leu Pro Asp Asp Ala Gly Glu Leu Pro Ala Ala 485 490 495

Val Val Leu Glu His Gly Lys Gly Gly Ser Gly Gly Ser Glu Asn 500 505 510

Leu Tyr Phe Gin Ser Gly Gly Ser Gly Gly Ser Ser Pro Glu Asp Glu 515 520 525

Leu Ala Ala Asn Glu Glu Glu Leu Gin Gin Asn Glu Gin Lys Leu Ala 530 535 540

Gin Ile Lys Gin Lys Leu Gin Ala Ile Lys Tyr Gly 545 550 555 <210> 77

<211> 1800 <212> DNA <213> Artificial Sequehce <220> <223> - <220> <221> GDS <222> (1) .. (1797) <400> 77 atg gag cag aag ctg ate agc gag gag gac ctg ggt tet gga gaa gat 48

Met Glu Gin Lys Leu Ile Ser Glu Glu Asp Leu Gly Ser Gly Glu Asp 15 10 15 gec aaa aac att aag aag ggc cca gcg cca ttc tac cca ete gaa gac 96

Ala Lys Asn Ile Lys Lys Gly Pro Ala Pro Phe Tyr Pro Leu Glu Asp 20 25 30 ggg acc gcc gg cag ctg cac aaa gcc atg aag ege tac gcc ctg 144

Gly Thr Ala Gly Glu Gin Leu His Lys Ala Met Lys Arg Tyr Ala Leu 35 40 45 gtg ccc ggc acc ate gcc ttt acc gac gca cat ate gag gtg gac att 192

Val Pro Gly Thr Ile Ala Phe Thr Asp Ala His Ile Glu Val Asp Ile 50 55 <60 acc tac gcc gag tac ttc gag atg agch gtt cgg ctg gca gaa get atg 240

Thr Tyr Ala Glu Tyr Phe Glu Met Ser Val Arg Leu Ala Glu Ala Met 65 70 75 80 aag ege tat ggg ctg aat aca aac cat cgg ate gtg gtg tgc agc gag 288

Lys Arg Tyr Gly Leu Asn Thr Asn His Arg Ile Val Val Cys Ser Glu 85 90 95 aat agc ttg Cag ttc ttc atg ccc gtg ttg ggt gcc ctg ttc ate ggt 336

Asn Ser Leu Gin Phe Phe Met Pro Val Leu Gly Ala Leu Phe Ile Gly 100 105 110 gtg get gtg gcc cca get aac gac ate tac aac gag ege gag ctg ctg 384

Val Ala Val Ala Pro Ala Asn Asp Asle Ile Tyr Asn Glu Arg Glu Leu Leu 115 120 125 aac agc atg ggc ate agc cag ccc acc gtc gta ttc gtg agc aag aaa 432

Asn Ser Met Gly Ile Ser Gin Pro Thr Val Val Phe Val Ser Lys Lys 130 135 140 ggg ctg caa aag ate ete aac gtg caa aag aag cta ccg ate ata caa 480

Gly Leu Gin Lys Ile Leu Asn Val Gin Lys Leu Pro Ile Ile Gin 145 150 155 160 aag ate ate ate atg gat agc aag acc gac tac cag ggc ttc caa agc 528

Lys Ile Ile Ile Met Asp Ser Lys Thr Asp Tyr Gin Gly Phe Gin Ser 165 170 175 atg tac acc ttc ct ccc tc ct ccc gc ttc aac gag tac 576

Met Tyr Thr Phe Val Thr Ser His Leu Pro Pro Gly Phe Asn Glu Tyr 180 185 190 gac ttc gtg ccc gag agc ttc gac cgg gac aaa acc ate gcc ctg ate 624

Asp Phe Val Pro Glu Ser Phe Asp Arg Asp Lys Thr Ile Ala Leu Ile 195 200 205 atg aac agt agt ggc agt acc gga ttg ccc aag ggc gta gcc cta ccg 672

Met Asn Ser Ser Gly Ser Ther Gly Leu Pro Lys Gly Val Ala Leu Pro 210 215 220 cac ege acc ttc gtc ega ttc agt cat gcc ege gac ccc ate ttc 720

His Arg Thr Ala Cys Val Arg Phe Ser His Ala Arg Asp Pro Ile Phe 225 230 235 240 ggc aac cag ate ate ccc gac acc get ate ete agc gtg gtg cca ttt 768

Gly Asn Gin Ile Pro Asp Thr Ala Ile Leu Ser Val Val Pro Phe 245 250 255 cac cac ggc ttc ggc atg ttc acc acg ctg ggc tac ttg ate tgc ggc 816

His His Gly Phe Gly Met Phe Thr Thr Leu Gly Tyr Leu Ile Cys Gly 260 265 270 ttt cgg gtc gtg ete atg tac cgd ttc gag gag cta ttc ttg ege 864

Phe Arg Val Val Leu Met Tyr Arg Phe Glu Glu Glu Leu Phe Leu Arg 275 280 285 agc ttg caa gac tat aag att caa tet gcc ctg ctg gtg ccc aca cta 912

Ser Leu Gin Asp Tyr Lys Ile Gin Ser Ala Leu Leu Val Pro Thr Leu 290 295 300 ttt agc ttc ttc get aag agc act ete ate gac aag tac gac cta agc 960

Phe Ser Phe Phe Ala Lys Ser Thr Leu Ile Asp Lys Tyr Asp Leu Ser 305 310 315 320 aac ttg cac gag ate gcc agc ggc ggg gcg ceg ete agc aag gag gta 1008

Asn Leu His Glu Ile Ala Ser Gly Gly Ala Pro Leu Ser Lys Glu Val 325 330 335 ggt gag gcc gtg gcc aaa ege ttc cac cta cca ggc ate ege cag ggc 1056

Gly Glu Ala Val Ala Lys Arg Phe His Leu Pro Gly Ile Arg Gin Gly 340 345 350 tac ggc ctg aca gaa aca acc agc gcc att ctg ate acc ccc gaa ggg 1104

Tyr Gly Leu Thr Glu Thr Thr Ser Ala Ile Leu Ile Thr Pro Glu Gly 355 360 365 gac gac aag cct ggc gca gta ggc aag gtg gtg ccc ttc ttc gag get 1152

