| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | 31.12.02 |
| PATENT TITLE |
cDNAs coding for human proteins having transmembrane domains |
| PATENT ABSTRACT |
The invention provides cDNAs coding for human proteins having transmembrane domains and eucaryotic cells expressing said cDNAs. The cDNAs of the invention can be utilized as probes for the gene diagnosis and gene sources for the gene therapy. Furthermore, the cDNAs can be utilized for large-scale expression of said proteins. Cells, wherein these membrane protein genes are introduced and membrane proteins are expressed in large amounts, can be utilized for detection of the corresponding ligands, screening of novel low-molecular pharmaceuticals, and so on. |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | August 21, 2000 |
| PATENT CT FILE DATE | October 2, 1998 |
| PATENT CT NUMBER | This data is not available for free |
| PATENT CT PUB NUMBER | This data is not available for free |
| PATENT CT PUB DATE | April 15, 1999 |
| PATENT FOREIGN APPLICATION PRIORITY DATA | This data is not available for free |
| PATENT REFERENCES CITED |
Michael Y. Galperin et al. Who's your neighbor? New computational approaches for functional genomics Nature Biotechnology vol. 18 Jun. 2000.* Adams, M.D. et al., "EST13893 Testis tumor Homo sapiens cDNA 5' end similar to similar to protein transport protein SEC61, mRNA sequence," EMBL Database entry HSZZ0146, Acc. No. AA301007 (Apr. 1997). Adams, M.D. et al., "EST100769 Pancreas tumor I Homo sapiens cDNA 5' end similar to similar to protein transport protein SEC61, mRNA sequence," EMBL Database entry HSZZ00740, Acc. No. AA295598 (Apr. 1997). Adams, M.D. et al., "EST83699 Pituitary gland, subtracted (prolactin/growth hormone) II Homo sapiens cDNA 5' end similar to similar to protein transport protein SEC61, mRNA sequence," EMBL Database entry HSZZ7695, Acc. No. AA371870 (Apr. 1997). Feng, Y. et al., "HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor," Science, May 10, 1996;272(5263):872-7. Gorlich, D. et al., "A mammalian homolog of SEC61p and SECYp is associated with ribosomes and nascent polypeptides during translocation," Cell, Oct. 30, 1992;71(3):489-503. Holloway, M.P. et al., "A hydrophobic domain of Ca2+-modulating cyclophilin ligand modulates calcium influx signaling in T lymphocytes," J. Biol. Chem., Apr. 12, 1996;271(15):8549-52. Kyte, J. et al., "A simple method for displaying the hydropathic character of a protein," J. Mol. Biol., May 5, 1982;157(1):105-32. Rommens, J.M. et al., "Identification of the cystic fibrosis gene: chromosome walking and jumping," Science, Sep. 8, 1989;245(4922):1059-65. |
| PATENT CLAIMS |
What is claimed is: 1. An isolated polynucleotide encoding a human sec61 protein, the polynucleotide comprising the nucleotide sequence set forth in SEQ ID NO:1 or 3. 2. An isolated polynucleotide encoding a humna sec61 protein, the polynucleotide consisting of the nucleotide sequence set forth in SEQ ID NO:1 or 3. 3. An isolated polynucleotide encoding a human translocon-associated protein comprising the amino acid sequence set forth in SEQ ID NO:4. 4. An isolated polynucleotide encoding a human translocon-associated protein, the polynucleotide comprising the nucleotide sequence set forth in SEQ ID NO:2 or 5. 5. An isolated polynucleotide encoding a human translocon-associated protein, the polynucleotide consisting of the nucleotide sequence set forth in SEQ ID NO:2 or 5. 6. An isolated nucleic acid molecule which hybridizes to the nucleic acid molecule of any one of claims 1, 2, 3, 4, or 5 under stringent conditions. 7. An isolated polynucleotide comprising a nucleotide sequence which is complementary to the polynucleotide of any one of claims 1, 2, 3, 4, or 5. 8. An isolated polynucleotide comprising the polynucleotide of any one of claims 1, 2, 3, 4, or 5, and a nucleotide sequence encoding a heterologous polypeptide. 9. An isolated polynucleotide of any one claims 5, 6, 7, 8, or 9, wherein the polynucleotide is operably linked to at least one expression control sequence. 10. A vector comprising the polynucleotide of any one of claims 1, 2, 3, 4, or 5. 11. The vector of claim 10, which is an expression vector. 12. A host cell transfected with the expression vector of claim 11. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
DESCRIPTION 1. Technical Field The present invention relates to cDNAs coding for human proteins having transmembrane domains and eucaryotic cells expressing said cDNAs. The human cDNAs of the present invention can be utilized as probes for the gene diagnosis and gene sources for the gene therapy. Furthermore, the cDNAs can be utilized as gene sources for large-scale production of the proteins encoded by said cDNAs. Cells, wherein said cDNAs are expressed, can be utilized for detection of the corresponding ligands, screening of novel low-molecular pharmaceuticals, and so on. 2. Background Art Membrane proteins play important roles, as signal receptors, ion channels, transporters, etc. in the material transportation and the information transmission which are mediated by the cell membrane. Examples thereof include receptors for a variety of cytokines, ion channels for the sodium ion, the potassium ion, the chloride ion, etc., transporters for saccharides and amino acids, and so on, where the genes of many of them have been cloned already. It has been clarified that abnormalities of these membrane proteins are associated with a number of hitherto-cryptogenic diseases. For instance, a gene of a membrane protein having twelve transmembrane domains was identified as the gene responsible for cystic fibrosis [Rommens, J. M. et al., Science 245: 1059-1065 (1989)]. In addition, it has been clarified that several membrane proteins act as receptors when a virus infects the cells. For instance, HIV-1 is revealed to infect into the cells through mediation of a membrane protein fusin having a membrane protein on the T-cell membrane, a CD-4 antigen, and seven transmembrane domains [Feng, Y. et al., Science 272: 872-877 (1996)]. Therefore, discovery of a new membrane protein is anticipated to lead to elucidation of the causes of many diseases, so that isolation of a new gene coding for the membrane protein has been desired. Heretofore, owing to difficulty in the purification, many membrane proteins have been isolated by an approach from the gene side. A general method is the so-called expression cloning which comprises transfection of a cDNA library in eucaryotic cells to express cDNAs and then detection of the cells expressing the target membrane protein on the membrane by an immunological technique using an antibody or a physiological technique on the change in the membrane permeability. However, this method is applicable only to cloning of a gene of a membrane protein with a known function. In general, membrane proteins possess hydrophobic transmembrane domains inside the proteins, wherein, after synthesis thereof in the ribosome, these domains remain in the phospholipid membrane to be trapped in the membrane. Accordingly, the evidence of the cDNA for encoding the membrane protein is provided by determination of the whole base sequence of a full-length cDNA followed by detection of highly hydrophobic transmembrane domains in the amino acid sequence of the protein encoded by said cDNA. DISCLOSURE OF INVENTION The object of the present invention