Novel human transferase family members and uses thereof (04-Dec-2003)

RELATED APPLICATIONS

[0001] This application is a continuation-in-part and claims priority to U.S. application Ser. No. 09/815,028, filed Mar. 22, 2001, and International Application Serial No. PCT/US01/09358, filed Mar. 22, 2001, which claim the benefit of U.S. Provisional Application Serial No. 60/191,964, filed Mar. 24, 2000; and U.S. application Ser. No. 09/801,220, filed Mar. 07, 2001, and International Application Serial No. PCT/US01/07269, filed Mar. 07, 2001, which claim the benefit of U.S. Provisional Application Serial No. 60/187,456, filed Mar. 07, 2000; and U.S. application Ser. No. 09/816,714, filed Mar. 23, 2001, and International Application Serial No. PCT/US01/09468, filed Mar. 23, 2001, which claim the benefit of U.S. Provisional Application Serial No. 60/191,865, filed Mar. 24, 2000; and U.S. application Ser. No. 09/844,948, filed Apr. 27, 2001, and International Application Serial No. PCT/US01/13805, filed Apr. 27, 2001, which claim the benefit of U.S. Provisional Application Serial No. 60/200,604, filed Apr. 28, 2000; and U.S. application Ser. No. 09/861,164, filed May 18, 2001, and International Application Serial No. PCT/US01/16292, filed May 18, 2001, which claim the benefit of U.S. Provisional Application Serial No. 60/205,408, filed May 19, 2000; and U.S. application Ser. No. 09/883,060, filed Jun. 15, 2001, and International Application Serial No. PCT/US01/19138, filed Jun. 15, 2001, which claim the benefit of U.S. Provisional Application Serial No. 60/212,079, filed Jun. 15, 2000; and U.S. application Ser. No. 09/962,678, filed Sep. 25, 2001, and International Application Serial No. PCT/US01/29963, filed Sep. 25, 2001, which claim the benefit of U.S. Provisional Application Serial No. 60/235,044, filed Sep. 25, 2000; and U.S. application Ser. No. 09/973,457, filed Oct. 09, 2001, which claims the benefit of U.S. Provisional Application Serial No. 60/238,849, filed Oct. 06, 2000; and U.S. application Ser. No. 10/072,285, filed Feb. 08, 2002, and International Application Serial No. PCT/US02/03736, filed Feb. 08, 2002, which claim the benefit of U.S. Provisional Application Serial No. 60/267,494, filed Feb. 08, 2001; and U.S. application Ser. No. 09/817,910, filed Mar. 26, 2001, and International Application Serial No. PCT/US01/09633, filed Mar. 26, 200 1, which claim the benefit of U.S. Provisional Application Serial No. 60/192,092, filed Mar. 24, 2000; and U.S. application Ser. No. 09/842,528, filed Apr. 25, 2001, and International Application Serial No. PCT/US01/40607, filed Apr. 25, 2001, which claim the benefit of U.S. Provisional Application Serial No. 60/199,500, filed Apr. 25, 2000; and U.S. application Ser. No. 09/882,836, filed Jun. 15, 2001, and International Application Serial No. PCT/US01/19543, filed Jun. 15, 2001, which claim the benefit of U.S. Provisional Application Serial No. 60/211,730, filed Jun. 15, 2000; and U.S. application Ser. No. 09/882,872, filed Jun. 15, 2001, and International Application Serial No. PCT/US01/19153, filed Jun. 15, 2001, which claim the benefit of U.S. Provisional Application Serial No. 60/212,077, filed Jun. 15, 2000, the contents of which are incorporated herein by reference.

[0002] 1

TABLE OF CONTENTS

	Gene IDs 33877 and 47179
	Background of the Invention	page 5
	Summary of the Invention	page 6
	Detailed Description of the Invention	page 30
	Gene ID 26886
	Background of the Invention	page 134
	Summary of the Invention	page 135
	Detailed Description of the Invention	page 144
	Gene ID 25552
	Background of the Invention	page 247
	Summary of the Invention	page 248
	Detailed Description of the Invention	page 254
	Gene ID 32132
	Background of the Invention	page 357
	Summary of the Invention	page 359
	Detailed Description of the Invention	page 363
	Gene ID 32244
	Background of the Invention	page 468
	Summary of the Invention	page 469
	Detailed Description of the Invention	page 474
	Gene ID 23680
	Background of the Invention	page 576
	Summary of the Invention	page 577
	Detailed Description of the Invention	page 582
	Gene ID 32624
	Background of the Invention	page 684
	Summary of the Invention	page 685
	Detailed Description of the Invention	page 688
	Gene ID 47174
	Background of the Invention	page 795
	Summary of the Invention	page 796
	Detailed Description of the Invention	page 803
	Gene ID 60491
	Background of the Invention	page 899
	Summary of the Invention	page 901
	Detailed Description of the Invention	page 906
	Gene IDs 46743 and 27417
	Background of the Invention	page 1007
	Summary of the Invention	page 1008
	Detailed Description of the Invention	page 1017
	Gene ID 27960
	Background of the Invention	page 1133
	Summary of the Invention	page 1134
	Detailed Description of the Invention	page 1139
	Gene ID 32252
	Background of the Invention	page 1241
	Summary of the Invention	page 1243
	Detailed Description of the Invention	page 1248
	Gene ID 53320
	Background of the Invention	page 1351
	Summary of the Invention	page 1352
	Detailed Description of the Invention	page 1358
	Brief Description of the Drawings	page 13
	Examples	page 1462
	Claims	page 1565
	Abstract	page 1568

BACKGROUND OF THE 33877 AND 47179 INVENTION

[0003] A great diversity of oligosaccharide structures and types of glycoconjugates is found in nature, and these are synthesized by a large number of glycosyltransferases. Glycosyltransferases catalyze the synthesis of glycoconjugates, including glycolipids, glycoproteins, and polysaccharides, by transferring an activated mono- or oligosaccharide residue to an existing acceptor molecule for the initiation or elongation of the carbohydrate chain. A catalytic reaction is believed to involve the recognition of both the donor and acceptor by suitable domains, as well as the catalytic site of the enzyme (Amado et al. (1999) Biochim Biophys Acta 1473:35-53; Kapitonov et al. (1999) Glycobiology 9:961-78).

[0004] Because the glycosylation reaction is highly specific with respect to both the configuration of the sugar residue and the site of the addition, it is expected that unique domain structures for substrate recognition and nucleotide-sugar binding are located within the enzyme molecule. Evidence indicates that formation of many glycosidic linkages is covered by large homologous glycosyltransferase gene families, and that the existence of multiple enzyme isoforms provides a degree of redundancy as well as a higher level of regulation of the glycoforms synthesized (Kapitonov et al. (1999) Glycobiology 9:961-78).

[0005] Glycosylation is the principal chemical modification to proteins as they pass through Golgi vesicles. Glycosyltransferases of the Golgi do not possess an obvious sequence homology which would suggest a common Golgi retention signal. However, they are all membrane proteins and share type II topology, consisting of an amino terminal cytoplasmic tail, a signal anchor transmembrane domain, a stem region, and a large luminal catalyitc domain. The membrane-spanning domain and its flanking regions contain necessary and sufficient information for Golgi retention of these enzymes (Jaskiewicz (1997) Acta Biochim Pol 44:173-9). ER localized glycosyltransferases can have either a type II topology, like the Golgi glycosyltransferases, or a type I topolgy, e.g., the N-terminus and catalytic domain inside the ER (Kapitonov et al. (1999) Glycobiology 9:961-78). Some glycosyltransferases are present on the cell surface and are thought to function as cell adhesion molecules by binding oligosaccharide substrates on adjacent cell surfaces or in the extracellular matrix. The best studied of these is beta 1,4-galactosyltransferase, which mediates sperm binding to the egg coat and selected cell interactions with the basal lamina (Shur (1993) Curr Opin Cell Biol 5:854-63).

SUMMARY OF THE 33877 AND 47179 INVENTION

[0006] The present invention is based, in part, on the discovery of a novel glycosyltransferase family members, referred to herein as “33877 and 47179.” The nucleotide sequence of a cDNA encoding 33877 is shown in SEQ ID NO: 1, and the amino acid sequence of a 33877 polypeptide is shown in SEQ ID NO: 2. In addition, the nucleotide sequences of the coding region are depicted in SEQ ID NO: 3. The nucleotide sequence of a cDNA encoding 47179 is shown in SEQ ID NO: 4, and the amino acid sequence of a 47179 polypeptide is shown in SEQ ID NO: 5. In addition, the nucleotide sequences of the coding region are depicted in SEQ ID NO: 6.

[0007] Accordingly, in one aspect, the invention features a nucleic acid molecule which encodes a 33877 or 47179 protein or polypeptide, e.g., a biologically active portion of the 33877 or 47179 protein. In a preferred embodiment the isolated nucleic acid molecule encodes a polypeptide having the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 5. In other embodiments, the invention provides isolated 33877 or 47179 nucleic acid molecules having the nucleotide sequence shown in SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, the sequence of the DNA insert of the plasmid deposited with ATCC Accession Number ______, or the sequence of the DNA insert of the plasmid deposited with ATCC Accession Number ______. In still other embodiments, the invention provides nucleic acid molecules that are substantially identical (e.g., naturally occurring allelic variants) to the nucleotide sequence shown in SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, the sequence of the DNA insert of the plasmid deposited with ATCC Accession Number ______, or the sequence of the DNA insert of the plasmid deposited with ATCC Accession Number ______. In other embodiments, the invention provides a nucleic acid molecule which hybridizes under a stringency condition described herein to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, the sequence of the DNA insert of the plasmid deposited with ATCC Accession Number ______, or the sequence of the DNA insert of the plasmid deposited with ATCC Accession Number ______, wherein the nucleic acid encodes a full length 33877 or 47179 protein or an active fragment thereof.

[0008] In a related aspect, the invention further provides nucleic acid constructs which include a 33877 or 47179 nucleic acid molecule described herein. In certain embodiments, the nucleic acid molecules of the invention are operatively linked to native or heterologous regulatory sequences. Also included, are vectors and host cells containing the 33877 or 47179 nucleic acid molecules of the invention e.g., vectors and host cells suitable for producing 33877 or 47179 nucleic acid molecules and polypeptides.

