CA2381699A1 - Novel methods of diagnosis of angiogenesis compostions and methods of screening for angiogenesis modulators - Google Patents

Abstract

Described herein are methods that can be used for diagnosis of angiogenesis and angiogenic phenotypes. Also described herein are methods that can be used to screen candidate bioactive agents for the ability to modulate angiogenesis.
Additionally, methods and molecular targets (genes and their products) for therapeutic intervention in disorders associated with angiogenesis are described.

Description

NOVEL METHODS OF DIAGNOSIS OF ANGIOGENESIS, COMPOSITIONS AND METHODS
OF SCREENING FOR ANGIOGENESIS MODULATORS
FIELD OF THE INVENTION
The invention relates to the identification of expression profiles and the nucleic acids involved in angiogenesis, and to the use of such expression profiles and nucleic acids in diagnosis of angiogenesis. The invention further relates to methods for identifying candidate agents and/or targets which modulate angiogenesis.
BACKGROUND OF THE INVENTION
New blood vessel development comprises the formation of veins (vasculogenesis) and arteries (angiogenesis). Angiogenesis plays a normal role in embryonic development, as well as menstration, wound healing. Angiogenesis also plays a crucial pathogenic role in a variety of disease states, including cancer, proliferative diabetic retinopathy, and maintaining blood flow to chronic inflammatory sites.
Angiogenesis has a number of stages. The early stages of angiogenesis include endothelial cell protease production, migration of cells and proliferation. The early stages also appear to require some growth factors, with VEGF, TGF-a, angiostatin, and selected chemokines all putatively playing a role.
Later stages of angiogenesis include the population of the vessels with mural cells (pericytes or smooth muscle cells), basement membrane production and the induction of vessel bed specializations. The final stages of vessel formation include what is known as "remodeling", wherein a 2 0 forming vasculature becomes a stable, mature vessel bed.
Thus, understanding the genes, proteins and regulatory mechanisms that occur during angiogenesis would be desirable. Accordingly, it is an object of the invention to provide methods that can be used to screen candidate bioactive agents for the ability to modulate angiogenesis.
Additionally, it is an object to provide molecular targets for therapeutic intervention in disease states which either have an undesirable excess or a deficit in angiogenesis.

SUMMARY OF THE INVENTION
The present invention provides novel methods for diagnosis and prognosis evaluation for angiogenesis, as well as methods for screening for compositions which modulate angiogenesis.
Methods of treatment of disorders associated with angiogenesis, as well as compositions are also provided herein.
In one aspect, a method of screening drug candidates comprises providing a cell that expresses an expression profile gene or fragments thereof. or fragments thereof. Preferred embodiments of the expression profile gene are genes which are differentially expressed in angiogenesis cells, compared to other cells. Preferred embodiments of expression profile genes used in the methods herein include but are not limited to the group consisting of AAA4, AAA1, Edg-1, alpha 5 beta1 integrin, endomucin and matrix metalloproteinase 10; fragments of the proteins of this group are also preferred. It is understood that molecules for use in the present invention may be from any figure or any subset of listed molecules. Therefore, for example, any one or more of the genes listed above can be used in the methods herein. In another embodiment, a nucleic acid is selected from Tables 1, 2, 3, 4 or 5.
Preferred nucleic acids are in Table 4, and most preferably Table 5. The method further includes adding a drug candidate to the cell and determining the effect of the drug candidate on the expression of the expression profile gene.
In one embodiment, the method of screening drug candidates includes comparing the level of expression in the absence of the drug candidate to the level of expression in the presence of the drug 2 0 candidate, wherein the concentration of the drug candidate can vary when present, and wherein the comparison can occur after addition or removal of the drug candidate. In a preferred embodiment, the cell expresses at least two expression profile genes. The profile genes may show an increase or decrease.
Also provided herein is a method of screening for a bioactive agent capable of binding to an angiogenesis modulator protein (AMP), the method comprising combining the AMP
and a candidate bioactive agent, and determining the binding of the candidate agent to the AMP. Preferably the AMP
is a protein or fragment thereof selected from the group consisting of AAA4, AAA1, Edg-1, alpha 5 beta1 integrin, endomucin and matrix metalloproteinase 10. In another embodiment, the proteins is encoded by a nucleic acid selected from Tables 1, 2, 3, 4 or 5. Preferred nucleic acids are in Table 4, 3 0 and most preferably Table 5.

Further provided herein is a method for screening for a bioactive agent capable of modulating the activity of an AMP. In one embodiment the method comprises combining the AMP
and a candidate bioactive agent, and determining the effect of the candidate agent on the bioactivity of the AMP.
Preferably the AMP is a protein or fragment thereof selected from the group consisting of AAA4, AAA1, Edg-1, alpha 5 beta1 integrin, endomucin and matrix metalloproteinase 10. In another embodiment, the proteins is encoded by a nucleic acid selected from Tables 1, 2, 3, 4 or 5. Preferred nucleic acids are in Table 4, and most preferably Table 5.
Also provided is a method of evaluating the effect of a candidate angiogenesis drug comprising administering the drug to a transgenic animal expressing or over-expressing the AMP, or an animal lacking the AMP, for example as a result of a gene knockout.
Additionally, provided herein is a method of evaluating the effect of a candidate angiogenesis drug comprising administering the drug to a patient and removing a cell sample from the patient. The expression profile of the cell is then determined. This method may further comprise comparing the expression profile to an expression profile of a healthy individual. In a preferred embodiment, the expression profile includes a gene of Table 1, Table 2, Table 3, Table 4 or Table 5.
Moreover, provided herein is a biochip comprising one or more nucleic acid segments which encode an angiogenesis protein, preferable selected from the group consisting of AAA4, AAA1, Edg-1, alpha 5 beta1 integrin, endomucin and matrix metalloproteinase , or fragment thereof, wherein the biochip comprises fewer than 1000 nucleic acid probes. Preferably at least two nucleic acid segments are 2 0 included. In another embodiment, the nucleic acid selected from Tables 1, 2, 3, 4 or 5. Preferred nucleic acids are in Table 4, and most preferably Table 5.
Furthermore, a method of diagnosing a disorder associated with angiogenesis is provided. The method comprises determining the expression of a gene which encodes an angiogenesis protein preferable selected from the group consisting of AAA4, AAA1, Edg-1, alpha 5 beta1 integrin, 2 5 endomucin and matrix metalloproteinase 10, or fragment thereof in a first tissue type of a first individual, and comparing the distribution to the expression of the gene from a second normal tissue type from the first individual or a second unaffected individual. In another embodiment, the proteins is encoded by a nucleic acid selected from Tables 1, 2, 3, 4 or 5. Preferred nucleic acids are in Table 4, and most preferably Table 5. A difference in the expression indicates that the first individual has a 3 0 disorder associated with angiogenesis.

In another aspect, the present invention provides an antibody which specifically binds to an angiogenesis preferably selected from the group consisting of AAA4, AAA1, Edg-1, alpha 5 beta1 integrin, endomucin and matrix metalloproteinase 10 or fragment thereof. . In another embodiment, the proteins is encoded by a nucleic acid selected from Tables 1, 2, 3, 4 or 5. Preferred nucleic acids are in Table 4, and most preferably Table 5. In a preferred embodiment the fragment of AAA1 is selected from AAA1 p1 or AAA1 p2. Other preferred fragments for the angiogenesis proteins are shown in the figures.
In one embodiment a method for screening for a bioactive agent capable of interfering with the binding of a angiogenesis modulating protein (AMP) or a fragment thereof and an antibody which binds to said AMP or fragment thereof. In a preferred embodiment, the method comprises combining an AMP or fragment thereof, a candidate bioactive agent and an antibody which binds to said AMP or fragment thereof. The method further includes determining the binding of said AMP or fragment thereof and said antibody. Wherein there is a change in binding, an agent is identified as an interfering agent.
The interfering agent can be an agonist or an antagonist. Preferably, the agent inhibits angiogenesis.
In a further aspect, a method for inhibiting angiogenesis is provided. In one embodiment, the method comprises administering to a cell a composition comprising an antibody to an angiogenesis modulating protein, preferably selected from the group consisting of AAA4, AAA1, Edg-1, alpha 5 beta1 integrin, endomucin and matrix metalloproteinase 10, or fragment thereof. In another embodiment, the proteins is encoded by a nucleic acid selected from Tables 1, 2, 3, 4 or 5. Preferred 2 0 nucleic acids are in Table 4, and most preferably Table 5. The method can be performed in vitro or in vivo, preferably in vivo to an individual. In a preferred embodiment the method of inhibiting angiogenesis is provided to an individual with a disorder associated with angiogenesis such as cancer.
As described herein, methods of inhibiting angiogenesis can be performed by administering an inhibitor of the activity of an angiogenesis protein, including an antisense molecule to the gene or its 2 5 gene products, and preferable small molecules.
Also provided herein are methods of eliciting an immune response in an individual. In one embodiment a method provided herein comprises administering to an individual a composition comprising an angiogenesis modulating protein, preferably selected from the group consisting of AAA4, AAA1, Edg-1, alpha 5 beta1 integrin, endomucin and matrix metalloproteinase 10, or fragment 3 0 thereof. In another embodiment, the proteins is encoded by a nucleic acid selected from Tables 1, 2, 3, 4 or 5. Preferred nucleic acids are in Table 4, and most preferably Table 5. In another aspect, said composition comprises a nucleic acid comprising a sequence encoding an angiogenesis modulating protein, preferably selected from the group consisting of AAA4, AAA1, Edg-1, alpha 5 beta1 integrin, endomucin and matrix metalloproteinase 10, or fragment thereof. In another embodiment, the proteins is encoded by a nucleic acid selected from Tables 1, 2, 3, 4 or 5.
Preferred nucleic acids are in Table 4, and most preferably Table 5.
Further provided herein are compositions capable of eliciting an immune response in an individual. In one embodiment, a composition provided herein comprises an angiogenesis modulating protein, preferably selected from the group consisting of AAA4, AAA1, Edg-1, alpha 5 beta1 integrin, endomucin and matrix metalloproteinase 10, or fragment thereof. In another embodiment, the proteins is encoded by a nucleic acid selected from Tables 1, 2, 3, 4 or 5.
Preferred nucleic acids are in Table 4, and most preferably Table 5. In another embodiment, said composition comprises a nucleic acid comprising a sequence encoding an angiogenesis modulating protein, preferably selected from the group consisting of AAA4, AAA1, Edg-1, alpha 5 beta1 integrin, endomucin and matrix metalloproteinase 10, or fragment thereof, and a pharmaceutically acceptable carrier.
In another embodiment the nucleic acid selected from Tables 1, 2, 3, 4 or 5.
Preferred nucleic acids are in Table 4, and most preferably Table 5.
A method of neutralizing the effect of an angiogenesis protein, preferably selected from the group consisting of AAA4, AAA1, Edg-1, alpha 5 beta1 integrin, endomucin and matrix metalloproteinase 10, or fragment thereof, comprising contacting an agent specific for said protein with said protein in an amount sufficient to effect neutralization. In another embodiment, the proteins is encoded by a nucleic acid selected from Tables 1, 2, 3, 4 or 5. Preferred nucleic acids are in Table 4, and most preferably 2 0 Table 5.
In another aspect of the invention, a method of treating an individual for a disorder associated with angiogenesis is provided. In one embodiment, the method comprises administering to said individual an inhibitor of Edg-1. In another embodiment, the method comprises administering to a patient having a disorder with angiogenesis an antibody to Edg-1 conjugated to a therapeutic moiety. Such a 2 S therapeutic moiety can be a cytotoxic agent or a radioisotope.
Novel sequences are provided herein. Compounds and compositions are also provided. Other aspects of the invention will become apparent to the skilled artisan by the following description of the invention.
DETAILED DESCRIPTION OF THE TABLES AND FIGURES

Table 1 provides the Accession numbers for 1774 genes, including expression sequence tags, (incorporated in their entirety here and throughout the application where Accession numbers are provided), whose expression levels change as a function of time in tissue undergoing angiogenesis compared to tissue that is not.
Table 2 provides the Accession numbers for a preferred subset of 559 genes, including expression sequence tags (incorporated in their entirety here and throughout the application where Accession numbers are provided), whose expression levels change as a function of time in tissue undergoing angiogenesis compared to tissue that is not. The sequences are characterized as predicted to encode secreted proteins (SS), or transmembrane proteins (TM) proteins.
Table 3 provides the Accession numbers for 1916 genes including expression sequence tags (incorporated in their entirety here and throughout the application where Accession numbers are provided), whose expression levels change as a function of time in tissue undergoing angiogenesis compared to tissue that is not.
Table 4 provides a preferred subset of 558 Accession numbers identified in Figure 4 whose expression levels change as a function of time in tissue undergoing angiogenesis compared to tissue that is not.
Table 5 provides a preferred subset of 20 Accession numbers identified in Figure 4 whose expression levels change as a function of time in tissue undergoing angiogenesis compared to tissue that is not.
Figure 1 is a graph of expression levels of sequences identified in Figure 1.
Expression profiles are 2 0 clustered into 4 groups. C1 (blue), C2 (red), C3 (green) and C4 (mustard).
Figure 2 shows an embodiment of a nucleic acid (mRNA) which includes a sequence encoding an angiogenesis protein, AAA4. The start and stop codons are underlined.
Figure 3 shows the open reading frame of a nucleic acid sequence encoding AAA4. The start and stop codons are underlined.
Figure 4 shows an embodiment of the amino acid sequence of AAA4. The signal peptide is double underlined, and the transmembrane sequence is underlined. In one embodiment herein, AAA4 is soluble. Thus, the signal peptide can be omitted, and the transmembrane domain deleted, inactivated, or truncated.

Figure 5 shows peptides AAA4p1 and AAA4p2.
Figure 6 shows the expression of AAA4 in angiogenesis models over time and in other, non-angiogenic tissues.
Figure 7 shows an embodiment of a nucleic acid sequence encoding an angiogenesis protein, AAA1.
A putative stop codon is underlined.
Figure 8 shows an embodiment of an amino acid sequence for AAA1. A
transmembrane domain is underlined. In one embodiment, AAA1 is soluble. In preferred embodiments, the transmembrane domain is deleted or inactivated, or AAA1 is truncated to delete the transmembrane domain.
Figure 9 shows AAA1 p1 and AAA1 p2.
Figure 10 shows a graph showing the relative expression of AAA1 in various tissues at different time points. "Exp 3" is an angiogenesis model showing tube formation over time using endothelial cells.
Figure 11 shows an embodiment of a nucleic acid, mRNA, which comprises a sequence encoding an angiogenesis protein, Edg-1. The start and stop codons are underlined.
Figure 12 shows the open reading frame encoding Edg-1, wherein the start and stop codons are underlined.
Figure 13 shows an embodiment of an amino acid sequence for an angiogenesis protein, Edg-1, wherein the transmembrane domains are underlined. In a preferred embodiment herein, a soluble 2 0 form of Edg-1 is provided. In one embodiment, the transmembrane domains are deleted, inactivated, and/or the protein is truncated so as to exclude the domains (with or without re-ligation of remaining soluble regions).
Figure 14 depicts four peptide sequences provided herein and their respective solubilities.
Figure 15 shows the expression of Edg-1 over a variety of tissues.
Figure 16 shows the time course of induction of Edg-1 in a model for angiogenesis (Expt 1, Expt 2, Expt 3) in which low passage human endothelial cells form into tube structures over a period of a few days in culture. The reproducible induction of Edg-1 occurred in a time frame consistent with its role in the tube forming process.
Figure 17 shows an embodiment of a nucleic acid sequence which includes the coding sequence for a tissue remodeling protein, alpha 5 beta 1 integrin (sometimes referred to as VLA-5), wherein the start and stop codon are underlined.
Figure 18 shows an embodiment of an amino acid sequence of a tissue remodeling protein, alpha 5 beta 1 integrin, wherein a transmembrane domain is underlined.
Figure 19 shows a bar graph depicting the results of 5 expression profiles of alpha 5 beta 1 integrin throughout the time course of tube formation. In particular, tube models 1, 2 and 3 show models which form tube structures from single isolated human endothelial cells; the "EC/PMA" model shows endothelial cells stimulated with pokeweed mitogen antigen, and the body atlas profile shows expression in various normal cell types and tissues.
Figures 20A and 20B show the results of antagonism of tube formation wherein Figure 20A is an isotype control and Figure 20B shows specific antibody antagonism after 48 hours.
Figure 21 shows an embodiment of a nucleic acid sequence which includes the coding sequence for an angiogenesis protein, endomucin, wherein the start and stop codon are boxed.
Figure 22 shows an embodiment of an amino acid sequence of an angiogenesis protein, endomucin, wherein a signal sequence is bolded and a transmembrane domain is underlined.
Figure 23 shows an embodiment of a nucleic acid sequence which includes the coding sequence for 2 0 an angiogenesis protein, matrix metalloproteinase 10 (also called stromolysin 2), wherein the start and stop codon are boxed.
Figure 24 shows expression of matrix metalloproteinase 10 over a variety of tissues.
Figure 25 shows expression of matrix metalloproteinase 10 over a variety of tissues.
DETAILED DESCRIPTION OF THE INVENTION

In accordance with the objects outlined above, the present invention provides novel methods for diagnosis of disorders associated with angiogenesis (sometimes referred to herein as angiogenesis disorders or AD), as well as methods for screening for compositions which modulate angiogenesis.
By "disorder associated with angiogenesis" or "disease associated with angiogenesis" herein is meant a disease state which is marked by either an excess or a deficit of vessel development. Angiogenesis disorders include, but are not limited to, cancer and proliferative diabetic retinopathy. Also provided are method for treating AD.
In one aspect, the expression levels of genes are determined in different patient samples for which diagnosis information is desired, to provide expression profiles. An expression profile of a particular sample is essentially a "fingerprint" of the state of the sample; while two states may have any particular gene similarly expressed, the evaluation of a number of genes simultaneously allows the generation of a gene expression profile that is unique to the state of the cell. That is, normal tissue may be distinguished from AD tissue. By comparing expression profiles of tissue in known different angiogenesis states, information regarding which genes are important (including both up- and down-regulation of genes) in each of these states is obtained. The identification of sequences that are differentially expressed in angiogenic versus non-angiogenic tissue allows the use of this information in a number of ways. For example, the evaluation of a particular treatment regime may be evaluated:
does a chemotherapeutic drug act to down-regulate angiogenesis and thus tumor growth or recurrence in a particular patient. Similarly, diagnosis may be done or confirmed by comparing patient 2 0 samples with the known expression profiles. Furthermore, these gene expression profiles (or individual genes) allow screening of drug candidates with an eye to mimicking or altering a particular expression profile; for example, screening can be done for drugs that suppress the angiogenic expression profile. This may be done by making biochips comprising sets of the important angiogenesis genes, which can then be used in these screens. These methods can also be done on 2 5 the protein basis; that is, protein expression levels of the angiogenic proteins can be evaluated for diagnostic purposes or to screen candidate agents. In addition, the angiogenic nucleic acid sequences can be administered for gene therapy purposes, including the administration of antisense nucleic acids, or the angiogenic proteins (including antibodies and other modulators thereof) administered as therapeutic drugs.
3 0 Thus the present invention provides nucleic acid and protein sequences that are differentially expressed in angiogenesis, herein termed "angiogenesis sequences". As outlined below, angiogenesis sequences include those that are up-regulated (i.e. expressed at a higher level) in disorders associated with angiogenesis, as well as those that are down-regulated (i.e. expressed at a lower level). In a preferred embodiment, the angiogenesis sequences are from humans; however, as will be appreciated by those in the art, angiogenesis sequences from other organisms may be useful in animal models of disease and drug evaluation; thus, other angiogenesis sequences are provided, from vertebrates, including mammals, including rodents (rats, mice, hamsters, guinea pigs, etc.), primates, farm animals (including sheep, goats, pigs, cows, horses, etc).
Angiogenesis sequences from other organisms may be obtained using the techniques outlined below.
Angiogenesis sequences can include both nucleic acid and amino acid sequences.
In a preferred embodiment, the angiogenesis sequences are recombinant nucleic acids. By the term "recombinant nucleic acid" herein is meant nucleic acid, originally formed in vitro, in general, by the manipulation of nucleic acid by polymerases and endonucleases, in a form not normally found in nature. Thus an isolated nucleic acid, in a linear form, or an expression vector formed in vitro by ligating DNA
molecules that are not normally joined, are both considered recombinant for the purposes of this invention. It is understood that once a recombinant nucleic acid is made and reintroduced into a host cell or organism, it will replicate non-recombinantly, i.e. using the in vivo cellular machinery of the host cell rather than in vitro manipulations; however, such nucleic acids, once produced recombinantly, although subsequently replicated non-recombinantly, are still considered recombinant for the purposes of the invention.
Similarly, a "recombinant protein" is a protein made using recombinant techniques, i.e. through the expression of a recombinant nucleic acid as depicted above. A recombinant protein is distinguished from naturally occurring protein by at least one or more characteristics. For example, the protein may 2 0 be isolated or purified away from some or all of the proteins and compounds with which it is normally associated in its wild type host, and thus may be substantially pure. For example, an isolated protein is unaccompanied by at least some of the material with which it is normally associated in its natural state, preferably constituting at least about 0.5%, more preferably at least about 5% by weight of the total protein in a given sample. A substantially pure protein comprises at least about 75% by weight of 2 5 the total protein, with at least about 80% being preferred, and at least about 90% being particularly preferred. The definition includes the production of an angiogenesis protein from one organism in a different organism or host cell. Alternatively, the protein may be made at a significantly higher concentration than is normally seen, through the use of an inducible promoter or high expression promoter, such that the protein is made at increased concentration levels.
Alternatively, the protein 3 0 may be in a form not normally found in nature, as in the addition of an epitope tag or amino acid substitutions, insertions and deletions, as discussed below.
In a preferred embodiment, the angiogenesis sequences are nucleic acids. As will be appreciated by those in the art and is more fully outlined below, angiogenesis sequences are useful in a variety of applications, including diagnostic applications, which will detect naturally occurring nucleic acids, as well as screening applications; for example, biochips comprising nucleic acid probes to the angiogenesis sequences can be generated. In the broadest sense, then, by "nucleic acid" or "oligonucleotide" or grammatical equivalents herein means at least two nucleotides covalently linked together. A nucleic acid of the present invention will generally contain phosphodiester bonds, although in some cases, as outlined below, nucleic acid analogs are included that may have alternate backbones, comprising, for example, phosphoramidate (Beaucage et al., Tetrahedron 49(10):1925 (1993) and references therein; Letsinger, J. Org. Chem. 35:3800 (1970);
Sprinzl et al., Eur. J.
Biochem. 81:579 (1977); Letsinger et al., Nucl. Acids Res. 14:3487 (1986);
Sawai et al, Chem. Lett.
805 (1984), Letsinger et al., J. Am. Chem. Soc. 110:4470 (1988); and Pauwels et al., Chemica Scripts 26:141 91986)), phosphorothioate (Mag et al., Nucleic Acids Res. 19:1437 (1991 ); and U.S. Patent No. 5,644,048), phosphorodithioate (Briu et al., J. Am. Chem. Soc. 111:2321 (1989), O-methylphophoroamidite linkages (see Eckstein, Oligonucleotides and Analogues:
A Practical Approach, Oxford University Press), and peptide nucleic acid backbones and linkages (see Egholm, J.
Am. Chem. Soc. 114:1895 (1992); Meier et al., Chem. Int. Ed. Engl. 31:1008 (1992); Nielsen, Nature, 365:566 (1993); Carlsson et al., Nature 380:207 (1996), all of which are incorporated by reference).
Other analog nucleic acids include those with positive backbones (Denpcy et al., Proc. Natl. Acad. Sci.
USA 92:6097 (1995); non-ionic backbones (U.S. Patent Nos. 5,386,023, 5,637,684, 5,602,240, 5,216,141 and 4,469,863; Kiedrowshi et al., Angew. Chem. Intl. Ed. English 30:423 (1991); Letsinger 2 0 et al., J. Am. Chem. Soc. 110:4470 (1988); Letsinger et al., Nucleoside &
Nucleotide 13:1597 (1994);
Chapters 2 and 3, ASC Symposium Series 580, "Carbohydrate Modifications in Antisense Research", Ed. Y.S. Sanghui and P. Dan Cook; Mesmaeker et al., Bioorganic & Medicinal Chem. Lett. 4:395 (1994); Jeffs et al., J. Biomolecular NMR 34:17 (1994); Tetrahedron Lett.
37:743 (1996)) and non-ribose backbones, including those described in U.S. Patent Nos. 5,235,033 and 5,034,506, and 2 5 Chapters 6 and 7, ASC Symposium Series 580, "Carbohydrate Modifications in Antisense Research", Ed. Y.S. Sanghui and P. Dan Cook. Nucleic acids containing one or more carbocyclic sugars are also included within one definition of nucleic acids (see Jenkins et al., Chem.
Soc. Rev. (1995) pp169-176). Several nucleic acid analogs are described in Rawls, C & E News June 2, 1997 page 35. All of these references are hereby expressly incorporated by reference. These modifications of the ribose-3 0 phosphate backbone may be done for a variety of reasons, for example to increase the stability and half-life of such molecules in physiological environments or as probes on a biochip.
As will be appreciated by those in the art, all of these nucleic acid analogs may find use in the present invention. In addition, mixtures of naturally occurring nucleic acids and analogs can be made;
alternatively, mixtures of different nucleic acid analogs, and mixtures of naturally occurring nucleic 3 5 acids and analogs may be made.

Particularly preferred are peptide nucleic acids (PNA) which includes peptide nucleic acid analogs.
These backbones are substantially non-ionic under neutral conditions, in contrast to the highly charged phosphodiester backbone of naturally occurring nucleic acids. This results in two advantages. First, the PNA backbone exhibits improved hybridization kinetics.
PNAs have larger changes in the melting temperature (Tm) for mismatched versus perfectly matched basepairs. DNA
and RNA typically exhibit a 2-4°C drop in Tm for an internal mismatch.
With the non-ionic PNA
backbone, the drop is closer to 7-9°C. Similarly, due to their non-ionic nature, hybridization of the bases attached to these backbones is relatively insensitive to salt concentration. In addition, PNAs are not degraded by cellular enzymes, and thus can be more stable.
The nucleic acids may be single stranded or double stranded, as specified, or contain portions of both double stranded or single stranded sequence. As will be appreciated by those in the art, the depiction of a single strand ("Watson") also defines the sequence of the other strand ("Crick"); thus the sequences described herein also includes the complement of the sequence. The nucleic acid may be DNA, both genomic and cDNA, RNA or a hybrid, where the nucleic acid contains any combination of deoxyribo- and ribo-nucleotides, and any combination of bases, including uracil, adenine, thymine, cytosine, guanine, inosine, xanthine hypoxanthine, isocytosine, isoguanine, etc. As used herein, the term "nucleoside" includes nucleotides and nucleoside and nucleotide analogs, and modified nucleosides such as amino modified nucleosides. In addition, "nucleoside"
includes non-naturally occurring analog structures. Thus for example the individual units of a peptide nucleic acid, each 2 0 containing a base, are referred to herein as a nucleoside.
An angiogenesis sequence can be initially identified by substantial nucleic acid and/or amino acid sequence homology to the angiogenesis sequences outlined herein. Such homology can be based upon the overall nucleic acid or amino acid sequence, and is generally determined as outlined below, using either homology programs or hybridization conditions.
2 5 The angiogenesis screen included comparing genes identified in an in vitro model of angiogenesis as described in Hiraoka, Cell 95:365 (1998), which is expressly incorporated by reference, with genes identified in controls. Samples of normal tissue and tissue undergoing angiogenesis are applied to biochips comprising nucleic acid probes. The samples are first microdissected, if applicable, and treated as is known in the art for the preparation of mRNA. Suitable biochips are commercially 3 0 available, for example from Affymetrix. Gene expression profiles as described herein are generated and the data analyzed.

In a preferred embodiment, the genes showing changes in expression as between normal and disease states are compared to genes expressed in other normal tissues, including, but not limited to lung, heart, brain, liver, breast, kidney, muscle, prostate, small intestine, large intestine, spleen, bone and placenta. In a preferred embodiment, those genes identified during the angiogenesis screen that are expressed in any significant amount in other tissues are removed from the profile, although in some embodiments, this is not necessary. That is, when screening for drugs, it is preferable that the target be disease specific, to minimize possible side effects.
In a preferred embodiment, angiogenesis sequences are those that are up-regulated in angiogenesis disorders; that is, the expression of these genes is higher in the disease tissue as compared to normal tissue. "Up-regulation" as used herein means at least about a two-fold change, preferably at least about a three fold change, with at least about five-fold or higher being preferred. All accession numbers herein are for the GenBank sequence database and the sequences of the accession numbers are hereby expressly incorporated by reference. GenBank is known in the art, see, e.g., Benson, DA, et al., Nucleic Acids Research 26:1-7 (1998) and http://www.ncbi.nlm.nih.gov/. In addition, these genes were found to be expressed in a limited amount or not at all in heart, brain, lung, liver, breast, kidney, prostate, small intestine and spleen.
In a preferred embodiment, angiogenesis sequences are those that are down-regulated in the angiogenesis disorder; that is, the expression of these genes is lower in angiogenic tissue as compared to normal tissue. "Down-regulation" as used herein means at least about a two-fold change, 2 0 preferably at least about a three fold change, with at least about five-fold or higher being preferred.
Angiogenesis sequences according to the invention may be classified into discrete clusters of sequences based on common expression profiles of the sequences. Expression levels of angiogenesis sequences may increase or decrease as a function of time in a manner that correlates with the induction of angiogenesis. Alternatively, expression levels of angiogenesis sequences may 2 5 both increase and decrease as a function of time. For example, expression levels of some angiogenesis sequences are temporarily induced or diminished during the switch to the angiogenesis phenotype, followed by a return to baseline expression levels. Table 1 depicts 1774 genes, the expression of which varies as a function of time in angiogenesis tissue when compared to normal tissue. Figure 1 depicts 4 discrete expression profiles of angiogenesis genes identified in Table 1.
3 0 A particularly preferred embodiment includes the sequences as described in Table 2 which depicts a preferred subset of 559 angiogenesis sequences, the expression of which is altered in angiogenesis when compared to normal tissue.

An additional embodiment includes the sequences as described in Table 3, which depicts 1916 genes including expression sequence tags (incorporated in their entirety here and throughout the application where Accession numbers are provided), whose expression levels change as a function of time in tissue undergoing angiogenesis compared to tissue that is not.
A preferred embodiment includes the sequences as described in Table 4 which depicts a preferred subset of 558 genes identified in Table 3 whose expression levels change as a function of time in tissue undergoing angiogenesis compared to tissue that is not.
A particularly preferred embodiment includes the sequences as described in Table 5 which provides a preferred subset of 20 Accession numbers identified in Table 3 whose expression levels change as a function of time in tissue undergoing angiogenesis compared to tissue that is not.
In a particularly preferred embodiment, angiogenesis sequences are those that are induced for a period of time followed by a return to the baseline levels. Sequences that are temporarily induced provide a means to target angiogenesis tissue, for example neovascularized tumors, while avoiding rapidly growing tissue that require perpetual vascularization. Such positive angiogenic factors include aFGF, bFGF, VEGF, angiogenin and the like.
Induced angiogenesis sequences also are further categorized with respect to the timing of induction.
For example, some angiogenesis genes may be induced at an early time period, such as with 10 minutes of the induction of angiogenesis. Others may be induced later, such as between 5 and 60 minutes, while yet others may be induced for a time period of about two hours or more followed by a 2 0 return to baseline expression levels.
In another preferred embodiment are angiogenesis sequences that are inhibited or reduced as a function of time followed by a return to "normal" expression levels.
Inhibitors of angiogenesis are examples of molecules that have this expression profile. These sequences also can be further divided into groups depending on the timing of diminished expression. For example, some molecules may 2 5 display reduced expression with 10 minutes of the induction of angiogenesis. Others may be diminished later, such as between 5 and 60 minutes, while others may be diminished for a time period of about two hours or more followed by a return to baseline. Examples of such negative angiogenic factors include thrombospondin and endostatin to name a few.

In yet another preferred embodiment are angiogenesis sequences that are induced for prolonged periods. These sequences are typically associated with induction of angiogenesis and may participate in induction and/or maintenance of the angiogenesis phenotype.
In another preferred embodiment are angiogenesis sequences, the expression of which is reduced or diminished for prolonged periods in angiogenic tissue. These sequences are typically angiogenesis inhibitors and their diminution is correlated with an increase in angiogenesis.
Angiogenesis proteins of the present invention may be classified as secreted proteins, transmembrane proteins or intracellular proteins. In a preferred embodiment the angiogenesis protein is an intracellular protein. Intracellular proteins may be found in the cytoplasm and/or in the nucleos.
Intracellular proteins are involved in all aspects of cellular function and replication (including, for example, signaling pathways); aberrant expression of such proteins results in unregulated or disregulated cellular processes. For example, many intracellular proteins have enzymatic activity such as protein kinase activity, protein phosphatase activity, protease activity, nucleotide cyclase activity, polymerase activity and the like. Intracellular proteins also serve as docking proteins that are involved in organizing complexes of proteins, or targeting proteins to various subcellular localizations, and are involved in maintaining the structural integrity of organelles.
An increasingly appreciated concept in characterizing intracellular proteins is the presence in the proteins of one or more motifs for which defined functions have been attributed. In addition to the highly conserved sequences found in the enzymatic domain of proteins, highly conserved sequences 2 0 have been identified in proteins that are involved in protein-protein interaction. For example, Src-homology-2 (SH2) domains bind tyrosine-phosphorylated targets in a sequence dependent manner.
PTB domains, which are distinct from SH2 domains, also bind tyrosine phosphorylated targets. SH3 domains bind to proline-rich targets. In addition, PH domains, tetratricopeptide repeats and WD
domains to name only a few, have been shown to mediate protein-protein interactions. Some of these may also be involved in binding to phospholipids or other second messengers.
As will be appreciated by one of ordinary skill in the art, these motifs can be identified on the basis of primary sequence;
thus, an analysis of the sequence of proteins may provide insight into both the enzymatic potential of the molecule and/or molecules with which the protein may associate.
In a preferred embodiment, the angiogenesis sequences are transmembrane proteins.
3 0 Transmembrane proteins are molecules that span the phospholipid bilayer of a cell. They may have an intracellular domain, an extracellular domain, or both. The intracellular domains of such proteins may have a number of functions including those already described for intracellular proteins. For example, the intracellular domain may have enzymatic activity and/or may serve as a binding site for additional proteins. Frequently the intracellular domain of transmembrane proteins serves both roles.
For example certain receptor tyrosine kinases have both protein kinase activity and SH2 domains. In addition, autophosphorylation of tyrosines on the receptor molecule itself, creates binding sites for additional SH2 domain containing proteins.
Transmembrane proteins may contain from one to many transmembrane domains. For example, receptor tyrosine kinases, certain cytokine receptors, receptor guanylyl cyclases and receptor serine/threonine protein kinases contain a single transmembrane domain.
However, various other proteins including channels and adenylyl cyclases contain numerous transmembrane domains. Many important cell surface receptors are classified as "seven transmembrane domain" proteins, as they contain 7 membrane spanning regions. Important transmembrane protein receptors include, but are not limited to insulin receptor, insulin-like growth factor receptor, human growth hormone receptor, glucose transporters, transferrin receptor, epidermal growth factor receptor, low density lipoprotein receptor, epidermal growth factor receptor, leptin receptor, interleukin receptors, e.g. IL-1 receptor, IL-2 receptor, etc.
Characteristics of transmembrane domains include approximately 20 consecutive hydrophobic amino acids that may be followed by charged amino acids. Therefore, upon analysis of the amino acid sequence of a particular protein, the localization and number of transmembrane domains within the protein may be predicted.
2 0 The extracellular domains of transmembrane proteins are diverse; however, conserved motifs are found repeatedly among various extracellular domains. Conserved structure and/or functions have been ascribed to different extracellular motifs. For example, cytokine receptors are characterized by a cluster of cysteines and a WSXWS (W= tryptophan, S= serine, X=any amino acid) motif.
Immunoglobulin-like domains are highly conserved. Mucin-like domains may be involved in cell 2 5 adhesion and leucine-rich repeats participate in protein-protein interactions.
Many extracellular domains are involved in binding to other molecules. In one aspect, extracellular domains are receptors. Factors that bind the receptor domain include circulating ligands, which may be peptides, proteins, or small molecules such as adenosine and the like. For example, growth factors such as EGF, FGF and PDGF are circulating growth factors that bind to their cognate 3 0 receptors to initiate a variety of cellular responses. Other factors include cytokines, mitogenic factors, neurotrophic factors and the like. Extracellular domains also bind to cell-associated molecules. In this respect, they mediate cell-cell interactions. Cell-associated ligands can be tethered to the cell for example via a glycosylphosphatidylinositol (GPI) anchor, or may themselves be transmembrane proteins. Extracellular domains also associate with the extracellular matrix and contribute to the maintenance of the cell structure.
Putative transmembrane angiogenesis proteins include those encoded by the sequences labeled with "Y" in the TM column depicted in Table 2.
Angiogenesis proteins that are transmembrane are particularly preferred in the present invention as they are good targets for immunotherapeutics, as are described herein. In addition, as outlined below, transmembrane proteins can be also useful in imaging modalities.
It will also be appreciated by those in the art that a transmembrane protein can be made soluble by removing transmembrane sequences, for example through recombinant methods.
Furthermore, transmembrane proteins that have been made soluble can be made to be secreted through recombinant means by adding an appropriate signal sequence.
In a preferred embodiment, the angiogenesis proteins are secreted proteins;
the secretion of which can be either constitutive or regulated. These proteins have a signal peptide or signal sequence that targets the molecule to the secretory pathway. Secreted proteins are involved in numerous physiological events; by virtue of their circulating nature, they serve to transmit signals to various other cell types. The secreted protein may function in an autocrine manner (acting on the cell that secreted the factor), a paracrine manner (acting on cells in close proximity to the cell that secreted the factor) or an endocrine manner (acting on cells at a distance). Thus secreted molecules find use in modulating 2 0 or altering numerous aspects of physiology. Angiogenesis proteins that are secreted proteins are particularly preferred in the present invention as they serve as good targets for diagnostic markers, for example for blood tests.
Putative secreted angiogenesis proteins include those encoded by the sequences depicted in Table 2 that are labeled with "Y" in the SS column, but a "N" in the TM column.
2 5 An angiogenesis sequence is initially identified by substantial nucleic acid and/or amino acid sequence homology to the angiogenesis sequences outlined herein. Such homology can be based upon the overall nucleic acid or amino acid sequence, and is generally determined as outlined below, using either homology programs or hybridization conditions.

As used herein, a nucleic acid is an "angiogenesis nucleic acid" if the overall homology of the nucleic acid sequence to one of the nucleic acids of Table 1, Table 2, Table 3, Table 4 or Table 5 is preferably greater than about 75%, more preferably greater than about 80%, even more preferably greater than about 85% and most preferably greater than 90%. In some embodiments the homology will be as high as about 93 to 95 or 98%. Homology in this context means sequence similarity or identity, with identity being preferred. A preferred comparison for homology purposes is to compare the sequence containing sequencing errors to the correct sequence. This homology will be determined using standard techniques known in the art, including, but not limited to, the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981 ), by the homology alignment algorith of Needleman & Wunsch, J. Mol. Biool. 48:443 (1970), by the search for similarity method of Pearson & Lipman, PNAS USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Drive, Madison, WI), the Best Fit sequence program described by Devereux et al., Nucl. Acid Res. 12:387-395 (1984), preferably using the default settings, or by inspection.
In a preferred embodiment, the sequences which are used to determine sequence identity or similarity are selected from the sequences set forth in the tables and figures, preferable those represented in Table 4, more preferably those represented in table 5, still more preferably those of Figures 2, 3, 7, 11, 12, 17, 21, 23 and fragments thereof. In one embodiment the sequences utilized herein are those set forth in the tables and figures. In another embodiment, the sequences are naturally occurring allelic 2 0 variants of the sequences set forth in the tables and figures. In another embodiment, the sequences are sequence variants as further described herein.
One example of a useful algorithm is PILEUP. PILEUP creates a multiple sequence alignment from a group of related sequences using progressive, pairwise alignments. It can also plot a tree showing the clustering relationships used to create the alignment. PILEUP uses a simplification of the progressive alignment method of Feng & Doolittle, J. Mol. Evol. 35:351-360 (1987); the method is similar to that described by Higgins & Sharp CABIOS 5:151-153 (1989). Useful PILEUP parameters including a default gap weight of 3.00, a default gap length weight of 0.10, and weighted end gaps.
Another example of a useful algorithm is the BLAST algorithm, described in Altschul et al., J. Mol. Biol.
215, 403-410, (1990) and Karlin et al., PNAS USA 90:5873-5787 (1993). A
particularly useful BLAST
3 0 program is the WU-BLAST-2 program which was obtained from Altschul et al., Methods in Enzymology, 266: 460-480 (1996); http://blast.wustll. WU-BLAST-2 uses several search parameters, most of which are set to the default values. The adjustable parameters are set with the following values: overlap span =1, overlap fraction = 0.125, word threshold (T) = 11.
The HSP S and HSP S2 parameters are dynamic values and are established by the program itself depending upon the composition of the particular sequence and composition of the particular database against which the sequence of interest is being searched; however, the values may be adjusted to increase sensitivity.
A % amino acid sequence identity value is determined by the number of matching identical residues divided by the total number of residues of the "longer" sequence in the aligned region. The "longer"
sequence is the one having the most actual residues in the aligned region (gaps introduced by WU-Blast-2 to maximize the alignment score are ignored).
Thus, "percent (%) nucleic acid sequence identity" is defined as the percentage of nucleotide residues in a candidate sequence that are identical with the nucleotide residues of the nucleic acids of the figures. A preferred method utilizes the BLASTN module of WU-BLAST-2 set to the default parameters, with overlap span and overlap fraction set to 1 and 0.125, respectively.
The alignment may include the introduction of gaps in the sequences to be aligned. In addition, for sequences which contain either more or fewer nucleotides than those of the nucleic acids of the figures, it is understood that the percentage of homology will be determined based on the number of homologous nucleosides in relation to the total number of nucleosides. Thus, for example, homology of sequences shorter than those of the sequences identified herein and as discussed below, will be determined using the number of nucleosides in the shorter sequence.
In one embodiment, the nucleic acid homology is determined through hybridization studies. Thus, for example, nucleic acids which hybridize under high stringency to the nucleic acids identified in the 2 0 figures, or their complements, are considered an angiogenesis sequence.
High stringency conditions are known in the art; see for example Maniatis et al., Molecular Cloning: A
Laboratory Manual, 2d Edition, 1989, and Short Protocols in Molecular Biology, ed. Ausubel, et al., both of which are hereby incorporated by reference. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures. An extensive guide to the hybridization of nucleic acids is found in Tijssen, Techniques in Biochemistry and Molecular Biology--Hybridization with Nucleic Acid Probes, "Overview of principles of hybridization and the strategy of nucleic acid assays" (1993). Generally, stringent conditions are selected to be about 5-10°C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength pH. The Tm is the temperature (under defined ionic strength, pH and nucleic acid 3 0 concentration) at which 50% of the probes complementary to the target hybridize to the target sequence at equilibrium (as the target sequences are present in excess, at Tm, 50% of the probes are occupied at equilibrium). Stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion concentration (or other salts) at pH

7.0 to 8.3 and the temperature is at least about 30°C for short probes (e.g. 10 to 50 nucleotides) and at least about 60°C for long probes (e.g. greater than 50 nucleotides).
Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide.
In another embodiment, less stringent hybridization conditions are used; for example, moderate or low stringency conditions may be used, as are known in the art; see Maniatis and Ausubel, supra, and Tijssen, supra.
In addition, the angiogenesis nucleic acid sequences of the invention are fragments of larger genes, i.e. they are nucleic acid segments. "Genes" in this context includes coding regions, non-coding regions, and mixtures of coding and non-coding regions. Accordingly, as will be appreciated by those in the art, using the sequences provided herein, additional sequences of the angiogenesis genes can be obtained, using techniques well known in the art for cloning either longer sequences or the full length sequences; see Maniatis et al., and Ausubel, et al., supra, hereby expressly incorporated by reference.
Once the angiogenesis nucleic acid is identified, it can be cloned and, if necessary, its constituent parts recombined to form the entire angiogenesis nucleic acid. Once isolated from its natural source, e.g., contained within a plasmid or other vector or excised therefrom as a linear nucleic acid segment, the recombinant angiogenesis nucleic acid can be further-used as a probe to identify and isolate other angiogenesis nucleic acids, for example additional coding regions. It can also be used as a "precursor" nucleic acid to make modified or variant angiogenesis nucleic acids and proteins.
2 0 The angiogenesis nucleic acids of the present invention are used in several ways. In a first embodiment, nucleic acid probes to the angiogenesis nucleic acids are made and attached to biochips to be used in screening and diagnostic methods, as outlined below, or for administration, for example for gene therapy and/or antisense applications. Alternatively, the angiogenesis nucleic acids that include coding regions of angiogenesis proteins can be put into expression vectors for the expression 2 5 of angiogenesis proteins, again either for screening purposes or for administration to a patient.
In a preferred embodiment, nucleic acid probes to angiogenesis nucleic acids (both the nucleic acid sequences outlined in the figures and/or the complements thereof) are made.
The nucleic acid probes attached to the biochip are designed to be substantially complementary to the angiogenesis nucleic acids, i.e. the target sequence (either the target sequence of the sample or to other probe 3 0 sequences, for example in sandwich assays), such that hybridization of the target sequence and the probes of the present invention occurs. As outlined below, this complementarity need not be perfect;

there may be any number of base pair mismatches which will interfere with hybridization between the target sequence and the single stranded nucleic acids of the present invention. However, if the number of mutations is so great that no hybridization can occur under even the least stringent of hybridization conditions, the sequence is not a complementary target sequence.
Thus, by "substantially complementary" herein is meant that the probes are sufficiently complementary to the target sequences to hybridize under normal reaction conditions, particularly high stringency conditions, as outlined herein.
A nucleic acid probe is generally single stranded but can be partially single and partially double stranded. The strandedness of the probe is dictated by the structure, composition, and properties of the target sequence. In general, the nucleic acid probes range from about 8 to about 100 bases long, with from about 10 to about 80 bases being preferred, and from about 30 to about 50 bases being particularly preferred. That is, generally whole genes are not used. In some embodiments, much longer nucleic acids can be used, up to hundreds of bases.
In a preferred embodiment, more than one probe per sequence is used, with either overlapping probes or probes to different sections of the target being used. That is, two, three, four or more probes, with three being preferred, are used to build in a redundancy for a particular target. The probes can be overlapping (i.e. have some sequence in common), or separate.
As will be appreciated by those in the art, nucleic acids can be attached or immobilized to a solid support in a wide variety of ways. By "immobilized" and grammatical equivalents herein is meant the 2 0 association or binding between the nucleic acid probe and the solid support is sufficient to be stable under the conditions of binding, washing, analysis, and removal as outlined below. The binding can be covalent or non-covalent. By "non-covalent binding" and grammatical equivalents herein is meant one or more of either electrostatic, hydrophilic, and hydrophobic interactions.
Included in non-covalent binding is the covalent attachment of a molecule, such as, streptavidin to the support and the non-2 5 covalent binding of the biotinylated probe to the streptavidin. By "covalent binding" and grammatical equivalents herein is meant that the two moieties, the solid support and the probe, are attached by at least one bond, including sigma bonds, pi bonds and coordination bonds.
Covalent bonds can be formed directly between the probe and the solid support or can be formed by a cross linker or by inclusion of a specific reactive group on either the solid support or the probe or both molecules.
3 0 Immobilization may also involve a combination of covalent and non-covalent interactions.

In general, the probes are attached to the biochip in a wide variety of ways, as will be appreciated by those in the art. As described herein, the nucleic acids can either be synthesized first, with subsequent attachment to the biochip, or can be directly synthesized on the biochip.
The biochip comprises a suitable solid substrate. By "substrate" or "solid support" or other grammatical equivalents herein is meant any material that can be modified to contain discrete individual sites appropriate for the attachment or association of the nucleic acid probes and is amenable to at least one detection method. As will be appreciated by those in the art, the number of possible substrates are very large, and include, but are not limited to, glass and modified or functionalized glass, plastics (including acrylics, polystyrene and copolymers of styrene and other materials, polypropylene, polyethylene, polybutylene, polyurethanes, TefIonJ, etc.), polysaccharides, nylon or nitrocellulose, resins, silica or silica-based materials including silicon and modified silicon, carbon, metals, inorganic glasses, plastics, etc. In general, the substrates allow optical detection and do not appreciably fluorescese. A preferred substrate is described in copending application entitled Reusable Low Fluorescent Plastic Biochip, U.S. Application Serial No.
09/270,214, filed March 15, 1999, herein incorporated by reference in its entirety.
Generally the substrate is planar, although as will be appreciated by those in the art, other configurations of substrates may be used as well. For example, the probes may be placed on the inside surface of a tube, for flow-through sample analysis to minimize sample volume. Similarly, the substrate may be flexible, such as a flexible foam, including closed cell foams made of particular 2 0 plastics.
In a preferred embodiment, the surface of the biochip and the probe may be derivatized with chemical functional groups for subsequent attachment of the two. Thus, for example, the biochip is derivatized with a chemical functional group including, but not limited to, amino groups, carboxy groups, oxo groups and thiol groups, with amino groups being particularly preferred. Using these functional 2 5 groups, the probes can be attached using functional groups on the probes.
For example, nucleic acids containing amino groups can be attached to surfaces comprising amino groups, for example using linkers as are known in the art; for example, homo-or hetero-bifunctional linkers as are well known (see 1994 Pierce Chemical Company catalog, technical section on cross-linkers, pages 155-200, incorporated herein by reference). In addition, in some cases, additional linkers, such as 3 0 alkyl groups (including substituted and heteroalkyl groups) may be used.

