WO2002016548A2

WO2002016548A2 - Novel g protein-coupled receptor

Info

Publication number: WO2002016548A2
Application number: PCT/IB2001/001446
Authority: WO
Inventors: Tatsuya Haga; Shigeki Takeda; Shigeki Mitaku
Original assignee: Japan Science And Technology Corporation
Priority date: 2000-08-04
Filing date: 2001-07-30
Publication date: 2002-02-28
Also published as: WO2002016548A3; CA2418130A1; WO2002016548A8; JP2002112793A

Abstract

It is intended to provide a novel G protein-coupled receptor (GPCR) gene which makes it possible to find a signal transduction mechanism in vivo or to identify a novel drug-target protein and a method of totally searching for a GPCR protein on data base. Open reading frames (ORFs) consisting of from 250 to 1000 amino acid residues are extracted from human-origin genome data and ORFs originating in DNA repeated sequences, ORFs containing many indefinite amino acids and ORFs having a single amino acid at a ratio of 20% or more are excluded therefrom. Then ORFs containing 6 to 8 transmembrane domains are extracted by using SOSUI. Among the ORFs thus obtained, a gene homologous with a known GPCR gene (preferably a gene showing the highest homology with a GPCR gene or a GPCR-associated gene in homology searching) is searched for.

Description

Description New G protein-coupled receptor technology

The present invention provides a method for exhaustively searching a novel G protein-coupled receptor gene and a novel G protein-coupled receptor protein on a database, and a novel G protein-coupled receptor obtained by such a method. The present invention relates to a receptor gene and a novel G protein-coupled receptor, and a method for screening endogenous and exogenous ligands such as agonists or antagonists of the gene and protein. Background art

G protein-coupled receptor (GPCR) is a protein that exists on the cell membrane and receives various information from outside the cell. GPCRs form a superfamily with a common structure that penetrates the membrane seven times, each of which acts as a sensory sensor for light, smell, taste, hormones, neurotransmitters, and bioactive substances. , by binding to the extracellular ligand, such as local mediators, by changing the Konhome one Chillon these receptors, G i, G t, G s, G o, G q, G proteins such as G ₁₂ '( It is known that GTP-binding protein is activated to transmit signals into cells. In addition, extracellular ligands that regulate complex functions in cells and organs of various living organisms are used as pharmaceuticals that regulate biological functions, and 30% to 50% of currently used clinical drugs Is considered to be a ligand targeting R. Due to the recent development of gene cloning technology, many "〇 rphan GPCR" genes whose ligands have not been identified have been found. Functional elucidation is required, and cloning of such a novel GPCR gene is known to be useful for searching for a GPCR-specific ligand such as agonist-ian gonist. However, not all of the GPCR is disclosed.

On the other hand, SOSUI (http://sosui.proteome.bio.tuat.ac.jp/sosuiframe0.html) uses the hydrophobic parameter of each amino acid from the primary structure of the protein to utilize its transmembrane region. It is a program developed for anticipation. It has already been applied to the structure prediction of many known and unknown proteins, and has also been used to identify translation regions (ORFs) that encode membrane-bound proteins on genomic gene sequences. I have.

GPCRs and their endogenous ligands are expected to be applied to new therapeutic methods such as research on drugs that act on them and application of the gene and its mutants to gene therapy. In addition, the discovery of new in vivo signaling mechanisms and the identification of new drug target proteins can be expected through analysis of new GPCR genes. An object of the present invention is to provide a method for comprehensively searched novel GPCR genes and GPCR proteins can allow the identification of discoveries and new drug targets proteins vivo information transmitting mechanism on the database _c Disclosure of the invention

In order to solve the above problems, the present inventors have conducted a trial and error test to determine whether a GPCR gene can be exhaustively searched on a database.As a result, the GPCR has a structural feature of penetrating the membrane seven times. Utilizing the fact that many known GPCR genes do not have introns in the translation region (ORF: 0 pen Reading Frame), the translation region that can serve as a catcher of the GPCR gene is extracted from human genome information and analyzed by SOSUI. Was done. Ma In addition, undefined bases in the genomic sequence were translated into amino acids, which are most likely to be transmembrane regions among amino acids that could be translated into amino acids. In the analysis using SOSUI, the signal peptide of GPCR may be determined as a transmembrane region, and the seventh transmembrane region on the GPCR structure tends to have low hydrophobicity. There is a possibility that the region cannot be determined as a through region. Taking these facts into consideration, ORFs predicted to contain 6 to 8 transmembrane regions are finally selected as GPCR candidates, and these candidate genes are examined for homology with known GPCR genes As a result, they have found that a novel GPCR gene can be identified, and have completed the present invention.

That is, the present invention extracts an open reading frame consisting of 200 to 150 amino acid residues and containing 6 to 8 transmembrane regions from human-derived genomic information. A method for searching for a G protein-coupled receptor gene and a Z or G protein-coupled receptor protein, wherein a gene having homology with a known G protein-coupled receptor gene is searched from the reading frame. (1) When extracting an open reading frame, an open reading frame derived from the repeating sequence of DNA, an open reading frame containing many undefined amino acids, and an open reading frame containing more than 20% of the same amino acids 2. The G protein-coupled receptor gene and / or the G protein-coupled receptor protein according to claim 1, wherein 2. The method of claim 1, wherein the gene having homology with a known G protein-coupled receptor gene is a G protein-coupled receptor gene or a G protein-coupled receptor-related gene. Or the method for retrieving the G protein-coupled receptor gene and the G protein-coupled receptor protein according to (2) or (3), wherein the G protein-coupled receptor has an endogenous ligand. Any one of ~ 3 A method for searching for a G protein-coupled receptor gene and / or a G protein-coupled receptor protein (Claim 4), and a G protein-coupled receptor having an endogenous ligand is a G protein other than an olfactory receptor and a taste receptor. The method for retrieving a G protein-coupled receptor gene and / or a G protein-coupled receptor protein according to claim 4, which is a coupled receptor (claim 5), or a G protein-coupled receptor having an endogenous ligand. The method for retrieving a G protein-coupled receptor gene and a Z or G protein-coupled receptor protein according to claim 4, wherein the body is a G protein-coupled receptor of an olfactory receptor. 5. The G protein-coupled receptor gene and the Z or G protein-coupled receptor protein according to claim 4, wherein the G protein-coupled receptor having an endogenous ligand is a G protein-coupled receptor of a taste receptor. Search method Regarding claim 7).

The present invention also provides a G protein-coupled receptor gene obtained by the method for searching for a G protein-coupled receptor gene and a Z or G protein-coupled receptor protein according to any one of claims 1 to 7. (Claim 8) or the following gene encoding the G protein-coupled receptor protein of (a) or (b) (a) SEQ ID NO: 2 n (n is any integer from 1 to 51) G protein-coupled receptor protein consisting of the amino acid sequence shown in (b) SEQ ID NO: 2 In the amino acid sequence shown in SEQ ID NO: 2 n (n is an integer from 1 to 51), one or more G protein-coupled receptor protein (Claim 9) consisting of an amino acid sequence in which two amino acids have been deleted, substituted or added, or SEQ ID NO: 2n_l (n = 1 to 51 Indicate an integer.) It hybridizes under stringent conditions to a DNA encoding a G protein-coupled receptor protein consisting of part or all of the DNA (claim 10) or to a DNA constituting the gene according to claim 10 under stringent conditions. And DNA encoding a G protein-coupled receptor protein (Claim 11) or a G protein of the following (a) or (b): Gene encoding a coupled receptor protein (a) G protein-coupled receptor protein (b) consisting of the amino acid sequence represented by SEQ ID NO: 2 n (n = any integer from 52 to 332) ) In the amino acid sequence represented by SEQ ID NO: 2n (n = any integer from 52 to 332), one or more amino acids are deleted, substituted, or added. Or a base sequence represented by SEQ ID NO: 2 n-1 (where n represents any integer from 52 to 322) or its complementary sequence A DNA encoding a G protein-coupled receptor protein consisting of a sequence and DNA containing a part or all of these sequences (claim 13); and a DNA that constitutes the gene according to claim 13 and stringent conditions. G-protein coupled receptor protein (A) or a gene encoding the following G protein-coupled receptor protein (a) or (b): (a) SEQ ID NO: 2 n (n = 33 to 3347 (B) an amino acid sequence represented by SEQ ID NO: 2 n (where n represents any integer from 33 to 34) A G protein-coupled receptor protein comprising an amino acid sequence in which one or several amino acids have been deleted, substituted or added (claim 15), or SEQ ID NO: 2 n-1 (n = 33 A DNA encoding a G protein-coupled receptor protein consisting of DNA containing a part or the whole of the base sequence represented by any one of the following: 6) and the DNA constituting the gene according to claim 16 and stringent conditions In High Priestess and soybean, and relates to DNA (claim 1 7) encoding the G protein-coupled receptor proteins.

The present invention also provides a G protein-coupled receptor gene and / or a G protein-coupled receptor protein obtained by the method according to any one of claims 1 to 7. And a G protein-coupled receptor protein (Claim 18) or a G protein-coupled protein comprising an amino acid sequence represented by SEQ ID NO: 2 n (where n represents any integer from 1 to 51) One or several amino acids are deleted or substituted in the receptor protein (claim 19) or the amino acid sequence shown in SEQ ID NO: 2 n (where n is an integer from 1 to 51) Alternatively, a G protein-coupled receptor protein comprising the added amino acid sequence (Claim 20) or the amino acid sequence represented by SEQ ID NO: 2 n (where n represents any integer from 52 to 32) In the G protein-coupled receptor protein (Claim 21) or the amino acid sequence represented by SEQ ID NO: 2 n (where n is an integer from 52 to 32), one or several G protein consisting of an amino acid sequence in which amino acids have been deleted, substituted or added Protein-coupled receptor protein (Claim 22), and a G protein-coupled receptor protein consisting of the amino acid sequence represented by SEQ ID NO: 2 n (n = any integer from 33 to 34) In the amino acid sequence shown in claim 23) or SEQ ID NO: 2 n (where n is an integer from 33 to 34), one or several amino acids are deleted or substituted. Or a G protein-coupled receptor protein comprising the added amino acid sequence (Claim 24); and a G protein-coupled receptor gene and Z or G protein-coupled receptor protein according to any one of Claims 1 to 7. The G protein-coupled receptor protein according to any one of claims 19 to 24, wherein a partial peptide of the G protein-coupled receptor protein (claim 25) or the G protein-coupled receptor protein obtained by the search method is the G protein-coupled receptor protein according to any one of claims 19 to 24. 25. The partial peptide according to claim 25, wherein 2 6) on.

Further, the present invention provides a fusion protein comprising a G protein-coupled receptor protein according to claim 18 or a partial peptide of the G protein-coupled receptor protein according to claim 25, and a marker protein and / or a peptide tag. Or the fusion peptide (Claim 27) or the G protein-coupled receptor protein, The fusion protein according to claim 27 (claim 28), which is a G protein-coupled receptor protein according to any one of the above, or the G protein-coupled receptor protein according to claim 18 An antibody (Claim 29) that binds specifically or a G protein-coupled receptor protein is the G protein shared receptor protein according to any one of Claims 19 to 24. 29. An antibody according to claim 29 (claim 30); a host cell comprising an expression system capable of expressing the G protein-coupled receptor protein according to claim 18 (claim 31); The host cell according to claim 31, wherein the receptor protein is the G protein-coupled receptor protein according to any one of claims 19 to 24 (claim 32), and claim 18, The function of the gene encoding the G protein-coupled receptor protein described above is defective on the chromosome, or the protein is A non-human animal characterized by overexpression (claim 33) or a G protein-coupled receptor protein is the G protein-coupled receptor protein according to any one of claims 19 to 24. The non-human animal according to claim 33 (claim 34) or the non-human animal according to claim 33 or 34, wherein the non-human animal is a mouse (claim 35) .