Asp Asp Lys Pro Gly Ala Val Gly Lys Val Val Pro Phe Phe Glu Ala 370 375 380 aag gtg gtg gac ttg gac acc ggt aag aca ctg ggt gtg aag cag ege 1200

Lys Val Val Asp Leu Asp Thr Gly Lys Thr Leu Gly Val Asn Gin Arg 385 390 395 400 ggc gg ctg tgc gtc cgt ggc ccc atg ate atg agc ggc tac gtt aac 1248

Gly Glu Leu Cys Val Arg Gly Pro Met Ile Met Ser Gly Tyr Val Asn 405 410 415 aac ccc gag get aca aac get ete ate gac aag gac ggc tgg ctg cac 1296

Asn Pro Glu Ala Thr Asn Ala Leu Ile Asp Lys Asp Gly Trp Leu His 420 425 430 agc ggc gac gac gac gac gac gac gac gac gac cac ttc ttc ate gtg 1344

Ser Gly Asp Ile Ala Tyr Trp Asp Glu Asp Glu His Phe Phe Ile Val 435 440 445 gac cgg ctg aag agc ctg ate aaa tac aag ggc tac cag gta gcc cca 1392

Asp Arg Leu Lys Ser Leu Ile Lys Tyr Lys Gly Tyr Gin Val Ala Pro 450 455 460 gcc aga ate ctg ctg caa cac ccc aac ate ttc gac gcc 1440

Ala Glu Leu Glu Ser Ile Leu Gin His Pro Asn Ile Phe Asp Ala 465 470 475 480 ggg gc gcc ggc ccc gcc gac gac gac gcc ggc gag ctg ccc gcc gca 1488

Gly Val Ala Gly Leu Pro Asp Asp Asp Ala Gly Glu Leu Pro Ala Ala 485 490 495 gtc gtc gtg ctg gaa cac ggt aaa ggc ggc ggc ggc ggc ggc gcc 1536

Val Val Leu Glu Gly Gly Gly Gly Gly Gly Gly Gly Gly Gly 500 505 510 ggc tca ccc gag gac gag ctt get aat gaa gag gag ttg cag 1584

Gly Ser Ser Pro Glu Asp Glu Leu Ala Ala Asn Glu Glu Glu Leu Gin 515 520 525 caa aat gaa caa aag ttg get caa att aag caa aaa ctt caa get ate 1632

Gin Asn Glu Gin Lys Leu Ala Gin Ile Lys Gin Lys Leu Gin Ala Ile 530 535 540 aaa tac ggt ggc ggc tet ggc ggc ggc gaa aat ttg tat ttc cag agt 1680

Lys Tyr Gly Gly Gly Gly Gly Gly Gly Gly Asn Leu Tyr Phe Gin Ser 545 550 555 560 ggc gcc tcc gga ggc tet tcc ccc gag gac gag ete cag cag gcc gag 1728

Gly Gly Ser Gly Gly Ser Ser Pro Glu Asp Glu Leu Gin Gin Ala Glu 565 570 575 gag gag ete tcc cag gcc gag cag aag aac tcc cag ctg aag gag aag 1776

Glu Glu Leu Ser Gin Ala Glu Gin Lys Asn Ser Gin Leu Lys Glu Lys 580 585 590 aac cag cag ctg aag tac ggc taa 1800