In this embodiment, the oligonucleotides are synthesized as is known in the art, and then attached to the surface of the solid support. As will be appreciated by those skilled in the art, either the 5' or 3' terminus may be attached to the solid support, or attachment may be via an internal nucleoside.
In an additional embodiment, the immobilization to the solid support may be very strong, yet non-covalent. For example, biotinylated oligonucleotides can be made, which bind to surfaces covalently coated with streptavidin, resulting in attachment.
Alternatively, the oligonucleotides may be synthesized on the surface, as is known in the art. For example, photoactivation techniques utilizing photopolymerization compounds and techniques are used. In a preferred embodiment, the nucleic acids can be synthesized in situ, using well known photolithographic techniques, such as those described in WO 95/25116; WO
95/35505; U.S. Patent Nos. 5,700,637 and 5,445,934; and references cited within, all of which are expressly incorporated by reference; these methods of attachment form the basis of the Affimetrix GeneChipT"' technology.
In a preferred embodiment, angiogenesis nucleic acids encoding angiogenesis proteins are used to make a variety of expression vectors to express angiogenesis proteins which can then be used in screening assays, as described below. The expression vectors may be either self-replicating extrachromosomal vectors or vectors which integrate into a host genome.
Generally, these expression vectors include transcriptional and translational regulatory nucleic acid operably linked to the nucleic acid encoding the angiogenesis protein. The term "control sequences" refers to DNA
sequences necessary for the expression of an operably linked coding sequence in a particular host 2 0 organism. The control sequences that are suitable for prokaryotes, for example, include a promoter, optionally an operator sequence, and a ribosome binding site. Eukaryotic cells are known to utilize promoters, polyadenylation signals, and enhancers.
Nucleic acid is "operably linked" when it is placed into a functional relationship with another nucleic 2 5 acid sequence. For example, DNA for a presequence or secretory leader is operably linked to DNA
for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide;
a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation. Generally, "operably linked" means that the DNA
sequences being linked are 3 0 contiguous, and, in the case of a secretory leader, contiguous and in reading phase. However, enhancers do not have to be contiguous. Linking is accomplished by ligation at convenient restriction sites. If such sites do not exist, the synthetic oligonucleotide adaptors or linkers are used in accordance with conventional practice. The transcriptional and translational regulatory nucleic acid will generally be appropriate to the host cell used to express the angiogenesis protein; for example, transcriptional and translational regulatory nucleic acid sequences from Bacillus are preferably used to express the angiogenesis protein in Bacillus. Numerous types of appropriate expression vectors, and suitable regulatory sequences are known in the art for a variety of host cells.
In general, the transcriptional and translational regulatory sequences may include, but are not limited to, promoter sequences, ribosomal binding sites, transcriptional start and stop sequences, translational start and stop sequences, and enhancer or activator sequences.
In a preferred embodiment, the regulatory sequences include a promoter and transcriptional start and stop sequences.
Promoter sequences encode either constitutive or inducible promoters. The promoters may be either naturally occurring promoters or hybrid promoters. Hybrid promoters, which combine elements of more than one promoter, are also known in the art, and are useful in the present invention.
In addition, the expression vector may comprise additional elements. For example, the expression vector may have two replication systems, thus allowing it to be maintained in two organisms, for example in mammalian or insect cells for expression and in a procaryotic host for cloning and amplification. Furthermore, for integrating expression vectors, the expression vector contains at least one sequence homologous to the host cell genome, and preferably two homologous sequences which flank the expression construct. The integrating vector may be directed to a specific locus in the host cell by selecting the appropriate homologous sequence for inclusion in the vector. Constructs for 2 0 integrating vectors are well known in the art.
In addition, in a preferred embodiment, the expression vector contains a selectable marker gene to allow the selection of transformed host cells. Selection genes are well known in the art and will vary with the host cell used.
The angiogenesis proteins of the present invention are produced by culturing a host cell transformed 2 5 with an expression vector containing nucleic acid encoding an angiogenesis protein, under the appropriate conditions to induce or cause expression of the angiogenesis protein. The conditions appropriate for angiogenesis protein expression will vary with the choice of the expression vector and the host cell, and will be easily ascertained by one skilled in the art through routine experimentation.
For example, the use of constitutive promoters in the expression vector will require optimizing the 3 0 growth and proliferation of the host cell, while the use of an inducible promoter requires the appropriate growth conditions for induction. In addition, in some embodiments, the timing of the harvest is important. For example, the baculoviral systems used in insect cell expression are lytic viruses, and thus harvest time selection can be crucial for product yield.
Appropriate host cells include yeast, bacteria, archaebacteria, fungi, and insect and animal cells, including mammalian cells. Of particular interest are Drosophila melangaster cells, Saccharomyces cerevisiae and other yeasts, E. coli, Bacillus subtilis, Sf9 cells, C129 cells, 293 cells, Neurospora, BHK, CHO, COS, HeLa cells, HUVEC (human umbilical vein endothelial cells),THP1 cells (a macrophage cell line) and human cells and lines.
In a preferred embodiment, the angiogenesis proteins are expressed in mammalian cells. Mammalian expression systems are also known in the art, and include retroviral systems.
A preferred expression vector system is a retroviral vector system such as is generally described in PCT/US97/01019 and PCT/US97/01048, both of which are hereby expressly incorporated by reference.
Of particular use as mammalian promoters are the promoters from mammalian viral genes, since the viral genes are often highly expressed and have a broad host range. Examples include the SV40 early promoter, mouse mammary tumor virus LTR promoter, adenovirus major late promoter, herpes simplex virus promoter, and the CMV promoter. Typically, transcription termination and polyadenylation sequences recognized by mammalian cells are regulatory regions located 3' to the translation stop codon and thus, together with the promoter elements, flank the coding sequence. Examples of transcription terminator and polyadenlytion signals include those derived form SV40.
The methods of introducing exogenous nucleic acid into mammalian hosts, as well as other hosts, is 2 0 well known in the art, and will vary with the host cell used. Techniques include dextrin-mediated transfection, calcium phosphate precipitation, polybrene mediated transfection, protoplast fusion, electroporation, viral infection, encapsulation of the polynucleotide(s) in liposomes, and direct microinjection of the DNA into nuclei.
In a preferred embodiment, angiogenesis proteins are expressed in bacterial systems. Bacterial 2 5 expression systems are well known in the art. Promoters from bacteriophage may also be used and are known in the art. In addition, synthetic promoters and hybrid promoters are also useful; for example, the tic promoter is a hybrid of the trp and lac promoter sequences.
Furthermore, a bacterial promoter can include naturally occurring promoters of non-bacterial origin that have the ability to bind bacterial RNA polymerise and initiate transcription. In addition to a functioning promoter sequence, 3 0 an efficient ribosome binding site is desirable. The expression vector may also include a signal peptide sequence that provides for secretion of the angiogenesis protein in bacteria. The protein is either secreted into the growth media (gram-positive bacteria) or into the periplasmic space, located between the inner and outer membrane of the cell (gram-negative bacteria). The bacterial expression vector may also include a selectable marker gene to allow for the selection of bacterial strains that have been transformed. Suitable selection genes include genes which render the bacteria resistant to drugs such as ampicillin, chloramphenicol, erythromycin, kanamycin, neomycin and tetracycline.
Selectable markers also include biosynthetic genes, such as those in the histidine, tryptophan and leucine biosynthetic pathways. These components are assembled into expression vectors.
Expression vectors for bacteria are well known in the art, and include vectors for Bacillus subtilis, E.
coli, Streptococcus cremoris, and Streptococcus lividans, among others. The bacterial expression vectors are transformed into bacterial host cells using techniques well known in the art, such as calcium chloride treatment, electroporation, and others.
In one embodiment, angiogenesis proteins are produced in insect cells.
Expression vectors for the transformation of insect cells, and in particular, baculovirus-based expression vectors, are well known in the art.
In a preferred embodiment, angiogenesis protein is produced in yeast cells.
Yeast expression systems are well known in the art, and include expression vectors for Saccharomyces cerevisiae, Candida albicans and C. maltosa, Hansenula polymorpha, Kluyveromyces fragilis and K. lactis, Pichia guillerimondii and P. pasforis, Schizosaccharomyces pombe, and Yarrowia lipolytica.
The angiogenesis protein may also be made as a fusion protein, using techniques well known in the art. Thus, for example, for the creation of monoclonal antibodies, if the desired epitope is small, the 2 0 angiogenesis protein may be fused to a carrier protein to form an immunogen. Alternatively, the angiogenesis protein may be made as a fusion protein to increase expression, or for other reasons.
For example, when the angiogenesis protein is an angiogenesis peptide, the nucleic acid encoding the peptide may be linked to other nucleic acid for expression purposes.
In one embodiment, the angiogenesis nucleic acids, proteins and antibodies of the invention are 2 5 labeled. By "labeled" herein is meant that a compound has at least one element, isotope or chemical compound attached to enable the detection of the compound. In general, labels fall into three classes:
a) isotopic labels, which may be radioactive or heavy isotopes; b) immune labels, which may be antibodies or antigens; and c) colored or fluorescent dyes. The labels may be incorporated into the angiogenesis nucleic acids, proteins and antibodies at any position. For example, the label should be 3 0 capable of producing, either directly or indirectly, a detectable signal.
The detectable moiety may be a radioisotope, such as 3H, "C, 32P, ssS, or '251, a fluorescent or chemiluminescent compound, such as fluorescein isothiocyanate, rhodamine, or luciferin, or an enzyme, such as alkaline phosphatase, beta galactosidase or horseradish peroxidase. Any method known in the art for conjugating the antibody to the label may be employed, including those methods described by Hunter et al., Nature, 144:945 (1962); David et al., Biochemistry, 13:1014 (1974); Pain et al., J. Immunol.
Meth., 40:219 (1981); and Nygren, J. Histochem. and Cytochem., 30:407 (1982).
Accordingly, the present invention also provides angiogenesis protein sequences. An angiogenesis protein of the present invention may be identified in several ways. "Protein"
in this sense includes proteins, polypeptides, and peptides. As will be appreciated by those in the art, the nucleic acid sequences of the invention can be used to generate protein sequences. There are a variety of ways to do this, including cloning the entire gene and verifying its frame and amino acid sequence, or by comparing it to known sequences to search for homology to provide a frame, assuming the angiogenesis protein has homology to some protein in the database being used.
Generally, the nucleic acid sequences are input into a program that will search all three frames for homology. This is done in a preferred embodiment using the following NCBI Advanced BLAST
parameters. The program is blastx or blastn. The database is nr. The input data is as "Sequence in FASTA format". The organism list is "none". The "expect" is 10; the filter is default. The "descriptions" is 500, the "alignments" is 500, and the "alignment view" is pairwise. The "Query Genetic Codes" is standard (1 ).
The matrix is BLOSUM62; gap existence cost is 11, per residue gap cost is 1;
and the lambda ratio is 85 default. This results in the generation of a putative protein sequence.
Also included within one embodiment of angiogenesis proteins are amino acid variants of the naturally 2 0 occurring sequences, as determined herein. Preferably, the variants are preferably greater than about 75% homologous to the wild-type sequence, more preferably greater than about 80%, even more preferably greater than about 85% and most preferably greater than 90%. In some embodiments the homology will be as high as about 93 to 95 or 98%. As for nucleic acids, homology in this context means sequence similarity or identity, with identity being preferred. This homology will be determined 2 5 using standard techniques known in the art as are outlined above for the nucleic acid homologies.
Angiogenesis proteins of the present invention may be shorter or longer than the wild type amino acid sequences. Thus, in a preferred embodiment, included within the definition of angiogenesis proteins are portions or fragments of the wild type sequences. herein. In addition, as outlined above, the angiogenesis nucleic acids of the invention may be used to obtain additional coding regions, and thus 3 0 additional protein sequence, using techniques known in the art.
In a preferred embodiment, the angiogenesis proteins are derivative or variant angiogenesis proteins as compared to the wild-type sequence. That is, as outlined more fully below, the derivative angiogenesis peptide will contain at least one amino acid substitution, deletion or insertion, with amino acid substitutions being particularly preferred. The amino acid substitution, insertion or deletion may occur at any residue within the angiogenesis peptide.
Also included within one embodiment of angiogenesis proteins of the present invention are amino acid sequence variants. These variants fall into one or more of three classes:
substitutional, insertional or deletional variants. These variants ordinarily are prepared by site specific mutagenesis of nucleotides in the DNA encoding the angiogenesis protein, using cassette or PCR
mutagenesis or other techniques well known in the art, to produce DNA encoding the variant, and thereafter expressing the DNA in recombinant cell culture as outlined above. However, variant angiogenesis protein fragments having up to about 100-150 residues may be prepared by in vitro synthesis using established techniques. Amino acid sequence variants are characterized by the predetermined nature of the variation, a feature that sets them apart from naturally occurring allelic or interspecies variation of the angiogenesis protein amino acid sequence. The variants typically exhibit the same qualitative biological activity as the naturally occurring analogue, although variants can also be selected which have modified characteristics as will be more fully outlined below.
While the site or region for introducing an amino acid sequence variation is predetermined, the mutation per se need not be predetermined. For example, in order to optimize the performance of a mutation at a given site, random mutagenesis may be conducted at the target codon or region and the expressed angiogenesis variants screened for the optimal combination of desired activity. Techniques 2 0 for making substitution mutations at predetermined sites in DNA having a known sequence are well known, for example, M13 primer mutagenesis and PCR mutagenesis. Screening of the mutants is done using assays of angiogenesis protein activities.
Amino acid substitutions are typically of single residues; insertions usually will be on the order of from about 1 to 20 amino acids, although considerably larger insertions may be tolerated. Deletions range 2 5 from about 1 to about 20 residues, although in some cases deletions may be much larger.
Substitutions, deletions, insertions or any combination thereof may be used to arrive at a final derivative. Generally these changes are done on a few amino acids to minimize the alteration of the molecule. However, larger changes may be tolerated in certain circumstances.
When small alterations in the characteristics of the angiogenesis protein are desired, substitutions are generally 3 0 made in accordance with the following chart:

Chart I
Original Residue Exemplary Substitutions Ala Ser Arg Lys Asn Gln, His Asp Glu Cys Ser Gln Asn Glu Asp Gly Pro His Asn, Gln Ile Leu, Val Leu Ile, Val Lys Arg, Gln, Glu Met Leu, Ile Phe Met, Leu, Tyr Ser Thr Thr Ser Trp Tyr 2 0 Tyr Trp, Phe Val Ile, Leu Substantial changes in function or immunological identity are made by selecting substitutions that are less conservative than those shown in Chart I. For example, substitutions may be made which more significantly affect: the structure of the polypeptide backbone in the area of the alteration, for example 2 5 the alpha-helical or beta-sheet structure; the charge or hydrophobicity of the molecule at the target site; or the bulk of the side chain. The substitutions which in general are expected to produce the greatest changes in the polypeptide's properties are those in which (a) a hydrophilic residue, e.g. seryl or threonyl, is substituted for (or by) a hydrophobic residue, e.g. leucyl, isoleucyl, phenylalanyl, valyl or alanyl; (b) a cysteine or proline is substituted for (or by) any other residue; (c) a residue having an 3 0 electropositive side chain, e.g. lysyl, arginyl, or histidyl, is substituted for (or by) an electronegative residue, e.g. glutamyl or aspartyl; or (d) a residue having a bulky side chain, e.g. phenylalanine, is substituted for (or by) one not having a side chain, e.g. glycine.
The variants typically exhibit the same qualitative biological activity and will elicit the same immune response as the naturally-occurring analogue, although variants also are selected to modify the 3 5 characteristics of the angiogenesis proteins as needed. Alternatively, the variant may be designed such that the biological activity of the angiogenesis protein is altered. For example, glycosylation sites may be altered or removed.
Covalent modifications of angiogenesis polypeptides are included within the scope of this invention.
One type of covalent modification includes reacting targeted amino acid residues of an angiogenesis polypeptide with an organic derivatizing agent that is capable of reacting with selected side chains or the N-or C-terminal residues of an angiogenesis polypeptide. Derivatization with bifunctional agents is useful, for instance, for crosslinking angiogenesis polypeptides to a water-insoluble support matrix or surface for use in the method for purifying anti-angiogenesis polypeptide antibodies or screening assays, as is more fully described below. Commonly used crosslinking agents include, e.g., 1,1-bis(diazoacetyl)-2-phenylethane, glutaraldehyde, N-hydroxysuccinimide esters, for example, esters with 4-azidosalicylic acid, homobifunctional imidoesters, including disuccinimidyl esters such as 3,3'-dithiobis(succinimidylpropionate), bifunctional maleimides such as bis-N-maleimido-1,8-octane and agents such as methyl-3-[(p-azidophenyl)dithio]propioimidate.
Other modifications include deamidation of glutaminyl and asparaginyl residues to the corresponding glutamyl and aspartyl residues, respectively, hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of Beryl, threonyl or tyrosyl residues, methylation of the a-amino groups of lysine, arginine, and histidine side chains [T.E. Creighton, Proteins: Structure and Molecular Properties, W.H.
Freeman & Co., San Francisco, pp. 79-86 (1983)], acetylation of the N-terminal amine, and amidation of any C-terminal carboxyl group.
Another type of covalent modification of the angiogenesis polypeptide included within the scope of this invention comprises altering the native glycosylation pattern of the polypeptide. "Altering the native 2 0 glycosylation pattern" is intended for purposes herein to mean deleting one or more carbohydrate moieties found in native sequence angiogenesis polypeptide, and/or adding one or more glycosylation sites that are not present in the native sequence angiogenesis polypeptide.
Addition of glycosylation sites to angiogenesis polypeptides may be accomplished by altering the 2 5 amino acid sequence thereof. The alteration may be made, for example, by the addition of, or substitution by, one or more serine or threonine residues to the native sequence angiogenesis polypeptide (for O-linked glycosylation sites). The angiogenesis amino acid sequence may optionally be altered through changes at the DNA level, particularly by mutating the DNA
encoding the angiogenesis polypeptide at preselected bases such that codons are generated that will translate into 3 0 the desired amino acids.
Another means of increasing the number of carbohydrate moieties on the angiogenesis polypeptide is by chemical or enzymatic coupling of glycosides to the polypeptide. Such methods are described in the art, e.g., in WO 87/05330 published 11 September 1987, and in Aplin and Wriston, CRC Crit. Rev.
Biochem., pp. 259-306 (1981).

Removal of carbohydrate moieties present on the angiogenesis polypeptide may be accomplished chemically or enzymatically or by mutational substitution of codons encoding for amino acid residues that serve as targets for glycosylation. Chemical deglycosylation techniques are known in the art and described, for instance, by Hakimuddin, et al., Arch. Biochem. Biophys., 259:52 (1987) and by Edge et al., Anal. Biochem., 118:131 (1981 ). Enzymatic cleavage of carbohydrate moieties on polypeptides can be achieved by the use of a variety of endo-and exo-glycosidases as described by Thotakura et al., Meth. Enzymol., 138:350 (1987).
Another type of covalent modification of angiogenesis comprises linking the angiogenesis polypeptide to one of a variety of nonproteinaceous polymers, e.g., polyethylene glycol, polypropylene glycol, or polyoxyalkylenes, in the manner set forth in U.S. Patent Nos. 4,640,835;
4,496,689; 4,301,144;
4,670,417; 4,791,192 or 4,179,337.
Angiogenesis polypeptides of the present invention may also be modified in a way to form chimeric molecules comprising an angiogenesis polypeptide fused to another, heterologous polypeptide or amino acid sequence. In one embodiment, such a chimeric molecule comprises a fusion of an angiogenesis polypeptide with a tag polypeptide which provides an epitope to which an anti-tag antibody can selectively bind. The epitope tag is generally placed at the amino-or carboxyl-terminus of the angiogenesis polypeptide. The presence of such epitope-tagged forms of an angiogenesis polypeptide can be detected using an antibody against the tag polypeptide.
Also, provision of the epitope tag enables the angiogenesis polypeptide to be readily purified by affinity purification using an 2 0 anti-tag antibody or another type of affinity matrix that binds to the epitope tag. In an alternative embodiment, the chimeric molecule may comprise a fusion of an angiogenesis polypeptide with an immunoglobulin or a particular region of an immunoglobulin. For a bivalent form of the chimeric molecule, such a fusion could be to the Fc region of an IgG molecule.
Various tag polypeptides and their respective antibodies are well known in the art. Examples include poly-histidine (poly-his) or poly-histidine-glycine (poly-his-gly) tags; the flu HA tag polypeptide and its antibody 12CA5 [Field et al., Mol. Cell. Biol., 8:2159-2165 (1988)]; the c-myc tag and the 8F9, 3C7, 6E10, G4, B7 and 9E10 antibodies thereto [Evan et al., Molecular and Cellular Biology, 5:3610-3616 (1985)]; and the Herpes Simplex virus glycoprotein D (gD) tag and its antibody [Paborsky et al., Protein Engineering, 3(6):547-553 (1990)]. Other tag polypeptides include the Flag-peptide [Hopp et 3 0 al., BioTechnology, 6:1204-1210 (1988)]; the KT3 epitope peptide [Martin et al., Science, 255:192-194 (1992)]; tubulin epitope peptide [Skinner et al., J. Biol. Chem., 266:15163-15166 (1991 )]; and the T7 gene 10 protein peptide tag [Lutz-Freyermuth et al., Proc. Natl. Acad. Sci.
USA, 87:6393-6**397 (1990)].

Also included with an embodiment of angiogenesis protein are other angiogenesis proteins of the angiogenesis family, and angiogenesis proteins from other organisms, which are cloned and expressed as outlined below. Thus, probe or degenerate polymerase chain reaction (PCR) primer sequences may be used to find other related angiogenesis proteins from humans or other organisms.
As will be appreciated by those in the art, particularly useful probe and/or PCR primer sequences include the unique areas of the angiogenesis nucleic acid sequence. As is generally known in the art, preferred PCR primers are from about 15 to about 35 nucleotides in length, with from about 20 to about 30 being preferred, and may contain inosine as needed. The conditions for the PCR reaction are well known in the art.
In addition, as is outlined herein, angiogenesis proteins can be made that are longer than those encoded by the nucleic acids of the figures, for example, by the elucidation of additional sequences, the addition of epitope or purification tags, the addition of other fusion sequences, etc.
Angiogenesis proteins may also be identified as being encoded by angiogenesis nucleic acids. Thus, angiogenesis proteins are encoded by nucleic acids that will hybridize to the sequences of the sequence listings, or their complements, as outlined herein.
In a preferred embodiment, when the angiogenesis protein is to be used to generate antibodies, for example for immunotherapy, the angiogenesis protein should share at least one epitope or determinant with the full length protein. By "epitope" or "determinant" herein is meant a portion of a protein which will generate and/or bind an antibody or T-cell receptor in the context of MHC. Thus, in 2 0 most instances, antibodies made to a smaller angiogenesis protein will be able to bind to the full length protein. In a preferred embodiment, the epitope is unique; that is, antibodies generated to a unique epitope show little or no cross-reactivity. In a preferred embodiment, the epitope is selected from AAA4p1 and AAA4p2. In another preferred embodiment the epitope is selected from AAA1p1 and AAA1 p2. In another preferred embodiment the epitope is selected from AAA7p1, AAA7p2, 2 5 AAA7p3 and AAA7p1 m.
In one embodiment, the term "antibody" includes antibody fragments, as are known in the art, including Fab, Fab2, single chain antibodies (Fv for example), chimeric antibodies, etc., either produced by the modification of whole antibodies or those synthesized de novo using recombinant DNA technologies.
3 0 Methods of preparing polyclonal antibodies are known to the skilled artisan. Polyclonal antibodies can be raised in a mammal, for example, by one or more injections of an immunizing agent and, if desired, an adjuvant. Typically, the immunizing agent and/or adjuvant will be injected in the mammal by multiple subcutaneous or intraperitoneal injections. The immunizing agent may include a protein encoded by a nucleic acid of the figures or fragment thereof or a fusion protein thereof. It may be useful to conjugate the immunizing agent to a protein known to be immunogenic in the mammal being immunized. Examples of such immunogenic proteins include but are not limited to keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. Examples of adjuvants which may be employed include Freund's complete adjuvant and MPL-TDM
adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate). The immunization protocol may be selected by one skilled in the art without undue experimentation.
The antibodies may, alternatively, be monoclonal antibodies. Monoclonal antibodies may be prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature, 256:495 (1975).
In a hybridoma method, a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes may be immunized in vitro. The immunizing agent will typically include a polypeptide encoded by a nucleic acid of Table 1, Table 2, Table 3, Table 4 or Table 5 or fragment thereof or a fusion protein thereof. Generally, either peripheral blood lymphocytes ("PBLs") are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form 2 0 a hybridoma cell [coding, Monoclonal Antibodies: Principles and Practice, Academic Press, (1986) pp.
59-103]. Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and human origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells may be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine ("HAT medium"), which substances prevent the growth of HGPRT-deficient cells.
In one embodiment, the antibodies are bispecific antibodies. Bispecific antibodies are monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different 3 0 antigens. In the present case, one of the binding specificities is for a protein encoded by a nucleic acid of figure 1 or 3-6 or a fragment thereof, the other one is for any other antigen, and preferably for a cell-surface protein or receptor or receptor subunit, preferably one that is tumor specific.

In a preferred embodiment, the antibodies to angiogenesis protein are capable of reducing or eliminating the biological function of angiogenesis protein, as is described below. That is, the addition of anti-angiogenesis protein antibodies (either polyclonal or preferably monoclonal) to angiogenic tissue (or cells containing angiogenesis) may reduce or eliminate the angiogenesis activity. Generally, at least a 25% decrease in activity is preferred, with at least about 50%
being particularly preferred and about a 95-100% decrease being especially preferred.
In a preferred embodiment the antibodies to the angiogenesis proteins are humanized antibodies.
Humanized forms of non-human (e.g., murine) antibodies are chimeric molecules of immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab')2 or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non-human immunoglobulin. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues form a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity and capacity. In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR
regions are those of a 2 0 human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin [Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol., 2:593-596 (1992)].
Methods for humanizing non-human antibodies are well known in the art.
Generally, a humanized 2 5 antibody has one or more amino acid residues introduced into it from a source which is non-human.
These non-human amino acid residues are often referred to as import residues, which are typically taken from an import variable domain. Humanization can be essentially performed following the method of Winter and co-workers [Jones et al., Nature, 321:522-525 (1986);
Riechmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)], by substituting rodent CDRs 3 0 or CDR sequences for the corresponding sequences of a human antibody.
Accordingly, such humanized antibodies are chimeric antibodies (U.S. Patent No. 4,816,567), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies.
Human antibodies can also be produced using various techniques known in the art, including phage display libraries (Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991 );
Marks et al., J. Mol. Biol., 222:581 (1991 )]. The techniques of Cole et al. and Boerner et al. are also available for the preparation of human monoclonal antibodies (Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R.
Liss, p. 77 (1985) and Boerner et al., J. Immunol., 147 1 :86-95 (1991 )].
Similarly, human antibodies can be made by introducing of human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire.
This approach is described, for example, in U.S. Patent Nos. 5,545,807; 5,545,806; 5,569,825;
5,625,126; 5,633,425;
5,661,016, and in the following scientific publications: Marks et al., Bio/Technoloay 10, 779-783 (1992); Lonberg et al., Nature 368 856-859 (1994); Morrison, Nature 368, 812-13 (1994); Fishwild et al., Nature Biotechnolo4y 14, 845-51 (1996); Neuberger, Nature Biotechnology 14, 826 (1996);
Lonberg and Huszar, Intern. Rev. Immunol. 13 65-93 (1995).
By immunotherapy is meant treatment of angiogenesis with an antibody raised against angiogenesis proteins. As used herein, immunotherapy can be passive or active. Passive immunotherapy as defined herein is the passive transfer of antibody to a recipient (patient).
Active immunization is the 2 0 induction of antibody and/or T-cell responses in a recipient (patient).
Induction of an immune response is the result of providing the recipient with an antigen to which antibodies are raised. As appreciated by one of ordinary skill in the art, the antigen may be provided by injecting a polypeptide against which antibodies are desired to be raised into a recipient, or contacting the recipient with a nucleic acid capable of expressing the antigen and under conditions for expression of the antigen.
2 5 In a preferred embodiment the angiogenesis proteins against which antibodies are raised are secreted proteins as described above. Without being bound by theory, antibodies used for treatment, bind and prevent the secreted protein from binding to its receptor, thereby inactivating the secreted angiogenesis protein.
In another preferred embodiment, the angiogenesis protein to which antibodies are raised is a 3 0 transmembrane protein. Without being bound by theory, antibodies used for treatment, bind the extracellular domain of the angiogenesis protein and prevent it from binding to other proteins, such as circulating ligands or cell-associated molecules. The antibody may cause down-regulation of the transmembrane angiogenesis protein. As will be appreciated by one of ordinary skill in the art, the antibody may be a competitive, non-competitive or uncompetitive inhibitor of protein binding to the extracellular domain of the angiogenesis protein. The antibody is also an antagonist of the angiogenesis protein. Further, the antibody prevents activation of the transmembrane angiogenesis protein. In one aspect, when the antibody prevents the binding of other molecules to the angiogenesis protein, the antibody prevents growth of the cell. The antibody also sensitizes the cell to cytotoxic agents, including, but not limited to TNF-a, TNF-~, IL-1, INF-y and IL-2, or chemotherapeutic agents including SFU, vinblastine, actinomycin D, cisplatin, methotrexate, and the like. In some instances the antibody belongs to a sub-type that activates serum complement when complexed with the transmembrane protein thereby mediating cytotoxicity. Thus, angiogenesis is treated by administering to a patient antibodies directed against the transmembrane angiogenesis protein.
In another preferred embodiment, the antibody is conjugated to a therapeutic moiety. In one aspect the therapeutic moiety is a small molecule that modulates the activity of the angiogenesis protein. In another aspect the therapeutic moiety modulates the activity of molecules associated with or in close proximity to the angiogenesis protein. The therapeutic moiety may inhibit enzymatic activity such as protease or collagenase activity associated with angiogenesis.
In a preferred embodiment, the therapeutic moiety may also be a cytotoxic agent. In this method, targeting the cytotoxic agent to angiogenesis tissue or cells, results in a reduction in the number of afflicted cells, thereby reducing symptoms associated with angiogenesis.
Cytotoxic agents are 2 0 numerous and varied and include, but are not limited to, cytotoxic drugs or toxins or active fragments of such toxins. Suitable toxins and their corresponding fragments include diptheria A chain, exotoxin A chain, ricin A chain, abrin A chain, curcin, crotin, phenomycin, enomycin and the like. Cytotoxic agents also include radiochemicals made by conjugating radioisotopes to antibodies raised against angiogenesis proteins, or binding of a radionuclide to a chelating agent that has been covalently 2 5 attached to the antibody. Targeting the therapeutic moiety to transmembrane angiogenesis proteins not only serves to increase the local concentration of therapeutic moiety in the angiogenesis afflicted area, but also serves to reduce deleterious side effects that may be associated with the therapeutic moiety.
In another preferred embodiment, the angiogenesis protein against which the antibodies are raised is 3 0 an intracellular protein. In this case, the antibody may be conjugated to a protein which facilitates entry into the cell. In one case, the antibody enters the cell by endocytosis.
In another embodiment, a nucleic acid encoding the antibody is administered to the individual or cell.
Moreover, wherein the angiogenesis protein can be targeted within a cell, i.e., the nucleus, an antibody thereto contains a signal for that target localization, i.e., a nuclear localization signal.
The angiogenesis antibodies of the invention specifically bind to angiogenesis proteins. By "specifically bind" herein is meant that the antibodies bind to the protein with a binding constant in the range of at least 10~'- 10-6 M'', with a preferred range being 10-' - 10-9 M-'.
In a preferred embodiment, the angiogenesis protein is purified or isolated after expression.
Angiogenesis proteins may be isolated or purified in a variety of ways known to those skilled in the art depending on what other components are present in the sample. Standard purification methods include electrophoretic, molecular, immunological and chromatographic techniques, including ion exchange, hydrophobic, affinity, and reverse-phase HPLC chromatography, and chromatofocusing.
For example, the angiogenesis protein may be purified using a standard anti-angiogenesis protein antibody column. Ultrafiltration and diafiltration techniques, in conjunction with protein concentration, are also useful. For general guidance in suitable purification techniques, see Scopes, R., Protein Purification, Springer-Verlag, NY (1982). The degree of purification necessary will vary depending on the use of the angiogenesis protein. In some instances no purification will be necessary.
Once expressed and purified if necessary, the angiogenesis proteins and nucleic acids are useful in a number of applications.
In one aspect, the expression levels of genes are determined for different cellular states in the angiogenesis phenotype; that is, the expression levels of genes in normal tissue (i.e. not undergoing 2 0 angiogenesis) and in angiogenesis tissue (and in some cases, for varying severities of angiogenesis that relate to prognosis, as outlined below) are evaluated to provide expression profiles. An expression profile of a particular cell state or point of development is essentially a "fingerprint" of the state; while two states may have any particular gene similarly expressed, the evaluation of a number of genes simultaneously allows the generation of a gene expression profile that is unique to the state 2 5 of the cell. By comparing expression profiles of cells in different states, information regarding which genes are important (including both up- and down-regulation of genes) in each of these states is obtained. Then, diagnosis may be done or confirmed: does tissue from a particular patient have the gene expression profile of normal or angiogenesis tissue.
"Differential expression," or grammatical equivalents as used herein, refers to both qualitative as well 3 0 as quantitative differences in the genes' temporal and/or cellular expression patterns within and among the cells. Thus, a differentially expressed gene can qualitatively have its expression altered, including an activation or inactivation, in, for example, normal versus angiogenic tissue. That is, genes may be turned on or turned off in a particular state, relative to another state. As is apparent to the skilled artisan, any comparison of two or more states can be made. Such a qualitatively regulated gene will exhibit an expression pattern within a state or cell type which is detectable by standard techniques in one such state or cell type, but is not detectable in both.
Alternatively, the determination is quantitative in that expression is increased or decreased; that is, the expression of the gene is either upregulated, resulting in an increased amount of transcript, or downregulated, resulting in a decreased amount of transcript. The degree to which expression differs need only be large enough to quantify via standard characterization techniques as outlined below, such as by use of Affymetrix GeneChipT""
expression arrays, Lockhart, Nature Biotechnology, 14:1675-1680 (1996), hereby expressly incorporated by reference. Other techniques include, but are not limited to, quantitative reverse transcriptase PCR, Northern analysis and RNase protection. As outlined above, preferably the change in expression (i.e. upregulation or downregulation) is at least about 50%, more preferably at least about 100%, more preferably at least about 150%, more preferably, at least about 200%, with from 300 to at least 1000% being especially preferred.
As will be appreciated by those in the art, this may be done by evaluation at either the gene transcript, or the protein level; that is, the amount of gene expression may be monitored using nucleic acid probes to the DNA or RNA equivalent of the gene transcript, and the quantification of gene expression levels, or, alternatively, the final gene product itself (protein) can be monitored, for example through 2 0 the use of antibodies to the angiogenesis protein and standard immunoassays (ELISAs, etc.) or other techniques, including mass spectroscopy assays, 2D gel electrophoresis assays, etc. Thus, the proteins corresponding to angiogenesis genes, i.e. those identified as being important in an angiogenesis phenotype, can be evaluated in an angiogenesis diagnostic test.
In a preferred embodiment, gene expression monitoring is done and a number of genes, i.e. an expression profile, is monitored simultaneously, although multiple protein expression monitoring can be done as well. Similarly, these assays may be done on an individual basis as well.
In this embodiment, the angiogenesis nucleic acid probes are attached to biochips as outlined herein for the detection and quantification of angiogenesis sequences in a particular cell. The assays are further described below in the example.
3 0 In a preferred embodiment nucleic acids encoding the angiogenesis protein are detected. Although DNA or RNA encoding the angiogenesis protein may be detected, of particular interest are methods wherein the mRNA encoding an angiogenesis protein is detected. The presence of mRNA in a sample is an indication that the angiogenesis gene has been transcribed to form the mRNA, and suggests that the protein is expressed. Probes to detect the mRNA can be any nucleotide/deoxynucleotide probe that is complementary to and base pairs with the mRNA and includes but is not limited to oligonucleotides, cDNA or RNA. Probes also should contain a detectable label, as defined herein. In one method the mRNA is detected after immobilizing the nucleic acid to be examined on a solid support such as nylon membranes and hybridizing the probe with the sample.
Following washing to remove the non-specifically bound probe, the label is detected. In another method detection of the mRNA is performed in situ. In this method permeabilized cells or tissue samples are contacted with a detectably labeled nucleic acid probe for sufficient time to allow the probe to hybridize with the target mRNA. Following washing to remove the non-specifically bound probe, the label is detected. For example a digoxygenin labeled riboprobe (RNA
probe) that is complementary to the mRNA encoding an angiogenesis protein is detected by binding the digoxygenin with an anti-digoxygenin secondary antibody and developed with vitro blue tetrazolium and 5-bromo-4-chloro-3-indoyl phosphate.
In a preferred embodiment, any of the three classes of proteins as described herein (secreted, transmembrane or intracellular proteins) are used in diagnostic assays. The angiogenesis proteins, antibodies, nucleic acids, modified proteins and cells containing angiogenesis sequences are used in diagnostic assays. This can be done on an individual gene or corresponding polypeptide level. In a preferred embodiment, the expression profiles are used, preferably in conjunction with high throughput 2 0 screening techniques to allow monitoring for expression profile genes and/or corresponding polypeptides.
As described and defined herein, angiogenesis proteins, including intracellular, transmembrane or secreted proteins, find use as markers of angiogenesis. Detection of these proteins in putative angiogenesis tissue or patients allows for a determination or diagnosis of angiogenesis. Numerous 2 5 methods known to those of ordinary skill in the art find use in detecting angiogenesis. In one embodiment, antibodies are used to detect angiogenesis proteins. A preferred method separates proteins from a sample or patient by electrophoresis on a gel (typically a denaturing and reducing protein gel, but may be any other type of gel including isoelectric focusing gels and the like). Following separation of proteins, the angiogenesis protein is detected by immunoblotting with antibodies raised 3 0 against the angiogenesis protein. Methods of immunoblotting are well known to those of ordinary skill in the art.
In another preferred method, antibodies to the angiogenesis protein find use in in situ imaging techniques. In this method cells are contacted with from one to many antibodies to the angiogenesis protein(s). Following washing to remove non-specific antibody binding, the presence of the antibody or antibodies is detected. In one embodiment the antibody is detected by incubating with a secondary antibody that contains a detectable label. In another method the primary antibody to the angiogenesis proteins) contains a detectable label. In another preferred embodiment each one of multiple primary antibodies contains a distinct and detectable label. This method finds particular use in simultaneous screening for a plurality of angiogenesis proteins. As will be appreciated by one of ordinary skill in the art, numerous other histological imaging techniques are useful in the invention.
In a preferred embodiment the label is detected in a fluorometer which has the ability to detect and distinguish emissions of different wavelengths. In addition, a fluorescence activated cell sorter (FACS) can be used in the method.
In another preferred embodiment, antibodies find use in diagnosing angiogenesis from blood samples.
As previously described, certain angiogenesis proteins are secreted/circulating molecules. Blood samples, therefore, are useful as samples to be probed or tested for the presence of secreted angiogenesis proteins. Antibodies can be used to detect the angiogenesis by any of the previously described immunoassay techniques including ELISA, immunoblotting (Western blotting), immunoprecipitation, BIACORE technology and the like, as will be appreciated by one of ordinary skill in the art.
In a preferred embodiment, in situ hybridization of labeled angiogenesis nucleic acid probes to tissue arrays is done. For example, arrays of tissue samples, including angiogenesis tissue and/or normal 2 0 tissue, are made. In situ hybridization as is known in the art can then be done.
It is understood that when comparing the fingerprints between an individual and a standard, the skilled artisan can make a diagnosis as well as a prognosis. It is further understood that the genes which indicate the diagnosis may differ from those which indicate the prognosis.
In a preferred embodiment, the angiogenesis proteins, antibodies, nucleic acids, modified proteins and 2 5 cells containing angiogenesis sequences are used in prognosis assays. As above, gene expression profiles can be generated that correlate to angiogenesis severity, in terms of long term prognosis.
Again, this may be done on either a protein or gene level, with the use of genes being preferred. As above, the angiogenesis probes are attached to biochips for the detection and quantification of angiogenesis sequences in a tissue or patient. The assays proceed as outlined above for diagnosis.

In a preferred embodiment any of the three classes of proteins as described herein are used in drug screening assays. The angiogenesis proteins, antibodies, nucleic acids, modified proteins and cells containing angiogenesis sequences are used in drug screening assays or by evaluating the effect of drug candidates on a "gene expression profile" or expression profile of polypeptides. In a preferred embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes after treatment with a candidate agent, Zlokarnik, et al., Science 279, 84-8 (1998), Heid, 1996 #69.
In a preferred embodiment, the angiogenesis proteins, antibodies, nucleic acids, modified proteins and cells containing the native or modified angiogenesis proteins are used in screening assays. That is, the present invention provides novel methods for screening for compositions which modulate the angiogenesis phenotype. As above, this can be done on an individual gene level or by evaluating the effect of drug candidates on a "gene expression profile". In a preferred embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes after treatment with a candidate agent, see Zlokarnik, supra.
Having identified the differentially expressed genes herein, a variety of assays may be executed. In a preferred embodiment, assays may be run on an individual gene or protein level. That is, having identified a particular gene as up regulated in angiogenesis, candidate bioactive agents may be screened to modulate this gene's response; preferably to down regulate the gene, although in some circumstances to up regulate the gene. "Modulation" thus includes both an increase and a decrease 2 0 in gene expression. The preferred amount of modulation will depend on the original change of the gene expression in normal versus tissue undergoing angiogenesis, with changes of at least 10%, preferably 50%, more preferably 100-300%, and in some embodiments 300-1000% or greater. Thus, if a gene exhibits a 4 fold increase in angiogenic tissue compared to normal tissue, a decrease of about four fold is desired; a 10 fold decrease in angiogenic tissue compared to normal tissue gives a 10 fold increase in expression for a candidate agent being desired.
As will be appreciated by those in the art, this may be done by evaluation at either the gene or the protein level; that is, the amount of gene expression may be monitored using nucleic acid probes and the quantification of gene expression levels, or, alternatively, the gene product itself can be monitored, for example through the use of antibodies to the angiogenesis protein and standard immunoassays.
3 0 In a preferred embodiment, gene expression monitoring is done and a number of genes, i.e. an expression profile, is monitored simultaneously, although multiple protein expression monitoring can be done as well.

In this embodiment, the angiogenesis nucleic acid probes are attached to biochips as outlined herein for the detection and quantification of angiogenesis sequences in a particular cell. The assays are further described below.
Generally, in a preferred embodiment, a candidate bioactive agent is added to the cells prior to analysis. Moreover, screens are provided to identify a candidate bioactive agent which modulates angiogenesis, modulates angiogenesis proteins, binds to an angiogenesis protein, or interferes between the binding of an angiogenesis protein and an antibody.
The term "candidate bioactive agent" or "drug candidate" or grammatical equivalents as used herein describes any molecule, e.g., protein, oligopeptide, small organic molecule, polysaccharide, polynucleotide, etc., to be tested for bioactive agents that are capable of directly or indirectly altering either the angiogenesis phenotype or the expression of an angiogenesis sequence, including both nucleic acid sequences and protein sequences. In preferred embodiments, the bioactive agents modulate the expression profiles, or expression profile nucleic acids or proteins provided herein. In a particularly preferred embodiment, the candidate agent suppresses an angiogenesis phenotype, for example to a normal tissue fingerprint. Similarly, the candidate agent preferably suppresses a severe angiogenesis phenotype. Generally a plurality of assay mixtures are run in parallel with different agent concentrations to obtain a differential response to the various concentrations. Typically, one of these concentrations serves as a negative control, i.e., at zero concentration or below the level of detection.
In one aspect, a candidate agent will neutralize the effect of an angiogenesis protein. By "neutralize"
2 0 is meant that activity of a protein is either inhibited or counter acted against so as to have substantially no effect on a cell.
Candidate agents encompass numerous chemical classes, though typically they are organic molecules, preferably small organic compounds having a molecular weight of more than 100 and less than about 2,500 daltons. Preferred small molecules are less than 2000, or less than 1500 or less 2 5 than 1000 or less than 500 D. Candidate agents comprise functional groups necessary for structural interaction with proteins, particularly hydrogen bonding, and typically include at least an amine, carbonyl, hydroxyl or carboxyl group, preferably at least two of the functional chemical groups. The candidate agents often comprise cyclical carbon or heterocyclic structures and/or aromatic or polyaromatic structures substituted with one or more of the above functional groups. Candidate 3 0 agents are also found among biomolecules including peptides, saccharides, fatty acids, steroids, purines, pyrimidines, derivatives, structural analogs or combinations thereof.
Particularly preferred are peptides.

Candidate agents are obtained from a wide variety of sources including libraries of synthetic or natural compounds. For example, numerous means are available for random and directed synthesis of a wide variety of organic compounds and biomolecules, including expression of randomized oligonucleotides. Alternatively, libraries of natural compounds in the form of bacterial, fungal, plant and animal extracts arE; available or readily produced. Additionally, natural or synthetically produced libraries and compounds are readily modified through conventional chemical, physical and biochemical means. Known pharmacological agents may be subjected to directed or random chemical modifications, such as acylation, alkylation, esterification, amidification to produce structural analogs.
In a preferred embodiment, the candidate bioactive agents are proteins. By "protein" herein is meant at least two covalently attached amino acids, which includes proteins, polypeptides, oligopeptides and peptides. The protein may be made up of naturally occurring amino acids and peptide bonds, or synthetic peptidomimetic structures. Thus "amino acid", or "peptide residue", as used herein means both naturally occurring and synthetic amino acids. For example, homo-phenylalanine, citrulline and noreleucine are considered amino acids for the purposes of the invention.
"Amino acid" also includes imino acid residues such as proline and hydroxyproline. The side chains may be in either the (R) or the (S) configuration. In the preferred embodiment, the amino acids are in the (S) or L-configuration.
If non-naturally occurring side chains are used, non-amino acid substituents may be used, for example to prevent or retard in vivo degradations.
2 0 In a preferred embodiment, the candidate bioactive agents are naturally occurring proteins or fragments of naturally occurring proteins. Thus, for example, cellular extracts containing proteins, or random or directed digests of proteinaceous cellular extracts, may be used. In this way libraries of procaryotic and eucaryotic proteins may be made for screening in the methods of the invention.
Particularly preferred in this embodiment are libraries of bacterial, fungal, viral, and mammalian 2 5 proteins, with the latter being preferred, and human proteins being especially preferred.
In a preferred embodiment, the candidate bioactive agents are peptides of from about 5 to about 30 amino acids, with from about 5 to about 20 amino acids being preferred, and from about 7 to about 15 being particularly preferred. The peptides may be digests of naturally occurring proteins as is outlined above, random peptides, or "biased" random peptides. By "randomized" or grammatical equivalents 3 0 herein is meant that each nucleic acid and peptide consists of essentially random nucleotides and amino acids, respectively. Since generally these random peptides (or nucleic acids, discussed below) are chemically synthesized, they may incorporate any nucleotide or amino acid at any position. The synthetic process can be designed to generate randomized proteins or nucleic acids, to allow the formation of all or most of the possible combinations over the length of the sequence, thus forming a library of randomized candidate bioactive proteinaceous agents.
In one embodiment, the library is fully randomized, with no sequence preferences or constants at any position. In a preferred embodiment, the library is biased. That is, some positions within the sequence are either held constant, or are selected from a limited number of possibilities. For example, in a preferred embodiment, the nucleotides or amino acid residues are randomized within a defined class, for example, of hydrophobic amino acids, hydrophilic residues, sterically biased (either small or large) residues, towards the creation of nucleic acid binding domains, the creation of cysteines, for cross-linking, prolines for SH-3 domains, serines, threonines, tyrosines or histidines for phosphorylation sites, etc., or to purines, etc.
In a preferred embodiment, the candidate bioactive agents are nucleic acids, as defined above.
As described above generally for proteins, nucleic acid candidate bioactive agents may be naturally occurring nucleic acids, random nucleic acids, or "biased" random nucleic acids. For example, digests of procaryotic or eucaryotic genomes may be used as is outlined above for proteins.
In a preferred embodiment, the candidate bioactive agents are organic chemical moieties, a wide variety of which are available in the literature.
After the candidate agent has been added and the cells allowed to incubate for some period of time, the sample containing the target sequences to be analyzed is added to the biochip. If required, the target sequence is prepared using known techniques. For example, the sample may be treated to 2 0 lyse the cells, using known lysis buffers, electroporation, etc., with purification and/or amplification such as PCR occurring as needed, as will be appreciated by those in the art.
For example, an in vitro transcription with labels covalently attached to the nucleosides is done.
Generally, the nucleic acids are labeled with biotin-FITC or PE, or with cy3 or cy5.
In a preferred embodiment, the target sequence is labeled with, for example, a fluorescent, a 2 5 chemiluminescent, a chemical, or a radioactive signal, to provide a means of detecting the target sequence's specific binding to a probe. The label also can be an enzyme, such as, alkaline phosphatase or horseradish peroxidase, which when provided with an appropriate substrate produces a product that can be detected. Alternatively, the label can be a labeled compound or small molecule, such as an enzyme inhibitor, that binds but is not catalyzed or altered by the enzyme. The label also 3 0 can be a moiety or compound, such as, an epitope tag or biotin which specifically binds to streptavidin.

For the example of biotin, the streptavidin is labeled as described above, thereby, providing a detectable signal for the bound target sequence. As known in the art, unbound labeled streptavidin is removed prior to analysis.
As will be appreciated by those in the art, these assays can be direct hybridization assays or can comprise "sandwich assays", which include the use of multiple probes, as is generally outlined in U.S.
Patent Nos. 5,681,702, 5,597,909, 5,545,730, 5,594,117, 5,591,584, 5,571,670, 5,580,731, 5,571,670, 5,591,584, 5,624,802, 5,635,352, 5,594,118, 5,359,100, 5,124,246 and 5,681,697, all of which are hereby incorporated by reference. In this embodiment, in general, the target nucleic acid is prepared as outlined above, and then added to the biochip comprising a plurality of nucleic acid probes, under conditions that allow the formation of a hybridization complex.
A variety of hybridization conditions may be used in the present invention, including high, moderate and low stringency conditions as outlined above. The assays are generally run under stringency conditions which allows formation of the label probe hybridization complex only in the presence of target. Stringency can be controlled by altering a step parameter that is a thermodynamic variable, including, but not limited to, temperature, formamide concentration, salt concentration, chaotropic s2!t concentration pH, organic solvent concentration, etc.
These parameters may also be used to control non-specific binding, as is generally outlined in U.S.
Patent No. 5,681,697. Thus it may be desirable to perform certain steps at higher stringency conditions to reduce non-specific binding.
2 0 The reactions outlined herein may be accomplished in a variety of ways, as will be appreciated by those in the art. Components of the reaction may be added simultaneously, or sequentially, in any order, with preferred embodiments outlined below. In addition, the reaction may include a variety of other reagents may be included in the assays. These include reagents like salts, buffers, neutral proteins, e.g. albumin, detergents, etc which may be used to facilitate optimal hybridization and 2 5 detection, and/or reduce non-specific or background interactions. Also reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may be used, depending on the sample preparation methods and purity of the target.
Once the assay is run, the data is analyzed to determine the expression levels, and changes in expression levels as between states, of individual genes, forming a gene expression profile.

The screens are done to identify drugs or bioactive agents that modulate the angiogenesis phenotype.
Specifically, there are several types of screens that can be run. A preferred embodiment is in the screening of candidate agents that can induce or suppress a particular expression profile, thus preferably generating the associated phenotype. That is, candidate agents that can mimic or produce an expression profile in angiogenesis similar to the expression profile of normal tissue is expected to result in a suppression of the angiogenesis phenotype. Thus, in this embodiment, mimicking an expression profile, or changing one profile to another, is the goal.
In a preferred embodiment, as for the diagnosis applications, having identified the differentially expressed genes important in any one state, screens can be run to alter the expression of the genes individually. That is, screening for modulation of regulation of expression of a single gene can be done; that is, rather than try to mimic all or part of an expression profile, screening for regulation of individual genes can be done. Thus, for example, particularly in the case of target genes whose presence or absence is unique between two states, screening is done for modulators of the target gene expression.
In a preferred embodiment, screening is done to alter the biological function of the expression product of the differentially expressed gene. Again, having identified the importance of a gene in a particular state, screening for agents that bind andlor modulate the biological activity of the gene product can be run as is more fully outlined below.
Thus, screening of candidate agents that modulate the angiogenesis phenotype either at the gene 2 0 expression level or the protein level can be done.
In addition screens can be done for novel genes that are induced in response to a candidate agent.
After identifying a candidate agent based upon its ability to suppress an angiogenesis expression pattern leading to a normal expression pattern, or modulate a single angiogenesis gene expression profile so as to mimic the expression of the gene from normal tissue, a screen as described above can 2 5 be performed to identify genes that are specifically modulated in response to the agent. Comparing expression profiles between normal tissue and agent treated angiogenesis tissue reveals genes that are not expressed in normal tissue or angiogenesis tissue, but are expressed in agent treated tissue.
These agent specific sequences can be identified and used by any of the methods described herein for angiogenesis genes or proteins. In particular these sequences and the proteins they encode find 3 0 use in marking or identifying agent treated cells. In addition, antibodies can be raised against the agent induced proteins and used to target novel therapeutics to the treated angiogenesis tissue sample.

Thus, in one embodiment, a candidate agent is administered to a population of angiogenic cells, that thus has an associated angiogenesis expression profile. By "administration" or "contacting" herein is meant that the candidate agent is added to the cells in such a manner as to allow the agent to act upon the cell, whether by uptake and intracellular action, or by action at the cell surface. In some embodiments, nucleic acid encoding a proteinaceous candidate agent (i.e. a peptide) may be put into a viral construct such as a retroviral construct and added to the cell, such that expression of the peptide agent is accomplished; see PCT US97/01019, hereby expressly incorporated by reference.
Once the candidate agent has been administered to the cells, the cells can be washed if desired and are allowed to incubate under preferably physiological conditions for some period of time. The cells are then harvested and a new gene expression profile is generated, as outlined herein.
Thus, for example, angiogenesis tissue may be screened for agents that reduce or suppress the angiogenesis phenotype. A change in at least one gene of the expression profile indicates that the agent has an effect on angiogenesis activity. By defining such a signature for the angiogenesis phenotype, screens for new drugs that alter the phenotype can be devised. With this approach, the drug target need not be known and need not be represented in the original expression screening platform, nor does the level of transcript for the target protein need to change.
In a preferred embodiment, as outlined above, screens may be done on individual genes and gene products (proteins). That is, having identified a particular differentially expressed gene as important in a particular state, screening of modulators of either the expression of the gene or the gene product 2 0 itself can be done. The gene products of differentially expressed genes are sometimes referred to herein as "angiogenesis proteins". In preferred embodiments the angiogenesis protein is as depicted in Figures 4, 8, 13, 18, and 22 or encoded by the sequences shown in figures 2, 3, 7, 12, 17, 21 and 23. The angiogenesis protein may be a fragment, or alternatively, be the full length protein to a fragment shown herein.
2 5 Preferably, the angiogenesis protein is a fragment of approximately 14 to 24 amino acids long. More preferably the fragment is a soluble fragment.
In a preferred embodiment, the fragment is from AAA1. Preferably, the fragment includes a non-transmembrane region. In a preferred embodiment, the AAA1 fragment has an N-terminal Cys to aid in solubility. Preferably, the fragment is selected from AAA1 p1 and AAA1 p2.

In a preferred embodiment, the fragment is charged and from the c-terminus of AAA4. In one embodiment, the c-terminus of the fragment is kept as a free acid and the n-terminus is a free amine to aid in coupling, i.e., to cysteine. In one embodiment the fragment is an internal peptide overlapping hydrophilic stretch of AAA4. In a preferred embodiment, the termini is blocked. Preferably, the fragment of AAA4 is selected from AAA4p1 or AAA4p2. In another preferred embodiment, the fragment is a novel fragment from the N-terminal. In one embodiment, the fragment excludes sequence outside of the N-terminal, in another embodiment, the fragment includes at least a portion of the N-terminal. "N-terminal" is used interchangeably herein with "N-terminus"
which is further described above.
In one embodiment the angiogenesis proteins are conjugated to an immunogenic agent as discussed herein. In one embodiment the angiogenesis protein is conjugated to BSA.
Thus, in a preferred embodiment, screening for modulators of expression of specific genes can be done. This will be done as outlined above, but in general the expression of only one or a few genes are evaluated.
In a preferred embodiment, screens are designed to first find candidate agents that can bind to differentially expressed proteins, and then these agents may be used in assays that evaluate the ability of the candidate agent to modulate differentially expressed activity.
Thus, as will be appreciated by those in the art, there are a number of different assays which may be run;
binding assays and activity assays.
2 0 In a preferred embodiment, binding assays are done. In general, purified or isolated gene product is used; that is, the gene products of one or more differentially expressed nucleic acids are made. In general, this is done as is known in the art. For example, antibodies are generated to the protein gene products, and standard immunoassays are run to determine the amount of protein present.
Alternatively, cells comprising the angiogenesis proteins can be used in the assays.
2 5 Thus, in a preferred embodiment, the methods comprise combining an angiogenesis protein and a candidate bioactive agent, and determining the binding of the candidate agent to the angiogenesis protein. Preferred embodiments utilize the human angiogenesis protein, although other mammalian proteins may also be used, for example for the development of animal models of human disease. In some embodiments, as outlined herein, variant or derivative angiogenesis proteins may be used.