[0009] In another related aspect, the invention provides nucleic acid fragments suitable as primers or hybridization probes for the detection of 33877 or 47179-encoding nucleic acids.

[0010] In still another related aspect, isolated nucleic acid molecules that are antisense to a 33877 or 47179 encoding nucleic acid molecule are provided.

[0011] In another aspect, the invention features, 33877 or 47179 polypeptides, and biologically active or antigenic fragments thereof that are useful, e.g., as reagents or targets in assays applicable to treatment and diagnosis of 33877 or 47179-mediated or -related disorders. In another embodiment, the invention provides 33877 or 47179 polypeptides having a 33877 or 47179 activity. Preferred polypeptides are 33877 or 47179 proteins including at least one glycosyltransferase domain, and, preferably, having a 33877 or 47179 activity, e.g., a 33877 or 47179 activity as described herein.

[0012] In other embodiments, the invention provides 33877 or 47179 polypeptides, e.g., a 33877 or 47179 polypeptide having the amino acid sequence shown in SEQ ID NO: 2, SEQ ID NO: 5, the amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC Accession Number ______, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC Accession Number ______; an amino acid sequence that is substantially identical to the amino acid sequence shown in SEQ ID NO: 2, SEQ ID NO: 5, the amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC Accession Number ______, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC Accession Number ______; or an amino acid sequence encoded by a nucleic acid molecule having a nucleotide sequence which hybridizes under a stringency condition described herein to a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, the sequence of the DNA insert of the plasmid deposited with ATCC Accession Number ______, or the sequence of the DNA insert of the plasmid deposited with ATCC Accession Number ______, wherein the nucleic acid encodes a full length 33877 or 47179 protein or an active fragment thereof.

[0013] In a related aspect, the invention further provides nucleic acid constructs which include a 33877 or 47179 nucleic acid molecule described herein.

[0014] In a related aspect, the invention provides 33877 or 47179 polypeptides or fragments operatively linked to non-33877 or 47179 polypeptides to form fusion proteins. In another aspect, the invention features antibodies and antigen-binding fragments thereof, that react with, or more preferably specifically bind 33877 or 47179 polypeptides.

[0015] In another aspect, the invention provides methods of screening for compounds that modulate the expression or activity of the 33877 or 47179 polypeptides or nucleic acids.

[0016] In still another aspect, the invention provides a process for modulating 33877 or 47179 polypeptide or nucleic acid expression or activity, e.g. using the screened compounds. In certain embodiments, the methods involve treatment of conditions related to aberrant activity or expression of the 33877 or 47179 polypeptides or nucleic acids, such as conditions involving aberrant or deficient cellular proliferation or differentiation, or immune conditions.

[0017] In yet another aspect, the invention provides methods for inhibiting the proliferation or inducing the killing, of a 33877 or 47179-expressing cell, e.g., a 33877 or 47179-expressing hyperproliferative or aberrant cell, comprising contacting the cell with a compound (e.g., a compound identified using the methods described herein) that modulates the activity, or expression, of the 33877 or 47179 polypeptide or nucleic acid.

[0018] In a preferred embodiment, the contacting step is effective in vitro or ex vivo. In other embodiments, the contacting step is effected in vivo, e.g., in a subject (e.g., a mammal, e.g., a human), as part of a therapeutic or prophylactic protocol.

[0019] In a preferred embodiment, the 33877- or 47179-expressing cell is found in a cancer tissue or cell, e.g., a solid tumor, a soft tissue tumor, or a metastatic lesion. In other embodiments, the 33877 or 47179-expressing cell is an immune cell, e.g., a cell from a myeloid, lymphoid or erythroid lineage, or a precursor cell thereof.

[0020] In a preferred embodiment, the compound is an inhibitor of a 33877 or 47179 polypeptide. Preferably, the inhibitor is chosen from a peptide, a phosphopeptide, a peptidomimetic, e.g., a phosphonate analog of a peptide substrate, a small organic molecule, a small inorganic molecule and an antibody (e.g., an antibody conjugated to a therapeutic moiety selected from a cytotoxin, a cytotoxic agent and a radioactive metal ion).

[0021] In a preferred embodiment, the compound is an inhibitor of a 33877 or 47179 nucleic acid, e.g., an antisense, a ribozyme, or a triple helix molecule.

[0022] In a preferred embodiment, the compound is administered in combination with a cytotoxic agent. Examples of cytotoxic agents include anti-microtubule agent, a topoisomerase I inhibitor, a topoisomerase II inhibitor, an anti-metabolite, a mitotic inhibitor, an alkylating agent, an intercalating agent, an agent capable of interfering with a signal transduction pathway, an agent that promotes apoptosis or necrosis, and radiation.

[0023] In another aspect, the invention features a method of treating or preventing a disorder characterized by aberrant activity or expression of a 33877 or 47179 nucleic acid or polypeptide in a subject. In one embodiment, the method includes administering to the subject an effective amount of an agent that modulates the activity or expression of a 33877 or 47179 polypeptide or nucleic acid such that the disorder is ameliorated or prevented. In one example, the disorder is a cellular proliferative or differentiative disorder. In another example, the disorder is an immune disorder. In one embodiment, the agent is a peptide, a phosphopeptide, a small molecule, an antibody, or any combination thereof. In another embodiment, the agent is an antisense, a ribozyme, a triple helix molecule, a 33877 or 47179 nucleic acid, or any combination thereof.

[0024] The invention also provides assays for determining the activity of or the presence or absence of 33877 or 47179 polypeptides or nucleic acid molecules in a biological sample, including for disease diagnosis. Preferably, the biological sample includes a cancerous or pre-cancerous cell or tissue. For example, the cancerous tissue can be a solid tumor, a soft tissue tumor, or a metastatic lesion. In other embodiments, the biological sample is an immune cell, e.g., a cell from a myeloid, lymphoid or erythroid lineage, or a precursor cell thereof.

[0025] In further aspect, the invention provides assays for determining the presence or absence of a genetic alteration in a 33877 or 47179 polypeptide or nucleic acid molecule, including for disease diagnosis. Preferably, the biological sample includes a cancerous or pre-cancerous cell or tissue. For example, the cancerous tissue can be a solid tumor, a soft tissue tumor, or a metastatic lesion. In other embodiments, the biological sample is an immune cell, e.g., a cell from a myeloid, lymphoid or erythroid lineage, or a precursor cell thereof.

[0026] In another aspect, the invention features a method of diagnosing, or staging, a 33877 or 47179-mediated disorder, e.g., an immune disorder, or a cancer disorder, in a subject. The method includes evaluating the expression or activity of a 33877 or 47179 nucleic acid or polypeptide, thereby diagnosis or staging the disorder. In a preferred embodiment, the expression or activity is compared with a reference value, e.g., a difference in the expression or activity level of the 33877 or 47179 nucleic or polypeptide relative to a normal subject or a cohort of normal subjects is indicative of the disorder, or a stage in the disorder.

[0027] In a preferred embodiment, the subject is a human. For example, the subject is a human suffering from, or at risk of, an immune or a cancer disorder as described herein.

[0028] In a preferred embodiment, the evaluating step occurs in vitro or ex vivo. For example, a sample, e.g., a blood or tissue sample, a biopsy, is obtained from the subject. Preferably, the sample contains a cancer or an immune cell.

[0029] In a preferred embodiment, the evaluating step occurs in vivo. For example, by administering to the subject a detectably labeled agent that interacts with the 33877 or 47179-associated nucleic acid or polypeptide, such that a signal is generated relative to the level of activity or expression of the 33877 or 47179 nucleic acid or polypeptide.

[0030] In preferred embodiments, the method is performed: on a sample from a subject, a sample from a human subject; e.g., a sample of a patient suffering from, or at risk of, an immune or a cancer disorder as described herein; to determine if the individual from which the target nucleic acid or protein is taken should receive a drug or other treatment; to diagnose an individual for a disorder or for predisposition to resistance to treatment, to stage a disease or disorder.

[0031] In a still further aspect, the invention provides methods for evaluating the efficacy of a treatment of a disorder, e.g., proliferative disorder, e.g., a cancer, or an immune disorder. The method includes: treating a subject, e.g., a patient or an animal, with a protocol under evaluation (e.g., treating a subject with one or more of: chemotherapy, radiation, and/or a compound identified using the methods described herein); and evaluating the expression of a 33877 or 47179 nucleic acid or polypeptide before and after treatment. A change, e.g., a decrease or increase, in the level of a 33877 or 47179 nucleic acid (e.g., mRNA) or polypeptide after treatment, relative to the level of expression before treatment, is indicative of the efficacy of the treatment of the disorder.

[0032] In a preferred embodiment, the evaluating step includes obtaining a sample (e.g., a tissue sample, e.g., a biopsy, or a fluid sample) from the subject, before and after treatment and comparing the level of expressing of a 33877 or 47179 nucleic acid (e.g., mRNA) or polypeptide before and after treatment.

[0033] In another aspect, the invention provides methods for evaluating the efficacy of a therapeutic or prophylactic agent (e.g., an anti-neoplastic agent). The method includes: contacting a sample with an agent (e.g., a compound identified using the methods described herein, a cytotoxic agent) and, evaluating the expression or activity of a 33877 or 47179 nucleic acid or polypeptide in the sample before and after the contacting step. A change, e.g., a decrease or increase, in the level of 33877 or 47179 nucleic acid (e.g., mRNA) or polypeptide in the sample obtained after the contacting step, relative to the level of expression in the sample before the contacting step, is indicative of the efficacy of the agent. The level of 33877 or 47179 nucleic acid or polypeptide expression can be detected by any method described herein.

[0034] In a preferred embodiment, the sample includes cells obtained from a cancerous or immune tissue where a 33877 or 47179 polypeptide or nucleic acid is obtained.

[0035] In a preferred embodiment, the sample is a tissue sample (e.g., a biopsy), a bodily fluid, a cultured cell (e.g., a tumor or immune cell line).