is to provide novel human proteins having transmembrane domains and DNAs coding for said proteins as well as transformation eucaryotic cells that are capable of expressing said cDNAs. As the result of intensive studies, the present inventors have been successful in cloning of cDNAs coding for proteins having transmembrane domains from the human full-length cDNA bank, thereby completing the present invention. In other words, the present invention provides cDNAs coding for human proteins having transmembrane domains, exemplified by cDNAs containing either of the base sequences represented by SEQ ID NO:1 and SEQ ID NO:2, as well as transformation eucaryotic cells that are capable of expressing said cDNAs. BRIEF DESCRIPTION OF DRAWINGS FIG. 1: A figure depicting the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP00567. FIG. 2: A figure depicting the hydrophobicity/hydrophilicity profile of the protein encoded by clone HP00991. BEST MODE FOR CARRYING OUT THE INVENTION The cDNAs of the present invention can be cloned, for example, from cDNA libraries of the human cell origin. These cDNA are synthesized by using as templates poly (A).sup.+ RNAs extracted from human cells. The human cells may be cells delivered from the human body, for example, by the operation or may be the culture cells. The cDNAs can be synthesized by using any method selected from the Okayama-Berg method [Okayama, H. and Berg, P., Mol. Cell. Biol. 2: 161-170 (1982)], the Gubler-Hoffman method [Gubler, U. and Hoffman, J. Gene 25: 263-269 (1983)], and so on, but it is preferred to use the capping method [Kato, S. et al., Gene 150: 243-250 (1994)], as exemplified in Examples, in order to obtain a full-length clone in an effective manner. The primary selection of one of the cDNAs coding for the human proteins having transmembrane domains is carried out by sequencing of a partial base sequence of a cDNA clone selected at random from cDNA libraries, sequencing of the amino acid sequence encoded by the base sequence, and recognition of the presence or absence of a hydrophobic site in the resulting N-terminal amino acid sequence region. Next, the secondary selection is carried out by determination of the whole sequence by the sequencing and the protein expression by in vitro translation. The cDNAs of the present invention are characterized by containing either of the base sequences represented by SEQ ID NO:1 and SEQ ID NO:2 or the base sequences represented by SEQ ID NO:3 and SEQ ID NO:4. Table 1 summarizes the clone number (HP number), the cells affording the cDNA, the total base number of the cDNA, and the number of the amino acid residues of the encoded protein, for each of the cDNAs. TABLE 1 Number of Number of SEQ ID NO: 1 HP No. Cell Nucleotides amino acids 1, 3 HP00567 PMA-U937 3570 476 2, 4 HP00991 stomach cancer 819 185 Hereupon, the same clones as the cDNAs of the present invention can be easily obtained by screening of the cDNA libraries constructed from the human cell lines and human tissues utilized in the present invention by the use of an oligonucleotide probe synthesized on the basis of the cDNA base sequence described in either of SEQ ID NO:1 and SEQ ID NO:2. In general, the polymorphism due to the individual difference is frequently observed in human genes. Accordingly, any cDNA that is subjected to insertion or deletion of one or plural nucleotides and/or substitution with other nucleotides in SEQ ID NO:1 to SEQ ID NO:4 shall come within the scope of the present invention. The cDNAs of the present invention include cDNA fragments (more than 10 bp) containing any partial base sequence in the base sequences represented by SEQ ID NO:1 and SEQ ID NO:2 or in the base sequences represented by SEQ ID NO:3 and SEQ ID NO:4. Also, DNA fragments consisting of a sense chain and an anti-sense chain shall come within this scope. These DNA fragments can be utilized as the probes for the gene diagnosis. In the case in which one of the cDNAs of the present invention is expressed in eucaryotic cells, the cDNA of the present invention can be expressed as a transmembrane protein on the cell-membrane surface, when the translation region of said cDNA is subjected to recombination to an expression vector for eucaryotic cells that has a promoter, a splicing region, a poly (A) addition site, etc., followed by introduction into the eucaryotic cells. The expression vector is exemplified by pKA1, pED6pdc2, pCDM8, pSVK3, pMSG, pSVL, pBK-CMV, pBK-RSV, EBV vector, pRS, pYES2, and so on. Examples of eucaryotic cells to be used in general include mammalian culture cells such as simian kidney cells COS7, Chinese hamster ovary cells CHO, etc., budding yeasts, fission yeasts, silkworm cells, Xenopus laevis egg cells, and so on, but any eucaryotic cells may be used, provided that they are capable of expressing the present cDNAs on the membrane surface. The expression vector can be introduced in the eucaryotic cells by methods known in the art such as the electroporation method, the potassium phosphate method, the liposome method, the DEAE-dextran method, and so on. In addition to the activities and uses described above, the polynucleotides and proteins of the present invention may exhibit one or more of the uses or biological activities (including those associated with assays cited herein) identified below. Uses or activities described for proteins of the present invention may be provided by administration or use of such proteins or by administration or use of polynucleotides encoding such proteins (such as, for example, in gene therapies or vectors suitable for introduction of DNA). Research Uses and Utilities The polynucleotides provided by the present invention can be used by the research community for various purposes. The polynucleotides can be used to express recombinant protein for analysis, characterization or therapeutic use; as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in disease states); as molecular weight markers on Southern gels; as chromosome markers or tags (when labeled) to identify chromosomes or to map related gene positions; to compare with endogenous DNA sequences in patients to identify potential genetic disorders; as probes to hybridize and thus discover novel, related DNA sequences; as a source of information to derive PCR primers for genetic fingerprinting; as a probe to "subtract-out" known sequences in the process of discovering other novel polynucleotides; for selecting and making oligomers for attachment to a "gene chip" or other support, including for examination of expression patterns; to raise anti-protein antibodiesusing DNA immunization techniques; and as an antigen to raise anti-DNA antibodies or elicit another immune response. Where the polynucleotide encodes a protein which binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction), the polynucleotide can also be used in interaction trap assays (such as, for example, that described in Gyuris et al., Cell 75:791-803 (1993)) to identify polynucleotides encoding the other protein with which binding occurs or to identify inhibitors of the binding interaction. The proteins provided by the present invention can similarly be used in assay to determine biological activity, including in a panel of multiple proteins for high-throughput screening; to raise antibodies or to elicit another immune response; as a reagent (including the labeled reagent) in