Generally, in a preferred embodiment of the methods herein, the angiogenesis protein or the candidate agent is non-diffusably bound to an insoluble support having isolated sample receiving areas (e.g. a microtiter plate, an array, etc.). The insoluble supports may be made of any composition to which the compositions can be bound, is readily separated from soluble material, and is otherwise compatible with the overall method of screening. The surface of such supports may be solid or porous and of any convenient shape. Examples of suitable insoluble supports include microtiter plates, arrays, membranes and beads. These are typically made of glass, plastic (e.g., polystyrene), polysaccharides, nylon or nitrocellulose, teflonT"', etc. Microtiter plates and arrays are especially convenient because a large number of assays can be carried out simultaneously, using small amounts of reagents and samples. The particular manner of binding of the composition is not crucial so long as it is compatible with the reagents and overall methods of the invention, maintains the activity of the composition and is nondiffusable. Preferred methods of binding include the use of antibodies (which do not sterically block either the ligand binding site or activation sequence when the protein is bound to the support), direct binding to "sticky" or ionic supports, chemical crosslinking, the synthesis of the protein or agent on the surface, etc. Following binding of the protein or agent, excess unbound material is removed by washing. The sample receiving areas may then be blocked through incubation with bovine serum albumin (BSA), casein or other innocuous protein or other moiety.
In a preferred embodiment, the angiogenesis protein is bound to the support, and a candidate bioactive agent is added to the assay. Alternatively, the candidate agent is bound to the support and 2 0 the angiogenesis protein is added. Novel binding agents include specific antibodies, non-natural binding agents identified in screens of chemical libraries, peptide analogs, etc. Of particular interest are screening assays for agents that have a low toxicity for human cells. A
wide variety of assays may be used for this purpose, including labeled in vitro protein-protein binding assays, electrophoretic mobility shift assays, immunoassays for protein binding, functional assays (phosphorylation assays, etc.) and the like.
The determination of the binding of the candidate bioactive agent to the angiogenesis protein may be done in a number of ways. In a preferred embodiment, the candidate bioactive agent is labelled, and binding determined directly. For example, this may be done by attaching all or a portion of the angiogenesis protein to a solid support, adding a labelled candidate agent (for example a fluorescent 3 0 label), washing off excess reagent, and determining whether the label is present on the solid support.
Various blocking and washing steps may be utilized as is known in the art.
By "labeled" herein is meant that the compound is either directly or indirectly labeled with a label which provides a detectable signal, e.g. radioisotope, fluorescers, enzyme, antibodies, particles such as magnetic particles, chemiluminescers, or specific binding molecules, etc.
Specific binding molecules include pairs, such as biotin and streptavidin, digoxin and antidigoxin etc.
For the specific binding members, the complementary member would normally be labeled with a molecule which provides for detection, in accordance with known procedures, as outlined above. The label can directly or indirectly provide a detectable signal.
In some embodiments, only one of the components is labeled. For example, the proteins (or proteinaceous candidate agents) may be labeled at tyrosine positions using '251, or with fluorophores.
Alternatively, more than one component may be labeled with different labels;
using'z51 for the proteins, for example, and a fluorophor for the candidate agents.
In a preferred embodiment, the binding of the candidate bioactive agent is determined through the use of competitive binding assays. In this embodiment, the competitor is a binding moiety known to bind to the target molecule (i.e. angiogenesis), such as an antibody, peptide, binding partner, ligand, etc.
Under certain circumstances, there may be competitive binding as between the bioactive agent and the binding moiety, with the binding moiety displacing the bioactive agent.
In one embodiment, the candidate bioactive agent is labeled. Either the candidate bioactive agent, or the competitor, or both, is added first to the protein for a time sufficient to allow binding, if present.
Incubations may be performed at any temperature which facilitates optimal activity, typically between 4 and 40°C. Incubation periods are selected for optimum activity, but may also be optimized to facilitate rapid high through put screening. Typically between 0.1 and 1 hour will be sufficient. Excess reagent 2 0 is generally removed or washed away. The second component is then added, and the presence or absence of the labeled component is followed, to indicate binding.
In a preferred embodiment, the competitor is added first, followed by the candidate bioactive agent.
Displacement of the competitor is an indication that the candidate bioactive agent is binding to the angiogenesis protein and thus is capable of binding to, and potentially modulating, the activity of the 2 5 angiogenesis protein. In this embodiment, either component can be labeled.
Thus, for example, if the competitor is labeled, the presence of label in the wash solution indicates displacement by the agent.
Alternatively, if the candidate bioactive agent is labeled, the presence of the label on the support indicates displacement.
In an alternative embodiment, the candidate bioactive agent is added first, with incubation and 3 0 washing, followed by the competitor. The absence of binding by the competitor may indicate that the bioactive agent is bound to the angiogenesis protein with a higher affinity.
Thus, if the candidate bioactive agent is labeled, the presence of the label on the support, coupled with a lack of competitor binding, may indicate that the candidate agent is capable of binding to the angiogenesis protein.
In a preferred embodiment, the methods comprise differential screening to identity bioactive agents that are capable of modulating the activitity of the angiogenesis proteins. In this embodiment, the methods comprise combining an angiogenesis protein and a competitor in a first sample. A second sample comprises a candidate bioactive agent, an angiogenesis protein and a competitor. The binding of the competitor is determined for both samples, and a change, or difference in binding between the two samples indicates the presence of an agent capable of binding to the angiogenesis protein and potentially modulating its activity. That is, if the binding of the competitor is different in the second sample relative to the first sample, the agent is capable of binding to the angiogenesis protein.
Alternatively, a preferred embodiment utilizes differential screening to identify drug candidates that bind to the native angiogenesis protein, but cannot bind to modified angiogenesis proteins. The structure of the angiogenesis protein may be modeled, and used in rational drug design to synthesize agents that interact with that site. Drug candidates that affect angiogenesis bioactivity are also identified by screening drugs for the ability to either enhance or reduce the activity of the protein.
Positive controls and negative controls may be used in the assays. Preferably all control and test samples are performed in at least triplicate to obtain statistically significant results. Incubation of all samples is for a time sufficient for the binding of the agent to the protein.
Following incubation, all samples are washed free of non-specifically bound material and the amount of bound, generally 2 0 labeled agent determined. For example, where a radiolabel is employed, the samples may be counted in a scintillation counter to determine the amount of bound compound.
A variety of other reagents may be included in the screening assays. These include reagents like salts, neutral proteins, e.g. albumin, detergents, etc which may be used to facilitate optimal protein-protein binding and/or reduce non-specific or background interactions.
Also reagents that 2 5 otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may be used. The mixture of components may be added in any order that provides for the requisite binding.
Screening for agents that modulate the activity of angiogenesis proteins may also be done. In a preferred embodiment, methods for screening for a bioactive agent capable of modulating the activity 3 0 of angiogenesis proteins comprise the steps of adding a candidate bioactive agent to a sample of angiogenesis proteins, as above, and determining an alteration in the biological activity of angiogenesis proteins. "Modulating the activity of angiogenesis proteins"
includes an increase in activity, a decrease in activity, or a change in the type or kind of activity present. Thus, in this embodiment, the candidate agent should both bind to angiogenesis proteins(although this may not be necessary), and alter its biological or biochemical activity as defined herein. The methods include both in vitro screening methods, as are generally outlined above, and in vivo screening of cells for alterations in the presence, distribution, activity or amount of angiogenesis proteins.
Thus, in this embodiment, the methods comprise combining an angiogenesis sample and a candidate bioactive agent, and evaluating the effect on angiogenesis. By "angiogenesis activity" or grammatical equivalents herein is meant one of angiogenesis's biological activities, including, but not limited to, its role in angiogenesis. In one embodiment, angiogenesis activity includes activation of AAA4, AAA1, Edg-1, alpha 5 beta1 integrin, endomucin and matrix metalloproteinase 10. An inhibitor of angiogenesis activity is the inhibition of any one or more angiogenesis activities.
In a preferred embodiment, the activity of the angiogenesis protein is increased; in another preferred embodiment, the activity of the angiogenesis protein is decreased. Thus, bioactive agents that are antagonists are preferred in some embodiments, and bioactive agents that are agonists may be preferred in other embodiments.
In a preferred embodiment, the invention provides methods for screening for bioactive agents capable of modulating the activity of an angiogenesis protein. The methods comprise adding a candidate bioactive agent, as defined above, to a cell comprising angiogenesis proteins.
Preferred cell types 2 0 include almost any cell. The cells contain a recombinant nucleic acid that encodes an angiogenesis protein. In a preferred embodiment, a library of candidate agents are tested on a plurality of cells.
In one aspect, the assays are evaluated in the presence or absence or previous or subsequent exposure of physiological signals, for example hormones, antibodies, peptides, antigens, cytokines, growth factors, action potentials, pharmacological agents including chemotherapeutics, radiation, 2 5 carcinogenics, or other cells (i.e. cell-cell contacts). In another example, the determinations are determined at different stages of the cell cycle process.
In this way, bioactive agents are identified. Compounds with pharmacological activity are able to enhance or interfere with the activity of the angiogenesis protein. In one embodiment, "angiogenesis protein activity" as used herein includes at least one of the following:
angiogenesis protein activity as 3 0 defined herein, binding to Edg-1, activation of Edg-1, or activation of substrates of Edg-1. In one embodiment, angiogenesis activity is defined as the unregulated proliferation of angiogenic tissue, or the growth of arteries in tissue. In one aspect, angiogenesis activity as defined herein is related to the activity of Edg-1 in the upregulation of Edg-1 in angiogenic tissue.
In another embodiment, angiogenesis protein activity includes at least one of the following:
angiogenesis activity, binding to one of AAA4, AAA1, Edg-1, alpha 5 beta 1 integrin, endomucin, matrix metalloproteinase 10, or activation of substrates of AAA4, AAA1, Edg-1, alpha 5 beta 1 integrin, endomucin, matrix metalloproteinase 10, respectively. In one preferred embodiment, AAA1 comprises its N-terminal end. In one aspect, angiogenesis activity as defined herein is related to the activity of AAA4, AAA1, Edg-1, alpha 5 beta 1 integrin, endomucin, matrix metalloproteinase 10, in the upregulation of AAA4, AAA1, Edg-1, alpha 5 beta 1 integrin, endomucin, matrix metalloproteinase 10, respectively in angiogenesis tissue.
In one embodiment, a method of inhibiting angiogenic cell division is provided. The method comprises administration of a angiogenesis inhibitor.
In another embodiment, a method of inhibiting angiogenesis is provided. The method comprises administration of an angiogenesis inhibitor.
In a further embodiment, methods of treating cells or individuals with angiogenesis are provided. The method comprises administration of an angiogenesis inhibitor.
In one embodiment, an angiogenesis inhibitor is an antibody as discussed above. In another embodiment, the angiogenesis inhibitor is an antisense molecule. Antisense molecules as used herein include antisense or sense oligonucleotides comprising a singe-stranded nucleic acid sequence 2 0 (either RNA or DNA) capable of binding to target mRNA (sense) or DNA
(antisense) sequences for angiogenesis molecules. A preferred antisense molecule is for AAA4, AAA1, Edg-1, alpha 5 beta 1 integrin, endomucin, or matrix metalloproteinase 10, more preferable the angiogenesis sequences in Table 5, or for a ligand or activator thereof. A most preferred antisense molecule is for Edg-1 or for a ligand or activator thereof. Antisense or sense oligonucleotides, according to the present invention, 2 5 comprise a fragment generally at least about 14 nucleotides, preferably from about 14 to 30 nucleotides. The ability to derive an antisense or a sense oligonucleotide, based upon a cDNA
sequence encoding a given protein is described in, for example, Stein and Cohen (Cancer Res.
48:2659, 1988) and van der Krol et al. (BioTechni4ues 6:958, 1988).
Antisense molecules may be introduced into a cell containing the target nucleotide sequence by 3 0 formation of a conjugate with a ligand binding molecule, as described in WO 91/04753. Suitable ligand binding molecules include, but are not limited to, cell surface receptors, growth factors, other cytokines, or other ligands that bind to cell surface receptors. Preferably, conjugation of the ligand binding molecule does not substantially interfere with the ability of the ligand binding molecule to bind to its corresponding molecule or receptor, or block entry of the sense or antisense oligonucleotide or its conjugated version into the cell. Alternatively, a sense or an antisense oligonucleotide may be introduced into a cell containing the target nucleic acid sequence by formation of an oligonucleotide-lipid complex, as described in WO 90/10448. It is understood that the use of antisense molecules or knock out and knock in models may also be used in screening assays as discussed above, in addition to methods of treatment.
The compounds having the desired pharmacological activity may be administered in a physiologically acceptable carrier to a host, as previously described. The agents may be administered in a variety of ways, orally, parenterally e.g., subcutaneously, intraperitoneally, intravascularly, etc. Depending upon the manner of introduction, the compounds may be formulated in a variety of ways. The concentration of therapeutically active compound in the formulation may vary from about 0.1-100 wt.°/a. The agents may be administered alone or in combination with other treatments, i.e., radiation.
The pharmaceutical compositions can be prepared in various forms, such as granules, tablets, pills, suppositories, capsules, suspensions, salves, lotions and the like.
Pharmaceutical grade organic or inorganic carriers and/or diluents suitable for oral and topical use can be used to make up compositions containing the therapeutically-active compounds. Diluents known to the art include 2 0 aqueous media, vegetable and animal oils and fats. Stabilizing agents, wetting and emulsifying agents, salts for varying the osmotic pressure or buffers for securing an adequate pH value, and skin penetration enhancers can be used as auxiliary agents.
Without being bound by theory, it appears that the various angiogenesis sequences are important in angiogenesis. Accordingly, disorders based on mutant or variant angiogenesis genes may be determined. In one embodiment, the invention provides methods for identifying cells containing variant angiogenesis genes comprising determining all or part of the sequence of at least one endogeneous angiogenesis genes in a cell. As will be appreciated by those in the art, this may be done using any number of sequencing techniques. In a preferred embodiment, the invention provides methods of identifying the angiogenesis genotype of an individual comprising determining all or part of 3 0 the sequence of at least one angiogenesis gene of the individual. This is generally done in at least one tissue of the individual, and may include the evaluation of a number of tissues or different samples of the same tissue. The method may include comparing the sequence of the sequenced angiogenesis gene to a known angiogenesis gene, i.e. a wild-type gene.

The sequence of all or part of the angiogenesis gene can then be compared to the sequence of a known angiogenesis gene to determine if any differences exist. This can be done using any number of known homology programs, such as Bestfit, etc. In a preferred embodiment, the presence of a a difference in the sequence between the angiogenesis gene of the patient and the known angiogenesis gene is indicative of a disease state or a propensity for a disease state, as outlined herein.
In a preferred embodiment, the angiogenesis genes are used as probes to determine the number of copies of the angiogenesis gene in the genome.
In another preferred embodiment, the angiogenesis genes are used as probes to determine the chromosomal localization of the angiogenesis genes. Information such as chromosomal localization finds use in providing a diagnosis or prognosis in particular when chromosomal abnormalities such as translocations, and the like are identified in the angiogenesis gene locus.
Thus, in one embodiment, methods of modulating angiogenesis in cells or organisms are provided. In one embodiment, the methods comprise administering to a cell an anti-angiogenesis antibody that reduces or eliminates the biological activity of an endogeneous angiogenesis protein. Alternatively, the methods comprise administering to a cell or organism a recombinant nucleic acid encoding an angiogenesis protein. As will be appreciated by those in the art, this may be accomplished in any number of ways. In a preferred embodiment, for example when the angiogenesis sequence is down-regulated in angiogenesis, the activity of the angiogenesis gene is increased by increasing the amount of angiogenesis in the cell, for example by overexpressing the endogeneous angiogenesis or by 2 0 administering a gene encoding the angiogenesis sequence, using known gene-therapy techniques, for example. In a preferred embodiment, the gene therapy techniques include the incorporation of the exogenous gene using enhanced homologous recombination (EHR), for example as described in PCT/US93/03868, hereby incorporated by reference in its entireity.
Alternatively, for example when the angiogenesis sequence is up-regulated in angiogenesis, the activity of the endogeneous angiogenesis gene is decreased, for example by the administration of a angiogenesis antisense nucleic acid.
In one embodiment, the angiogenesis proteins of the present invention may be used to generate polyclonal and monoclonal antibodies to angiogenesis proteins, which are useful as described herein.
Similarly, the angiogenesis proteins can be coupled, using standard technology, to affinity 3 0 chromatography columns. These columns may then be used to purify angiogenesis antibodies. In a preferred embodiment, the antibodies are generated to epitopes unique to a angiogenesis protein; that is, the antibodies show little or no cross-reactivity to other proteins. These antibodies find use in a number of applications. For example, the angiogenesis antibodies may be coupled to standard affinity chromatography columns and used to purify angiogenesis proteins. The antibodies may also be used as blocking polypeptides, as outlined above, since they will specifically bind to the angiogenesis protein.
In one embodiment, a therapeutically effective dose of an angiogenesis proteins and modulator thereof is administered to a patient. By "therapeutically effective dose"
herein is meant a dose that produces the effects for which it is administered. The exact dose will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques. As is known in the art, adjustments for angiogenesis degradation, systemic versus localized delivery, and rate of new protease synthesis, as well as the age, body weight, general health, sex, diet, time of administration, drug interaction and the severity of the condition may be necessary, and will be ascertainable with routine experimentation by those skilled in the art.
A "patient" for the purposes of the present invention includes both humans and other animals, particularly mammals, and organisms. Thus the methods are applicable to both human therapy and veterinary applications. In the preferred embodiment the patient is a mammal, and in the most preferred embodiment the patient is human.
The administration of the angiogenesis proteins and modulators thereof of the present invention can be done in a variety of ways as discussed above, including, but not limited to, orally, subcutaneously, intravenously, intranasally, transdermally, intraperitoneally, intramuscularly, intrapulmonary, vaginally, 2 0 rectally, or intraocularly. In some instances, for example, in the treatment of wounds and inflammation, the angiogenesis proteins and modulators may be directly applied as a solution or spray.
The pharmaceutical compositions of the present invention comprise an angiogenesis protein in a form suitable for administration to a patient. In the preferred embodiment, the pharmaceutical compositions are in a water soluble form, such as being present as pharmaceutically acceptable salts, which is meant to include both acid and base addition salts. "Pharmaceutically acceptable acid addition salt"
refers to those salts that retain the biological effectiveness of the free bases and that are not biologically or otherwise undesirable, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malefic acid, malonic acid, succinic 3 0 acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like.
"Pharmaceutically acceptable base addition salts" include those derived from inorganic bases such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Particularly preferred are the ammonium, potassium, sodium, calcium, and magnesium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine.
The pharmaceutical compositions may also include one or more of the following:
carrier proteins such as serum albumin; buffers; fillers such as microcrystalline cellulose, lactose, corn and other starches;
binding agents; sweeteners and other flavoring agents; coloring agents; and polyethylene glycol.
Additives are well known in the art, and are used in a variety of formulations.
In a preferred embodiment, angiogenesis proteins and modulators are administered as therapeutic agents, and can be formulated as outlined above. Similarly, angiogenesis genes (including both the full-length sequence, partial sequences, or regulatory sequences of the angiogenesis coding regions) can be administered in gene therapy applications, as is known in the art.
These angiogenesis genes can include antisense applications, either as gene therapy (i.e. for incorporation into the genome) or as antisense compositions, as will be appreciated by those in the art.
In a preferred embodiment, angiogenesis genes are administered as DNA
vaccines, either single genes or combinations of angiogenesis genes. Naked DNA vaccines are generally known in the art.
Brower, Nature Biotechnology, 16:1304-1305 (1998).
2 0 In one embodiment, angiogenesis genes of the present invention are used as DNA vaccines.
Methods for the use of genes as DNA vaccines are well known to one of ordinary skill in the art, and include placing an angiogenesis gene or portion of an angiogenesis gene under the control of a promoter for expression in an angiogenesis patient. The angiogenesis gene used for DNA vaccines can encode full-length angiogenesis proteins, but more preferably encodes portions of the angiogenesis proteins including peptides derived from the angiogenesis protein. In a preferred embodiment a patient is immunized with a DNA vaccine comprising a plurality of nucleotide sequences derived from an angiogenesis gene. Similarly, it is possible to immunize a patient with a plurality of angiogenesis genes or portions thereof as defined herein. Without being bound by theory, expression of the polypeptide encoded by the DNA vaccine, cytotoxic T-cells, helper T-cells and 3 0 antibodies are induced which recognize and destroy or eliminate cells expressing angiogenesis proteins.

In a preferred embodiment, the DNA vaccines include a gene encoding an adjuvant molecule with the DNA vaccine. Such adjuvant molecules include cytokines that increase the immunogenic response to the angiogenesis polypeptide encoded by the DNA vaccine. Additional or alternative adjuvants are known to those of ordinary skill in the art and find use in the invention.
In another preferred embodiment angiogenesis genes find use in generating animal models of angiogenesis. As is appreciated by one of ordinary skill in the art, when the angiogenesis gene identified is repressed or diminished in angiogenesis tissue, gene therapy technology wherein antisense RNA directed to the angiogenesis gene will also diminish or repress expression of the gene.
An animal generated as such serves as an animal model of angiogenesis that finds use in screening bioactive drug candidates. Similarly, gene knockout technology, for example as a result of homologous recombination with an appropriate gene targeting vector, will result in the absence of the angiogenesis protein. When desired, tissue-specific expression or knockout of the angiogenesis protein may be necessary.
It is also possible that the angiogenesis protein is overexpressed in angiogenesis. As such, transgenic animals can be generated that overexpress the angiogenesis protein.
Depending on the desired expression level, promoters of various strengths can be employed to express the transgene.
Also, the number of copies of the integrated transgene can be determined and compared for a determination of the expression level of the transgene. Animals generated by such methods find use as animal models of angiogenesis and are additionally useful in screening for bioactive molecules to 2 0 treat angiogenesis.
It is understood that the examples described above in no way serve to limit the true scope of this invention, but rather are presented for illustrative purposes. All references and sequences of accession numbers cited herein are incorporated by reference in their entirety.
EXAMPLES
2 5 Example 1 Tissue Preparation, Labeling Chips, and Fingerprints Purify total RNA from tissue using TRlzol Reagent Estimate tissue weight. Homogenize tissue samples in 1 ml of TRlzol per 50mg of tissue using a Polytron 3100 homogenizer. The generator/probe used depends upon the tissue size. A

generator that is too large for the amount of tissue to be homogenized will cause a loss of sample and lower RNA yield. Use the 20mm generator for tissue weighing more than 0.6g. If the working volume is greater than 2m1, then homogenize tissue in a 15m1 polypropylene tube (Falcon 2059).
Fill tube no greater than 10m1.
HOMOGENIZATION
Before using generator, it should have been cleaned after last usage by running it through soapy H20 and rinsing thoroughly. Run through with EtOH to sterilize. Keep tissue frozen until ready.
Add TRlzol directly to frozen tissue then homogenize.
Following homogenization, remove insoluble material from the homogenate by centrifugation at 7500 x g for 15 min. in a Sorvall superspeed or 12,000 x g for 10 min. in an Eppendorf centrifuge at 4°C. Transfer the cleared homogenate to a new tube(s). The samples may be frozen now at -60 to -70°C (and kept for at least one month) or you may continue with the purification.
PHASE SEPARATION
Incubate the homogenized samples for 5 minutes at room temperature.
Add 0.2m1 of chloroform per 1 ml of TRlzol reagent used in the original homogenization.
Cap tubes securely and shake tubes vigorously by hand (do not vortex) for 15 seconds.
Incubate samples at room temp. for 2-3 minutes. Centrifuge samples at 6500rpm in a Sorvall superspeed for 30 min. at 4°C. (You may spin at up to 12,000 x g for 10 min. but you risk breaking your tubes in the centrifuge.) Transfer the aqueous phase to a fresh tube. Save the organic phase if isolation of DNA or protein is desired. Add 0.5m1 of isopropyl alcohol per 1 ml of TRlzol reagent used in the original homogenization. Cap tubes securely and invert to mix. Incubate samples at room temp. for 10 minutes. Centrifuge samples at 6500rpm in Sorvall for 20min. at 4°C.

Pour off the supernate. Wash pellet with cold 75% ethanol. Use 1 ml of 75%
ethanol per 1 ml of TRlzol reagent used in the initial homogenization. Cap tubes securely and invert several times to loosen pellet. (Do not vortex). Centrifuge at <8000rpm (<7500 x g) for 5 minutes at 4°C.
Pour off the wash. Carefully transfer pellet to an eppendorf tube (let it slide down the tube into the 3 0 new tube and use a pipet tip to help guide it in if necessary). Depending on the volumes you are working with, you can decide what size tubes) you want to precipitate the RNA
in. When I tried WO 01/11086 PCT/~1500/22061 leaving the RNA in the large 15m1 tube, it took so long to dry (i.e. it did not dry) that I eventually had to transfer it to a smaller tube. Let pellet dry in hood. Resuspend RNA in an appropriate volume of DEPC H20. Try for 2-5ug/ul. Take absorbance readings.
Purify poly A+ mRNA from total RNA or clean up total RNA with Qiagen' s RNeasy kit Purification of poly A' mRNA from total RNA. Heat oligotex suspension to 37°C and mix immediately before adding to RNA. Incubate Elution Buffer at 70°C. Warm up 2 x Binding Buffer at 65°C if there is precipitate in the buffer. Mix total RNA with DEPC-treated water, 2 x Binding Buffer, and Oligotex according to Table 2 on page 16 of the Oligotex Handbook.
Incubate for 3 minutes at 65°C. Incubate for 10 minutes at room temperature.
Centrifuge for 2 minutes at 14,000 to 18,000 g. If centrifuge has a "soft setting," then use it.
Remove supernatant without disturbing Oligotex pellet. A little bit of solution can be left behind to reduce the loss of Oligotex. Save sup until certain that satisfactory binding and elution of poly A+
mRNA has occurred.
Gently resuspend in Wash Buffer OW2 and pipet onto spin column. Centrifuge the spin column at full speed (soft setting if possible) for 1 minute.
Transfer spin column to a new collection tube and gently resuspend in Wash Buffer OW2 and centrifuge as describe herein.
Transfer spin column to a new tube and elute with 20 to 100 u1 of preheated (70°C) Elution Buffer.
2 0 Gently resuspend Oligotex resin by pipetting up and down. Centrifuge as above. Repeat elution with fresh elution buffer or use first eluate to keep the elution volume low.
Read absorbance, using diluted Elution Buffer as the blank.
Before proceeding with cDNA synthesis, the mRNA must be precipitated.
Some component leftover or in the Elution Buffer from the Oligotex purification procedure will 2 5 inhibit downstream enzymatic reactions of the mRNA.
Ethanol Precipitation Add 0.4 vol. of 7.5 M NH40Ac + 2.5 vol. of cold 100% ethanol. Precipitate at -20°C 1 hour to overnight (or 20-30 min. at -70°C). Centrifuge at 14,000-16,000 x g for 30 minutes at 4°C. Wash pellet with 0.5m1 of 80%ethanol (-20°C) then centrifuge at 14,000-16,000 x g for 5 minutes at room temperature. Repeat 80% ethanol wash. Dry the last bit of ethanol from the pellet in the hood.
(Do not speed vacuum). Suspend pellet in DEPC HZO at 1 ug/ul concentration.
Clean up total RNA using Qiagen's RNeasy kit Add no more than 100ug to an RNeasy column. Adjust sample to.a volume of 100u1 with RNase-free water. Add 350u1 Buffer RLT then 250u1 ethanol (100%) to the sample. Mix by pipetting (do not centrifuge) then apply sample to an RNeasy mini spin column. Centrifuge for 15 sec at >10,OOOrpm. If concerned about yield, re-apply flowthrough to column and centrifuge again.
Transfer column to a new 2-ml collection tube. Add 500u1 Buffer RPE and centrifuge for 15 sec at >10,OOOrpm. Discard flowthrough. Add 500u1 Buffer RPE and centrifuge for 15 sec at >10,OOOrpm. Discard flowthrough then centrifuge for 2 min at maximum speed to dry column membrane. Transfer column to a new 1.5-ml collection tube and apply 30-50u1 of RNase-free water directly onto column membrane. Centrifuge 1 min at >10,OOOrpm. Repeat elution.
Take absorbance reading. If necessary, ethanol precipitate with ammonium acetate and 2.5X
volume 100% ethanol.
Make cDNA using Gibco's "Superscript Choice System for cDNA Synthesis" kit First Strand cDNA Synthesis Use 5ug of total RNA or 1 ug of polyA+ mRNA as starting material. For total RNA, use 2u1 of Superscript RT. For polyA+ mRNA, use 1 u1 of Superscript RT. Final volume of first strand 2 0 synthesis mix is 20u1. RNA must be in a volume no greater than 10u1.
Incubate RNA with 1 u1 of 100pmol T7-T24 oligo for 10 min at 70C. On ice, add 7 u1 of: 4u1 5X 15' Strand Buffer, 2u1 of 0.1 M DTT, and 1 u1 of 10mM dNTP mix. Incubate at 37C for 2 min then add Superscript RT
Incubate at 37C for 1 hour.
Second Strand Synthesis 2 5 Place 1 S' strand reactions on ice.
Add: 91 u1 DEPC H20 30u1 5X 2"d Strand Buffer 3u1 10mM dNTP mix 1 u1 10U/ul E.coli DNA Ligase 3 0 4u1 10U/ul E.coli DNA Polymerase 1 u1 2U/ul RNase H
Make the above into a mix if there are more than 2 samples. Mix and incubate 2 hours at 16C.

Add 2u1 T4 DNA Polymerase. Incubate 5 min at 16C. Add 10u1 of 0.5M EDTA
Clean up cDNA
PhenoI:Chloroform:lsoamyl Alcohol (25:24:1 ) purification using Phase-Lock gel tubes:
Centrifuge PLG tubes for 30 sec at maximum speed. Transfer cDNA mix to PLG
tube. Add equal volume of phenol:chloroform:isamyl alcohol and shake vigorously (do not vortex). Centrifuge 5 minutes at maximum speed. Transfer top aqueous solution to a new tube. Ethanol precipitate:
add 7.5X 5M NH40ac and 2.5X volume of 100% ethanol. Centrifuge immediately at room temp.
for 20 min, maximum speed. Remove sup then wash pellet 2X with cold 80%
ethanol. Remove as much ethanol wash as possible then let pellet air dry. Resuspend pellet in 3u1 RNase-free water.
In vitro Transcription (IVT) and labeling with biotin Pipet 1.5u1 of cDNA into a thin-wall PCR tube.
Make NTP labeling mix:
Combine at room temperature: 2u1 T7 10xATP (75mM) (Ambion) 2u1 T7 10xGTP (75mM) (Ambion) 1.5u1 T7 10xCTP (75mM) (Ambion) 1.5u1 T7 10xUTP (75mM) (Ambion) 3.75u1 10mM Bio-11-UTP (Boehringer-Mannheim/Roche or Enzo) 2 0 3.75u1 1 OmM Bio-16-CTP (Enzo) 2u1 10x T7 transcription buffer (Ambion) 2u1 10x T7 enzyme mix (Ambion) Final volume of total reaction is 20u1. Incubate 6 hours at 37C in a PCR
machine.
RNeasy clean-up of IVT product 2 5 Follow previous instructions for RNeasy columns or refer to Qiagen's RNeasy protocol handbook.
cRNA will most likely need to be ethanol precipitated. Resuspend in a volume compatible with the fragmentation step.

15 ug of labeled RNA is usually fragmented. Try to minimize the fragmentation reaction volume;
a 10 u1 volume is recommended but 20 u1 is all right. Do not go higher than 20 u1 because the magnesium in the fragmentation buffer contributes to precipitation in the hybridization buffer.
Fragment RNA by incubation at 94 C for 35 minutes in 1 x Fragmentation buffer.
5 x Fragmentation buffer:
200 mM Tris-acetate, pH 8.1 500 mM KOAc 150 mM MgOAc The labeled RNA transcript can be analyzed before and after fragmentation.
Samples can be heated to 65C for 15 minutes and electrophoresed on 1 % agarose/TBE gels to get an approximate idea of the transcript size range Hybridization 200 u1 (10ug cRNA) of a hybridization mix is put on the chip. If multiple hybridizations are to be done (such as cycling through a 5 chip set), then it is recommended that an initial hybridization mix of 300 u1 or more be made.
Hybrization Mix: fragment labeled RNA (50ng/ul final cone) 50 pM 948-b control oligo 1.5 pM BioB
5 pM BioC
2 0 25 pM BioD
100 pM CRE
0.1mg/ml herring sperm DNA
0.5mg/ml acetylated BSA
to 300 u1 with 1xMES hyb. buffer 2 5 The instruction manuals for the products used herein are incorporated herein in their entirety.
Labeling Protocol Provided Herein Hybridization reaction:
Start with non-biotinylated IVT (purified by RNeasy columns) (see example 1 for steps from tissue to IVT) 3 0 IVT antisense RNA; 4 fig: NI

Random Hexamers (1 Ng/~tl): 4 ~I
HzO: ~I
14 ~I
- Incubate 70°C, 10 min. Put on ice.
Reverse transcription:

5X First Strand (BRL) 6 NI
buffer:

0.1 M DTT: 3 NI

50X dNTP mix: 0.6 NI

H20: 2.4 ~I

Cy3 or Cy5 dUTP (1 mM):3 NI

SS RT II (BRL): 1 NI

16 ~I
- Add to hybridization reaction.
- Incubate 30 min., 42°C.
- Add 1 NI SSII and let go for another hour.
Put on ice.
50X dNTP mix (25mM of cold dATP, dCTP, and dGTP, 10mM of dTTP: 25 ~I each of 100mM
2 0 dATP, dCTP, and dGTP; 10 ~I of 100mM dTTP to 15 ~I H20. dNTPs from Pharmacia) RNA degradation:
86 ~I HZO
- Add 1.5 ~I 1 M NaOH/ 2mM EDTA, incubate at 65°C, 10 min. 10 ~I 10N
NaOH
4 NI 50mM EDTA
2 5 U-Con 30 500 NI TE/sample spin at 70008 for 10 min, save flow through for purification Qiagen purification:
-suspend u-con recovered material in 500N1 buffer PB
-proceed w/ normal Qiagen protocol 3 0 DNAse digest:
- Add 1 ~I of 1/100 dil of DNAse/30N1 Rx and incubate at 37°C for 15 min.
-5 min 95°C to denature enzyme Sample preparation:
- Add:
Cot-1 DNA: 10 NI
50X dNTPs: 1 ~I
20X SSC: 2.3 ~1 Na pyro phosphate: 7.5 NI
10mg/ml Herring sperm DNA 1u1 of 1/10 dilution 21.8 final vol.
- Dry down in speed vac.
- Resuspend in 15 ~I H20.
- Add 0.38 ~I 10% SDS.
- Heat 95°C, 2 min.
- Slow cool at room temp, for 20 min.
Put on slide and hybridize overnight at 64°C.
Washing after the hybridization:
3X SSC/0.03% SDS: 2 min. 37.5 mls 20X SSC+0.75m1s 10% SDS in 250m1s Hz0 1X SSC: 5 min. 12.5 mls 20X SSC in 250m1s H20 0.2X SSC: 5 min. 2.5 mls 20X SSC in 250m1s H20 Dry slides in centrifuge, 1000 RPM, 1 min.
2 0 Scan at appropiate PMT's and channels.
The results are shown in the tables and figures. The lists of genes come from cells cultured in an in vitro angiogenesis model. As indicated, some of the Accession numbers include expression sequence tags (ESTs). Thus, in one embodiment herein, genes within an expression profile, also termed expression profile genes, include ESTs and are not necessarily full length.

Accession Cluster#/ Gene Description PROBESET

3 AB000450 vaccinia related kinase 2 4 AB002380 Human mRNA for KIAA382 gene; partial cds 4 AB003103 proteasome (prosome; macropain) 26S subunit;
non-ATPase; 12 4 AB004884 Homo sapiens mRNA for PKU-alpha; partial cds 1 AF000573 rna1homogentisate 1;2-dioxygenase (homogentisate oxidase) 3 AF008937 Homo sapiens syntaxin-16C mRNA, complete cds 3 AF009301 Homo sapiens TEB4 protein mRNA; complete cds 3 AF009368 Homo sapiens Luman mRNA; complete cds 4 D00591 chromosome condensation 1 4 D00760 proteasome (prosome; macropain) subunit;
alpha type; 2 tissue inhibitor of metalloproteinase 1 1 D11139 (erythroid potentiating activity;
collagenase inhibitor) 4 D14657 Human mRNA for KIAA11 gene; complete cds 4 D14878 D123 gene product mannosyl (alpha-1;6-)-glycoprotein 1 D17716 beta-1;6-N-acetyl-glucosaminyltransferase 4 D21090 RAD23 (S. cerevisiae) homolog B

1 D26135 diacylglycerol kinase; gamma (9kD) 1 D26528 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 7 (RNA helicase; 52kD) 2 0 1 D30742 calcium/calmodulin-dependent protein kinase IV

4 D31762 Human mRNA for KIAA57 gene; complete cds 4 D31765 Human mRNA for KIAA61 gene; partial cds 3 D31888 Homo sapiens clone 2479 mRNA sequence 4 D38128 prostaglandin I2 (prostacyclin) receptor (1P) 2 5 2 D38500 postmeiotic segregation increased 2-like 4 D38551 RAD21 (S. pombe) homolog 4 D42087 Human mRNA for KIAA118 gene; partial cds Human mRNA for Apo1_Human (MERS(Aop1-Mouse)-like 3 D49396 protein);
complete cds Human monocyte PABL (pseudoautosomal boundary-like 4 D55640 sequence) mRNA, clone Mo2 platelet-activating factor acetylhydrolase;
3 0 1 D63391 isoform Ib; gamma subunit (29kD) 3 D63477 Human mRNA for KIAA143 gene; partial cds 4 D63483 acetyl LDL receptor; SREC

4 D64015 TIA1 cytotoxic granule-associated RNA-binding protein-like 1 4 D79990 Human mRNA for KIAA168 gene; complete cds 3 5 4 D79997 Human mRNA for KIAA175 gene; complete cds 4 D80010 Human mRNA for KIAA188 gene; partial cds 1 D84276 CD38 antigen (p45) 4 D86425 Homo sapiens mRNA for nidogen-2 4 D86978 Human mRNA for KIAA225 ene; artial cds Accession Cluster#/ Gene Description PROBESET

1 D87012 Homo Sapiens clone 24675 mRNA sequence 4 D87075 Human mRNA for KIAA238 gene; partial cds 4 D87432 solute carrier family 7 (cationic amino acid transporter; y+ system);

Homo sapiens mRNA for DNA topoisomerase 4 D87448 II binding protein; complete cds 2 D87845 platelet-activating factor acetylhydrolase 2 (4kD) 1 HG1098-HT1098Cystatin D

4 HG2167-HT2237Protein Kinase Ht3l, Camp-Dependent 1 HG2415-HT2511Transcription Factor E2f-2 1 HG2825-HT2949Ret Transforming Gene 1 HG2887-HT3031Sry-Related Hmg-Box 12 Protein (Gb:X73039) r 4 HG4660-HT5073Microtubule-Associated Protein 1 b 3 HG4704-HT5146Glial Growth Factor 2 4 HG884-HT884 Oncogene E6-Ap, Papillomavirus 1 HG919-HT919 Dna Polymerase, Epsilon, Catalytic Subunit 4 J00212 f Accession not listed in Genbank 4 J04029 keratin 1 (epidermolytic hyperkeratosis;
keratosis palmaris et plantaris) 5;1-methylenetetrahydrofolate dehydrogenase;
4 5;1-methylenetetrahydrofolate cyclohydrolase;
04031 1-formyltetrahydrofolate synthetase 4 J04088 topoisomerase (DNA) II alpha (17kD) 4 J04543 annexin VII (synexin) 2 0 4 L06139 TEK tyrosine kinase; endothelial MADS box transcription enhancer factor 4 L08895 2; polypeptide C (myocyte enhancer factor 2C) 1 L11239 gastrulation brain homeo box 1 1 L11353 neurofibromin 2 (bilateral acoustic neuroma) 4 L13773 Human AF-4 mRNA; complete cds 4 L13800 Homo Sapiens liver expressed protein gene, 3' end 4 L14922 replication factor C (activator 1 ) 1 (145kD) 4 L15189 heat shock 7kD protein 9B (mortalin-2) 4 L15388 Human G protein-coupled receptor kinase (GRKS) mRNA, complete cds 3 0 3 L16895 lysyl oxidase 4 L27476 Friedreich ataxia region gene X14 (tight junction protein ZO-2) 1 L32976 mixed lineage kinase 3 1 L33404 protease; serine; 6 (chymotryptic; stratum corneum) cytokine suppressive anti-inflammatory 3 5 4 L35263 drug binding protein 1 (p38 MAP
kinase) 1 L37347 natural resistance-associated macrophage protein 2 4 L40371 thyroid hormone receptor interactor 4 4 L40391 Homo sa iens clone s153 mRNA fra ment Accession Cluster#/ Gene Description PROBESET

4 L41607 glucosaminyl (N-acetyl) transferase 2;
I-branching enzyme 1 L77566 Homo sapiens DGS-I mRNA; 3' end 1 M13928 aminolevulinate; delta-; dehydratase 1 M14016 uroporphyrinogen decarboxylase 4 M14219 decorin 4 M15796 proliferating cell nuclear antigen 4 M21305 Human alpha satellite and satellite 3 junction DNA sequence Human neural cell adhesion molecule (N-CAM) 4 M22092 gene, exon SEC and partial cds 4 M22898 tumor protein p53 (Li-Fraumeni syndrome) 3 M22995 RAP1A; member of RAS oncogene family 3 M23379 RAS p21 protein activator (GTPase activating protein) 1 1 M24364 major histocompatibility complex; class II; DO beta 1 1 M24400 chymotrypsinogen B1 3 M25753 cyclin B1 4 M27691 cAMP responsive element binding protein 4 M28213 RAB2; member RAS oncogene family SUBUNIT; BETA ISOFORM

1 M29971 O-6-methylguanine-DNA methyltransferase 4 M30269 nidogen (enactin) 2 0 4 M31158 protein kinase; cAMP-dependent; regulatory;
type II; beta 3 M31166 pentaxin-related gene; rapidly induced by IL-1 beta 3 M31210 endothelial differentiation; sphingolipid G-protein-coupled receptor; 1 1 M55420 Human IgE chain, last 2 exons prostaglandin-endoperoxide synthase 1 (prostaglandin 4 M59979 G/H synthase and cyclooxygenase) 2 5 4 M62810 transcription factor 6-like 1 (mitochondria) transcription factor 1-like) 4 M63838 interferon; gamma-inducible protein 16 1 M64710 Human C-type natriuretic peptide gene, complete cds Human phosphatidylcholine 2-acylhydrolase 3 M68874 (cPLA2) mRNA, complete cds 3 M74524 ubiquitin-conjugating enzyme E2A (RAD6 homology PEPTIDYL-PROLYL CIS-TRANS ISOMERASE; MITOCHONDRIAL

sphingomyelin phosphodiesterase 1; acid 1 M81780 cds3 lysosomal (acid sphingomyelinase) 4 M83822 Human beige-like protein (BGL) mRNA; partial cds 1 M87338 replication factor C (activator 1 ) 2 (4kD) 3 5 1 M96326 rna1 azurocidin 1 (cationic antimicrobial protein 37) 4 M96954 TIA1 cytotoxic granule-associated RNA-binding protein-like 1 4 M98833 Friend leukemia virus integration 1 1 S66793 arrestin 3; retinal X-arrestin Accession Cluster#/ Gene Description PROBESET

1 S72370 pyruvate carboxylase 4 S78569 laminin; alpha 4 4 S79873 lysosomal-associated membrane protein 2 1 S83325 aspartate beta-hydroxylase putative RabS-interacting protein {clone 4 S83364 L1-57} [human, HeLa cells, mRNA Partial, 366 nt) putative RabS-interacting protein {clone 1 S83365 L1-94} [human, HeLa cells, mRNA Partial, 369 nt) 1 001212 Human olfactory marker protein (OMP) gene, complete cds 1 001922 deafness; X-linked 1; progressive 4 002556 Human RP3 mRNA; complete cds 4 002680 protein tyrosine kinase 9 4 003272 fibrillin 2 4 004209 Human associated microfibrillar protein mRNA; complete cds 4 005237 fetal Alzheimer antigen 1 007225 purinergic receptor P2Y; G-protein coupled;

3 007620 protein kinase mitogen-activated 1 (MAP
kinase) 4 009759 protein kinase mitogen-activated 9 (MAP
kinase) 4 009820 alpha thalassemia/mental retardation syndrome X-linked 3 011313 sterol carrier protein 2 3 014518 centromere protein A (17kD) 2 0 4 014575 protein phosphatase 1; regulatory (inhibitor) subunit 8 3 015173 BCL2/adenovirus E1 B 19kD-interacting protein 4 015932 dual specificity phosphatase 5 4 018291 cell division cycle 16; anaphase promoting complex 6 4 018300 damage-specific DNA binding protein 2 (48kD) 2 5 4 018383 nuclear respiratory factor 1 4 020536 caspase 6; apoptosis-related cysteine protease 4 021551 Human ECA39 mRNA; complete cds 4 023028 eukaryotic translation initiation factor 2B; subunit 5 (epsilon; 82kD) 1 023752 SRY (sex-determining region Y)-box 11 3 0 4 025435 Human transcriptional repressor (CTCF) mRNA; complete cds 4 025997 stanniocalcin 4 028251 cds2 zinc finger protein 169 Human protein immuno-reactive with anti-PTH
4 028831 polyclonal antibodies mRNA; partial cds Human myelomonocytic specific protein (MNDA) 4 030245 gene, 5' flanking sequence and complete exon 1 3 5 4 032315 Human syntaxin 3 mRNA; complete cds 4 032439 regulator of G-protein signalling 7 3 032849 N-myc (and STAT) interactor 4 035139 necdin (mouse) homolog 1 036764 eukaryotic translation initiation factor 3; subunit 2 (beta; 36kD) 4 0 4 039400 chromosome 11 open reading frame 4 ~ U39657 protein kinase; mitogen-activated; kinase 6 (MAP kinase kinase 6) Accession Cluster#/ Gene Description PROBESET

4 041344 proline arginine-rich end leucine-rich repeat protein 3 041766 a disintegrin and metalloproteinase domain 9 (meltrin gamma) 3 041813 homeo box A9 3 041815 Human nucleoporin 98 (NUP98) mRNA, complete cds 4 043286 Human selenophosphate synthetase 2 (SPS2) mRNA; complete cds 4 044378 MAD (mothers against decapentaplegic; Drosophila) homolog 4 4 044754 small nuclear RNA activating complex; polypeptide 1; 43kD

1 047011 cdsl fibroblast growth factor 8 (androgen-induced) Human DNA-dependent protein kinase catalytic 4 047077 subunit (DNA-PKcs) mRNA; complete cds 4 048251 Homo sapiens protein kinase C-binding protein RACK7 mRNA; partial cds 4 050535 Human BRCA2 region; mRNA sequence CG6 4 056833 von Hippel-Lindau binding protein 1 4 058091 cullin 4B

1 058837 cyclic nucleotide gated channel beta 1 4 059289 cadherin 13; H-cadherin (heart) 4 059863 TNF receptor-associated factor 2 4 067122 ubiquitin-like 1 (sentrin) 4 067319 caspase 7; apoptosis-related cysteine protease 3 068019 MAD (mothers against decapentaplegic; Drosophila) homolog 3 a disintegrin and metalloproteinase domain 2 0 1 069611 17 (tumor necrosis factor;
alpha; converting enzyme) 4 070322 karyopherin (importin) beta 2 4 073524 Human putative ATP/GTP-binding protein (HEAB) mRNA; complete cds 4 079267 Human clone 2384 mRNA; partial cds 4 079291 Human clone 23721 mRNA sequence 2 5 4 082671 cds2 Homo sapiens clone LM1955 H15e3 gene; partial cds 4 084573 procollagen-lysine; 2-oxoglutarate 5-dioxygenase (lysine hydroxylase) 2 4 090914 carboxypeptidase D

1 091316 Homo Sapiens mRNA for brain acyl-CoA hydrolase;
complete cds 4 091932 clathrin-associated/assemblyladaptor protein;
small 3; 22-kD; Sigma3A

3 0 4 096131 Homo sapiens HPV16 E1 protein binding protein mRNA; complete cds 4 097018 echinoderm microtubule-associated protein-like Homo Sapiens putative RNA binding protein 4 097188 KOC (koc) mRNA; complete cds 4 V00503 collagen; type I; alpha 2 3 X04327 2;3-bisphosphoglycerate mutase 3 5 1 X06389 synaptophysin 1 X07496 apolipoprotein A-I

2 X07820 matrix metalloproteinase 1 (stromelysin 2) 3 X14787 thrombos ondin 1 Accession Cluster#/ Gene Description PROBESET

4 X15525 rna1 acid phosphatase 2; lysosomal NAD-DEPENDENT METHYLENETETRAHYDROFOLATE

4 X16609 ankyrin 1; erythrocytic 4 X53586 rnal Human mRNA for integrin alpha 6 1 X54936 placental growth factor; vascular endothelial growth factor-related protein 4 X55740 5' nucleotidase (CD73) 2 X57025 insulin-like growth factor 1 (somatomedin C) 2 X60673 rna1 adenylate kinase 3 dipeptidylpeptidase IV (CD26; adenosine 4 X60708 deaminase complexing protein 2) 4 X62048 wee1+ (S, pombe) homolog 2 X63097 Rhesus blood group; D antigen 4 X63563 polymerase (RNA) II (DNA directed) polypeptide B (14kD) 4 X64037 general transcription factor IIF; polypeptide 1 (74kD subunit) 4 X69636 hect domain and RLD 2 4 X69878 fms-related tyrosine kinase 4 4 X70649 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3 X72841 H.sapiens IEF 7442 mRNA

4 X74987 ribonuclease L (2 ;5'-oligoisoadenylate synthetase-dependent) inhibitor 2 0 4 X83107 BMX non-receptor tyrosine kinase 3 X84194 acylphosphatase 1; erythrocyte (common) type 4 X85753 cyclin-dependent kinase 8 1 X87870 H.sapiens mRNA for hepatocyte nuclear factor 4a 4 X89066 transient receptor potential channel 1 2 5 4 X89398 cds2 uracil-DNA glycosylase 1 X89399 Homo sapiens mRNA for Ins(1;3;4;5)P4-binding protein 3 X89426 H.sapiens mRNA for ESM-1 protein 4 X91247 thioredoxin reductase 1 4 X91648 H.sapiens mRNA for pur alpha extended 3'untranslated region 3 0 4 X92098 H.sapiens mRNA for transmembrane protein rnp24 4 X92110 H.sapiens mRNA for hcgVlll protein 4 X94703 RAB28; member RAS oncogene family 1 X96506 H.sapiens mRNA for NC2 alpha subunit Homo sapiens natural killer-associated 1 X97230 f transcript 5 (NKAT5) mRNA;
complete cds 3 5 4 X98263 H.sapiens mRNA for M-phase phosphoprotein;
mpp6 ubiquitin specific protease 9; X chromosome 4 X98296 (Drosophila fat facets related) 4 X99584 H.sa lens mRNA for SMT3A rotein Accession Cluster#/ Gene Description PROBESET

4 Y00264 amyloid beta (A4) precursor protein (protease nexin-II; Alzheimer disease) 4 Y07566 H.sapiens mRNA for RIT protein 3 Y07759 myosin VA (heavy polypeptide 12; myoxin) 1 Y07827 Human butyrophilin (BTFS) mRNA; complete cds 4 Y07867 pirin 4 Y09443 alkylglycerone phosphate synthase 4 Y09858 H.sapiens mRNA for unknown protein 4 Y12394 karyopherin alpha 3 (importin alpha 4) 3 211559 iron-responsive element binding protein 4 211695 protein kinase; mitogen-activated 1 (MAP
kinase 1; p4; p41) 3 215005 centromere protein E (312kD) 1 246261 H.sapiens DNA for histone H3a 2 AA011243 s ESTs 2 AA018418 ESTs 2 AA018758 ESTs 2 AA018804 Homo sapiens clone 23675 mRNA sequence 3 AA031993 Homo sapiens HRIHFB2115 mRNA; partial cds 2 AA044217 ESTs; Weakly similar to similar to cuticle collagen [C.elegans]

SWI/SNF related; matrix associated; actin 4 AA046548 dependent regulator of chromatin; subfamily e; member 1 ESTs; Moderately similar to !!!! ALU SUBFAMILY
2 0 2 AA057447 s SB WARNING ENTRY
!!!! [H.sapiens]

Sjogren syndrome antigen A2 (6kD; ribonucleoprotein 2 AA058376 autoantigen SS-A/Ro) 4 AA083572 v-ral simian leukemia viral oncogene homolog A (ras related) 4 AA085696 ESTs 2 AA088744 ESTs ESTs; Weakly similar to putative T1/ST2 2 5 2 AA089688 receptor binding protein precursor [H.sapiens]

4 AA091284 ESTs 2 AA092700 ESTs 1 AA092968 ESTs 4 AA094800 eukaryotic translation initiation factor 3; subunit 7 (zeta; 66/67kD) 3 0 4 AA100219 ESTs 4 AA114885 ESTs ESTs; Weakly similar to !!!! ALU SUBFAMILY
4 AA129547 SQ WARNING ENTRY !!!!
[H.sapiens]

4 AA133016 ESTs 3 AA149507 homolog of mouse quaking QKI (KH domain RNA binding protein) 3 5 2 AA151005 sperm surface protein zp61b6.r1 Stratagene endothelial cell 937223 4 AA187101 Homo sapiens cDNA clone IMAGE:624659 5', mRNA sequence 3 AA195179 s ESTs Accession Cluster#/ Gene Description PROBESET

2 AA203138 low density lipoprotein receptor (familial hypercholesterolemia) 2 AA203645 ESTs; Moderately similar to SH3-containing protein p415 [R.norvegicus]

zq54c6.r1 Stratagene neuroepithelium (#937231 3 ) Homo sapiens cDNA
A206236 clone IMAGE:645418 5' similar to TR:G122922 INFLAMMATORY FACTOR-1. ;, mRNA sequence 1 AA227621 ESTs; Weakly similar to weak similarity to collagens [C.elegans]

ESTs; Weakly similar to X-linked retinopathy 4 AA248283 protein {C-terminal; clone XEH.Bc} [H.sapiens]

3 AA249611 H.sapiens mRNA for 21-Glutamic Acid-Rich Protein (21-GARP) 2 AA282640 ESTs 2 AA287199 Human mRNA for KIAA81 gene; partial cds ESTs; Highly similar to HYPOTHETICAL 3.5 2 AA313990 KD PROTEIN C3A5.3 IN
CHROMOSOME III [Caenorhabditis elegans]

EST18611 Colon carcinoma (HCC) cell line 2 AA314256 II Homo sapiens cDNA 5' end, mRNA sequence ESTs; Highly similar to ADP-RIBOSYLATION

[Saccharomyces cerevisiae]

ESTs; Moderately similar to !!!! ALU SUBFAMILY
2 AA324364 J WARNING ENTRY !!!!
[H.sapiens]

3 AA329211 s ESTs 2 AA399187 ESTs 4 AA421079 ESTs 2 AA422029 ESTs 3 AA425230 Human GAP SH3 binding protein mRNA; complete cds ESTs; Highly similar to N-terminal asparagine 4 AA447052 amidohydrolase [M.musculus]

4 AA452000 ESTs 2 0 4 AA456687 ESTs ESTs; Weakly similar to X-linked retinopathy 4 AA487015 s protein {C-terminal; clone XEH.Bc} [H.sapiens]

2 AB002326 Human mRNA for KIAA328 gene; partial cds 4 AFFX-BioB-3 2 C01527 ESTs 2 5 4 C01714 Homo sapiens serum-inducible kinase mRNA;
complete cds 3 C01811 f ESTs ESTs; Moderately similar to !!!! ALU SUBFAMILY
2 C02352 s SO WARNING ENTRY
!!!! [H.sapiens]

1 C02375 Human mRNA containing an Alu repeat and its reverse complement 3 0 4 D16611 s coproporphyrinogen oxidase (coproporphyria;
harderoporphyria) 2 D25216 Human mRNA for KIAA14 gene; complete cds 2 D31352 ESTs; Weakl similar to h othetical rotein H.sa lens Accession Cluster#/ Gene Description PROBESET