[0036] In another aspect, the invention features a two dimensional array having a plurality of addresses, each address of the plurality being positionally distinguishable from each other address of the plurality, and each address of the plurality having a unique capture probe, e.g., a nucleic acid or peptide sequence. At least one address of the plurality has a capture probe that recognizes a 33877 or 47179 molecule. In one embodiment, the capture probe is a nucleic acid, e.g., a probe complementary to a 33877 or 47179 nucleic acid sequence. In another embodiment, the capture probe is a polypeptide, e.g., an antibody specific for 33877 or 47179 polypeptides. Also featured is a method of analyzing a sample by contacting the sample to the aforementioned array and detecting binding of the sample to the array.

[0037] In another aspect, the invention features a method for identifying an agent that modulates the activity or expression of a 33877 or 47179 polypeptide or nucleic acid. The method includes the steps of: contacting the 33877 or 47179 polypeptide or nucleic acid with an agent; and determining the effect of the agent on the activity or expression of the polypeptide or nucleic acid. In one embodiment, the method includes contacting a 33877 or 47179 polypeptide with the agent and determining the effect of the agent on glycosyltransferase activity of the 33877 or 47179 polypeptide. In another embodiment, the method includes contacting a 33877 or 47179 polypeptide with the agent and determining the effect of the agent on the ability of the 33877 or 47179 polypeptide to modulate protein processing, protein folding, or protein secretion. The agent can be a peptide, a phosphopeptide, a small molecule, an antibody, or any combination thereof. In addition, the agent can be an antisense, a ribozyme, a triple helix molecule, a 33877 or 47179 nucleic acid, or any combination thereof.

[0038] Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0039] FIGS. 1A-1C depict a cDNA sequence (SEQ ID NO: 1) and predicted amino acid sequence (SEQ ID NO: 2) of human 33877. The methionine-initiated open reading frame of human 33877 (without the 5′ and 3′ untranslated regions) extends from nucleotide position 402 to position 2060 of SEQ ID NO: 1 (coding sequence shown in SEQ ID NO: 3).

[0040] FIG. 2 depicts a hydropathy plot of human 33877. Relative hydrophobic residues are shown above the dashed horizontal line, and relative hydrophilic residues are below the dashed horizontal line. The cysteine residues (cys) are indicated by short vertical lines just below the hydropathy trace. The numbers corresponding to the amino acid sequence of human 33877 are indicated. Polypeptides of the invention include fragments which include: all or part of a hydrophobic sequence, i.e., a sequence above the dashed line, e.g., the sequence from about amino acid 225 to 235, from about 275 to 285, and from about 310 to 330 of SEQ ID NO: 2; all or part of a hydrophilic sequence, i.e., a sequence below the dashed line, e.g., the sequence of from about amino acid 40 to 75, from about 255 to 270, and from about 420 to 440 of SEQ ID NO: 2; a sequence which includes a Cys, or a glycosylation site.

[0041] FIG. 3 depicts a series of plots summarizing an analysis of the primary and secondary protein structure of human 33877. The particular algorithm used for each plot is indicated at the right hand side of each plot. The following plots are depicted: Gamier-Robson plots providing the predicted location of alpha, beta, turn, and coil regions (Gamier et al. (1978) J. Mol Biol. 120:97); Chou-Fasman plots providing the predicted location of alpha, beta, and turn regions (Chou and Fasman (1978) Adv. In Enzymol. Mol. 47:45-148); Kyte-Doolittle hydrophilicity/hydrophobicity plots (Kyte and Doolittle (1982) J. Mol. Biol. 157:105-132); Eisenberg plots providing the predicted location of alpha- and beta-amphipathic regions (Eisenberg et al. (1982) Nature 299:371-374); a Karplus-Schulz plot providing the predicted location of flexible regions (Karplus and Schulz (1985) Naturwissens-Chafen 72:212-213); a plot of the antigenic index (Jameson-Wolf) (Jameson and Wolf (1988) CABIOS 4:121-136); and a surface probability plot (Emini algorithm) (Emini et al. (1985) J. Virol. 55:836-839). The numbers corresponding to the amino acid sequence of human 33877 are indicated. Polypeptide fragments of the invention include polypeptides which have all or part of any of the regions described in this figure. Also included are variants having a mutation in a selected region shown in this figure.

[0042] FIG. 4 depicts an alignment of the glycosyl transferase group 2 domain of human 33877 with a consensus amino acid sequence derived from a hidden Markov model (HMM) from PFAM. The upper sequence is the consensus amino acid sequence (SEQ ID NO: 7), while the lower amino acid sequence corresponds to amino acids 114 to 292 of SEQ ID NO: 2.

[0043] FIGS. 5A-5B depict a cDNA sequence (SEQ ID NO: 4) and predicted amino acid sequence (SEQ ID NO: 5) of human 47179. The methionine-initiated open reading frame of human 47179 (without the 5′ and 3′ untranslated regions) extends from nucleotide position 29 to position 1279 of SEQ ID NO: 4 (coding sequence shown in SEQ ID NO: 6).

[0044] FIG. 6 depicts a hydropathy plot of human 47179. Relative hydrophobic residues are shown above the dashed horizontal line, and relative hydrophilic residues are below the dashed horizontal line. The cysteine residues (cys) and N glycosylation site (Ngly) are indicated by short vertical lines just below the hydropathy trace. The numbers corresponding to the amino acid sequence of human 47179 are indicated. Polypeptides of the invention include fragments which include: all or part of a hydrophobic sequence, i.e., a sequence above the dashed line, e.g., the sequence from about amino acid 110 to 120, from about 240 to 250, and from about 310 to 320 of SEQ ID NO: 5; all or part of a hydrophilic sequence, i.e., a sequence below the dashed line, e.g., the sequence of from about amino acid 230 to 240, from about 270 to 290, and from about 395 to 405 of SEQ ID NO: 5; a sequence which includes a Cys, or a glycosylation site.

[0045] FIG. 7 depicts a series of plots summarizing an analysis of the primary and secondary protein structure of human 47179. The particular algorithm used for each plot is indicated at the right hand side of each plot. The following plots are depicted: Gamier-Robson plots providing the predicted location of alpha, beta, turn, and coil regions (Gamier et al. (1978) J. Mol. Biol. 120:97); Chou-Fasman plots providing the predicted location of alpha, beta, and turn regions (Chou and Fasman (1978) Adv. In Enzymol. Mol. 47:45-148); Kyte-Doolittle hydrophilicity/hydrophobicity plots (Kyte and Doolittle (1982) J. Mol. Biol. 157:105-132); Eisenberg plots providing the predicted location of alpha- and beta-amphipathic regions (Eisenberg et al. (1982) Nature 299:371-374); a Karplus-Schulz plot providing the predicted location of flexible regions (Karplus and Schulz (1985) Naturwissens-Chafen 72:212-213); a plot of the antigenic index (Jameson-Wolf) (Jameson and Wolf (1988) CABIOS 4:121-136); and a surface probability plot (Emini algorithm) (Emini et al. (1985) J. Virol. 55:836-839). The numbers corresponding to the amino acid sequence of human 47179 are indicated. Polypeptide fragments of the invention include polypeptides which have all or part of any of the regions described in this figure. Also included are variants having a mutation in a selected region shown in this figure.

[0046] FIG. 8 depicts an alignment of glycosyl transferase group 1 domain of human 47179 with a consensus amino acid sequence derived from a hidden Markov model (HMM) from PFAM. The upper sequence is the consensus amino acid sequence (SEQ ID NO: 8), while the lower amino acid sequence corresponds to amino acids 211 to 393 of SEQ ID NO: 5.

[0047] FIGS. 9A-9C depicts a cDNA sequence (SEQ ID NO: 9) and predicted amino acid sequence (SEQ ID NO: 10) of human 26886. The methionine-initiated open reading frame of human 26886 (without the 5′ and 3′ untranslated regions) starts at nucleotide 272 and continues through to nucleotide 2683 of SEQ ID NO: 9 (coding sequence also shown in SEQ ID NO: 11).

[0048] FIG. 10 depicts a hydropathy plot of human 26886. Relative hydrophobic residues are shown above the dashed horizontal line, and relative hydrophilic residues are below the dashed horizontal line. The cysteine residues (Cys) are indicated by short vertical lines just below the hydropathy trace. The numbers corresponding to the amino acid sequence of human 26886 are indicated. Polypeptides of the invention include 26886 fragments which include: all or part of a hydrophobic sequence (a sequence above the dashed line; all or part of a hydrophilic fragment (e.g., a fragment below the dashed line). Other fragments include a cysteine or a glycosylation site.

[0049] FIG. 11 depicts an alignment of the carnitine acyltransferase domain of human 26886 with a consensus amino acid sequence derived from a hidden Markov model. The upper sequence is the consensus amino acid sequence (SEQ ID NO: 12), while the lower amino acid sequence corresponds to amino acids 170 to 760 of SEQ ID NO: 10.

[0050] FIG. 12 is a bar graph depicting the expression of 26886 RNA in a panel of normal and tumor human tissues, including colon and liver, detected using TaqMan analysis. The following tissues are shown: normal colon (bars 1-6); adenomas (bars 7-8); colonic adenocarcinomas (bars 9-21); normal liver (bars 22-27); colon-liver metastasis (bars 28-33); and colon abdominal (bar 34). Elevated expression was detected in normal and malignant colon.

[0051] FIG. 13 is a bar graph depicting the expression of 26886 RNA in a panel of normal and tumor human tissues, including breast, colon, liver, and lung, detected using TaqMan analysis. The following tissues are shown: normal breast (bars 1-3); breast tumors, including invasive carcinoma (IDC) (bars 4-9); normal ovary (bars 10-11); ovarian tumor (bars 12-16); normal lung (bars 17-19); lung tumors, including small and non-small cell carcinoma, and adenocarcinomas (bars 20-26); normal colon (bars 27-29); colon tumors (bars 30-33); colon-liver metastasis (bars 34-35); normal liver (36); hemangioma (bar 37); human microvesicular endothelial cells (arrested and proliferating) (bars 38-39, respectively); normal prostate (bars 40-41); prostate tumor (bars 42-44); and prostate liver metastasis (bar 45). Elevated expression of 26886 mRNA was detected in breast tumors, lung small cell carcinomas, and endothelial cells.