assays designed to quantitatively determine levels of the protein (or its receptor) in biological fluids; as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in a disease state); and, of course, to isolate correlative receptors or ligands. Where the protein binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction), the protein can be used to identify the other protein with which binding occurs or to identify inhibitors of the binding interaction. Proteins involved in these binding interactions can also be used to screen for peptide or small molecule inhibitors or agonists of the binding interaction. Any or all of these research utilities are capable of being developed into reagent grade or kit format for commercialization as research products. Methods for performing the uses listed above are well known to those skilled in the art. References disclosing such methods include without limitation "Molecular Cloning: A Laboratory Manual", 2d ed., Cold Spring Harbor Laboratory Press, Sambrook, J., E. F. Fritsch and T. Maniatis eds., 1989, and "Methods in Enzymology: Guide to Molecular Cloning Techniques", Academic Press, Berger, S. L. and A. R. Kimmel eds., 1987. |
| PATENT EXAMPLES |
EXAMPLES The present invention is embodied in more detail by the following examples, but this embodiment is not intended to restrict the present invention. The basic operations and the enzyme reactions with regard to the DNA recombination are carried out according to the literature ["Molecular Cloning. A Laboratory Manual", Cold Spring Harbor Laboratory, 1989]. Unless otherwise stated, restrictive enzymes and a variety of modification enzymes to be used were those available from TAKARA SHUZO. The manufacturer's instructions were used for the buffer compositions as well as for the reaction conditions, in each of the enzyme reactions. The cDNA synthesis was carried out according to the literature [Kato, S. et al., Gene 150: 243-250 (1994)]. (1) Preparation of Poly(A).sup.+ RNA The histiocyte lymphoma cell line U937 (ATCC CRL 1593) stimulated by phorbol ester and tissues of stomach cancer delivered by the operation were used for human cells to extract mRNAs. The cell line was incubated by a conventional procedure. After about 1 g of the human cells was homogenized in 20 ml of a 5.5 M guanidinium thiocyanate solution, a total mRNA was prepared according to the literature [Okayama, H. et al., "Method in Enzymology", Vol. 164, Academic Press, 1987]. This was subjected to chromatography on oligo (dT)-cellulose column washed with a 20 mM Tris-hydrochloride buffer solution (pH 7.6), 0.5 M NaCl, and 1 mM EDTA to obtain a poly(A).sup.+ RNA according to the above-described literature. (2) Construction of cDNA Library Ten micrograms of the above-mentioned poly(A).sup.+ RNA were dissolved in a 100 mM Tris-hydrochloride buffer solution (pH 8), one unit of an RNase-free, bacterial alkaline phosphatase was added, and the reaction was run at 37.degree. C. for one hour. After the reaction solution was subjected to phenol extraction, followed by ethanol precipitation, the resulting pellet was dissolved in a solution containing 50 mM sodium acetate (pH 6), 1 mM EDTA, 0.1% 2-mercaptoethanol, and 0.01% Triton X-100. Thereto was added one unit of a tobacco-origin acid pyrophosphatase (Epicentre Technologies) and a total 100 .mu.l volume of the resulting mixture was reacted at 37.degree. C. for one hour. After the reaction solution was subjected to phenol extraction, followed by ethanol precipitation, the resulting pellet was dissolved in water to obtain a solution of a decapped poly(A).sup.+ RNA. The decapped poly(A).sup.+ RNA and 3 nmol of a chimeric DNA-RNA oligonucleotide (5'-dG-dG-dG-dG-dA-dA-dT-dT-dC-dG-dA-G-G-A-3') (SEQ ID NO:8) were dissolved in a solution containing 50 mM Tris-hydrochloride buffer solution (pH 7.5), 0.5 mM ATP, 5 mM MgCl.sub.2, 10 mM 2-mercaptoethanol, and 25% polyethylene glycol, whereto was added 50 units of T4RNA ligase and a total 30 .mu.l volume of the resulting mixture was reacted at 20.degree. C. for 12 hours. After the reaction solution was subjected to phenol extraction, followed by ethanol precipitation, the resulting pellet was dissolved in water to obtain a chimeric-oligo-capped poly(A).sup.+ RNA. After digestion of vector pKA1 (Japanese Patent Kokai Publication No. 1992-117292) developed by the present inventors With KpnI, about 60 dT tails were added using a terminal transferase. A vector primer to be used below was prepared by digestion of this product with EcoRV to remove a dT tail at one side. After 6 .mu.g of the previously-prepared chimeric-oligo-capped poly (A).sup.+ RNA was annealed with 1.2 .mu.g of the vector primer, the resulting product was dissolved in a solution containing 50 mM Tris-hydrochloride buffer solution (pH 8.3), 75 mM KCl, 3 mM MgCl.sub.2, 10 mM dithiothreitol, and 1.25 mM dNTP (dATP+dCTP+dGTP+dTTP), 200 units of a reverse transcriptase (GIBCO-BRL) were added, and the reaction in a total 20 .mu.l volume was run at 42.degree. C. for one hour. After the reaction solution was subjected to phenol extraction, followed by ethanol precipitation, the resulting pellet was dissolved in a solution containing 50 mM Tris-hydrochloride buffer solution (pH 7.5), 100 mM NaCl, 10 mM MgCl.sub.2, and 1 mM dithiothreitol. Thereto were added 100 units of EcoRI and a total 20 .mu.l volume of the resulting mixture was reacted at 37.degree. C. for one hour. After the reaction solution was subjected to phenol extraction, followed by ethanol precipitation, the resulting pellet was dissolved in a solution containing 20 mM Tris-hydrochloride buffer solution (pH7.5), 100 mM KCl, 4mM MgCl.sub.2, 10 mM (NH.sub.4).sub.2 SO.sub.4, and 50 .mu.g/ml of the bovine serum albumin. Thereto were added 60 units of an Escherichia coli DNA ligase and the resulting mixture was reacted at 16.degree. C. for 16 hours. To the reaction solution were added 2 .mu.l of 2 mM dNTP, 4 units of Escherichia coli DNA polymerase I, and 0.1 unit of Escherichia coli RNase H and the resulting mixture was reacted at 12.degree. C. for one hour and then at 22.degree. C. for one hour. Next, the cDNA-synthesis reaction solution was used for transformation of Escherichia coli DH12S (GIBCO-BRL). The transformation was carried out by the electroporation method. A portion of the transformant was sprayed on the 2.times.YT agar culture medium containing 100 .mu.g/ml ampicillin and the mixture was incubated at 37.degree. C. overnight. A colony formed on the agar medium was picked up at random and inoculated on 2 ml of the 2.times.YT culture medium containing 100 .mu.g/ml ampicillin. After incubation at 37.degree. C. overnight, the culture mixture was centrifuged to separate the mycelia, from which a plasmid DNA was prepared by the alkaline lysis method. The plasmid DNA was subjected to double digestion with EcoRI and NotI, followed by 0.8% agarose gel electrophoresis, to determine the size of the cDNA insert. Furthermore, using the thus-obtained plasmid as a template, the sequence reaction was carried out by using an M13 universal primer labeled with a fluorescent dye and a Taq polymerase (a kit of Applied Biosystems) and then the product was examined with a fluorescent DNA sequencer (Applied Biosystems) to determine an about 400-bp base sequence at the 5'-terminus of the cDNA. The sequence data were filed as the homo/protein cDNA