Asn Gin Gin Leu Lys Tyr Gly 595 <210> 78 <211> 599

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <4Q> 78

Met Glu Gin Lys Leu Ile Ser Glu Glu Asp Leu Gly Ser Gly Glu Asp 15 10 15

Ala Lys Asn Ile Lys Lys Gly Pro Ala Pro Phe Tyr Pro Leu Glu Asp 20 25 30

Gly Thr Ala Gly Glu Gin Leu His Lys Ala Met Lys Arg Tyr Ala Leu 35 40 45

Val Pro Gly Thr Ile Ala Phe Thr Asp Ala His Ile Glu Val Asp Ile 50 55 60

Thr Tyr Ala Glu Tyr Phe Glu Met Ser Val Arg Leu Ala Glu Ala Met 65 70 75 80

Lys Arg Tyr Gly Leu Asn Thr Asn His Arg Ile Val Val Cys Ser Glu 85 90 95

Asn Ser Leu Gin Phe Phe Met Pro Val Leu Gly Ala Leu Phe Ile Gly 100 105 110

Val Ala Val Ala Pro Ala Asn Asp Ile Tyr Asn Glu Arg Glu Leu Leu 115 120 125

Asn Ser Met Gly Ile Ser Gin Pro Thr Val Val Phe Val Ser Lys Lys 130 135 140

Gly Leu Gin Lys Ile Leu Asn Val Gin Lys Leu Pro Ile Ile Gin 145 150 155 160

Lys Ile Ile Ile Met Asp Ser Lys Thr Asp Tyr Gin Gly Phe Gin Ser 165 170 175

Met Tyr Thr Phe Val Thr Ser His Leu Pro Pro Gly Phe Asn Glu Tyr 180 185 190

Asp Phe Val Pro Glu Ser Phe Asp Arg Asp Lys Thr Ile Ala Leu Ile 195 200 205

Met Asn Ser Ser Gly Ser Thr Gly Leu Pro Lys Gly Val Ala Leu Pro 210 215 220

His Arg Thr Ala Cys Val Arg Phe Ser His Ala Arg Asp Pro Ile Phe 225 230 235 240

Gly Asn Gin Ile Pro Asp Thr Ala Ile Leu Ser Val Val Pro Phe 245 250 255

His Gly Phe Gly Met Phe Thr Thr Leu Gly Tyr Leu Ile Cys Gly 260 265 270

Phe Arg Val Val Leu Met Tyr Arg Phe Glu Glu Glu Leu Phe Leu Arg 275 280 285

Ser Leu Gin Asp Tyr Lys Ile Gin Ser Ala Leu Leu Val Pro Thr Leu 290 295 300

Phe Ser Phe Phe Ala Lys Ser Thr Leu Ile Asp Lys Tyr Asp Leu Ser 305 310 315 320

Asn Leu His Glu Ile Ala Ser Gly Gly Ala Pro Leu Ser Lys Glu Val 325 330 335

Gly Glu Ala Val Ala Lys Arg Phe His Leu Pro Gly Ile Arg Gin Gly 340 345 350

Tyr Gly Leu Thr Glu Thr Thr Ser Ala Ile Leu Ile Thr Pro Glu Gly 355 360 365

Asp Asp Lys Pro Gly Ala Val Gly Lys Val Val Pro Phe Phe Glu Ala 370 375 380

Lys Val Val Asp Leu Asp Thr Gly Lys Thr Leu Gly Val Asn Gin Arg 385 390 395 400

Gly Glu Leu Cys Val Arg Gly Pro Met Ile Met Ser Gly Tyr Val Asn 405 410 415

Asn Pro Glu Ala Thr Asn Ala Leu Ile Asp Lys Asp Gly Trp Leu His 420 425 430

Ser Gly Asp Ile Ala Tyr Trp Asp Glu Asp Glu His Phe Phe Ile Val 435 440 445

Asp Arg Leu Lys Ser Leu Ile Lys Tyr Lys Gly Tyr Gin Val Ala Pro 450 455 460

Ala Glu Leu Glu Ser Ile Leu Leu Gin His Pro Asn Ile Phe Asp Ala 465 470 475 480

Gly Val Ala Gly Leu Pro Asp Asp Ala Gly Glu Leu Pro Ala Ala 485 490 495

Val Val Leu Glu Gly Gly Gly Gly Gly Gly Gly Ser Gly 500 505 510

Gly Ser Ser Pro Glu Asp Glu Leu Ala Ala Asn Glu Glu Glu Leu Gin 515 520 525

Gin Asn Glu Gin Lys Leu Ala Gin Ile Lys Gin Lys Leu Gin Ala Ile 530 535 540

Lys Tyr Gly Gly Gly Gly Gly Gly Gly Asn Leu Tyr Phe Gin Ser 545 550 555 560

Gly Gly Ser Gly Gly Ser Ser Pro Glu Asp Glu Leu Gin Gin Ala Glu 565 570 575

Glu Glu Leu Ser Gin Ala Glu Gin Lys Asn Ser Gin Leu Lys Glu Lys 580 585 590

Asn Gin Gin Leu Lys Tyr Gly 595 <210> 79 <211> 381

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1). . (378) <400> 79 atg tcc ccg gaa gat gag ate cag caa ctg gaa gaa gaa ate get cag 43

Met Ser Pro Glu Asp Glu Ile Gin Gin Leu Glu Glu Glu Ile Ala Gin 15 10 15 ctg gaa cag aaa aac gca gcg ctg aaa gag aaa aac cag gcg ctg aaa gg

Leu Glu Gin Lys Asn Ala Lea Lys Glu Lys Asn Gin Ala Leu Lys 20 25 30 tac ggt ggc ggc ggc tet ggc ggc tet aac gtg gtg gtg cac cag gcc ggc 144

Tyr Gly Gly Gly Gly Gly Gly Ser Asn Val Val Val His Gin Ala Gly 35 40 45 ggc tet ggc ggc tet acc atg acc gag aag gag ate gtg gac tat gtg 192

Gly Ser Gly Gly Ser Thr Met Thr Glu Lys Glu Ile Val Asp Tyr Val 50 55 60 gcc agc cag gtt aca acc gcc aag aag ctg ege ggt ggt gtt gtt ttc 240

Ala Ser Gin Val Thr Thr Ala Lys Lys Leu Arg Gly Gly Val Val Phe 65 70 75 80 gtg gac gag gtg cct aaa gga ctg acc ggc aag ttg gac gcc ege aag 288

Val Asp Glu Val Pro Lys Gly Leu Le Thr Gly Lys Leu Asp Ala Arg Lys 85 90 95 ate ege gag att ete att aag gcc aag aag ggc ggc aag ate gcc gtg 335

Ile Arg Glu Ile Leu Ile Lys Ala Lys Lys Gly Gly Lys Ile Ala Val 100 105 110 aat agt ggt tet gga tac cca tac gat gtt cca gat tac get taa 331

Asn Ser Gly Ser Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala 115 120 125

<210> 80 <211> 126 <212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 80

Met Ser Pro Glu Asp Glu Ile Gin Gin Leu Glu Glu Glu Ile Ala Gin 15 10 15

Leu Glu Gin Lys Asn Ala Lea Lys Glu Lys Asn Gin Ala Leu Lys 20 25 30

Tyr Gly Gly Gly Ser Gly Gly Ser Asn Val Val Val His Gin Ala Gly 35 40 45

Gly Ser Gly Gly Ser Thr Met Thr Glu Lys Glu Ile Val Asp Tyr Val 50 55 60

Ala Ser Gin Val Thr Thr Ala Lys Lys Leu Arg Gly Gly Val Val Phe 65 70 75 80

Val Asp Glu Val Pro Lys Gly Leu Thr Gly Lys Leu Asp Ala Arg Lys 85 90 95

Ile Arg Glu Ile Leu Ile Lys Ally Lys Lys Gly Lly Ile Ala Val 100 105 110

Asn Ser Gly Ser Gly Tyr Pro Tyr Asp Val Pro Asp Tyr Ala 115 120 125 <210> 81 <211> 1049

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> promoter <222> (17) .. (294) <220>

<221> CDS <222> (330) .. (1046) <400> 81 atacggtggc accggtactc tatcaatgat agagttgctg gccggggtac cactctatca 60 atgatagagt ttgacacagc gcagggactc tatcaatgat agagtgcggc cgcatgtcac 120 gactctatca atgatagagt tcgcccgtac atccaaactc tatcaatgat agagttgcgg 180 cgtttggtcc tactctatca atgatagagt agtgggtgcc gccaaaggat cctgtacggg 240 ccagatatac gcgttgagat cttagagggt atataatgga agctcgactt ccagctcgag 300 ggcaatccgg tactgttggt aaagccacc atg gtg agc aag ggc gag gag ctg 353