ESTs; Weakly similar to probable hormone 4 D58024 s receptor EMR1 precursor [H.sapiens]

1 D80897 Homo sapiens clone 24736 mRNA sequence 3 D82614 ESTs 4 D87845 platelet-activating factor acetylhydrolase 2 (4kD) 1 D89377 i msh (Drosophila) homeo box homolog 2 2 H06583 cAMP responsive element binding protein-like 1 H40732 ESTs yp19h1.r1 Soares breast 3NbHBst Homo sapiens 4 H46617 cDNA clone IMAGE:187921 5', mRNA sequence 1 H56731 ESTs 1 0 1 H75570 ESTs 2 H78886 ESTs ESTs; Highly similar to ERYTHROID KRUEPPEL-LIKE

FACTOR [Mus musculus]

1 L36531 integrin; alpha 8 2 M63154 gastric intrinsic factor (vitamin B synthesis) 4 M63180 threonyl-tRNA synthetase 2 M91504 ESTs 2 N56191 Homo sapiens protocadherin 68 (PCH68) mRNA;
complete cds 2 N78483 ESTs 2 N79268 zinc finger protein 198 2 0 2 814652 Homo sapiens PAC clone DJ872F7 from 7q31 yg33f12.r1 Soares infant brain 1NIB Homo 2 820459 sapiens cDNA clone IMAGE:34345 5', mRNA sequence 3 822303 ESTs; Weakly similar to putative p15 [H.sapiens]

2 833779 ESTs; Weakly similar to p4 [H.sapiens]

2 836553 ESTs; Weakly similar to KIAA681 protein [H.sapiens]

2 5 2 864534 ESTs 4 866475 ESTs 4 870621 Homo sapiens mRNA for KIAA896 protein;
partial cds 3 879356 ESTs; Weakly similar to PROTEIN Q3 [Mus musculus]

2 884933 ESTs; Weakly similar to putative p15 [H.sapiens]

3 0 3 RC AA007160 ESTs ESTs; Highly similar to protein tyrosine 2 RC AA007234 phosphatase epsilon cytoplasmic s isoform [H.sapiens]

2 RC AA018409 ESTs 4 RC AA025351 ESTs 3 RC AA027168 ESTs ESTs; Weakly similar to !!!! ALU SUBFAMILY
3 5 1 RC AA027317 J WARNING ENTRY !!!!
[H.sapiens]

3 RC AA029423 ESTs 4 RC AA031357 ESTs 4 RC AA045136 ESTs 1 RC AA053400 ESTs Accession Cluster#/ Gene Description PROBESET

ESTs; Weakly similar to !!!! ALU SUBFAMILY
3 RC AA055829 J WARNING ENTRY !III
[H.sapiens]

3 RC AA065217 ESTs 1 RC AA116054 ESTs 1 RC AA126311 ESTs 4 RC AA129390 ESTs ESTs; Highly similar to DOSAGE COMPENSATION

[Drosophila melanogaster]

2 RC AA142919 ESTs 4 RC AA150205 ubiquitous Kruppel-like transcription factor 1 RC AA176867 ESTs ESTs; Highly similar to U1 small nuclear 2 RC AA180321 ribonucleoprotein 1 SNRP
homolog [H.sapiens]

2 RC_AA180487 Homo sapiens TACC1 (TACC1 ) mRNA; complete cds 4 RC AA187634 eukaryotic translation initiation factor 3; subunit 1 (alpha; 35kD) 3 RC AA195399 ESTs 3 RC AA234717 ESTs 4 RC AA234743 ESTs 3 RC AA234957 Homo sapiens mRNA for MTMR1 protein 3 RC AA235604 ESTs ESTs; Weakly similar to PROBABLE E5 PROTEIN
3 RC AA236559 [Human papillomavirus type 58]

3 RC AA242868 ESTs; Weakly similar to house-keeping protein [M.musculus]

2 0 4 RC AA251776 jun D proto-oncogene 4 RC AA251909 Homo sapiens protein kinase homolog (BUBR1 ) mRNA; complete cds diptheria toxin resistance protein required 3 RC AA252672 for diphthamide biosynthesis s (Saccharomyces)-like 2 3 RC AA256157 ESTs 4 RC AA256680 ESTs 2 5 3 RC AA258873 ESTs 1 RC AA262727 ESTs 4 RC AA281451 ESTs 4 RC AA281545 ESTs 3 RC AA282069 Homo sapiens mRNA for KIAA63 protein; complete cds 3 0 1 RC AA283044 ESTs 3 RC AA283930 ESTs 4 RC AA284755 ESTs; Weakly similar to unknown [H.sapiens]

4 RC AA291268 ESTs 1 RC AA291927 ESTs 3 5 2 RC AA343514 ESTs 3 RC AA398109 ESTs 4 RC AA405737 ESTs 4 RC AA406610 ESTs 4 RC AA411465 ESTs 4 0 3 RC AA416886 ESTs; Weakl similar to redicted usin Genefinder C.ele ans Accession Cluster#/ Gene Description PROBESET

4 RC AA424013 Homo sapiens clone 23767 and 23782 mRNA
sequences 4 RC_AA424148 ESTs 2 RC_AA424558 ESTs; Weakly similar to 33-kDa phototransducing protein [H.sapiens]

4 RC AA424961 Homo sapiens TEB4 protein mRNA; complete s cds 3 RC_AA425367 ESTs 1 RC_AA425921 Homo sapiens I-1 receptor candidate protein mRNA; complete cds 4 RC AA426220 Homo sapiens mRNA for KIAA523 protein;
partial cds 4 RC AA427735 ESTs 4 RC AA430673 ESTs 4 RC AA432248 ESTs 4 RC_AA435896 ESTs 3 RC_AA436705 Homo sapiens mRNA for KIAA766 protein;
complete cds 3 RC_AA446561 Homo sapiens mRNA for KIAA47 protein; complete cds 4 RC_AA448238 Homo Sapiens mRNA for KIAA915 protein;
complete cds 3 RC AA448688 ESTs; Weakly similar to KIAA638 protein [H.sapiens) 3 RC AA449756 ESTs; Weakly similar to rA8 [R.norvegicus) 4 RC AA450303 ESTs 3 RC AA452411 ESTs 4 RC AA454566 ribosomal protein L13 2 0 4 RC AA454667 ESTs 4 RC AA456437 ESTs 4 RC AA456646 ESTs 4 RC AA456826 ESTs 4 RC AA456981 ESTs 2 5 4 RC AA458959 ESTs 3 RC AA459950 ESTs ESTs; Highly similar to PROBABLE PHOSPHOSERINE
3 RC AA460449 AMINOTRANSFERASE [Oryctolagus cuniculus]

3 RC AA463910 ESTs 4 RC AA464603 ESTs 3 0 3 RC AA464606 ESTs 4 RC AA465093 TIA1 cytotoxic granule-associated RNA-binding protein 3 RC AA465692 Homo sapiens mRNA for KIAA648 protein;
partial cds 3 RC AA476473 Homo sapiens Trio mRNA; complete cds 1 RC AA478109 ESTs 3 5 4 RC AA478474 ESTs 3 RC AA480889 ESTs 1 RC AA485223 ESTs 1 RC AA485254 ESTs 4 RC AA486183 ESTs; Weakly similar to Yhr1wp [S.cerevisiae]

4 0 3 RC AA496936 ESTs; Weakly similar to B cell growth factor [H.sapiens]

4 RC AA598589 ESTs 4 RC AA598831 ESTs f 4 RC AA600150 ESTs Accession Cluster#/ Gene Description PROBESET

4 RC AA608545 ESTs 3 RC AA609210 ESTs ESTs; Highly similar to PROBABLE PEPTIDYL-PROLYL
3 RC_AA610108 CIS-TRANS
ISOMERASE C21E11.5C [Schizosaccharomyces pombe]

4 RC AA620582 ESTs; Weakly similar to (defline not available 424227) [H.sapiens]

ESTs; Highly similar to HYPOTHETICAL 98.3 4 RC AA621239 KD PROTEIN R1 E12.1 IN
CHROMOSOME III [Caenorhabditis elegans]

3 RC AA621714 ESTs 1 RC AA621718 ESTs 1 RC D19673 ESTs 1 RC D25755 ESTs s 1 RC_D51095 ESTs 4 RC D60272 ESTs; Weakly similar to macrophage lectin i 2 [H.sapiens]

2 T08879 cathepsin F

UDP-N-acetyl-alpha-D-galactosamine:polypeptide 3 T34527 N-acetylgalactosaminyltransferase 1 (GaINAc-T1 ) 2 T40327 s ESTs 3 T62771 s Homo sapiens nucleoplasmin-3 (NPM3) mRNA;
complete cds 1 T63174 s ESTs; Weakly similar to neuronal thread protein AD7c-NTP [H.sapiens]

2 T83444 Homo sapiens mRNA for KIAA887 protein;
partial cds 1 T93641 ESTs 2 048263 prepronociceptin 2 0 2 049065 interleukin 1 receptor-like 2 2 079300 Human clone 23629 mRNA sequence 1 088573 Human NBR2 mRNA; complete cds 2 093867 Human RNA polymerase III subunit (RPC62) mRNA; complete cds 4 W01094 ESTs 2 5 2 W01568 ESTs 2 W26853 ESTs 2 W27179 BCL2/adenovirus E1B l9kD-interacting protein 3-like 2 W27965 epimorphin Homo sapiens RRM RNA binding protein Gry-rbp 3 W36280 s (GRY-RBP) mRNA;
complete cds 3 0 2 W47063 ESTs 4 W79060 ESTs; Weakly similar to Ras-binding protein SUR-8 [M.musculus]

4 W88550 ESTs; Moderately similar to trg gene product [R.norvegicus]

1 X60486 H4 histone family; member G

2 X78931 s H.sapiens HZF8 mRNA for zinc finger protein 3 5 1 214077 s YY1 transcription factor 1 RC AA004711 ESTs 1 RC AA015761 ESTs Accession Cluster#/ Gene Description PROBESET

2 RC AA018772 ESTs r potassium voltage-gated channel; delayed-rectifier;
2 RC AA024835 subfamily S; member 2 RC AA025858 ESTs 1 RC AA027229 ESTs 1 RC AA029428 ESTs 3 RC AA035143 ESTs 1 RC AA035237 ESTs 1 RC AA040740 ESTs 3 RC AA041551 ESTs 1 RC AA045513 ESTs 1 RC AA055348 ESTs 2 RC AA056582 ESTs s 1 RC AA056697 ESTs 3 RC AA057678 ESTs 2 RC AA058681 ESTs 2 0 2 RC AA058686 ESTs zm5c1.s1 Stratagene corneal stroma (#937222) 2 Homo sapiens cDNA
C AA062840 clone IMAGE:513234 3' similar to gb:S71381 PROTEASOME BETA
CHAIN (HUMAN);, mRNA sequence zm5f3.s1 Stratagene fibroblast (#937212) 2 RC AA064859 Homo sapiens cDNA clone IMAGE:52985 3', mRNA sequence zm12e11.s1 Stratagene pancreas (#93728) 1 RC AA065069 Homo Sapiens cDNA clone IMAGE:525452 3', mRNA sequence zm67g3.s1 Stratagene neuroepithelium (#937231 ) Homo Sapiens cDNA
1 clone IMAGE:5374 3' similar to gb:S66915_cds1 GAMMA CHAIN, MITOCHONDRIAL PRECURSOR (HUMAN);, mRNA
sequence zm6h5.s1 Stratagene fibroblast (#937212) 2 RC AA070799 Homo Sapiens cDNA clone s IMAGE:5373 3', mRNA sequence zm6a1.s1 Stratagene fibroblast (#937212) 2 Homo Sapiens cDNA clone C AA070815 IMAGE:529992 3' similar to gb:X67951 PROLIFERATION-ASSOCIATED
PROTEIN PAG (HUMAN);, mRNA sequence zm87a1.s1 Stratagene ovarian cancer (#937219) 2 RC AA075374 Homo sapiens cDNA
clone IMAGE:544872 3', mRNA sequence zm91g8.s1 Stratagene ovarian cancer (#937219) 2 RC AA076382 Homo Sapiens cDNA
clone IMAGE:545342 3', mRNA sequence 1 RC AA078787 ESTs Accession Cluster#/ Gene Description PROBESET

zm92h1.s1 Stratagene ovarian cancer (#937219) 2 RC AA078986 Homo Sapiens cDNA
clone IMAGE:545425 3', mRNA sequence zm95h11.s1 Stratagene colon HT29 (#937221 1 ) Homo Sapiens cDNA
C AA079393 clone IMAGE:545733 3' similar to gb:X1656 CYTOCHROME C OXIDASE
POLYPEPTIDE VIIC PRECURSOR (HUMAN);, mRNA
sequence zm97f8.s1 Stratagene colon HT29 (#937221 2 RC AA079487 ) Homo sapiens cDNA clone IMAGE:545895 3', mRNA sequence 2 RC AA083256 vinculin zn6g9.s1 Stratagene hNT neuron (#937233) 2 RC AA084415 Homo Sapiens cDNA clone IMAGE:546688 3', mRNA sequence znlf1.s1 Stratagene colon HT29 (#937221 2 ) Homo sapiens cDNA clone C AA085274 IMAGE:546169 3' similar to gb:X15341 CYTOCHROME
C OXIDASE
POLYPEPTIDE VIA-LIVER (HUMAN);, mRNA sequence 2 RC_AA088678 ESTs 3 RC AA100925 ESTs; Weakly similar to predicted using Genefinder [C.elegans]

ESTs; Highly similar to J KAPPA-RECOMBINATION

PROTEIN [Homo sapiens]

3 RC AA126474 stanniocalcin 2 2 RC AA127017 ESTs ESTs; Weakly similar to protein phosphatase 2 RC AA129968 2A 13 kDa regulatory subunit [H.sapiens]

2 RC AA130240 ESTs 1 RC AA131866 ESTs ESTs; Moderately similar to !!!! ALU SUBFAMILY
2 RC AA132039 J WARNING ENTRY !!!!
[H.sapiens) ESTs; Moderately similar to C-1-TETRAHYDROFOLATE
3 RC AA132983 SYNTHASE;
CYTOPLASMIC [Saccharomyces cerevisiae]

ESTs; Weakly similar to NADH-UBIQUINONE

CHAIN 4 [Caenorhabditis elegans]

1 RC AA133583 high-mobility group (nonhistone chromosomal) s protein isoform I-C

2 0 4 RC AA135941 ESTs zo9e6.s1 Stratagene neuroepithelium NT2RAM1 2 RC AA148650 937234 Homo Sapiens cDNA clone IMAGE:56722 3', mRNA sequence 2 RC AA151110 ESTs ESTs; Moderately similar to !!!! ALU SUBFAMILY

!!!! [H.sapiens]

4 RC AA156125 ESTs 2 5 2 RC AA156289 ESTs 1 RC AA156997 ESTs 2 RC AA157291 ESTs Accession Cluster#/ Gene Description PROBESET

2 RC AA157293 ESTs 2 RC AA164293 ESTs f 1 RC_AA164676 EST

1 RC AA167375 Homo sapiens mRNA for KIAA53 protein; partial cds ESTs; Moderately similar to !!!! ALU SUBFAMILY

!!!! [H.sapiens]

4 RC AA187144 endothelin 1 s 3 RC AA189170 ESTs f 4 RC AA192757 ESTs 2 RC AA205650 ESTs ESTs; Weakly similar to neural differentiation-associated 4 RC AA233342 protein [M.musculus]

3 RC AA233472 ESTs 2 RC AA234110 ESTs 4 RC D80981 ESTs ESTs; Weakly similar to HYPOTHETICAL PROTEIN
3 RC F01660 H134 [Haemophilus influenzae]

1 RC F02206 EST; Highly similar to ether-a-go-go-related protein [H.sapiens]

4 RC F02208 ESTs 4 RC F02544 ESTs 2 0 4 RC F03918 ESTs 4 RC F04258 ESTs; Highly similar to INORGANIC PYROPHOSPHATASE
s [Bos taurus]

4 RC F04600 ESTs 4 RC F08998 ESTs 2 RC F09605 ESTs 4 RC F11115 ESTs 3 RC H06371 ESTs 1 RC H10995 ESTs ESTs; Weakly similar to HYPOTHETICAL 97.6 SHP1-SEC17 INTERGENIC REGION [Saccharomyces cerevisiae]

4 RC H16568 ESTs 3 0 4 RC H 16772 ESTs ESTs; Moderately similar to seven-pass 1 RC H18951 transmembrane receptor precursor [M.musculus]

1 RC H20859 ESTs 1 RC H23747 ESTs 1 RC H38087 ESTs 3 5 1 RC H40331 ESTs 1 RC H40567 ESTs Accession Cluster#/ Gene Description PROBESET

1 RC H46966 ESTs yq99a5.s1 Soares fetal liver spleen 1 NFLS
1 RC_H56640_i Homo Sapiens cDNA clone I MAGE:23888 3', mRNA sequence 1 RC H57154 ESTs; Weakly similar to RST [M.musculus]

1 RC H96712 ESTs 1 RC_N20814 ESTs 3 RC N25249 synaptosomal-associated protein; 23kD

1 RC_N27100 ESTs 1 RC N39616 RNA (guanine-7-) methyltransferase 1 RC N48982 ESTs 1 RC_N51957 ESTs 1 RC_N52271 Homo Sapiens LIM protein mRNA; complete cds 1 RC_N59435 ESTs; Weakly similar to No definition line found [H.sapiens]

1 RC N64139 ESTs; Weakly similar to Ndr protein kinase [H.sapiens]

3 RC N66981 ESTs 1 RC N68640 ESTs ESTs; Highly similar to PRE-MRNA SPLICING
4 RC_N69352 FACTOR RNA HELICASE
PRP22 [Saccharomyces cerevisiae]

4 RC N95226 Homo sapiens mRNA for KIAA758 protein;
partial cds 1 RC 800138 ESTs ESTs; Weakly similar to !!!! ALU SUBFAMILY
1 RC_R07998 J WARNING ENTRY !!!!
[H.sapiens]

2 0 1 RC 808929 ubiquitin-conjugating enzyme E2G 2 (homologous to yeast UBC7) 1 RC 810307 ESTs 3 RC 833354 ESTs 1 RC 836083 ESTs 1 RC 837938 ESTs f ydlg4.s1 Soares infant brain 1NIB Homo 2 5 1 RC 839330 Sapiens cDNA clone IMAGE:24282 3', mRNA sequence 1 RC 840816 cullin 4A
s 1 RC 843162 ESTs s ESTs; Weakly similar to Similarity to Salmonella 3 RC 845698 regulatory protein UHPC
(C.elegans]

2 RC 854554 ESTs ESTs; Weakly similar to alternatively spliced 3 0 1 RC 868425 product using exon 13A
[H.sapiens]

1 RC 868568 ESTs 3 RC 868763 ESTs 1 RC 870467 ESTs ESTs; Moderately similar to !!!! ALU SUBFAMILY
1 RC_R73565 SX WARNING ENTRY
!!!! [H.sapiens]

3 5 4 RC 873640 ESTs Accession Cluster#/ Gene Description PROBESET

1 RC T03865 ESTs 3 RC T03872 ESTs 1 RC T10072 ESTs 1 RC_T10080 ESTs 1 RC T10132 Homo sapiens mRNA for KIAA478 protein;
complete cds 1 RC T15343 ESTs 2 RC T23457 ESTs 1 RC T23555 ESTs 2 RC T23670 ESTs 4 RC T23948 ESTs 4 RC T33464 ESTs 1 RC T34413 ESTs 2 RC T34611 ESTs 2 RC T40920 ESTs 4 RC T55182 ESTs 1 RC T84039 ESTs 2 0 1 RC T86458 ESTs 1 RC T87693 ESTs 2 RC T89350 ESTs s 1 RC T90945 ESTs 2 RC T90987 ESTs 2 5 1 RC T91863 ESTs 1 RC T93783 ESTs s 1 RC T96687 ESTs 2 RC T96944 ESTs 3 0 3 RC T97307 ESTs; Weakly similar to neuronal thread protein AD7c-NTP [H.sapiens]

1 RC T97764 ESTs 2 RC W48817 ESTs 2 RC W58343 ESTs 1 RC W59949 ESTs; Highly similar to RAS-LIKE PROTEIN
TC1 [Homo sapiens]

3 5 1 RC W74644 ESTs ESTs; Highly similar to UBIQUITIN-CONJUGATING

[Caenorhabditis elegans]

1 RC W74802 ESTs 1 RC W81205 ESTs 2 RC W81237 ESTs 4 0 3 RC W90146 ESTs f 1 RC W92798 ESTs 1 RC 238709 inositol 1;4;5-tri hos hate rece tor; t a 2 Accession Cluster#/ Gene Description PROBESET

1 RC_Z38904 ESTs 2 RC 239103 core-binding factor; runt domain; alpha subunit 2; translocated to; 2 2 RC 239930 ESTs f 2 RC_Z39939 ESTs 3 RC 240012 Homo sapiens mRNA for KIAA587 protein;
i complete cds 2 RC 240377 ESTs s 1 RC 240820 ESTs 3 RC 241680 ESTs 4 AFFX-BioB-3 2 RC AA005112 Human zinc-finger domain-containing protein mRNA; partial cds ESTs; Highly similar to ANTI-SILENCING
4 RC AA005432 PROTEIN 1 [Saccharomyces cerevisiae]

4 RC AA010163 Human mRNA for KIAA312 gene; partial cds 4 RC AA026356 ESTs 2 RC AA026901 ESTs 4 RC AA036867 ESTs 1 RC_AA044644 Pp52 4 RC AA046426 Homo Sapiens MSE55-related protein (UB1 ) mRNA; complete cds ESTs; Weakly similar to X-linked retinopathy 4 RC AA054515 protein {C-terminal; clone XEH.Bc} [H.sapiens]

zn17h6.s1 Stratagene neuroepithelium NT2RAM1 2 RC AA084162 937234 Homo Sapiens cDNA clone IMAGE:547739 3', mRNA sequence 2 0 4 RC AA085749 Homo sapiens mRNA for ATP binding protein;
complete cds 4 RC AA098874 ESTs zn25b3.s1 Stratagene neuroepithelium NT2RAM1 2 937234 Homo Sapiens C AA101056 cDNA clone IMAGE:548429 3' similar to contains L1.b3 L1 repetitive element ;, mRNA sequence 1 RC AA102746 ESTs; Moderately similar to cytotoxic ligand TRAIL receptor [H.sapiens]

2 RC AA114250 Homo Sapiens mRNA for KIAA512 protein;
s complete cds 2 5 4 RC AA126561 ESTs s ESTs; Weakly similar to !!!! ALU SUBFAMILY

i [H.sapiens) ESTs; Highly similar to 6S RIBOSOMAL PROTEIN
4 RC AA129757 L22 [Rattus norvegicus]

4 RC AA129921 ESTs 2 RC AA133331 Homo sapiens mRNA for KIAA741 protein;
complete cds 3 0 2 RC AA135958 ESTs 4 RC AA136524 ESTs s 4 RC AA147044 ESTs; Weakly similar to transformation-related protein [H.sapiens]

4 RC AA148885 ESTs 4 RC AA150043 ESTs 3 5 2 RC AA151621 ESTs 4 RC AA155743 ESTs Accession Cluster#/ Gene Description PROBESET

2 RC AA156335 ESTs 4 RC AA156336 Homo sapiens nuclear receptor co-repressor N-CoR mRNA; complete cds 2 RC AA159181 ESTs 2 RC AA159825 ESTs 2 RC AA234185 ESTs 4 RC AA234929 ESTs 1 RC AA234935 ESTs 4 RC AA236359 ESTs 2 RC AA236466 ESTs 2 RC AA236535 ESTs 4 RC AA236935 Human normal keratinocyte mRNA
s 2 RC AA236942 ESTs 4 RC AA237018 ESTs 2 RC AA237025 ESTs 2 RC AA242751 Homo Sapiens mRNA for KIAA93 protein; partial cds 3 RC AA242760 ESTs 3 RC AA242763 Homo sapiens Cdc14B1 phosphatase mRNA;
complete cds ESTs; Weakly similar to !!!! ALU SUBFAMILY
2 RC AA242809 J WARNING ENTRY !!!!
[H.sapiens]

ESTs; Highly similar to SERINE/THREONINE-PROTEIN

[Saccharomyces cerevisiae]

2 0 4 RC AA243495 ESTs 3 RC AA243706 ESTs zs6e2.s1 NCI CGAP_GCB1 Homo sapiens cDNA
4 RC AA250848 clone IMAGE:68441 3', mRNA sequence 2 RC AA250868 ESTs 4 RC AA251152 ESTs 2 5 2 RC AA251544 ESTs s 4 RC AA251792 ESTs 4 RC AA252063 Homo Sapiens mRNA for PCDH7 (BH-Pcdh)c;
complete cds 3 RC AA252144 ESTs 4 RC AA252524 ESTs 3 0 3 RC AA253461 ESTs 4 RC AA255522 ESTs 2 RC AA256468 ESTs 4 RC AA256528 ESTs 2 RC AA257976 ESTs 3 5 4 RC AA258296 Homo Sapiens mRNA for KIAA579 protein;
partial cds 3 RC AA258409 H.sapiens gene from PAC 313L4; similar to Myelin PO

2 RC AA258421 Homo sa iens clone 683 unknown mRNA; com lete se uence Accession Cluster#/ Gene Description PROBESET

Human NAD+-dependent succinate-semialdehyde 3 RC AA262077 dehydrogenase (SSADH) mRNA; 3' end 4 RC AA278650 ESTs 2 RC AA278766 ESTs 4 RC AA279667 natural killer-tumor recognition sequence s 3 RC AA280791 eukaryotic translation initiation factor 4 RC AA280819 ESTs 4 RC AA280828 ESTs 4 RC AA282195 ESTs; Weakly similar to ORF YNL292w [S.cerevisiae]

2 RC AA283127 Homo sapiens clone LM1955 H15e3 gene; partial s cds 2 RC AA284694 Homo sapiens CG1 mRNA; complete cds 3 RC AA291137 ESTs 3 RC AA291708 ESTs; Moderately similar to hypothetical protein [H.sapiens]

Homo sapiens BAC clone 255A7 from 8q21 3 RC AA293495 containing NBS1 gene;
complete sequence ESTs; Weakly similar to NADH-UBIQUINONE

CHAIN 4 [Caenorhabditis elegansj 4 RC AA398474 ESTs s 4 RC AA398512 ESTs 2 RC AA400277 ESTs; Weakly similar to putative p15 [H.sapiensj 4 RC AA400896 ESTs 3 RC AA404494 CTP synthase 2 0 2 RC AA410345 ESTs; Weakly similar to A33 antigen precursor [H.sapiens]

4 RC AA416733 ESTs; Weakly similar to neuronal thread protein AD7c-NTP [H.sapiens]

4 RC AA425154 ESTs 4 RC AA426573 ESTs 2 RC AA431418 N-acetylglucosaminidase; alpha- (Sanfilippo disease IIIB) 2 5 4 RC AA436182 ESTs 2 RC AA437099 ESTs 4 RC AA446585 ESTs 3 RC AA446887 ESTs ESTs; Highly similar to HYPOTHETICAL 8.7 ERG7-NMD2 INTERGENIC REGION [Saccharomyces cerevisiae]

3 0 2 RC AA447709 ESTs; Moderately similar to putative transcription factor CA15 [H.sapiens]

4 RC AA453624 deoxynucleotidyltransferase; terminal 4 RC AA455044 ESTs 4 RC AA456045 ESTs 4 RC AA460454 ESTs; Weakly similar to KIAA512 protein s [H.sapiens]

3 5 4 RC AA476494 ESTs; Weakly similar to KIAA512 protein [H.sapiens]

4 RC AA476738 ESTs; Highly similar to FLI-LRR associated protein-1 [M.musculus]

4 RC AA481422 Homo sapiens mRNA for H-2K binding factor-2;
complete cds 3 RC AA482269 inte ral membrane rotein 1 Accession Cluster#I Gene Description PROBESET

2 RC AA482595 ESTs; Highly similar to p36 4 RC AA485084 ESTs s 4 RC_AA485431 ESTs s 4 RC AA489057 H.sapiens mRNA for nuclear protein SA-2 4 RC AA489638 ESTs 2 RC AA491000 ESTs 3 RC AA491250 ESTs 4 RC_AA505133 ESTs 4 RC AA598447 Homo sapiens exportin t mRNA; complete cds 3 RC AA599243 ESTs 3 RC AA599574 ESTs i 4 RC AA600153 DEK gene 4 RC AA609309 ESTs ESTs; Highly similar to HYPOTHETICAL GTP-BINDING

PM14-PAC2 INTERGENIC REGION [Saccharomyces cerevisiae) 4 RC AA610068 H.sapiens mRNA for PIBF1 protein; complete 1 RC AA621399 ESTs Human 26S proteasome-associated pad1 homolog 4 RC AA621752 (POH1 ) mRNA;
complete cds 2 RC C21523 ESTs 2 RC D12160 ESTs; Weakly similar to unknown [H.sapiens]

2 0 4 RC_D19708 ESTs 2 RC D25801 ESTs; Highly similar to KIAA445 protein [H.sapiens]

2 RC D45652 ESTs; Weakly similar to unknown [H.sapiens]

4 RC D60208 ESTs f 3 RC D80504 zinc finger protein 198 s 2 5 2 RC F03010 ESTs; Weakly similar to ZINC FINGER PROTEIN
HRX [Homo sapiens]

ESTs; Weakly similar to !!!! ALU CLASS
4 RC F04247 A WARNING ENTRY !!!!
[H.sapiens]

ESTs; Weakly similar to !!!! ALU SUBFAMILY
4 RC F10966 J WARNING ENTRY !!!!
[H.sapiens]

Homo sapiens ribonuclease P protein subunit 4 RC F13700 p4 (RPP4) gene; complete cds 4 RC H05063 ESTs ESTs; Highly similar to ERYTHROPOIETIN

[Homo Sapiens]

4 RC H17315 karyopherin alpha 1 (importin alpha 5) s ESTs; Highly similar to protein tyrosine 4 RC H22566 phosphatase epsilon cytoplasmic isoform [H.sapiens]

4 RC H48459 Human mRNA for KIAA186 gene; complete cds s 3 5 4 RC H53073 ESTs 2 RC H56559 Homo sapiens mRNA for KIAA61 protein; partial s cds 3 RC H57957 ESTs s Accession Cluster#/ Gene Description PROBESET

2 RC H64938 ESTs s 2 RC H64973 ESTs 4 RC H69535 ESTs ESTs; Moderately similar to alternatively 2 RC H73110 spliced product using exon 13A
[H.sapiens]

2 RC H81783 ESTs 1 RC H86259 Homo sapiens chromosome 19; cosmid 832611 2 RC H88353 ESTs; Weakly similar to reverse transcriptase related protein [H.sapiens]

2 RC H88639 ESTs 4 RC H88675 ESTs s ESTs; Weakly similar to !!!! ALU SUBFAMILY
4 RC N22107 J WARNING ENTRY !!!!
[H.sapiens]

3 RC N24046 ESTs; Weakly similar to 6S RIBOSOMAL PROTEIN
L1 [Homo sapiens]

2 RC N27028 ESTs 2 RC N30205 ESTs; Weakly similar to hypothetical protein [H.sapiens]

1 RC N30621 ESTs 4 RC N33258 Homo sapiens nuclear receptor co-repressor N-CoR mRNA; complete cds 2 RC N40180 EST; Weakly similar to putative p15 [H.sapiens]

2 0 3 RC N45979 SH3 domain protein 1 B
s 2 RC N48913 ESTs 4 RC N49394 Homo sapiens mRNA for KIAA716 protein;
complete cds 1 RC N50656 ESTs; Highly similar to mosaic protein LR11 [H.sapiens]

4 RC N50721 kinesin family protein 3B

4 RC N53143 ESTs 2 RC N53359 ESTs 4 RC N55326 ESTs yv5c2.s1 Soares fetal liver spleen 1 NFLS
2 RC N55493 Homo sapiens cDNA clone IMAGE:246146 3', mRNA sequence 2 RC N62955 ESTs; Weakly similar to ankyrin G [H.sapiens]

4 RC N63520 EST; Weakly similar to mariner transposase [H.sapiens]

4 RC N63604 ESTs 2 RC N64166 frizzled (Drosophila) homolog 7 3 5 2 RC N64168 ESTs 2 RC N64191 ESTs ESTs; Weakly similar to !!!! ALU CLASS
4 RC N66845 B WARNING ENTRY !!!!
[ H.sapiens]

4 RC N67135 ESTs Accession Cluster#/ Gene Description PROBESET

2 RC N67295 ESTs 4 RC N68399 H2B histone family; member N

4 RC N68963 ESTs 4 RC N69331 peptidylprolyl isomerase C (cyclophilin C) 2 RC N70777 ESTs 1 RC N71364 ESTs; Weakly similar to transformation-related s protein [H.sapiens]

4 RC N71545 ESTs; Moderately similar to hypothetical s protein [H.sapiens]

2 RC N71571 ESTs 4 RC N75594 ESTs 2 RC N80279 ESTs; Highly similar to (def)ine not available 4239677) [H.sapiens]

4 RC N91797 ESTs 4 RC N92454 karyopherin (importin) beta 1 4 RC N94581 actin; beta 4 RC N94746 ESTs 4 RC N98238 ESTs ESTs; Weakly similar to !!!! ALU CLASS
2 RC 816833 F WARNING ENTRY !!II
[H.sapiens]

2 0 3 RC 841828 myosin VA (heavy polypeptide 12; myoxin) s 2 RC 843203 ESTs 4 RC 846395 ESTs; Moderately similar to Unknown gene product [H.sapiens]

2 RC 858863 ESTs 2 RC 878248 ESTs 2 5 4 RC T11483 ESTs 4 RC T16896 ESTs 2 RC T23820 cyclin T2 4 RC T30222 ESTs; Weakly similar to tetracycline transporter-like protein [M.musculus]

4 RC W15275 ESTs s 3 0 2 RC W38194 Accession not listed in Genbank 3 RC W42414 ESTs s 4 RC W46577 H.sapiens mRNA for ESM-1 protein s 4 RC W49632 Human clone 2398 mRNA sequence s 2 RC W57613 ESTs 4 RC W61118 ESTs 4 RC W65344 ESTs; Highly similar to ICH-2 PROTEASE
PRECURSOR [Homo Sapiens]

2 RC W69216 ESTs ESTs; Weakly similar to mitochondria) inner 2 RC W69379 membrane protease 1 [ S.cerevisiae]

4 0 4 RC W86728 ESTs Accession Cluster#/ Gene Description PROBESET

4 RC 238499 ESTs; Weakly similar to protein phosphatase [H.sapiens]

2 RC 238630 Homo sapiens 1kD protein (BC1 ) mRNA;
complete cds 4 RC 239494 ESTs 4 RC 239623 ESTs 3 RC 240071 BMX non-receptor tyrosine kinase s 4 AFFX-BioB-3 4 AFFX-BioC-3 3 AFFX-DapX-5 1 AFFX-LysX-M

3 RC AA166965 ESTs 1 RC AA169599 ESTs s 3 RC AA171724 ESTs 2 RC AA171739 ESTs 3 RC AA177105 ESTs 2 RC AA182626 ESTs ESTs; Highly similar to cell cycle progression 2 0 3 RC AA186324 restoration 8 protein [H.sapiens]

1 RC AA192099 zinc finger protein 148 (pHZ-52) ESTs; Moderately similar to !!!! ALU SUBFAMILY

!!!! (H.sapiens]

3 RC AA192553 ESTs; Moderately similar to RGC-32 [R.norvegicus]

2 5 3 RC AA194851 ESTs 3 RC AA195520 ESTs s ESTs; Moderately similar to !!!! ALU SUBFAMILY

!!!! [H.sapiens]

3 RC AA196517 Lon protease-like protein 3 RC AA196549 ESTs zq9a3.s1 Stratagene muscle 93729 Homo 3 sapiens cDNA clone 0 C AA196721 IMAGE:629164 3' similar to TR:G746415 6746415 I KAPPA BR. ;, mRNA
sequence ESTs; Weakly similar to !!!! ALU SUBFAMILY
3 RC AA196729 J WARNING ENTRY !!!!
i [H.sapiens]

ESTs; Moderately similar to RETROVIRUS-RELATED

(H.sapiens]

2 RC AA206828 ESTs; Weakly similar to ubiquitous TPR
motif; Y isoform [H.sapiens]

3 RC AA207123 immunoglobulin supertamily; member 3 3 5 1 RC AA214539 ESTs i 3 RC AA226914 TR2 nuclear hormone rece for s Accession Cluster#/ Gene Description PROBESET

3 RC AA227260 Zic family member 3 (odd-paired Drosophila homolog; heterotaxy 1 ) ESTs; Highly similar to CALCIUM/CALMODULIN-DEPENDENT
3 RC AA233122 PROTEIN KINASE TYPE II DELTA CHAIN (Rattus norvegicus]

3 RC AA233334 Homo sapiens josephin MJD1 mRNA; cds s Homo sapiens zinc finger protein 216 splice 3 RC AA233347 variant 2 (ZNF216) mRNA;
complete cds 1 RC AA233519 ESTs; Weakly similar to neuronal thread protein AD7c-NTP [H.sapiens]

1 RC AA233714 Apg12 (autophagy; yeast) homolog 1 RC AA233796 ESTs 1 RC AA235050 ESTs f ESTs; Weakly similar to Wiscott-Aldrich 1 RC AA235704 Syndrome protein homolog [M.musculus]

3 RC AA236031 ESTs 1 RC AA236352 ESTs 1 RC AA236390 ESTs s 1 RC AA236453 ESTs 2 RC AA250947 ESTs 3 RC AA251083 ESTs 3 RC AA251113 ESTs 4 RC AA251973 ESTs 2 0 3 RC AA252023 ESTs; Moderately similar to (defline not available 397874) [H.sapiens]

1 RC AA252414 ESTs 1 RC AA252650 protein kinase; mitogen-activated; kinase 7 (MAP kinase kinase 7) 3 RC AA255523 ESTs 3 RC AA258128 ESTs 2 5 3 RC AA262105 Human mRNA for KIAA331 gene; complete cds 1 RC AA262107 ESTs 1 RC AA262235 ESTs zs8b3.s1 NCI CLAP GCB1 Homo sapiens cDNA
3 RC AA278298 clone IMAGE:73757 3', mRNA sequence 1 RC AA278529 ESTs; Highly similar to serine/threonine i protein kinase [H.sapiens]

3 0 1 RC AA278721 ESTs 1 RC AA280036 ESTs 1 RC AA280648 ESTs; Weakly similar to rab-related GTP-binding protein [H.sapiens]

1 RC AA280738 ESTs 3 RC AA280794 ESTs 3 5 1 RC AA280837 ESTs ESTs; Moderately similar to alternatively 1 RC AA280886 spliced product using exon 13A
[H.sapiens]

1 RC AA280934 ESTs 1 RC AA281535 Homo sa iens mRNA for KIAA879 rotein; com lete cds Accession Cluster#/ Gene Description PROBESET

Homo Sapiens basic transcription factor 4 2 p44 (btf2p44) gene; partial cds;
C AA281797 neuronal apoptosis inhibitory protein (naip) s and survival motor neuron protein (smn) genes; complete cds 1 RC AA282047 ESTs 1 RC AA283002 Human zinc finger protein (SRE-ZBP) mRNA;
3' end 3 RC AA283709 ESTs ESTs; Weakly similar to X-linked retinopathy 1 RC AA283902 protein {C-terminal; clone XEH.Bc} [H.sapiens]

Human DNA from chromosome 19-specific cosmid 1 RC AA284108 F25965; genomic sequence Human DNA sequence from clone 71 L16 on 1 chromosome Xp11. Contains C AA284109 a probable Zinc Finger protein (pseudo)gene;
an unknown putative gene;
a pseudogene with high similarity to part of antigen KI-67; a pu 1 RC AA284371 Homo sapiens clone 23967 unknown mRNA;
partial cds 3 RC AA284744 ESTs f 1 RC AA284784 ESTs 1 RC AA284840 ESTs 1 RC AA286844 ESTs 3 RC AA287032 ESTs 1 RC AA287546 ESTs 1 RC AA287553 ESTs s ESTs; Weakly similar to !!!! ALU CLASS
3 RC AA287556 B WARNING ENTRY !Ill (H.sapiens]

1 RC AA287564 ribosomal protein L37 1 RC AA291015 CDC7 (cell division cycle 7; S. cerevisiae;
s homology-like 1 1 RC AA291749 ESTs s 1 RC AA302430 ESTs 2 5 1 RC AA302820 purinergic receptor P2X; ligand-gated ion s channel; 4 1 RC AA310499 ESTs 1 RC AA321890 EST24442 Cerebellum II Homo sapiens cDNA
3' end, mRNA sequence 1 RC AA340622 ESTs 3 0 1 RC AA342457 ESTs i 3 RC AA342828 glycoprotein V (platelet) s 1 RC AA342864 ESTs 1 RC AA342973 ESTs 1 RC AA346495 ESTs 3 5 1 RC AA347573 Homo sapiens KIAA45 mRNA; complete cds 1 RC AA347614 ESTs 1 RC AA347717 ESTs Accession Cluster#/ Gene Description PROBESET

1 RC AA348913 ESTs 1 RC AA349773 ESTs ESTs; Moderately similar to alternatively 1 RC AA350541 spliced product using exon 13A
s [H.sapiens]

i 3 RC AA357172 ESTs i 1 RC AA369856 Human hVps4lp (hVPS41) mRNA; alternative s splice variant; partial cds 1 RC AA370472 ESTs s 1 RC AA370867 ESTs 3 RC AA377296 ESTs 4 RC AA383902 ESTs 3 RC AA385934 EST; Highly similar to predicted using Genefinder [C.elegans]

ESTs; Highly similar to MEMBRANE GLYCOPROTEIN
2 RC AA386266 M6-B [Mus musculus]

1 RC AA398014 ESTs 3 RC AA398222 ESTs 1 RC AA398235 ESTs 2 0 3 RC AA398348 ESTs 3 RC AA398482 ESTs 1 RC AA398504 ESTs 1 RC AA398505 ESTs 1 RC AA398507 ESTs ESTs; Weakly similar to !!!! ALU SUBFAMILY
2 5 1 RC AA398523 SO WARNING ENTRY !Ill [H.sapiens]

1 RC AA398625 ESTs 4 RC AA398632 ESTs 3 RC AA398633 ESTs 3 RC AA398894 ESTs 1 RC AA398900 ESTs 1 RC AA399122 ESTs; Weakly similar to mitochondria) citrate transport protein [H.sapiens]

3 RC AA399371 ESTs 3 5 1 RC AA399373 ESTs; Highly similar to KIAA568 protein [H.sapiens]

1 RC AA399441 ESTs 3 RC AA399636 ESTs 1 RC AA399640 ESTs 1 RC AA399680 ESTs Accession Cluster#/ Gene Description PROBESET

1 RC AA400262 ESTs 1 RC AA400725 ESTs 3 RC AA400748 ESTs 1 RC AA400780 ESTs zv65b9.s1 Soares_total_fetus Nb2HF8 9w 3 RC AA40163 Homo sapiens cDNA clone 1 IMAGE:758489 3', mRNA sequence 1 RC AA401688 ESTs 3 RC AA402227 ESTs; Moderately similar to N-tropomodulin [R.norvegicus]

3 RC AA402329 ESTs 1 RC AA402398 ESTs 1 RC AA402468 ESTs 2 RC AA403268 ESTs s 2 RC AA403314 ESTs 1 RC AA404260 ESTs 1 RC AA404271 Human glutamate/kainate receptor subunit (EEA3) mRNA; complete cds 3 RC AA405026 ESTs 2 0 1 RC AA405182 ESTs ESTs; Moderately similar to alternatively 1 RC AA405237 spliced product using exon 13A
[H.sapiens]

1 RC AA406063 ESTs 1 RC AA406335 ESTs 1 RC AA411801 Human mRNA for KIAA37 gene; complete cds 1 RC AA411804 ESTs 1 RC AA411833 ESTs; Highly similar to (defline not available 4521278) [H.sapiens]

3 0 1 RC AA412219 ESTs 3 RC AA412259 ESTs 2 RC AA412497 Human Line-1 repeat mRNA with 2 open reading frames 1 RC AA412498 ESTs 1 RC AA416586 ESTs 1 RC AA416874 ESTs 1 RC AA421133 ESTs ESTs; Highly similar to ELONGATION FACTOR
4 RC AA422079 G; MITOCHONDRIAL
PRECURSOR [Rattus norvegicusJ

4 0 1 RC AA423837 ESTs 1 RC AA424328 ESTs 1 RC AA424339 ESTs Accession Cluster#/ Gene Description PROBESET

3 RC AA424469 ESTs s 1 RC AA424502 ESTs 3 RC AA425004 ESTs 1 RC AA425734 ESTs; Weakly similar to neuronal thread protein AD7c-NTP [H.sapiens]

1 RC AA425887 ESTs 3 RC AA426456 ESTs 3 RC AA427396 ESTs 1 RC AA427555 Human mRNA for KIAA23 gene; complete cds 3 RC AA428218 ESTs 1 0 3 RC AA428242 ESTs 3 RC AA428994 ESTs 1 RC AA429666 ESTs 3 RC AA430181 ESTs 1 RC AA430184 Human putative ATP/GTP-binding protein s (HEAB) mRNA; complete cds 3 RC AA431288 CD3D antigen; delta polypeptide (TiT3 complex) s 1 RC AA431293 ESTs 3 RC AA431478 ESTs 4 RC AA434411 ESTs 3 RC AA435512 ESTs i 2 5 1 RC AA435698 ESTs 1 RC AA435711 Homo sapiens mRNA for KIAA712 protein;
complete cds 3 RC AA435815 Clk-associating RS-cyclophilin s 3 RC AA435842 ESTs 3 RC AA436475 ESTs 3 0 3 RC AA436489 ESTs 3 RC AA442060 ESTs 3 RC AA443151 ESTs 4 RC AA446133 ESTs 3 5 1 RC AA447145 Homo sapiens KIAA399 mRNA; partial cds 1 RC AA447643 ESTs 1 RC AA447742 dynein; axonemal; heavy polypeptide 17-like s zw96c1.s1 Soares_total_fetus Nb2HF8 9w 3 RC AA44822 Homo sapiens cDNA clone 6 IMAGE:784818 3', mRNA sequence 1 RC AA449444 ESTs 3 RC AA450087 re ulator of Gz-selective rotein si nalin Accession Cluster#/ Gene Description PROBESET

1 RC AA450244 ESTs 3 RC AA452123 ESTs; Weakly similar to Tcp-1 [M.musculus]

3 RC AA452155 zinc finger protein 198 3 RC AA453036 ESTs 3 RC AA453526 ESTs 3 RC AA454103 ESTs 1 RC AA454642 ESTs 1 RC AA454935 ESTs 3 RC AA456323 ESTs aa26c7.s1 NCI_CGAP_GCB1 Homo sapiens cDNA
3 RC AA458850 clone IMAGE:81438 3' similar to contains L1.t3 L1 repetitive element ;, mRNA sequence Homo Sapiens 3-hydroxyisobutyryl-coenzyme 3 RC AA459668 A hydrolase mRNA;
complete cds ESTs; Weakly similar to The KIAA191 gene 1 RC AA459679 is expressed ubiquitously.
s [H.sapiens]

1 RC AA459702 ESTs 4 RC AA460017 ESTs f 2 0 3 RC AA460324 ESTs 3 RC AA461509 ESTs; Weakly similar to hypothetical protein II [H.sapiens]

3 RC AA464414 ESTs i 1 RC AA464428 ESTs 3 RC AA470084 ESTs 2 5 3 RC AA476606 ESTs s 3 RC AA478521 ESTs ESTs; Moderately similar to !!!! ALU SUBFAMILY
3 RC AA478523 J WARNING ENTRY !!!!
[H.sapiens]

3 RC AA479949 ESTs 3 0 1 RC AA485351 ESTs; Weakly similar to predicted using Genefinder [C.elegans]

1 RC AA487264 ESTs 1 RC AA489072 Homo Sapiens mRNA for KIAA87 protein;
complete cds 1 RC AA489630 Homo sapiens mRNA for KIAA665 protein;
complete cds 2 RC AA490225 ESTs 3 5 3 RC AA490227 ESTs 3 RC AA490255 ESTs 1 RC AA490890 ESTs 2 RC AA490916 ESTs s 3 RC AA490925 Homo sa iens laforin EPM2A mRNA; artial cds Accession Cluster#/ Gene Description PROBESET

1 RC AA490955 ESTs; Weakly similar to bullous pemphigoid antigen [M.musculus]

1 RC AA495812 ESTs 3 RC AA495824 ESTs 1 RC AA496369 ESTs 3 RC AA504125 ESTs s 1 RC AA521473 Human brain secretory protein hSec1 p (HSEC1 ) mRNA; complete cds 1 RC AA598440 ESTs 3 RC AA598899 ESTs i 3 RC AA599244 Homo sapiens mRNA for KIAA53 protein; partial cds 1 RC AA599694 Human mRNA for KIAA133 gene; complete cds s 1 RC AA600037 ESTs 1 RC AA609582 Homo sapiens p6 katanin mRNA; complete cds 3 RC AA609684 ESTs 3 RC AA609839 ESTs 1 RC AA609862 Homo sapiens mRNA for RBP-MS/type 3; complete cds 1 RC AA621364 ESTs 2 0 2 RC C20653 ESTs ' 3 RC D20085 ESTs 1 RC D20749 ESTs 2 RC D51285 ESTs s 4 RC D59972 ESTs i 2 5 4 RC F04112 ESTs f 2 RC F13604 ESTs 1 RC H01662 ESTs 1 RC H05135 ESTs i 3 RC H12245 splicing factor; arginine/serine-rich 7 (35kD) 1 RC H30894 ESTs 2 RC H43442 Human mRNA for KIAA28 gene; partial cds s 3 RC H45996 ESTs 2 RC H69281 ESTs i 3 5 3 RC H69485 ESTs f 1 RC H69899 ESTs; Moderately similar to unknown [H.sapiens]

4 RC H70627 ESTs s 1 RC H73050 Rhesus blood group; D antigen s 1 RC H73260 ESTs 4 0 1 RC H77531 HIR (histone cell cycle regulation defective;
s S. cerevisiae) homolog A

4 RC H80737 lysyl oxidase s 1 RC H93412 ESTs 3 RC H94892 v-ral simian leukemia viral onto ene homolo s A ras related Accession Cluster#/ Gene Description PROBESET

4 RC H95643 neurotrophic tyrosine kinase; receptor;
s type 1 2 RC H96552 ESTs ESTs; Highly similar to G protein-coupled 4 RC H97146 receptor kinase 6; splice variant B [H.sapiens]

2 RC H99131 ESTs s 1 RC H99462 ribosomal protein; mitochondrial; L12 s 1 RC H99837 ESTs s ESTs; Highly similar to TUBULIN GAMMA CHAIN
2 RC N22140 [Euplotes octocarinatus]

2 RC N22197 ESTs 1 RC N23756 Human mRNA for KIAA238 gene; partial cds s 2 RC N24134 eukaryotic translation initiation factor 1A; Y chromosome 4 RC N24195 Homo sapiens mRNA for RanBPM; complete cds 1 RC N26739 CAAX box 1 1 RC N27637 ESTs 4 RC N33090 ESTs; Weakly similar to translation initiation factor [H.sapiens]

1 RC N35967 ESTs Homo sapiens chaperonin containing t-complex 1 RC N38959 polypeptide 1; beta f subunit (Cctb) mRNA; complete cds 2 RC N39069 ESTs 1 RC N46441 ESTs 2 0 2 RC N48270 ESTs f 2 RC N48365 ESTs s 2 RC N51316 ESTs 1 RC N51499 ESTs s 4 RC N53976 ESTs 2 5 2 RC N54157 ESTs 2 RC N54300 ESTs 1 RC N54831 ESTs; Weakly similar to neuronal thread protein AD7c-NTP [H.sapiens]

2 RC N59849 ESTs 4 RC N62132 ESTs 4 RC N63138 ESTs 1 RC N63172 cell division cycle 42 (GTP-binding protein;
25kD) Homo sapiens DNA sequence from PAC 434014 on chromosome 2 1q32.3.-41. Contains the HSD11B1 gene for C N63772 Hydroxysteroid (11-beta) Dehydrogenase 1; the ADORA2BP adenosine A2b receptor LIKE
pseudogene; the IRF

2 RC N63787 ESTs za11c1.s1 Soares fetal liver spleen 1NFLS
3 5 2 RC N68168 Homo sapiens cDNA clone IMAGE:292224 3', mRNA sequence 2 RC N68201 ESTs; Weakly similar to hypothetical protein [H.sapiens]

2 RC N68300 ESTs Accession Cluster#/ Gene Description PROBESET

1 RC N68321 solute carrier family 2 (facilitated glucose transporter); member 3 2 RC N75007 ESTs 1 RC N75542 ESTs 2 RC N90066 Homo sapiens clone 24689 mRNA sequence 1 RC N91246 ESTs ESTs; Weakly similar to cyclic nucleotide-gated 1 RC N92751 channel beta subunit [R.norvegicus]

2 RC N93214 ESTs s 2 RC N99148 ESTs; Highly similar to MKR2 PROTEIN [Mus musculus]

ESTs; Weakly similar to HYPOTHETICAL PROTEIN

[Haemophilus influenzae]

1 RC 810865 alpha-fetoprotein f 2 RC 811056 ESTs 2 RC 811488 ESTs 1 RC 822947 ESTs 2 RC 823930 ESTs s 1 RC 826589 ESTs f 4 RC 837588 GDS-related protein s 2 RC 837613 ESTs 1 RC 838398 Homo sapiens clone 23758 mRNA sequence 2 0 2 RC 839179 ESTs f 1 RC 840923 ESTs 1 RC 841179 Human mRNA for KIAA328 gene; partial cds 2 RC 841294 ESTs s 1 RC 842307 early development regulator 2 (homolog f of polyhomeotic 2) f 3 RC 843306 ESTs 1 RC 844357 ESTs 1 RC 844519 EST; Moderately similar to Pro-Pol-dUTPase polyprotein [M.musculus]

yg38g4.s1 Soares infant brain 1 NIB Homo 2 RC 845088 Sapiens cDNA clone IMAGE:34896 3', mRNA sequence 3 0 2 RC 847948 ESTs i 1 RC 851524 ESTs 1 RC 854950 ESTs 1 RC 859585 ESTs 3 5 1 RC 860044 ESTs 2 RC 860872 ESTs 1 RC 866690 ESTs 2 RC 867266 exostoses (multiple)-like 1 s 1 RC 873588 ESTs 4 0 3 RC 879403 ESTs Accession Cluster#/ Gene Description PROBESET