Further, the present invention provides a G protein-coupled receptor protein according to any one of claims 18 to 24, a partial peptide according to claims 25 or 26, or a cell expressing the protein or partial peptide. A method for screening a substance that promotes or suppresses the function of a G protein-coupled receptor or a substance that promotes or suppresses the expression of a G protein-coupled receptor, characterized by using a membrane and a test substance (Claim 36) And, a G protein-coupled receptor protein according to any one of claims 18 to 24, a partial peptide according to claim 25 or 26, or a membrane of a cell expressing the protein or partial peptide, A G protein-coupled receptor function-promoting or inhibiting substance or a G protein-coupled receptor characterized by using a G protein or a partial peptide of the G protein and a test substance. A screening method for an expression promoting or inhibiting substance (Claim 37), and a method for expressing a G protein-coupled receptor protein according to any one of Claims 18 to 24 or a partial peptide according to Claim 25 or 26. A method for screening a substance that promotes or suppresses the function of a G protein-coupled receptor or a substance that promotes or suppresses the expression of a G protein-coupled receptor, characterized by using a cell that is present and a test substance (Claim 38) Or a cell expressing the G protein-coupled receptor protein according to any one of claims 18 to 24 or the partial peptide according to claim 25 or 26, wherein the cell according to claim 31 or 32 is A method for screening a substance that promotes or suppresses the function of a G protein-coupled receptor or a substance that promotes or suppresses the expression of a G protein-coupled receptor according to any one of claims 36 to 38 (claim). 3 9 ) Or the non-human animal according to any one of claims 33 to 35, and a test substance, wherein the substance promotes or suppresses the function of a G protein-coupled receptor or the expression of a G protein-coupled receptor. The present invention relates to a method for screening a promoting or inhibiting substance (claim 40).

Further, the present invention provides a method for screening a G protein-coupled receptor function promoting or inhibiting substance or a G protein-coupled receptor expression promoting or inhibiting substance according to any one of claims 36 to 40. A substance that promotes or suppresses the function of a G protein-coupled receptor or a substance that promotes or suppresses the expression of a G protein-coupled receptor (Claim 41); 42. The substance for promoting or suppressing the function of a G protein-coupled receptor or the G protein-coupled receptor according to claim 41, wherein the substance for promoting or suppressing the expression of the protein-coupled receptor is a ligand for the G protein-coupled receptor. A pharmaceutical composition used to treat a patient in need of a substance that promotes or suppresses the expression of a G protein-coupled receptor (Claim 42), or that promotes the function or enhances the expression of a G protein-coupled receptor. Claims 18 to 2 as active ingredients A drug comprising the protein according to any one of claims 4, the partial peptide according to claim 25 or 26, or the substance that promotes the function or expression of the G protein-coupled receptor according to claim 41 or 42. A composition (Claim 43) or a pharmaceutical composition used for treating a patient in need of suppressing the function or expression of a G protein-coupled receptor, wherein the active ingredient is a pharmaceutical composition according to any one of Claims 18 to 2. A pharmaceutical composition comprising the protein according to any one of claims 4, the partial peptide according to claims 25 or 26, or the substance that suppresses the function or expression of the G protein-coupled receptor according to claim 41 or 42. (Claim 44).

Further, the present invention provides a G protein-coupled method comprising comparing a DNA sequence encoding a G protein-coupled receptor protein in a sample with a DNA sequence encoding a protein according to any one of claims 18 to 24. A method for diagnosing a disease associated with the function or expression of a receptor (Claim 45), or the whole or all of the antisense strand of DNA or RNA encoding the protein according to any one of Claims 18 to 24. A diagnostic probe for a disease associated with the function or expression of a G protein-coupled receptor comprising a part thereof (claim 46), the diagnostic probe of claim 46, and / or the diagnostic probe of claim 29 or 30. A diagnostic agent for a disease associated with the function or expression of a G protein-coupled receptor, which comprises an antibody (claim 47). BEST MODE FOR CARRYING OUT THE INVENTION

The method for searching for the GPCR gene and the Z or GPCR protein of the present invention includes an open source consisting of 200 to 150 amino acid residues from human-derived genomic information and containing 6 to 8 transmembrane regions. A gene having homology to a known GPCR gene, preferably a GPCR gene or a GPCR-related gene, particularly preferably a GPCR gene having an endogenous / external ligand is extracted from the obtained open reading frames. The method is not particularly limited as long as it is a method of searching for a gene that is a gene. Preferably, when extracting an open reading frame, an open reading frame or an uncertain It is desirable to exclude open reading frames containing many amino acids and open reading frames containing 20% or more of the same amino acid. In order to extract the open reading frame containing 6 to 8 transmembrane domains, for example, using the hydrophobic parameters for each amino acid from the primary structure of the protein as described above, it is necessary to predict the transmembrane domain. A developed program such as SOSUI can be used. In addition, a known homology search system such as BLAST can be used to search for a homologous gene.

The GPCR gene of the present invention may be any GPCR gene as long as it is a GPCR gene obtained by the above homology search.For example, SEQ ID NO: 2 n (n is an integer from 1 to 51 ) Genes encoding GPCR proteins other than the olfactory receptor and taste receptor consisting of the amino acid sequence shown in (1) and SEQ ID NO: 2n (n is an integer from 52 to 332) A gene encoding the GPCR protein of the olfactory receptor consisting of the amino acid sequence shown in SEQ ID NO: 2; One or several amino acids are deleted or substituted in the gene encoding the GPCR protein of the taste receptor or in the amino acid sequence shown in SEQ ID NO: 2 n (indicating any integer from n = l to 347) Or an added amino acid sequence? These GPCR genes are based on their DNA sequence information. For example, in the case of human-derived GPCR genes, a human gene library and a human cDNA library are used. For example, it can be prepared by a known method. The DNA encoding the GPCR protein of the present invention includes a base sequence represented by SEQ ID NO: 2n-11 (in which n is any integer from 1 to 347) or a complementary sequence thereof, or a sequence thereof. And DNAs that hybridize to various DNA libraries under stringent conditions and encode the GPCR protein using these DNAs as probes. Hybridization conditions for obtaining such DNA include, for example, hybridization at 42 ° C and 1XSSC at 42 ° C with a buffer containing 0.1% SDS. Washing treatment can be mentioned, and more preferably washing at 65 ° C with a hybridization solution at 65 ° C and a buffer containing 0.1 XSSC and 0.1% SDS. it can. The factors affecting the stringency of the hybridization include various factors other than the above-mentioned temperature conditions, and those skilled in the art can appropriately combine the various factors and use the above-described examples of the hybridization. It is possible to achieve the same stringency as the stringency.

The GPCR protein of the present invention may be any GPCR protein as long as it is obtained by the above-mentioned screening method.For example, SEQ ID NO: 2 n (n is any integer from 1 to 51 GPCR protein other than the olfactory receptor and the taste receptor consisting of the amino acid sequence shown in), and the amino acid shown in SEQ ID NO: 2 n (n is an integer from 52 to 32) GPCR protein of an olfactory receptor consisting of an acid sequence, and GPCR of a taste receptor consisting of an amino acid sequence represented by SEQ ID NO: 2 n (n = any integer from 3333 to 347) In the protein or the amino acid sequence shown in SEQ ID NO: 2 n (in which n represents any integer from l to 347), one or several amino acids are deleted, substituted, or added. Specific examples include GPCR proteins comprising a sequence and these recombinant proteins. Further, the partial peptide of the above GPCR protein which is an object of the present invention includes an amino acid sequence comprising a part of the above GPCR protein and recognizing various G proteins or an amino acid which specifically binds to various G proteins. There is no particular limitation as long as it has a sequence. The GPCR protein and partial peptides of the GPCR protein, which are the objects of the present invention, and the recombinant proteins and peptides to which antibodies specifically binding to these proteins and peptides specifically bind, are collectively referred to. Hereafter, it may be referred to as “the subject protein · peptide”. The protein / peptide of the present invention can be prepared by a known method based on its DNA sequence information and the like, and its origin is not particularly limited.

The fusion protein or fusion peptide of the present invention may be any fusion protein or peptide as long as it is a protein / peptide coupled to a marker protein or z- or peptide tag, and is conventionally known as a marker-protein. Any marker protein may be used, for example, alkaline phosphatase, the Fc region of an antibody, HRP, GFP, etc., and specific examples thereof. For example, a conventionally known peptide tag such as a Myc tag, a His tag, a FLAG tag, and a GST tag can be specifically exemplified. Such a fusion protein can be prepared by a conventional method. Purification of a GPCR protein using the affinity of the Ni—NTA and His tags, detection of the GPCR protein, and detection of an antibody against the GPCR protein It is also useful as a reagent for quantification and other research in this field.

Specific examples of the antibody that specifically binds to the present protein or peptide of the present invention include immunospecific antibodies such as monoclonal antibodies, polyclonal antibodies, chimeric antibodies, single-chain antibodies, and humanized antibodies. And these are

Two The protein can be prepared by a conventional method using a protein such as the above GPCR protein or a part thereof as an antigen. Among them, a monoclonal antibody is more preferable in view of its specificity. An antibody that specifically binds to a GPCR protein such as a monoclonal antibody is useful, for example, for diagnosing a disease caused by mutation or deletion of a GPCR protein or for elucidating the molecular mechanism of a GPCR protein.

Further, the antibody of the present invention is obtained by administering a fragment containing the present protein / peptide or epitope or a cell expressing the protein / peptide on the membrane surface to an animal (preferably other than human) using a conventional protocol. For example, monoclonal antibodies can be prepared by the hybridoma method (Nature 256, 495-497, 1975), the trioma method, or the human priming method, which results in the viable body produced by continuous cell line culture. B cell hybridoma method (Immunology Today 4, 72, 1983) and EBV-hybridoma method (MONOCLONAL ANTIBODIES AND CANCER THERAPY, pp.77-96, Alan R.Liss, Inc., 1985) A method can be used. Production of a monoclonal antibody that specifically binds to a mouse-derived GPCR protein, that is, an anti-mGPCR (mouse GPCR) monoclonal antibody, using the mouse-derived GPCR protein as an example, as the present protein and peptide Explain the method.

The anti-mG PCR monoclonal antibody can be produced by culturing an anti-mG PCR monoclonal antibody-producing hybridoma in in vivo or in vitro by a conventional method. For example, it can be obtained by culturing in the intraperitoneal cavity of a rodent, preferably a mouse or rat in the in vivo system, and by culturing in an animal cell culture medium in the in vitro system. The culture medium for culturing hybridomas in an in vitro system includes R containing streptomycin and antibiotics such as benicillin. Cell culture media such as PMI 1640 or MEM can be exemplified. Anti-mG PCR monoclonal antibody-producing hybridomas are obtained, for example, by immunizing BAL B / c mice with GPCR obtained from mice and the like, and immunizing spleen cells of mouse and mouse NS-1 cell (AT CCTIB -18) is fused with a conventional method and screened by immunofluorescence staining pattern to produce an anti-mG PCR monoclonal antibody-producing hybridoma. As a method for separating and purifying the monoclonal antibody, any method may be used as long as it is a method generally used for protein purification, and specific examples thereof include liquid chromatography such as affinity mouth chromatography. can do.

In order to produce a single-chain antibody against the present protein / peptide of the present invention, a single-chain antibody preparation method (US Pat. No. 4,946,778) can be applied. In addition, transgenic mice or other mammals may be used to express the humanized protein, or a clone expressing the protein / peptide of the present invention may be isolated and identified using the above-mentioned antibodies. The polypeptide can be purified by affinity chromatography. The protein of the present invention.Antibodies against the peptide, including the peptide and its antigen peptide, are useful for elucidating the molecular mechanism of the GPCR protein. It is. Recombinant proteins or peptides to which these antibodies specifically bind are also included in the present protein / peptide of the present invention as described above.