Met Val Ser Lys Gly Glu Glu Leu 1 5 ttc acc ggg gg gta gac gta aac 401

Phe Thr Gly Val Val Pro Ile Leu Val Glu Leu Asp Gly Asp Val Asn 10 15 20 ggc cac aag ttc agc gtg tcc ggc gag ggc gag gg gc gc acc tac 449

Gly His Lys Phe Ser Val Gly Gly Gly Gly Gly Asp Ala Thr Tyr 25 30 35 40 ggc aag ctg acc ctg aag ttc ate tgc acc acc ggc aag ctg ccc gtg 497

Gly Lys Leu Thr Leu Lys Phe Ile Cys Thr Thr Gly Lys Leu Pro Val 45 50 55 ccc tgg ccc acc ete gt acc acc ttc ggc tac ggc ctg atg tgc ttc 545

Pro Trp Pro Thr Le Thr Thr Thhe Phe Gly Tyr Gly Leu Met Cys Phe 60 65 70 gcc ege tac ccc gac cac atg aag cag cac gac ttc ttc aag tcc gcc 593

Ala Arg Tyr Pro Asp His Met Lys Gin His Asp Phe Lhe Ser Ala 75 80 85 atg ccc gaa ggc tac gtc cag gag ege acc ate ttc ttc aag gac gac 641

Met Pro Glu Gly Tyr Val Gin Glu Arg Thr Ile Phe Phe Lys Asp Asp 90 95 100 ggc aac tac aag acc ege gcc gag gtg aag ttc gag ggc gac acc ctg 689

Gly Asn Tyr Lys Thr Arg Ala Glu Val Lys Phe Glu Gly Asp Thr Leu 105 110 115 120 gtg aac cgc ate gag ctg aag ggc ate gac ttc aag gag gac ggc aac 737

Val Asn Arg Ile Glu Leu Lys Gly Ile Asp Phe Lys Glu Asp Gly Asn 125 130 135 ate ctg ggg cac aag ctg gag tac aac tac aac agc cac aac gtc tat 785

Ile Leu Gly His Lys Leu Glu Tyr Asn Tyr Asn Ser His Asn Val Tyr 140 145 150 ate atg gcc gac aag cag aag aac ggc ate aag gtg aac ttc aag ate 833

Ile Met Ala Asp Lys Gin Lys Asn Gly Ile Lys Val Asn Phe Lys Ile 155 160 165 cg cac aac ate gag gac ggc agc gtg cag ete gcc gac cac tac cag 881

Arg His Asn Ile Glu Asp Gly Ser Val Gin Leu Ala Asp His Tyr Gin 170 175 180 cag aac acc ccc ate ggc gac ggc ccc gtg ctg ctg ccc gac aac cac 929

Gin Asn Thr Pro Ile Gly Asp Gly Pro Val Leu Leu Pro Asp Asn His 185 190 195 200 tac ctg agc tac cag tcc gcc ctg agc aaa gac ccc aac gag aag ege 977

Tyr Leu Ser Tyr Gin Ser Ala Leu Ser Lys Asp Pro Asn Glu Lys Arg 205 210 215 gat cac atg gtc ctg ctg gag ttc gtg acc gcc gcc ggg ate act ete 1025

Asp His Met Val Leu Glu Phe Val Thr Ala Gly Ile Thr Leu 220 225 230 ggc atg gac gag ctg tac aag taa 1049

Gly Met Asp Glu Leu Tyr Lys 235 <210> 82 <211> 239

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 82

Met Val Ser Lys Gly Glu Glu Leu Phe Thr Gly Val Val Pro Ile Leu 15 10 15

Val Glu Leu Asp Gly Asp Val Asn Gly His Lys Phe Ser Val Ser Gly 20 25 30

Glu Gly Glu Gly Asp Ala Thr Tyr Gly Lys Leu Thr Leu Lys Phe Ile 35 40 45

Cys Thr Thr Gly Lys Leu Pro Val Pro Trp Pro Thr Leu Val Thr Thr 50 55 60

Phe Gly Tyr Gly Leu Met Cys Phe Ala Arg Tyr Pro Asp His Met Lys 65 70 75 80

Gin His Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Val Gin Glu 85 90 95

Arg Thr Ile Phe Phe Lys Asp Asp Gly Asn Tyr Lys Thr Arg Ala Glu 100 105 110

Val Lys Phe Glu Gly Asp Thr Leu Val Asn Arg Ile Glu Leu Lys Gly 115 120 125

Ile Asp Phe Lys Glu Asp Gly Asn Ile Leu Gly His Lys Leu Glu Tyr 130 135 140

Asn Tyr Asn Ser His Asn Val Tyr Ile Met Ala Asp Lys Gin Lys Asn 145 150 155 160

Gly Ile Lys Val Asn Phe Lys Ile Arg His Asn Ile Glu Asp Gly Ser 165 170 175

Val Gin Leu Ala Asp His Tyr Gin Gin Asn Thr Pro Ile Gly Asp Gly 180 185 190

Pro Val Leu Leu Pro Asp Asn His Tyr Leu Ser Tyr Gin Ser Ala Leu 195 200 205

Ser Lys Asp Pro Asn Glu Lys Arg Asp His Met Val Leu Leu Glu Phe 210 215 220

Val Thr Ala Ala Gly Ile Thr Leu Gly Met Asp Glu Leu Tyr Lys 225 230 235 <210> 83 <211> 2865

<212> DNA <213> Artificial Sequence <220> <223> - <220> <221> CDS <222> (1) .. (2856) <400> 83 atg ca cac cac cac cac cac gac tac aaa gac cat gac ggt gat tat 48

Met His His His His House His Asp Tyr Lys Asp His Asp Gly Asp Tyr 15 10 15 aaa gat cat gac ate gat tac aag gat gac gat gac aag atg gcc ccc 96

Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Lys Met Ala Pro 20 25 30 aag aag aag agg aag gtg ggc att cac ege ggg gta cct atg gtg gac 144

Lys Lys Lys Arg Lys Val Gly Ile His Arg Gly Val Pro Met Val Asp 35 40 45 ttg agg aca ete ggt tat teg caa cag caa cag gag aaa ate aag cct 192