1 RC 887647 ESTs 2 RC 893622 ESTs 4 RC 899599 heterogeneous nuclear ribonucleoprotein s U (scaffold attachment factor A) 4 RC 899612 ESTs FB14D6 Fetal brain, Stratagene Homo sapiens 1 RC T02888 cDNA clone FB14D6 3'end, mRNA sequence hbc313 Human pancreatic islet Homo Sapiens 2 RC T10465 cDNA clone hbc313 3'end, mRNA sequence 1 RC T15418 ESTs f 1 RC T15597 Homo sapiens mRNA for KIAA661 protein;
f complete cds 2 RC T15652 ESTs i 2 RC T16898 ash2 (absent; small; or homeotic; Drosophila;
s homology-like 1 RC T26644 ESTs; Weakly similar to zinc finger protein i ZNF139 (H.sapiens]

2 RC T40841 ESTs yb15c11.s1 Stratagene placenta (#937225) 1 Homo sapiens cDNA clone C T47566 i IMAGE:71252 3' similar to similar to gb:Z2157 ELONGATION FACTOR
1-DELTA (HUMAN), mRNA sequence ESTs; Moderately similar to EA22 GENE PROTEIN
2 RC T50116 [Bacteriophage lambda]

2 RC T50145 FSHD region gene 1 s ESTs; Moderately similar to !!!! ALU SUBFAMILY
2 RC T58615 J WARNING ENTRY !!!!
[H.sapiens]

1 RC T59940 ESTs f 4 RC T63595 ESTs ydlc2.s1 Soares fetal liver spleen 1NFLS
2 0 2 RC T64891 Homo sapiens cDNA clone IMAGE:66722 3', mRNA sequence 2 RC T64924 ESTs 2 RC T64933 ESTs; Weakly similar to hypothetical protein r [H.sapiens]

yc3f5.s1 Stratagene liver (#937224) Homo 2 RC T68875 sapiens cDNA clone IMAGE:8229 3', mRNA sequence 2 RC T69027 ESTs yc19d3.s1 Stratagene lung (#93721 ) Homo 3 RC T69924 Sapiens cDNA clone I MAGE:81125 3', mRNA sequence 3 RC T70353 ESTs ESTs; Weakly similar to PUTATIVE MITOCHONDRIAL

s YBR291 C [Saccharomyces cerevisiae]

2 RC T79951 ESTs 3 RC T80174 ESTs s 3 0 3 RC T80622 ESTs; Weakly similar to envelope protein RIC-7 [H. sapiens]

1 RC T85352 ESTs 1 RC T85373 ESTs Accession Cluster#/ Gene Description PROBESET

2 RC T86284 ESTs; Weakly similar to transformation-related protein [H.sapiens]

Homo sapiens E2F-related transcription 1 RC T89579 factor (DP-1 ) mRNA; complete s cds 3 RC T90360 ESTs 2 RC T94328 ESTs i ye4a3.s1 Soares fetal liver spleen 1 NFLS
1 Homo Sapiens cDNA clone C T95590 IMAGE:12172 3' similar to gb~M1817~IGURRAA
Iguana iguana 5S
(rRNA);, mRNA sequence 4 RC T97257 ESTs; Weakly similar to hypothetical protein f [H.sapiens]

2 RC T97599 ESTs i 2 RC T97620 ESTs; Weakly similar to unknown [H.sapiens]

4 RC T97775 ESTs 3 RC T98152 fibrillin 2 1 RC W31479 ESTs 1 RC W37999 ESTs 2 RC W38240 Accession not listed in Genbank 2 RC W40150 human chromosome-associated polypeptide (bamacan) 2 RC W45435 Homo sapiens mRNA for KIAA784 protein;
partial cds 2 RC W58202 ESTs 1 RC W58344 ESTs 2 RC W58650 ESTs Human DNA sequence from clone 1189824 on chromosome Xq25-26.3.
4 Contains NADH-Ubiquinone Oxidoreductase C W68736 MLRQ subunit (EC 1.6.5.3;
EC 1.6.99.3; CI-MLRQ); Tubulin Beta and Proto-oncogene Tyrosine-protein 2 0 2 RC W69106 ESTs 2 RC W69111 ESTs 1 RC W69385 H.sapiens NuMA gene (Clone T33) s 3 RC W69399 ATPase; Ca++ transporting; plasma membrane s 1 3 RC W69459 ESTs 2 RC W72424 S1 calcium-binding protein A9 (calgranulin B) 2 RC W72724 ESTs 2 RC W72834 ESTs 1 RC W73955 Homo Sapiens chromosome 19; cosmid 826445 2 RC W74701 ESTs 3 0 2 RC W76540 ESTs 2 RC W79397 ESTs ESTs; Weakly similar to synapse associated 2 RC W85888 protein sap47-2 [D.melanogaster]

2 RC W86038 ESTs 2 RC W86881 ESTs 3 5 2 RC W87804 ESTs zh7b5.s1 Soares fetal_liver_spleen_1NFLS
2 RC W88942 S1 Homo sapiens cDNA
clone IMAGE:417393 3', mRNA se uence Accession Cluster#/ Gene Description PROBESET

3 RC_W90022 ESTs; Highly similar to LECT2 precursor [H.sapiens]

2 RC W92272 Homo sapiens zinc-finger helicase (hZFH) mRNA; complete cds TUMOR NECROSIS FACTOR-INDUCIBLE PROTEIN

s PRECURSOR

2 RC_W93040 ESTs 3 RC W93092 neutral sphingomyelinase (N-SMase) activation associated factor 2 RC W93523 ESTs 2 RC W93659 ESTs 2 RC W94003 ESTs s 2 RC W94401 ESTs s 2 RC W94688 Homo sapiens mRNA for perilipin; complete cds 2 RC W94787 ESTs s 2 RC 238294 ESTs s 3 RC 238311 ESTs 2 RC 238465 ESTs s 2 RC 238525 ESTs s 2 RC 238538 ESTs f 2 RC 238551 ESTs s cat+-dependent activator protein for secretion;
2 RC 238783 Ca2+-regulated s cytoskeletal protein (CAPS) 2 0 2 RC 239113 ESTs 4 RC 239255 ESTs f 2 RC 239783 ESTs s ESTs; Highly similar to NADH-CYTOCHROME
2 RC 239920 B5 REDUCTASE [Bos taurus]

2 5 2 RC 240166 ESTs f 3 RC 240388 ESTs s 2 RC 240646 ESTs 2 RC 241697 ESTs 2 RC 299349 ESTs 3 0 2 RC 299394 ESTs~ Weakl similar to transformation-related s rotein H.sa iens Table 2 0 o X ~j U v U

U x o U v U ~
~

Z Z

(~ ~ fB (p ~
f0 -d d ~ a d d .. a Q
Q ~

E- H- E- f- H f- H H H

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~- >- Z Z

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a - - - - - _ ~ _ .n a~ a~ a~ a~ a~ m a~ a~ a~
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> >, >. >, > >, >, T
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f- f- H

Z 7- Z Z Z Z Z Z ~ Z ~ ~ >- Z Z Z Z ~ Z Z Z ~ Z Z ~ Z >- Z
Z ~ Z Z r 7- Z Z Z Z ~ ~ ~ Z Z Z ~ Z Z Z Z >- J- Z Z ~ Z Z
f6 t C L f' f~0 N
O Y U
d '00 _Q. w w a0 O
N O N 41 " ~ C
d ~ C C ~- O
O) .C d ~ N
O O N >' O "_O _a y L N f0 o a c o N
p ~ .U M V N N ~ ~ ~ ~ v E
O
L X O O 7 ~ ~ d N C ~ ~ N
N a7 v Y Y " Q7 L _ ~ N l' O O ~ ~ a f9 d (O ca M ~ y C N C7 a d C ~ N O O
L L ~ ~ ' ~ O N N ~ ~ ~ ~ 'D N =' ~ U U
C C 'p O J J fD (O N N 07 w ~ O v NN~CC 10 c4 C~ _R .L-T.
7 d C :D ~ _ ' .. v- ~V ~V
CCCC _CNNCN~NO O.a~O~O~ICOO aOnL
~7 O f' m L y U U C ~ ~ L N N N Q ~ a Q O O
ao _a~ o_ a o _a y .. o ~ o - T _T v o o m ~° ~° ~ U U :__ m a~
m ..
N ~ N ~U ~U ~ L + d U O O O L L . _ C C
c = N N C ~ Q c Y c~ a a a a c_ ~ ~ ~ a c X
N O C C ~ m ~7 U N N ~ ~ U F- O O U N N N L L C 01 U ~ Q N In c c ~' ... ~ m ~ y Z c ~ ~ c o~ a~ o io m m ~ ~ m o~ ~c a~ ~ w a~ a~ ~' u' 0 0 o m ~ ~ E ~ c .~ c c '~ m m a v v' ~ ~ ~ ~ '~ m c ~ _> _>
Q U 'N ~N c0 ca C N O ~~ N Y ~~ p O X C C C L L C C C d O ~ O p~ N U U U
VJ C O U ~ ~ ~ L >, Q d ~ ~ ~U E C d 'O_ ~d ~ .~1 ~N N d L M t0 ~ ~ ~ N C C C
(D U U ~U ~U ~ ~- E tn ~ ~ f0 IO O N f0 f0 N cC f0 l0 f0 fG O O O D t O p p O
>, N ~Q Q ~4 f9 N f9 f0 f0 Q L U U U U U U U U U U U U U U U U U U U U U U
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~ X ~ Y J D D ~ J ~ ~ ~ ~ J Z J ~ ~ ~ d.' ~ ~ ~ X Z cn ~ X ~ Z ~ ~ ~ X
~I ~I Q ~I ~I .-I ~I .-i 01 .-I O Z ml ~I ~I ~I .-I .-I .-I ~I .-I ~I .-I p .-I
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1~ N V (D ~ V1 O V O '~! ~ ~ ~ N ~t M ~Y (D M (D 1l1 t0 m N 1~ ~1 1~ ~ O ~ st 1~ ~ O
M O 01 M M O M M N (D N O O ~ at tf ~ N M O V' V O O M
M M M O M O M M O O O O O O M O N M N N M O O O M O M O O O O N O
U ~ ~ ~ U U U N N ~ U ~ U U U N U ~ N N N U ~ N N U N U U ~ ~ U U
U U O U U U O U U U U O U O U U O O U O O O O O U U U O O O ~ U U O
lJJ L1J LJJ W tJJ UJ W L!J LIJ W W L!J lJJ W ~J w W W u1 w ~J W UJ UJ w llJ
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N v ~q ' C C 10 ~ C ~ O
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M O O~ J ~ M O V ~T 'V ~ O O I~ N N 1A N M Q) O M O I ~ O N N N ~T ~' aD O N N M ~O ~O sf O O N N
Q V O O O O O N N N N N N M ~ ~f V
N = N ~ O ~ ~ h ~V sf ~ p V ~ O ~ M
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U
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~I ~I ~I ~I ~I ~1 ~I ~I ~I
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M O N M O '~! O_ N M h ~ h '~ M 00 ~f7 h CO ~ M O M h N_ (D ~ N
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M N ~O CO N N N N O) 07 O ~ ~ a0 N M (O h t~ 1~ 00 N N M V O O M O
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0 0 C) ~ ~ ~ ~ 0 ~ C) W W W W CL <L W W l1J LIJ LLJ UJ W W w 111 w W lJJ 111 w l1J W LL W U! W UJ UJ
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d d - d f- H f-Z Z Z Z Z Z ~ Z ~ Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z ~ Z Z Z Z Z
Z Z Z Z >- Z Z Z Z ~ Z Z Z Z Z Z Z Z Z ~ Z Z Z Z Z Z Z Z Z Z Z Z Z
N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N
f-E-HHHHHHhf-HI""1-"HHf"f-E-H1"~f-HH~E"_~ f"'f-'f-_1-f-f-~f-ln fn (n (n (n In (n (n In fn (n fn (n (n (n In fn (n fn In (n N fn fn (n (n fn fn fn fn fn (n UJ fn In W LL w lJJ w L1J U! W W W lJJ W W w w W W lJJ W 111 W LL W LL V! lJJ W w W W W
LL LI! W W
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U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U U
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~1 ~1 I ~I ~i ~I ~I ~I ~I
Q Q Q Q Q Q Q Q m m m m m m m m m m m m m m m m m m m m U U U U U U U
M V M O~ O (D h ~ M O (O t~ O f0 (D 01 O N M O 1~ O O ~ 00 ~
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O O O O O O O O O O O O O O O O
In (n In (n In (n fn N In In (n In (n In (n (n fn In Cn !n fn (n fn In fn fn fn fn fn fn In (n (n fn In O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O
W l1J W w W W W LL lJJ 111 W LL w W L!J LlJ W w W W V! W W W W LJJ W w w lJJ w lJJ W 111 llJ

~'a~le 2, c~nt~
O U O U

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U U U o U o U O U O

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Z Z Z ~ Z

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U

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Z Z Z Z

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a~ a~ ~ a~ a a a a a a ET H H H H H

7- r Z Z Z Z Z Z Z Z Z ~ Z ~ Z Z Z Z Z 7- Z Z Z Z Z Z Z Z Z Z Z Z ?~ Z
~ Z Z Z Z Z Z 7- Z Z Z Z Z Z Z Z Z Z Z 7- Z Z Z 7- Z Z Z Z Z Z Z Z 7- Z
N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N
f- f- E- f- H- f- I-_ f- I-_ I-'y- ~ f- I- f" I-' f- f- f- ~ H H H H f- H I-t"_ f- ~.. I- H H I- H"
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U U '-I U Z U
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U U UI U DI DI D D D D D Z Z ZI Z QI CSI QI Q U U Q Q m Q Q Q Q Q Q Q QI Q U Q
Q~ M N (O tn V N ~- O) f~ h O U7 (O O M 1~ fD f~ CO O t0 OD 01 V h N ~ M (O f0 O 00 '- M
1A ~ 00 a0 C ~ (D 00 Of M ~ t0 O ~ M ~ a0 f0 <D ~ ~ N ~ M ~ QI O a0 I~ 00 N In e-N O~ O O N N_ t_~ N O~ O N N M st tn a0 O sf of tn ~ (O Iv CO O_ O_ ~_ ~_ ~_ (O m_ O_~ M M 00 (D f0 f~ f~ O N M ~ ~ 1n 1~ h f~ 07 O Q~ 01 O O O O O N N N
N N N N N N N N N N N N N N N M M M M M M M M M M M M M M M M
lJJ w w W UJ W UJ LJJ lJJ V! l1J L1J W lJJ tJJ V! L1J LJJ LJJ L1J w W W W W w 111 lJJ lJJ 111 W W W lJJ l1J

'Table 2, oon~

x U U
U

U

>. o U X

Z

Z

_ (B

N N
1Z a Z Z Z Z Z Z Z Z Z Z Z Z Z ~ Z
Z Z Z Z Z Z ~ Z Z Z Z Z Z Z
Z Z Z Z Z Z

U X
Z N

_ Z_ N

_ a_ a~ a~
a a H H

Z Z Z Z Z Z z Z Z Z Z Z Z ~ Z Z Z Z Z Z Z 7- Z Z Z Z Z Z Z Z Z Z Z Z Z
z z z ~- z z z z z z z z z z z z r z z ~ z ~ z z r z z z ~ z z z z z r M ao ~ ~ <o ~ ~ ~, E ~ ' cn cn cn cn cn cn "' z °' o o Z ~ ~ t a ~ >- >- >- r >- ~ m d c ~ H z O O J_ J_ J_ J_ J_ J_ J_ a v v v Wn H
w m c U ~ ~ ~ ~ ~ ~ ~ ~ m a Q' ~
a> a~ a~ a~ a~ O z ~~ r tn Q Q Q Q Q Q Q 'm 'm N
m m m m m d z c ~°, ~ ~ I~ I~ u' t~ u' u' m c>o = O Q
g > > > > > > > o m m m m m ~ ~ '~ .~ U ~ (n fn fn (n fn fn c c N m U
o » » » » ~ ~ ~ ~ Q g O O O O O g ~ p Q J J J J J J J J C c C
c c c c c ~ ~ Q Q Q Q Q Q Q Q c 'c o ~, O
a~ a> u~ c~ u~ ~ -: _: -: -_: .: _: -: _: ~ c ~ Y a Q
c c c c c ~ Z o _. _. _. _. _. _. _. _. ~ a O O O O O O O O O O O O O
(n .t.. > .:
m m c'a <'n m m c'a m m m c'n m p 0 0 0 0 0 0 0 0 0 ~E '~ ~E y y E 'E 'E E ~E ~E ~E ~E
f9 W f9 l9 _A _(O _IC W _(O ~N 'N 'N 'N 'N 'N 'N 'N 'N 'N 'N 'N 'N O
T >. T T 7, T T >, >, T T 7. T E
E E_ E E E E E_ E E ~ a~ a~ ~ a~ a~ ~ a~ a~ a~ ~ a~ a~ ' N N N N N N N N N O R ~ ~ ~ ~ ~ ~ ~ ~ O ~ tp T
T T T _T >. ?. >v >. T ~ N C7 d N O 47 N N d N N d Y
L L L L t L L L L 'p ~ ~ ~p ~ -p ~ ~ ~ ~ ~ ~ ~ (d ~ O O O O O O O O O O O O O d FN H H H H F- FN IN H H EN H F- fN IN H H fN h H IN IN H F- h H fN EN H H ~ ~
EN IN H
tn N tn ~ (n (n (n (n (n (n (n (n (n tn In (n tn (n (n (n (n (n fn (n fn fn (n tn (n !n (n In In fn tn LL w W LL L!J W W lJJ LL 111 w LU 111 w lJJ L1J w UJ lJJ W W lJJ W W L!J UJ W
W lJJ UJ W LLJ LJJ UJ 111 D U U I Q U Q U ~-1 Q U
M ao ~ M_ m ao ~ o ~ cc r~ a~ a~ v ~n a~ o a~ ~ co I n N
a~ v Wn I v t ~_ o~ n ca ao c M ao ca r~ ao w U o~ c~ I
p v1 N Q a~ N m N U Q m wn o~ o o ~ v ~_ o_ n ao M o r~ ~ M o o m ~ 1W M N N I 00 MI O 00 O O N f0 V 00 N V_ ~ ~ N O 1~ O ~I7 O) 07 t< D ~ ~' Q_7 'vt O O ~p N V I N ~ ~f O p N O (O I sf V' st tn O M st ~ O N st N ~ sf N tn N
v I 1 I I ~ I O I .- v I M I ,~ I I I I I I I I I I I I I I I op I I I N
d' ~ ~ d' Z ~ ~ d' ~ d' h ~ ~ ~ ~ d' ~ ~ ~ ~ ~ d' ~ ~ ~ ~ O ~
Q m m Q QI Q m Q QI Q Q Q Q Q QI Q Q QI Q QI ml 00 D U Q U D Q D Q Q Q ml Q Q
O Q~ O 07 O Q_~ m N M O ~t'f O N ~ a0 ~' ~ 00 4'! f0 N O_ h f~ O f0 M ~ OD fD
O_7 O h m M_ f~ C N 07 O O ~ st N h 07 O~ O st 00 O t0 O a0 O tn Q~ O~ ~ N V N_ 01 O O O N V a0 N O~ O 00 ~ O 1~ M 1~ O st OD M (~ f~ 00 N ~ (D O N ~ ~(7 N O
N M M M M M M M ~ sf ~ th O~ (D t0 cD (D pp N ,-. p7 ~ 1~ N 11) M (D a0 ~ N ~1 V
M M M M M M M M M M M M M N M O O O O N N O N O N O N O O M
In fn fn fn fn (n fn In In fn (n fn N !n In UJ (/J fn UJ (n fn fn (n fn In V7 (n (n V7 fn fn (n fn fn (n O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O
w l1! 111 W w W lJJ IJJ W w W L!J w lJJ lJJ W <L W lJJ U~ V! UJ W UJ L!J Ii!
lJJ W LL W LL W lJJ U! w Table 2, coat.

x U

U U U T U U

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U U U
U U

Z Z z Z
Z Z

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_ _ _(U _ _ _ _ m N m m N N

a d d d Q. a. a.

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~

Z Z Z Z ~ >- Z Z Z Z Z Z Z Z >- Z Z Z ?- Z >-~ Z Z Z Z Z Z Z

U
U U U
U U

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Z
Z Z

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~ _ _ _ _ N N N N N N N
n n n n n a a >, T >, T >. ~, f- H H I- f- H f-z z z z ~ z r r z z z z z z z z z r z z z r z r r z z z z z N
Z Z Z 7- Z Z r Z Z Z Z a Z Z Z Z Z Z Z Z Z Z Z Z Z Z ~ Z Z H Z
f9 '--' 'V O ~ ~ D O Z O _N ~U E N
N C N C O n ~ N N ~ M p~ n X
v ~ _p ~a~ m 'a~ y O ~ c_ Z L m d ~ c ca o J ~ Z U E O N U O O N n E' fa C ~ N O
L Q n E O Z ~ E C_ c9 E U ~X U n Z O O n O O 07 f0 O O O 7 7 N U 01 'D O n O ~ O) N a0 a0 C E N C N
f9 l1J E N T O d N O f9 V- U ~ ~ O N N O N C ~ C N
O O .L... O O ~ d a U p N N C O v L ~ X V O C
m c a E ~ o n a'~ :°_ v ,a a~ a~ 0 ~ ~ E °~ ~ c d c ~ n m ~ ~ ~ a N o c . o N Y n p y ~ v ~ o~
~ a~ c = Q c ~ c p o' n ° m M ~' ~ ~ ~ c p ~ ~ ~ ~ . c N ~ a N c ~ L o o ~ p o Q m Q ~ ~ E N E ~ ~ '~ y U m o n c m N y ~ N cc n ~ c n p E U
N t4 O ~ n C ~ C O E
_ "7 E Z C O N. (n M N ~ w ~ C ~ '(p O t C O C N O O E w O
0 0 0 0 0 0 0 0 0 0 0 0 o y c ~ -- ~ c E o. n ~ ~ ~ Q ~, s N N c4 fa f0 f0 ca fC l9 c0 f0 l0 t4 C C O ~ C C ~ ~ O N O ~ 'O" U ~ z C d O
~E E E E ~E ~E ~E ~E E E E E ~E ~ia ~ia °W n m ~ ~_ v 'a o ~ ~ ~
° ~°- ~ ~ a~ E
~fn ~N ~N ~N ~N ~fn ~t/1 ~Vl ~N ~N ~N ~N 4! N N ~ ~ ~ ~ J ~ O ~ C C p ~ Z Z E
M N
7. 7, 7, T T T T T T T 7. ~ >, vp t w ~ a T d d N ' N ~ O ~N
YYYYYY-YYYYYYY _~ _~ C_~a ny O p O O U IC E E
N O 'N N d N O N N N N N N U U L C C f0 .17 ~ U p ~ p U 7 N
~O ~O 'D ~~ ~ Q m ~ ~ ~C C O O C N G7 N N N ~
N N N N N fn N f/1 .fn N N t/1 N ~ ~ O C ~ C C O ~ O O O 'C N N fn0 N N fn4 t I- F- ~ ~ F- ~ H ~ ~ I- F- I~ ~ Y Y T O E ~E n n N A N N N 1/! N N
!n (n (n ~ (n (n (n (n (n (n fn fn ~ > > ~ ~ ~ (9 f0 O f0 d ~ ~ 7 '~!
lJJ CJJ W 111 lJJ W w LGJ W W W V! W N d :~ w Ii. C ~.. w C7 O m C7 U' O _ D o n ~ n ~ ~ v t n UI U UI I
~'I O v N ~ N ~ ~ M ~ ~ N 1- ~ ~ ~i ~I M v aOD MV M N O ~ ~ ~Cl ~V ~ ~ O _ = Q EI _ U U m fN~ ~ ~ ~ f- ~ ~ ~ ~ ~ N ~ O ~ O O ~ f0 ~ N O M C~0 ~ O N H '? (D OOD
o U UI N U U U U U U U U U o M 'r N M M N N ip N c v n ~ M I I ~ ~ o ~ n. ~ °~ o C7 ~n m yn o m ~ in ~n ao U U p, o 0 I I I I I I I t I 1 I I 1 X ~ ~ X 2 X ~ J J X X X ~ ~ X X ~ ~ X X X
Q U Q Q Q Q m m D Q Q Q D .-I ~t .-I ~I ~i r-I .-I ~I ~I ~I ~I ~I ~t .-I ~I Q
DI D ~I ~I ~t O~ (D ~ ~ N h 1~ f~ (O O M O O ~ M h M fD O N h N h N_ 07 ~ M_ ~ 00 'Q N CO CD
07 CO O_ O st c0 ~ t~ a0 st V N M N N a0 OD O ~ et M sf ~ t0 N O M O (O (O a0 O 00 (D 01 07 st ~ O CO a0 (D h M t0 O~ ID N_ h 00 O tn N M st N c0 M O N
N 1~ (D OD K1 N M N M N 1!7 (O M N N O N C~ ~ N N N M M In M M M N
M O N O M N M O O M O O O N O O O O M M O O O O M M N M O O M
(n fn (n fn (n (n (n fn fn N (n (n In (n (n In fn In N (n (I7 (n (n fn fn In In In (n fn !n In In In fn O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O
lJJ UJ w LJJ W (1J w l1J w lJJ LL! W W <L LL lJJ W lJJ LJJ LU W W IL LL W Lll W W W W UJ W W UJ W
l Table 2, conk o T

U U
U

U w. .r j ~ Z Z

i z Z

N f4 ~ f>3 _ N

N N N ~ N N

d a Q. d d. Q.

f- F- E- H f- H

Z >- Z ]- Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z ~- Z
~ Z Z ~-Z

U U
a~ Z Z

N c0 L ~ - f0 =

O' a T
~

> , > T >.
, . H H H
H N >
~ f- N

z r z ~ r z r z z z z z z z z z z z z z z z z z z z z z a~ r z r r z z z ~ z z r r z z z z z r r z r r r r z z z z z z z r ° z z r z N H U U U U U U ... >
Z O U
°~ c E ~ m m iu is m o 0 o E ~ ~ °- ,n Q ~ Q Z m ~ a' c r r r r r ~ '. .r Y a~ E ~ Y c Q Z ~-x U N a~ m m m m m U n c d 'a~ Z ~ E H
w U a~ a~ ~ hi c o a a a n n M M M J E y U o ~ E o ~ n c c c c c o 0 0 ~ c°~ o ° o. E "' n, -- a~ a m ~ ~ ° 'a~ '~ 'a~ 'a, '~ ~ ~ ~ v N ~ o ~ Y E
M ~ y O tC W >. ~ ~ d a a d a U ~ ~ i(~7 tNC Z ~ L C V N ~O ,>J
O C U n C7 N G7 U
m Q Q Q a °' ~' ~ ~ v ~ a~°o m ~ r ~ ~ ~ 'c E .~ ~ o ~ ~ ~ o ~_ o Z 5i N ~ ~ !r ~ v v ~ N- ° 0 0 0 0 ~ n p Q D m 'a~ ~ °' ~ ~ ~ a ~ o E E v>
t E E E ~ 'N ual ~° Y Q Q Q U ° Q. m y °-' a~ E oo d L a~
Q Y Y Y Y Y c Z Z Z Z s a ~ o ~ E . ~ U ,o"
Y ~ co ca t~ !r - Q Q Q m '- ~ ~ ~ ~ O
O Z V '° N N N E ~ y ~ " ~ ~ .~0. ~ w w U U U y ~ O ~ Q V c9 ~ Q ~
O
Q ° t o 0 o a Q Q Q Q Q Q Q Q Q Q Q 'N ~ ? L o Q :° ~ o ~ o a o ~ ~ N U U U U oWG E E E E E E E E E E E E .~ ~ c~ ~ ~ N a° ~ '-° o :o O f9 N N Vl V1 fn !A M N N f/7 N tA M t/) N V! N N f/f f6 C - O ~ E -L ~ Q
C ~ C C C C C C C C C C C C C C C C C C C > C '~ O M A O N O.
U y O VOf Q d d t1 d d d d d d d d d d d Q d d d ~ T 7, ~ O N EO O O t0/) d ~ X (9 N f0 f0 f9 f9 f0 la f9 f6 f0 (O f0 f9 lO l0 f0 fQ f0 f0 U U U C7 CJ L L
!!~ d ~' E E
L O C N M N N N N N N (A 4! In 4) 1I! N tIl fn 1/l N N C C C C C C C C C C C C
(n O -1C O O O O O O O O O O O O O O O O O O O cC ffl N fa l0 c9 cG N c0 la tG
f0 ° E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E
y y y ~ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 > > > > > > > > > > > >
x r L L x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x tn Q a~ Q Q 1 Q
I M O M M M Q I 00 CO w CO
O U O V N 1~ at V M O I
H' ~I J a00 000 O ~ ~''~ ~I (~O vc) OM0 (OD aMD
x Q Io v_so c_~~U oM.-m o v_ CO O O N Q7 CO O ~ O tW 07 M ~ N Z ~ ~I ~ O ~ ~ ~ ~ N N ~ 10f1 (M0 (~O
N O O t!7 M M I N o v I I o~ 1 1 r~ ~ I I N 1 ~ ~ ~ ~ ~ ~ ~ a I ao ~ t~ I
U o o n c~ N o~ U o o .p U U r~ U U r~ ao U U M U .p co ~ N .Q ca o U o co v U
x J X ~ ~ Z J ~ ~ Q ~ ~ ~ ~ ~ ~ Z p ~ ~ ~ ~ ~ ~ > > J J ~ ~ ~ ~ >
-I ~I Q ~I Q ~I ~I ~I ml Q Q Q mI Q ~I m m Z Q ~I ~I ~I ~I ~'I ~-1 <'I ~'I Q
~I ~I ~I Q
00 h ~f h O O V ~ N N (D N I~ CO tL1 t~ tn OD h O M 1~ tff CO ID O N t0 N tl) to f~
00 O M t~ ~ i~ N m ~ ~ a0 O O M M O M V N tn 01 M O 01 (D M O ~ N 1~ N
O 00 t0 ~ 1~ V O~ ~ O 1~ Q7 (O f~ O~ ~ aD M O~ O X17 M M M ID O O_ N_ ~ st ~ O
M
O M O O O M M O O O M M N M M M M O ~ O N N O ~ O M O O O M O O O O M
C) L!J W W lJJ UJ W W W W W l1J W l1J lJJ W LJJ LJJ lJJ W W W W LU liJ U! UJ W V!
w 111 UJ W t1J lJJ UJ

Table 2, cont.

x o a~

x U

a>

U >, r.. U

U Z

Z

f0 (B ~ f0 Q d Q. d Q. d f F- f- I-' Z Z Z Z Z Z Z Z ]- ~ >- Z Z Z Z Z Z Z Z Z Z ~ Z
~ Z Z Z
Z
Z
Z
Z

U Z

l9 O (Q N - f9 a ma a a ~'H T H H
~

f E
F

r Z r ~ Z Z Z Z Z Z Z Z Z Z Z r r r Z Z Z Z Z Z Z Z Z Z r Z Z Z Z
z r r ~' z z z z z z z z z r r r r z r r z z z z z r r z r z r z z c O ~ N ~ ~ - - - _ ~ e4 tC
O O ~ X X X
O N N N N C L d d U ~ L d (d L L L p ' O . p N N 41 C C ~ ~ ~ O y O E O V1 V1 N O 'tn N N N > 7 > > a O O
U U a ~ T _f6 f' Q7 f0 !9 (C M tt L ~ t O D
c0 f0 m 01 m r r o m E ° '_' °' a~ a~ a~ c_ c v m ~ ti ti f9 c9 U ~ ~ ~ ~' m C C C OJ ~N ~..p. O C _N N
d d a N ~ L ~ C C C C N O O U N Y E N Q
l4 O N N td d d d w l0 f9 CC~'~U '~ C_C_C_C O1QI~N~ C CC
of o> E _" ~ '° Z m 'E 'E 'E y C C N N O 'o o a~ a~
C y C ~ ~ ~ V M N C_ C U U d ~ ~ n C f0 N
N .: p O _C ~ _O N N M ~p O L L, ~ p d N C_ ~ ~ 'N N GI
O7 m ~ 'O
O E ~ O U C 07 O O) L U p p E E ~ y N V O
G7 U d w '~ C C C ~ ~ V V C C 7 O N 'p0 '0 N N C d C C
U y U ~ N C ~ ~ 'D O f6 ~ O O ~ O C fC d Y Y T v c v a~ o ° c c c L L w ~N ~N c Q a a~ ~ p c ~ o o N 'm 'm ~ CO N ~ O ~ '~ ~' Q Q Q N O ~ ~ L L O U °U O ~ p ~ ~E ~ l0 Y O (G
C O
Z Z U ~ m N ~' ~ D O D ~ U a~ oW° ~° _° d ° a~
o T r ~ ~ d d ~ ~ v i t ~ m a~ '.- v y a> a~ ~ ~ ~ c c m ~ ao m t -°' c ~' ~ ~ t L
E E ~ 'C .- .O d (p .,.. ~ O O O ~ J Y Y 7 7 CO Y Y C O O H ~ O ~ tn V ;O O O
C C C C C C C C ~ O O O p C C ~C O O N ~ y (A a C O N G1 C C y L
fn -N p (9 N f4 f4 7 7 7 7 7 7 O 7 E L L L ~O ~N ~f/1 ~N ~ d ~ r ~ C ~ ~ ~ C U E ~ 3 E N Q Q
v E c c c c c c c c c c c c ~ ~ y ~[ y N c9 J O T T ~
N ~ O OO O Q NI NI U
a0 ~ N ~ n UI N M 1~ N O_ f0 ~p M 1 ~ M Q' N O ~ NI h I H I ~ N O f0 XI C XI = c0 Q = n7 t_O m a~ ~ ao 'Q M N O ~ 'p Of) et N ~V M O ~ (p M 00 ('~ M V M t~ N f0 N 1~ ~ O M N N N M
OD ~ 00 M f~ M = CO 1~ ~ N ~ CD ~ N M ~ (~O Or0 O CO OWD in ~ ~ 01 ~ O
~ N ~ ~ c0 ~T N C~ U QOf ~ ~ t( C~ M (O N M U N p U ~ N COO 00 U h U O U 000 nC1 O O ~ > > ~ > > Z ~ ~ ~ X X Z ~ ~ ~ ~ ~ D r ~ X X O ~ ~ tn ~ ~ ~ > > Q
~I D ~I ~I .-I ~I .-I ~I ~I ~I .-I Q ~I ~I U ~I .-I ~I ~I D .-I m ~I Q ~I ~I Q
N O (O M et 00 h OD tD fD OD t0 (O N h 00 (O O tn h 07 O O~ 1~ N Qf Q~ O O tn at N ~ 'C N ~ ~1' O ~ '? f0 ~ (D O 00 GO O h Q1 CO ~ N ~ M ~ (O 00 Q) (O N N M O
N
(D M M V V IO M f~ (O M 1~ O t0 1n ~ sf _~f O O ~ ~ OO N fD ~ O '? N a0 f~ V
O ~ N N N V O M O t~ M N O O N M N N N ~ N a0 C7 N N7 Q7 N N 00 M O M O O O O M O M N M O O O O M M O M M M M M O M O N M M M N O O N
~ N U U ~ N U U ~ N N N U
O p O O O O O U O O O O O O O O O O O U U U O U U U O U U O 0 U O O O
w lJJ W L1J W LlJ llJ l1.1 W LL lJJ l1J V! w W 111 W LL! W LL W UJ IL lJ.l IL
111 UJ W W W w w W V! W

Table 2, coot.

V V

U U U L

U ~ Z

Z ~ Z ~ Z

_(U .D - .~

N N

!Z Q

T ~ a T

Z Z Z Z ~ Z Z Z Z Z Z Z Z Z Z Z Z ~ ~ Z Z Z Z Z ~ Z Z Z
Z >- Z Z Z

x d ~ z Z
Z

m a a a T H H

z z z z z r r z z z z z z z z z z z z r r z z z z z r z z z z z z r z r r r z r r z z z z z z z z z z z r r z r z z z z z r z z z r r z o c v _ v ~ o O L ~ C CO O O 7 N ~ N C U D1 d (9 N GI L O L j (NC ate.. C
C
y ~ ~V <U C N N
O O tU/f C _j d r N _ O
U NN ~ O N O V..~'. ~ dU
. _ N E p O T .a O x U O
p C
U.7, N UC LEC_ ~ O-Lp ON _ :YO NNO
p ~ ~ tpn m O p ~ ~p d ~ ~ N T N N ~ C E
E ~° ~- a E v ° o a ~ v ~, °' ~' ~ °? ~ ~c ~
a~
j< a O ~ ~ ~ N d N T ~ C v N (9 GO N C N
N N ' N C ~ N ~ U f0 0p O " (p ~ C'7 Q T c9 C ~ N U ~ (~ ~ ~ O N
N d :°_ v N > ~ m ayn v ? '~ ~v' y m o .- ° ~ E '° o ~ c m L o a N c_ c ~ C~ v ~ d p o o ~ a ~ . ~ v ~ m o °' Q, E c a ~ ~ . ~ .- o ~ x ._ N O w. 0I ~ ~ C X p p C
_=' (4 (9 C ~ O C L y L ~, ' a = y '_. O' E N O Q ~ ~ p N O v C C O U . O O1 a V L d U C E p7 f6 N N ~ N ~ cC Q
C ~ 01 V
°.' :_' ~ _m E '~ - -'' c a~ E y X of c:i °' C > y ~ ~_ ~ N
C O O cD O y ' r d ~ E ~ O ~ C Q U .~C r ~ ~ ' C O p' C
O O O ~ 07 L ~ E O ~ O Z N O ~ '~ )' N loll f0/7 O O N y U N ~>' Ip p ~ ~ Cp <6 U y ~ Of ~ ~ 3 O = 'U ~ E' fC f0 fC = ~ ~ C d U C O ~ C L
N O N N L E N U ~ U d L E ~ w C ~ _N C E ~O ~O O O t~ ~~ ' .~ O ~(C ~ O O
~ E E O N U ~ ~ C_ C C C C U f9 ~O O C ~X O L L L ~' C C ~ . d ~ _U ~0 !C
C C v f0 E O ~ ~ ~N ~N ~N O .. 7, N N ~ ~ N N N N .r0" E ~ O O E V .'- ~ N d O
C N G7 O O O O O E U U U Y C ' O O O ~ N N W ' N p O O O O
f0 N fa i6 N V O >, >. T 7. T O U 7 7 C Q y y t L L . m O O O O
E E E E E E ~ E E E E E c c Z c c o a a a a o_ a a a a a a a a a a o_ n I D NI (D
w ~ ~ wI O O 1"~ NI O
HI f~ f0 N O NI 00 NO
M O ' M ~ _I
O In O M V O (D ~ et N ~ M C'7 OI N (D fD 00 O O ~ ~ ~ (D G1 ~ Q1 M O I~ ~ (O
V M N N ~ O ~ ~ ~ O In Z U N ~ ~ ~ ~ ~ N sf ~ f0 ~ In ~ et ~ M t~ N O
ID C~ O~ a0 I 10 .~ N N M o7 I I O O O M I ~ ~ I ~t M I ~ I I (D OD O~
M IMn l~n o V ~ C7 0 't o V V ~o ago ~ ~ U ~ ch U °~ U o U m U f~ p'rp N (h N o~
D X X X ~ ~ Z J ~ ~ '~ ~ ~ ~ D ~ ~ ~ D ~ D ~ ~ J ~ ~ ~ ~ ~ ~ ~ ~ J D
I (a r-I .-I ~I Q r-I ~I CJ O ~I ~I .-I ~I Q .-I ~I ~I Q Q ~I Q ~-I m Q Q
t~ N t0 ~ 00 O~ a0 O 10 (O ~f ~ 01 1f7 O h N h !'~ O ef 00 t~ c'~ h In N V ~
f0 c_~I O
h 10 (D ~ V M W ~ t~ In N m Q1 a0 CD 1f7 O N 1~ 1~ fD N h O 00 N 1~ (O N O t~
OJ f~
O Ip O~ 00 O (D 1~ O_ N O N O O C7 c_0 1l7 ~T O '.t O aO N 01 sf Q1 f~ M M In O M O_ O f_~
O c~7 N N O~ N O O) N 10 sT at O 10 O O ~ 10 t~7 O O M h ~ N h O c'~ O O N O O O N O M N P'7 O O O O O t~ O O O f~ f~ c~ O O O O ('~ O O fh O
(n fn In fn fn (n N (n In fn fn fn (n fn (n (n (n fn (n (n fn fn In fn fn (n tn (n (n fn fn fn (n !n (n w w w w w w w w w w w w w w w w w w w w w w w w w w w w w w w w w w w Table 2, coot o V ~ U

V U U

U U "

o o > x ~ Z

o ~ .
- Z

Z -Z

_ ca ca c~ ~ -~ -a~
n ~ a n a . .
a 7, T >. >, Z Z Z Z Z ~' Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z ~- Z Z Z Z
]- Z ~- ~ Z Z

U X
N Z Z N

O N

c4 L - ~

N

1" H

Z Z Z Z Z >' ~ Z Z Z Z Z Z Z Z Z Z Z Z ~ ~- Z Z Z Z Z ~ Z Z Z Z Z Z
z r r r z r ~- z z z z z z z z z z z r r z ~- z z z z z r z z z r r z o c v ~ ~ o O 19 t O C pp O 7 y .D ? ~ ~ N C
Q7 ~ N
U ~ ~ j U 47 =~ V ..~'. r T V d U
N W O) T L X O
N UC LEC ~ ~~ Ou1 - :Y~.0-00 tOn~O
N ~ T O m O p N ~w d O t/W' d N ~j C N E
N
U . E N N E ~ O O d ~ ~ ~, O T ~ ~ ~ .C L N
X N O' ~ ~ ~ N O d t/1 >. C v . _ N f9 W _O C f/1 d C ~ C C C ~ N U ;O ~ ~ O. U ~' (~ ~ ~ O y f9 ~ N N
_ ~ ~ B_ 7 ~T' ~~ t6 d O _ _ ° " O O Q ~ L ~ O cC9 ~ Of ~ C a fE N ~ L C O N ~ X
_ f' T IOn N N a N ~ U O. O " ~ f0 C d O E L O O ~ O E C
m m c ~ c r a~ L >. d Q 1° ai ° E hi o o ?? In c~ m C C O Y ~ O 01 T V ~ ~ V ~ E O ~ ~ N ~ ~ N O ~ O N
'a~ 'ao ~ ~ E '~ ~ a~ E y X ~ ~ N c ' > ~ o ~ ~ ~o ~ c o C OO O _c0 ° Y ~C _O d ~ E E p1 'O ' Q U ~C ~, V ~ d Q 01 'N N N
E O O O C O ~ ~ O ~ O Z N O C ~' ~, 10/1 N N O O N y U N T O O' C
p O. ~ f6 p ~ U ~ p1 N ~ ~ 3 U 7 ' ~ E _d _d ~ 7 p) ~ X O
~ N N t E N ~ ~ U d L E O ~ C W N C ~ ~O O O O M T ' ~° ~ c0 L' ~ N
r C7 E E o o ~, p v cc c c c '° ~ ° c ~X a~ L L L Z' ~ c ~ _c~
_~ m p v v C c0 E C O N ~O ~O ~O ~ O E V ~U U Y C ~ O O O 7 ~ ~~ 'O ~ E T O
'W fC N i0 d V O T 7. T T 7. O U > > C Q O y ,= L L ."' O O O E O O O O
E E E E E E ~ E E E E E c c Z c c o a a a n a a a a a a a a a a a n. a I O N M
v O .~1 O at~o M NI NI O
M H I M O C (O O ~.1 O 00 ~ =I
0 0 ~ wn ~ M
sT M N N O O O ~ N 01 ~ Z U N ~ ~ ~1 ~ ~ N '? ~ ~ (O W f7 ~ 'at ~ M h N O
W'rno~~Z~ ~~~a'~D~~~O~O~~J~°~d'»~~~JD
O x x X I 1 1 I I I 1 I 1 I I I 1 I 1 1 I I I I I 1 I I
~I ml ~I ~I ~I Q ~I .-I D D ~ ~ ~ ~ Q r- .- ~ Q Q ~ Q ~- m Q Q
M N cD In 00 01 a0 O In tD V ~ O ~ O h N 1~ M O st a0 I~ M h 10 N ~ ~ tD M O
h In (O V V M In ~ Im0 N 01 O 00 OD tn 01 N 1~ 1~ f0 N h O 00 N t~ 10 N 07 h OO h O Ip pi cp O~ t0 I~ O N O N O 01 M cD In V O s_t O 00 N O) V m ~ M O ~ O M O
O> 1_ O M N N 01 N O 01 N ~ ~ O Ih O C 117 M O O M 1~ ~ CV f~ 'Q' O M O O N O O O N O M N ~ O O O O O M O ~ O M M M O O O O M O O M O
U U ~ ~ U ~ U U U N U U U ~ U U U U N U ~ ~ U ~ U U ~ N U U N
O O U O O O O O O O U O O O O O O O O O O O O U O O O O O O O U O O
W W LIJ LL! W LJJ w W V! W LlJ w w W LJJ tJJ w V! W W w l1J W Lll LL U~ W w W
W U~ w W LL W

'Table 2~ cont r X
U U V

U U U U U

> U

z Z v Z

Z Z

N N

~ .17 f13 ~ ~ . -d d r E- f ~ Z Z Z Z Z Z Z Z Z Z Z Z >- Z Z >- Z Z Z Z >->- Z Z Z Z

Z Z Z Z ~
]-X X ~ U
O O

N N Z Z ~p c0 Z Z

~ a ~ a ~ - _ a a Q n H H H H H

H H

z z r r z z r z z z z z z r z z z z z z r z z r z z z z r z z z z z r z r z r r z z r z z z z z z z r z z z z z r z z r z r z z z z a~ a~ y ° T m o c o 0 o E o~ ~ o E
E ~n L ° ~y c v ~ o L o c _ o r. >. ° ° o. o, ° E
O O7 N V ° ~ L d in d d ~ C tn ~ d ~ E E O M U E O Z
'.~ E N N.U N ~C ~ fir- ~ Q' C
U ~ V N ~ U N ~ C p_ T ~ C l9 C O L V O
E O O C N .C N w C O ~ f0 . p N Q7 N L f0 C . m p C
~ o. a rc ' o c .° Q o r- D v' v a~ ~ E a ~ E c °
O) N N d J ~ E L T ~ L C O 7 N O y ° 7 _f6 ~ ~>
v v ! (0 C C v O ~~ t v 100 L f0 U N C ~ ~ E d O
c . .~ o o n- m E aWo _a'~ o ~?? a~ ' >. ~ o~
E ~ ~ 'E C T = N ~ j ~ C V 'E E ~ ~ a ~ Y .E ,°'n ~ v o ~ °
E
L U a ~ C N O N p ° L O O O N T N f' ~
N .~ .o v d~ 't E E
L L Q ~ U O Y (~ C v O O N ~ O_ C O w U a O ~ L C y > l0 C
N N N ~ _O N - ~ ° y 01 C C N d y ~ T ~ > f0 O ' ~ O N f_6 1/! y O O N E U ~y C ~ O T C U ~p ~ ~ C (0 E ~ L E (~ d X ~ N ~N O E t r s m ~ L ~° D ~, ' °' ~ ° °.' 3 0 ~i ~' v o °' ° a~ c~
N d ~ O ~ ~ d d V G) ~ ~ C N ~ C a Q O ~ m ~ C ~ ~ H ~ O C N N O
N C C p C O ~ ' a O C ~ -p d O C O O f' m -_ O
-- om, C E
N ~ ~ N d E ~ O_ ' Y O ~ V y " p C ~ O O ~ p C f0 L 'N E, C ~ ~ E ~ (C (/7 C t9 d ~ ~ 7 ~ ~ ~ ~ ~X O V U L ' C O E O M Y p O ' r '° a ~ tn 0 v ~ ° °' 'x ° = c :°_ ~ ~ ~ a~
a~ ° ~ a~ aW 'n m E_ C C C ? O Y C ~ O [yJ C p ~ O t0 O ~ ~ ~ N O V ~ D1 Y E E C C ~ O ~ fn N m 01 (O l0 7 V C E Q O E L 41 (=/1 C C C C C d O ~O E N ~ ~ j~ N
d d d ' In Vl II) ~ f/7 Vl In N N N N r. r r .r. r. r..
aoi M N
1 v ~ ~ ~I m Q
ao ~ o ~ n co ~ NI m a~ M r- ~ n r~l n r~ ~ ,~ NI M rn tn tp (O O O M O M ~ O 07 O O ~ ~ Q~ ~ 00 O 1l7 (O h t0 m ca ooN Io~co,~NN~N~IajN~oN~m°M°~ I~p~NO~_a~oOMO~ Wn I
N ~ ~ D U ~ ~ ~ Z ~ N ~ U ~ X ~ X D J D ~ ~ O ~ ~ ~ ~ D X ~ ~ >
~I ~I ~1 ~I DI ~I ~I ~I ~I Q ~I ~I U ~I ~I Q ~I r1 ~I ~I m ~1 ~I ~I ~I ~I ~I
~I ~I ~I ~I ~I QI ~I ml a0 ~ 00 ~_t'f N O~ ~ O O CO O~ O ~ '~1 00 ~t1 t0 M V' N Qf O ~_ ~f'f O 00 CO O
O u7 a0 V O M V M ~ O ~ ~ n t_D ~ 10 a0 O 10 t0 O O h h 01 h 00 O) N (D _~- ~ O) M
N
N 1~ ~ N M M ~ O) O fD N ~ O f_' O (O O (D N M
M O O Q) O N O a0 ~ M M M O M M M ~ M M M M O) M M
O M N O O O M M N M M M O O M M M O O O M M M O M N M M O
N (n fn CO In UJ (O (n N (n (O (O N In (n (O (n In (O fn N (n fn (O N fn (n (n In (O (n In (n fn fO
C) w W IL W W W w W W W w LL W W IL W w LL W W W W W w W W LL LJJ w W W w U~ w 11.1 Table 2, conk p U O U T O O O >

~ ~ ~ U

U

U X U ~ o U U U o O > T O X 7, >, >, X
U z O U U U O

Z Z
Z ~ ~ Z ~ Z Z Z

_ _ _ _ _ _ _ _ _ _(~ ~

N N O N N N N N O O
O

o_ n. a a n_ a a a a n.
o_ f- f-- >' f-~ ~ ~

y- ~ Z ~- ~ >- Z Z Z ~- Z Z Z >-Z Z Z Z Z Z Z Z Z ~ Z Z Z

N > ~ N X ~. ~. >~
O U O

U z Z U U
Z ~ ~ Z ~ Z Z

._-_-_ ___- _m -_-_ ._ a_ a~ d a~ a~ a~ d d d a~ a~
a o. a a a d o. a a a a a H H FT- H H H H H IT H
ET

z z z z z z z z r r r z r r ~ r z r ~ z z z ~- z z z z z r z N z z r rz z z r r rz z ~ z z z z ~- z z z z zz z z z z z z c ~~o O U d d ~, E E a~
~ N

_ C O d N 7 =
~Q ~

f4 O X
E ~ E ~ ~' U
O a0f0 N 0- 3 C v E
C . .

= O .C7 O 41 N
O O

E Z ~ v N c0O
M

V _ ~11~ d ~ _ N 7 d ~ ~. N

~ ? c ~ D c v N o a~ o ~' n o y ~ a~ _a~ ~ ~ Q m n ~ m N

OI C O N N ~ - O O >
O S'c O N y C N C d ~ U C y O

' U ~ E a''a~~ 'a~ ~ ~ a~m ~, ' > _ C O . Y
' 'vo c o ~ ~ L ~ . U
o o~ u, i a '~a~ a ~o' ~ c c E o o C ~ i1 E ~ U L N E y E Z ~ O
O '- O

p7 C I o ~ _m a~ ~ p O L U ~
m ca r ~ L O C U ~ O O ~ ~ d C U d X ~

~ O O N d j N ~ O __ ~ O ~

(n ~ O r ~ O ~ O U ~ N
~ ~ V

fn Q ~ O N L N C " O C

CO E11f7 Cr C L j DN ~ f0C

f~j~ pp d~ C O C C CC y C ' CN CpN C1 O

C N X E ~ u N VIN N (/7N N N f/1 0 ~ N
-c0 ~ O N C 'pU 7> GI~ C V1E ' ~ ~ F-H F-!-H F-F-F-F-h H F
O U fl)(l)(n(n(nfl)fl)!1)f/) VJ

U C ~ >.E~ ~ O f0(C(4f4~ L O O >'fG~ C C (/J(l~fl)ILU!LJJ111111ILl1!liJUJ
N ~ U IL ILIlllJJ UJ
' T N N N mm CD.oU U Uc U U U v C~N
>.