Antibodies such as the above-mentioned anti-mGPCR monoclonal antibody include, for example, fluorescent substances such as FITC (fluorescein isocyanate) or tetramethylrhodamine sosinate, ¹²⁵ I, ³² P, ¹⁴ C ³⁵ S or ³ H Labeled with an enzyme such as radioisotope II, alkaline phosphatase, peroxidase, / 3-galactosidase or phycoerythrin, or a fusion protein of a fluorescent protein such as green fluorescent protein (GFP).

Four By using the synthetic protein, functional analysis of the present protein / peptide can be performed. Examples of the immunological measurement method include a method such as an RIA method, an ELISA method, a fluorescent antibody method, a plaque method, a spot method, a hemagglutination reaction method, and an octolony method.

The present invention also relates to a host cell comprising an expression system capable of expressing the present protein / peptide. Such a gene encoding the present protein / peptide is introduced into host cells by Davis et al. (BAS IC METHODS IN MOLECULAR BIOLOGY, 1986) and Sambrook et al. (MOLECULAR CLONING: A LABORATORY MANUAL, 2nd Ed., Cold Spring Harbor Laboratory Press). , Cold Spring Harbor, NY, 1989) and methods described in many standard laboratory manuals, e.g., calcium phosphate transfection, DEAE-dextran mediated transfection, transvection. , Microinjection, cationic lipid-mediated transfection, electoporation, transduction, scrape loading, scrape loading> bal 1 istic int rodtion, infection, and the like. Examples of host cells include bacterial prokaryotic cells such as Escherichia coli, Streptomyces, Bacillus subtilis, Streptococcus, and Staphylococcus; fungal cells such as yeast and Aspergillus; and insect cells such as Drosophila S2 and Spodoptera Sf9. , L cells, CHO cells, COS cells, HeLa cells, C127 cells, BAL BZc3T3 cells (including mutants lacking dihydrofolate reductase / thymidine kinase), BHK21 Cells, HEK293 cells, Bowes melanoma cells, animal and plant cells such as oocytes, and the like.

The expression system may be any expression system capable of expressing the present protein / peptide in a host cell, and may be any expression system derived from chromosomes, episodes and viruses, for example, From bacterial plasmid, Vectors derived from yeast plasmid, papovavirus such as SV40, vaccinia virus, adenovirus, fowlpox virus, pseudorabies virus, retrovirus, vectors derived from bacteriophage, transposon, and vectors derived from combinations thereof. First, for example, plasmids such as cosmid phagemid and those derived from the genetic elements of pacteriophage can be mentioned. These expression systems may contain control sequences that not only cause expression but also regulate expression.

The host cell comprising the above expression system, the cell membrane of such a cell, and the protein peptide of the present invention obtained by culturing such a cell can be used in the screening method of the present invention as described later. For example, as a method for obtaining a cell membrane, the method of F. Pietri-Rouxel (Eur. J. Biochei., 247, 1174-1179, 1997) and the like can be used. To recover and purify the protein peptide from cell culture, ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity Known methods including chromatographigraphy, hydroxyapatite chromatography and lectin chromatography, preferably high performance liquid chromatography are used. In particular, as a column used for affinity chromatography, for example, a column to which an antibody against the protein or peptide of the present invention such as an anti-GPCR monoclonal antibody is bound, or a normal peptide tag is added to the protein or peptide of the present invention. In this case, the protein / peptide of the present invention can be obtained by using a column to which a substance having an affinity for this peptide tag is bound. The method for purifying the present protein / peptide can be applied to peptide synthesis.

In the present invention, the non-human animal overexpressing the present protein / peptide may be used. A non-human animal is a non-human animal that produces a large amount of the present protein / peptide compared to a wild-type non-human animal, and a non-human animal whose gene function encoding the present protein / peptide is deficient on the chromosome This means that part or all of the gene encoding the present protein and the peptide on the chromosome is inactivated by gene mutation such as disruption, deletion, or substitution, and the function of expressing the present protein or peptide is lost. Non-human animals. Examples of the non-human animal in the present invention include, but are not limited to, non-human animals such as egrets and rodents such as mice and rats.

By the way, homozygous non-human animals born according to Mendel's law include the present protein / peptide deficient type or overexpressed type and its wild-type littermate, and the defective type in these homozygous non-human animals. Alternatively, the simultaneous use of an over-expressed type and its littermate wild-type allows accurate comparison experiments at the individual level, and thus the function of the gene encoding the wild-type non-human animal, ie, the protein of the present invention and the peptide, is It is preferable to use an animal of the same species as the non-human animal deficient or overexpressed on the chromosome, or an animal of the same litter, for example, in the screening of the present invention described below. Methods for producing non-human animals in which the gene function encoding the peptide is deficient or overexpressed on the chromosome have been developed using GPCR protein knockout mice and transgenic mice. The diethyl nick mice is described below as an example. For example, a mouse in which the function of a gene encoding a GPCR protein is deficient on a chromosome, that is, a GPCR protein knockout mouse, uses a gene fragment obtained by a method such as PCR from a mouse gene library. The gene encoding the GPCR protein is screened, the gene encoding the screened GPCR protein is subcloned using a viral vector or the like, and identified by DNA sequencing. this

7 All or part of the gene encoding the GPCR protein of the clone is replaced with a PMC1 neo gene cassette or the like, and the diphtheria toxin A fragment (DT-A) gene or the simple virus thymidine quina is inserted at the 3 'end. By introducing a gene such as the Iseze (HSV-tk) gene, an evening get vector is prepared.

The prepared targeting vector is linearized, introduced into ES cells by electroporation (electroporation) or the like, and homologous recombination is performed. From among the homologous recombinants, G418 Select ES cells that have undergone homologous recombination with an antibiotic such as ganciclovir (GANC). In addition, it is preferable to confirm whether the selected ES cell is the target recombinant by the Southern blot method or the like. The confirmed clones of ES cells are microinjected into mouse blastocysts, and the blastocysts are returned to the foster mother mice to produce chimeric mice. When this chimeric mouse is intercrossed with a wild-type mouse, a heterozygous mouse can be obtained. By intercrossing the heterozygous mouse, a GPCR protein knockout mouse of the present invention is produced. can do. In addition, methods for confirming whether or not GPCR protein knockout mice have occurred include, for example, isolating RNA from mice obtained by the above method and examining them by the Northern blot method or the like. There is a method of examining the expression of the gene by Western blotting or the like.

The GPCR protein transgenic mouse contains a promoter encoding chicken i3-actin, mouse neurofilament, SV40, etc., and a rabbit i3-globin, SV40, etc., in the cDNA encoding the GPCR protein. A transgene is constructed by fusing poly A or intron, and the transgene is microinjected into the pronucleus of a mouse fertilized egg, and the obtained egg cell

8 After culturing, the transplanted animal is transplanted into the oviduct of the foster mother mouse, and then the animal to be transplanted is bred.The transgenic mouse can be created by selecting pups having the cDNA from the pups born. it can. In addition, selection of pups carrying cDNA can be performed by extracting the crude DNA from the tail of the mouse, using the dot hybridization method using the gene encoding the introduced GPCR protein as a probe, or using a specific primer. It can be performed by the PCR method or the like.

As a method for screening the substance for promoting or inhibiting the function of the protein / peptide of the present invention such as the GPCR of the present invention, a method using the cell membrane expressing the protein / peptide or the protein / peptide of the present invention and a test substance is used. A method using the protein / peptide of the present invention or a cell membrane expressing the protein / peptide of the present invention, a G protein, and a test substance; a cell expressing the protein of the present invention; Examples of the method include a method using a test substance and a method using a test substance and a non-human animal such as a knockout mouse or a transgenic mouse of the present protein * peptide.

The screening method using the test substance and the cell membrane expressing the protein of the present invention, the peptide or the protein of the present invention and the test substance includes the protein of the present invention, the peptide of the present invention, the peptide expressed on the surface of the cell membrane, and the test substance. And a method for measuring and evaluating the binding state between the present protein / peptide or the present protein / peptide expressed on the cell membrane surface and the test substance. The method using the protein of the present invention, the peptide or the cell membrane expressing the protein of the present invention, the G protein, and the test substance includes the protein of the present invention, the peptide or the protein of the present invention expressed on the cell membrane surface. And a G protein and a test substance are brought into contact with each other to measure and evaluate the interaction between the G protein and the protein / peptide of the present invention or the protein / peptide expressed on the cell membrane surface. As a method of using the test substance and a non-human animal such as the knockout mouse or transgenic mouse of the present protein / peptide, the present protein / peptide expressing cells obtained from the non-human animal and the test substance are used. After pre-contacting in vitro, the cells expressing the present protein / peptide are cultured in the presence of a G protein, and the response to the G protein in the present protein / peptide expressing cells is measured and evaluated. After bringing the protein / peptide expressing cells obtained from an animal into contact with a G protein in vitro, the protein / peptide expressing cells are cultured in the presence of a test substance, and then the protein / peptide is expressed. A method for measuring and evaluating a response to a G protein such as a binding state to the G protein in a peptide-expressing cell; After the test substance has been administered to the non-human animal, the cells expressing the protein of the present invention and the peptide obtained from the non-human animal are cultured in the presence of the G protein, and the response to the G protein of the cells expressing the present protein and the peptide is measured and evaluated. Methods can be mentioned.

The substance that promotes or suppresses the function of the protein or peptide of the present invention or the substance that promotes or suppresses the expression of the protein or peptide of the present invention, for example, a ligand of GPCR can be obtained by the above-described screening method. Further, the pharmaceutical composition of the present invention may contain, as an active ingredient, a substance that promotes or suppresses the function of the present protein-peptide or a substance that promotes or suppresses the expression of the present protein or peptide, in addition to the above-mentioned protein and peptide of the present invention. The pharmaceutical composition is not particularly limited.Patients who need to promote the function or enhance the expression of the protein or peptide of the present invention or patients who need to suppress the function or expression of the protein or peptide of the present invention Can be used to treat Furthermore, as a method for diagnosing a disease associated with the function or expression of the present protein / peptide, a DNA sequence encoding the GPCR protein of the present invention in a sample is encoded by encoding the GPCR protein of the present invention. Those who compare with DNA sequence The method is not particularly limited as long as it is a method, and the probe for diagnosing a disease associated with the function or expression of the protein or peptide of the present invention may be an antisense strand of DNA or RNA encoding the GPCR protein of the present invention. There is no particular limitation as long as it is composed entirely or in part, and the diagnostic agent for a disease associated with the function or expression of the present protein / peptide includes the diagnostic probe or the antibody described above. If there is, there is no particular limitation.

Hereinafter, the present invention will be described in more detail with reference to examples, but the scope of the present invention is not limited to these examples.

Examination of whether or not GPCR genes other than olfactory and taste receptors reported so far contain introns shows that 95 GPCR genes do not contain introns, and 63 GPCR genes contain introns. This confirms that about 60% of GPCR genes do not have introns. The presence of introns in human olfactory and taste receptors has not been reported. Therefore, I searched for GPCR without intron as follows.

[Extraction of putative GPCR gene from human genome data]

Using human genome data (as of August 18, 2000), open reading frames (ORFs) that could be candidates for GPCR genes were extracted and analyzed by S〇SUI. Was. Since the human genome data used in this study contains the same unidentified sequence redundantly, the entire human genome is about 3 G base pairs, whereas the whole human genome is about 4.5 Gbp. Consists of G base pairs. Approximately 210,000 ORFs consisting of DNA coding for 200 to 150 amino acid residues were extracted from human genome data, and from these, it is thought to be derived from DNA repeats. There are many defined amino acids 0 RF or the same amino acid 2 Approximately 130,000 ORFs were obtained by eliminating RFs containing 0% or more.Before analyzing 130,000 RFs by SOSUI, the effectiveness of S 0 SUI analysis was examined. .