Leu Arg Thr Leu Gly Tyr Ser Gin Gin Gin Gin Glu Lys Ile Lys Pro 50 55 60 aag gtc agg agc acc gtc gcg caa cac cac gag gcg ctt gtg ggg cat 240

Lys Val Arg Ser Thr Val Ala Gin His His Glu Ala Leu Val Gly His 65 70 75 80 ggc ttc act cat gcg cat att gtc gcg ctt tca cag cac cct gcg gcg 288

Gly Phe Thr His Ala His Ile Val Ala Leu Ser Gin His Pro Ala Ala 85 90 95 ctt ggg acg gtg get gtc aaa tac caa gat atg att gcg gcc ctg ccc 336

Leu Gly Thr Val Ala Val Lys Tyr Gin Asp Met Ile Ala Lea Pro 100 105 110 gaa gcc acg cac gag gca gta ggg gtc ggt aaa cag tgg teg gga 384

Glu Ala Thr His Glu Ala Ile Val Gly Val Gly Lys Gin Trp Ser Gly 115 120 125 gcg ega gta ctt gag gcg ctg ctg act gtg gcg ggt gag ctt agg ggg 432

Ala Arg Ala Leu Glu Ala Leu Leu Thr Val Ala Gly Glu Leu Arg Gly 130 135 140 cct ccg ete cag ete gac acc ggg cag ctg ctg aag ate gcg aag aga 480

Pro Pro Leu Gin Leu Asp Thr Gly Gin Leu Leu Lys Ile Ala Lys Arg 145 150 155 160 ggg gga gta aca gcg gta gag gca gtg cac gcc tgg ege aat gcg ete 528

Gly Gly Val Thr Ala Val Glu Ala Val His Ala Trp Arg Asn Ala Leu 165 170 175 acc ggg gcc ccg ctg aat ctg aca ccg gaa cag gtt gtt gca att gca 576

Thr Gly Ala Pro Leu Asn Leu Thr Pro Glu Gin Val Val Ala Ile Ala 180 185 190 agc cat gat ggt ggt aaa cag gca ctg gaa acc gtt cag cgt ctg ctg 624

Ser His Asp Gly Gly Lys Gin Ala Leu Glu Thr Val Gin Arg Leu Leu 195 200 205 ccg gtt ctg tgt cag gca cat ggt ctg acc cct gaag cag gtg gtg gcc 672

Pro Val Leu Cys Gin Ala His Gly Leu Thr Pro Glu Gin Val Val Ala 210 215 220 att gcc agt aat ggt ggt ggc aaa cag gcg tta gaa aca gtg cag ege 720

Ile Ala Ser Asn Gly Gly Gly Lys Gin Ala Leu Glu Thr Val Gin Arg 225 230 235 240 ctg ctg cct gtt tta tgc cag gcc cat ggc ctg aca cca gag cag gta 768

Leu Leu Pro Val Leu Cys Gin Ala His Gly Leu Thr Pro Glu Gin Val 245 250 255 gtg gcg att gcg agc aat att ggc ggt aaa caa gcc ctt gaa acc gtg 816

Val Ala Ile Ala Ser Asn Ile Gly Gly Lys Gin Ala Leu Glu Thr Val 260 265 270 cag gca tta ctg ccg gtg ctg tgc caa gcg cac ggc ctg acc cca gaa 864

Gin Ala Leu Leu Pro Val Leu Cys Gin Ala His Gly Leu Thr Pro Glu 275 280 285 caa gtt gtt gcg ate gca tca aat ggt ggc ggt aag cag get ttg gaa 912

Gin Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gin Ala Leu Glu 290 295 300 acg gtg cg cgt tta ctg cca gtg tta tgt cag gcg cat ggt tta aca 960

Thr Val Gin Arg Leu Leu Pro Val Leu Cys Gin Ala His Gly Leu Thr 305 310 315 320 ccg gaa caa gtg gtg gca ate gcc tca cat gat ggc gga aaa caa gca 1008

Pro Glu Gin Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gin Ala 325 330 335 tta gag act gtt caa cgc ctg ctg cca gtg ctt tgc cag gca cac ggc 1056

Leu Glu Thr Val Gin Arg Leu Leu Pro Val Leu Cys Gin Ala His Gly 340 345 350 tta aca cct gaa cag gtc gta gcg att gca tca aat att ggt gga aaa 1104

Leu Thr Pro Glu Gin Val Val Ala Ile Ala Ser Asn Ily Gly Gly Lys 355 360 365 cag gcc ttg gag act gta cag gca ctg ctg cct gta ctg tgt caa gcc 1152

Gin Ala Leu Glu Thr Val Gin Ala Leu Leu Pro Val Leu Cys Gin Ala 370 375 380 cac gga tta acg cca gaa cag gtt gtg gct ate gcc agc aat tca ggc 1200

His Gly Leu Thr Pro Glu Gin Val Val Ala Ile Ala Ser Asn Ser Gly 385 390 395 400 ggt aaa cag gcg ete gag aca gtt cag gcc ctg ctg ccg gtc tta tgt 1248

Gly Lys Gin Ala Leu Glu Thr Val Gin Ala Leu Leu Pro Val Leu Cys 405 410 415 caa gct cac gga ctg act ccc gag cag gtt gtc gcc att gcc tca aat 1296

Gin Ala His Gly Leu Thr Pro Glu Gin Val Val Ala Ile Ala Ser Asn 420 425 430 ggt ggt ggt aaa caa gct ete gaa acg gta cag aga ctg ctg ccc gtc 1344

Gly Gly Gly Lys Gin Ala Leu Glu Thr Val Gin Arg Leu Leu Pro Val 435 440 445 ctg tgc cag gcg cat gga ctt acg cct gag caa gtt gtg gca att gca 1392

Leu Cys Gin Ala His Gly Leu Thr Pro Glu Gin Val Val Ala Ile Ala 450 455 460 aat aat ggg ggt aag caa gcg ctg gaa aca gtt caa cgc tta ctg 1440

Ser Asn Asn Gly Gly Lys Gin Ala Leu Glu Thr Val Gin Arg Leu Leu 465 470 475 480 cct gtc ttg tgc caa gca cat ggt tta acc cca gag cag gtc gtt gct 1488