I
U

n N ~IO
~

N O

O ~Y N M ~ O 1t7f_DtDM_O)N ttC7 O Z O N O ~"~ V ~ O~n (D
1- (D
H M

I a0 n n MM n n O ~ ~ ~ OO n ~ p O ~ (OO ~ n O lf7n n ~ N
( ( M O n M O n O ~ Q) f0 N

N ~ ~~ O ~ a0p ~~ tn0 ~ ~0 l~l7t~~ '~MN
M X M ~ p C
~ O

_ ~ _ ~ ~
I I I l ao~ n n ~ o ~ M o Z ~ UZ
I I -D O Z ~ ~Q X X J N J D Z> > J ~
f~ ~

o d0 O O OO (DM o tnM~ n 01COe-'~sf O n tnM~O~ 1 O NEOM O O~
n n O n N of N 0OOa0 f0 n ~faON n (O O)t0O _ N (DQ)O Q7_ 00Q7O Q1f0t(7 CO f0 O

N N M (D~O~Dst4DN N 00sfO N n sfO O ~ O O N ODM (Dn n n N t0 ~ n M ~ '?'vt~~ ~ ~ O
~
N

M V ~OM On M N M _ MM O ~ O ON O O M n N N~tO O O OO O O O
O M NN M O O MO M OO O O

M N N In(n(n(n(nIn(n(n(nfnInfnV7fn(nN InIn(nfnfnfn(n(nfnfnIn(nN
M O fn fn In (n (n fn O O O O OO O O O O OO O O O OO O O O O O OO O O O OO O O O
O O O

UJ l1J V!W WLLW llJlJJW WW lJJW W UJW W UJW W w LllV!W L1JV!WW UJW lJJ
W LLI UJ

Table 2, cont O O O X

U U

(j U

V U U U

Z Z Z

N ~ N

d d d f1 >, >, T

Z Z Z Z Z Z Z Z Z ~- Z Z Z Z ~ Z Z ~ ~ Z Z Z Z Z Z Z Z Z
Z Z Z Z

U U U

N
d N N
p d Q d , f- H H

z z z z z z z z z r z z z z z z z r z z r z >- z z z z z z z z z z z z r z z z z z z z z r z z z z z z z r z z z z z z z z z z z N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N
f- f- H E- ~ f- ~ ~ f- ~ f- H F- E- ~ H f- H f- H H" f- ~ ~ ~ ~ f ~ H ~ f- ~ ~
f" f-W W W W W W W W W W W W W W W W W W W W ~ W W W W W ~ W W W W W W w W
1('! I~ Q) (O OD V O ~ ~ p~ M h O 000 CO 01 1n O
cD a0 O O~ 1~ N N aD O M O O
_ Of N ~ f0 N ~ N O~ N h ~ O h f~ OO V ~_ ~ N t~ O (O ~ tC~ M
WM17 ~ 0~0 n t0 N p n a0 M O~ M M u7 0~ (O M O ~ op u7 OD O~ M O h ID fD M 01 O~
N N M h N N tn M M Wn ~ GO (p ~1 1n ~C1 N ~ O M I~ m CO 1~ O M ~ ~ M 1~ ID
C 'ct 'Q V ~ O N p (_O m '~1 (O M N N N ~ '~t '? O M CO CO N (D O M 00 ~ N_ M
O~
LL Z Z Z ~ h- 0 ti Z I ~ ~ ~ ~ Z ~ ~ Q
pp ~ ~ N M ~ f0 t~ a0 t~ t0 M O M (~ ~ Q~ t~ 'Q Q_~ M M (D M tn M c0 O~ 01 N N
N
M ~(7 pp M N O QO M OJ O M M (D Q1 O O) N h V f~ V (D ~ r_' O CO X17 M O t~ O
00 O) N
O O O N h (O O ~"> M O CD O (O O O O O 1~ CO N ~ <D O O O V OW f7 ~C1 a0 ~f1 Q~ Q~
OOOOOOOOOpOO M V_u7_~_~_O_O_O_O_n_OONNNNNNNN
f~ N f~ f~ l~ t~ t~ f~ !~ f~ f~ N (~ l~ N f~ (~ f~ V7 (~ N N f~ N N N f~ (~ N
(~ f~ f~ (~ N f~
l1J W W W V! W UJ W 111 W 111 w 111 w 11.1 W w W W W w V! w W w UJ W W w W W w U! W W

Table 2, coot.
O U
U
U o T X
U O
Z Z
N O
Q d T
Z ~ Z Z Z ~ Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z
x U O
a C C
o. a °' °' -a 'o.
m m N N
N
.: .: C
_. .. O
U -' Z
Q Q ~ Z
z r z z z z z z z r z z z z z z z z r ~ >- ~ z z >.. ° z z z r ~ z ~
z Z cn u~ ~ cn a ° p ~ '~ ~ _ ~ z Z
u. N . o z z J J J J J ~ O S ~ ~a ~ ~p ~ ~ M "7 a c a Q Q Q Q Q --co ~ C a .H l1! '~ ~ ~ J_ J_ J N Q LL lL ll LL lL ~ = O C cC'4 (~
Q m w > > > > ~ a ~ ... Z ' In fn Q Q
_N ~ fn U) tn U) U) C ~ N ~ o U) ~ U7 In ~ lL
J J J J J C ~ O M L ~ ~ U U fn fn M : .: .: .:
Q Q Q Q Q ~ U a~ ti Z F- Q Q Q Q
O _ . -. _. _. _.
U o 0 0 0 0 0 0 0 0 0 0 0 o uJ .: _: _: .:
vYtn'm'm~'aco'm'mcem''m~'oca'moo00 0 0 0 -~ -~ ~~ -~ ~~ -~ ~E y y p ~N ~N ~N ~N ~N ~N ~N ~N ~N ~N ~N ~N ~ ~
7. T_T_>. T_>._>._T_T T Tj. E ~E ~E ~E
E E E ~ N N d 41 N N O N d N 1U ~N ~N ~f/1 N
N N N ~ f9 (C N (4 f' fC (C 10 f0 N f9 ~., >. T 7 7. 7. T y N G7 G7 d N N d d N N O Y Y Y -1C
t t t W ~ ~ ~ 'O 'O 'D ~ ~ ~ 'O ~ O !4 (D N
01 O~ OI O O O O O O O O O O O O d d O d N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N
f- ~ f- f" f- f- f- ~ f- ~"" ~ f" ~- ~ ~ ~ H ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ f" f' ~ f"
N (n tn (n fn fn In In fn (n (n (n N fn (n tn In fn In (n (n (n (n (n In fn In (n (n fn (n fn V7 (n W W w w W W w W W W W w W W W w w W W W W W w w W W W w W W w W W W
O M M O M M M OO _M 00 O CO 01 O h M M M f~ '~f ~l1 ~D
M O ~c7 O~ 00 N M O ~f tn O O (D 00 ~ CO ~ ~ 00 V N M O
V ~t7 ~ ~ M N 1~ ~ et O 07 O a0 ~_ O_ h t0 N 07 C~ M h a0 tD M tn ~ O tD
OD ~ M tD c0 O_ O (D tn M N 07 f~ N N f0 M 00 00 t~ O OD N tn O ~ O O tD st ~
M 1n N y11 tn V M M O ~ M 1~ O0 M tW 'p (D tn O t~ O CO O~ Q~ M_ CO ~ O ~ M CO O CD
M_ O O O N O 'Q ~ ~ ~ N 'at tt et ~ ~t O tn M O O (D '? ~O M M O '~t O O N (p O N
o ~ ~ ~ ~ o ~ ~ ~ ~ ~ ~ v ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ z ~ ~ z ~
O~ a0 N M n cD o ~ o M O M ~C) N (D N M o M fD f0 o M ~_ o U7 O tfi h tD G_O
(D ~ ~ O 1~ a0 a0 N O) M O) N OO O tn 00 M m of IO m O ~ h N ~ O1 O O ~ O
N N I~ W_l1 10 (O m O O N N 01 O ~f N M h a0 O ~ 1~ h. t0 a0 M (D 07 m ~ 1~ f0 a0 O O O N M M M ~ V 1f7 V_ ~ h 01 V ~ M M ~ 00 ~ M ~ N V ~ ~J '? N a0 N M M M M M M M M M M M M M M N N O N N N O O N N M N N M O
~ N ~ ~ ~ ~ ~ ~ N N N ~ N ~ N ~ N N ~ ~ U
O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O
W V! W W U! W LJJ W IJJ W W W W 111 W W tJJ w W W LL W w W W W UJ LL W 111 UJ
W W UJ LJJ

Table 2, coast o X
x °' U
U
U
U Z
Z
_f0 d H
Z Z Z Z >- Z Z ~ Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z ?~ Z Z
U
U Z
_fC
N
a a H
N
_d Z Z Z Z >- Z Z ~ Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z a> Z Z Z Z 7- Z Z
d .o E
O O
U
N N

Q. C C
N N
d z z z r z z z z r z ~ z z z r z z z z z r r r ~ z >- ~~ z r z z r z r O U U ~ 4f N Z T N
M N Q ~ O E ~ ~ ~ N
a ago U Q '° ~ c%~ c c ~ r r E o ~ z Y E Q o v d M M ~ C O r ~ ~, r U N N O O y D ~' N Z H N N
a~ a~ ~ °~ c m c v~ o o a a a a c C7 C7 ~ v v ~ t a~ a>
.a .D ~ E C 'U ~x O d ~ C_ C_ C_ ~ E O a E U U U C a N N
f0 f4 Q d p C ~ y M d G7 N N N ~ O V ~ (/) C f0 f9 ~9 E ~ y y y yo E ", c ~ ~ x ~ E o 0 0 ~ ~ ~' ~ cc z 'a~ r r r ~ o ° a N f~D = d ~ C U ~ ~ ~ ~ C V d d d Q Q ' ~ C E a d d j U T E
O O = w j 'V7 ~ C C E C7 O Q (D O) ~ N ~ ~ ~ O ~ U O N 41 N U Z T U
C C ~ ~ ~G ..O- O E T Z sf f~ Q1 C l6 T U C C C O U
a~ a~ p c N ~a ~ M ~.°? o E o ~o ~ ° o o ~ a ~ E ~Y a o~ ?~ m a~
a~ c ~ m Q
C C ~ p ~ N N 'P_ O d C .C p E O N ~ O 01 O Q> Q1 p E N Z
C C N d Q ~p ~ ~ ~ Y Q f4 N N v OO (D O M 01 C p ~ ctn'oQL ~v ~.n ,~'n'-°~YYY cZp o c ~ aVooo ~'o p O O O O O .a d p C C Z ~ E d ~ N w w .Ø. w w U N O d ..p.. ~ tn d V p °3 ~ :°_ m o E
C c0 N m m m m m m o 'o °~ a E Q Q Q Q Q Q u~
_E~ E d E o~~~~~~ ~, ~ N jYYY-a 'In 'V1 N ~4) 'N ~ d O C O Y E T T ~ U E E E E E E N ~3 C C -~ w ~ '~O- O
T 7. T T T ~ ~ N H d V ~ ~ ~ V O C C C C C C C C A O- - t4 ~p Z Z Z Z U ~ d m m a - - - - -m m ~ v c Q > > Z a, "- a> > a~ a~ a~ a~ a~ a~ a~ a~ a a a o ~
~ ~ ~ ~ t d a> a~ a~ a~ a~ ~ c_ ° Z c Z m m ~ 'o ~ ~ ~~ m m m m m m m C7 r !~ E E E
E ~ a a ~ G7 C ~ y ~ O ' ~ 1n N N N M M N ~1 C C C C C C C C C C C
(D p C ~C Q ~p. N ~ ~ O O O O O O O O f9 l0 (6 ffl (0 f0 N !4 cC N f0 H >. ,°n 'a v ~ c N N L E E E E E E E E E E E E E E E E E E E E E
(O (O (O In CO ~ Y cc ?~ o ~ v o 0 0 0 0 0 0 0 0 0 > > > > ~ > > ~ >
IL uJ IL LU uJ :~ ti v~ m o> C~ Z S Z t Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z Z
Z
M
O
O ~ M ~ O
N f~ n t!7 M (O Q~ ~ ~ sf M O O t0 ~ ~ ~ f0 N ~ h M M O OO O 07 f0 M M Q1 ~ n O aD p~ (O ~ M ~ aD 00 ~ ~1 c0 M 1~ py0 tW 00 N (O O O O OD O t0 M 00 N N ~ ~
O
O ~ O M M a0 ~ O ~ M _ O 07 V N f'~ M Q~ sf st O n O M M ~ O ~ f00 ~ ~ of a0 N (O N O C '~ N O~ O O O h M O I~ tt (O V M
O Q~ M V7 O M C7 f0 (D fD ~ I~ 00 tn CO N O O tn '? 00 m O N O N
~ X > > _ ~ X X X Z J ~ Z ~ D Z ~ N.' ~ J ~ O D ~ Q X
Q> O c0 M 1~ 1~ 1~ 1~ M_ ~_ ~f O CO 00 (D ~ t0 00 M O a0 N N f~ a0 f0 CO O f~
1~ t0 'Q
(D ~ f0 O M a0 M ~ ~ O ~_ a0 00 M N 1~ 07 ~O M ~ O N 1~ O) N s_T
N V M M O t_~ ~ ~ ~ N ~ O N O O~ ~ Q~ a0 M M O> O) ~ M O_ M ~ ,~ O N N M O N
~p ~p v(7 t(7 M M M N O V fn N M O M 00 N f0 O O_ O ~
N O N O M M M O O O O M O M N M O O M O O O M O M O M O ~ O O
N N N N ~ ~ ~ N ~ ~ N ~ ~ ~ ~ ~ ~ N N N
W L1J LlJ W W W U~ w IlJ W lL l1J lJJ L1J W !JJ 111 L1J W UJ lJJ W lJJ w W W
UJ LLI W w UJ W llJ UJ LL

'Table ~ coal.

x U U

U

U U

0 0 >, X X U

Z
Z

_ _ N

_(9 .a ~_ _(0 _.

~ N N N

d a d d a T ?. ~, >. >, f- E- H ~- f-Z Z Z ?- Z Z Z Z Z Z Z Z ~- ]- Z Z
Z Z Z Z Z Z Z Z Z Z Z Z Z
Z ~- ~- Z Z

X X U

Z
Z

_ _ f0 _m a_ a_ _m -_ a~ a~ d a~ a~

n n n n n T T T 7. T
H H H H H

z Z z r z z z z z z z z z z z z z z z z z r r z z z z r r z z z z z r z z r r z r z r r z z r z z r r z z z r z z z r z z r z r z z r z w t L m N ~ N N L
n a ,~ in a 0 ~ o ~ c~ m c o. v°m°ny~a)'o~c_~c°'' 'O ~9 O E O N J U V ~ C U O N
C L O D ~ N U - 7 U - ~ O T
ch O UUVN tpn a'v_V t VV p_N
'O U '- O ~ - N
N N ~ T C d 4=. O ~O -O ~ 7 n n - E T 'Y O d O y d n E ~ f0 N C N O - C ~ U ~.' L' C
_y E ' ~ . . . p Q
E C E p N C n n _C v u0- O 7, d U V YO ~O N p N
V y C ~ ~ ~ C U U ~ Or C n ~ ~ ~ N ~ ~ L ~ C O
U N d N ~M L O- f0 L L ~ O d m O) ~ ~ 'D N N ' U ~ ~ ~ C C
n O C ' C O C N n M of t4 N .. ' d m O 'O O, N C r 0I O ~ V d C_ C_ C C ~d .C C 'Y 01 ~7 ~ ~O ~ N ~p ~ N
L ~ N N O n O p N ~O ~p O ~O ~ ~C O) 10/1 N ~ > > A N '~ _fp G7 C 10 L U O' N n V E c9 Y p p O l9 m ~ N Q L ~ . p C
17 ~ d ~ C ~ O ~ _ N n n U (0 - y U ~1 N~ p Q ~N N C U
p ~ (p ~p L _Y Vl d t m ~' d O L ~ ~ O ~ N p~ ~ ~ y ~ O f0 N N O C C O ~ ~ ~ d N
c Z _n ~ ~ ~C O) ~ n O O y N L L _f0 ~c °: a a~ a~ c° a~ a~ v ~
~ c c ~ m j ~ O = C ~ N U 19 a C ~ ~ O O O ~ E ~ ~ ' ~ Q O D) Of C X N N O ~ C
O O N T O 01 '~ O
E .Y L ~ N v U ~ E E
C ~ ~ = O O N C C C O X E E ~ ~ f6 N N C C C
f0 ~ ' _v n d U ~ c0 i. o o . °-' c°j E ~E °' c ~E ~E ~ E m Q Q m m a~ i. ~ ~ r r ~ m m m m o 'o o ~0 0 0 ~ C7 c c c ,~ Y ;~ m m ~ T >. g ~ E E E E c n n a a a a o. a n n a n n a rn M
H_ _ ~ O (O Cn0 _ 0~0 t~D
N ~ a0 tt> M tD N 'Q O tp O op c0 'p N O N N N N Of c0 ~ ~ (O M ~ ~ ~!7 O N n t(~ O tn O U Ot~7 O N N O ~ O 00 O t~~7 N m m COO st ~ M O off ~ p O. I' at M ~ ~ f~ '?
of t' O M
Z ~ X ~ O > j ~ ~ ti > > j X X ~ D ~ ~ ~ ~ r X ~ ~ ~ ~ ~ ~ X Q
0o m o ~ M o o~ o~ v o v v v <o cmn M o n M v v M n o w_ _n v o M
O st 01 N O) 1~ Q1 a0 aO (D O N M O (O t0 ~ ~ N t0 1~ N N (D N a0 (O O 01 O M
M (O O a0 _~ O ~ M (O O~ (D st op h V f0 pW O M (O O s_t e- CO O Q~ 07 s_! 07 M O~ O O O~ N
O O N M N N N M N O N N N N N N M ~f N N O M I~ ~ N M N N
N O ~ O O M O M O M O M N O O M O O M M M O O O M O O O M O O M O M O
~ ~ U ~ ~ ~ U ~ N U ~ U U N U N N U N ~ N N ~ ~ U
O O O O O O U O O U U U O O O U O U U O O O O O O O O O O U O O O O O
W LIJ W tlJ W w w UJ V! W LIJ W V! tJJ lJJ l1! V! W W W w W U~ W W lJJ V! W IL
W w W LJJ llJ w Table 2, cont x o U

~, U

> U w' Z U

~ Z

_(0 _ _(0 _ _ N ~ N N

Q. d d a. Q

T T T T T
~

Z Z Z Z ]- Z Z Z Z Z Z ~ Z Z Z Z Z
Z Z Z ~ ~ Z Z Z Z Z Z Z

> U O
Z r.

O
Z
m m -! - ! . _ E _m M ' >. T T >. T
f- N
H H H H ~1 Z Z Z Z ~ Z Z Z Z Z Z Z Z ~ Z Z Z Z Z ~ Z ~ ~ Z Z Z ? Z Z w Z Z
Z Z Z ~ >- Z Z Z Z 7- ~ Z Z ~ Z ~ Z ~ Z ~ Z ~ Z Z Z Z N Z Z '~ Z Z
D> O U Z Z C f' f' G7 ~ N N U N O
o Q '° vi o m '-> ~. ~. a 'a ~ c c p E
0 o E v v ~ Q Q ~ N ~a n °' o Z
~ L O Q O d d C >~ ~ O E E O O N (/~ N
N DON-L-' ~rQd E X00 =OOE~M
r ~ :~ tn In ~ a~ m o ai ai a c L L o o Z = = Z m p c O t11 IL x ~ c " c c m ~ c N ~ m a a~
E U ~ Z Z ~ c °~ .n ~ m m ~ ° ~ ~ M t~ r~ Z = ~ U
i0 c C ~ ~ ~ N E p O N N C ~ d O O O ~ M N Q
y O 7 N ~ C T N O O L p O U U # ~ ~ C Z N d 'O (n m C T ~ O v U U U U C C C f' L
Q O j, ~ ~ O ~ ~ E ~ C m m y N m O O C CI O) a w j O
~C L Y U 'D N Q a ~ C L ~ C O .O m m D1 E O L N fR 7 p C C - ~
U - U m ~ N N y U E ~ E E . ~ C ~ C
o ' ~ ' c c ~ ~ a ° E o ~ 0 0 ~ c o > ~> m a~ ;~ m a~
c .~ ~ ~ m - ~ Y ~C C O ~ ~ ~ 7 d ' n. m ~ E o E m m ~ ~ ~ c y N m ~ m o 0 0 ~~_ a 3 N m s_ o L L o ~ y ~ E 'E a~ ~ a~ N N N a~
O C ~> C O L E U U ~~ ~ C w U U ~ U 3 V d _d N ~ L .Ø. Y Y ' ~ m ~ ~ ~ N
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Exemplar Accession Com lete Title UniGeneID

D86425 Homo sa iens mRNA for nido en-2 Hs.82733 D86983 Human mRNA for KIAA0230 ene; artial Hs.118893 cds HG1098-HT1098C statin D

HG1103-HT1103"Guanine Nucleotide-Bindin Protein Ral, Ras-Onco ene HG3342-HT3519Id 1 J03764 lasmino en activator inhibitor; t Hs.82085 a I

L06797 chemokine C-X-C motif ; rece for 4 Hs.89414 fusin L15388 "Human G rotein-cou led rece for kinaseHs.211569 GRK5 mRNA, phosphodiesterase 4B; cAMP-specific L20971 (dunce Hs.188 Droso hila -homolo hos hodiesterase L35545 endothelial cell rotein C/activated Hs.82353 rotein C rece for L76380 calcitonin rece tor-like Hs.152175 M21305 Human al ha satellite and satellite Hs.247946 3 'unction DNA se uence M24736 selectin E endothelial adhesion moleculeHs.89546 M31166 entaxin-related ene; ra idl induced Hs.2050 b IL-1 beta M31551 lasmino en activator inhibitor; t Hs.75716 a II ar inine-ser in M32334 intercellular adhesion molecule 2 Hs.83733 2 0 M61916 laminin; beta 1 Hs.82124 M68874 "Human hos hatid Icholine 2-ac Ih drolase cPLA2 mRNA, M74719 transcri tion factor 4 Hs.75356 M92934 connective tissue rowth factor Hs.75511 M94856 fatt acid bindin rotein 5 soriasis-associatedHs.153179 2 5 003057 sin ed Droso hila -like sea urchin Hs.118400 fascin homolo like 003877 EGF-containin fibulin-like extracellularHs.76224 matrix rotein 1 018300 dama e-s ecific DNA bindin rotein Hs.77602 2 48kD

027109 Human re romultimerin mRNA; com lete Hs.32934 cds 031384 uanine nucleotide bindin rotein 11 Hs.83381 3 0 033053 rotein kinase C-like 1 Hs.2499 059423 MAD mothers a ainst deca enta 1e ic; Hs.79067 Droso hila homolo 1 070322 ka o herin im ortin beta 2 Hs.168075 081607 kinase scaffold rotein ravin Hs.788 083463 s ndecan bindin rotein s ntenin Hs.8180 3 5 089942 I s I oxidase-like 2 Hs.83354 X04729 Human mRNA for lasmino en activator inhibitor t a 1 X06256 inte rin; al ha 5 fibronectin rece Hs.149609 tor; al ha of a tide X07820 matrix metallo roteinase 10 stromel Hs.2258 sin 2 X54925 matrix metallo roteinase 1 interstitialHs.83169 colla enase 4 0 X54936 lacental rowth factor; vascular endothelialHs.2894 rowth factor-related X60957 t rosine kinase with immuno lobulin Hs.78824 and a idermal rowth factor X67235 hemato oieticall ex ressed homeobox Hs.118651 Exemplar Accession Com lete Title UniGeneID

X67951 roliferation-associated ene A naturalHs.180909 killer-enhancin factor A

X69910 H.sa iens 63 mRNA for transmembrane Hs.74368 rotein X79981 cadherin 5; VE-cadherin vascular a Hs.76206 ithelium 218951 caveolin 1; caveolae rotein; 22kD Hs.247266 "zp61 b6.r1 Stratagene endothelial AA187101 cell 937223 Homo sapiens cDNA clone IMAGE:624659 5', mRNA se uence"

N24990 ESTs Hs.26418 881003 Homo sa iens serine rotease mRNA; Hs.154737 com lete cds AA025351 ESTs Hs.134797 AA027168 ESTs Hs.10031 AA040465 ESTs Hs.8728 AA045136 ESTs Hs.22575 AA054087 hos holi ase A2; rou IVC c osolic; Hs.18858 calcium-inde endent AA071089 ESTs; Moderatel similar to !!!! ALU Hs.187932 SUBFAMILY SC WARNING

AA085918 H.sa iens HUNK/ mRNA Hs.247482 AA187490 ESTs Hs.21941 AA227926 ESTs Hs.6682 AA234743 ESTs Hs.22120 AA236559 ESTs; Weakl similar to neuronal threadHs.8768 rotein AD7c-NTP

AA292694 ESTs Hs.3807 2 0 AA398243 ESTs; Moderatel similar to defline Hs.21806 not available 3694664 AA406363 ESTs Hs.30822 AA411465 ESTs Hs.8619 AA412284 oliovirus rece for Hs.171844 AA423987 ESTs Hs.7567 2 5 AA425309 ESTs Hs.33287 AA435896 ESTs Hs.18397 AA448238 Homo sa iens mRNA for KIAA0915 rotein;Hs.16714 com lete cds AA478778 ESTs Hs.16450 AA621714 ESTs Hs.25338 3 0 D51069 Human isolate JuSo MUC18 I co rotein Hs.211579 mRNA 3' variant ;

UDP-N-acetyl-alpha-D-galactosamine:polypeptide T34527 N-acet I alactosamin Itransferase Hs.80120 1 GaINAc-T1 097519 odocal xin-like Hs.16426 AA127221 ESTs Hs.71059 ESTs; Moderately similar to C-1-TETRAHYDROFOLATE
AA132983 SYNTHASE; CYTOPLASMIC H.sa lens Hs.44155 3 5 AA135606 ESTs; Weakl similar to !!!! ALU SUBFAMILYHs.189384 SB WARNING

AA156125 ESTs Hs.72116 AA179845 RAB6 interactin ; kinesin-like rabkinesin6Hs.73625 AA232645 ESTs Hs.42699 F10399 ESTs Hs.14763 Exemplar Accession Com lete Title UniGeneID

H16772 ESTs Hs.31444 N39584 ESTs Hs.17404 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N52006 N-acet I alactosamin Itransferase 1 Hs.80120 GaINAc-T1 N53375 Homer; neuronal immediate earl ene; Hs.166146 N54067 Homo sa iens mRNA for NIK; artial cds Hs.3628 N64436 ESTs Hs.20813 826892 ESTs Hs.221434 T33637 ESTs Hs.6841 "yc20g11.s1 Stratagene lung (#937210) T57112 Homo sapiens cDNA
clone IMAGE:81284 3', mRNA se uence."

W80763 ESTs; Moderatel similar to FK506-bindinHs.3849 rotein 65kD

AA046808 ESTs; Hi hl similar to 40S RIBOSOMAL Hs.108957 AA253217 ESTs Hs.41271 AA255991 ESTs Hs.175319 AA258138 ESTs Hs.88297 AA426573 ESTs Hs.41135 AA443793 ESTs Hs.94761 AA490588 ESTs Hs.43118 AA496257 ESTs; Weakl similar to defline not Hs.72165 available 3513303 AA609717 ESTs; Weakl similar to MICROTUBULE-ASSOCIATEDHs.66048 2 0 D59570 ESTs Hs.17132 F13787 ESTs Hs.58596 H88157 ESTs Hs.41105 H98988 ESTs Hs.42612 N34287 unc5 C.ele ans homolo C Hs.44553 2 5 N52090 EST Hs.47420 N66845 ESTs; Weakl similar to !!!! ALU CLASS Hs.165411 B WARNING ENTRY !!!!

N68905 small inducible c okine A5 RANTES

832894 ESTs Hs.45514 861715 ESTs Hs.138237 "yi54c08.s1 Soares placenta Nb2HP Homo sapiens cDNA clone IMAGE:143054 3' similar to gb~M87908~HUMALNE32 0 71234 Human carcinoma cell-derived Alu RNA transcript, (rRNA); gb:S41458 ROD CGMP-SPECIFIC 3',5'-CYCLIC PHOSPHODIESTERASE

"yr30g11.s1 Soares fetal liver spleen 898105 1 NFLS Homo sapiens cDNA
clone IMAGE:206852 3', mRNA se uence."

T97186 small inducible c okine A5 RANTES

W80814 ESTs; Moderatel similar to !!!! ALU Hs.193700 SUBFAMILY SB WARNING

AA404418 EST Hs.144953 3 5 AA405747 ESTs; Moderatel similar to HMG-box Hs.97865 transcri tion factor Exemplar Accession Com lete Title UniGeneID

AA488687 ESTs; Moderatel similar to !!!! ALU Hs.190307 SUBFAMILY SQ WARNING

AA599143 ESTs; Moderatel similar to !!!! ALU
SUBFAMILY SQ WARNING

AA608588 ESTs Hs.193634 AA608751 ESTs; Moderatel similar to !!!! ALU Hs.244904 SUBFAMILY SC WARNING

C13961 EST Hs.210115 D60302 ESTs Hs.108977 H94892 v-ral simian leukemia viral onto ene Hs.6906 homolo A ras related N93521 transcri tion factor 4 Hs.241362 N95477 ESTs Hs.102943 860044 ESTs; Weakl similar to !!!! ALU SUBFAMILYHs.106706 J WARNING

870506 ESTs; Moderatel similar to transformation-relatedHs.107159 rotein "ye20f05.s1 Stratagene lung (#937210) Homo sapiens cDNA
91518 clone IMAGE:118305 3' similar to contains Alu repetitive element;contains MER12 re etitive element ;, mRNA se uence."

T95333 ESTs; Weakl similar to Strabismus Hs.122730 D.melano aster 845630 ESTs; Hi hl similar to KIAA0372 H.sa Hs.170098 iens "yg05c07.r1 Soares infant brain 1NIB
820839 Homo sapiens cDNA clone IMAGE:31444 5', mRNA se uence."

823858 ESTs; Moderatel similar to envelo Hs.23986 a rotein H.sa lens A1024874 ESTs; Weakl similar to defline not Hs.57958 available 3882257 W26247 U5 snRNP-s ecific rotein 220 kD ; Hs.6413 ortholo of S. cerevisiae AA856990 ESTs Hs.125058 2 0 AA136653 ESTs AA358869 ESTs; Hi hl similar to SEC13-RELATED Hs.227949 PROTEIN H.sa lens AI123976 ESTs Hs.105689 AI369384 a Isulfatase D

AA379500 ESTs Hs.193155 2 5 849693 ESTs Hs.107708 AA195678 Homo sa iens mRNA for KIAA0465 rotein;Hs.108258 artial cds M30257 vascular cell adhesion molecule 1 Hs.109225 AA028131 ESTs Hs.110342 M10321 "Human von Willebrand factor mRNA, Hs.110802 3' end"

3 0 J03040 secreted rotein; acidic; c steine-richHs.111779 osteonectin M86933 amelo enin Y chromosome Hs.1238 AA012933 tubulin-s ecific cha erone d Hs.241687 AA286710 m hoc a ada for rotein Hs.13131 I

AA243278 ribosomal rotein; mitochondrial; L12 Hs.109059 3 5 D59711 ESTs Hs.237289 " ye36g7.s1 Stratagene lung (#93721 T94452 I ) Homo sapiens cDNA clone Hs.241207 MAGE:119868 3', mRNA se uence"

Exemplar Accession Com lete Title UniGeneID

AA053400 ESTs Hs.241227 AA370302 Homo sa iens mRNA; cDNA DKFZ 58611518 Hs.21739 from clone J05008 endothelin 1 Hs.2271 U85193 nuclear factor I/B Hs.33287 AA256153 ESTs Hs.23912 X83107 BMX non-rece for t rosine kinase Hs.27372 AA046593 ESTs Hs.28959 AA410480 ESTs Hs.30089 D45304 ESTs Hs.31595 M90657 transmembrane 4 su erfamil member 1 Hs.3337 AA010163 a stream re ulato element bindin roteinHs.3383 AA136353 ESTs Hs.38022 Y07867 irin Hs.38842 U84573 rocolla en-I sine; 2-oxo lutarate 5-dioxHs.41270 enase I sine X60486 H4 histone famil ; member G Hs.46423 AA132969 metallo rotease 1 itril sin famil Hs.4812 AA114250 KIAA0512 ene roduct Hs.48924 F13782 LIM bindin domain 2 Hs.4980 AA283035 ESTs; Weakl similar to !!!! ALU SUBFAMILYHs.54813 J WARNING

2 0 AB002301 Human mRNA for KIAA0303 ene; artial Hs.54985 cds AA056731 S'o ren s ndrome anti en A2 60kD; ribonucleoHs.554 rotein U68019 MAD mothers a ainst deca enta 1e ic; Hs.211578 Droso hila homolo 3 H99198 ESTs; Moderatel similar to THYMOSIN Hs.56145 BETA-4 H.sa iens AA598702 bone mor ho enetic rotein 6 Hs.6101 2 5 N77151 Homo sa iens mRNA for KIAA0799 rotein;Hs.61638 artial cds AA505133 ESTs Hs.62273 AB000584 rostate differentiation factor Hs.116577 D12763 interleukin 1 rece tor-like 1 Hs.66 AA253193 ESTs Hs.6631 3 0 AA432248 ESTs Hs.6738 AA083572 v-ral simian leukemia viral onto ene Hs.6906 homolo A ras related AA479713 ESTs Hs.71962 L40395 Homo sa iens clone 23689 mRNA; tom Hs.170001 lete cds X52947 a 'unction rotein; al ha 1; 43kD connexinHs.74471 3 5 W80846 vesicle-associated membrane rotein Hs.74669 5 m obrevin M34539 FK506-bindin rotein 1A l2kD Hs.752 D67029 SEC14 S. cerevisiae -like Hs.75232 U09587 I c I-tRNA s nthetase Hs.75280 M85289 "Human he aran sulfate roteo I can Hs.211573 HSPG2 mRNA, tom lete 4 0 D10522 m risto lated alanine-rich rotein kinaseHs.75607 C substrate MARCKS;

W84712 calumenin Hs.7753 D29992 tissue factor athwa inhibitor 2 Hs.78045 Exemplar Accession Com lete Title UniGeneID

L34657 latelet/endothelial cell adhesion Hs.78146 molecule CD31 anti en S78569 laminin; al ha 4 Hs.78672 D43636 Human mRNA for KIAA0096 ene; artial Hs.79025 cds U97188 IGF-II mRNA-bindin rotein 3 Hs.79440 AA487558 ESTs Hs.8135 M28882 "Human MUC18 I co rotein mRNA, com Hs.211579 lete cds"

X70683 SRY sex determinin re ion Y -box 4 Hs.83484 X14787 thrombos ondin 1 Hs.87409 AA236324 ESTs; Weakl similar to !!!! ALU CLASSHs.92381 A WARNING ENTRY !!!!

C15324 ESTs Hs.93668 AA452000 ESTs Hs.94030 D83174 colla en-bindin rotein 2 colli en Hs.9930 D00596 Homo sa iens ene for th mid late s Hs.196351 nthase; exons 1; 2; 3; 4; 5;

D11428 eri heral m elfin rotein 22 Hs.103724 D13640 ma'or histocom atibilit com lex; classHs.183618 I; C

D14874 adrenomedullin Hs.394 D26129 ribonuclease; RNase A famil ; 1 ancreaticHs.78224 D28476 th roid hormone rece for interactor Hs.138617 D86425 Homo sa iens mRNA for nido en-2 Hs.82733 2 0 D86983 Human mRNA for KIAA0230 ene; artial Hs.118893 cds D87953 N-m c downstream re ulated Hs.75789 HG1862-HT1897Calmodulin T a I

HG2614-HT2710"Colla en, T a Viii, AI ha 1"

HG2639-HT2735Sin le-Stranded Dna-Bindin Protein Mss -1 2 5 HG2855-HT2995"Heat Shock Protein, 70 Kda Gb:Y00371 "

HG3044-HT3742"Fibronectin, Alt. S lice 1"

HG3342-HT3519Id1 HG3543-HT3739Insulin-Like Growth Factor 2 HG4069-HT4339Monoc a Chemotactic Protein 1 3 0 HG417-HT417Cathe sin B

J03764 lasmino en activator inhibitor; t Hs.82085 a I

L06797 chemokine C-X-C motif ; rece for 4 Hs.89414 fusin L08246 m eloid cell leukemia se uence 1 BCL2-relatedHs.86386 L12711 transketolase Wernicke-Korsakoff s Hs.89643 ndrome 3 5 L13977 rol Icarbox a tidase an iotensinase Hs.75693 C

L15388 "Human G rotein-cou led rece for kinase GRK5 mRNA, L19871 activatin transcri tion factor 3 Hs.460 L20859 Human leukemia virus rece for 1 GLVR1Hs.78452 mRNA; com lete cds L42176 four and a half LIM domains 2 Hs.8302 4 0 L49169 Human GOS3 mRNA; com fete cds Hs.75678 L76380 calcitonin rece tor-like Hs.152175 M15990 v- es-1 Yama uchi sarcoma viral onco Hs.194148 ene homolo 1 M23254 ~ calpain; large polypeptide L2 Hs.76288 Exemplar Accession Com lete Title UniGeneID

M24736 selectin E endothelial adhesion moleculeHs.89546 M26576 colla en; t a IV; al ha 1 Hs.119129 M27396 as ara ine s nthetase Hs.75692 M31166 entaxin-related ene; ra idl induced Hs.2050 b IL-1 beta M31994 "Homo sa iens aldeh de deh dro enase ALDH1 ene, exon 13 M32334 intercellular adhesion molecule 2 Hs.83733 M35878 insulin-like rowth factor bindin roteinHs.77326 M36429 ostmeiotic se re ation increased 2-likeHs.89672 M57730 a hrin-A1 Hs.1624 M57731 GR02 onco ene Hs.75765 M60858 nucleolin Hs.79110 M62994 filamin B; beta actin-bindin rotein-278Hs.81008 M68874 "Human hos hatid Icholine 2-ac Ih drolase cPLA2 mRNA, M69043 nuclear factor of ka a Ii ht of a tideHs.81328 ene enhancer in B-cells M74719 transcri tion factor 4 Hs.75356 M75126 hexokinase 1 Hs.118625 CD59 antigen p18-20 (antigen identified M84349 by monoclonal antibodies Hs.119663 16.3A5; EJ16; EJ30; EL32 and 6344 M92843 zinc fin er rotein homolo ous to Zf Hs.198309 -36 in mouse M92934 connective tissue rowth factor Hs.75511 2 0 M93056 rotease inhibitor 2 anti-elastase ; Hs.183583 monoc e/neutro hil M94856 fatt acid bindin rotein 5 soriasis-associatedHs.153179 M95787 traps elfin Hs.75777 S76965 Protein kinase inhibitor human; neuroblastomaHs.75209 cell line S81914 DIFFERENTIATION-DEPENDENT GENE 2 Hs.76095 2 5 003057 sin ed Droso hila -like sea urchin Hs.118400 fascin homolo like 003100 catenin cadherin-associated rotein Hs.178452 ; al ha 1 102kD

003877 EGF-containin fibulin-like extracellularHs.76224 matrix rotein 1 008021 nicotinamide N-meth Itransferase Hs.76669 014391 m osin IC Hs.82251 3 0 031384 uanine nucleotide bindin rotein 11 Hs.83381 032944 d nein; c o lasmic; Ii ht of a tide Hs.5120 040369 "Human s ermidine/s ermine N1-acet Itransferase SSAT ene, 041767 "Human metar idin recursor mRNA, com lete cds"

048959 Homo sa iens m osin Ii ht chain kinaseHs.75950 MLCK mRNA;

3 5 051010 "Human nicotinamide N-meth Itransferase ene, exon 1 and 5' 051478 ATPase; Na+/K+ traps ortin ; beta 3 Hs.76941 0l a tide Human ovarian cancer downregulated 053445 myosin heavy chain Hs.15432 homolo Doc1 mRNA; com lete cds 059289 cadherin 13; H-cadherin heart Hs.63984 059423 MAD mothers a ainst deca enta 1e ic; Hs.79067 Droso hila homolo 1 4 0 062015 "Homo sa iens C r61 mRNA, com lete cds"

Exemplar Accession Com lete Title UniGeneID

063825 Human he atitis delta anti en interactinHs.66713 rotein A di A mRNA;

067963 Human I so hos holi ase homolo HU-K5 Hs.6721 mRNA; com lete 073379 Human c clin-selective ubi uitin carrierHs.93002 rotein mRNA; com lete 073824 euka otic translation initiation factorHs.183684 4 amma; 2 077604 microsomal lutathione S-transferase Hs.81874 081607 kinase scaffold rotein ravin Hs.788 089942 I s I oxidase-like 2 Hs.83354 X04412 elsolin am loidosis; Finnish t a Hs.80562 X06985 heme ox enase dec clin 1 Hs.75967 X07820 matrix metallo roteinase 10 stromel Hs.2258 sin 2 X12876 keratin 18 Hs.65114 X15729 DEAD/H As -Glu-Ala-As /His box of a Hs.76053 tide 5 RNA helicase;

X52541 earl rowth res onse 1 Hs.738 X53416 filamin A; al ha actin-bindin rotein-280Hs.76279 X54489 GR01 onco ene melanoma rowth stimulatinHs.789 activit ; al ha X54925 matrix metallo roteinase 1 interstitialHs.83169 colla enase X57206 inositol 1;4;5-tris hos hate 3-kinase Hs.78877 B

X59798 c clin D1 PRAD1: arath roid adenomatosisHs.82932 X60957 t rosine kinase with immuno lobulin Hs.78824 and a idermal rowth factor 2 0 X65965 H.sa iens SOD-2 ene for man anese su eroxide dismutase X69111 inhibitor of DNA bindin 3; dominant Hs.76884 ne ative helix-loo -helix X70940 euka otic translation elon ation factorHs.2642 1 al ha 2 X87838 catenin cadherin-associated rotein Hs.171271 ; beta 1 88kD

X91247 thioredoxin reductase 1 Hs.13046 2 5 X97748 H.sa lens PTX3 ene romotor re ion Y00815 rotein t rosine hos hatase; rece for Hs.75216 t e; F

AA303711 a hrin-B1 Hs.144700 L44538 ESTs Hs.156044 AA025351 ESTs Hs.134797 3 0 AA027050 ESTs Hs.31189 AA029462 ESTs Hs.17235 AA045136 ESTs Hs.22575 AA047437 ESTs Hs.22968 AA054087 hos holi ase A2; rou IVC c osolic; Hs.18858 calcium-inde endent 3 5 AA071089 ESTs; Moderatel similar to !!!! ALU Hs.187932 SUBFAMILY SC WARNING

AA156450 ESTs; Weakl similar to Similar to Rat Hs.8982 tr ene roduct AA187490 ESTs Hs.21941 ESTs; Moderately similar to PROBABLE
AA195031 G PROTEIN-COUPLED Hs.9305 RECEPTOR APJ H.sa iens AA205724 ESTs Hs.10119 4 0 AA227926 ESTs Hs.6682 ~

Exemplar Accession Com lete Title UniGeneID

AA227986 ESTs Hs.25329 AA234743 ESTs Hs.22120 AA253216 ESTs Hs.22283 AA256210 oncomodulin Hs.199134 AA256268 ESTs Hs.10283 AA279397 ESTs; Moderatel similar to fibronectinHs.25001 H.sa iens AA292379 ESTs; Moderatel similar to !!!! ALU Hs.20340 SUBFAMILY SQ WARNING

AA292717 ESTs; Weakl similar to JM2 H.sa iens Hs.7891 AA346551 ESTs Hs.23457 AA400292 ESTs Hs.23786 AA404338 ESTs Hs.21812 AA412284 oliovirus rece for Hs.171844 AA423987 ESTs Hs.7567 AA428594 ESTs Hs.21321 AA430108 ESTs Hs.6019 AA431462 ESTs Hs.28329 ESTs; Weakly similar to CAMP-DEPENDENT
AA431470 PROTEIN KINASE Hs.3407 INHIBITOR; MUSCLE/BRAIN FORM H.sa iens AA443756 ESTs; Moderatel similar to defline Hs.6673 not available 4105275 AA449479 ESTs; Hi hl similar to defline not Hs.5216 available 5106787 2 0 AA459916 brad kinin rece for B2 Hs.25021 AA465226 ESTs Hs.28631 AA478778 ESTs Hs.16450 AA479037 ESTs Hs.7961 AA482597 ESTs; Hi hl similar to defline not Hs.26054 available 4704739 AA487561 ESTs; Hi hl similar to RAS-RELATED Hs.9813 AA489245 ESTs; Weakl similar to s erm s ecificHs.5682 rotein H.sa iens AA504110 ESTs Hs.18063 ESTs; Highly similar to SERINE/THREONINE
AA520989 PROTEIN Hs.9195 H.sa iens AA599434 ESTs Hs.25035 3 0 AA608649 Homo sa iens clone 23742 mRNA; artialHs.6354 cds AA609519 ESTs Hs.26458 D51069 Human isolate JuSo MUC18 I co rotein Hs.185718 mRNA 3' variant ;

U97519 odocal xin-like Hs.16426 W28391 roliferation-associated 2G4; 38kD Hs.5181 3 5 AA035638 Homo sa iens mRNA; cDNA DKFZ 564F053 Hs.71968 from clone AA083514 ESTs Hs.68301 AA121315 ESTs Hs.70823 AA147186 ESTs Hs.92387 AA156125 ESTs Hs.72116 4 0 AA188932 ESTs Hs.85640 Exemplar Accession Com lete Title UniGeneID

AA219653 ESTs Hs.87125 AA232645 ESTs Hs.42699 F10078 ESTs Hs.13233 H48032 ESTs Hs.9645 H82117 ESTs Hs.28043 N39584 ESTs Hs.17404 N54067 Homo sa iens mRNA for NIK; artial Hs.3628 cds N59858 ESTs Hs.33032 N90933 ESTs Hs.4867 N93764 ESTs; Moderatel similar to !!!! ALU Hs.10175 CLASS C WARNING ENTRY

826124 ESTs Hs.24024 827957 ESTs Hs.24230 855470 ESTs; Moderatel similar to K02E10.2 Hs.11067 C.ele ans T16550 ESTs; Hi hl similar to vacuolar roteinHs.6650 sortin homolo h-v s45 T26674 ESTs; Weakl similar to neuronal threadHs.6966 rotein AD7c-NTP

"yc20g11.s1 Stratagene lung (#937210) T57112 Homo sapiens cDNA Hs.8881 clone IMAGE:81284 3', mRNA se uence."

T88700 ESTs Hs.173374 T90527 ESTs Hs.7890 W42789 ESTs Hs.31446 2 0 W60002 lastin 3 T isoform Hs.4114 W78175 ESTs Hs.17901 W84768 ESTs Hs.141742 W94427 ESTs; Weakl similar to Na;K-ATPase Hs.3807 amma subunit AA253217 ESTs Hs.41271 2 5 AA426573 ESTs Hs.41135 AA432374 ESTs Hs.48029 AA446622 ESTs Hs.74313 AA478771 ESTs Hs.50841 AA482594 ESTs Hs.62684 3 0 AA490588 ESTs Hs.43118 D59570 ESTs Hs.17132 H88157 ESTs Hs.41105 H94648 ESTs Hs.41995 H97538 ESTs Hs.42392 3 5 H98670 ESTs; Weakl similar to defline not Hs.49753 available 4884081 N22107 ESTs; Moderatel similar to !!!! ALU Hs.172241 SUBFAMILY SC WARNING

W38197 Accession not listed in Genbank W80814 ESTs; Moderatel similar to !!!! ALU Hs.196785 SUBFAMILY SB WARNING

AA287347 ESTs Hs.105088 4 0 AA402799 ESTs Hs.182538 Exemplar Accession Com lete Title UniGeneID

AA404418 EST Hs.144953 AA425107 ESTs Hs.97016 AA425435 ESTs; Moderatel similar to !!!! ALU Hs.98438 SUBFAMILY J WARNING

AA442872 ESTs Hs.110771 AA452860 ESTs; Moderatel similar to !!!! ALU Hs.197214 SUBFAMILY SP WARNING

AA488687 ESTs; Moderatel similar to !!!! ALU Hs.190307 SUBFAMILY SO WARNING

AA599674 ESTs; Weakl similar to ORF D.melano Hs.108115 aster F13673 ESTs Hs.99769 H99093 DEAD/H As -Glu-Ala-As /His box of a Hs.6179 tide 72kD

"yw35g11.s1 Morton Fetal Cochlea Homo N22495 sapiens cDNA clone Hs.102415 IMAGE:254276 3', mRNA se uence."

N23031 m osin; heav of a tide 7; cardiac muscle;Hs.929 beta 815740 carboh drate chondroitin 6/keratan Hs.104576 sulfotransferase 1 839610 cal ain; lar a of a tide L2 Hs.76288 .

W45560 ESTs Hs.102541 239833 H.sa iens mRNA for Rho6 rotein Hs.124940 240583 ESTs Hs.101259 AA825437 ESTs 866613 Homo sa iens mRNA; cDNA DKFZ 564F053 from clone AA868063 carboh drate chondroitin 6/keratan sulfotransferase 1 "z116dO8.r1 Soares_pregnant_uterus_NbHPU
2 0 AA128075 Homo sapiens cDNA clone IMAGE:502095 5', mRNA se uence."

N66570 ESTs A1051390 ESTs AA627122 ESTs X02761 fibronectin 1 Hs.118162 2 5 AF010193 MAD mothers a ainst deca enta 1e ic; Hs.100602 Droso hila homolo 7 AA149044 ESTs; Hi hl similar to the KIAA0195 Hs.10086 ene is ex ressed 082108 solute carrier famil 9 sodium/h dro Hs.101813 en exchan er ; isoform 3 D78676 ESTs; Moderatel similar to defline Hs.105509 not available 4529890 L35240 eni ma LIM domain rotein Hs.102948 3 0 AA598737 lactate deh dro enase B Hs.180414 869417 ESTs Hs.107055 ESTs; Weakly similar to Human pre-mRNA
AA232837 cleavage factor I 68 Hs.107125 kDa subunit H.sa iens N72695 ESTs Hs.108557 M30257 vascular cell adhesion molecule 1 Hs.109225 inhibitor of DNA binding 2; dominant 3 5 M96843 negative helix-loop-helix Hs.109617 rotein X68277 dual s ecificit hos hatase 1 Hs.171695 AA292440 m eloid differentiation rima res onse Hs.110571 J 03040 secreted rotein; acidic; c steine-richHs.111779 osteonectin Exemplar Accession Com lete Title UniGeneID

AA228107 ESTs Hs.54642 AA449789 connective tissue rowth factor Hs.75511 W01367 ESTs Hs.170980 AA610116 ESTs; Hi hl similar to defline not Hs.11663 available 4325180 AA258308 Homo sa iens mRNA; cDNA DKFZ 564F053 Hs.165618 from clone AA460273 Homo sa iens mRNA for KIAA0517 rotein;Hs.12372 artial cds AA286710 I m hoc a ada for rotein Hs.13131 T68873 metallothionein 1 L Hs.143289 D63476 PAK-interactin exchan a factor beta Hs.172813 M62403 insulin-like rowth factor-bindin roteinHs.1516 X55740 5' nucleotidase CD73 Hs.153952 L10284 calnexin Hs.155560 AA243278 ribosomal rotein; mitochondrial; L12 Hs.109059 AA430032 ituita tumor-transformin 1 Hs.159626 H16402 ESTs Hs.17121 D59711 ESTs Hs.17132 "ye36g7.s1 Stratagene lung (#93721 T94452 ) Homo sapiens cDNA clone IMAGE:119868 3', mRNA se uence"

AA431571 ESTs Hs.17894 879356 Homo sa iens mRNA for KIAA0544 rotein;Hs.19280 artial cds 2 0 AA280375 ESTs Hs.19928 249269 small inducible c okine subfamil A Hs.20144 C s-C s ; member 14 241740 ESTs Hs.24462 AA121543 Homo sa iens mRNA for KIAA0758 rotein;Hs.22039 artial cds J05008 endothelin 1 Hs.2271 2 5 AA101878 ESTs Hs.22793 ESTs; Highly similar to (defline not T35341 available 4519883) Hs.22880 H.sa iens N87590 ESTs Hs.23037 AA256153 ESTs Hs.23912 W74533 Homo sa iens mRNA for KIAA0786 rotein;Hs.24212 artial cds 3 0 U25997 stanniocalcin Hs.25590 V01512 v-fos FBJ murine osteosarcoma viral Hs.25647 onto ene homolo V01512 v-fos FBJ murine osteosarcoma viral Hs.25647 onto ene homolo V01512 v-fos FBJ murine osteosarcoma viral Hs.25647 onto ene homolo V01512 v-fos FBJ murine osteosarcoma viral Hs.25647 onto ene homolo 3 5 X56681 ' un D roto-onto ene Hs.2780 AA161292 nterteron; al ha-inducible rotein 27 Hs.2867 i AA491465 ESTs Hs.28792 AA046593 ESTs Hs.28959 D50914 Human mRNA for KIAA0124 ene; artial Hs.30736 cds 4 0 D45304 ESTs Hs.31595 M90657 t ransmembrane 4 su erfamil member 1 Hs.3337 Exemplar Accession Complete Title UniGeneID

W69127 _ Hs.3449 ESTs; Weakl similar to zinc fin er rotein ZNF191 H.sa iens AA316186 ESTs; Hi hl similar to defline not Hs.34549 available 4262136 AA384503 ESTs Hs.179260 AA136353 ESTs Hs.38022 AA044755 ESTs; Weakl similar to !!!! ALU SUBFAMILYHs.173705 SX WARNING

procollagen-lysine; 2-oxoglutarate U84573 5-dioxygenase (lysine Hs.41270 h drox lase 2 AA058911 ESTs; Weakl similar to membrane I Hs.4193 co rotein M.musculus AA620962 d nein; c o lasmic; Ii ht intermediateHs.44251 of a tide 2 AA285290 small EDRK-rich factor 2 Hs.44499 X60486 H4 histone famil ; member G Hs.46423 831641 ESTs Hs.197148 AA489190 ESTs Hs.48320 F13782 LIM bindin domain 2 Hs.4980 AA257993 Janus kinase 1 a rotein t rosine kinaseHs.50651 M24283 intercellular adhesion molecule 1 Hs.168383 CD54 ; human rhinovirus ESTs; Weakly similar to PIM-1 PROTO-ONCOGENE
AA443114 SERINE/THREONINE-PROTEIN KINASE H.sa Hs.5326 lens T35289 casein kinase 1; al ha 1 Hs.195206 N23817 Homo sa iens clone 23675 mRNA se uenceHs.5807 AA047151 ESTs Hs.5897 2 0 N77151 Homo sa iens mRNA for KIAA0799 rotein;Hs.61638 artial cds AA480074 ESTs Hs.62206 Y00787 interleukin 8 Hs.624 T99789 ESTs Hs.64313 W84341 tissue inhibitor of metallo roteinaseHs.6441 2 5 L09209 am loid beta A4 recursor-like rotein Hs.64797 D12763 interleukin 1 rece tor-like 1 Hs.66 T16484 ESTs Hs.6607 AA253193 ESTs Hs.6631 AA432248 ESTs Hs.6738 3 0 X82200 stimulated traps-actin factor 50 kDa Hs.68054 AA083572 v-ral simian leukemia viral onco ene Hs.6906 homolo A ras related L00352 low densit Ii o rotein rece for familialHs.181182 h ercholesterolemia N75791 ESTs Hs.7153 X57579 H.sa iens activin beta-A subunit exon 3 5 X02612 c ochrome P450; subfamil I aromatic Hs.72912 com ound-inducible ;

H44631 i mmediate earl rotein Hs.737 AA090257 su eroxide dismutase 2; mitochondrialHs.177781 X83703 H.sa iens mRNA for c okine inducible Hs.74019 nuclear rotein L40395 Homo sa iens clone 23689 mRNA; com Hs.170001 lete cds 4 0 AA227913 ESTs Hs.198456 Exemplar Accession Com lete Title UniGeneID

X52947 a 'unction rotein; al ha 1; 43kD connexinHs.74471 M11313 al ha-2-macro lobulin Hs.74561 L14837 ti ht 'unction rotein 1 zona occludensHs.74614 M60721 "Human homeobox ene, com lete cds"

D90209 activatin transcri tion factor 4 tax-resHs.181243 onsive enhancer element "yc28e12.s1 Stratagene liver (#937224) T67986 Homo sapiens cDNA Hs.75106 clone IMAGE:82030 3' similar to b:X14723 CLUSTERIN

AA148318 Human mRNA for KIAA0069 ene; artial Hs.75249 cds 097105 dih dro rimidinase-like 2 Hs.173381 T25747 H.sa lens OZF mRNA Hs.75471 K02574 Accession not listed in Genbank tyrosine 3-monooxygenase/tryptophan D78577 5-monooxygenase Hs.75544 activation rotein; eta of a tide X53331 matrix Gla rotein Hs.75742 S73591 a re ulated b 1;25-dih drox itamin Hs.179526 X95735 z xin Hs.75873 L16862 G rotein-cou led rece for kinase 6 Hs.76297 044975 Homo sa iens Kru el-like zinc fin Hs.76526 er rotein Zf9 mRNA;

M97796 inhibitor of DNA bindin 2; dominant Hs.180919 ne ative helix-loo -helix 086782 26S roteasome-associated ad1 homolo Hs.178761 AA099391 ESTs Hs.77310 2 0 M19267 tro om osin 1 al ha Hs.77899 D29992 tissue factor athwa inhibitor 2 Hs.78045 L19314 hos ho lase kinase; beta Hs.195217 S78569 laminin; al ha 4 Hs.78672 028811 "Human c steine-rich fibroblast rowth factor rece for CFR-1 2 5 L77886 rotein t rosine hos hatase; rece for Hs.79005 t e; K

C14407 neuronal tissue-enriched acidic roteinHs.79516 M60278 di htheria toxin rece for he arin-bindinHs.799 a idermal rowth 881509 s licin factor; ar inine/serine-rich Hs.184571 AA487558 ESTs Hs.8135 3 0 D86962 KIAA0207 ene roduct Hs.81875 AA478971 disabled Droso hila homolo 2 mito Hs.81988 en-res onsive D50683 transformin rowth factor; beta rece Hs.82028 for II 70-80kD

056637 ca in rotein actin filament muscle Hs.184270 Z-line; al ha 1 M61199 Human cleava a si nal 1 rotein mRNA; Hs.82767 com lete cds 35 M28882 "Human MUC18 I co rotein mRNA, com lete cds"

X15183 CDW52 anti en CAMPATH-1 anti en Hs.180532 S53911 CD34 Hs.85289 Exemplar Accession Com lete Title UniGeneID

U20734 Human transcri tion factor'unB 'unB Hs.198951 ene; 5' re ion and D28235 rosta landin-endo eroxide s nthase Hs.92309 2 rosta landin G/H

AA236324 ESTs; Weakl similar to !!!! ALU CLASSHs.92381 A WARNING ENTRY !!!!