[Effectiveness of SOSUI analysis]

In the analysis using SOSUI, the signal peptide of GPCR may be determined as a transmembrane region, and the seventh transmembrane region on the GPCR structure tends to have low hydrophobicity. May not be able to be determined as a transmembrane region. Therefore, by analyzing the amino acid sequence of the known GPCR with S〇SUI, the extent to which the SOSUI is GP can be determined. We first examined whether it would be effective in searching for a scale. Analysis of 207 GPCRs other than the olfactory and taste receptors reported so far by S0SUI revealed that 95% of the 1997 GPCRs contained 6 to 8 transmembrane domains. And the analysis result was obtained. The same analysis was also performed for 43 types of olfactory receptors, and it was found that 33 types of GPCR equivalent to 77% contained 6 to 8 transmembrane regions. Was. Therefore, the expected ability of SOSUI was about 95% for GPCR other than olfactory and taste receptors, and about 77% for olfactory receptors. The above-mentioned 207 GPCRs other than the olfactory and taste receptors reported so far are available on the website http: 〃www.gpcr.org / 7tm / seq / dna.html. The unoloading gene was used, and the olfactory receptor gene used was down-loaded from the website http://ycmi.med.yale.edu/senselab/ORDB.

[Search for homology (B LA ST)]

As a result of analyzing 130,000 ORFs by SOSUI, 1150 ORFs containing 6 to 8 transmembrane regions were obtained. The sequence of the obtained GPCR candidate 1150 ORFs was coded using BLAST to August 20, 2000. As a result of querying the current database "nr" and examining the homology with known GPCRs, we obtained 522 homologues with known GPCRs. Furthermore, by eliminating duplicates from these sequences, 203 known olfactory receptor genes, one known taste receptor gene, and one known GPCR gene other than olfactory receptors and taste receptors 64 The type could be identified. On the other hand, new GPCR genes other than olfactory receptors and taste receptors, which have homology to known GPCR genes by BLAST search, new GPCR genes of olfactory receptors, and taste receptor A new GPCR gene was obtained.

[Analysis by amino acid sequence]

The novel GPCR gene obtained by the above BLAST search was analyzed using an amino acid sequence. As for the analysis of the amino acid sequence, in addition to the above S0SUI, the signal sequence was identified using PSORT, and it was further examined whether the length of the loop between the transmembrane regions was appropriate. In addition, in order to determine the possibility that the ORF is a pseudogene for the gene sequence, we searched for the presence of TATAbox and CpGis1 and upstream of the ORF. As a result, a new GPCR other than olfactory and taste receptors can be inferred. 51 RFs and a new GPCR of olfactory receptors can be predicted 281 ORFs (of which 218 are olfactory receptors) Thus, 15 types of ORFs that could be inferred to be novel GPCRs of taste receptors were confirmed. The nucleotide sequence of a novel GPCR other than the 51 types of olfactory and taste receptors described above is shown in SEQ ID NO: 2 n-1 (indicating any integer from n = l to 51). The amino acid sequence of the novel GPCR protein encoded by the novel GPCR gene is shown in SEQ ID NO: 2n (n is any integer from 1 to 51). In addition, the nucleotide sequence of a novel GPCR gene of 28 1 olfactory receptor was changed to SEQ ID NO: 2 η-1 (η = 5 2 The amino acid sequence of a novel GPCR protein of these 28 olfactory receptors is shown in SEQ ID NO: 2 n (n = 52 to 33 Is shown as an integer). 1 The nucleotide sequences of the novel GPCR genes for the five types of taste receptors are shown in SEQ ID NO: 2 n-1 (n = any integer from 33 to 347). The amino acid sequence of the novel GPCR protein of the receptor is shown in SEQ ID NO: 2 n (n is an integer from 33 to 347). The transmembrane domains (TM) of the above-mentioned 347 new GPCR proteins and the names of the proteins with the highest homology at the amino acid level are shown below. The number following TM indicates the number of the transmembrane region, and the numerical range following the number indicates the number in the sequence list of amino acid residues constituting the transmembrane region, and the number in the sequence list of amino acid residues. (P) following the number indicates that the properties as a transmembrane region are very clear, and (S) indicates that the properties as a transmembrane region are somewhat weak. The number following the name of the protein with the highest homology at the amino acid level indicates the accession number, and indicates the exact amino amino acid number for all amino acids and its percentage (%). After that, if the expression site was confirmed by RT-PCR, the expression site is shown.

SEQ ID NO: 2 [TM1; 26_50 (P), TM2; 59-83 (P), TM3; 92-116 (P), TM4; 130-154 ( P), TM5; 1668-192 (P), TM6; 203-227 (P), TM7; 241-265 (P)]

ret inoic acid induced 3 (putative G protein-coupled receptor) (A F095448); 138/290 (47%)

Spleen, lungs, heart, liver, kidney, Teng, small intestine, large intestine

SEQ ID NO: 4 [TM 1; 17-40 (S), TM 2; 66-88 (P), TM3; 99-123 (S), TM4; 138-162 (S), TM5; 222-246 (P), TM6; 256-280 (P)]

hypothetical protein PI.11659-3-1 human (AC004472); 302/307 (98%) heart, large intestine

SEQ ID NO: 6 [TM 1; 1-21 (S), TM 2; 92-16 (P), TM 3; 126-148 (P), TM 4; 177-19 7 (S), TM 5; 20 7-2 3 1 (S), TM 6; 2 5 5-2 7 9 (P), TM 7; 2 9 8-3 2 2 (P)]

putative chemokine receptor; GTP-binding protein (PROTEIN-COUPLED RECEPTOR HM74) (D10923); 122/294 (41%)

SEQ ID NO: 8 [TM 1; 18-42 (P), TM 2; 49-73 (S), TM 3; 100—120 (S), TM4; (P), TM 5; 178-202 (S), TM 6; 219-243 (P)]

putative chemokine receptor; GTP-binding protein (PROTEIN-COUPLE D RECEPTOR HM74) (D10923); 178/341 (52%)

SEQ ID NO: 10 [TM 1; 31-55 (P), TM 2; 65-89 (P), TM 3; 99-123 (S), TM4; 154—178 (P), TM5; 194-218 (P), TM6; 242-266 (S), TM7; 274-298 (P)]

FML and GORGO FMLP-RELATED RECEPTOR I (X97738); 90/324 (27%) SEQ ID NO: 12 [TM 1; 24-48 (P) TM 2; 69-90 (S), TM 3; 9 6-120 (S), TM4; 135-159 (P), TM5; 186-210 (P), TM6; 231-251 (P), TM 7; 2 7 7— 3 0 1 (P)]

P2Y5_CHIC P2Y PURINOCEPTOR 5 (P2Y5) (protein-coupled receptor) (L06109); 113/284 (39%) SEQ ID NO: 14 [TM 1; 37-61 (P), TM 2; 80-102 (S), TM 3; 118-142 (P), TM4; 150- 1 74 (P), TM 5; 200-222 (P), TM 6; 240—264 (P)]

purinergic receptor P2Y, G-protein coupled 1 (U22829); 109/299 (36%)

Brain, spleen, lung, liver, large intestine

SEQ ID NO: 16 [TM1; 27-51 (P), TM2; 69-93 (P), TM3; 103-124 (S), TM4; 144-168 (P), TM5; 185-209 (P), TM6; 223-247 (P), TM7; 2627-291 (S)]

MAS1 oncogene (J03823); 111/294 (37%)

Heart, small intestine, large intestine

SEQ ID NO: 18 [TM1; 8-32 (P), TM2; 61-85 (S), TM3; 92-116 (S), TM4; 154-178 ( P), TM5; 1962-220 (P), TM6; 250-274 (P)]

G-protein coupled receptor GPR34 (AF039686); 77/323 (23%) Brain, spleen, lung, heart, lung, kidney, Teng, stomach, small intestine, large intestine

SEQ ID NO: 20 [TM 1; 5-23 (S), TM 2; 50-74 (P),

TM3; 87-111 (S), TM4; 123-147 (P), TM5; 165-189 (P), TM6; 211-23 5 (P)]

5-hydroxytryptamine (serotonin) receptor ID (AB041379); 72/272 (2

6¾)

Gut

SEQ ID NO: 22 [TM 1; 2-2 (P), TM 2; 29-53 (P), TM 3; 64-88 (S), TM 4; 94-117 (P), TM 5; 2 13-2 3 7 (P), TM 6; 2 9 7-3 2 1 (S)] CG2114 gene product (AE003476); 71/302 (23%)

Stomach, small intestine

SEQ ID NO: 24 [TM 1; 37-61 (P), M2; 76-100 (S) 'TM 3; 113-13 7 (P), TM4; 15 1 -175 (P), TM5; 189-213 (P), TM6; 250-274 (P), TM7; 290-310 (S)]

sphingosine to phosphate receptor Edg-8 (AF223649); 343/397 (86%) SEQ ID NO: 26 [TM1; 25-49 (P), TM2; 58-82 (S), TM3; 9 7-12 1 (P), TM4; 13 8-16 2 (P), TM 5; 18 4-28 (P), TM 6; 23 33-254 (P), TM 7; 2 7

4-2 9 3 (S)]

gene product, putative G protein-coupled receptor; G protein coupled receptor for proof-glucose (D13626); 149/314 (47¾)

Brain, spleen, heart, stomach, large intestine

SEQ ID NO: 28 [TM 1; 39-63 (P), TM 2; 72-96 (S), TM 3; 148-170 (P), TM4; 202-22 5 (P), TM

5; 248-272 (P), TM6; 286-310 (S)]

GALS— MOUSE GAL AN IN RECEPTOR TYPE 2 (AF042784); 109/299 (36%)

SEQ ID NO: 30 [TM 1; 43-67 (P), TM 2; 79-103 (P), TM 3; 113-137 (P), TM 4; 154 17 4 (S), TM 5; 206-230 (P), TM 6; 28 7-31 1 (P), TM 7; 3 24 — 345 (S)]

PROBABLE G PROTEIN-COUPLED RECEPTOR (D43633); 179/429 (41%) SEQ ID NO: 3 2 [TM 1; 13 5-15 7 (S), TM2; 16 1-18 4 (P), TM 3; 19 1-2 15 (P), TM4; 230-2 54 (P), TM 5; 26 6-290 (P), TM 6; 3 18-32 (P)] seven transmembrane receptor (AB019120); 71/302 (23%)

SEQ ID NO: 34 [TM1; 43-67 (P), TM2; 79-103 (P), TM3; 113-137 (P), TM4; 154-17 8 (S), TM5; 206-230 (P), TM6; 280—302 (P), TM7; 312

-3 3 6 (P)]

PROBABLE G PROTEIN-COUPLED RECEPTOR (D43633); 125/312 (40¾) SEQ ID NO: 36 [TM 1; 38-62 (P), TM 2; 89-113 (S), TM 3; 1 1 8-14 2 (P), TM4; 16-18 8 (P), TM 5; 20 8-2 32 (P), TM 6; 248-27 2 (S), TM 7 2 7 6

-2 9 8 (S)]

G-protein coupled receptor SALPR; somatostatin and angiotens in-l ike

(G- protein coupled receptor SALPR) (D88437); 141/322 (43%) kidney, small intestine

SEQ ID NO: 38 [TM 1; 7-31 (P), TM 2; 42-66 (S), TM 3; 79-.103 (S), TM 4; 120-144 (P), TM5; 159-183 (P), TM6; 224-248 (P), TM7; 264-288 (S)]