Pro Val Leu Cys Gin Ala His Gly Leu Thr Pro Glu Gin Val Val Ala 485 490 495 att gac tet aac att gga ggc aaa cag gct ctt gaa act gtc cag gcc 1536

Ile Ala Ser Asn Ile Gly Gly Lys Gin Ala Leu Glu Thr Val Gin Ala 500 505 510 ctg tta cct gtt ctg tgc cag gct cac ggt ttg act cca gag caa gtg 1584

Leu Leu Pro Val Leu Cys Gin Ala His Gly Leu Thr Pro Glu Gin Val 515 520 525 gtt gca ata gcc agc aac ggt ggg ggt aaa caa gct tta gaa acc gtc 1632

Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gin Ala Leu Glu Thr Val 530 535 540 caa cgt ctg tta cca gtg ctg tgt caa gct cat ggc ctt aca ccc gaa 1680

Gin Arg Leu Leu Pro Val Leu Cys Gin Ala His Gly Leu Thr Pro Glu 545 550 555 560 caa gta gtt gcc att gcg agt aac att ggt ggg aag caa gca ctt gaa 1728

Gin Val Val Ala Ile Ala Ser Asn Ile Gly Gly Lys Gin Ala Leu Glu 565 570 575 acg gtt cag gcg ctg ctt cta gta tta tgc cag gcg cac gga ete act 1776

Thr Val Gin Ala Leu Leu Pro Val Leu Cys Gin Ala His Gly Leu Thr 580 585 590 cca gaa cag gta gta gca ate gca agt aat aac ggt ggg aaa caa gcg 1824

Pro Glu Gin Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gin Ala 595 600 605 ttg gag aca gtc caa aga ctg ctt ccg gtt ctt tgc caa gcc cac ggt 1872

Leu Glu Thr Val Gin Arg Leu Leu Pro Val Leu Cys Gin Ala His Gly 610 615 620 ctt aca ccg cag cag gtt gta gct att gct agt aat att gga ggt cgt 1920

Leu Thr Pro Gin Gin Val Val Ala Ile Ala Ser Asn Ile Gly Gly Arg 625 630 635 640 ccg gca ctg gaa agc att gtt gca cag ctg agc cgt cct gat ccg gca 1968

Pro Ala Leu Glu Ser Ile Val Ala Gin Leu Ser Arg Pro Asp Pro Ala 645 650 655 ctg gca gca ctg acc aat gat cat ctg gtt gca ctg gca tgt ctg ggt 2016

Leu Ala Ala Leu Thr Asn Asp His Leu Val Ala Leu Ala Cys Leu Gly 660 665 670 ggt cct gcc ctg gat gca gtt aaa aaa ggt ctg ccg cat gct ccc 2064

Gly Arg Pro Ala Leu Asp Ala Val Lys Lys Gly Leu Pro Ala Pro 675 680 685 gca ttg ate aaa aga acc aac cgg ccc att ccc gag aga act tcc cat 2112

Ala Leu Ile Lys Arg Thr Asn Arg Arg Ile Pro Glu Arg Thr Ser His 690 695 700 ega gtc gcg ggt tcc gat act tat agat tat att gat act tat aga tat 2160

Arg Val Ala Gly Ser Asp Thr Tyr Arg Tyr Ile Asp Thr Tyr Arg Tyr 705 710 715 720 att gaa ttc cca aag aag aaa cgg aag gtg cct aag aag aag aga aag 2208

Ile Glu Phe Pro Lys Lys Lys Arg Lys Lys Lys Lys Lys Lys Lys Arg Lys 725 730 735 gtt cct aaa aag aaa aga aaa gtc gac gcc cct ccg aoc gat gtc agc 2256

Val Pro Lys Lys Lys Arg Lys Val Asp Ala Pro Pro Thr Asp Val Ser 740 745 750 ctg ggg gac gag ctc cac tta gac ggc gag gac gtg gcg atg gcg cat 2304

Leu Gly Asp Glu Leu His Leu Asp Gly Glu Asp Val Ala Met Ala His 755 760 765 gcc gac gcg cta gac gat ttc gat ctg gac atg ttg ggg gac ggg gat 2352

Ala Asp Ala Leu Asp Asp Asp Asp Asp Asp Met Leu Gly Asp Asp Gp Asp 770 775 780 tcc ccg ggt ccg gga ttt acc ccc cac gac tcc gcc ccc tac ggc gct 2400

Ser Pro Pro Gly Pro Gly Phe Thr Pro His Asp Ser Ala Pro Tyr Gly Ala 785 v 790 795 800 ctg gat atg gcc ttc gag ttt gag cag atg ttt acc gat gcc ctt 2448

Leu Asp Met Ala Asp Phe Glu Phe Glu Gin Met Phe Thr Asp Ala Leu 805 810 815 gga att gac gag tac ggt ggg ggc gaa aac ctc tac ttc cag agc ggc 2496

Gly Ile Asp Glu Tyr Gly Gly Gly Gly Asn Leu Tyr Phe Gin Ser Gly 820 825 830 ggt ggt ggt gct ttg tet cct cag cac tet gct gtc act caa gga agt 2544

Gly Gly Gly Ala Leu Ser Pro Gin His Ser Ala Val Thr Gin Gly Ser 835 840 845 ate ate aag aac aag gag ggc atg gat gct aag tca cta act gcc tgg 2592

Ile Ile Lys Asn Lys Glu Gly Met Asp Ala Lys Ser Leu Thr Ala Trp 850 855 860 tcc cgg aca ctg gtg acc ttc aag gat gta ttt gtg gac ttc acc agg 2640

Ser Arg Thr Leu Val Thr Phe Lys Asp Val Phe Val Asp Phe Thr Arg 865 870 875 880 gag tgg aag ctg ctg gac act gct cag cag ate gtg tac aga aat 2688

Glu Glu Trp Lys Leu Leu Asp Thr Ala Gin Gin Ile Val Tyr Arg Asn 885 890 895 gtg atg ctg gag aac tat aag aac ctg gtt tcc ttg ggt tat cag ctt 2736