AA148923 Homo sa iens mRNA for DEPP decidual Hs.93675 rotein induced b AA174183 ESTs Hs.93872 AA456311 ESTs; Weakl similar to !!!! ALU CLASSHs.93961 A WARNING ENTRY !!!!

L08069 heat shock rotein; DNAJ-like 2 Hs.94 AA452000 ESTs Hs.94030 AA282140 ESTs Hs.9587 J02854 m osin re ulato Ii ht chain 2; smoothHs.9615 muscle isoform AA442054 hos holi ase C; amma 1 formerl subt Hs.993 a 148 AB000450 vaccinia related kinase 2 AB002380 KIAA0382 rotein AB003103 roteasome rosome; macro ain 26S subunit;
non-ATPase; 12 AB004884 tousled-like kinase 2 AF000573 homo entisate 1;2-diox enase homo entisate oxidase AF009301 similar to S. cerevisiae SSM4 AF009368 cAMP res onsive element bindin rotein 3 luman 2 0 D00591 chromosome condensation 1 D00760 roteasome rosome; macro ain subunit;
al ha t e; 2 D11139 tissue inhibitor of metallo roteinase 1 a hyoid otentiatin D14657 KIAA0101 ene roduct D14878 D123 ene roduct mannosyl (alpha-1;6-)-glycoprotein D17716 beta-1;6-N-acet I- lucosamin Itransferase D21090 RAD23 S. cerevisiae homolo B

D26135 diac I I cerol kinase; amma 90kD

D26528 DEAD/H As -Glu-Ala-As /His box of a tide 7 RNA helicase;

D30742 calcium/calmodulin-de endent rotein kinase IV

3 0 D31762 KIAA0057 ene roduct; TRAM-like rotein D31765 KIAA0061 rotein D31888 KIAA0071 rotein D38128 rosta landin 12 rostac clin rece for IP

D38500 ostmeiotic se re ation increased 2-like 3 5 D38551 RAD21 S. ombe homolo D42087 KIAA0118 rotein D49396 antioxidant rotein 1 D63391 latelet-activatin factor acet Ih drolase;
isoform Ib; amma Exemplar Accession Com lete Title UniGeneID 11/29/99 D63477 KIAA0143 rotein D63483 acet I LDL rece tor; SREC

D64015 TIA1 c otoxic ranule-associated RNA-bindin rotein-like 1 D79990 KIAA0168 ene roduct D79997 KIAA0175 ene roduct D80010 KIAA0188 rotein D84276 CD38 anti en 45 D86425 nido en 2 D86978 KIAA0225 rotein D87012 Human lambda DNA for immuno lobin Ii ht chain D87075 solute carrier famil 23 nucleobase traps orters ; member 1 D87432 solute carrier famil 7 cationic amino acid traps orter; +

D87448 to oisomerase DNA II bindin rotein D87845 latelet-activatin factor acet Ih drolase 2 40kD

2 5 J04029 keratin 10 a idermol is h erkeratosis;
keratosis almaris et methylenetetrahydrofolate dehydrogenase J04031 (NADP+ dependent);
methen Itetrah drofolate c cloh drolase;
form Itetrah drofolate J04088 to oisomerase DNA II al ha 170kD

J04543 annexin A7 TEK tyrosine kinase; endothelial (venous L06139 malformations; multiple cutaneous and mucosal 3 0 L07540 re lication factor C activator 1 5 36.5kD

L08895 MADS box transcri tion enhancer factor 2; of a tide C

L11239 astrulation brain homeo box 1 L11353 neurofibromin 2 bilateral acoustic neuroma myeloid/lymphoid or mixed-lineage L13773 leukemia (trithorax Droso hila homolo ; translocated to;

L14922 re lication factor C activator 1 1 145kD

L15189 heat shock 70kD rotein 9B mortalin-2 L15388 G rotein-cou led rece for kinase 5 L16895 I s I oxidase 4 0 L27476 ~ ight junction protein 2 (zona occludens t 2) Exemplar Accession Com lete Title UniGeneID

L27624 tissue factor athwa inhibitor 2 L32976 mito en-activated rotein kinase kinase kinase 11 L33404 kallikrein 7 ch mot tic; stratum corneum L35263 mito en-activated rotein kinase 14 L37347 solute carrier Tamil 11 roton-cou led divalent metal ion L40371 th roid hormone rece for interactor L40391 Homo sa iens clone s153 mRNA fra ment L41607 lucosamin I N-acet I transferase 2;
I-branchin enz me L77566 DiGeor a s ndrome critical re ion ene DGSI

M13928 aminolevulinate; delta-; deh dratase M13928 aminolevulinate; delta-; deh dratase M14016 uro or h rino en decarbox lase M14219 decorin M15796 roliferatin cell nuclear anti en M21305 Human al ha satellite and satellite 3 'unction DNA se uence M22898 tumor rotein 53 Li-Fraumeni s ndrome M22995 RAP1A; member of RAS onto ene famil M23379 RAS 21 rotein activator GTPase activatin rotein 1 2 0 M24364 ma'or histocom atibilit tom )ex; class I I; DQ beta 1 M24400 ch mot sino en B1 M25753 c clin B1 M27691 cAMP res onsive element bindin rotein M28213 RAB2; member RAS onto ene famil 2 5 M29550 rotein hos hatase 3 former) 2B ; catal is subunit; al ha M29971 O-6-meth I uanine-DNA meth Itransferase M30269 nido en enactin M31158 rotein kinase; cAMP-de endent; re ulato ; t a II; beta M31166 entaxin-related ene; ra id) induced b IL-1 beta endothelial differentiation; sphingolipid 3 0 M31210 G-protein-coupled rece tor; 1 M55420 E silon ; I E

M59979 rosta landin-endo eroxide s nthase 1 rosta landin G/H

M62810 transcri tion factor 6-like 1 mitochondria) transcri tion factor M63838 interferon; amma-inducible rotein 3 5 M64710 Human CNP ene for C-t a natriuretic a tide M74524 ubi uitin-con'u atin enz me E2A RAD6 homolo M80254 a tid I rol I isomerase F c clo hilin F

M81780 s hin om elfin hos hodiesterase 1;
acid I sosomal acid 40 M81780 s hin om elfin hos hodiesterase 1;
acid I sosomal acid Exemplar Accession Com lete Title UniGeneID

M81780 s hin om elfin hos hodiesterase 1;
acid I sosomal acid Homo Sapiens acid sphingomyelinase M81780 (SMPD1 ) gene; complete cds; ORF's 1-3; com lete cds's Homo Sapiens acid sphingomyelinase M81780 (SMPD1 ) gene; complete cds; ORF's 1-3; com lete cds's M83822 cell division c cle 4-like M86934 DNA se ment; numerous co ies; ex ressed robes GS1 ene M87338 re lication factor C activator 1 2 40kD

M96326 azurocidin 1 cationic antimicrobial rotein 37 M96954 TIA1 c otoxic ranule-associated RNA-bindin rotein-like 1 M98833 Friend leukemia virus inte ration S66793 arrestin 3; retinal X-arrestin S72370 ruvate carbox lase S78569 laminin; al ha 4 S79873 I sosomal-associated membrane rotein S83325 as artate beta-h drox lase 001212 olfacto marker rotein s mbol rovisional 001922 translocase of inner mitochondria) membrane 8 east homolo A

002556 t-com lex-associated-testis-ex ressed 1-like 2 0 002680 rotein t rosine kinase 9 003272 fibrillin 2 con enital contractural arachnodact I

004209 microfibrillar-associated rotein 1 005237 fetal Alzheimer anti en 007225 uriner is rece for P2Y; G- rotein cou led; 2 2 5 007620 mito en-activated rotein kinase 10 009759 mito en-activated rotein kinase 9 009820 al ha thalassemia/mental retardation s ndrome X-linked 011313 sterol carrier rotein 2 014518 centromere rotein A 17kD

30 014575 rotein hos hatase 1; re ulato inhibitor subunit 8 015173 BCL2/adenovirus E1B 19kD-interactin rotein 2 015932 dual s ecificit hos hatase 5 018291 CDC16 cell division c cle 16; S. cerevisiae;
homolo 018300 dama e-s ecific DNA bindin rotein 2 48kD

3 5 018383 nuclear res irato factor 1 020536 cas ase 6; a o tosis-related c steine rotease 021551 branched chain aminotransferase 1;
c osolic 023028 euka otic translation initiation factor 2B; subunit 5 a silon;

023752 SRY sex-determinin re ion Y -box 11 4 0 025435 t ranscri tional re ressor 025997 stanniocalcin Exemplar Accession Com lete Title UniGeneID

028251 zinc fin er rotein 169 032315 s ntaxin 3A

032439 re ulator of G- rotein si nallin 7 032849 N-m c and STAT interactor 035139 necdin mouse homolo 036764 euka otic translation initiation factor 3; subunit 2 beta; 36kD

039400 chromosome 11 o en readin frame 4 039657 mito en-activated rotein kinase kinase 041344 roline ar inine-rich end leucine-rich re eat rotein 041766 a disinte rin and metallo roteinase domain 9 meltrin amma 041813 homeo box A9 041815 nucleo orin 98kD

043286 seleno hos hate s nthetase 2 044378 MAD mothers a ainst deca enta 1e ic;
Droso hila homolo 4 044754 small nuclear RNA activatin com lex;
of a tide 1; 43kD

047011 fibroblast rowth factor 8 andro en-induced 047011 fibroblast rowth factor 8 andro en-induced 2 0 047011 fibroblast rowth factor 8 andro en-induced 047011 fibroblast rowth factor 8 andro en-induced 047077 rotein kinase; DNA-activated; catal is of a tide 048251 rotein kinase C bindin rotein 1 050535 Human BRCA2 re ion; mRNA se uence CG006 2 5 056833 von Hi el-Lindau bindin rotein 1 058091 cullin 4B

058837 c clic nucleotide ated channel beta 059289 cadherin 13; H-cadherin heart 059863 TRAF famil member-associated NFKB activator 3 0 067122 ubi uitin-like 1 sentrin 067319 cas ase 7; a o tosis-related c steine rotease 068019 MAD mothers a ainst deca enta 1e ic;
Droso hila homolo 3 a disintegrin and metalloproteinase 069611 domain 17 (tumor necrosis factor; al ha; convertin enz me 070322 ka o herin im ortin beta 2 3 5 073524 ATP/GTP-bindin rotein 079267 rotein hos hatase 4; re ulato subunit 079291 Human clone 23721 mRNA se uence 082671 Homo sa iens clone LM1955 H105e3 ene;
artial cds 082671 zinc fin er rotein 185 LIM domain 4 0 084573 rocolla en-I sine; 2-oxo lutarate 5-diox enase I sine 090914 carbox a tidase D

091316 c osolic ac I coenz me A thioester h drolase 091932 ada tor-related rotein com lex 3; si ma 1 subunit Exemplar Accession Com lete Title UniGeneID

096131 Homo sa iens HPV16 E1 rotein bindin rotein mRNA;

097018 echinoderm microtubule-associated rotein-like 097188 IGF-II mRNA-bindin rotein 3 V00503 colla en; t a I; al ha 2 X04327 2;3-bis hos ho I cerate mutase X06389 s na to h sin X07496 a oli o rotein A-I

X07820 matrix metallo roteinase 10 stromel sin 2 X14787 thrombos ondin 1 X15525 acid hos hatase 2; I sosomal methylene tetrahydrofolate dehydrogenase X16396 (NAD+ dependent);
methen Itetrah drofolate c cloh drolase X16609 ank rin 1; a hroc is X53586 inte rin; al ha 6 X53586 inte rin; al ha 6 X53793 multifunctional of a tide similar to SAICAR s nthetase and AIR

X54936 lacental rowth factor; vascular endothelial rowth factor-related X55740 5' nucleotidase CD73 X57025 insulin-like rowth factor 1 somatomedin C

X60673 aden late kinase 3 2 0 X60673 aden late kinase 3 X60708 di a tid I a tidase IV CD26; adenosine deaminase com lexin X62048 wee1+ S. ombe homolo X63097 Rhesus blood rou ; D anti en X63563 0l merase RNA II DNA directed of a tide B 140kD

2 5 X64037 eneral transcri tion factor IIF; of a tide 1 74kD subunit X69636 hect domain and RLD 2 X69878 fms-related t rosine kinase 4 X70649 DEAD/H As -Glu-Ala-As /His box of a tide 1 X72841 retinoblastoma-bindin rotein 7 3 0 X74987 ATP-bindin cassette; sub-famil E OABP
; member 1 X83107 BMX non-rece for t rosine kinase X84194 ac I hos hatase 1; a hroc a common t a X85753 c clin-de endent kinase 8 X87870 he atoc a nuclear factor 4; al ha 3 5 X89066 transient rece for otential channel X89398 uracil-DNA I cos lase X89398 uracil-DNA I cos lase X89399 RAS 21 rotein activator GTPase activatin rotein 3 X89426 endothelial cell-s ecific molecule 4 0 X91247 t hioredoxin reductase 1 X91648 H.sa iens mRNA for ur al ha extended 3'untranslated re ion WO 01/11086 PCT/~JS00/22061 Exemplar Accession Com lete Title UniGeneID

X92098 coated vesicle membrane rotein X92110 H.sa lens mRNA for he VIII rotein X94703 RAB28; member RAS onco ene famil X96506 DR1-associated rotein 1 ne ative cofactor 2 al ha X97230 killer cell immuno lobulin-like rece tor; three domains; Ion X98263 M- hase hos ho rotein 6 X98296 ubi uitin s ecific rotease 9; X chromosome Droso hila fat X99584 SMT3 su ressor of mif two 3; east homolo Y00264 am loid beta A4 recursor rotein rotease nexin-II; Alzheimer Y07566 Ric Droso hila -like; ex ressed in man tissues Y07759 m osin VA heav of a tide 12; m oxin Y07827 but ro hilin; subfamil 3; member A1 Y07867 Pirin Y09443 alk I I cerone hos hate s nthase Y09858 H.sa lens mRNA for unknown rotein Y12394 ka o herin al ha 3 im ortin al ha 4 211559 iron-res onsive element bindin rotein 211695 mito en-activated rotein kinase 1 215005 centromere rotein E 312kD

2 0 246261 H3 histone famil ; member A

AA011243 0l rC -bindin rotein 2 ESTs; Weakly similar to type-1 protein AA018418 phosphatase skeletal muscle I co en tar etin subunit H.sa iens AA018758 ESTs AA018804 Homo sa iens clone 23675 mRNA se uence 2 5 AA031993 SUMO-1 activatin enz me subunit 2 AA044217 ESTs; Weakl similar to colla en al ha 2 I chain R.norve icus SWI/SNF related; matrix associated;
AA046548 actin dependent regulator of chromatin; subfamil e; member 1 AA057447 ESTs; Moderatel similar to alternativel s liced roduct usin AA058376 S'o ren s ndrome anti en A2 60kD; ribonucleo rotein 3 0 AA083572 v-ral simian leukemia viral onco ene homolo A ras related AA088744 ESTs AA091284 ESTs; Hi hl similar to HSPC030 H.sa iens 3 5 AA092700 ESTs AA092968 ESTs AA094800 euka otic translation initiation factor 3; subunit 7 zeta; 66/67kD

AA100219 ESTs AA114885 ESTs Exemplar Accession Com lete Title UniGeneID

AA129547 met roto-onco ene he atoc a rowth factor rece for AA133016 ESTs AA149507 homolo of mouse uakin QKI KH domain RNA bindin rotein AA151005 s erm surface rotein AA195179 euka otic translation initiation factor 4A; isoform 2 AA203138 low densit Ii o rotein rece for familial h ercholesterolemia AA203645 Ar /Abl-interactin rotein Ar BP2 AA227621 ESTs; Weakl similar to weak similarit to colla ens C.ele ans AA248283 ESTs; Weakl similar to rostate-s ecific traps lutaminase AA249611 SH3-bindin domain lutamic acid-rich rotein AA282640 ubi uitination factor E4B homolo ous to east UFD2 AA287199 KIAA0081 rotein AA313990 DKFZP564M112 rotein AA314256 ESTs; Hi hl similar to CGI-94 rotein H.sa iens AA314389 ADP-ribos lation factor-like 5 AA324364 ESTs AA329211 NS1-associated rotein 1 2 0 AA399187 DKFZP434A043 rotein AA421079 ESTs; Weakl similar to Sox-like transcri tional factor H.sa iens AA422029 ESTs AA425230 Ras-GTPase-activatin rotein SH3-domain-bindin rotein AA447052 KIAA0251 rotein AA452000 Homo sa iens mRNA; cDNA DKFZ 586E1624 from clone AA456687 ESTs AA487015 Homo sa iens mRNA; cDNA DKFZ 586L0120 from clone AB002326 Human mRNA for KIAA0328 ene; artial cds -BioB-3 3 0 C01527 ESTs C01714 serum-inducible kinase C01811 Homo sa iens clone 24921 mRNA se uence C02352 ESTs; Hi hl similar to CGI-121 rotein H.sa iens C02375 ESTs D16611 co ro or h rino en oxidase co ro or h ria; hardero or h ria D25216 KIAA0014 ene roduct D31352 ESTs D58024 ESTs; Weakl similar to KIAA0768 rotein H.sa iens 4 0 D80897 KIAA1036 rotein ~ D82614 ~ ESTs Exemplar Accession Com lete Title UniGeneID

D87845 latelet-activatin factor acet Ih drolase 2 40kD

D89377 msh Droso hila homeo box homolo 2 H06583 cAMP res onsive element bindin rotein-like H40732 ESTs H46617 ESTs H56731 ESTs H75570 ESTs H78886 ESTs H81241 Kru el-like factor 8 L36531 inte rin; al ha 8 M63154 astric intrinsic factor vitamin B s nthesis M63180 threon I-tRNA s nthetase M91504 ESTs N56191 rotocadherin 68 N78483 ESTs; Weakl similar to F20D12.3 ene roduct C.ele ans N79268 zinc fin er rotein 198 814652 Homo sa iens PAC clone DJ0872F07 from 820459 ESTs 822303 ESTs; Weakl similar to utative 150 H.sa iens 2 0 833779 ESTs; Weakl similar to 40 H.sa iens 836553 ESTs; Weakl similar to KIAA0681 rotein H.sa lens 864534 ESTs 866475 ESTs 870621 KIAA0896 rotein 2 5 879356 KIAA0544 rotein 884933 ESTs AA007160 Homo sa iens mRNA; cDNA DKFZ 564D016 from clone AA007234 ESTs AA018409 ESTs 3 0 AA025351 ESTs AA027168 KIAA0955 rotein AA027317 ESTs ESTs; Weakly similar to PUTATIVE PRE-MRNA

FACTOR RNA HELICASE H.sa iens AA031357 ESTs; Weakl similar to N-WASP H.sa iens 3 5 AA045136 ESTs AA053400 ESTs AA055829 ESTs; Weakl similar to !!!! ALU SUBFAMILY
J WARNING

AA065217 ESTs AA116054 ESTs; Weakl similar to KIAA0638 rotein H.sa iens 4 0 AA126311 ESTs AA129390 ESTs ~ AA130273 ESTs; Weakly similar to hypothetical protein; similar to Exemplar Accession Com lete Title UniGeneID

AA142919 ESTs AA150205 Kru el-like factor 7 ubi uitous AA176867 ESTs AA180321 Homo sa iens clone S164 mRNA; 3' end of cds AA180487 transformin ; acidic coiled-coil containin rotein 1 AA187634 euka otic translation initiation factor 3; subunit 1 al ha; 35kD

AA195399 ESTs AA234717 ESTs AA234743 ESTs AA234957 m otubularin related rotein 1 AA235604 Homo sa iens clone 25007 mRNA se uence AA236559 ESTs; Weakl similar to !!!! ALU SUBFAMILY
SQ WARNING

AA242868 ESTs; Weakl similar to house-kee in rotein M.musculus AA251776 'un D roto-onco ene AA251909 buddin uninhibited b benzimidazoles 1 east homolo ; beta diptheria toxin resistance protein AA252672 required for diphthamide bios nthesis Saccharom ces -like 2 AA256157 ESTs AA256680 Homo sa iens mRNA; cDNA DKFZ 564H1916 from clone AA258873 ESTs 2 0 AA262727 KIAA1033 rotein AA281451 DKFZP564A043 rotein AA281545 nuclear rece for co-re ressor 1 AA282069 KIAA0603 ene roduct AA283044 ESTs 2 5 AA283930 ESTs AA284755 CDW52 anti en CAM PATH-1 anti en AA291268 DKFZP586L0724 rotein AA291927 ESTs AA343514 ESTs 3 0 AA398109 ESTs AA405737 ESTs AA406610 ESTs AA411465 ESTs; Moderatel similar to HMG-box transcri tion factor AA416886 Homo sa iens mRNA; cDNA DKFZ 564C1563 from clone 3 5 AA424013 Homo sa iens clone 23767 and 23782 mRNA se uences AA424148 DKFZP4341116 rotein AA424558 hosducin-like AA424961 similar to S. cerevisiae SSM4 AA425367 ESTs 4 0 AA425921 ESTs AA426220 KIAA0523 rotein Exemplar Accession Com lete Title UniGeneID

AA427735 ESTs AA430673 ESTs AA432248 ESTs AA435896 ESTs AA436705 KIAA0766 ene roduct AA446561 KIAA0470 ene roduct AA448238 KIAA0915 rotein AA448688 ESTs; Weakl similar to KIAA0638 rotein H.sa iens AA449756 ESTs; Weakl similar to !!!! ALU SUBFAMILY
J WARNING

1 0 AA450303 ESTs AA452411 ESTs; Hi hl similar to mediator H.sa iens AA454566 hemo lobin; amma G

AA454667 ESTs AA456437 ESTs 1 5 AA456646 ESTs AA456826 ESTs AA456981 ESTs AA458959 ESTs AA459950 ESTs 2 0 AA460449 ESTs; Hi hl similar to hos hoserine aminotransferase AA463910 ESTs AA464603 ESTs AA464606 MRS1 rotein AA465093 TIA1 c otoxic ranule-associated RNA-bindin rotein 2 5 AA465692 KIAA0648 rotein AA476473 tri 1e functional domain PTPRF interactin AA478109 ESTs AA478474 ESTs AA480889 ESTs 3 0 AA485223 ESTs AA485254 ESTs AA486183 ESTs; Weakl similar to similar to ox sterol-bindin roteins AA496936 ESTs AA598589 ESTs 3 5 AA598831 ESTs AA600150 ESTs AA608545 RAD51 S. cerevisiae homolo E coli RecA
homolo AA609210 ESTs AA610108 ESTs; Hi hl similar to CGI-124 rotein H.sa iens 4 0 AA620582 ESTs; Weakl similar to KIAA0869 rotein H.sa lens AA621239 ESTs; Hi hl similar to ALG-2 interactin rotein AIP1 AA621714 ESTs Exemplar Accession Com lete Title UniGeneID 11/29/99 AA621718 ESTs; Moderatel similar to CGI-74 rotein H.sa iens D19673 ESTs D25755 ESTs D51095 DKFZP586E1621 rotein D60272 ESTs; Weakl similar to macro ha a lectin 2 H.sa iens T08879 cathe sin F

UDP-N-acetyl-alpha-D-galactosamine:polypeptide T34527 N-acet I alactosamin Itransferase 1 GaINAc-T1 T40327 lun resistance-related rotein T62771 nucleo hosmin/nucleo lasmin; 3 T63174 Homo sa iens mRNA; cDNA DKFZ 58610324 from clone T83444 KIAA0887 rotein T93641 ESTs 048263 re ronocice tin 049065 interleukin 1 rece tor-like 2 079300 Human clone 23629 mRNA se uence 093867 0l merase RNA III DNA directed 62kD

W01094 ESTs W01568 ESTs cartilage oligomeric matrix protein W26853 (pseudoachondroplasia;
a i h seal d s lasia 1; multi 1e W27179 BCL2/adenovirus E1 B 19kD-interactin rotein 3-like W36280 NS1-associated rotein 1 W47063 ESTs 2 5 W79060 isocitrate deh dro enase 2 NADP+ ;
mitochondrial W88550 KIAA1058 rotein X60486 H4 histone famil ; member G

X78931 zinc fin er rotein 272 214077 YY1 transcri tion factor AA004711 ESTs AA015761 ESTs AA018772 ESTs AA024835 otassium volta e- ated channel; dela ed-rectifier; subfamil S;

AA025858 Homo sa iens mRNA; cDNA DKFZ 58681024 from clone AA027229 ESTs; Weakl similar to F45E12.5 C.ele ans AA029428 ESTs 4 0 AA035143 ESTs ~ AA035237 butyrate response factor 2 (EGF-response I factor 2) Exemplar Accession Com lete Title UniGeneID

AA040740 ESTs AA041551 ESTs AA045513 ESTs AA045745 ESTs AA055348 ESTs AA056582 KIAA0372 ene roduct AA056697 ESTs 1 0 AA057678 ESTs AA058681 ESTs AA058686 ESTs AA070799 zinc fin er rotein 6 CMPX1 AA078787 ESTs AA088678 ESTs stress-associated endoplasmic reticulum 3 0 AA100925 protein 1; ribosome associated membrane rotein 4 AA101255 Homo sa iens mRNA for H-2K bindin factor-2;
com lete cds AA126474 stanniocalcin 2 AA127017 ESTs ESTs; Weakly similar to PROTEIN PHOSPHATASE
AA129968 PP2A; 130 KD REGULATORY SUBUNIT H.sa iens 3 5 AA130240 ESTs AA131866 ESTs; Weakl similar to DY3.6 C.ele ans AA132039 ESTs AA132983 DKFZP586G1517 rotein AA133250 ESTs 4 0 AA133583 hi h-mobilit rou nonhistone chromosomal rotein isoform I-C

AA135941 ESTs ' AA148650 - _ _ -~

Exemplar Accession Com lete Title UniGeneID 11/29/99 AA151110 ESTs ESTs; Moderately similar to hedgehog-interacting AA156125 protein M.musculus AA156289 ESTs AA156997 ESTs AA157293 ESTs AA164293 ESTs ESTs; Weakly similar to weak similarity AA164676 to S. cerevisiae intracellular rotein traps ort rotein US 1 C.ele ans AA167375 KIAA0530 rotein AA167550 Homo sa iens mRNA; cDNA DKFZ 564M113 from clone AA187144 endothelin 1 1 5 AA189170 ESTs AA192757 ESTs AA205650 ESTs AA233342 ESTs; Weakl similar to WD40 rotein Ciao 1 H.sa iens AA233472 ESTs 2 0 AA234110 ESTs D80981 ESTs F01660 ESTs F02206 EST; Hi hl similar to ether-a- o-o-related rotein H.sa lens F02208 ESTs 2 5 F02544 ESTs F03918 ESTs F04258 ro hos hatase inor anic F04600 ESTs F08998 ESTs 3 0 F09605 ESTs F11115 ESTs H06371 Homo sa iens clone 24993 mRNA se uence H10995 Homo sa iens mRNA full len th insert cDNA clone EUROIMAGE

H11938 ESTs; Hi hl similar to histone acet Itransferase H.sa lens 3 5 H16568 ESTs H16772 ESTs H18951 ESTs; Moderatel similar to dJ1163J1.1 H.sa iens H20859 ESTs H23747 ESTs 4 0 H38087 ESTs; Weakl similar to NG22 H.sa iens H40331 ESTs H40567 ~ ESTs _ _ ~ _ Exemplar Accession Com lete Title UniGeneID

H46966 ESTs H56640 ESTs H57154 ESTs; Weakl similar to or anic anion traps orter 1 H.sa iens H96712 ESTs N20814 ESTs N25249 s pa tosomal-associated rotein; 23kD

N27100 keratin 5 a idermol sis bullosa sim lex;

N39616 RNA uanine-7- meth Itransferase N48982 ESTs 1 0 N51957 ESTs N52271 LIM rotein similar to rat rotein kinase C-bindin eni ma N59435 ESTs; Hi hl similar to CGI-112 rotein H.sa lens N64139 ESTs; Weakl similar to lar a tumor su ressor 1 H.sa iens N66981 ESTs 1 5 N68640 ESTs N69352 DEAD/H As -Glu-Ala-As /His box of a tide 15 N95226 KIAA0758 rotein 800138 ESTs 807998 ESTs; Weakl similar to !!!! ALU SUBFAMILY
J WARNING

2 0 808929 ubi uitin-con'u atin enz me E2G 2 homolo ous to east UBC7 810307 ESTs 833354 ESTs 836083 ESTs 837938 KIAA0440 rotein 840816 cullin 4A

843162 ESTs 845698 ESTs; Weakl similar to cAMP inducible 2 rotein M.musculus 854554 ESTs 3 0 868425 ESTs 868568 ATX1 antioxidant rotein 1; east homolo 868763 ESTs 870467 ESTs 873565 Homo sa iens mRNA; cDNA DKFZ 564M113 from clone 3 5 873640 ESTs T03865 ESTs T03872 ESTs 4 0 T10072 ESTs T10080 ESTs T10132 KIAA0478 gene product Exemplar Accession Com lete Title UniGeneID 11/29/99 T15343 ESTs T23457 ESTs T23555 ESTs T23670 ESTs T23948 ESTs T33464 ESTs T34413 ESTs T34611 ESTs T40920 ESTs T55182 ESTs; Hi hl similar to IGF-II mRNA-bindin rotein 2 H.sa iens T77453 ESTs T84039 ESTs T86458 ESTs 1 5 T89350 ESTs T90945 ESTs T90987 ESTs T91863 ESTs T91881 KIAA0563 ene roduct 2 0 T93783 ESTs T96687 ESTs T96944 Homo sa iens mRNA; cDNA DKFZ 434H132 from clone T97307 ESTs; Moderatel similar to !!!! ALU
SUBFAMILY J WARNING

T97764 ESTs 2 5 W48817 ESTs W58343 DKFZP586B2420 rotein W59949 ESTs; Moderatel similar to GTP-BINDING

W74644 ESTs W74761 ESTs; Hi hl similar to ubi uitin-con'u atin enz me HBUCE1 3 0 W74802 ESTs W81205 ESTs W81237 ESTs W90146 ESTs W92798 ESTs 238709 inositol 1;4;5-tri hos hate rece tor;
t a 2 238904 ESTs; Weakl similar to KIAA0970 rotein H.sa lens 239103 core-bindin factor; runt domain; al ha subunit 2; translocated to;

239930 calreticulin 4 0 239939 ESTs 2 40012 NCK-associated rotein 1 '2 40377 I ESTs Exemplar Accession Com lete Title UniGeneID 11/29/99 240820 ESTs 241680 Homo sa iens mRNA; cDNA DKFZ 566P013 from clone -BioB-3 AA005112 LIM domain onl 7 AA005432 DKFZP547E2110 rotein AA010163 a stream re ulato element bindin rotein AA026356 ESTs AA026901 ESTs AA036867 ESTs; Weakl similar to coded for b C. ele ans cDNA k30b3.5 AA044644 I m hoc e-s ecific rotein 1 AA046426 Cdc42 effector rotein 3 AA054515 ESTs; Weakl similar to rostate-s ecific traps lutaminase AA085749 ATP bindin rotein associated with cell differentiation AA098874 DKFZP4341116 rotein AA102746 ESTs AA114250 KIAA0512 ene roduct AA126561 stanniocalcin 2 0 AA128980 ESTs AA129757 ESTs; Weakl similar to 60S RIBOSOMAL

AA129921 S-adenos Ihomoc steine h drolase-like AA133331 KIAA0741 ene roduct AA135958 ESTs 2 5 AA136524 euka otic translation elon ation factor 1 al ha 1 AA147044 ESTs; Weakl similar to !!!! ALU CLASS
C WARNING ENTRY !!!!

AA148885 minichromosome maintenance deficient S. cerevisiae 4 AA150043 ESTs AA151621 ESTs 3 0 AA155743 ferritin; Ii ht of a tide AA156335 ESTs AA156336 nuclear rece for co-re ressor 1 AA159181 ESTs; Weakl similar to L a8 S.cerevisiae AA159825 ESTs; Weakl similar to ORF YNL227c S.cerevisiae 3 5 AA234185 ESTs AA234929 ESTs AA234935 ESTs AA236359 ESTs AA236466 ESTs 4 0 AA236535 Human clone 23654 mRNA se uence AA236935 Human normal keratinoc a mRNA

~ AA236942 ESTs ~

Exemplar Accession Com lete Title UniGeneID 11/29/99 AA237018 ESTs AA237025 ESTs AA242751 KIAA0903 rotein AA242763 CDC14 cell division c cle 14; S. cerevisiae homolo B

AA242809 ESTs; Weakl similar to !!!! ALU SUBFAMILY
J WARNING

AA243133 serine/threonine kinase 15 AA243495 lectin; mannose-bindin ; 1 AA243706 ESTs 1 0 AA250848 ESTs AA250868 ESTs AA251152 ESTs AA251544 ESTs AA251792 fatt -acid-Coenz me A Ii ase; Ion -chain 4 AA252063 BH- rotocadherin brain-heart AA252144 ESTs AA253461 ESTs AA255522 ESTs; Weakl similar to INHIBITOR OF

2 0 AA256468 ESTs AA256528 ESTs AA257976 ESTs AA258296 KIAA0579 rotein AA258409 m elfin rotein zero-like 1 2 5 AA258421 h othetical rotein AA262077 aldeh de deh dro enase 5 famil ; member AA278650 ESTs; Weakl similar to similar to the beta transducin famil AA278766 ESTs AA279667 natural killer-tumor reco nition se uence 3 0 AA280791 euka otic translation initiation factor AA280819 MADS box transcri tion enhancer factor 2; of a tide C

AA280828 Homo sa iens mRNA; cDNA DKFZ 586M141 from clone AA282195 ESTs; Weakl similar to Unknown H.sa iens AA283127 Homo sa iens clone LM1955 H105e3 ene;
artial cds 3 5 AA284694 nucleo orin-like rotein 1 AA291137 ESTs AA291708 ESTs; Weakl similar to !!!! ALU SUBFAMILY
SO WARNING

AA293495 chromosome 8 o en readin frame 1 AA347193 ESTs 4 0 AA398474 Homo sa iens mRNA; cDNA DKFZ 586H051 from clone ~ AA398512 STs ~

Exemplar Accession Com lete Title UniGeneID

AA400277 ESTs AA400896 ESTs AA404494 CTP s nthase AA410345 ESTs; Weakl similar to 'unctional adhesion molecule H.sa iens AA416733 ESTs; Weakl similar to !!!! ALU SUBFAMILY
SC WARNING

AA425154 ESTs AA426573 ESTs; Moderatel similar to endomucin M.musculus AA431418 N-acet I lucosaminidase; al ha- Sanfili o disease IIIB

Human DNA sequence from clone 44A20 on chromosome 6q23.1-24.3. Contains a gene for a A436182 novel protein similar to MTHFD1 (methylenetetrahydrofolate dehydrogenase (NADP+
de endent ; methen Itetrah drofolate c cloh drolase;

1 0 AA437099 ESTs AA446585 ESTs AA446887 ESTs AA447224 ESTs; Weakl similar to cDNA EST CEESW54F
comes from this AA447709 ESTs; Moderatel similar to utative transcri tion factor CA150 AA453624 deox nucleotid Itransferase; terminal AA455044 ESTs AA456045 ESTs AA460454 ESTs; Weakl similar to KIAA0512 rotein H.sa iens AA476494 ESTs; Weakl similar to KIAA0512 rotein H.sa iens 2 0 AA476738 leucine rich re eat in FLII interactin rotein 1 AA481422 Homo sa iens mRNA for H-2K bindin factor-2;
tom lete cds AA482269 inte ral membrane rotein 1 AA482595 ESTs; Weakl similar to F25B5.3 C.ele ans AA485084 ESTs 2 5 AA485431 ESTs AA489057 stromal anti en 2 AA489638 DKFZP564M2423 rotein AA491000 Homo sa iens mRNA; cDNA DKFZ 586N1720 from clone AA491250 ESTs 3 0 AA505133 solute carrier famil 2 facilitated lucose traps orter ; member 3 AA598447 ex ortin; tRNA nuclear ex ort rece for for tRNAs AA599243 eneral transcri tion factor IIIA

AA599574 i ase; endothelial l AA600153 DEK onto ene DNA bindin 3 5 AA609309 ESTs; Weakl similar to !!!! ALU SUBFAMILY
J WARNING

AA609710 Human chromosome 3 21.1 ene se uence AA610068 PIBF1 ene roduct AA621399 ESTs ' AA621752 6S proteasome-associated padl homolog ~2 Exemplar Accession Com lete Title UniGeneID 11/29/99 C21523 ESTs D12160 ESTs; Moderatel similar to !!!! ALU
SUBFAMILY J WARNING

D19708 ESTs D25801 ESTs; Hi hl similar to KIAA0445 rotein H.sa lens a disintegrin-like and metalloprotease D45652 (reprolysin type) with thrombos ondin t a 1 motif; 4; a recap D60208 ESTs D80504 zinc fin er rotein 198 F03010 m eloid/I m hold or mixed-lines a leukemia 2 F04247 ESTs F10966 Homo sa iens mRNA; cDNA DKFZ 434M196 from clone F13700 ribonuclease P; 40kD subunit H05063 ESTs; Weakl similar to / rediction H16758 a hro oietin rece for H22556 utative translation initiation factor H22566 ESTs H48459 KIAA0186 ene roduct H56559 KIAA0601 rotein H64938 ESTs H64973 ESTs H69535 ESTs H73110 ESTs 2 5 H81783 ESTs H86259 Homo sa iens chromosome 19; cosmid H88353 ESTs; Weakl similar to line-1 rotein ORF2 H.sa iens H88639 YY1-associated factor 2 H88675 nuclear rece for co-re ressor 1 3 0 H93708 s erm s ecific anti en 2 N22107 ESTs N24046 ESTs N27028 ESTs N30205 ESTs 3 5 N30621 ESTs N33258 nuclear rece for co-re ressor 1 EST; Highly similar to similar to N45198 Cdc14B1 phosphatase H.sa iens 4 0 N45979 SH3 domain rotein 1 B

Exemplar Accession Com lete Title UniGeneID

N48913 ESTs N49394 KIAA0716 ene roduct N50656 ESTs; Hi hl similar to mosaic rotein LR11 H.sa lens N50721 si nal se uence rece tor; amma translocon-associated rotein N53143 Homo sa iens clone 25218 mRNA se uence N53359 ESTs; Weakl similar to beta-TrCP rotein E3RS-Ika aB

N55326 ESTs N62955 ESTs; Weakl similar to KIAA0396 H.sa iens N63604 ESTs N64166 frizzled Droso hila homolo 7 N64168 ESTs N64191 ESTs N66845 ESTs; Weakl similar to !!!! ALU CLASS
B WARNING ENTRY !!!!

N67135 ESTs N67295 ESTs N68399 H2B histone famil ; member N

2 0 N68963 ESTs N69331 a tid I rol I isomerase C c clo hilin C

N70777 ESTs N71364 ESTs N71545 ESTs 2 5 N71571 ESTs N75594 ESTs N79035 ESTs N80279 h othetical rotein 3 0 N91797 ESTs N92454 ka o herin im ortin beta 1 N94581 actin; beta N94746 ESTs N98238 ESTs 3 5 802384 ESTs ESTs; Weakly similar to !!!! ALU SUBFAMILY

ENTRY !!!! H.sa iens 841828 m osin VA heav of a tide 12; m oxin 846395 DKFZP566A0946 rotein 4 0 858863 ESTs 878248 ESTs; Weakl similar to KIAA0970 rotein H.sa iens L T11483 _ ESTs - _ ~

Exemplar Accession Com lete Title UniGeneID 11/29/99 T16896 ESTs T23820 c clin T2 T30222 ESTs; Moderatel similar to tetrac cline trans orter-like rotein W15275 Homo sa iens mRNA; cDNA DKFZ 586E1624 from clone W42414 MAD mothers a ainst deca enta 1e ic;
Droso hila homolo 3 W46577 endothelial cell-s ecific molecule W49632 Human clone 23908 mRNA se uence W57613 ESTs W61118 ESTs W65344 ESTs; Moderatel similar to h othetical rotein H.sa lens W69216 ESTs W69379 Homo sa iens mRNA; cDNA DKFZ 586D0923 from clone W86728 ESTs 238499 MKP-1 like rotein t rosine hos hatase 238630 bladder cancer related rotein 10kD

239494 ESTs 239623 ESTs 2 0 240071 BMX non-rece for t rosine kinase 240174 ESTs AA166965 ESTs AA169599 ESTs AA171724 ESTs; Weakl similar to ORF YNL059c S.cerevisiae AA171739 ESTs ESTs; Weakly similar to MITOCHONDRIAL

H.sa lens 3 0 AA182626 ESTs AA186324 cell c cle ro ression 8 rotein AA192099 zinc fin er rotein 148 HZ-52 AA192173 ESTs AA192415 ESTs 3 5 AA192553 ESTs; Hi hl similar to RGC-32 R.norve icus AA194851 ESTs AA195520 ESTs AA196300 ESTs; Weakl similar to alternativel s liced roduct usin exon AA196517 rotease; serine; 15 4 0 AA196549 ESTs WO 01/11086 PCT/tJS00/22061 Exemplar Accession Com lete Title UniGeneID

AA196729 ESTs AA196979 ESTs; Weakl similar to rotease H.sa lens AA207123 immuno lobulin su ertamil ; member AA214539 TIA1 c otoxic ranule-associated RNA-bindin rotein AA226914 nuclear rece for subfamil 2; rou C;
member 1 AA227260 Zic famil member 3 odd- aired Droso hila homolo ; heterotax ESTs; Highly similar to multifunctional AA233122 calcium/calmodulin-de endent rotein kinase II delta2 isoform Machado-Joseph disease (spinocerebellar AA233334 ataxia 3;
olivo ontocerebellar ataxia 3; autosomal dominant; ataxin 3 AA233347 zinc fin er rotein 216 AA233519 ESTs; Weakl similar to evectin-1 R.norve icus AA233714 A 12 auto ha 12; S. cerevisiae -like AA233796 euka otic translation initiation factor 1 5 AA235050 ESTs AA235704 ESTs; Weakl similar to Wiscott-Aldrich S ndrome rotein AA236031 ESTs AA236352 ESTs AA236390 ESTs 2 0 AA236453 ESTs AA250947 ESTs AA251083 ESTs AA251113 ESTs 2 5 AA251973 ESTs AA252023 ESTs; Weakl similar to HRIHFB2157 H.sa iens AA252414 ESTs AA252650 mito en-activated rotein kinase kinase AA255523 ESTs 3 0 AA258128 ESTs AA262105 Homo sa iens mRNA; cDNA DKFZ 564L1916 from clone AA262107 ESTs AA262235 ESTs AA278298 M- hase hos ho rotein 1 3 5 AA278529 serine/threonine kinase 18 AA278721 ESTs AA280036 euka otic translation initiation factor 4A; isoform 2 AA280648 ESTs; Weakl similar to rab-related ~ GTP-bindin rotein AA280738 ESTs 4 0 280794 ~ ESTs Exemplar Accession Com lete Title UniGeneID

AA280837 ESTs AA280886 ESTs AA280934 ESTs AA281535 KIAA0879 rotein AA281797 eneral transcri tion factor IIH; of a tide 2 44kD subunit AA282047 ESTs AA283002 zinc fin er rotein 187 AA283709 cal ain like rotease AA283902 ESTs AA284108 Human DNA from chromosome 19-s ecific cosmid F25965;

Human DNA sequence from clone 71 L16 on chromosome Xp11.
A284109 Contains a probable Zinc Finger protein (pseudo)gene; an unknown utative ene; a seudo ene with hi h similarit to art AA284371 interleukin 13 rece tor; al ha 1 AA284744 ESTs; Hi hl similar to refoldin subunit 2 M.musculus AA284784 mitochondrial ribosome rec clin factor 1 5 AA284840 ESTs AA286844 ESTs AA287032 ESTs AA287038 ESTs AA287546 ESTs 2 0 AA287553 ESTs AA287556 ESTs; Weakl similar to !!!! ALU CLASS
B WARNING ENTRY !!!!

AA287564 IDN3 rotein AA291015 CDC7 cell division c cle 7; S. cerevisiae;
homolo -like 1 AA291716 ESTs 2 5 AA291749 estro en rece for 1 AA293656 ESTs Human DNA sequence from clone 141 H5 on chromosome A302430 Xq22.1-23. Contains parts of a novel Chordin LIKE protein with von Willebrand factor t a C domains.
Contains ESTs; STSs and AA302820 uriner is rece for P2X; Ii and- ated ion channel; 4 3 0 AA310499 ESTs AA340622 ESTs AA342457 ESTs; Moderatel similar to !!!! ALU
SUBFAMILY SQ WARNING

3 5 AA342828 I co rotein V latelet AA342864 ESTs AA342973 ESTs AA346495 ESTs I AA347573 fibronectin leucine rich transmembrane ~ protein 2 Exemplar Accession Com lete Title UniGeneID

AA347614 ESTs AA347717 ESTs AA348913 ESTs AA349773 ESTs AA350541 ESTs AA357172 ESTs AA369856 vacuolar rotein sortin 41 east homolo AA370472 ESTs AA370867 ESTs AA377296 ESTs AA383902 ESTs; Weakl similar to !!!! ALU SUBFAMILY
J WARNING

AA385934 EST; Hi hl similar to redicted usin Genefinder C.ele ans AA386266 ESTs; Weakl similar to M6a H.sa iens AA398014 ESTs 2 0 AA398222 ESTs AA398235 ESTs AA398348 ESTs AA398504 ESTs 2 5 AA398505 ESTs AA398507 nucleo orin 50kD

AA398523 ESTs AA398625 ESTs AA398632 ESTs 3 0 AA398633 ESTs AA398894 ESTs AA398900 ESTs 3 5 AA399122 ESTs; Weakl similar to mitochondria) citrate trans ort rotein AA399371 ESTs; Weakl similar to zinc fin er rotein SALL1 H.sa iens AA399373 ESTs; Hi hl similar to KIAA0568 rotein H.sa lens AA399441 ESTs AA399636 ESTs 4 0 AA399640 ESTs AA399680 ESTs AA400080 ESTs AA400262 ESTs Exemplar Accession Com lete Title UniGeneID

AA400725 ESTs AA400748 Homo sa iens mRNA; cDNA DKFZ 434D024 from clone AA400780 ESTs AA401631 ESTs AA401688 ESTs AA402227 ESTs; Weakl similar to TROPOMODULIN
H.sa lens phosphodiesterase 4A; CAMP-specific AA402329 (dunce Droso hila -homolo hos hodiesterase AA402398 ESTs AA402468 ESTs AA403268 ESTs AA403314 ESTs 1 5 AA404260 ESTs AA404271 lutamate rece tor; ionotro ic; kainate AA405026 ESTs AA405182 ESTs AA406063 ESTs AA406335 ESTs 2 5 AA411801 KIAA0307 ene roduct AA411804 ESTs AA411833 ESTs; Hi hl similar to Trad H.sa iens AA412219 ESTs AA412259 ESTs AA412498 ESTs AA416586 ESTs AA416874 ESTs 3 5 AA421133 ESTs AA422079 ESTs; Weakl similar to RAR-RESPONSIVE

AA423837 ESTs AA424328 ESTs 4 0 AA424339 ESTs AA424469 ESTs ~ AA424502 ESTs ~

Exemplar Accession Com lete Title UniGeneID

AA425004 ESTs AA425734 ESTs; Weakl similar to h othetical rotein H.sa lens AA425887 ESTs AA426456 ESTs AA427396 ESTs AA427555 KIAA0203 ene roduct AA428218 ESTs AA428242 transcri tion factor 9 binds GC-rich se uences AA428994 ESTs AA429666 ESTs AA430181 ESTs AA430184 ATP/GTP-bindin rotein AA431288 CD3D anti en; delta of a tide TiT3 com lex AA431293 ESTs AA431478 ESTs 2 0 AA432278 ESTs AA434411 ESTs AA435512 ESTs AA435698 ESTs AA435711 KIAA0712 ene roduct 2 5 AA435815 Clk-associatin RS-c clo hilin AA435842 ESTs AA436475 ESTs AA436489 ESTs AA442060 ESTs 3 0 AA442079 ESTs AA443151 ESTs; Weakl similar to weak similarit with uinone AA446133 ESTs AA447145 Homo sa iens KIAA0399 mRNA; artial cds 3 5 AA447643 ESTs AA447742 d nein; axonemal; heav of a tide 17-like AA449444 ESTs 4 0 AA450087 e ulator of Gz-selective rotein si r nalin AA450244 ESTs AA452123 ESTs; Weakl similar to T-com lex rotein 1 OA H.sa iens AA452155 inc fin er rotein 198 z Exemplar Accession Com lete Title UniGeneID

AA453036 ESTs; Weakl similar to similar to mol bdoterin bios nthesis AA453526 ESTs AA454103 ESTs AA454642 ESTs AA454935 nuclear res irato factor 1 AA456323 ESTs AA457395 ESTs AA459662 ESTs AA459668 3-h drox isobut I-Coenz me A h drolase AA459679 ESTs; Weakl similar to The KIAA0191 ene is ex ressed AA459702 ESTs AA460017 ESTs; Weakl similar to dia hanous-related formin M.musculus AA460324 ESTs AA461509 ESTs; Weakl similar to utative 150 H.sa iens AA464414 ESTs AA464428 ESTs 2 0 AA470084 ESTs AA476606 ESTs AA478521 ESTs AA478523 ESTs; Moderatel similar to !!!! ALU
SUBFAMILY J WARNING

AA479949 RAB2; member RAS onto ene famil 2 5 AA481252 onto ene TC21 AA485351 KIAA1067 rotein AA487264 ESTs AA489072 KIAA0870 rotein AA489630 KIAA0665 ene roduct 3 0 AA490225 ESTs AA490227 ESTs AA490255 ESTs AA490890 ESTs AA490916 ESTs 3 5 AA490925 a ile s ; ro ressive m oclonic a ile s ; t a 2 ene; Lafora AA490955 ESTs; Weakl similar to bullous em hi oid anti en M.musculus AA495812 ESTs AA495824 ESTs AA496369 ESTs 4 0 AA504125 ESTs AA521473 SEC10 (S. cerevisiae)-like 1 Exemplar Accession Com lete Title UniGeneID

AA598899 Homo sa iens mRNA; cDNA DKFZ 564D036 from clone AA599244 KIAA0530 rotein AA599694 KIAA0133 ene roduct AA600037 ESTs AA609135 ESTs AA609582 katanin 60 ATPase-containin subunit AA609684 ESTs AA609839 4-vitro hen I hos hatase domain and non-neuronal SNAP25-like AA609862 RNA-bindin rotein eve with multi )e s licin AA620747 ESTs AA621364 ESTs C20653 ESTs D20085 ESTs; Weakl similar to KIAA0742 rotein H.sa iens D20749 ESTs D51285 ESTs D59972 cullin 5 F04112 ESTs 2 0 F13604 ESTs H01662 ESTs H05135 ESTs 2 5 H30894 ESTs H43442 leuc I-tRNA s nthetase; mitochondria) H45996 utative G rotein-cou led rece for H69281 ESTs H69485 ESTs 3 0 H69899 ESTs; Moderate) similar to unknown H.sa lens H70627 ESTs; Weakl similar to !!!! ALU CLASS
E WARNING ENTRY !!!!