DOP and DROME DOPAMINE RECEPTOR 1 PRECURSOR (D-DOPl) (X77234); 95/350 (27¾)

SEQ ID NO: 40 [TM 1; 3-27 (S), TM 2; 36-60 (P), TM 3; 64-87 (S), TM4; 94-116 (S), TM 5; 2 13-2 3 1 (S), TM 6; 2 5 1-2 7 3 (P)]

cadherin EGF LAG seven-pass G-type receptor (AF031572); 40/112 (35%) SEQ ID NO: 42 [TM 1; 27-51 (S), TM 2; 103-122 (S) , TM 3; 139-160 (P), TM4; 180-204 (S), TM 5; 2 2 1-24 5 (P), TM 6; 26 3-28 1 (S)]

RTA—RAT PROBABLE G PROTEIN-COUPLED RECEPTOR RTA (M35297); 120/332 (36%)

SEQ ID NO: 44 [TM1; 28-52 (P), TM2; 63-87 (P), TM3; 95-117 (P), TM4; 141-165 (P), TM5; 179-203 (P), TM6; 216-240 (P), TM7; 252-276 (S)]

MAS1 oncogene (J03823); 108/283 (38%)

Spleen, lung, large intestine

SEQ ID NO: 46 [TM 1; 18-42 (S), TM 2; 96-120 (P), TM 3; 140-16 4 (P), TM4; 1 78- 20 2 (P), TM 5;

3 1 8-3 4 2 (P), TM 6; 3 5 3-3 7 4 (S)]

(AE003422) EG: 22E5.11 gene product (AE003422); 98/364 (26¾) Lung

SEQ ID NO: 48 [TM 1; 12-36 (P), TM 2; 47-71 (S), TM 3; 97-121 (P), TM4; 133-1 57 (S)> TM5; 183-207 (P), TM6; 226-250 (P)]

frizzled 6 (AB012911); 286/314 (91¾)

SEQ ID NO: 50 [TM 1; 16-40 (P), TM 2; 45-69 (S), TM 3; 80-104 (P), TM4; 1 16-13 8 (S), TM 5;

1 64-188 (S), TM 6; 278-302 (P), TM 7; 354-378 (P)]

unnamed protein product (AK000922); 286/370 (77%)

SEQ ID NO: 52 [TM 1; 64-88 (P), TM 2; 98-120 (P), TM 3; 122-146 (S), TM4; 17 2-1 9 6 (P), TM 5;

2 13-2 37 (S), TM 6; 25 3-27 7 (P), TM 7; 284 -3 0 8 (P)]

putative pheromone receptor V2R2 (AF053989); 250/327 (76¾) nose

SEQ ID NO: 54 [TM 1; 84-106 (P), TM 2; 110-132 (P), TM 3; 136-158 (P), TM4; 173 — 194 (P), TM5; 200-224 (P), TM6; 230-251 (P), TM7; 267-291 (P)]

insul in-1 ike growth factor I, brain-spec ific-Thai catfish (A53697); 28/88 (31%)

SEQ ID NO: 56 [TM1; 90-114 (S), TM2; 117-140 (S;), TM3; 151-168 (S), TM4; 17 4—198 (P), TM5; 209-233 (S), TM6; 238-262 (P)]

hypothetical protein T06E4.7-Caenorhabdi t is elegans (Z70756); 25/67 (37%)

Lung

SEQ ID NO: 58 [TM 1; 0-64 (P), TM 2; 71-95 (S), TM 3; 124-148 (P), TM 4; 15 3-17 7 (P), TM 5; 204-228 (P), TM 6; 243-265 (P), TM 7; 283

-3 0 7 (S)]

cysteinyl leukotriene receptor 1 (AF119711); 114/298 (38%) SEQ ID NO: 60 [TM1; 16-38 (P), TM2; 51-73 (P), TM3; 91- 1 13 (P), TM4; 13 3—15 5 (S), TM 5; 17 8-19 9 (P), TM 6; 27 1-29 3 (S)]

G protein-coupled seven-transmembrane receptor (D43633); 117/365 (32%)

SEQ ID NO: 6 2 [TM 1; 17-39 (S), TM 2; 67-89 (P), TM3; 101-123 (S), TM4; 135-157 (P), TM5;

17 8-19 6 (S), TM 6; 20 2-2 2 1 (S)]

allatostatin receptor (AF163775); 43/154 (11%)

Lung, heart, kidney, small intestine

SEQ ID NO: 64 [TM1; 9-31 (S), TM2; 48-70 (S), TM3; 92-114 (S), TM4; 207-229 (S), TM5; 269-290 (P), TM6; 315-337 (P), TM7; 348-370 (P)]

pheromone receptor VN3 (U36895); 84/277 (30%)

Nose

SEQ ID NO: 66 [TM1; 118-140 (P), TM2; 153-175 (S), TM3; 199-221 (S), TM4; 2 36-258 (P), TM5; 281-303 (P), TM6; 326-348 (P), TM7; 362-238 (P )]

G protein-coupled receptor LGR5 (AF061444); 120/269 (44%) SEQ ID NO: 6 8 [TM 1; 33-5 4 (S), TM 2; 97-1 19 (P), TM 3; 168-190 (S), TM4; 264-286 (P), TM5;

2 9 1-3 13 (S), TM 6; 4 05-4 2 7 (P)]

interleukin 9 receptor precursor (L39064); 30/105 (28%)

SEQ ID NO: 70 [TM 1; 5-27 (P), TM 2; 55-76 (STM 3; 85-107 (Ρ), ΤΜ4; 1 26-148 (S) , TM5; 164-186 (P), TM6; 2667-289 (P), TM7; 304-

3 2 6 (S)]

pheromone receptor VN6 (U36898); 99/310 (31%)

Nose

SEQ ID NO: 72 [TM 1; 1-21 (S), TM 2; 27-43 (S), T

Three 3; 5 1-7 3 (S), TM4; 9 2-11 4 (S), TM 5; 13 1 — 15 3 (S) TM 6; 18 3-205 (P)]

pheromone receptor 1 (Y12725); 64/155 (41%)

Nose

SEQ ID NO: 74 [TM 1; 20-42 (P), TM 2; 50-72 (S), TM 3; 84-106 (P), TM 4; 123-1 44 (P), TM5; 167-189 (S), TM6; 228-250 (P), TM7; 259-281 (S)]

putative G- Protein coupled receptor, EDG6 (AJ000479); 81/268 (30%) Skeletal muscle

SEQ ID NO: 76 [TM 1; 21-43 (P), TM 2; 55-77 (P), TM 3; 100-122 (S), TM4; 1 36-1 5 8 (P), TM 5; 18 1-203 (P), TM 6; 22 7-247 (P), TM 7; 27 0

-2 7 2 (S)]

putative purinergic receptor P2Y10 (AF000545); 148/292 (50%) SEQ ID NO: 78 [TM 1; 24-46 (P), TM 2; 57-79 (P), TM 3; 98-1 20 (P), TM4; 136-158 (P), TM5; 189-12-111 (P), TM6; 234-255 (P), TM7; 2 8 0

-3 0 0 (S)]

KIAAOOOl gene pr oduc t (Dl 3626); 140/295 (47%)

Brain, thymus, lung, kidney, stomach, large intestine

SEQ ID NO: 80 [TM1; 1-23 (P), TM2; 36-58 (S), TM3; 249-271 (P), TM4; 296-318 (P), TM5; 3332-354 (P), TM6; 3668-390 (P), TM7; 412-434 (P), TM8; 45 8-4 8 0 (S)]

seven transmembrane receptor (AB019120); 191/487 (39%) SEQ ID NO: 8 2 [TM 1; 5-25 (S), TM 2; 80-97 (S), TM 3; 103-124 (P), TM4; 133-1 55 (P), TM 5;

1 65-18 7 (S), TM 6; 2 17-2 39 (P)]

unnamed protein product (AK000922); 304/357 (85%)

SEQ ID NO: 84 [TM 1; 16—34 (S), TM 2; 2 16—2 38 (P) TM 3; 247-269 (S), TM4; 285-3 0 7 (S), TM 5; 36 7-3 89 (P), TM 6; 40 3-4 25 (P)]

seven transmembrane receptor (AB019120); 95/326 (29%)

SEQ ID NO: 86 [TM 1; 1-23 (S), TM 2; 41-63 (S), TM 3; 95-117 (P), TM 4; 128-15 0 (P), TM 5; 1

5 7-17 9 (P), TM 6; 190-2 12 (S), TM 7; 2 16-

2 3 8 (P), TM 8; 260-282 (P)]

neuropeptide Y receptor Y6 (U58367); 23/88 (26%)

SEQ ID NO: 8 [TM 1; 14-36 (S), TM 2; 55-77 (P), TM 3; 94-116 (P), TM 4; 126-14 7 (P), TM5; 185-207 (P), TM6; 215-237 (S)]

orphan G protein-coupled receptor (AF045764); 199/236 (84%) SEQ ID NO: 90 [TM 1; 31-53 (P), TM 2; 69-91 (P), TM 3; 1 1 0-13 2 (S), TM 4; 19 5-2 17 (P), TM 5; 400-422 (P), TM 6; 4 34-4 56 (P)]

G-protein coupled receptor RE2 (AF091890); 63/192 (32%)

SEQ ID NO: 92 [T M1; 1-23 (P), TM2; 36-58 (P), T

M3; 99-121 (P), TM4; 135-157 (S), TM5; 1

6 5-1 8 7 (P), TM 6; 1 8 9-2 1 1 (S), TM 7; 3 9-3 6 1 (P), TM 8; 3 7 9-4 0 1 (S )]

Frizzled-1 protein homolog (T42210); 27/82 (32%) SEQ ID NO: 94 [TM 1; 24-46 (P), TM 2; 83-105 (P), TM 3; 122-144 (P), TM 4; 16 6 — 18 88 (S), TM 5; 2 27-249 (P), TM 6; 25 8-280 (S)]

putative G- Protein coupled receptor (AJ000479); 76/268 (28%) SEQ ID NO: 96 [TM 1; 22-44 (P), TM 2; 1 13-1 35 (P) TM 3; 1 59-181 (P), TM4; 203-225 (S), TM5; 228-250 (P), TM6; 272-294 (S)]

Frizzled-10 (AB027464); 23/96 (23%)

SEQ ID NO: 98 [TM 1; 11-33 (S), TM 2; 41-63 (S), TM 3; 71-93 (S), TM4; 96-118 ( P), TM5; 122-14 (S), TM6; 146-165 (S)]

beta3- adrenergic receptor (AF109930); 39/120 (32¾)

SEQ ID NO: 100 [TM 1; 8 to 29 (P), TM 2; 31 to 52 (P), TM 3; 55 to 73 (P), TM 4; 79 to 100 ( P), TM5; 110-132 (S), TM6; 147-169 (P)> TM7; 177—199 (P), TM8; 201 -2 2 2 (P)]

putative pheromone receptor V2R1 (AF053985); 51/219 (23%) SEQ ID NO: 102 [TM 1; 6-28 (P), TM 2; 60-82 (S), TM 3; 90- 1 1 1 (S), TM4; 127-149 (P), TM5; 181-203 (S), TM6; 237-259 (P)]

pheromone receptor VN6 (U36898); 79/236 (33¾)

SEQ ID NO: 104 [TM 1; 5-27 (S), TM 2; 41-63 (P), TM 3; 82-104 (S), TM4; 106-128 (P), TM5; 153-175 (S), TM6; 191-213 (P), TM7; 235-257 (P), TM8; 2 8 9-3 1 1 (S)]

odorant receptor S19 (AF121976); 106/228 (46%) SEQ ID NO: 106 [TM 1; 1-23 (S TM 2; 44-66 (S), TM 3; 85-106 (P), TM4; 14 9-17 1 (P ), TM 5;