bank database. (3) Selection of cDNAs Encoding Proteins Having Transmembrane Domains A base sequence registered in the homo/protein cDNA bank was converted to three frames of amino acid sequences and the presence or absence of an open reading frame (ORF) beginning from the initiation codon was examined. Then, the selection was made for the presence of a signal sequence that is characteristic to a secretory protein at the N-terminus of the portion encoded by the ORF. These clones were sequenced from the both 5' and 3' directions by the use of the deletion method using exonuclease III to determine the whole base sequence. The hydrophobicity/hydrophilicity profiles were obtained for proteins encoded by the ORF by the Kyte-Doolittle method [Kyte, J. & Doolittle, R. F., J. Mol. Biol. 157: 105-132 (1982)] to examine the presence or absence of a hydrophobic region. In the case in which there is a hydrophobic region of a putative transmembrane domain in the amino acid sequence of an encoded protein, this protein was judged as a membrane protein. (4) Protein Synthesis by In Vitro Translation The plasmid vector bearing the cDNA of the present invention was used for in vitro transcription/translation with a T.sub.N T rabbit reticulocyte lysate kit (Promega). In this case, [.sup.35 S]methionine was added to label the expression product with a radioisotope. Each of the reactions was carried out according to the protocols attached to the kit. Two micrograms of the plasmid was reacted at 30.degree. C. for 90 minutes in a total 25 .mu.l volume of the reaction solution containing 12.5 .mu.l of T.sub.N T rabbit reticulocyte lysate, 0.5 .mu.l of a buffer solution (attached to kit), 2 .mu.l of an amino acid mixture (methionine-free), 2 .mu.l of [.sup.35 S]methionine (Amersham) (0.37 MBq/.mu.l), 0.5 .mu.l of T7RNA polymerase, and 20 U of RNasin. To 3 .mu.l of the resulting reaction solution was added 2 .mu.l of the SDS sampling buffer (125mM Tris-hydrochloric acid buffer, pH 6.8, 120 mM 2-mercaptoethanol, 2% SDS solution, 0.025% bromophenol blue, and 20% glycerol) and the resulting mixture was heated at 95.degree. C. for 3 minutes and then subjected to SDS-polyacrylamide gel electrophoresis. The molecular weight of the translation product was determined by carrying out the autoradiograph. (5) Expression by COS7 After Escherichia coli (host: JM109) bearing the expression vector of the protein of the present invention was incubated at 37.degree. C. for 2 hours in 2 ml of the 2.times.YT culture medium containing 100 .mu.g/ml of ampicillin, the helper phage M13KO7 (50 .mu.l) was added and the incubation was continued at 37.degree. C. overnight. A supernatant separated by centrifugation underwent precipitation with polyethylene glycol to obtain single-stranded phage particles. These particles were suspended in 100 .mu.l of 1 mM Tris-0.1 mM EDTA, pH 8 (TE). Also, there were used as controls suspensions of single-stranded phage particles prepared in the same manner from pSSD3 and from the vector pKA1-UPA containing a full-length cDNA of urokinase [Yokoyama-Kobayashi, M. et al., Gene 163: 193-196 (1995)]. The culture cells originating from the simian kidney, COS7, were incubated at 37.degree. C. in the presence of 5% CO.sub.2 in the Dulbecco's modified Eagle's culture medium (DMEM) containing 10% fetal calf albumin. Into a 6-well plate (Nunc Inc., 3 cm in the well diameter) were inoculated 1.times.10.sup.5 COS7 cells and incubation was carried out at 37.degree. C. for 22 hours in the presence of 5% CO.sub.2. After the culture medium was removed, the cell surface was washed with a phosphate buffer solution and then washed again with DMEM containing 50 mM Tris-hydrochloric acid (pH 7.5) (TDMEM). To the resulting cells was added a suspension of 1 .mu.l of the single-stranded phage suspension, 0.6 ml of the DMEM culture medium, and 3 .mu.l of TRANSFECTAM.TM. (IBF Inc.) and the resulting mixture was incubated at 37.degree. C. for 3 hours in the presence of 5% CO.sub.2. After the sample solution was removed, the cell surface was washed with TDMEM, 2 ml per well of DMEM containing 10% fetal calf albumin was added, and the incubation was carried out at 37.degree. C. for 2 days in the presence of 5% CO.sub.2. Furthermore, after the incubation was continued for one hour in the culture medium containing [.sup.35 S] cystine or [.sup.35 S]methionine, the cells were collected, dissolved, and then subjected to SDS-PAGE, whereby there was observed the presence of a band corresponding to the expression product of each protein. For instance, HP00991 produced a band of 18 kDa on the membrane fraction. (6) Clone Examples Determination of the whole base sequence of the cDNA insert of clone HP00567 obtained from cDNA libraries of the human histiocyte lymphoma cell line U937 stimulated by phorbol ester revealed the structure consisting of a 119-bp 5'-nontranslation region, a 1431-bp ORF, and a 2020-bp 3'-nontranslation region. The ORF codes for a protein consisting of 476 amino acid residues and there existed at least nine transmembrane domains. FIG. 1 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in the observation that there was not any band corresponding to the molecular weight of 52,264 predicted from the ORF and a smear translation product of a high molecular weight was formed. The search of the protein data base by using the amino acid sequence of the present protein revealed that the protein was completely identical with the rat protein translocation protein Sec61 .alpha. subunit (SWISS-PROT Accession No. P38378). Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the presence of sequences that possessed a homology of 90% or more (for example, Accession No. AA301007) in EST, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention. The rat protein translocation protein Sec61 .alpha. subunit plays an important role in protein translocation across the endoplasmic reticulum membrane [Gorlich, D. et al., Cell 71: 489-503 (1992)]. Accordingly, the present protein is a human homologue of the rat protein translocation protein Sec61 .alpha. subunit. The present cDNAs can be utilized for the diagnosis and treatment of diseases that are associated with the function insufficiency of endoplasmic reticulum. Determination of the whole base sequence of the cDNA insert of clone HP00991 obtained from cDNA libraries of human stomach cancer revealed the structure consisting of a 65-bp 5'-nontranslation region, a 558-bp ORF, and a 196-bp 3'-nontranslation region. The ORF codes for a protein consisting of 185 amino acid residues and there existed four transmembrane domains. FIG. 2 depicts the hydrophobicity/hydrophilicity profile, obtained by the Kyte-Doolittle method, of the present protein. In vitro translation resulted in formation of a translation product of 21 kDa that was almost consistent with the molecular weight of 21,080 predicted from the ORF. The search of the protein data base by using the amino acid sequence of the present protein revealed that the protein was analogous to the rat translocon-associated protein .gamma. subunit (SWISS-PROT Accession No. Q08013). Table 2 shows the comparison of the amino acid sequence between the human protein of the present invention (HP) (SEQ ID NO:6) and the rat translocon-associated protein .gamma. subunit (RN) (SEQ ID NO:7). Therein, the marks of -, *, and . represent a gap, an amino acid residue identical with the protein of the present invention, and an amino acid residue analogous to the protein of the present invention, respectively. The both proteins possessed a homology of 98.4% in the entire region. TABLE 2 HP MAPKGSSKQQSEEDLLLQDFSRNLSAKSSALFFGNAFIVSAIPIWLYWRIWHMDLIQSAV *****.