H73050 Rhesus blood rou ; D anti en H73260 ESTs H77531 HIR histone cell c cle re ulation defective; S. cerevisiae H80737 I s I oxidase H93412 ESTs; Weakl similar to ORF YGR101w S.cerevisiae H94892 v-ral simian leukemia viral onto eve homolo A ras related H95643 neurotro hit t rosine kinase; rece tor; t a 1 4 0 H96552 ESTs H97146 ESTs; Hi hl similar to G rotein-cou led rece for kinase 6;

H99131 ESTs Exemplar Accession Com lete Title UniGeneID

H99462 ribosomal rotein; mitochondrial; L12 H99837 ESTs N22140 ESTs; Weakl similar to beta-tubulin H.sa lens N22197 Sec23-interactin rotein 125 N23756 solute carrier famil 23 nucleobase traps orters ; member 1 N24134 euka otic translation initiation factor 1A; Y chromosome N24195 novel centrosomal rotein RanBPM

N26739 DKFZP564B147 rotein 1 0 N27637 ESTs N33090 DEAD/H As -Glu-Ala-As /His box of a tide 19 Db 5; east;

N35967 serinelthreonine kinase 24 Ste20; east homolo N38959 cha eronin containin TCP1; subunit 2 beta N39069 ESTs 1 5 N46441 ESTs N48270 ESTs N48365 ESTs N51316 ESTs N51499 A kinase PRKA anchor rotein 2 2 0 N53976 ESTs N54157 ESTs N54300 ESTs N54831 ESTs N59849 ESTs 2 5 N62132 ESTs N63138 ESTs N63172 cell division c cle 42 GTP-bindin rotein;
25kD

novel putative protein similar to YIL091C
N63772 yeast hypothetical 84 kD
rotein from SGA1-KTR7 3 0 N63787 sema domain; immuno lobulin domain I ; short basic domain;

N68201 ESTs N68300 ESTs N75007 ESTs; Moderatel similar to KIAA1004 rotein H.sa iens N75542 transcri tion factor 4 O-linked N-acetylglucosamine (GIcNAc) N90066 transferase UDP-N-acet I lucosamine: of a tide-N-acet I lucosamin I

N91246 ESTs 4 0 N92751 ESTs; Weakl similar to MICROTUBULE-ASSOCIATED

N93214 KIAA0318 protein Exemplar Accession Com lete Title UniGeneID

N99148 ESTs; Weakl similar to ZINC FINGER
PROTEIN 83 H.sa iens 807876 ESTs; Weakl similar to unknown S.cerevisiae 810865 al ha-feto rotein 811056 ESTs 811488 ESTs 822947 ESTs 823930 ESTs; Hi hl similar to rediabetic NOD sera-reactive autoanti en 826589 ESTs 837588 RAB2; member RAS onco ene famil -like 837613 Homo sa iens clone 25027 mRNA se uence 838398 Homo sa iens clone 23758 mRNA se uence 839179 ESTs 840923 ESTs 841179 Human mRNA for KIAA0328 ene; artial cds 1 5 841294 ESTs 842307 earl develo ment re ulator 2 homolo of of homeotic 2 843189 ESTs 843306 ESTs 844357 ESTs; Weakl similar to cDNA EST EMBL:T01421 comes from 2 0 844519 EST; Moderatel similar to Pro-Pol-dUTPase of rotein 847948 ESTs 851524 ESTs 854950 ESTs 2 5 855241 ESTs 859585 ESTs 860044 ESTs; Hi hl similar to BETA-CATENIN
H.sa lens 860872 ESTs 866690 ESTs 3 0 867266 exostoses multi 1e -like 1 873588 ESTs 879403 ESTs 887647 ESTs 893622 euka otic translation initiation factor 2; subunit 2 beta; 38kD

3 5 899599 hetero eneous nuclear ribonucleo rotein U scaffold attachment 899612 ESTs; Moderatel similar to !!!! ALU
SUBFAMILY J WARNING

T15597 KIAA0661 ene roduct T15652 ~ ESTs Exemplar Accession Com lete Title UniGeneID

T16898 ash2 absent; small; or homeotic; Droso hila; homolo -like T26644 ESTs; Weakl similar to zinc fin er rotein H.sa iens T40841 ESTs T58615 ESTs T59940 ESTs T63595 ESTs T64924 ESTs ESTs; Weakly similar to !!!! ALU SUBFAMILY

ENTRY !!!! H.sa lens T69027 ESTs T70353 ESTs T79780 ESTs; Weakl similar to CGI-69 rotein H.sa iens T79951 ESTs T80174 ESTs; Moderatel similar to similar to NEDD-4 H.sa lens 2 0 T80622 ESTs; Weakl similar to envelo a H.sa lens T85352 ESTs T85373 ESTs T86284 ESTs T89579 transcri tion factor D -1 2 5 T90360 ESTs T94328 ESTs T97257 ESTs T97599 ESTs 3 0 T97620 ESTs T98152 fibrillin 2 con enital contractural arachnodact I

W31479 ESTs W37999 ESTs W40150 chondroitin sulfate roteo I can 6 bamacan W45435 KIAA0784 rotein W58202 ESTs W58344 ESTs 4 0 W58650 ESTs Human DNA sequence from clone 1189B24 on chromosome Xq25-26.3. Contains NADH-Ubiquinone 68736 Oxidoreductase MLRO
subunit (EC 1.6.5.3; EC 1.6.99.3; CI-MLRQ);
Tubulin Beta and Proto-onco ene T rosine- rotein Kinase FER EC 2.7.1.112;

Exemplar Accession Com lete Title UniGeneID

W69106 chromobox homolo 3 Droso hila HP1 amma W69111 ESTs W69385 nuclear mitotic a aratus rotein 1 W69399 H1 histone famil ; member 0 W69459 sex comb on midle Droso hila -like W72424 S100 calcium-bindin rotein A9 cal ranulin B

W72724 ESTs W72834 ESTs W73955 Homo sa iens chromosome 19; cosmid W74701 ESTs W76540 DKFZP564G2022 rotein W79397 ESTs W85888 ESTs; Moderatel similar to !!!! ALU
SUBFAMILY SQ WARNING

W86038 ESTs W86881 ESTs W87804 ESTs W90022 ESTs; Hi hl similar to LECT2 recursor H.sa lens W92272 chromodomain helicase DNA bindin rotein 2 0 W92764 tumor necrosis factor; al ha-induced rotein 6 W93040 Homo sa iens aired mesoderm homeo box 1 PMX1 ; mRNA

W93092 neutral s hin om elinase N-SMase activation associated factor W93523 ESTs 2 5 W93659 ESTs W94003 ESTs W94401 ESTs W94688 erili in W94787 destrin actin de of merizin factor 3 0 238294 ESTs 238311 ESTs 238465 ESTs 238525 ESTs 238538 ESTs 3 5 238551 ESTs 238783 Ca2+-de endent activator rotein for secretion 239113 ESTs 239255 YDD19 rotein 4 0 239783 ESTs; Weakl similar to K01 H12.1 C.ele ans 239920 ESTs; Weakl similar to NADH-CYTOCHROME

240166 ESTs 240388 ESTs Exemplar Accession Com lete Title UniGeneID

240646 ESTs 241697 ESTs 299349 ESTs 299394 zinc fin er rotein 36 KOX 18 Exemplar UniGeneID(11/29/
Accession Complete Title 99) D86425 Homo sapiens mRNA for nidogen-2 Hs.82733 D86983 Human mRNA for KIAA0230 gene; partial Hs.118893 cds HG1098-HT1098Cystatin D

HG1103-HT1103Guanine Nucleotide-Binding Protein Ral, Ras-Oncogene Related HG3342-HT3519Id 1 J03764 plasminogen activator inhibitor; type Hs.82085 I

L06797 chemokine (C-X-C motif); receptor 4 (fusin)Hs.89414 L15388 Human G protein-coupled receptor kinase Hs.211569 (GRKS) mRNA, complete cds phosphodiesterase 4B; cAMP-specific (dunce L20971 (Drosophila)-homolog Hs.188 phosphodiesterase E4) L35545 endothelial cell protein C/activated proteinHs.82353 C receptor L76380 calcitonin receptor-like Hs.152175 M21305 Human alpha satellite and satellite 3 Hs.247946 junction DNA sequence M24736 selectin E (endothelial adhesion moleculeHs.89546 1 ) M31166 pentaxin-related gene; rapidly induced Hs.2050 by IL-1 beta M31551 plasminogen activator inhibitor; type Hs.75716 II (arginine-serpin) M32334 intercellular adhesion molecule 2 Hs.83733 2 0 M61916 laminin; beta 1 Hs.82124 Human phosphatidylcholine 2-acylhydrolase M68874 (cPLA2) mRNA, complete cds M74719 transcription factor 4 Hs.75356 M92934 connective tissue growth factor Hs.75511 M94856 fatty acid binding protein 5 (psoriasis-associated)Hs.153179 003057 singed (Drosophila)-like (sea urchin fascinHs.118400 homolog like) 003877 EGF-containing fibulin-like extracellularHs.76224 matrix protein 1 018300 damage-specific DNA binding protein 2 Hs.77602 (48kD) 027109 Human prepromultimerin mRNA; complete Hs.32934 cds 031384 guanine nucleotide binding protein 11 Hs.83381 3 0 033053 protein kinase C-like 1 Hs.2499 059423 MAD (mothers against decapentaplegic; Hs.79067 Drosophila) homolog 1 070322 karyopherin (importin) beta 2 Hs.168075 081607 kinase scaffold protein gravin Hs.788 083463 syndecan binding protein (syntenin) Hs.8180 3 5 089942 l ysyl oxidase-like 2 Hs.83354 X04729 Human mRNA for plasminogen activator inhibitor type 1 N-terminus X06256 i ntegrin; alpha 5 (fibronectin receptor; Hs.149609 alpha polypeptide) X07820 matrix metalloproteinase 10 (stromelysin Hs.2258 2) X54925 matrix metalloproteinase 1 (interstitial Hs.83169 collagenase) 4 0 X54936 placental growth factor; vascular endothelialHs.2894 growth factor-related protein t yrosine kinase with immunoglobulin and X60957 epidermal growth factor Hs.78824 homology domains X67235 hematopoietically expressed homeobox Hs.118651 X67951 proliferation-associated gene A (natural Hs.180909 killer-enhancing factor A) Exemplar UniGeneID(11/29/
Accession Complete Title 99) X69910 H.sapiens p63 mRNA for transmembrane proteinHs.74368 X79981 cadherin 5; VE-cadherin (vascular epithelium)Hs.76206 218951 caveolin 1; caveolae protein; 22kD Hs.247266 zp61 b6.r1 Stratagene endothelial cell AA187101 937223 Homo sapiens cDNA
clone IMAGE:624659 5', mRNA sequence N24990 ESTs Hs.26418 881003 Homo sapiens serine protease mRNA; completeHs.154737 cds AA025351 ESTs Hs.134797 AA027168 ESTs Hs.10031 AA040465 ESTs Hs.8728 AA045136 ESTs Hs.22575 AA054087 phospholipase A2; group IVC (cytosolic; Hs.18858 calcium-independent) ESTs; Moderately similar to !!!! ALU SUBFAMILY
AA071089 SC WARNING ENTRY Hs.187932 !!!! [H.sapiens]

AA085918 H.sapiens HUNKI mRNA Hs.247482 AA187490 ESTs Hs.21941 AA227926 ESTs Hs.6682 AA234743 ESTs Hs.22120 AA236559 ESTs; Weakly similar to neuronal thread Hs.8768 protein AD7c-NTP [H.sapiens]

AA292694 ESTs Hs.3807 AA398243 ESTs; Moderately similar to (defline not Hs.21806 available 3694664) [H.sapiens]

2 0 AA406363 ESTs Hs.30822 AA411465 ESTs Hs.8619 AA412284 poliovirus receptor Hs.171844 AA423987 ESTs Hs.7567 AA425309 ESTs Hs.33287 2 5 AA435896 ESTs Hs.18397 AA448238 Homo sapiens mRNA for KIAA0915 protein; Hs.16714 complete cds AA478778 ESTs Hs.16450 AA621714 ESTs Hs.25338 Human isolate JuSo MUC18 glycoprotein D51069 mRNA (3' variant); complete Hs.211579 cds UDP-N-acetyl-alpha-D-galactosamine:polypeptide 3 0 T34527 N-acetylgalactosaminyltransferase 1 (GaINAc-T1Hs.80120 ) U97519 podocalyxin-like Hs.16426 AA127221 ESTs Hs.71059 ESTs; Moderately similar to C-1-TETRAHYDROFOLATE
AA132983 SYNTHASE; Hs.44155 CYTOPLASMIC [H.sapiens]

ESTs; Weakly similar to !!!! ALU SUBFAMILY
AA135606 SB WARNING ENTRY !!!! Hs.189384 [H.sapiens]

3 5 AA156125 ESTs Hs.72116 AA179845 RAB6 interacting; kinesin-like (rabkinesin6)Hs.73625 AA232645 ESTs Hs.42699 F10399 ESTs Hs.14763 H16772 ESTs Hs.31444 40 N39584 ~ ESTs Hs.17404 ~

Exemplar UniGeneID(11/29/
Accession Complete Title 99) UDP-N-acetyl-alpha-D-galactosamine:polypeptide N52006 N-acetylgalactosaminyltransferase 1 (GaINAc-T1Hs.80120 ) N53375 Homer; neuronal immediate early gene; Hs.166146 N54067 Homo sapiens mRNA for NIK; partial cds Hs.3628 N64436 ESTs Hs.20813 826892 ESTs Hs.221434 T33637 ESTs Hs.6841 yc20g11.s1 Stratagene lung (#937210) Homo T57112 sapiens cDNA clone IMAGE:81284 3', mRNA sequence.

W80763 ESTs; Moderately similar to FK506-bindingHs.3849 protein 65kD [M.musculus]

AA046808 ESTs; Highly similar to 40S RIBOSOMAL Hs.108957 PROTEIN S27 [H.sapiens]

AA253217 ESTs Hs.41271 AA255991 ESTs Hs.175319 AA258138 ESTs Hs.88297 AA426573 ESTs Hs.41135 AA443793 ESTs Hs.94761 AA490588 ESTs Hs.43118 AA496257 ESTs; Weakly similar to (defline not availableHs.72165 3513303) [H.sapiens]

ESTs; Weakly similar to MICROTUBULE-ASSOCIATED
AA609717 PROTEIN 1 B Hs.66048 [H.sapiens]

D59570 ESTs Hs.17132 F13787 ESTs Hs.58596 2 0 H88157 ESTs Hs.41105 H98988 ESTs Hs.42612 N34287 unc5 (C.elegans homology C Hs.44553 N52090 EST Hs.47420 ESTs; Weakly similar to !!!! ALU CLASS
N66845 B WARNING ENTRY !!!! Hs.165411 [H.sapiens]

2 5 N68905 small inducible cytokine A5 (RANTES) 832894 ESTs Hs.45514 861715 ESTs Hs.138237 yi54c08.s1 Soares placenta Nb2HP Homo sapiens cDNA clone 71234 IMAGE:143054 3' similar to gb~M87908~HUMALNE32 Human carcinoma cell-derived Alu RNA transcript, (rRNA);
gb:S41458 ROD

yr30g11.s1 Soares fetal liver spleen 1 898105 NFLS Homo sapiens cDNA clone IMAGE:206852 3', mRNA sequence.

3 0 T97186 small inducible cytokine A5 (RANTES) ESTs; Moderately similar to !!!! ALU SUBFAMILY
W80814 ! SB WARNING ENTRY
!!! [H.sapiens] s.193700 AA404418 EST Hs.144953 AA405747 ESTs; Moderately similar to HMG-box transcriptionHs.97865 factor [M.musculus]

ESTs; Moderately similar to !!!! ALU SUBFAMILY

! !!! [H.sapiens] s.190307 ESTs; Moderately similar to !!!! ALU SUBFAMILY

! !!! [H.sapiens]

AA608588 ESTs Hs.193634 Exemplar UniGeneID(11/29/
Accession Complete Title 99) ESTs; Moderately similar to !!!! ALU SUBFAMILY
AA608751 SC WARNING ENTRY Hs.244904 !!!! [H.sapiens]

C13961 EST Hs.210115 D60302 ESTs Hs.108977 H94892 v-ral simian leukemia viral oncogene homologHs.6906 A (ras related) N93521 transcription factor 4 Hs.241362 N95477 ESTs Hs.102943 ESTs; Weakly similar to !!!! ALU SUBFAMILY
860044 J WARNING ENTRY !!!! Hs.106706 [H.sapiens]

870506 ESTs; Moderately similar to transformation-relatedHs.107159 protein [H.sapiens]

ye20f05.s1 Stratagene lung (#937210) Homo T91518 sapiens cDNA clone IMAGE:118305 3' similar to contains Alu repetitive element;contains T95333 ESTs; Weakly similar to Strabismus [D.melanogaster]Hs.122730 845630 ESTs; Highly similar to KIAA0372 [H.sapiens]Hs.170098 yg05c07.r1 Soares infant brain 1 NIB Homo 820839 sapiens cDNA clone IMAGE:31444 5', mRNA sequence.

823858 ESTs; Moderately similar to envelope proteinHs.23986 [H.sapiens]

A1024874 ESTs; Weakly similar to (defline not availableHs.57958 3882257) [H.sapiens]

W26247 U5 snRNP-specific protein (220 kD); orthologHs.6413 of S. cerevisiae Prp8p AA856990 ESTs Hs.125058 AA136653 ESTs AA358869 ESTs; Highly similar to SEC13-RELATED Hs.227949 PROTEIN [H.sapiens]

AI123976 ESTs Hs.105689 2 0 AI369384 arylsulfatase D

AA379500 ESTs Hs.193155 849693 ESTs Hs.107708 AA195678 Homo sapiens mRNA for KIAA0465 protein; Hs.108258 partial cds M30257 vascular cell adhesion molecule 1 Hs.109225 2 5 AA028131 ESTs Hs.110342 M10321 Human von Willebrand factor mRNA, 3' end Hs.110802 J03040 secreted protein; acidic; cysteine-rich Hs.111779 (osteonectin) M86933 amelogenin (Y chromosome) Hs.1238 AA012933 ubulin-specific chaperone d Hs.241687 t 3 0 AA286710 ymphocyte adaptor protein Hs.13131 l AA243278 ibosomal protein; mitochondrial; L12 Hs.109059 r D59711 ESTs Hs.237289 ye36g7.s1 Stratagene lung (#93721 ) Homo T94452 I sapiens cDNA clone Hs.241207 MAGE:119868 3', mRNA sequence AA053400 ESTs Hs.241227 Homo sapiens mRNA; cDNA DKFZp58611518 3 5 AA370302 (from clone Hs.21739 DKFZp58611518) J05008 endothelin 1 Hs.2271 U85193 nuclear factor IlB Hs.33287 AA256153 ESTs Hs.23912 X83107 BMX non-receptor tyrosine kinase Hs.27372 4 0 AA046593 ESTs Hs.28959 ~ ~

Exemplar UniGeneID(11/29/
Accession Complete Title 99) AA410480 ESTs Hs.30089 D45304 ESTs Hs.31595 M90657 transmembrane 4 superfamily member 1 Hs.3337 AA010163 upstream regulatory element binding proteinHs.3383 AA136353 ESTs Hs.38022 Y07867 pirin Hs.38842 U84573 procollagen-lysine; 2-oxoglutarate 5-dioxygenaseHs.41270 (lysine hydroxylase) 2 X60486 H4 histone family; member G Hs.46423 AA132969 metalloprotease 1 (pitrilysin family) Hs.4812 AA114250 KIAA0512 gene product Hs.48924 F13782 LIM binding domain 2 Hs.4980 ESTs; Weakly similar to IIII ALU SUBFAMILY
AA283035 J WARNING ENTRY IIII Hs.54813 [H.sapiens]

AB002301 Human mRNA for KIAA0303 gene; partial Hs.54985 cds Sjogren syndrome antigen A2 (60kD; ribonucleoprotein AA056731 autoantigen Hs.554 SS-A/Ro) U68019 MAD (mothers against decapentaplegic; Hs.211578 Drosophila) homolog 3 H99198 ESTs; Moderately similar to THYMOSIN BETA-4Hs.56145 [H.sapiens]

AA598702 bone morphogenetic protein 6 Hs.6101 N77151 Homo sapiens mRNA for KIAA0799 protein; Hs.61638 partial cds AA505133 ESTs Hs.62273 2 0 AB000584 prostate differentiation factor Hs.116577 D12763 interleukin 1 receptor-like 1 Hs.66 AA253193 ESTs Hs.6631 AA432248 ESTs Hs.6738 AA083572 v-ral simian leukemia viral oncogene homologHs.6906 A (ras related) 2 5 AA479713 ESTs Hs.71962 L40395 Homo sapiens clone 23689 mRNA; complete Hs.170001 cds X52947 gap junction protein; alpha 1; 43kD (connexinHs.74471 43) W80846 vesicle-associated membrane protein 5 Hs.74669 (myobrevin) M34539 FK506-binding protein 1A (12kD) Hs.752 3 0 D67029 SEC14 (S. cerevisiae)-like Hs.75232 U09587 glycyl-tRNA synthetase Hs.75280 M85289 Human heparan sulfate proteoglycan (HSPG2)Hs.211573 mRNA, complete cds D10522 myristoylated alanine-rich protein kinaseHs.75607 C substrate (MARCKS; 80K-L) W84712 calumenin Hs.7753 3 5 D29992 tissue factor pathway inhibitor 2 Hs.78045 L34657 platelet/endothelial cell adhesion moleculeHs.78146 (CD31 antigen) S78569 laminin; alpha 4 Hs.78672 D43636 Human mRNA for KIAA0096 gene; partial Hs.79025 cds U97188 IGF-II mRNA-binding protein 3 Hs.79440 4 0 AA487558 ESTs Hs.8135 M28882 Human MUC18 glycoprotein mRNA, complete Hs.211579 cds X70683 SRY (sex determining region Y)-box 4 Hs.83484 X14787 ~t hrombospondin 1 Hs.87409 Exemplar UniGeneID(11/29/
Accession Complete Title 99) ESTs; Weakly similar to !!!! ALU CLASS
AA236324 A WARNING ENTRY !!!! Hs.92381 [H.sapiens]

C15324 ESTs Hs.93668 AA452000 ESTs Hs.94030 D83174 collagen-binding protein 2 (colligen 2) Hs.9930 Homo Sapiens gene for thymidylate synthase;
D00596 exons 1; 2; 3; 4; 5; 6; 7; Hs.196351 complete cds D11428 peripheral myelin protein 22 Hs.103724 D13640 major histocompatibility complex; class Hs.183618 I; C

D14874 adrenomedullin Hs.394 D26129 ribonuclease; RNase A family; 1 (pancreatic)Hs.78224 D28476 thyroid hormone receptor interactor 12 Hs.138617 D86425 Homo sapiens mRNA for nidogen-2 Hs.82733 D86983 Human mRNA for KIAA0230 gene; partial cds Hs.118893 D87953 N-myc downstream regulated Hs.75789 HG1862-HT1897Calmodulin Type I

HG2614-HT2710Collagen, Type Viii, Alpha 1 HG2639-HT2735Single-Stranded Dna-Binding Protein Mssp-1 HG2855-HT2995Heat Shock Protein, 70 Kda (Gb:Y00371 ) HG3044-HT3742Fibronectin, Alt. Splice 1 H 63342-HT3519Id 1 2 0 HG3543-HT3739Insulin-Like Growth Factor 2 HG4069-HT4339Monocyte Chemotactic Protein 1 HG417-HT417Cathepsin B

J03764 plasminogen activator inhibitor; type I Hs.82085 L06797 chemokine (C-X-C motif); receptor 4 (fusin)Hs.89414 L08246 myeloid cell leukemia sequence 1 (BCL2-related)Hs.86386 L12711 t ransketolase (Wernicke-Korsakoff syndrome)Hs.89643 L13977 prolylcarboxypeptidase (angiotensinase Hs.75693 C) L15388 Human G protein-coupled receptor kinase (GRK5) mRNA, complete cds L19871 activating transcription factor 3 Hs.460 3 0 L20859 Human leukemia virus receptor 1 (GLVR1 Hs.78452 ) mRNA; complete cds L42176 f our and a half LIM domains 2 Hs.8302 L49169 Human GOS3 mRNA; complete cds Hs.75678 L76380 calcitonin receptor-like Hs.152175 M15990 v-yes-1 Yamaguchi sarcoma viral oncogene Hs.194148 homolog 1 3 5 M23254 calpain; large polypeptide L2 Hs.76288 M24736 s electin E (endothelial adhesion molecule Hs.89546 1 ) M26576 c ollagen; type IV; alpha 1 Hs.119129 M27396 a sparagine synthetase Hs.75692 M31166 p entaxin-related gene; rapidly induced by Hs.2050 IL-1 beta Homo sapiens aldehyde dehydrogenase (ALDH1 4 0 M31994 c ) gene, exon 13 and omplete cds M32334 i ntercellular adhesion molecule 2 Hs.83733 ~ M35878 i nsulin-like growth factor binding protein Hs.77326 Exemplar UniGeneID(11/29/
Accession Complete Title 99) M36429 postmeiotic segregation increased 2-like Hs.89672 M57730 ephrin-A1 Hs.1624 M57731 GR02 oncogene Hs.75765 M60858 nucleolin Hs.79110 M62994 filamin B; beta (actin-binding protein-278)Hs.81008 Human phosphatidylcholine 2-acylhydrolase M68874 (cPLA2) mRNA, complete cds nuclear factor of kappa light polypeptide M69043 gene enhancer in B-cells Hs.81328 inhibitor; alpha M74719 transcription factor 4 Hs.75356 M75126 hexokinase 1 Hs.118625 CD59 antigen p18-20 (antigen identified M84349 by monoclonal antibodies Hs.119663 16.3A5; EJ16; EJ30; EL32 and 6344) M92843 zinc finger protein homologous to Zfp-36 Hs.198309 in mouse M92934 connective tissue growth factor Hs.75511 M93056 protease inhibitor 2 (anti-elastase); monocyte/neutrophilHs.183583 M94856 fatty acid binding protein 5 (psoriasis-associated)Hs.153179 M95787 transgelin Hs.75777 Protein kinase inhibitor [human; neuroblastoma S76965 cell line SH-SY-5Y; Hs.75209 mRNA; 2147 nt]

S81914 DIFFERENTIATION-DEPENDENT GENE 2 Hs.76095 003057 singed (Drosophila)-like (sea urchin fascinHs.118400 homolog like) 003100 catenin (cadherin-associated protein); Hs.178452 alpha 1 (102kD) 2 0 003877 EGF-containing fibulin-like extracellular Hs.76224 matrix protein 1 008021 nicotinamide N-methyltransferase Hs.76669 014391 myosin IC Hs.82251 031384 guanine nucleotide binding protein 11 Hs.83381 032944 dynein; cytoplasmic; light polypeptide Hs.5120 Human spermidine/spermine N1-acetyltransferase 2 5 040369 (SSAT) gene, complete cds 041767 Human metargidin precursor mRNA, complete cds 048959 Homo sapiens myosin light chain kinase Hs.75950 (MLCK) mRNA; complete cds Human nicotinamide N-methyltransferase 051010 gene, exon 1 and 5' flanking region 051478 ATPase; Na+/K+ transporting; beta 3 polypeptideHs.76941 Human ovarian cancer downregulated myosin 3 0 053445 heavy chain homolog Hs.15432 (Doc1 ) mRNA; complete cds 059289 cadherin 13; H-cadherin (heart) Hs.63984 059423 MAD (mothers against decapentaplegic; Drosophila)Hs.79067 homolog 1 062015 Homo sapiens Cyr61 mRNA, complete cds Human hepatitis delta antigen interacting 063825 protein A (dipA) mRNA; Hs.66713 complete cds 3 5 067963 Human lysophospholipase homolog (HU-K5) Hs.6721 mRNA; complete cds 073379 Human cyclin-selective ubiquitin carrier Hs.93002 protein mRNA; complete cds 073824 eukaryotic translation initiation factor Hs.183684 4 gamma; 2 077604 microsomal glutathione S-transferase 2 Hs.81874 ~ U81607 kinase scaffold protein gravin Hs.788 Exemplar UniGeneID(11/29/
Accession Complete Title 99) 089942 lysyl oxidase-like 2 Hs.83354 X04412 gelsolin (amyloidosis; Finnish type) Hs.80562 X06985 heme oxygenase (decycling) 1 Hs.75967 X07820 matrix metalloproteinase 10 (stromelysin Hs.2258 2) X12876 keratin 18 Hs.65114 X15729 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptideHs.76053 5 (RNA helicase; 68kD) X52541 early growth response 1 Hs.738 X53416 filamin A; alpha (actin-binding protein-280)Hs.76279 X54489 GR01 oncogene (melanoma growth stimulatingHs.789 activity; alpha) X54925 matrix metalloproteinase 1 (interstitial Hs.83169 collagenase) X57206 inositol 1;4;5-trisphosphate 3-kinase B Hs.78877 X59798 cyclin D1 (PRAD1: parathyroid adenomatosisHs.82932 1) tyrosine kinase with immunoglobulin and X60957 epidermal growth factor Hs.78824 homology domains X65965 H.sapiens SOD-2 gene for manganese superoxide dismutase X69111 inhibitor of DNA binding 3; dominant negativeHs.76884 helix-loop-helix protein X70940 eukaryotic translation elongation factor Hs.2642 1 alpha 2 X87838 catenin (cadherin-associated protein); Hs.171271 beta 1 (88kD) X91247 thioredoxin reductase 1 Hs.13046 X97748 H.sapiens PTX3 gene promotor region 2 0 Y00815 protein tyrosine phosphatase; receptor Hs.75216 type; F

AA303711 ephrin-B1 Hs.144700 L44538 ESTs Hs.156044 AA025351 ESTs Hs.134797 AA027050 ESTs Hs.31189 2 5 AA029462 ESTs Hs.17235 AA045136 ESTs Hs.22575 AA047437 ESTs Hs.22968 AA054087 phospholipase A2; group IVC (cytosolic; Hs.18858 calcium-independent) ESTs; Moderately similar to !!!! ALU SUBFAMILY

!~!! [H.sapiens] s.187932 3 0 AA156450 ESTs; Weakly similar to Similar to Rat Hs.8982 trg gene product [C.elegans]

AA187490 ESTs Hs.21941 ESTs; Moderately similar to PROBABLE G
AA195031 PROTEIN-COUPLED Hs.9305 RECEPTOR APJ [H.sapiens]

AA205724 ESTs Hs.10119 AA227926 ESTs Hs.6682 3 5 AA227986 ESTs Hs.25329 AA234743 ESTs Hs.22120 AA253216 ESTs Hs.22283 AA256210 oncomodulin Hs.199134 AA256268 ESTs Hs.10283 4 0 AA279397 ESTs; Moderately similar to fibronectin Hs.25001 [H.sapiens]

ESTs; Moderately similar to !!!! ALU SUBFAMILY
AA292379 SO WARNING ENTRY Hs.20340 ! !!! H.sa lens Exemplar UniGeneID(11/29/
Accession Complete Title 99) AA292717 ESTs; Weakly similar to JM2 [H.sapiens] Hs.7891 AA346551 ESTs Hs.23457 AA400292 ESTs Hs.23786 AA404338 ESTs Hs.21812 AA412284 poliovirus receptor Hs.171844 AA423987 ESTs Hs.7567 AA428594 ESTs Hs.21321 AA430108 ESTs Hs.6019 AA431462 ESTs Hs.28329 ESTs; Weakly similar to CAMP-DEPENDENT
AA431470 PROTEIN KINASE Hs.3407 INHIBITOR; MUSCLE/BRAIN FORM [H.sapiens]

AA443756 ESTs; Moderately similar to (defline not Hs.6673 available 4105275) [H.sapiens]

AA449479 ESTs; Highly similar to (defline not availableHs.5216 5106787) [H.sapiens]

AA459916 bradykinin receptor B2 Hs.25021 AA465226 ESTs Hs.28631 AA478778 ESTs Hs.16450 AA479037 ESTs Hs.7961 AA482597 ESTs; Highly similar to (defline not availableHs.26054 4704739) [H.sapiens]

AA487561 ESTs; Highly similar to RAS-RELATED PROTEINHs.9813 RAB-1A [H.sapiens]

AA489245 ESTs; Weakly similar to sperm specific Hs.5682 protein [H.sapiens]

2 0 AA504110 ESTs Hs.18063 ESTs; Highly similar to SERINE/THREONINE
AA520989 PROTEIN Hs.9195 [H.sapiens]

AA599434 ESTs Hs.25035 AA608649 Homo sapiens clone 23742 mRNA; partial Hs.6354 cds AA609519 ESTs Hs.26458 Human isolate JuSo MUC18 glycoprotein 2 5 D51069 mRNA (3' variant); complete Hs.185718 cds 097519 podocalyxin-like Hs.16426 W28391 proliferation-associated 2G4; 38kD Hs.5181 Homo sapiens mRNA; cDNA DKFZp564F053 (from AA035638 clone Hs.71968 DKFZp564F053) AA083514 ESTs Hs.68301 3 0 AA121315 ESTs Hs.70823 AA147186 ESTs Hs.92387 AA156125 ESTs Hs.72116 AA188932 ESTs Hs.85640 AA219653 ESTs Hs.87125 3 5 AA232645 ESTs Hs.42699 F10078 ESTs Hs.13233 H48032 ESTs Hs.9645 H82117 ESTs Hs.28043 N39584 ESTs Hs.17404 4 0 N54067 Homo sapiens mRNA for NIK; partial cds Hs.3628 ~ N59858 ~ ESTs Hs.33032 Exemplar UniGeneID(11/29/
Accession Complete Title 99) N90933 ESTs Hs.4867 ESTs; Moderately similar to !!!! ALU CLASS
N93764 C WARNING ENTRY !!!! Hs.10175 [H.sapiens]

826124 ESTs Hs.24024 827957 ESTs Hs.24230 855470 ESTs; Moderately similar to K02E10.2 [C.elegans]Hs.11067 ESTs; Highly similar to vacuolar protein T16550 sorting homolog h-vps45 Hs.6650 [H.sapiens]

T26674 ESTs; Weakly similar to neuronal thread Hs.6966 protein AD7c-NTP [H.sapiens]

yc20g11.s1 Stratagene lung (#937210) Homo T57112 sapiens cDNA clone Hs.8881 IMAGE:81284 3', mRNA sequence.

T88700 ESTs Hs.173374 T90527 ESTs Hs.7890 W42789 ESTs Hs.31446 W60002 plastin 3 (T isoform) Hs.4114 W78175 ESTs Hs.17901 W84768 ESTs Hs.141742 W94427 ESTs; Weakly similar to Na;K-ATPase gammaHs.3807 subunit [H.sapiens]

AA253217 ESTs Hs.41271 AA426573 ESTs Hs.41135 AA432374 ESTs Hs.48029 AA446622 ESTs Hs.74313 2 0 AA478771 ESTs Hs.50841 AA482594 ESTs Hs.62684 AA490588 ESTs Hs.43118 D59570 ESTs Hs.17132 H88157 ESTs Hs.41105 H94648 ESTs Hs.41995 H97538 ESTs ' Hs.42392 H98670 ESTs; Weakly similar to (defline not availableHs.49753 4884081 ) [H.sapiens]

ESTs; Moderately similar to !!!! ALU SUBFAMILY
N22107 SC WARNING ENTRY Hs.172241 !!!! [H.sapiens]

W38197 Accession not listed in Genbank ESTs; Moderately similar to !!!! ALU SUBFAMILY
3 0 W80814 SB WARNING ENTRY Hs.196785 !!!! [H.sapiens]

AA287347 ESTs Hs.105088 AA402799 ESTs Hs.182538 AA404418 EST Hs.144953 AA425107 ESTs Hs.97016 ESTs; Moderately similar to !!!! ALU SUBFAMILY
3 5 AA425435 J WARNING ENTRY Hs.98438 ! !!! [H.sapiens]

AA442872 ESTs Hs.110771 ESTs; Moderately similar to !!!! ALU SUBFAMILY
AA452860 SP WARNING ENTRY Hs.197214 ! !!! [H.sapiens]

ESTs; Moderately similar to !!!! ALU SUBFAMILY
AA488687 SQ WARNING ENTRY Hs.190307 ! !!! [H.sapiens]

AA599674 ESTs; Weakly similar to ORF [D.melanogaster]Hs.108115 Exemplar UniGeneID(11/29/
Accession Complete Title 99) F13673 ESTs Hs.99769 H99093 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptideHs.6179 (72kD) yw35g11.s1 Morton Fetal Cochlea Homo Sapiens N22495 cDNA clone Hs.102415 IMAGE:254276 3', mRNA sequence.

N23031 myosin; heavy polypeptide 7; cardiac muscle;Hs.929 beta 815740 carbohydrate (chondroitin 6/keratan) sulfotransferaseHs.104576 839610 calpain; large polypeptide L2 Hs.76288 W45560 ESTs Hs.102541 239833 H.sapiens mRNA for Rho6 protein Hs.124940 240583 ESTs Hs.101259 1 0 AA825437 ESTs Homo sapiens mRNA; cDNA DKFZp564F053 (from 866613 clone DKFZp564F053) AA868063 carbohydrate (chondroitin 6/keratan) sulfotransferase z116d08.r1 Soares_pregnant uterus NbHPU
AA128075 Homo sapiens cDNA clone IMAGE:502095 5', mRNA sequence.

N66570 ESTs A1051390 ESTs AA627122 ESTs X02761 fibronectin 1 Hs.118162 AF010193 MAD (mothers against decapentaplegic; Hs.100602 Drosophila) homolog 7 ESTs; Highly similar to the KIAA0195 gene AA149044 is expressed ubiquitously. Hs.10086 [H.sapiens]

solute carrier family 9 (sodium/hydrogen 2 0 U82108 exchanger); isoform 3 Hs.101813 regulatory factor 2 D78676 ESTs; Moderately similar to (defline not Hs.105509 available 4529890) (H.sapiens]

L35240 enigma (LIM domain protein) Hs.102948 AA598737 lactate dehydrogenase B Hs.180414 869417 ESTs Hs.107055 ESTs; Weakly similar to Human pre-mRNA
2 5 AA232837 cleavage factor I 68 kDa Hs.107125 subunit [H.sapiens]

N72695 ESTs Hs.108557 M30257 vascular cell adhesion molecule 1 Hs.109225 M96843 inhibitor of DNA binding 2; dominant negativeHs.109617 helix-loop-helix protein X68277 dual specificity phosphatase 1 Hs.171695 3 0 AA292440 myeloid differentiation primary response Hs.110571 J03040 secreted protein; acidic; cysteine-rich Hs.111779 (osteonectin) AA228107 ESTs Hs.54642 AA449789 connective tissue growth factor Hs.75511 W01367 ESTs Hs.170980 3 5 AA610116 ESTs; Highly similar to (defline not availableHs.11663 4325180) [H.sapiens]

Homo Sapiens mRNA; cDNA DKFZp564F053 (from AA258308 clone Hs.165618 DKFZp564F053) AA460273 Homo Sapiens mRNA for KIAA0517 protein; Hs.12372 partial cds AA286710 lymphocyte adaptor protein Hs.13131 T68873 metallothionein 1 L Hs.143289 Exemplar UniGeneID(11/29/
Accession Complete Title 99) D63476 PAK-interacting exchange factor beta Hs.172813 M62403 insulin-like growth factor-binding proteinHs.1516 X55740 5' nucleotidase (CD73) Hs.153952 L10284 calnexin Hs.155560 AA243278 ribosomal protein; mitochondrial; L12 Hs.109059 AA430032 pituitary tumor-transforming 1 Hs.159626 H16402 ESTs Hs.17121 D59711 ESTs Hs.17132 ye36g7.s1 Stratagene lung (#93721 ) Homo T94452 sapiens cDNA clone IMAGE:119868 3', mRNA sequence AA431571 ESTs Hs.17894 879356 Homo Sapiens mRNA for KIAA0544 protein; Hs.19280 partial cds AA280375 ESTs Hs.19928 249269 small inducible cytokine subfamily A (Cys-Cys);Hs.20144 member 14 241740 ESTs Hs.24462 AA121543 Homo sapiens mRNA for KIAA0758 protein; Hs.22039 partial cds J05008 endothelin 1 Hs.2271 AA101878 ESTs Hs.22793 T35341 ESTs; Highly similar to (defline not availableHs.22880 4519883) [H.sapiens]

N87590 ESTs Hs.23037 2 0 AA256153 ESTs Hs.23912 W74533 Homo sapiens mRNA for KIAA0786 protein; Hs.24212 partial cds U25997 stanniocalcin Hs.25590 V01512 v-fos FBJ murine osteosarcoma viral oncogeneHs.25647 homolog X56681 jun D proto-oncogene Hs.2780 2 5 AA161292 interferon; alpha-inducible protein 27 Hs.2867 AA491465 ESTs Hs.28792 AA046593 ESTs Hs.28959 D50914 Human mRNA for KIAA0124 gene; partial Hs.30736 cds D45304 ESTs Hs.31595 3 0 M90657 transmembrane 4 supertamily member 1 Hs.3337 W69127 ESTs; Weakly similar to zinc finger proteinHs.3449 ZNF191 [H.sapiens]

AA316186 ESTs; Highly similar to (defline not availableHs.34549 4262136) [H.sapiens]

AA384503 ESTs Hs.179260 AA136353 ESTs Hs.38022 ESTs; Weakly similar to !!!! ALU SUBFAMILY
3 5 AA044755 SX WARNING ENTRY !!!! Hs.173705 [H.sapiens]

U84573 procollagen-lysine; 2-oxoglutarate 5-dioxygenaseHs.41270 (lysine hydroxylase) 2 AA058911 ESTs; Weakly similar to membrane glycoproteinHs.4193 [M.musculus]

AA620962 dynein; cytoplasmic; light intermediate Hs.44251 polypeptide 2 AA285290 small EDRK-rich factor 2 Hs.44499 4 0 X60486 H4 histone family; member G Hs.46423 831641 ESTs Hs.197148 AA489190 ESTs Hs.48320 F13782 ~ LIM binding domain 2 Hs.4980 Exemplar UniGeneID(11/29/
Accession Complete Title 99) AA257993 Janus kinase 1 (a protein tyrosine kinase)Hs.50651 M24283 intercellular adhesion molecule 1 (CD54); Hs.168383 human rhinovirus receptor ESTs; Weakly similar to PIM-1 PROTO-ONCOGENE
AA443114 SERINE/THREONINE-PROTEIN KINASE [H.sapiens]Hs.5326 T35289 casein kinase 1; alpha 1 Hs.195206 N23817 Homo sapiens clone 23675 mRNA sequence Hs.5807 AA047151 ESTs Hs.5897 N77151 Homo sapiens mRNA for KIAA0799 protein; Hs.61638 partial cds AA480074 ESTs Hs.62206 Y00787 interleukin 8 Hs.624 T99789 ESTs Hs.64313 W84341 tissue inhibitor of metalloproteinase 2 Hs.6441 L09209 amyloid beta (A4) precursor-like protein Hs.64797 D12763 interleukin 1 receptor-like 1 Hs.66 T16484 ESTs Hs.6607 AA253193 ESTs Hs.6631 AA432248 ESTs Hs.6738 X82200 stimulated trans-acting factor (50 kDa) Hs.68054 AA083572 v-ral simian leukemia viral oncogene homologHs.6906 A (ras related) L00352 low density lipoprotein receptor (familialHs.181182 hypercholesterolemia) 2 0 N75791 ESTs Hs.7153 X57579 H.sapiens activin beta-A subunit (exon 2) cytochrome P450; subfamily I (aromatic X02612 compound-inducible); Hs.72912 polypeptide 1 H44631 immediate early protein Hs.737 AA090257 superoxide dismutase 2; mitochondria) Hs.177781 2 5 X83703 H.sapiens mRNA for cytokine inducible nuclearHs.74019 protein L40395 Homo sapiens clone 23689 mRNA; complete Hs.170001 cds AA227913 ESTs Hs.198456 X52947 gap junction protein; alpha 1; 43kD (connexinHs.74471 43) M11313 alpha-2-macroglobulin Hs.74561 3 0 L14837 tight junction protein 1 (zona occludens Hs.74614 1 ) M60721 Human homeobox gene, complete cds D90209 activating transcription factor 4 (tax-responsiveHs.181243 enhancer element B67) yc28e12.s1 Stratagene liver (#937224) Homo T67986 sapiens cDNA clone Hs.75106 IMAGE:82030 3' similar to gb:X14723 CLUSTERIN
PRECURSOR

AA148318 Human mRNA for KIAA0069 gene; partial cds Hs.75249 3 5 097105 dihydropyrimidinase-like 2 Hs.173381 T25747 H.sapiens OZF mRNA Hs.75471 K02574 Accession not listed in Genbank tyrosine 3-monooxygenase/tryptophan 5-monooxygenase D78577 activation Hs.75544 protein; eta polypeptide X53331 matrix Gla protein Hs.75742 40 S73591 upregulated by 1;25-dihydroxyvitamin D-3 Hs.179526 X95735 Zyxin ___. Hs.75873 I

Exemplar UniGeneID(11/29/
Accession Complete Title 99) L16862 G protein-coupled receptor kinase 6 Hs.76297 044975 Homo Sapiens Kruppel-like zinc finger Hs.76526 protein Zf9 mRNA; complete cds M97796 inhibitor of DNA binding 2; dominant negativeHs.180919 helix-loop-helix protein 086782 26S proteasome-associated pad1 homolog Hs.178761 AA099391 ESTs Hs.77310 M19267 tropomyosin 1 (alpha) Hs.77899 D29992 tissue factor pathway inhibitor 2 Hs.78045 L19314 phosphorylase kinase; beta Hs.195217 S78569 laminin; alpha 4 Hs.78672 Human cysteine-rich fibroblast growth 028811 factor receptor (CFR-1 ) mRNA, complete cds L77886 protein tyrosine phosphatase; receptor Hs.79005 type; K

C14407 neuronal tissue-enriched acidic protein Hs.79516 diphtheria toxin receptor (heparin-binding M60278 epidermal growth factor-like Hs.799 growth factor) 881509 splicing factor; arginine/serine-rich Hs.184571 AA487558 ESTs Hs.8135 D86962 KIAA0207 gene product Hs.81875 AA478971 disabled (Drosophila) homolog 2 (mitogen-responsiveHs.81988 phosphoprotein) D50683 transforming growth factor; beta receptorHs.82028 II (70-80kD) 056637 capping protein (actin filament) muscle Hs.184270 Z-line; alpha 1 2 0 M61199 Human cleavage signal 1 protein mRNA; Hs.82767 complete cds M28882 Human MUC18 glycoprotein mRNA, complete cds X15183 CDW52 antigen (CAMPATH-1 antigen) Hs.180532 S53911 CD34 Hs.85289 020734 Human transcription factor junB QunB) Hs.198951 gene; 5' region and complete cds prostaglandin-endoperoxide synthase 2 2 5 D28235 (prostaglandin G/H synthase Hs.92309 and cyclooxygenase) ESTs; Weakly similar to !!!! ALU CLASS
AA236324 A WARNING ENTRY !!!! Hs.92381 [H.sapiens]

Homo Sapiens mRNA for DEPP (decidual protein AA148923 induced by Hs.93675 progesterone); complete cds AA174183 ESTs Hs.93872 ESTs; Weakly similar to !!!! ALU CLASS
AA456311 A WARNING ENTRY !!!! Hs.93961 [H.sapiens]

3 0 L08069 heat shock protein; DNAJ-like 2 Hs.94 AA452000 ESTs Hs.94030 AA282140 ESTs Hs.9587 J02854 myosin regulatory light chain 2; smooth Hs.9615 muscle isoform ~ AA442054 phospholipase C; gamma 1 (formerly subtypeHs.993 ~ 148) AccessionUniGeneIDTitle Gene Eos # #

AA426573Hs.41135ESTs; Moderately similar to endomucin AAA9 [M.musculus]

D58024 Hs.57958ESTs; Weakly similar to KIAA0768 AAA8 protein [H.sapiens]

endothelial differentiation; sphingolipid M31210 Hs.154210G-protein-coupled EDG1 AAA7 receptor; 1 X06256 Hs.149609integrin; alpha 5 (fibronectin ITGA5 AAB1 receptor; alpha polypeptide) L20859 Hs.78452solute carrier family 20 (phosphateSLC20A1AAB3 transporter); member 1 X07820 Hs.2258matrix metalloproteinase 10 (stromelysinMMP10 AAB4 2) AA234743Hs.22120ESTs AAB5 U97519 Hs.16426podocalyxin-like PODXL AAB6 U03877 Hs.76224EGF-containing fibulin-like extracellularEFEMP1AAB8 matrix protein 1 M28882 Hs.211579melanoma adhesion molecule MCAM AAB9 X54925 Hs.83169matrix metalloproteinase 1 (interstitialMMP1 AAC1 collagenase) AA045136Hs.22575ESTs AAC2 AA423987Hs.7567ESTs AAC3 AA234743Hs.22120ESTs AAC4 ESTs; Moderately similar to hedgehog-interacting AA156125Hs.72116protein AAC5 (M.musculus]

AA025351Hs.134797ESTs AAC6 AA432248Hs.6738ESTs AAC7 2 0 AA227926Hs.6682ESTs AAC8 AA187490Hs.21941ESTs AAD1 ~ AA232645Hs.42699ESTs AAD2 ~ ~

Claims (33)

We claim:

1. A method of screening drug candidates comprising:
a) providing a cell that expresses an expression profile gene which encodes a protein selected from the group consisting of a nucleic acid of Table 1, Table 2, Table 3, Table 4 and Table 5 or a fragment thereof;
b) adding a drug candidate to said cell; and c) determining the effect of said drug candidate on the expression of said expression profile gene.

2. A method according to claim 1 wherein said determining comprises comparing the level of expression in the absence of said drug candidate to the level of expression in the presence of said drug candidate, wherein the concentration of said drug candidate can vary when present, and wherein said comparison can occur after addition or removal of the drug candidate.

3. A method according to claim 1 wherein the expression of said profile gene is decreased as a result of the introduction of the drug candidate.

4. A method of screening for a bioactive agent capable of binding to a angiogenesis modulator protein (AMP), wherein said AMP is encoded by a nucleic acid selected from the group consisting of a nucleic acid of Table 1, Table 2, Table 3, Table 4 and Table 5, or a fragment thereof, said method comprising combining said AMP and a candidate bioactive agent, and determining the binding of said candidate agent to said AMP.

5. A method for screening for a bioactive agent capable of modulating the activity of a angiogenesis modulator protein (AMP), wherein said AMP is encoded by a nucleic acid selected from the group consisting of a nucleic acid of Table 1, Table 2, Table 3, Table 4 and Table 5, or a fragment thereof, said method comprising:
a) combining said AMP and a candidate bioactive agent; and b) determining the effect of said candidate agent on the bioactivity of said AMP.

6. A method of evaluating the effect of a candidate angiogenesis drug comprising:~
a) administering said drug to a patient;
b) removing a cell sample from said patient; and c) determining the expression profile of said cell.

7. A method according to claim 6 further comprising comparing said expression profile to an expression profile of a healthy individual.

8. A method of diagnosing angiogenesis comprising:
a) determining the expression of one or more genes selected from the group consisting of a nucleic acid of Table 1, Table 2, Table 3, Table 4 and Table 5, or a fragment thereof in a first tyupe of a first individual; and b) comparing said expression of said gene(s) from a second normal tissue type from said first individual or a second unaffected individual, wherein a difference in said expression indicates that the first individual has tissue that is undergoing angiogenesis.

9. A biochip comprising a nucleic acid segment selected from the group consisting of the sequences set forth in Table 1, Table 2, Table 3, Table 4 and Table 5, wherein said biochip comprises fewer than 1000 nucleic acid probes.

10. A biochip according to claim 9 comprising at least two nucleic acid segments.

11. A method for screening for a bioactive agent capable of interfering with the binding of an angiogenesis modulator protein (AMP) or a fragment thereof and an antibody which binds to said AMP or fragment thereof, said method comprising:
a) combining anAMP or fragment thereof, a candidate bioactive agent and an antibody which binds to said AMP or fragment thereof; and b) determining the binding of said AMP or fragment thereof and said antibody.

12. A method for inhibiting the activity of an angiogenesis modulator protein (AMP), wherein said AMP is encoded by a nucleic acid selected from the group consisting of a nucleic acid of Table 1, Table 2, Table 3, Table 4 and Table 5 or a fragment thereof, said method comprising binding an inhibitor to said AMP.

13. A method according to claim 12 wherein said inhibitor is an antibody.

14. A method of treating a disorder associated with angiogenesis comprising administering to a patient an inhibitor of n angiogenesis modulator protein (AMP), wherein said AMP is encoded by a nucleic acid selected from the group consisting of a nucleic acid of Table 1, Table 2, Table 3, Table 4 and Table 5 or a fragment thereof.

15. A method according to claim 14 wherein said inhibitor is an antibody.

16. A method of neutralizing the effect of an AMP, or a fragment thereof, comprising contacting an agent specific for said protein with said protein in an amount sufficient to effect neutralization.

17. A method for localizing a therapeutic moiety to angioggenic tissue comprising exposing said tissue to an antibody to an AMP or fragment thereof conjugated to said therapeutic moiety.

18. The method of Claim 17, wherein said therapeutic moiety is a cytotoxic agent.

19. The method of Claim 17, wherein said therapeutic moiety is a radioisotope.

20. A method for inhibiting angiogenesis in a cell, wherein said method comprises administering to a cell a composition comprising antisense molecules to a nucleic acid of Table 1, Table 2, Table 3, Table 4 or Table 5.

21. An antibody which specifically binds to a protein encoded by a nucleic acid of Table 1, Table 2, Table 3, Table 4 or Table 5 or a fragment thereof.

22. The antibody of Claim 21, wherein said antibody is a monoclonal antibody.

23. The antibody of Claim 21, wherein said antibody is a humanized antibody.

24. The antibody of Claim 21, wherein said antibody is an antibody fragment.

25. A nucleic acid having a sequence at least 95% homologous to a sequence of a nucleic acid of Table 1, Table 2, Table 3, Table 4 or Table 5 or its complement.

26. A nucleic acid which hybridizes under high stringency to a nucleic acid of Table 1, Table 2, Table 3, Table 4 or Table 5 or its complement.

27. A polypeptide encoded by the nucleic acid of Claim 25 or 26.

28. A method of eliciting an immune response in an individual, said method comprising administering to said individual a composition comprising the polypeptide of Claim 27 or a fragment thereof.

29. A method of eliciting an immune response in an individual, said method comprising administering to said individual a composition comprising a nucleic acid comprising a sequence of a nucleic acid of Table 1, Table 2, Table 3, Table 4 or Table 5 or a fragment thereof.

30. A method for determining the prognosis of an individual with a disorder associated with angiogenesis comprising determining the level of a AMP in a sample, wherein a high level of the AMP indicates a poor prognosis.

31. A method of treating a disorder associated with angiogenisis comprising administering to an individual having a disorder associated with angiogenesis an antibody to a AMP
or fragment thereof conjugated to a therapeutic moiety.

32. The method of Claim 31, wherein said therapeutic moiety is a cytotoxic agent.

33. The method of Claim 31, wherein said therapeutic moiety is a radioisotope.