1 83-205 (S), TM 6; 2 17-2 38 (S)]

odorant receptor S18 (AF121975); 159/222 (71¾)

SEQ ID NO: 108 [TM 1; 3-25 (P), TM 2; 96-118 (S), TM 3; 120-142 (S), TM 4; 1 49 -171 (P), TM5;

1 82-204 (P), TM 6; 2 1 1-2 3 1 (P)]

odorant receptor Al 6 (AB030896); 122/244 (50%)

SEQ ID NO: 1 1 0 [TM 1; 3 1-53 (P), TM 2; 64-86 (S), TM 3; 100-122 (S), TM 4; 1 38-1 6 0 (P), TM 5; 17 1-19 3 (S), TM 6; 19 9-22 1 (P)]

ol factory receptor- 1 ike protein C0R3 'beta (L17432)' 106/217 (48%) SEQ ID NO: 1 1 2 [TM l; 30-52 (P), TM 2; 65-87 (P ), TM3; 105-127 (S), TM4; 134-156 (S), TM5; 203-225 (P), TM6; 243-2 6 5 (P), TM 7; 2 7 2

-2 9 4 (S)]

odorant receptor S18 (AF121975); 184/303 (60%)

SEQ ID NO: 1 1 4 [TMl; 29-51 (P), TM2; 59-81 (S), TM3; 99-121 (S), TM4; 144- 16 6 (P), TM5; 179-102 (S), TM6; 204-225 (P), TM7; 242

-2 64 (P), TM 8; 26 9-29 1 (S)]

odorant receptor M0R83 (AB030894); 155/306 (50%)

SEQ ID NO: 1 16 [TMl; 4-26 (S), TM2; 32-53 (PTM3; 65-87 (P), TM4; 99-121 (S) , TM5; 123-144 (P), TM6; 162-184 (S), TM7: 189-221 (P)] odorant receptor M0R83 (AB030894); 121/226 (53%)

SEQ ID NO: 1 18 [TM 1; 26-48 (P), TM 2; 61-83 (S), TM 3; 98-120 (S), TM4; 14 1-16 3 (S), TM5; 204-225 (P), TM6; 239-261 (P)]

odorant receptor M0R83 (AB030894); 156/303 (51%)

SEQ ID NO: 120 [TM 1; 25-47 (P), TM 2; 57-79 (S), TM 3; 88-109 (S), TM4; 13 1-15 3 (P), TM5; 201-223 (P), TM6; 242-264 (S)]

CfOLFl (U53679); 107/235 (45%)

SEQ ID NO: 1 2 2 [TM 1; 29-51 (S), TM 2; 83-105 (P) TM 3; 114-36 (P), TM4; 1 49- 17 1 (S), TM 5; 192-2-14 (S), TM 6; 25 9-28 1 (P), TM 7; 294- 3 16 (P)]

odorant receptor S51 (AF121981); 127/159 (79%)

SEQ ID NO: 1 2 4 [TM 1; 35-57 (P), TM 2; 68-90 (P), TM 3; 96-118 (S), TM4; 147-16 9 (S), TM5; 210-232 (P), TM6; 246-268 (P), TM7; 278-300 (S)]

MOR 3 'Betal (AF133300); 119/308 (38%)

SEQ ID NO: 12 6 [TM 1; 15-37 (S), TM 2; 64-86 (P), TM 3; 93-115 (S), TM4; 14 1-16 3 (S), TM5; 206-228 (P), TM6; 230-259 (P)]

odorant receptor S51 (AF121981); 85/128 (66%)

SEQ ID NO: 12 8 [TM 1; 6-28 (S), TM 2; 32-53 (P), TM 3; 59-81 (S), TM 4; 97—11 9 ( S), TM5; 145-16-17 (P), TM6; 205-226 (P), TM7; 236--2 5 8 (P), TM 8; 26 8-29 0 (S)]

similar to rat olfactory receptor 0R18 (AC004908); 209/311 (67%) SEQ ID NO: 130 [TM 1; 1-23 (S), TM 2; 28—50 (P), TM 3; 6 3-85 (S), TM4; 14 2-16 3 (P), TM 5; 20 3-25 (P), TM 6; 23 8-26 0 (P), TM 7; 2 7 1-

2 9 3 (P)]

olfactory receptor-like protein C0R3 'bet a (LI 7432); 147/299 (49%) SEQ ID NO: 13 2 [TM 1; 31-53 (S), TM 2; 63-85 (S) , TM3; 999-121 (S), TM4; 149-17-11 (P), TM5; 205-227 (P), TM6; 244-266 ( S), TM 7; 27 3-295 (P)]

putative G-protein coupled receptor RAlc (AF079864); 142/299 (47%) SEQ ID NO: 1 3 4 [TM 1; 1-23 (S), TM 2; 26-48 (S), TM 3; 5 1-7 3 (S), TM4; 8 5-10 7 (S), TM 5; 15 1-17 2 (P), TM 6; 18 2-204 (P), TM 7; 2 1 2-2

34 (S)]

odorant receptor S19 (AF121976); 142/246 (57%)

SEQ ID NO: 13 6 (TM 1; 11-33 (S), TM 2; 37-59 (P), TM 3; 71-93 (P), TM4; 107-1 2 9 (P), TM5; 151-17-13 (S), TM6; 207-1229 (P), TM7; 249-271 (P)]

olfactory receptor-like protein C0R3 'beta (L17432); 134/306 (43%) SEQ ID NO: 1 3 8 [TM 1; 11-32 (S), TM 2; 49-71 (S), TM 3; 9 1-11 3 (P), TM4; 1 28-150 (S), TM 5; 17 0-19 2 (P), TM 6; 23 1-25 3 ( P), TM 7; 26 8 1 290 (S) TM 8; 3 12-3 3 4 (S)] olfactory receptor-like protein C0R3 'beta (L17432); 149/313 (47%) SEQ ID NO: 140 [TM 1; 1-23 (S), TM 2; 30-52 (P), TM 3 67-89 (S), TM4; 102-124 (S), TM5; 1

37-159 (S), TM6; 202-224 (P), TM7; 239-261 (P), TM8; 271-293 (P )]

olfactory receptor-like protein C0R3 'beta (L17432); 156/298 (52%) SEQ ID NO: 142 [TM 1; 2-24 (S), TM 2; 33-55 (P), TM 3; 6 9-91 (P), TM4; 106-128 (S), TM5; 1

4 2-16 4 (S), TM6; 208-230 (P), TM 7; 244-266 (S), TM 8; 27 6-298 (S)]

putative G-protein coupled receptor RAlc (AF079864); 171/305 (56%) SEQ ID NO: 144 [TM 1; 31-53 (P), TM 2; 65-87 (P), TM 3; 14 1-16 3 (S), TM4; 18 3-205 (P), TM 5; 21 22-34 (P), TM 6; 240-26 2 (P) , TM7; 273-295 (S)]

olfactory receptor 64 (AF071080); 161/302 (53%)

SEQ ID NO: 14 6 [TM 1; 6-28 (P), TM 2; 42-64 (S), TM 3; 87-109 (P), TM 4; 144-16 6 ( P), TM5; 183-205 (P), TM6; 217-237 (S)]

olfactory receptor-like protein C0R3 'beta (L17432); 129/249 (51%) SEQ ID NO: 1 4 8 [TM 1; 1-18 (P), TM 2; 43-65 (S), TM 3 67-88 (S), TM4; 99-121 (S), TM5; 136-158 (S), TM6; 175-197 (P)]

putative G-protein coupled receptor RAlc (AF079864); 73/151 (48%) SEQ ID NO: 150 [TMl; 31-53 (P), TM2; 66-88 (P), TM3 104-126 (S), TM4; 141-163 (S), TM5; 2 05-2 27 (P), TM 6; 24 6-26 8 (S), TM 7; 27 4-29 6 (S) 3

odorant receptor S18 (AF121975); 142/308 (46%)

SEQ ID NO: 15 2 [TM 1; 6-26 (S), TM 2; 29-51 (P), TM 3; 53 3-75 (P), TM 4; 97-1 19 ( S), TM5; 133-155 (S), TM6; 202-224 (P), TM7; 2337-259 (P), TM8; 269 -2 9 1 (S)]

putative G-protein coupled receptor RAlc (AF079864); 298/318 (93%) SEQ ID NO: 15 4 [TM 1; 1-23 (S), TM 2; 29-51 (P), TM 3; 6 7-89 (P), TM4; 104—126 (S), TM 5; 1

45-166 (S), TM6; 206-228 (P), TM7; 244-266 (S), TM8; 277-298 (S)]

putative G-protein coupled receptor RAlc (AF079864); 157/301 (52%) SEQ ID NO: 15 6 [TM1; 18-40 (P), TM2; 44-65 (P), TM3; 6 9-9 1 (S), TM 4; 1 5—1 3 7 (P), TM 5; 1

5 4-1 7 6 (P), TM 6; 2 14-2 3 6 (P), TM 7; 2 5 5-2 7 7 (P), TM 8; 2 8 2-3 04 (S)]

putative G-protein coupled receptor RAlc (AF079864); 184/307 (59%) SEQ ID NO: 1 58 [TM 1; 30-52 (P), TM 2; 58-80 (S), TM 3 83-105 (S), TM4; 204-226 (P), TM5; 240-262 (P), TM6; 274-296 (S) ]

putative G-protein coupled receptor RAlc (AF079864); 180/299 (60%) SEQ ID NO: 160 [TM1; 2-24 (S), TM2; 30-52 (P), TM3; 64 -86 (S), TM4; 100-122 (S) TM5; 141-163 (S), TM6; 204-226 (P), TM7; 2 7 3-2 9 5 (S)] odorant receptor S18 (AF121975); 164/303 (54%)

SEQ ID NO: 16 2 [TM 1; 30-52 (P), TM 2; 64-86 (P), TM 3; 102-124 (S), TM 4; 142- 164 (S), TM5; 205-227 (P), TM6; 241-263 (S), TM7: 273-295 (S)]

odorant receptor S18 (AF121975); 166/305 (54¾)

SEQ ID NO: 1 64 [TM 1; 33-55 (P), TM 2; 67-89 (P), TM 3; 104-126 (S), TM4; 146-16 8 (P), TM5; 214-236 (S), TM6; 246-268 (P), TM7; 276-298 (S)]

odorant receptor S19 (AF121976); 140/304 (46%)

SEQ ID NO: 16 6 [TM 1; 14-36 (S), TM 2; 42-64 (P), TM 3; 78-100 (S), TM4; 1 15-13 7 (P), TM 5;

1 5 3-1 7 4 (S), TM 6; 2 1 7-2 3 9 (P)]

odorant receptor S18 (AF121975); 209/248 (84%)

SEQ ID NO: 16 8 [TM 1; 36-58 (P), TM 2; 68-90 (P), TM 3; 103-125 (P), TM 4; 146- 1668 (S), TM5; 208-230 (P), TM6; 245-267 (P), TM7; 275-297 (S)]

odorant receptor S18 (AF121975); 123/298 (41¾)

SEQ ID NO: 170 [TM 1; 31-53 (S), TM 2; 63-85 (P), TM 3; 100-122 (S), TM4; 140-1 6 2 (S), TM 5;

204-226 (P), TM6; 239-260 (P)]

MOR 3'Betal (AF133300); 103/259 (39%)

SEQ ID NO: 17 2 [TM 1; 29-51 (P), TM 2; 63-85 (P), TM 3; 99-121 (S), TM4; 144-1 6 5 (S), TM 5; 17 7-19 9 (S), TM 6; 204-2 26 (S)]

putative G-protein coupled receptor RAlc (AF079864); 112/247 (45%), SEQ ID NO: 17 4 [TM 1; 10-32 (P), TM 2; 44-66 (P), TM 3 73-93 (S), TM4; 128-150 (S), TM5; 158-179 (S), TM6; 181-203 (P) ]

olfactory receptor (AF179805); 27/101 (26%)