****************************************************** RN MAPKGGSKQQSEEDLLLQDFSRNLSAKSSALFFGNAFIVSAIPIWLYWRIWHMDLIQSAV HP LYSVMTLVSTYLVAFAYKNVKFVLKHKVAQKREDAVSKEVTRKLSEADNRKMSRKEKDER ************************************************************ RN LYSVMTLVSTYLVAFAYKNVKFVLKHKVAQKREDAVSKEVTRKLSEADNRKMSRKEKDER HP ILWKKNEVADYEATTTSIFYNNTLFLVVVIVASFFILKNFNPTVNYILSISASSGLIALL ***************************.************** ***************** RN ILWKKNEVADYEATTFSIFYNNTLFLVLVIVASFFILKNFNPRVNYILSISASSGLIALL HP STGSK ***** RN STGSK Furthermore, the search of the GenBank using the base sequences of the present cDNA has revealed the presence of sequences that possessed a homology of 90% or more (for example, Accession No. AA317439) in EST, but, since they are partial sequences, it can not be judged whether or not any of these sequences codes for the same protein as the protein of the present invention. The rat translocon-associated protein .gamma. subunit is one of the subunits of the complex that are associated with the localization of endoplasmic reticulum proteins [Hartmann, E. et al., Eur. J. Biochem. 214: 375-381 (1993)]. Accordingly, the present protein is considered to play an important role in the protein retention and folding in the endoplasmic reticulum. The present cDNAs can be utilized for the diagnosis and treatment of diseases that are associated with the function insufficiency of endoplasmic reticulum. INDUSTRIAL APPLICABILITY The present invention provides cDNAs coding for human proteins having transmembrane domains and eucaryotic cells expressing said cDNAs. The cDNAs of the present invention can be utilized as probes for the gene diagnosis and gene sources for the gene therapy. Furthermore, the cDNAs can be utilized for large-scale expression of said proteins. Cells, wherein these membrane protein genes are introduced and membrane proteins are expressed in large amounts, can be utilized for detection of the corresponding ligands, screening of novel low-molecular pharmaceuticals, and so on. The present invention also provides genes corresponding to the polynucleotide sequences disclosed herein. "Corresponding genes" are the regions of the genome that are transcribed to produce the mRNAs from which cDNA polynucleotide sequences are derived and may include contiguous regions of the genome necessary for the regulated expression of such genes. Corresponding genes may therefore include but are not limited to coding sequences, 5' and 3' untranslated regions, alternatively spliced exons, introns, promoters, enhancers, and silencer or suppressor elements. The corresponding genes can be isolated in accordance with known methods using the sequence information disclosed herein. Such methods include the preparation of probes or primers from the disclosed sequence information for identification and/or amplification of genes in appropriate genomic libraries or other sources of genomic materials. An "isolated gene" is a gene that has been separated from the adjacent coding sequences, if any, present in the genome of the organism from which the gene was isolated. Organisms that have enhanced, reduced, or modified expression of the gene(s) corresponding to the polynucleotide sequences disclosed herein are provided. The desired change in gene expression can be achieved through the use of antisense polynucleotides or ribozymes that bind and/or cleave the mRNA transcribed from the gene (Albert and Morris, 1994, Trends Pharmacol. Sci. 15(7): 250-254; Lavarosky et al., 1997, Biochem. Mol. Med. 62(1): 11-22; and Hampel, 1998, Prog. Nucleic Acid Res. Mol. Biol. 58: 1-39; all of which are incorporated by reference herein). Transgenic animals that have multiple copies of the gene(s) corresponding to the polynucleotide sequences disclosed herein, preferably produced by transformation of cells with genetic constructs that are stably maintained within the transformed cells and their progeny, are provided. Transgenic animals that have modified genetic control regions that increase or reduce gene expression levels, or that change temporal or spatial patterns of gene expression, are also provided (see European Patent No. 0 649 464 B1, incorporated by reference herein). In addition, organisms are provided in which the gene(s) corresponding to the polynucleotide sequences disclosed herein have been partially or completely inactivated, through insertion of extraneous sequences into the corresponding gene(s) or through deletion of all or part of the corresponding gene(s). Partial or complete gene inactivation can be accomplished through insertion, preferably followed by imprecise excision, of transposable elements (Plasterk, 1992, Bioessays 14 (9): 629-633; Zwaal et al., 1993, Proc. Natl. Acad. Sci. USA 90(16): 7431-7435; Clark et al., 1994, Proc. Natl. Acad. Sci. USA 91(2): 719-722; all of which are incorporated by reference herein), or through homologous recombination, preferably detected by positive/negative genetic selection strategies (Mansour et al., 1988, Nature 336: 348-352; U.S. Pat. Nos. 5,464,764; 5,487,992; 5,627,059; 5,631,153; 5,614, 396; 5,616,491; and 5,679,523; all of which are incorporated by reference herein). These organisms with altered gene expression are preferably eukaryotes and more preferably are mammals. Such organisms are useful for the development of non-human models for the study of disorders involving the corresponding gene(s), and for the development of assay systems for the identification of molecules that interact with the protein product(s) of the corresponding gene(s). Where the protein of the present invention is membrane-bound (e.g., is a receptor), the present invention also provides for soluble forms of such protein. In such forms part or all of the intracellular and transmembrane domains of the protein are deleted such that the protein is fully secreted from the cell in which it is expressed. The intracellular and transmembrane domains of proteins of the invention can be identified in accordance with known techniques for determination of such domains from sequence information. Proteins and protein fragments of the present invention include proteins with amino acid sequence lengths that are at least 25% (more preferably at least 50%, and most preferably at least 75%) of the length of a disclosed protein and have at least 60% sequence identity (more preferably, at least 75% identity; most preferably at least 90% or 95% identity) with that disclosed protein, where sequence identity is determined by comparing the amino acid sequences of the proteins when aligned so as to maximize overlap and identity while minimizing sequence gaps. Also included in the present invention are proteins and protein fragments that contain a segment preferably comprising 8 or more (more preferably 20 or more, most preferably 30 or more) contiguous amino acids that shares at least 75% sequence identity (more preferably, at least 85% identity; most preferably at least 95% identity) with any such segment of any of the disclosed proteins. Species homologs of the disclosed polynucleotides and proteins are also provided