[0052] FIG. 14 is a bar graph depicting the changes in 26886 mRNA expression in synchronized colorectal adenocarcinoma DLD-1 cell lines. DLD-1 cells were treated with nocodazole, which induces cell cycle arrest at the G2/M phase of the cell cycle. The profiling and Taqman experiments indicate that 26886 expression is upregulated during the transition from G2/M to G0/G1 phase.

[0053] FIG. 15 is a bar graph depicting the expression of 26886 RNA in a panel of tumor cell lines after transplantion in mice. Elevated expression of 26886 mRNA was detected in breast, ovarian, and baby kidney cell lines after transplant.

[0054] FIGS. 16A-16B depicts a cDNA sequence (SEQ ID NO: 13) and predicted amino acid sequence (SEQ ID NO: 14) of human 25552. The methionine-initiated open reading frame of human 25552 (without the 5′ and 3′ untranslated regions) starts at nucleotide 57 and ends at nucleotide 980 until the end of SEQ ID NO: 13 (shown also as coding sequence (SEQ ID NO: 15

[0055] FIG. 17 depicts a hydropathy plot of human 25552. Relative hydrophobic residues are shown above the dashed horizontal line, and relative hydrophilic residues are below the dashed horizontal line. The cysteine residues (cys) are indicated by short vertical lines just below the hydropathy trace. The numbers corresponding to the amino acid sequence of human 25552 are indicated. Polypeptides of the invention include fragments which include: all or part of a hydrophobic sequence, i.e., a sequence above the dashed line, e.g., the sequence of 220-260; all or part of a hydrophilic sequence, i.e., a sequence below the dashed line, e.g., the sequence of 105-140; a sequence which includes a Cys, or a glycosylation site.

[0056] FIG. 18 depicts an alignment of the ubiE methyltransferase domain of human 25552 with a consensus amino acid sequence derived from a hidden Markov model. The upper sequence is the consensus amino acid sequence (SEQ ID NO: 16), while the lower amino acid sequence corresponds to amino acids 37 to 306 of SEQ ID NO: 14.

[0057] FIG. 19 depicts a series of plots summarizing an analysis of the primary and secondary protein structure of human 33395. The particular algorithm used for each plot is indicated at the right hand side of each plot. The following plots are depicted: Gamier-Robson plots providing the predicted location of alpha-, beta-, turn and coil regions (Gamier et al. (1978) J. Mol. Biol. 120:97); Chou-Fasman plots providing the predicted location of alpha-, beta-, turn and coil regions (Chou and Fasman (1978) Adv. In Enzymol. Mol. 47:45-148); Kyte-Doolittle hydrophilicity/hydrophobicity plots (Kyte and Doolittle (1982) J. Mol. Biol. 157:105-132); Eisenberg plots providing the predicted location of alpha- and beta-amphipathic regions (Eisenberg et al. (1982) Nature 299:371-374); a Karplus-Schultz plot providing the predicted location of flexible regions (Karplus and Schulz (1985) Naturwissens-Chafen 72:212-213); a plot of the antigenic index (Jameson-Wolf) (Jameson and Wolf (1988) CABIOS 4:121-136); and a surface probability plot (Emini algorithm) (Emini et al. (1985) J. Virol. 55:836-839). The numbers corresponding to the amino acid sequence of human 33395 are indicated. Polypeptide fragments of the invention include polypeptides which have all or part of any of the regions described in this figure. Also included are variants having a mutation in a selected region shown in this figure.

[0058] FIG. 20 is a bar graph depicting 25552 mRNA expression levels in various human tissues as detected by TaqMan analysis. As shown, 25552 mRNA is particularly prevalent in fetal heart, heart, brain cortex, glial cells, kidney, fetal liver, epithelial cells (from prostate), skeletal muscle, undifferentiated osteoblasts, and human umbilical vein endothelial cells (HUMVEC).

[0059] FIG. 21 is a bar graph depicting 25552 mRNA expression levels in various human tissues as detected by TaqMan analysis. As shown, 25552 mRNA is particularly prevalent in heart, kidney, and skeletal tissue.

[0060] FIG. 22 is a bar graph depicting 25552 mRNA expression levels in various human tissues as detected by TaqMan analysis. As shown, 25552 mRNA is particularly prevalent in aortic smooth muscle cells, human microvascular endothelial cells, and adipose tissue.

[0061] FIG. 23 is a bar graph depicting 25552 mRNA expression levels in various human tissues and cell lines as detected by TaqMan analysis. As shown, 25552 mRNA is particularly prevalent in fetal liver.

[0062] FIG. 24 is a bar graph depicting 25552 mRNA expression levels in various human cells as detected by TaqMan analysis. As shown, 25552 mRNA is particularly prevalent in erythroid cells and hepatic cells such as HepG2 and Hep3B cell lines.

[0063] FIG. 25 is a bar graph depicting 25552 mRNA expression levels in various xenotransplanted human tumors as detected by TaqMan analysis. As shown, 25552 mRNA is particularly prevalent in xenotransplanted tumors from breast tumors and colon tumors.

[0064] FIG. 26 is a bar graph depicting 25552 mRNA expression levels in various human tumors as detected by TaqMan analysis. As shown, 25552 mRNA expression is elevated in a number of breast, ovarian, and lung tumors.

[0065] FIG. 27 is a bar graph depicting 25552 mRNA expression levels in various normal and cancerous human tissues as detected by TaqMan analysis. As shown, 25552 mRNA is elevated in some metastatic liver tissues, in normal brain, a brain tumor, and fetal adrenal and liver tissue.

[0066] FIG. 28 is a bar graph depicting 25552 mRNA expression levels in various normal and cancerous human tissues as detected by TaqMan analysis. As shown, 25552 mRNA is particularly prevalent in liver metastases.

[0067] FIG. 29 is a bar graph depicting 25552 mRNA expression levels in a genetically modified ES cell line relative to its wild-type counterpart. 25552 mRNA mRNA expression is increased in ES cells that have a non-functional APC the adenomatous polyposis coli (APC) tumor suppressor gene.

[0068] FIG. 30A is a bar graph depicting increased 25552 mRNA expression in metastatic liver samples. FIG. 30B is a bar graph depicted averaged 25552 mRNA expression for normal colon, colon tumors, metastatic tumors, and normal liver. 25552 mRNA expression is increased in colon tumors, and even more so in metastatic tumors relative to normal tissues.

[0069] FIG. 31 is a schematic depicting the synthesis of ubiquinone, and indicating the activity of ubiE polypeptides in catalyzing the conversion of (VII) to (VIII).

[0070] FIG. 32 depicts a hydropathy plot of human 32132. Relative hydrophobic residues are shown above the dashed horizontal line, and relative hydrophilic residues are below the dashed horizontal line. Numbers corresponding to positions in the amino acid sequence of human 32132 are indicated. Polypeptides of the invention include fragments which include: all or part of a hydrophobic sequence, i.e., a sequence above the dashed line, e.g., the sequence from about amino acid 8 to 28, from about 75 to 91, and from about 293 to 305 of SEQ ID NO: 20; all or part of a hydrophilic sequence, i.e., a sequence below the dashed line, e.g., the sequence of from about amino acid 60 to 74, from about 190 to 206, and from about 306 to 320 of SEQ ID NO: 20.

[0071] FIG. 33 depicts a BLAST alignment of the fucosyltransferase domain of human 32132 with a consensus amino acid sequence derived from a ProDomain No. 1416 (Release 1999.2; see also ProDom families PD003529 and PD002778 (ProDomain Release 2001.1); http://www.toulouse.inra.fr/prodom.html). The lower sequence is the consensus amino acid sequence (SEQ ID NO: 22), while the upper amino acid sequence corresponds to the fucosyltransferase domain of human 32132, about amino acids 57 to 355 of SEQ ID NO: 20.

[0072] FIG. 34 depicts an alignment of the fucosyltransferase domain of human 32132 with a consensus amino acid sequence (PFAM identifier PF00852) derived from a hidden Markov model. The upper sequence is the consensus amino acid sequence (SEQ ID NO: 23), while the lower amino acid sequence corresponds to amino acids 29 to 388 of SEQ ID NO: 20.

[0073] FIG. 35 depicts a hydropathy plot of human 32244. Relative hydrophobic residues are shown above the dashed horizontal line, and relative hydrophilic residues are below the dashed horizontal line. Numbers corresponding to positions in the amino acid sequence of human 32244 are indicated. Polypeptides of the invention include fragments which include: all or part of a hydrophobic sequence, i.e., a sequence above the dashed line, e.g., the sequence from about amino acid 245 to 270, from about 327 to 340, and from about 516 to 522 of SEQ ID NO: 26; and all or part of a hydrophilic sequence, i.e., a sequence below the dashed line, e.g., the sequence of from about amino acid 60 to 80, from about 434 to 446, and from about 523 to 535 of SEQ ID NO: 26.

[0074] FIG. 36 depicts an alignment of the AMP-binding enzyme domain of human 32244 with a consensus amino acid sequence derived from a hidden Markov model (HMM) from PFAM. The upper sequence is the consensus amino acid sequence (SEQ ID NO: 28), while the lower amino acid sequence corresponds to amino acids 67 to 504 of SEQ ID NO: 26.

[0075] FIG. 37 depicts a hydropathy plot of human 23680. Relative hydrophobic residues are shown above the dashed horizontal line, and relative hydrophilic residues are below the dashed horizontal line. The cysteine residues (cys) are indicated by short vertical lines below the hydropathy trace. The numbers corresponding to the amino acid sequence of human 23680 are indicated. Polypeptides of the invention include fragments which include: all or part of a hydrophobic sequence, i.e., a sequence above the dashed line, e.g., the sequence of residues 310-330 or 355-370 of SEQ ID NO: 33; all or part of a hydrophilic sequence, i.e., a sequence below the dashed line, e.g., the sequence of residues 30-50, 170-190 or 460-490 of SEQ ID NO: 33; a sequence which includes a Cys; or a glycosylation site.

[0076] FIGS. 38A-38B depicts an alignment of two aminotransferase domains of human 23680 with a consensus amino acid sequence derived from a hidden Markov model. In each of the alignments, the upper sequence is the consensus amino acid sequence (FIG. 38A: SEQ ID NO: 35; FIG. 38B: SEQ ID NO: 36), while the lower amino acid sequence corresponds to amino acids 40-141 and 165-415 of SEQ ID NO: 33.