Val Met Leu Glu Asn Tyr Lys Asn Leu Val Leu Gly Tyr Gin Leu 900 905 910 act aag cca gat gtg ate ctc cgg ttg gag aag gaga gaag ggg ccc tgg 2784

Thr Lys Pro Asp Val Ile Leu Arg Leu Glu Lys Gly Glu Glu Pro Trp 915 920 925 ctg gtg gag aga gaa att cac caa gag acc cat cct gat tca gag act 2832

Leu Val Glu Arg Glu Ile His Gin Glu Thr His Pro Asp Ser Glu Thr 930 935 940 gca ttt gaa ate aaa tca tca gtt tetagataa 2865

Ala Phe Glu Ile Lys Ser Ser Val 945 950 <210> 84 <211> 952

<212> PRT <213> Artificial Sequence <220> <223> Synthetic Construct <400> 84

Met His His His His His Asp Tyr Lys Asp His Asp Gly Asp Tyr 15 10 15

Lys Asp His Asp Ile Asp Tyr Lys Asp Asp Asp Lys Met Ala Pro 20 25 30

Lys Lys Lys Arg Lys Val Gly Ile His Arg Gly Val Pro Met Val Asp 35 40 45

Leu Arg Thr Leu Gly Tyr Ser Gin Gin Gin Gin Lys Ile Lys Pro 50 55 60

Lys Val Arg Ser Thr Val Ala Gin His His Glu Ala Leu Val Gly His 65 70 75 80

Gly Phe Thr His Ala His Ile Val Ala Leu Ser Gin His Pro Ala Ala 85 90 95

Leu Gly Thr Val Ala Val Lys Tyr Gin Asp Met Ile Ala Lea Pro 100 105 110

Glu Ala Thr His Glu Ala Ile Val Gly Val Gly Lys Gin Trp Ser Gly 115 120 125

Ala Arg Ala Leu Glu Ala Leu Leu Thr Val Ala Gly Glu Leu Arg Gly 130 135 140

Pro Pro Leu Gin Leu Asp Thr Gly Gin Leu Leu Lys Ile Ala Lys Arg 145 150 155 160

Gly Gly Val Thr Ala Val Glu Ala Val His Ala Trp Arg Asn Ala Leu 165 170 175

Thr Gly Ala Pro Leu Asn Leu Thr Pro Glu Gin Val Val Ala Ile Ala 180 185 190

Ser His Asp Gly Gly Lys Gin Ala Leu Glu Thr Val Gin Arg Leu Leu 195 200 205

Pro Val Leu Cys Gin Ala His Gly Leu Thr Pro Glu Gin Val Val Ala 210 215 220

Ile Ala Ser Asn Gly Gly Gly Lys Gin Ala Leu Glu Thr Val Gin Arg 225 230 235 240

Leu Leu Pro Val Leu Cys Gin Ala His Gly Leu Thr Pro Glu Gin Val 245 250 255

Val Ala Ile Ala Ser Asn Ile Gly Gly Lys Gin Ala Leu Glu Thr Val 260 265 270

Gin Ala Leu Leu Pro Val Leu Cys Gin Ala His Gly Leu Thr Pro Glu 275 280 285

Gin Val Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gin Ala Leu Glu 290 295 300