by the present invention. As used herein, a "species homologue" is a protein or polynucleotide with a different species of origin from that of a given protein or polynucleotide, but with significant sequence similarity to the given protein or polynucleotide, as determined by those of skill in the art. Species homologs may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source from the desired species. The invention also encompasses allelic variants of the disclosed polynucleotides or proteins; that is, naturally-occurring alternative forms of the isolated polynucleotide which also encode proteins which are identical, homologous, or related to that encoded by the polynucleotides. The invention also includes polynucleotides with sequences complementary to those of the polynucleotides disclosed herein. The present invention also includes polynucleotides capable of hybridizing under reduced stringency conditions, more preferably stringent conditions, and most preferably highly stringent conditions, to polynucleotides described herein. Examples of stringency conditions are shown in the table below: highly stringent conditions are those that are at least as stringent as, for example, conditions A-F; stringent conditions are at least as stringent as, for example, conditions G-L; and reduced stringency conditions are at least as stringent as, for example, conditions M-R. TABLE 3 Hybrid Wash Stringency Polynucleotide Length Hybridization Temperature Temperature Condition Hybrid (bp).sup..dagger-dbl. and Buffer.sup..dagger. and Buffer.sup..dagger. A DNA : DNA .gtoreq.50 65.degree. C.; 1 .times. SSC -or- 65.degree. C.; 0.3 .times. SSC 42.degree. C.; 1 .times. SSC, 50% formamide B DNA : DNA <50 T.sub.B *; 1 .times. SSC T.sub.B *; 1 .times. SSC C DNA : RNA .gtoreq.50 67.degree. C.; 1 .times. SSC -or- 67.degree. C.; 0.3 .times. SSC 45.degree. C.; 1 .times. SSC, 50% formamide D DNA : RNA <50 T.sub.D *; 1 .times. SSC T.sub.D *; 1 .times. SSC E RNA : RNA .gtoreq.50 70.degree. C.; 1 .times. SSC -or- 70.degree. C.; 0.3 .times. SSC 50.degree. C.; 1 .times. SSC, 50% formamide F RNA : RNA <50 T.sub.F *; 1 .times. SSC T.sub.F *; 1 .times. SSC G DNA : DNA .gtoreq.50 65.degree. C.; 4 .times. SSC -or- 65.degree. C.; 1 .times. SSC 42.degree. C.; 4 .times. SSC, 50% formamide H DNA : DNA <50 T.sub.H *; 4 .times. SSC T.sub.H *; 4 .times. SSC I DNA : RNA .gtoreq.50 67.degree. C.; 4 .times. SSC -or- 67.degree. C.; 1 .times. SSC 45.degree. C.; 4 .times. SSC, 50% formamide J DNA : RNA <50 T.sub.J *; 4 .times. SSC T.sub.J *; 4 .times. SSC K RNA : RNA .gtoreq.50 70.degree. C.; 4 .times. SSC -or- 67.degree. C.; 1 .times. SSC 50.degree. C.; 4 .times. SSC, 50% formamide L RNA : RNA <50 T.sub.L *; 2 .times. SSC T.sub.L *; 2 .times. SSC M DNA : DNA .gtoreq.50 50.degree. C.; 4 .times. SSC -or- 50.degree. C.; 2 .times. SSC 40.degree. C.; 6 .times. SSC, 50% formamide N DNA : DNA <50 T.sub.N *; 6 .times. SSC T.sub.N *; 6 .times. SSC O DNA : RNA .gtoreq.50 55.degree. C.; 4 .times. SSC -or- 55.degree. C.; 2 .times. SSC 42.degree. C.; 6 .times. SSC, 50% formamide P DNA : RNA <50 T.sub.P *; 6 .times. SSC T.sub.P *; 6 .times. SSC Q RNA : RNA .gtoreq.50 60.degree. C.; 4 .times. SSC -or- 60.degree. C.; 2 .times. SSC 45.degree. C.; 6 .times. SSC, 50% formamide R RNA : RNA <50 T.sub.R *; 4 .times. SSC T.sub.R *; 4 .times. SSC .dagger-dbl.The hybrid length is that anticipated for the hybridized region(s) of the hybridizing polynucleotides. When hybridizing a polynucleotide to a target polynucleotide of unknown sequence, the hybrid length is assumed to be that of the hybridizing polynucleotide. When polynucleotides of known sequence are hybridized, the hybrid length can be determined by aligning the sequences of the polynucleotides and identifying the region or # regions of optimal sequence complementarity. .dagger.SSPE (1 .times. SSPE is 0.15 M NaCl, 10 mM NaH.sub.2 PO.sub.4, and 1.25 mM EDTA, pH 7.4) can be substituted for SSC (1 .times. SSC is 0.15 M NaCl and 15 mM sodium citrate) in the hybridization and wash buffers; washes are performed for 15 minutes after hybridization is complete. *T.sub.B -T.sub.R : The hybridization temperature for hybrids anticipated to be less than 50 base pairs in length should be 5-10.degree. C. less than the melting temperature (T.sub.m) of the hybrid, where T.sub.m, is determined according to the following equations. For hybrids less than 18 base pairs in length, T.sub.m (.degree. C.) = 2(#of A + T bases) + 4(# of G + C bases). For hybrids between # 18 and 49 base pairs in length, T.sub.m (C) = 81.5 + 16.6(log.sub.10 [Na.sup.+ ]) + 0.41 (%G + C) - (600/N), where N is the number of bases in the hybrid, and [Na.sup.+ ] is the concentration of sodium ions in the hybridization buffer ([Na.sup.+ ] for 1 .times. SSC = 0.165 M). Additional examples of stringency conditions for polynucleotide hybridization are provided in Sambrook, J., E. F. Fritsch, and T. Maniatis, 1989, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., chapters 9 and 11, and Current Protocols in Molecular Biology, 1995, F. M. Ausubel et al., eds., John Wiley & Sons, Inc., sections 2.10 and 6.3-6.4, incorporated herein by reference. Preferably, each such hybridizing polynucleotide has a length that is at least 25% (more preferably at least 50%, and most preferably at least 75%) of the length of the polynucleotide of the present invention to which it hybridizes, and has at least 60% sequence identity (more preferably, at least 75% identity; most preferably at least 90% or 95% identity) with the polynucleotide of the present invention to which it hybridizes, where sequence identity is determined by comparing the sequences of the hybridizing polynucleotides when aligned so as to maximize overlap and identity while minimizing sequence gaps. SEQUENCE LISTING <100> GENERAL INFORMATION: <160> NUMBER OF SEQ ID NOS: 8 <200> SEQUENCE CHARACTERISTICS: <210> SEQ ID NO 1 <211> LENGTH: 1428 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 1 atggcaatca aatttctgga agtcatcaag cccttctgtg tcatcctgcc ggaaattcag 60 aagccagaga ggaagattca gtttaaggag aaagtgctgt ggaccgctat caccctcttt 120 atcttcttag tgtgctgcca gattcccctg tttgggatca tgtcttcaga ttcagctgac 180 cctttctatt ggatgagagt gattctagcc tctaacagag gcacattgat ggagctaggg 240 atctctccta ttgtcacgtc tggccttata atgcaactct tggctggcgc caagataatt 300 gaagttggtg acaccccaaa agaccgagct ctcttcaacg gagcccaaaa gttatttggc 360 atgatcatta ctatcggcca gtctatcgtg tatgtgatga ccgggatgta tggggaccct 420 tctgaaatgg gtgctggaat ttgcctgcta atcaccattc agctctttgt tgctggctta 480 attgtcctac ttttggatga actcctgcaa aaaggatatg gccttggctc tggtatttct 540 ctcttcattg caactaacat ctgtgaaacc atcgtatgga aggcattcag ccccactact 600 gtcaacactg gccgaggaat ggaatttgaa ggtgctatca tcgcactttt ccatctgctg 660 gccacacgca cagacaaggt ccgagccctt cgggaggcgt tctaccgcca gaatcttccc 720 aacctcatga atctcatcgc caccatcttt gtctttgcag tggtcatcta tttccagggc 780 ttccgagtgg acctgccaat caagtcggcc cgctaccgtg gccagtacaa cacctatccc 840 atcaagctct tctatacgtc caacatcccc atcatcctgc agtctgccct ggtgtccaac 900 ctttatgtca tctcccaaat gctctcagct cgcttcagtg gcaacttgct ggtcagcctg 960 ctgggcacct ggtcggacac gtcttctggg ggcccagcac gtgcttatcc agttggtggc 1020 ctttgctatt acctgtcccc tccagaatct tttggctccg tgttagaaga cccggtccat 1080 gcagttgtat acatagtgtt catgctgggc tcctgtgcat tcttctccaa aacgtggatt 1140 gaggtctcag gttcctctgc caaagatgtt gcaaagcagc tgaaggagca gcagatggtg 1200 atgagaggcc accgagagac