[0077] FIG. 39 depicts a hydropathy plot of human 32624. Relative hydrophobic residues are shown above the dashed horizontal line, and relative hydrophilic residues are below the dashed horizontal line. Numbers corresponding to positions in the amino acid sequence of human 32624 are indicated. Polypeptides of the invention include fragments which include: all or part of a hydrophobic sequence, i.e., a sequence above the dashed line, e.g., the sequence from about amino acid residues 89 to 108, from about 145 to 170, and from about 491 to 507 of SEQ ID NO: 39; all or part of a hydrophilic sequence, i.e., a sequence below the dashed line, e.g., the sequence of from about amino acid residues 80 to 88, from about 136 to 144, and from about 433 to 457 of SEQ ID NO: 39.

[0078] FIGS. 40A-40B depict an alignment of the UDP-glucuronosyl and glycosyl transferase domain of human 32624 with a consensus amino acid sequence derived from a hidden Markov model (HMM) from PFAM. The upper sequence is the consensus amino acid sequence (SEQ ID NO: 41), while the lower amino acid sequence corresponds to amino acids 24 to 525 of SEQ ID NO: 39.

[0079] FIG. 41 depicts a hydropathy plot of human 47174. Relative hydrophobic residues are shown above the dashed horizontal line, and relative hydrophilic residues are below the dashed horizontal line. The cysteine residues (cys) are indicated by short vertical lines just below the hydropathy trace. The numbers corresponding to the amino acid sequence of human 47174 are indicated. Polypeptides of the invention include fragments that include: all or a part of a hydrophobic sequence (a sequence above the dashed line); or all or part of a hydrophilic fragment (a sequence below the dashed line). Other fragments include a cysteine residue.

[0080] FIG. 42 depicts an alignment of the glycosyltransferase group 2 domain of human 47174 with a consensus amino acid sequence derived from a hidden Markov model. The upper sequence is the consensus amino acid sequence (SEQ ID NO: 45), while the lower amino acid sequence corresponds to amino acids 154 to 336 of SEQ ID NO: 43.

[0081] FIG. 43 depicts an alignment of the ricin group 3 domain of human 47174 with a consensus amino acid sequence derived from a hidden Markov model. The upper sequence is the consensus amino acid sequence (SEQ ID NO: 46), while the lower amino acid sequence corresponds to amino acids 465 to 595 of SEQ ID NO: 43.

[0082] FIG. 44 depicts an alignment of the N-acetylgalatosaminyltransferase domain of human 47174 with a consensus amino acid sequence derived from a hidden Markov model. The upper sequence is the consensus amino acid sequence (SEQ ID NO: 47), while the lower amino acid sequence corresponds to amino acids 312 to 458 of SEQ ID NO: 43.

[0083] FIG. 45 depicts a hydropathy plot of human 60491. Relative hydrophobic residues are shown above the dashed horizontal line, and relative hydrophilic residues are below the dashed horizontal line. The cysteine residues (Cys) are indicated by short vertical lines just below the hydropathy trace. Numbers corresponding to positions in the amino acid sequence of human 60491 are indicated. Polypeptides of the invention include fragments which include: all or part of a hydrophobic sequence, i.e., a sequence above the dashed line, e.g., the sequence from about amino acid 163 to 179, from about 342 to 359, and from about 450 to 472 of SEQ ID NO: 49; all or part of a hydrophilic sequence, i.e., a sequence below the dashed line, e.g., the sequence of from about amino acid 228 to 235 and from about 337 to 346 of SEQ ID NO: 49; a sequence which includes a Cys, or a glycosylation site.

[0084] FIG. 46 depicts an alignment of the acyltransferase domain of human 60491 with a consensus amino acid sequence derived from a hidden Markov model (HMM) from PFAM. The upper sequence is the consensus amino acid sequence (SEQ ID NO: 51), while the lower amino acid sequence corresponds to amino acids 190 to 393 of SEQ ID NO: 49.

[0085] FIG. 47 depicts alignments of the acyltransferase domain of human 60491 with a consensus amino acid sequence derived from SMART. The upper sequence is the consensus amino acid sequence for the phosphate acyltransferase domain (SEQ ID NO: 52), while the lower amino acid sequence corresponds to amino acids of about 199 to about 333 of SEQ ID NO: 49.

[0086] FIGS. 48A-48D depicts a BLAST alignment of the acyltransferase domain of human 60491 with a consensus amino acid sequence derived from a ProDomain Nos. 353751, 7717, 025192, and 042760 (7717 is from the Release 1999.2; 353751, 025192, and 042760 are from the Release 2001.1; http://www.toulouse.inra.fr/prodom.html). The lower sequence is the consensus amino acid sequence (SEQ ID NOs: 53-56, respectively), while the upper amino acid sequence corresponds to the acyltransferase domain of human 60491, about amino acids 40 to 125, 104 to 395, 442 to 593, and 690 to 773 of SEQ ID NO: 49, respectively.

[0087] FIGS. 49A-49B depict a cDNA sequence (SEQ ID NO: 57) and predicted amino acid sequence (SEQ ID NO: 58) of human 46743. The coding sequence (without the 5′ and 3′ untranslated regions), which starts at the methionine-initiated open reading frame of human 46743 and extends until the termination codon, is also indicated (shown as SEQ ID NO: 59).

[0088] FIG. 50 depicts a hydropathy plot of human 46743. Relative hydrophobic residues are shown above the dashed horizontal line, and relative hydrophilic residues are below the dashed horizontal line. The cysteine residues (cys) and N-glycosylation sites (Ngly) are indicated by short vertical lines just below the hydropathy trace. The numbers corresponding to the amino acid sequence of human 46743 are indicated. Polypeptides of the invention include fragments comprising: all or part of a hydrophobic sequence (a sequence above the dashed line); or all or part of a hydrophilic fragment (a sequence below the dashed line). Other fragments include a cysteine residue or an N-glycosylation site.

[0089] FIG. 51 depicts a series of plots summarizing an analysis of the primary and secondary protein structure of human 46743. The particular algorithm used for each plot is indicated at the right hand side of each plot. The following plots are depicted: Gamier-Robson plots providing the predicted location of alpha, beta, turn, and coil regions (Gamier et al. (1978) J. Mol. Biol. 120:97); Chou-Fasman plots providing the predicted location of alpha, beta, and turn regions (Chou and Fasman (1978) Adv. In Enzymol. Mol. 47:45-148); Kyte-Doolittle hydrophilicity/hydrophobicity plots (Kyte and Doolittle (1982) J. Mol. Biol. 157:105-132); Eisenberg plots providing the predicted location of alpha- and beta-amphipathic regions (Eisenberg et al. (1982) Nature 299:371-374); a Karplus-Schulz plot providing the predicted location of flexible regions (Karplus and Schulz (1985) Naturwissens-Chafen 72:212-213); a plot of the antigenic index (Jameson-Wolf) (Jameson and Wolf (1988) CABIOS 4:121-136); and a surface probability plot (Emini algorithm) (Emini et al. (1985) J. Virol. 55:836-839). The numbers corresponding to the amino acid sequence of human 46743 are indicated.

[0090] FIGS. 52A-52B depict BLAST alignments of the acyltransferase domain of human 46743 with consensus amino acid sequences derived from ProDomain Nos. 37511 and 21987 (Release 1999.2; see also ProDom families PD036247 and PD022151 (ProDomain Release 2000.1); http://www.toulouse.inra.fr/prodom.html). ProDomain No. 37511 is a consensus amino acid sequence of an N-terminal fragment of a lysophosphatidic acid acyltransferase domain, while ProDomain No. 21987 is a consensus amino acid sequence of a C-terminal fragment of a lysophosphatidic acid acyltransferase domain. In FIG. 52A, the lower sequence is the consensus sequence of ProDomain No. 37511 (SEQ ID NO: 60), while the upper amino acid sequence corresponds to an N-terminal fragment of the acyltransferase domain of human 46743, about amino acids 26 to 214 of SEQ ID NO: 58. In FIG. 52B, the lower sequence is the amino acid sequence of ProDomain No. 21987 (SEQ ID NO: 61), while the upper amino acid sequence corresponds to a C-terminal fragment of the acyltransferase domain of human 46743, about amino acids 215 to 328 of SEQ ID NO: 58.

[0091] FIG. 53 is a bar graph depicting the expression of 46743 RNA in a panel of normal human normal and tumor tissues detected using Taqman analysis, including blood vessels (arteries, veins, smooth muscle cells, human umbilical vascular endothelial cells (HUVECs) (columns 1-6)), heart, normal and diseased (CHF) (columns 7-8), kidney (column 9), skeletal muscle (column 10), adipose tissue (column 11), pancreas (column 12), bone cells (column 13-14), skin (column 15), brain tissues, including spinal cord, cortex, hypothalamus, nerve cell, dorsal root ganglia, glial cells (columns 16-21, respectively), glioblastoma (column 22), normal and tumor breast (columns 23-24, respectively), normal and tumor ovary (columns 25-26, respectively), normal and tumor prostate (columns 27-28, respectively), epithelial cells (column 29), colon (columns 30-31, respectively and 35), normal, tumor and COPD lung (columns 32-34, respectively), normal and metastatic liver (columns 36-37, respectively), spleen and hematopoietic tissues (columns 39-46, respectively). Expression of 46743 RNA was detected in the kidney, skeletal muscle, heart, glial cells, liver, ovary, aortic smooth muscle cells (SMCs), bone marrow, colon, and brain. Reduced expression of 46743 was observed in tumor tissue from the ovary and the colon.