Thr Val Gin Arg Leu Leu Pro Val Leu Cys Gin Ala His Gly Leu Thr 305 310 315 320

Pro Glu Gin Val Val Ala Ile Ala Ser His Asp Gly Gly Lys Gin Ala 325 330 335

Leu Glu Thr Val Gin Arg Leu Leu Pro Val Leu Cys Gin Ala His Gly 340 345 350

Leu Thr Pro Glu Gin Val Val Ala Ile Ala Ser Asn Ile Gly Gly Lys 355 360 365

Gin Ala Leu Glu Thr Val Gin Ala Leu Leu Pro Val Leu Cys Gin Ala 370 375 380

His Gly Leu Thr Pro Glu Gin Val Val Ala Ile Ala Ser Asn Ser Gly 385 390 395 400

Gly Lys Gin Ala Leu Glu Thr Val Gin Ala Leu Leu Pro Val Leu Cys 405 410 415

Gin Ala His Gly Leu Thr Pro Glu Gin Val Val Ala Ile Ala Ser Asn 420 425 430

Gly Gly Gly Lys Gin Ala Leu Glu Thr Val Gin Arg Leu Leu Pro Val 435 440 445

Leu Cys Gin Ala His Gly Leu Thr Pro Glu Gin Val Val Ala Ile Ala 450 455 460

Ser Asn Asn Gly Gly Lys Gin Ala Leu Glu Thr Val Gin Arg Leu Leu 465 470 475 480

Pro Val Leu Cys Gin Ala His Gly Leu Thr Pro Glu Gin Val Val Ala 485 490 495

Ile Ala Ser Asn Ile Gly Gly Lys Gin Ala Leu Glu Thr Val Gin Ala 500 505 510

Leu Leu Pro Val Leu Cys Gin Ala His Gly Leu Thr Pro Glu Gin Val 515 520 525

Val Ala Ile Ala Ser Asn Gly Gly Gly Lys Gin Ala Leu Glu Thr Val 530 535 540

Gin Arg Leu Leu Pro Val Leu Cys Gin Ala His Gly Leu Thr Pro Glu 545 550 555 560

Gin Val Val Ala Ile Ala Ser Asn Ily Gly Gly Lys Gin Ala Leu Glu 565 570 575

Thr Val Gin Ala Leu Leu Pro Val Leu Cys Gin Ala His Gly Leu Thr 580 585 590

Pro Glu Gin Val Val Ala Ile Ala Ser Asn Asn Gly Gly Lys Gin Ala 595 600 605

Leu Glu Thr Val Gin Arg Leu Leu Pro Val Leu Cys Gin Ala His Gly 610 615 620

Leu Thr Pro Gin Gin Val Val Ala Ile Ala Ser Asn Ile Gly Gly Arg 625 630 635 640

Pro Ala Leu Glu Ser Ile Val Ala Gin Leu Ser Arg Pro Asp Pro Ala 645 650 655

Leu Ala Ala Leu Thr Asn Asp His Leu Val Ala Leu Ala Cys Leu Gly 660 665 670

Gly Arg Pro Ala Leu Asp Ala Val Lys Gly Leu Pro Ala Pro 675 680 685

Ala Leu Ile Lys Arg Thr Asn Arg Arg Ile Pro Glu Arg Thr Ser His 690 695 700

Arg Val Ala Gly Ser Asp Thr Tyr Arg Tyr Ile Asp Thr Tyr Arg Tyr 705 710 715 720

Ile Glu Phe Pro Lys Lys Lys Arg Lys Lys Lys Lys Lys Lys Lys Lys Lys 725 730 735

Val Pro Lys Lys Lys Arg Lys Val Asp Ala Pro Pro Thr Asp Val Ser 740 745 750

Leu Gly Asp Glu Leu His Leu Asp Gly Glu Asp Val Ala Met Ala His 755 760 765

Ala Asp Ala Leu Asp Asp Asp Leu Asp Met Leu Gly Asp Gp Asp 770 775 780

Ser Pro Gly Pro Gly Phe Thr Pro His Asp Ser Ala Pro Tyr Gly Ala 785 790 795 800

Leu Asp Met Ala Asp Phe Glu Phe Glu Gin Met Phe Thr Asp Ala Leu 805 810 815

Gly Ile Asp Glu Tyr Gly Gly Gly Gly Asn Leu Tyr Phe Gin Ser Gly 820 825 830

Gly Gly Gly Ala Leu Ser Pro Gin His Ser Ala Val Thr Gin Gly Ser 835 840 845

Ile Ile Lys Asn Lys Glu Gly Met Asp Ala Lys Ser Leu Thr Ala Trp 850 855 860

Ser Arg Thr Leu Val Thr Phe Lys Asp Val Phe Val Asp Phe Thr Arg 865 870 875 880

Glu Glu Trp Lys Leu Leu Asp Thr Ala Gin Gin Ile Val Tyr Arg Asn 885 890 895

Val Met Leu Glu Asn Tyr Lys Asn Leu Val Leu Gly Tyr Gin Leu 900 905 910

Thr Lys Pro Asp Val Ile Leu Arg Leu Glu Lys Gly Glu Glu Pro Trp 915 920 925

Leu Val Glu Arg Glu Ile His Gin Glu Thr His Pro Asp Ser Glu Thr 930 935 940

Ala Phe Glu Ile Lys Ser Ser Val 945 950

Claims (15)

Patent claims A combination of two or more orthogonal split proteases that recognize a target sequence comprising at least 6 amino acids with dimerization domains that enable the functional reconstitution of protease activity and target proteins with a target sequence recognized by proteases. A combination of orthogonal split proteases with dimerization domains according to claim 1, characterized in that the combination comprises at least two orthogonal proteases selected from the families of the potentially NIa protease proteases, preferably TEV, PPV, SuMMV and SbMV viruses. A combination of orthogonal split proteases with dimerization domains according to any one of claims 1 or 2, characterized in that at least one of the split proteases is composed of two proteins with the protein sequence of SEQ ID 4 and SEQ ID 6, SEQ ID. 10 and SEQ ID. 12, SEQ ID. 16 and SEQ ID. 18, SEQ ID. 22 and SEQ ID. 24, or their homologs having at least 30% similarity of the amino acid sequence. A combination of orthogonal cleaved proteases with dimerization domains according to any one of claims 1 or 3, characterized in that the split proteases are associated with dimerization domains that allow their assembly and are: (i) spontaneously assembled domains and / or (ii) their assembly is induced by cellular or external physical, chemical or biological signals. A combination of orthogonal split proteases with dimerization domains according to any one of claims 1 or 4, characterized in that the dimerization domains that are spontaneously assembled domains are selected from domains that spontaneously form dimers, preferably dimming proteins, hinges, beta structures, preferably having orthogonal properties. A combination of orthogonal cleaved proteases with dimerization domains according to any one of claims 1 or 5, characterized in that the assembly of the dimerization domain is triggered by (i) an intracellular signal such as: a change in the metabolite concentration, a secondary messenger, a change in the enzyme activity, or a (ii) external signals such as temperature change, pH value, mechanical stress, change in osmotic pressure, ultrasound, light, chemical or biological signal. A combination of orthogonal split proteases with dimerization domains according to any one of claims 5 or 6, characterized in that at least one of the split proteases is associated with the dimerization domains of FKBP and FRB or the dimerization domains of CRY2 and CIBN or Ml3 and CaM. A combination of orthogonal split proteases with dimerization domains according to any one of claims 1 or 7, characterized in that one part of the split protease TEV or PPV is associated with the dimerization domain CRY2 and the other part of the split protease associated with the CIBN, which allows activation of the signal path via light signal. A combination of orthogonal split proteases with dimerization domains according to claim 5, characterized in that the dimerization domains that spontaneously assembled domains are selected from orthogonal convoluted helix. A combination of orthogonal split proteases with dimerization domains according to any one of claims 1 to 9, characterized in that the target protein with a recognizable sequence for proteases is a native, recombinant or artificially generated protein. A combination of orthogonal split proteases with dimerization domains according to any one of claims 1 to 10, characterized in that the target protein comprising a recognizable cleavage site with at least one of the orthogonal split proteases is a protein for activating the transcription. A combination of orthogonal cleaved proteases with dimerization domains according to any one of claims 1 to 10, characterized in that the target protein comprising a recognizable cleavage site with at least one of the orthogonal split proteases is an enzyme whose activity depends on cleavage by split protease. A combination of orthogonal cleaved proteases with dimerization domains according to any one of claims 1 to 10, characterized in that the target protein comprising a recognizable cleavage site with at least one of the orthogonal split proteases, a protein, a peptide or a hormone, the secretion of which cells depend on cleavage with split protease. Cells of a human, animal, fungus, plant, or bacterium expressing a combination of orthogonal split proteases with dimerization domains according to any one of claims 1 to 13. Cells according to claim 14, characterized in that they are human or animal cells, preferably neurons or other nervous system cells, T-lymphocytes, immune-response cells, pancreatic beta cells, and express a combination of orthogonal split proteases with dimerization domains after any Claims 1 to 13.