ctccatggtc catgaactca accggtacat ccccacagcc 1260 gcggcctttg gtgggctgtg catcggggcc ctctcggtcc tggctgactt cctaggcgcc 1320 attgggtctg gaaccgggat cctgctcgca gtcacaatca tctaccagta ctttgagatc 1380 ttcgttaagg agcaaagcga ggttggcagc atgggggccc tgctcttc 1428 <200> SEQUENCE CHARACTERISTICS: <210> SEQ ID NO 2 <211> LENGTH: 555 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 2 atggctccta aaggcagctc caaacagcag tctgaggagg acctgctcct gcaggatttc 60 agccgcaatc tctcggccaa gtcctccgcg ctcttcttcg gaaacgcgtt catcgtgtct 120 gccatcccca tctggttata ctggcgaata tggcatatgg atcttattca gtctgctgtt 180 ttgtatagtg tgatgaccct agtaagcaca tatttggtag cctttgcata caagaatgtg 240 aaatttgttc tcaagcacaa agtagcacag aagagggagg atgctgtttc caaagaagtg 300 actcgaaaac tttctgaagc tgataataga aagatgtctc ggaaggagaa agatgaaaga 360 atcttgtgga agaagaatga agttgctgat tatgaagcta caacattttc catcttctat 420 aacaacactc tgttcctggt cgtggtcatt gttgcttcct tcttcatatt gaagaacttc 480 aaccccacag tgaactacat attgtccata agtgcttcat caggactcat cgccctcctg 540 tctactggct ccaaa 555 <200> SEQUENCE CHARACTERISTICS: <210> SEQ ID NO 3 <211> LENGTH: 3570 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (120)..(1547) <223> OTHER INFORMATION: At position 3120, n = any nucleotide <400> SEQUENCE: 3 actgacgtgt ctctcggcgg agctgctgtg cagtggaacg cgctgggccg cgggcagcgt 60 cgcctcacgc ggagcagagc tgagctgaag cgggacccgg agcccgagca gccgccgcc 119 atg gca atc aaa ttt ctg gaa gtc atc aag ccc ttc tgt gtc atc ctg 167 Met Ala Ile Lys Phe Leu Glu Val Ile Lys Pro Phe Cys Val Ile Leu 1 5 10 15 ccg gaa att cag aag cca gag agg aag att cag ttt aag gag aaa gtg 215 Pro Glu Ile Gln Lys Pro Glu Arg Lys Ile Gln Phe Lys Glu Lys Val 20 25 30 ctg tgg acc gct atc acc ctc ttt atc ttc tta gtg tgc tgc cag att 263 Leu Trp Thr Ala Ile Thr Leu Phe Ile Phe Leu Val Cys Cys Gln Ile 35 40 45 ccc ctg ttt ggg atc atg tct tca gat tca gct gac cct ttc tat tgg 311 Pro Leu Phe Gly Ile Met Ser Ser Asp Ser Ala Asp Pro Phe Tyr Trp 50 55 60 atg aga gtg att cta gcc tct aac aga ggc aca ttg atg gag cta ggg 359 Met Arg Val Ile Leu Ala Ser Asn Arg Gly Thr Leu Met Glu Leu Gly 65 70 75 80 atc tct cct att gtc acg tct ggc ctt ata atg caa ctc ttg gct ggc 407 Ile Ser Pro Ile Val Thr Ser Gly Leu Ile Met Gln Leu Leu Ala Gly 85 90 95 gcc aag ata att gaa gtt ggt gac acc cca aaa gac cga gct ctc ttc 455 Ala Lys Ile Ile Glu Val Gly Asp Thr Pro Lys Asp Arg Ala Leu Phe 100 105 110 aac gga gcc caa aag tta ttt ggc atg atc att act atc ggc cag tct 503 Asn Gly Ala Gln Lys Leu Phe Gly Met Ile Ile Thr Ile Gly Gln Ser 115 120 125 atc gtg tat gtg atg acc ggg atg tat ggg gac cct tct gaa atg ggt 551 Ile Val Tyr Val Met Thr Gly Met Tyr Gly Asp Pro Ser Glu Met Gly 130 135 140 gct gga att tgc ctg cta atc acc att cag ctc ttt gtt gct ggc tta 599 Ala Gly Ile Cys Leu Leu Ile Thr Ile Gln Leu Phe Val Ala Gly Leu 145 150 155 160 att gtc cta ctt ttg gat gaa ctc ctg caa aaa gga tat ggc ctt ggc 647 Ile Val Leu Leu Leu Asp Glu Leu Leu Gln Lys Gly Tyr Gly Leu Gly 165 170 175 tct ggt att tct ctc ttc att gca act aac atc tgt gaa acc atc gta 695 Ser Gly Ile Ser Leu Phe Ile Ala Thr Asn Ile Cys Glu Thr Ile Val 180 185 190 tgg aag gca ttc agc ccc act act gtc aac act ggc cga gga atg gaa 743 Trp Lys Ala Phe Ser Pro Thr Thr Val Asn Thr Gly Arg Gly Met Glu 195 200 205 ttt gaa ggt gct atc atc gca ctt ttc cat ctg ctg gcc aca cgc aca 791 Phe Glu Gly Ala Ile Ile Ala Leu Phe His Leu Leu Ala Thr Arg Thr 210 215 220 gac aag gtc cga gcc ctt cgg gag gcg ttc tac cgc cag aat ctt ccc 839 Asp Lys Val Arg Ala Leu Arg Glu Ala Phe Tyr Arg Gln Asn Leu Pro 225 230 235 240 aac ctc atg aat ctc atc gcc acc atc ttt gtc ttt gca gtg gtc atc 887 Asn Leu Met Asn Leu Ile Ala Thr Ile Phe Val Phe Ala Val Val Ile 245 250 255 tat ttc cag ggc ttc cga gtg gac ctg cca atc aag tcg gcc cgc tac 935 Tyr Phe Gln Gly Phe Arg Val Asp Leu Pro Ile Lys Ser Ala Arg Tyr 260 265 270 cgt ggc cag tac aac acc tat ccc atc aag ctc ttc tat acg tcc aac 983 Arg Gly Gln Tyr Asn Thr Tyr Pro Ile Lys Leu Phe Tyr Thr Ser Asn 275 280 285 atc ccc atc atc ctg cag tct gcc ctg gtg tcc aac ctt tat gtc atc 1031 Ile Pro Ile Ile Leu Gln Ser Ala Leu Val Ser Asn Leu Tyr Val Ile 290 295 300 tcc caa atg ctc tca gct cgc ttc agt ggc aac ttg ctg gtc agc ctg 1079 Ser Gln Met Leu Ser Ala Arg Phe Ser Gly Asn Leu Leu Val Ser Leu 305 310 315 320 ctg ggc acc tgg tcg gac acg tct tct ggg ggc cca gca cgt gct tat 1127 Leu Gly Thr Trp Ser Asp Thr Ser Ser Gly Gly Pro Ala Arg Ala Tyr 325 330 335 cca gtt ggt ggc ctt tgc tat tac ctg tcc cct cca gaa tct ttt ggc 1175 Pro Val Gly Gly Leu Cys Tyr Tyr Leu Ser Pro Pro Glu Ser Phe Gly 340 345 350 tcc gtg tta gaa gac ccg gtc cat gca gtt gta tac ata gtg ttc atg 1223 Ser Val Leu Glu Asp Pro Val His Ala Val Val Tyr Ile Val Phe Met 355 360 365 ctg ggc tcc tgt gca ttc ttc tcc aaa acg tgg att gag gtc tca ggt 1271 Leu Gly Ser Cys Ala Phe Phe Ser Lys Thr Trp Ile Glu Val Ser Gly 370 375 380 tcc tct gcc aaa gat gtt gca aag cag ctg aag gag cag cag atg gtg 1319 Ser Ser Ala Lys Asp Val Ala Lys Gln Leu Lys Glu Gln Gln Met Val 385 390 395 400 atg aga ggc cac cga gag acc tcc atg gtc cat gaa ctc aac cgg tac 1367 Met Arg Gly His Arg Glu Thr Ser Met Val His Glu Leu Asn Arg Tyr 405 410 415 atc ccc aca gcc gcg gcc ttt ggt ggg ctg tgc atc ggg gcc ctc tcg 1415 Ile Pro Thr Ala Ala Ala Phe Gly Gly Leu Cys Ile Gly Ala Leu Ser 420 425 430 gtc ctg gct gac ttc cta ggc gcc att ggg tct gga acc ggg atc ctg 1463 Val Leu Ala Asp Phe Leu Gly Ala Ile Gly Ser Gly Thr Gly Ile Leu 435 440 445 ctc gca gtc aca atc atc tac cag tac ttt gag atc ttc gtt aag gag 1511 Leu Ala Val Thr Ile Ile Tyr Gln Tyr Phe Glu Ile Phe Val Lys Glu 450 455 460 caa agc gag gtt ggc agc atg ggg gcc ctg ctc ttc tgagcccgtc 1557 Gln Ser Glu Val Gly Ser Met Gly Ala Leu Leu Phe 465 470 475 tcccggacag gttgaggaag ctgctccaga agcgcctcgg aaggggagct ctcatcatgg 1617 cgcgtgctgc tgcggcatat ggacttttaa taatgttttt gaatttcgta ttctttcatt 1677 ccactgtgta aagtgctaga cattttccaa tttaaaattt tgctttttat cctggcactg 1737 gcaaaaagaa ctgtgaaagt gaaattttat tcagccgact gccagagaag tgggaatggt 1797 ataggattgt ccccaagtgt ccatgtaact tttgttttaa cctttgcacc ttctcagtgc 1857 tgtatgcggc tgcagccgtc tcacctgttt ccccacaaag ggaatttctc actctggttg 1917 gaagcacaaa cactgaaatg tctacgtttc attttggcag tagggtgtga agctgggagc 1977 agatcatgta tttcccggag acgtgggacc ttgctggcat gtctccttca caatcaggcg 2037 tgggaatatc tggcttagga ctgtttctct ctaagacacc attgttttcc cttattttaa 2097 aagtgatttt tttaaggaca gaacttcttc caaaagagag ggatggcttt cccagaagac 2157 actcctggcc atctgtggat ttgtctgtgc acctattggc tcttctagct gactcttctg 2217 gttgggctta gagtctgcct gtttctgcta gctccgtgtt tagtccactt gggtcatcag 2277 ctctgccaag ctgagcctgg ccaagctagg tggacagacc cttgcagtga tgtccgtttg 2337 tccagattct gccagtcatc actggacacg tctcctcgca gctgccctag caaggggaga 2397 cattgtggta gctatcagac atggacagaa actgacttag tgctcacaag cccctacacc 2457 ttctgggctg aagatcaccc agctgtgttc agaattttct tactgtgctt aggactgcac 2517 gcaagtgagc agacaccacc gacttccttt ctgcgtcacc agtgtcgtca gcagagagag 2577 gacagcacag gctcaaggtt ggtagtgaag tcaggttcgg ggtgcatggg ctgtggtggt 2637 gttgatcagt tgctccagtg tttgaaataa gaagactcat gtttatgtct ggaataagtt 2697 ctgtttgtgc tgacaggtgg cctaggtcct ggagatgagc accctctctc tggcctttag 2757 ggagtcccct cttaggacag gcactgccca gcagcaaggg cagcagagtt gggtgctaag 2817 atcctgagga gctcgaggtt tcgagctggc tttagacatt ggtgggacca aggatgtttt 2877 gcaggatgcc ctgatcctaa gaagggggcc tgggggtgcg tgcagcctgt cggggagacc 2937 ccactctgac agtgggcaca cggcagcctg caaagcacag ggccaccgcc acagcccggc 2997 agaggggcac actctggaga ccttgctggc