[0092] FIGS. 54A-54B are bar graphs depicting the expression of 46743 RNA in a panel of normal and human tumor tissues, including breast (columns 1-10 of FIG. 54A), normal ovary (columns 11-13 of FIG. 54A), tumor ovary (columns 14-21 of FIG. 54A), normal lung (column 22-25 of FIG. 54A), tumor lung (columns 26-33 of FIG. 54A), normal colon (columns 1-4 of FIG. 54B), tumor colon (columns 5-9 of FIG. 54B), metastatic liver (columns 10-13), normal liver (columns 14-15), normal brain (columns 16-19), astrocytes (column 20), brain tumor (columns 21-24), HUVEC (columns 25-26), placenta (column 27), fetal liver (columns 28-29) Wilm's tumor (column 30), and renal and endometrial tumors (columns 31-32). FIG. 54A is a bar graph showing a comparison of 46743 RNA expression in normal and tumorous tissues from the breast, ovary, and lung. The expression of 46743 is reduced in tumors of the ovary relative to normal ovary tissue, and may be elevated in tumors of the lung relative to normal lung tissue. FIG. 54B is a bar graph showing a comparison of 46743 RNA expression in normal and tumorous tissues from the colon, liver, and brain. The expression of 46743 is reduced in tumors of the brain relative to normal brain tissue.

[0093] FIG. 55 is a bar graph depicting the temporal expression levels of 46743 RNA in two distinct isolates of human breast cancer (MCF) cell lines that have been stimulated with epidermal growth factor (EGF). In both cell lines, expression of 46743 RNA begins to increase about one hour after the cells have been exposed to EGF, continues to increase until about the 4^th hour of EGF exposure, and has started to return to basal levels by the 8^th hour of EGF exposure.

[0094] FIGS. 56A-56C depicts a cDNA sequence (SEQ ID NO: 62) and predicted amino acid sequence (SEQ ID NO: 63) of human 27417. The coding sequence (without the 5′ and 3′ untranslated regions), which starts at the methionine-initiated open reading frame of human 27147 and extends until the termination codon, is also indicated (shown as SEQ ID NO: 64).

[0095] FIG. 57 depicts a hydropathy plot of human 27417. Relative hydrophobic residues are shown above the dashed horizontal line, and relative hydrophilic residues are below the dashed horizontal line. The cysteine residues (cys) and N-glycosylation sites (Ngly) are indicated by short vertical lines just below the hydropathy trace. The numbers corresponding to the amino acid sequence of human 27417 are indicated. Polypeptides of the invention include fragments comprising: all or part of a hydrophobic sequence (a sequence above the dashed line); or all or part of a hydrophilic fragment (a sequence below the dashed line). Other fragments include a cysteine residue or an N-glycosylation site.

[0096] FIG. 58 depicts a series of plots summarizing an analysis of the primary and secondary protein structure of human 27417. The particular algorithm used for each plot is indicated at the right hand side of each plot. The following plots are depicted: Gamier-Robson plots providing the predicted location of alpha, beta, turn, and coil regions (Gamier et al. (1978) J. Mol. Biol. 120:97); Chou-Fasman plots providing the predicted location of alpha, beta, and turn regions (Chou and Fasman (1978) Adv. In Enzymol. Mol. 47:45-148); Kyte-Doolittle hydrophilicity/hydrophobicity plots (Kyte and Doolittle (1982) J. Mol. Biol. 157:105-132); Eisenberg plots providing the predicted location of alpha- and beta-amphipathic regions (Eisenberg et al. (1982) Nature 299:371-374); a Karplus-Schulz plot providing the predicted location of flexible regions (Karplus and Schulz (1985) Naturwissens-Chafen 72:212-213); a plot of the antigenic index (Jameson-Wolf) (Jameson and Wolf (1988) CABIOS 4:121-136); and a surface probability plot (Emini algorithm) (Emini et al. (1985) J. Virol. 55:836-839). The numbers corresponding to the amino acid sequence of human 27417 are indicated.

[0097] FIGS. 59A-59B depict BLAST alignments of the acyltransferase domain of human 27417 with consensus amino acid sequences derived from ProDomain Nos. 4009 and 123477 (Release 1999.2; see also ProDom families PD000989 and PD107727 (ProDomain Release 2000.1); http://www.toulouse.inra.fr/prodom.html). ProDomain No. 4009 is a consensus amino acid sequence of an N-terminal fragment of a lysophosphatidic acid (1-acyl-glycerol-3 phosphate) acyltransferase domain, while ProDomain No. 123477 is a consensus amino acid sequence of a C-terminal fragment of a lysophosphatidic acid (1-acyl-3-glycerol phosphate) acyltransferase domain. In FIG. 59A, the lower sequence is the consensus sequence of ProDomain No. 4009 (SEQ ID NO: 65), while the upper amino acid sequence corresponds to an N-terminal fragment of the acyltransferase domain of human 27417, about amino acids 71 to 220 of SEQ ID NO: 63. In FIG. 59B, the lower sequence is the amino acid sequence of ProDomain No. 123477 (SEQ ID NO: 66), while the upper amino acid sequence corresponds to a C-terminal fragment of the acyltransferase domain of human 27147, about amino acids 197 to 363 of SEQ ID NO: 63.

[0098] FIG. 60 depicts an alignment of the acyltransferase domain of human 27417 with a consensus amino acid sequence derived from a hidden Markov model. The upper sequence is the consensus amino acid sequence (SEQ ID NO: 67), while the lower amino acid sequence corresponds to amino acids 77 to 288 of SEQ ID NO: 63.

[0099] FIG. 61 is a bar graph depicting the expression of 27147 RNA in a panel of normal human tissues, including heart, kidney, liver, and skeletal muscle, as well as some diseased tissues, detected using Taqman analysis. Expression of 27147 RNA is highest in skeletal muscle, but is present in all of the tissues analyzed. Elevated expression of 27147 RNA is present in diseased heart tissue, as compared to normal heart tissue.

[0100] FIG. 62 is a bar graph depicting the expression of 27417 RNA in a panel of normal tissues, including heart, kidney, skeletal muscle, and liver, and several diseased human liver tissue samples. Expression of 27417 is elevated in at least some diseased liver samples, as compared to normal liver samples.

[0101] FIG. 63 is a bar graph depicting the expression of 27417 RNA in a panel of normal human artery and vein tissue samples, as well as a couple of diseased human artery and vein tissue samples. Elevated expression of 27147 can be observed in a few of the tissue samples, including samples of a normal vein and endothelial cells isolated from human microvesicular endothelial cells (hmvec's). Elevated expression of 27147 can also be observed in the diseased artery sample.

[0102] FIG. 64 depicts a hydropathy plot of human 27960. Relative hydrophobic residues are shown above the dashed horizontal line, and relative hydrophilic residues are below the dashed horizontal line. The cysteine residues (cys) are indicated by short vertical lines just below the hydropathy trace. The numbers corresponding to the amino acid sequence of human 27960 are indicated. Polypeptides of the invention include fragments that include: all or part of a hydrophobic sequence, i.e., a sequence above the dashed line, e.g., the sequence of residues 100-119 of SEQ ID NO: 73; all or part of a hydrophilic sequence, i.e., a sequence below the dashed line, e.g., the sequence of residues 15-20; a sequence that includes a Cys, e.g., the sequence of residues 118-120 of SEQ ID NO: 73.

[0103] FIGS. 65A-65B depict alignment of the ubiquitin-conjugating enzyme domain of human 27960 with a consensus amino acid sequence derived from hidden Markov models using PFAM (UQ_con) and SMART (ubc_—7) programs, respectively. In FIG. 65A, the upper sequence is the consensus amino acid sequence (SEQ ID NO: 75), while the lower amino acid sequence corresponds to amino acids 1 to 148 of SEQ ID NO: 73. In FIG. 65B, the upper sequence is the consensus amino acid sequence (SEQ ID NO: 76), while the lower amino acid sequence corresponds to amino acids 6 to 151 of SEQ ID NO: 73.

[0104] FIG. 66 depicts a hydropathy plot of human 32252. Relative hydrophobic residues are shown above the dashed horizintal line, and relative hydrophilic residues are below the dashed horizontal line. The cysteine residues (cys) are indicated by short vertical lines just below the hydropathy trace. Two glycosylation sites are also indicated. The numbers corresponding to the amino acid sequence of human 32252 are indicated. Polypeptides of the invention include fragments which include: all or part of a hydrophobic sequence, i.e., a sequence above the dashed line, e.g., the sequence from about amino acid 170 to 180, from about 335 to 355, and from about 430 to 450 of SEQ ID NO: 78; all or part of a hydrophilic sequence, i.e., a sequence below the dashed line, e.g., the sequence of from about amino acid 210 to 225, and from about 495 to 510 of SEQ ID NO: 78.

[0105] FIGS. 67A-67B depicts an alignment (BLAST) of amino acids 136 to 2151 of human 32252 (upper sequence; SEQ ID NO: 78) with amino acids 1 to 672 of acetoacetyl-CoA synthetase of Rattus norvegicus (lower sequence; SEQ ID NO: 80). The middle sequence is the consensus sequence (SEQ ID NO: 81).

[0106] FIGS. 68A-68F depicts an alignment (BLAST) of nucleotides 66 to 2158 of SEQ ID NO: 77 (upper sequence) with nucleotides 39 to 2131 of a Rattus norvegicus acetoacetyl-CoA synthetase cDNA (lower sequence: SEQ ID NO: 82).

[0107] FIG. 69 depicts a hydropathy plot of human 53320. Relative hydrophobic residues are shown above the dashed horizontal line, and relative hydrophilic residues are below the dashed horizontal line. Numbers corresponding to positions in the amino acid sequence of human 53320 are indicated. Polypeptides of the invention include fragments which include: all or a part of a hydrophobic sequence (a sequence above the dashed line); or all or part of a hydrophilic fragment (a sequence below the dashed line).

[0108] FIG. 70 depicts an alignment of the acyltransferase domain of human 53320 with a consensus amino acid sequence derived from a hidden Markov model. The upper sequence is the consensus amino acid sequence (SEQ ID NO: 86), while the lower amino acid sequence corresponds to amino acids 71 to 261 of SEQ ID NO: 84.

[0109] FIG. 71 depicts structural features of one embodiment of the 53320 polypeptide.