SEQ ID NO: 17 6 [TM 1; 5-27 (P), TM 2; 46-68 (S), TM 3; 85-107 (S), TM 4; 123-14 5 (S), TM 5;

154-176 (P), TM6; 182-204 (S), TM7; 216-37 (S)]

odorant receptor S18 (AFl 21975); 149/250 (59%)

SEQ ID NO: 17 8 [TM 1; 1-23 (S), TM 2; 28-50 (S), TM 3; 96-18 (S), TM4; 134-1 56 (S), TM5; 196-218 (P), TM6; 238-260 (P), TM7; 69-291 (S)]

putative G-protein coupled receptor RAlc (AF079864); 172/307 (56%) SEQ ID NO: 180 [TM1; 6-28 (S), TM2; 40-62 (P), TM3; 7 2-9 4 (S), TM4; 11 1-13 3 (S), TM 5; 15 8-18 0 (P), TM 6; 21 4-23 6 (P), TM 7; 25 2-27 4 (P), TM 8; 28 3-30 5 (S)]

olfactory receptor-like protein C0R3 'eta (L17432); 167/304 (54%) SEQ ID NO: 18 2 [TMl; 29-51 (S), TM2; 65-87 (S), TM 3; 108-130 (S), TM4; 144-165 (P), TM 5;

210-223 (P), TM6; 240-262 (P), TM7; 271-293 (S)]

ol factory rece tor-like protein C0R3 'beta (L17432); 153/296 (51¾) SEQ ID NO: 18 4 [TM 1; 2-24 (S), TM 2; 30-52 (P), TM 3; 64-86 (S), TM4; 105-127 (S), TM 5; 2

04-226 (P), TM6; 240-262 (P), TM7; 274-296 (S)]

olfactory recept or-1 ike protein C0R3 'beta (L17432); 150/303 (49%) SEQ ID NO: 18 6 [TM 1; 4-26 (S), TM 2; 35-57 (P), TM3; 72-94 (S), TM4; 115-137 (S), TM5; 151-172 (S), TM6; 191-213 (P ), TM 7; 249-271 (S)> TM 8; 281-303 (S)]

MOR 3'Betal (AF133300); 157/298 (52%)

SEQ ID NO: 18 8 [TM 1; 36-58 (P), TM 2; 74-96 (P), TM 3; 108-130 (P), TM 4; 19-17 1 (S), TM 5; 209-231 (P), TM 6; 260-282 (P)]

MOR 3 'Betal (AF133300); 123/307 (40%)

SEQ ID NO: 190 (TM1; 30-52 (S), TM2; 67-89 (STM3; 103-125 (S), TM4; 205--2) 2 7 (P), TM 5; 24 2-26 4 (S), TM 6; 26 9—29 1 (S)]

MOR 3'Betal (AF133300); 172/307 (56¾)

SEQ ID NO: 19 2 [TM 1; 31-53 (P), TM 2; 56-78 (S) TM 3; 81-103 (S), TM4; 107-1 2 9 (S), TM5;

1 45-1 6 7 (P), TM 6; 1 84-206 (P)]

putative G-protein coupled receptor RAlc (AF079864); 98/210 (46%) SEQ ID NO: 19 4 [TM 1; 34-56 (P), TM 2; 71-93 (P), TM 3 ; 108-130 (S), TM4; 144-166 (P), TM5; 191-21-2 (P), TM6; 224-246 (P), TM 7; 2 5 1-2 7 3 (S)] odorant receptor 5.24 (AF158963); 168/328 (51%)

SEQ ID NO: 19 6 [TM 1; 8-30 (S), TM 2; 53-75 (P), TM 3; 105-127 (P), TM4; 139-1 6 1 (S), TM 5; 16 7-18 9 (P), TM 6; 200-222 (P), TM 7; 23 1-25 3 (P)]

olfactory receptor OR18 (S29710); 189/268 (70%)

SEQ ID NO: 19 8 [TM 1; 28-50 (P), TM 2; 84-106 (S)

TM3; 117-139 (S), TM4; 144-166 (S), TM5;

185-207 (P), TM6; 213-235 (S), TM7; 243-1265 (P), TM8; 274-296 (S) ]

odorant receptor S19 (AF121976); 192/299 (64%)

SEQ ID NO: 200 [TM1; 7-29 (S), TM2; 35-57 (S), TM3; 64-86 (S), TM4; 95-117 ( S), TM 5; 14 1-16 3 (S), TM 6; 200-22 1 (P)]

olfactory receptor 17-1 (AF095725); 95/96 (98%)

SEQ ID NO: 202 [TM 1; 26-48 (P), TM 2; 62-84 (S), TM 3; 96-118 (P), TM4; 14 1-16 3 (S), TM 5;

2 04-2 25 (P), TM 6; 23 9-26 1 (P), TM 7; 26 8-29 0 (S)]

odorant receptor MOR83 (AB030894); 159/301 (52%)

Discharge number 204 [TM 1; 31-53 (P), TM 2; 65-87 (S), TM 3; 104-126 (S), TM4; 205-2 2 7 (P), TM 5; 24 3-26 5 (S), TM 6; 26 9-29 1 (S)]

odorant receptor S18 (AF121975); 163/310 (52%)

SEQ ID NO: 206 [TM 1; 1-23 (S), TM 2; 27-49 (P), TM 3; 65-87 (S), TM4; 108-130 ( S), TM 5; 2 0 5-2 27 (P), TM 6; 242-264 (S), TM 7; 268-290 (S)]

olfactory receptor 67 (AF133300); 158/309 (51%)

SEQ ID NO: 208 [TM 1; 32-54 (P), TM 2; 66-88 (P), TM 3; 98-120 (S), TM4; 13 7-15 9 (S), TM5; 2 10-2 3 1 (P), TM 6; 24 3-26.5 (P)]

odorant receptor S51 (AF121981); 112/159 (70%)

SEQ ID NO: 2 10 [TM 1; 30—52 (P), TM 2; 100—122 (P) TM 3; 127-149 (P), TM4; 15 3 — 17 5 (P), TM 5; 2 09-2 3 1 (P), TM 6; 243-2 65 (S), TM 7; 2 74-2 9 6 (S)]

odorant receptor S46 (AFl 1979); 198/307 (64%)

SEQ ID NO: 2 1 2 [TM 1; 34-56 (P), TM 2; 104-126 (P) TM 3; 149-171 (P), TM4; 210-2 3 2 (P), TM 5; 247-269 (S), TM 6; 276-298 (S) 3

odorant receptor S46 (AF121979); 209/307 (68%)

SEQ ID NO: 2 1 4 [TM 1; 3-25 (S), TM 2; 31-53 (P), TM 3; 106-128 (P), TM4; 132-1 54 (S), TM5;

15 6-17 8 (S), TM 6; 203-25 (P), TM 7; 22-26 4 (P), TM 8; 27 1-29 3 (S )]

odorant receptor S46 (AFl 21979); 174/306 (56%)

SEQ ID NO: 2 16 [TM 1; 36-58 (P), TM 2; 101-123 (P) TM 3; 141-16 3 (P), TM4; 18 1 -203 (P), TM5;

206-227 (P), TM6; 270-292 (S)]

odorant receptor S46 (AF121979); 178/307 (57%)

SEQ ID NO: 2 18 [TM 1; 26-48 (P), TM 2; 65-8 7 (S), TM3; 104-126 (S), TM4; 142-164 (S), TM5; 204-226 (P), TM6; 240-262 (P ), TM 7; 2 7 6

-2 9 7 (S)]

olfactory receptor-like protein C0R3 'beta (L17432); 159/301 (52%) SEQ ID NO: 220 [ΤΜ 1; 21-43 (P), TM 2; 84-106 (S) TM 3 ; 1 16-1 38 (S), TM; 1 45-1 67 (P), TM 5; 18 2-204 (S), TM 6; 210-2 32 (P ), TM 7; 240

-26 2 (S), TM 8; 27 2-294 (S)]

odorant receptor S46 (AFl 1979); 192/310 (61%)

SEQ ID NO: 22 2 [TM 1; 27-49 (S), TM 2; 75-97 (S), TM 3; 113-135 (P), TM 4; 140 — 16 2 (P), TM 5; 16 9-19 0 (S), TM 6; 20 3-2 25 (S)]

olfactory receptor (AJ 133430); 190/247 (76%)

SEQ ID NO: 2 24 [TM 1; 1-20 (S) TM 2; 28-50 (P), TM 3; 61-83 (S), TM 4; 92-114 (S ), TM5; 133-155 (P), TM6; 195-217 (P)]

HUMAN OLFACTORY RECEPTOR 511 (Q13606); 95/214 (44%)

SEQ ID NO: 2 26 [TM1; 27-49 (P), TM2; 58-80 (S), TM3; 93-115 (S), TM4; 1443-1 65 (S), TM5; 178-200 (S), TM6; 206-227 (P), TM7; 241

-26 3 (P), TM 8; 26 8-29 0 (S)]

odorant receptor 0R83 (AB030894); 171/307 (55%)

SEQ ID NO: 2 28 [TM 1; 25-47 (P), TM 2; 55-77 (S), TM 3; 100-122 (S), TM 4; 144-1 65 (P), TM5; 170-192 (S), TM6; 205-226 (P), TM7; 24 1

-2 6 3 (P)] odorant receptor M0R83 (AB030894); 158/308 (51¾)

SEQ ID NO: 230 [TM 1; 1-23 (P), TM 2; 27-49 (S), TM 3; 81-103 (P), TM4; 144-16 5 (P), TM 5; 18 4—206 (P), TM 6; 2 14—2 36 (P)]

olfactory receptor [Homo sapiens] (AJ003147); 154/249 (61%) SEQ ID NO: 23 [TM 1; 27-49 (P), TM 2; 63-85 (P), TM 3; 103-125 (S), TM4; 144-165 (S), TM5; 204-226 (P), TM6; 238-259 (S ), TM 7; 2 7 3

-2 95 (S)]

olfactory receptor P2 [Mus musculus] (AF247657); 194/302 (64%) SEQ ID NO: 2 3 4 [ΤΜ1; 34-55 (S), TM 2; 104—126 (P) TM 3 148-170 (S), TM4; 204-226 (P), TM5; 242-264 (S), TM6; 273-294 (S) ]

HsOLFl [Homo sapiens] (U56420); 153/304 (50%)

SEQ ID NO: 23 6 [TM 1; 22-44 (S), TM 2; 62-84 (S), TM 3; 97-119 (P), TM 4; 144-16 5 (P), TM 5; 207-229 (P), TM 6; 242-263 (S), TM 7; 278

-3 0 0 (S)]

olfactory receptor C6 [Mus musculus] (AF102523); 149/305 (48%) SEQ ID NO: 2 38 [TM 1; 34-56 (P), TM 2; 95-117 (S) TM 3; 140-162 (P), TM4; 166-188 (S), TM5; 220-224 (P), TM6; 238-260 (S) ]

odorant receptor [Mus musculus] (X92969); 201/276 (72%)

SEQ ID NO: 240 [TM1; 26-48 (P), TM2; 69-91 (P), TM3; 95-117 (S), TM4; 136-15-1 8 (P), TM5; 166-188 (S), TM6; 205-227 (P), TM7; 237 One 25 9 (S), TM 8; 27 1-29 2 (S)]

odorant receptor [Mus musculus] (X92969); 270/309 (87%)

SEQ ID NO: 24 2 [TM 1; 26-48 (P), TM 2; 60-82 (S), TM 3; 93-115 (P), TM 4; 144-16 6 (S), TM5; 176-198 (S), TM6; 202-223 (P), TM7; 234