agtgctagcc aggaaacaga gtgaccaagg 3057 gacaagaagg gacttgccta aagccaccca gcaactcagc agcagaacca agatgggccc 3117 agngctcctc catatggccc agggcttacc accctatcac acgtggcctt gtctagaccc 3177 agtcctgagc aggggagagg ctcttgagac ctgatgccct cctacccaca tggttctccc 3237 actgccctgt ctgctctgct gctacagagg ggcagggcct cccccagccc acgcttagga 3297 atgcttggcc tctggcaggc aggcagctgt acccaagctg gtgggcaggg ggctggaagg 3357 caccaggcct caggaggagc cccatagtcc cgcctgcagc ctgtaaccat cggctgggcc 3417 ctgcaaggcc cacactcacg ccctgtgggt gatggtcacg gtgggtgggt gggggctgac 3477 cccagcttcc aggggactgt cactgtggac gccaaaatgg cataactgag ataaggtgaa 3537 taagtgacaa ataaagccag ttttttacaa ggt 3570 <200> SEQUENCE CHARACTERISTICS: <210> SEQ ID NO 4 <211> LENGTH: 476 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 4 Met Ala Ile Lys Phe Leu Glu Val Ile Lys Pro Phe Cys Val Ile Leu 1 5 10 15 Pro Glu Ile Gln Lys Pro Glu Arg Lys Ile Gln Phe Lys Glu Lys Val 20 25 30 Leu Trp Thr Ala Ile Thr Leu Phe Ile Phe Leu Val Cys Cys Gln Ile 35 40 45 Pro Leu Phe Gly Ile Met Ser Ser Asp Ser Ala Asp Pro Phe Tyr Trp 50 55 60 Met Arg Val Ile Leu Ala Ser Asn Arg Gly Thr Leu Met Glu Leu Gly 65 70 75 80 Ile Ser Pro Ile Val Thr Ser Gly Leu Ile Met Gln Leu Leu Ala Gly 85 90 95 Ala Lys Ile Ile Glu Val Gly Asp Thr Pro Lys Asp Arg Ala Leu Phe 100 105 110 Asn Gly Ala Gln Lys Leu Phe Gly Met Ile Ile Thr Ile Gly Gln Ser 115 120 125 Ile Val Tyr Val Met Thr Gly Met Tyr Gly Asp Pro Ser Glu Met Gly 130 135 140 Ala Gly Ile Cys Leu Leu Ile Thr Ile Gln Leu Phe Val Ala Gly Leu 145 150 155 160 Ile Val Leu Leu Leu Asp Glu Leu Leu Gln Lys Gly Tyr Gly Leu Gly 165 170 175 Ser Gly Ile Ser Leu Phe Ile Ala Thr Asn Ile Cys Glu Thr Ile Val 180 185 190 Trp Lys Ala Phe Ser Pro Thr Thr Val Asn Thr Gly Arg Gly Met Glu 195 200 205 Phe Glu Gly Ala Ile Ile Ala Leu Phe His Leu Leu Ala Thr Arg Thr 210 215 220 Asp Lys Val Arg Ala Leu Arg Glu Ala Phe Tyr Arg Gln Asn Leu Pro 225 230 235 240 Asn Leu Met Asn Leu Ile Ala Thr Ile Phe Val Phe Ala Val Val Ile 245 250 255 Tyr Phe Gln Gly Phe Arg Val Asp Leu Pro Ile Lys Ser Ala Arg Tyr 260 265 270 Arg Gly Gln Tyr Asn Thr Tyr Pro Ile Lys Leu Phe Tyr Thr Ser Asn 275 280 285 Ile Pro Ile Ile Leu Gln Ser Ala Leu Val Ser Asn Leu Tyr Val Ile 290 295 300 Ser Gln Met Leu Ser Ala Arg Phe Ser Gly Asn Leu Leu Val Ser Leu 305 310 315 320 Leu Gly Thr Trp Ser Asp Thr Ser Ser Gly Gly Pro Ala Arg Ala Tyr 325 330 335 Pro Val Gly Gly Leu Cys Tyr Tyr Leu Ser Pro Pro Glu Ser Phe Gly 340 345 350 Ser Val Leu Glu Asp Pro Val His Ala Val Val Tyr Ile Val Phe Met 355 360 365 Leu Gly Ser Cys Ala Phe Phe Ser Lys Thr Trp Ile Glu Val Ser Gly 370 375 380 Ser Ser Ala Lys Asp Val Ala Lys Gln Leu Lys Glu Gln Gln Met Val 385 390 395 400 Met Arg Gly His Arg Glu Thr Ser Met Val His Glu Leu Asn Arg Tyr 405 410 415 Ile Pro Thr Ala Ala Ala Phe Gly Gly Leu Cys Ile Gly Ala Leu Ser 420 425 430 Val Leu Ala Asp Phe Leu Gly Ala Ile Gly Ser Gly Thr Gly Ile Leu 435 440 445 Leu Ala Val Thr Ile Ile Tyr Gln Tyr Phe Glu Ile Phe Val Lys Glu 450 455 460 Gln Ser Glu Val Gly Ser Met Gly Ala Leu Leu Phe 465 470 475 <200> SEQUENCE CHARACTERISTICS: <210> SEQ ID NO 5 <211> LENGTH: 819 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: CDS <222> LOCATION: (66)..(620) <400> SEQUENCE: 5 gtcaagggcc tttgcccgcc ttggcggccg gctctacgtt ccctgttctc gcctgcagct 60 ccgcc atg gct cct aaa ggc agc tcc aaa cag cag tct gag gag gac ctg 110 Met Ala Pro Lys Gly Ser Ser Lys Gln Gln Ser Glu Glu Asp Leu 1 5 10 15 ctc ctg cag gat ttc agc cgc aat ctc tcg gcc aag tcc tcc gcg ctc 158 Leu Leu Gln Asp Phe Ser Arg Asn Leu Ser Ala Lys Ser Ser Ala Leu 20 25 30 ttc ttc gga aac gcg ttc atc gtg tct gcc atc ccc atc tgg tta tac 206 Phe Phe Gly Asn Ala Phe Ile Val Ser Ala Ile Pro Ile Trp Leu Tyr 35 40 45 tgg cga ata tgg cat atg gat ctt att cag tct gct gtt ttg tat agt 254 Trp Arg Ile Trp His Met Asp Leu Ile Gln Ser Ala Val Leu Tyr Ser 50 55 60 gtg atg acc cta gta agc aca tat ttg gta gcc ttt gca tac aag aat 302 Val Met Thr Leu Val Ser Thr Tyr Leu Val Ala Phe Ala Tyr Lys Asn 65 70 75 gtg aaa ttt gtt ctc aag cac aaa gta gca cag aag agg gag gat gct 350 Val Lys Phe Val Leu Lys His Lys Val Ala Gln Lys Arg Glu Asp Ala 80 85 90 95 gtt tcc aaa gaa gtg act cga aaa ctt tct gaa gct gat aat aga aag 398 Val Ser Lys Glu Val Thr Arg Lys Leu Ser Glu Ala Asp Asn Arg Lys 100 105 110 atg tct cgg aag gag aaa gat gaa aga atc ttg tgg aag aag aat gaa 446 Met Ser Arg Lys Glu Lys Asp Glu Arg Ile Leu Trp Lys Lys Asn Glu 115 120 125 gtt gct gat tat gaa gct aca aca ttt tcc atc ttc tat aac aac act 494 Val Ala Asp Tyr Glu Ala Thr Thr Phe Ser Ile Phe Tyr Asn Asn Thr 130 135 140 ctg ttc ctg gtc gtg gtc att gtt gct tcc ttc ttc ata ttg aag aac 542 Leu Phe Leu Val Val Val Ile Val Ala Ser Phe Phe Ile Leu Lys Asn 145 150 155 ttc aac ccc aca gtg aac tac ata ttg tcc ata agt gct tca tca gga 590 Phe Asn Pro Thr Val Asn Tyr Ile Leu Ser Ile Ser Ala Ser Ser Gly 160 165 170 175 ctc atc gcc ctc ctg tct act ggc tcc aaa tagaccatgt cagcttcacc 640 Leu Ile Ala Leu Leu Ser Thr Gly Ser Lys 180 185 ccctggcttt gtgtctatgg gtggcctgtg gtatatggaa aagtagcagg gtggtcaggg 700 tgggagacac aagatgtttt tatagtctag agcctttaaa aaacccagca gaatgtaatt 760 cagtatttgt ttattggctg ttttttgaca gattgttgaa attaaatgaa ttgaaaggg 819 <200> SEQUENCE CHARACTERISTICS: <210> SEQ ID NO 6 <211> LENGTH: 185 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 6 Met Ala Pro Lys Gly Ser Ser Lys Gln Gln Ser Glu Glu Asp Leu Leu 1 5 10 15 Leu Gln Asp Phe Ser Arg Asn Leu Ser Ala Lys Ser Ser Ala Leu Phe 20 25 30 Phe Gly Asn Ala Phe Ile Val Ser Ala Ile Pro Ile Trp Leu Tyr Trp 35 40 45 Arg Ile Trp His Met Asp Leu Ile Gln Ser Ala Val Leu Tyr Ser Val 50 55 60 Met Thr Leu Val Ser Thr Tyr Leu Val Ala Phe Ala Tyr Lys Asn Val 65 70 75 80 Lys Phe Val Leu Lys His Lys Val Ala Gln Lys Arg Glu Asp Ala Val 85 90 95 Ser Lys Glu Val Thr Arg Lys Leu Ser Glu Ala Asp Asn Arg Lys Met 100 105 110 Ser Arg Lys Glu Lys Asp Glu Arg Ile Leu Trp Lys Lys Asn Glu Val 115 120 125 Ala Asp Tyr Glu Ala Thr Thr Phe Ser Ile Phe Tyr Asn Asn Thr Leu 130 135 140 Phe Leu Val Val Val Ile Val Ala Ser Phe Phe Ile Leu Lys Asn Phe 145 150 155 160 Asn Pro Thr Val Asn Tyr Ile Leu Ser Ile Ser Ala Ser Ser Gly Leu 165 170 175 Ile Ala Leu Leu Ser Thr Gly Ser Lys 180 185 <200> SEQUENCE CHARACTERISTICS: <210> SEQ ID NO 7 <211> LENGTH: 185 <212> TYPE: PRT <213> ORGANISM: Rattus sp. <400> SEQUENCE: 7 Met Ala Pro Lys Gly Ser Ser Lys Gln Gln Ser Glu Glu Asp Leu Leu 1 5 10 15 Leu Gln Asp Phe Ser Arg Asn Leu Ser Ala Lys Ser Ser Ala Leu Phe 20 25 30 Phe Gly Asn Ala Phe Ile Val Ser Ala Ile Pro Ile Trp Leu Tyr Trp 35 40 45 Arg Ile Trp His Met Asp Leu Ile Gln Ser Ala Val Leu Tyr Ser Val 50 55 60 Met Thr Leu Val Ser Thr Tyr Leu Val Ala Phe Ala Tyr Lys Asn Val 65 70 75 80 Lys Phe Val Leu Lys His Lys Val Ala Gln Lys Arg Glu Asp Ala Val 85 90 95 Ser Lys Glu Val Thr Arg Lys Leu Ser Glu Ala Asp Asn Arg Lys Met 100 105 110 Ser Arg Lys Glu Lys Asp Glu Arg Ile Leu Trp Lys Lys Asn Glu Val 115 120 125 Ala Asp Tyr Glu Ala Thr Thr Phe Ser Ile Phe Tyr Asn Asn Thr Leu 130 135 140 Phe Leu Val Val Val Ile Val Ala Ser Phe Phe Ile Leu Lys Asn Phe 145 150 155 160 Asn Pro Thr Val Asn Tyr Ile Leu Ser Ile Ser Ala Ser Ser Gly Leu 165 170 175 Ile Ala Leu Leu Ser Thr Gly Ser Lys 180 185 <200> SEQUENCE CHARACTERISTICS: <210> SEQ ID NO 8 <211> LENGTH: 14 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence chimeric DNA-RNA oligonucleotide <400> SEQUENCE: 8 ggggaattcg agga 14 |
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