[0110] FIGS. 72 and 73 depict bar graphs of 53320 expression in endothelial cells. 2

TABLE 1
FIG. 4 data

Cell	53320Ave CT	B2m Ave CT	Expression

1	26.23	21.23	31.3108270	prolif
2	28.32	21.87	11.4777599	−GF
3	26.095	21.52	41.9616901	T5
4	27.95	22.335	20.4041817	T25
5	27.22	23.035	55.1237407	T2
6	27.145	23.21	66.4863730	T6
7	27.31	22.46	35.2386543	T16
8	27.765	22.47	25.5262526	T6
9	27.245	24.035	108.160625	T2
10	26.8	22.46	49.4962475	T6
11	27.405	23.025	49.2892646	T16
12	28.64	23.515	28.6606789	T4
13	29.2	26.14	125.528039	T19
14	28.255	23.255	31.2867919	T2
15	28.635	23.81	37.4636912	T17
16	28.545	24.115	46.3924760	T24
17	26.98	22.37	41.8383390	T43
18	27.52	23.26	52.2042797	C48
19	29	22.755	13.1853344	A24

[0111] 3

TABLE 2
FIG. 5 data

Cell	53320 Ave Ct	B2m 5′ Ave Ct	Expression

1	27.38	21.535	17.41487319	prolif
2	28.54	20.615	4.115902467	conf
3	29.325	20.34	2.138020854	GF(−)
4	28.005	19.765	3.379368496	prolif
5	32.975	21.165	0.286276814	conf
6	29.4	22.02	6.224113378	prolif
7	30.28	21.14	1.772881585	conf
8	28.22	20.45	4.621174573	prolif
9	30.285	19.67	1.487867597	conf
10	29.255	20.235	1.946678328	GT(−)
11	30.53	22.625	4.214321241	prolif
12	31.135	21.57	1.324421995	conf
13	31.075	21.475	1.292329333	GT(−)
14	27.06	22.24	34.95633018	293

DETAILED DESCRIPTION OF 33877 AND 47179

Human 33877

[0112] The human 33877 sequence (FIGS. 1A-1C; SEQ ID NO: 1), which is approximately 2493 nucleotides long including untranslated regions, contains a predicted methionine-initiated coding sequence of about 1659 nucleotides (nucleotides 402-2060 of SEQ ID NO: 1; SEQ ID NO: 3). The coding sequence encodes a 552 amino acid protein (SEQ ID NO: 2). Human 33877 protein of SEQ ID NO: 2 includes an amino-terminal hydrophobic amino acid sequence, consistent with a signal sequence, of about 30 amino acids (from amino acid 1 to about amino acid 30 of SEQ ID NO: 2), which upon protease removal results in the production of the mature protein.

[0113] This mature protein form is approximately 522 amino acid residues in length (from about amino acid 31 to amino acid 552 of SEQ ID NO: 2). Human 33877 contains the following regions or other structural features: a glycosyl transferase group 2 domain (PFAM Accession PF00535) located at about amino acid residues 114 to 292 of SEQ ID NO: 2; and a predicted transmembrane domain which extends from about amino acid residue 475 to 492 of SEQ ID NO: 2.

[0114] The 33877 protein also includes the following domains: one cAMP- and cGMP-dependent protein kinase phophorylation site (PS0004) located at about amino acids 2-5 of SEQ ID NO: 2; 10 predicted Protein Kinase C phosphorylation sites (PS00005) located at about amino acids 5-7, 27-29, 41-43, 84-86, 89-91, 130-132, 313-315, 355-357, 399-401, and 433-435 of SEQ ID NO: 2; eight predicted Casein Kinase II phosphorylation sites (PS00006) located at about amino 35-38, 45-48, 196-199, 200-203, 237-240, 241-244, 387-390, and 507-510 of SEQ ID NO: 2; two predicted tyrosine kinase phosphorylation sites (PS00007) located at about amino acids 68-74 and 401-408 of SEQ ID NO: 2; six predicted N-myristoylation sites (PS00008) located at about amino acids 178-183, 186-191, 192-197, 346-351, 383-388, and 526-531 of SEQ ID NO: 2; and a predicted vacuolar targeting motif located at about amino acids 164-167 of SEQ ID NO: 2.

[0115] For general information regarding PFAM identifiers, PS prefix and PF prefix domain identification numbers, refer to Sonnhammer et al. (1997) Protein 28:405-420 and http://www.psc.edu/general/software/packages/pfam/pfam.html.

[0116] A plasmid containing the nucleotide sequence encoding human 33877 (clone “Fbh33877FL”) was deposited with American Type Culture Collection (ATCC), 10801 University Boulevard, Manassas, Va. 20110-2209, on ______ and assigned Accession Number ______. This deposit will be maintained under the terms of the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure. This deposit was made merely as a convenience for those of skill in the art and is not an admission that a deposit is required under 35 U.S.C. §112.

Human 47179

[0117] The human 47179 sequence (FIGS. 5A-5C; SEQ ID NO: 4), which is approximately 1620 nucleotides long including untranslated regions, contains a predicted methionine-initiated coding sequence of about 1251 nucleotides (nucleotides 29-1279 of SEQ ID NO: 4; SEQ ID NO: 6). The coding sequence encodes a 416 amino acid protein (SEQ ID NO: 5).

[0118] Human 15977 contains the following regions or other structural features: a glycosyl transferase group 1 domain (PFAM Accession PF00534) located at about amino acid residues 211 to 293 of SEQ ID NO: 5; and a predicted transmembrane domain which extends from about amino acid residue 81 to 105 of SEQ ID NO: 5.

[0119] The 47179 protein also includes the following domains: two predicted N-glycosylation sites (PS00001) located at about amino acids 204-207 and 239-242 of SEQ ID NO: 5; one cAMP- and cGMP-dependent protein kinase phosphorylation site (PS00004) located at about amino acids 146-149 of SEQ ID NO: 5; four predicted Protein Kinase C phosphorylation sites (PS00005) located at about amino acids 145-147, 187-189, 304-306, and 381-383 of SEQ ID NO: 5; five predicted Casein Kinase II phosphorylation sites (PS00006) located at about amino acids 145-148, 192-195, 206-209, 255-258, and 302-305 of SEQ ID NO: 5; five predicted N-myristoylation sites (PS00008) located at about amino acids 25-30, 78-83, 85-90, 168-173, and 294-299 of SEQ ID NO: 5; and one predicted amidation site (PS00009) located at about amino acids 222-225 of SEQ ID NO: 5.

[0120] A plasmid containing the nucleotide sequence encoding human 47179 (clone “Fbh47179FL”) was deposited with American Type Culture Collection (ATCC), 10801 University Boulevard, Manassas, Va. 20110-2209, on ______ and assigned Accession Number ______. This deposit will be maintained under the terms of the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure. This deposit was made merely as a convenience for those of skill in the art and is not an admission that a deposit is required under 35 U.S.C. §112. 4

TABLE 1
Summary of Sequence Information for 33877 and 47179

					ATCC
					Accession
Gene	cDNA	ORF	Polypeptide	Figure	Number
33877	SEQ ID	SEQ ID	SEQ ID
	NO: 1	NO: 3	NO: 2
47179	SEQ ID	SEQ ID	SEQ ID
	NO: 4	NO: 6	NO: 5

[0121] 5

TABLE 2
Summary of Selected Domains of 33877 and 47179

	Glycosyltransferase	Transmembrane
Protein	Domain	Domain
33877	About amino acids 114-292	About amino acids 475-492
	of SEQ ID NO:2	of SEQ ID NO:2
47179	About amino acids 211-393	About amino acids 81-105
	of SEQ ID NO:5	of SEQ ID NO:5

[0122] The 33877 and 47179 proteins contain a significant number of structural characteristics in common with members of the glycosyltransferase family. The term “family” when referring to the protein and nucleic acid molecules of the invention means two or more proteins or nucleic acid molecules having a common structural domain or motif and having sufficient amino acid or nucleotide sequence homology as defined herein. Such family members can be naturally or non-naturally occurring and can be from either the same or different species. For example, a family can contain a first protein of human origin as well as other distinct proteins of human origin, or alternatively, can contain homologues of non-human origin, e.g., rat or mouse proteins. Members of a family can also have common functional characteristics.

[0123] Members of the glycosyltransferase family of proteins are characterized by the ability to catalyze the synthesis of glycoconjugates, including glycolipids, glycoproteins, and polysaccharides, by transferring an activated mono- or oligosaccharide residue to an existing acceptor molecule for the initiation or elongation of the carbohydrate chain. The acceptor can be a lipid, a protein, a heterocyclic compound, or another carbohydrate residue. Glycosyltransferases can be divided into numerous subfamilies based upon their specificity for sugar moieties and acceptor molecules. The glycosyltransferase domain of human 33877 bears similarity to a subfamily designated “group 2” glycosyltransferases. These enzymes comprise a diverse subfamily, whose members transfer sugar from UDP-glucose, UDP-N-acetyl-galactosamine, GDP-mannose or CDP-abequose, to a range of substrates including cellulose, dolichol phosphate and teichoic acids. The glycosyltransferase domain of human 47179 bears similarity to a subfamily designated “group 1” glycosyltransferases. Members of this family-transfer activated sugars to a variety of substrates, including glycogen, fructose-6-phosphate and lipopolysaccharides. Members of this family transfer UDP, ADP, GDP or CMP linked sugars. Based on the sequence similarities, the 33877 or 47179 molecules of the present invention are predicted to have similar biological activities as glycosyltransferase family members.

[0124] Glycosyltransferases play roles in diverse cellular processes. For example, the major target of the natural IgM and IgG antibodies during hyperacute xenograft rejection is the terminal carbohydrate epitope Gal alpha(1,3)Gal, formed by the alpha 1,3galactosyl transferase, which places a terminal galactose residue in an alpha-linkage to another galactose (Sandrin et al. (1994) Immunol Rev 141:169-90). As another example, mutations in the Piga gene, the protein product of which mediates N-acetylglucosamine attachment to phosphatidylinositol, results in the clonal hematologic disorder, paroxysmal nocturnal hemoglobinuria (Ware et al. (1994) Blood 83:2418-22). Additionally, UDP-galactose:ceramide galactosyltransferase is the enzyme responsible for the biosynthesis of galactosylceramide, a molecule thought to play a critical role in myelin formation, signal transduction, viral and microbial adhesion, and oligodendrocyte development (Kapitonov et al. (1999) Glycobiology 9:961-78).

[0125] Glycosylation of glycoproteins and glycolipids is one of many molecular changes that accompany malignant transformation. GlcNAc-branched N-glycans and terminal Lewis antigen sequences have been observed to increase in some cancers, and to correlate with poor prognosis (Dennis et al. (1999) Biochim Biophys Acta 1473:21-34). Cellular membrane over-expression and shedding of acidic glycosphingolipids into the interstitial spaces and blood of cancer patients may play a central role in increased tumor cell growth, lack of immune cell recognition and neovascularization and could represent a molecular target for cancer therapy (Fish (1996) Med Hypotheses 46:140-44). Thus, the molecules of the present invention may be involved in: 1) the transfer of an activated sugar residue to an acceptor molecule; 2) the processing, folding, and secretion of proteins; 3) the modulation of tumor cell growth and invasion; 4) myelin formation; 5) signal transduction; 6) viral and microbial adhesion; 7) oligodendrocyte development; 8) sperm-egg binding; 9) evasion of immune detection; 10) xenograft rejection; and 11) the ability to antagonize or inhibit, competitively or non-competitively, any of 1-11.

[0126] A 33877 or 47179 polypeptide can include a “glycosyltransferase domain” or regions homologous with a “glycosyltransferase domain”.

[0127] As used herein, the term “glycosyltransferase domain” includes an amino acid sequence of about 100-250 amino acid residues in length and having a bit score for the alignment of the sequence to the glycosyltransferase domain (HMM) of at least 30. Preferably, a glycosyltransferase domain includes at least about 120-220 amino acids, more preferably about 120-200 amino acid residues, or about 130-180 amino acids and has a bit score for the alignment of the sequence to the glycosyltransferase domain (HMM) of at least 50 or greater. Glycosyltransferase domains (HMM) have been assigned numerous PFAM Accession Numbers, including PF00534 (group 1) and PF00535 (group 2) (http://pfam.wustl.edu/). An alignment of the glycosyltransferase domain (amino acids 114 to 292 of SEQ ID NO: 2) of human 33877 with a consensus amino acid sequence (group 2 glycosyltransferases) derived from a hidden Markov model is depicted in FIG. 4. An alignment of the glycosyltransferase domain (amino acids 211 to 393 of SEQ ID NO: 5) of human 47179 with a consensus amino acid sequence (group 1 glycosyltransferases) derived from a hidden Markov model is depicted in FIG. 8.

[0128] In a preferred embodiment 33877 or 47179 polypeptide or protein has a “glycosyltransferase domain” or a region which includes at least about 120-220 more preferably about 120-200 or 130-180 amino acid residues and has at least about 70% 80% 90% 95%, 99%, or 100% homology with a “glycosyltransferase domain,” e.g., the glycosyltransferase domain of human 33877 or 47179 (e.g., residues 114 to 292 of SEQ ID NO: 2 or residues 211 to 393 of SEQ ID NO: 5).

[0129] To identify the presence of a “glycosyltransferase” domain in a 33877 or 47179 protein sequence, and make the determination that a polypeptide or protein of interest has a particular profile, the amino acid sequence of the protein can be searched against the Pfam database of HMMs (e.g., the Pfam database, release 2.1) using the default parameters (http://www.sanger.ac.uk/Software/Pfam/HMM_search). For example, the hmmsf program, which is available as part of the HMMER package of search programs, is a family specific default program for MILPAT0063 and a score of 15 is the default threshold score for determining a hit. Alternatively, the threshold score for determining a hit can be lowered (e.g., to 8 bits). A description of the Pfam database can be found in Sonhammer et al. (1997) Proteins 28(3):405-420 and a detailed description of HMMs can be found, for example, in Gribskov et al. (1990) Meth. Enzymol. 183:146-159; Gribskov et al. (1987) Proc. Natl. Acad. Sci. USA 84:4355-4358; Krogh et al. (1994) J. Mol. Biol. 235:1501-1531; and Stultz et al. (1993) Protein Sci. 2:305-314, the contents of which are incorporated herein by reference.

[0130] A 33877 or 47179 molecule can further include a transmembrane domain.

[0131] As used herein, the term “transmembrane domain” includes an amino acid sequence of about 15 amino acid residues in length that spans a phospholipid membrane. More preferably, a transmembrane domain includes about at least 18, 20, 22, 24, 25, 30, 35 or 40 amino acid residues and spans a phospholipid membrane. Transmembrane domains are rich in hydrophobic residues, and typically have an α-helical structure. In a preferred embodiment, at least 50%, 60%, 70%, 80%, 90%, 95% or more of the amino acids of a transmembrane domain are hydrophobic, e.g., leucines, isoleucines, tyrosines, or tryptophans. Transmembrane domains are described in, for example, http://pfam.wustl.edu/cgi-bin/getdesc?name=7tm-1, and Zagotta W. N. et al, (1996) Annual Rev. Neuronsci. 19: 235-63, the contents of which are incorporated herein by reference.

[0132] In a preferred embodiment, a 33877 or 47179 polypeptide or protein has at least one transmembrane domain or a region which includes at least 18, 20, 22, 24, 25, 30, 35 or 40 amino acid residues and has at least about 60%, 70% 80% 90% 95%, 99%, or 100% homology with a “transmembrane domain,” e.g., at least one transmembrane domain of human 33877 (e.g., amino acid residues 475-492 of SEQ ID NO: 2) or human 47179 (e.g., amino acid residues 81-105 of SEQ ID NO: 5).

[0133] In another embodiment, a 33877 or 47179 protein includes at least one “non-transmembrane domain.” As used herein, “non-transmembrane domains” are domains that reside outside of the membrane. When referring to plasma membranes, non-transmembrane domains include extracellular domains (i.e., outside of the cell) and intracellular domains (i.e., within the cell). When referring to membrane-bound proteins found in intracellular organelles (e.g., mitochondria, endoplasmic reticulum, Golgi, peroxisomes and microsomes), non-transmembrane domains include those domains of the protein that reside in the cytosol (i.e., the cytoplasm), the lumen of the organelle, or the matrix or the intermembrane space (the latter two relate specifically to mitochondria organelles). The C-terminal amino acid residue of a non-transmembrane domain is adjacent to an N-terminal amino acid residue of a transmembrane domain in a naturally-occurring 33877 or 47179, or 33877 or 47179-like protein.

What is claimed is:

1. An isolated nucleic acid molecule selected from the group consisting of: a) a nucleic acid comprising the nucleotide sequence of SEQ ID NO: 1, 3, 4, 6, 9, 11, 13, 15, 19, 21, 25, 27, 32, 34, 38, 40, 42, 44, 48, 50, 57, 59, 62, 64, 72, 74, 77, 79, 83, or 85; and b) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, 5, 10, 14, 20, 26, 33, 39, 43, 49, 58, 63, 73, 78, or 84.

2. The nucleic acid molecule of claim 1, further comprising vector nucleic acid sequences.

3. The nucleic acid molecule of claim 1, further comprising nucleic acid sequences encoding a heterologous polypeptide.

4. A host cell which contains the nucleic acid molecule of claim 1.

5. An isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 2, 5, 10, 14, 20, 26, 33, 39, 43, 49, 58, 63, 73, 78, or 84.

6. The polypeptide of claim 5 further comprising heterologous amino acid sequences.

7. An antibody or antigen-binding fragment thereof that selectively binds to a polypeptide of claim 5.

8. A method for producing a polypeptide comprising the amino acid sequence of SEQ ID NO: 2, 5, 10, 14, 20, 26, 33, 39, 43, 49, 58, 63, 73, 78, or 84, the method comprising culturing the host cell of claim 4 under conditions in which the nucleic acid molecule is expressed.

9. A method for detecting the presence of a polypeptide of claim 5 in a sample, comprising: a) contacting the sample with a compound which selectively binds to the polypeptide; and b) determining whether the compound binds to the polypeptide in the sample.

10. The method of claim 9, wherein the compound which binds to the polypeptide is an antibody.

11. A kit comprising a compound which selectively binds to a polypeptide of claim 5 and instructions for use.

12. A method for detecting the presence of a nucleic acid molecule of claim 1 in a sample, comprising the steps of: a) contacting the sample with a nucleic acid probe or primer which selectively hybridizes to the nucleic acid molecule; and b) determining whether the nucleic acid probe or primer binds to a nucleic acid molecule in the sample.

13. The method of claim 12, wherein the sample comprises mRNA molecules and is contacted with a nucleic acid probe.

14. A kit comprising a compound which selectively hybridizes to a nucleic acid molecule of claim 1 and instructions for use.

15. A method for identifying a compound which binds to a polypeptide of claim 5 comprising the steps of: a) contacting a polypeptide, or a cell expressing a polypeptide of claim 5 with a test compound; and b) determining whether the polypeptide binds to the test compound.

16. A method for modulating the activity of a polypeptide of claim 5, comprising contacting a polypeptide or a cell expressing a polypeptide of claim 5 with a compound which binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide.

17. A method of inhibiting aberrant activity of a 33877, 47179, 26886, 25552, 32132, 32244, 23680, 32624, 47174, 60491, 46743, 27417, 27960, 32252, or 53320-expressing cell, comprising contacting a 33877, 47179, 26886, 25552, 32132, 32244, 23680, 32624, 47174, 60491, 46743, 27417, 27960, 32252, or 53320-expressing cell with a compound that modulates the activity or expression of a polypeptide of claim 5, in an amount which is effective to reduce or inhibit the aberrant activity of the cell.

18. The method of claim 17, wherein the compound is selected from the group consisting of a peptide, a phosphopeptide, a small organic molecule, and an antibody.

19. A method of treating or preventing a disorder characterized by aberrant activity of a 33877, 47179, 26886, 25552, 32132, 32244, 23680, 32624, 47174, 60491, 46743, 27417, 27960, 32252, or 53320-expressing cell, in a subject, comprising: administering to the subject an effective amount of a compound that modulates the activity or expression of a nucleic acid molecule of claim 1, such that the aberrant activity of the 33877, 47179, 26886, 25552, 32132, 32244, 23680, 32624, 47174, 60491, 46743, 27417, 27960, 32252, or 53320-expressing cell is reduced or inhibited.