-25 5 (S), TM 8; 26 9-29 1 (S)]

odorant receptor MORI 8 [Mus musculus] (AB030895); 183/303 (60%) SEQ ID NO: 244 [TM 1; 8-30 (S), TM 2; 43-65 (S), TM 3; 8 7-10 9 (P), TM4; 13 1-15 3 (S), TM 5; 17 3-19 5 (S), TM 6; 23 3-25 5 (P), TM 7; 2 7 1

-29 2 (P), TM8; 30 2-3 2 3 (P)]

odorant receptor MORI 8 [Mus musculus] (AB030895); 195/301 (64%) SEQ ID NO: 24 6 [TM 1; 45-67 (P), TM 2; 1 12-134 (S) TM 3; 143-165 (S), TM4; 167-1890 (S), TM5; 192-214 (S), TM6; 219—240 ( P), TM 7; 2 5 1

-27 3 (P), TM 8; 28 1-30 3 (P)]

odorant receptor A16 [Mus musculus] (AB030896); 161/300 (53%) SEQ ID NO: 24 8 [TM 1; 118-140 (P), TM 2; 159-181 (P ), TM3; 186-208 (S), TM4; 222-244 (P) TM5; 263-285 (P), TM6; 294-316 ( S)] odorant receptor MORI 8 [Mus musculus] (AB030895); 114/193 (59%) SEQ ID NO: 250 [TM 1; 2-24 (S), TM 2; 28-49 (S) , TM3; 56-78 (S), TM4; 91-113 (P), TM5; 123-145 (S), TM6; 161-18 ( S), TM7; 201-222 (P)]

olfactory receptor 0R18-rat (S29710); 175/263 (66%) SEQ ID NO: 25 2 [TM 1; 5-27 (S), TM 2; 51-73 (P), TM 3; 123-144 (P), TM4; 167-1 8 9 (P), TM 5; 2 16-2 38 (P), TM 6; 26 1-2 83 (P), TM 7; 2 95-3 17 (S)]

odorant receptor M0R18 [Mus musculus] (AB030895); 257/301 (85%) SEQ ID NO: 25 4 [TM 1; 28-49 (S), TM 2; 14 3-16 5 (S) TM 3 176-198 (S), TM 4; 202-223 (P), TM 5; 235-257 (P), TM 6; 264-286 ( S)]

odorant receptor MORI 8 [Mus musculus] (AB030895); 169/307 (55%) SEQ ID NO: 25 6 [TM 1; 13—35 (S), TM 2; 156—178 (P) TM 3; 192-2-14 (P), TM 4; 252-2-74 (P), TM 5; 28 7 -309 (P), TM 6; 3 13-3 3 5 (S)]

olfactory receptor 0R18-rat (S29710); 181/300 (60%)

SEQ ID NO: 25 CTM l; 25-47 (P), TM 2; 58-80 (P), TM 3; 93-115 (S), TM4; 140- 16 2 (P), TM 5; 18 9-2 11 (P), TM 6; 23 7-25 9 (P)]

olfactory receptor 0R18 one rat (S29710); 183/302 (60%)

SEQ ID NO: 260 [TM 1; 9-31 (P), TM 2; 67-88 (S TM 3; 90-112 (P), TM4; 1 16-1 38 ( S), TM5; 144-166 (P), TM6; 179—201 (S), TM7; 210-231 (P), TM8; 270 -2 9 2 (S)]

HsOLFl [Homo sapiens] (U56420); 166/307 (54%)

SEQ ID NO: 26 2 [TM 1; 20-42 (P), TM 2; 60-82 (S), TM 3; 100-122 (S), TM 4; 1 4 6-1 6 8 (P), TM 5; 202-224 (P), TM 6; 242-264 (S), TM 7; 27 0-292 (P)] olfactory receptor [Homo sapiens] (AF065860); 159/214 (74%) SEQ ID NO: 26 4 [TM 1; 17-39 (S), TM 2; 91-113 (S) TM 3; 1 17-1 39 (P), TM4; 144-166 (P), TM5;

183-205 (S), TM6; 208-229 (P), TM7; 244-265 (S), TM8; 274-295 (S) ]

HsOLFl [Homo sapiens] (U56420); 161/306 (52%)

SEQ ID NO: 26 6 [TM 1; 31-53 (P), TM 2; 63-85 (S), TM 3; 102-124 (P), TM 4; 142- 1 64 (P), TM 5;

20 3-2 25 (P), TM 6; 24 1-26 2 (S), TM 7; 27 1-29 3 (S)]

HsOLFl [Homo sapiens] (U56420); 180/313 (57%)

SEQ ID NO: 26 8 [TM1; 44-66 (P), TM2; 70-92 (S), TM3; 94-116 (P), TM4; 152-174 ( P), TM 5;

1 82-204 (S), TM 6; 210-2 32 (P)]

olfactory receptor [Homo sapiens] (AF065860); 142/216 (65%) SEQ ID NO: 27 0 [TM 1; 45-67 (P), TM 2; 78-100 (S) TM 3; 1 16-138 (P), TM4; 158-180 (P), TM5; 193-215 (P), TM6; 224-245 (P), TM 7; 258-280 (S), TM 8; 290-311 (S)]

olfactory receptor H7 [Mus musculus] (AF102540); 147/222 (66%) SEQ ID NO: 27 2 [TM1; 29-51 (P), TM2; 64-86 (P), TM3; 9 8-12 0 (P), TM4; 14 3-16 5 (P), TM 5;

2 0 1-2 2 3 (P), TM 6; 2 3 8-2 5 9 (S), TM 7; 2 69 1 2 9 1 (S)]

olfactory receptor C6 [Mus musculus] (AF102523); 140/302 (46%) SEQ ID NO: 27 4 [TM1; 26-48 (P), TM2; 61-83 (P), TM3; 98-120 (P), TM4; 135-157 (P), TM5; 196-218 (P), TM6; 239-260 (S)]

olfactory protein [Rattus norvegicus] (M64378); 115/258 (44%) SEQ ID NO: 27 6 [TM 1; 48-70 (P), TM 2; 91-113 (S), TM 3 13 0-15 2 (S), TM4; 17 6-19 8 (S), TM 5; 23 7-25 9 (P), TM 6; 29 9-3 2 1 ( S)]

HsOLFl [Homo sapiens] (U56420); 167/303 (55%)

SEQ ID NO: 27 8 [TM 1; 32-54 (P), TM 2; 96-18 (P), TM 3; 14 5-16 7 (P), TM 4; 2 23 (P), TM 5; 23 9-26 1 (P), TM 6; 26 9-29 1 (S)]

olfactory receptor 0R93Gib [Hylobates lar] (AF045580); 166/304 (54%) SEQ ID NO: 2 80 [TM 1; 7-29 (P)> TM 2; 7 0-9 2 (P), TM4; 11 5-13 7 (S), TM 5; 17 7-19 9 (P), TM 6; 247-26 8 (P)]

olfactory receptor 4 [Gallus gallus] (X94744); 156/282 (55%) SEQ ID NO: 28 2 [TM 1; 38-60 (P), TM 2; 103-125 (P), TM3; 132-154 (P), TM4; 167-189 (P), TM5; 207-229 (P), TM6; 246-267 (P ), TM 7; 2 78-29 9 (P)]

olfactory receptor OR93Gib [Hylobates lar] (AF045580); 161/302 (53%) SEQ ID NO: 28 4 [TM 1; 28-50 (P), TM 2; 98-120 (P). TM 3; 140-162 (P), TM4; 210-232 (P), TM5; 240-262 (S), TM6; 272-294 (S) ]

olfactory receptor OR93Ch [Pan troglodytes] (AF045577); 165/308 (53¾)

SEQ ID NO: 2886 [TM1; 1-23 (S), TM2; 25-47 (P), TM3; 56-78 (S), TM4; 90-112 (S), TM5; 142-164 (S), TM6; 198-220 (P ), TM7; 236-258 (P), TM8; 2669-290 (S)]

olfactory receptor P2 [Mus musculus] (AF247657); 134/302 (44%) SEQ ID NO: 2 8 8 [TM 1; 93-1 15 (S) TM 2; 1 28-150 (S), TM3; 161-183 (P), TM4; 212-234 (P), TM5; 264-286 (P), TM6: 305-237 (S)] ol factory receptor [Homo sapiens] (AJ003147); 183/305 (60%) SEQ ID NO: 290 [TM1; 5-27 (S), TM2; 40-62 (S) , TM 3; 83-105 (P), TM4; 135-157 (P), TM 5;

1 8 1-2 0 3 (S), TM 6; 2 13-2 3 5 (S)]

olfactory receptor [Homo sapiens] (Z98744); 160/250 (64¾) SEQ ID NO: 29 2 [TM 1; 30-52 (P), TM 2; 99-121 (P) TM 3; 1 47-169 (P), TM4; 207-229 (P), TM5; 243-265 (S), TM6; 274-296 (S)]

chick olfactory receptor 7 [Gallus gal lus] (Z79586); 151/306 (49%) SEQ ID NO: 2 94 [TM 1; 28-50 (P), TM 2; 66-88 (S), TM 3; 104-126 (S), TM4; 130-160 (P), TM 5;

221-223 (P), TM6; 242-264 (P), TM7; 270-292 (S)]

olfactory receptor 4 [Gallus gallus] (X94744); 161/310 (51%) SEQ ID NO: 29 6 [TM 1; 20-42 (P), TM 2; 61-83 (P), TM 3 9 5-11 (S), TM4; 14 3-16 5 (S), TM 5; 17 7-19 9 (S), TM 6; 206-2 27 (P )]

olfactory receptor 2 [Gallus gallus] (X94742); 106/233 (45%) SEQ ID NO: 298 [TM1; 26-48 (P), TM2; 62-84 (S),

Five TM 3; 104-126 (P), TM4; 142-164 (P), TM 5; 207-228 (P), TM 6; 27 1-293 (S ), TM 7; 30 6-3 2 8 (P)]

odorant receptor [Mus musculus] (X92969); 145/302 (48¾)

SEQ ID NO: 300 [TM 1; 7-29 (S), TM 2; 53-75 (P), TM 3; 101-123 (S), TM4; 132-1 54 (S), TM5;

1 6 3-18 5 (P), TM 6; 19 8-2 20 (S)]

dJ88J8.1 (novel 7 transmembrane receptor (rhodops in family) (ol factory receptor like) protein) (hs6Ml-l 5)) [Homo sapiens] (AL035402); 173/261 (66%)

SEQ ID NO: 30 2 [TM 1; 19-41 (S), TM 2; 83-105 (S) TM 3; 16-186 (S), TM4; 203-2 25 (P), TM 5;

2 39-26 0 (S), TM 6; 27 2-29 3 (S)]

olfactory receptor [Homo sapiens] (Z98744); 253/310 (81%) SEQ ID NO: 304 [TM 1; 8-30 (S), TM 2; 51-73 (S), TM 3; 9 4-1 16 (P), TM4; 172-194 (P), TM5; 21-22 (S), TM6; 232-254 (S)]

olfactory receptor 4 [Gallus gallus] (X94744); 126/267 (47%) SEQ ID NO: 30 [TM 1; 32-54 (P), TM 2; 62-84 (S), TM 3; 134-156 (P), TM4; 206-228 (P), TM5; 245-267 (S), TM6; 276-298 (S)]

chick olfactory receptor 4 [Gallus gallus] (Z79593); 154/309 (49%) SEQ ID NO: 30 [TM 1; 41-63 (P), TM 2; 73-95 (S), TM 3; 106-128 (S), TM4; 147—169 (P), TM5; 211-241 (P), TM6; 287-309 ( S)]

HsOLFl [Homo sapiens] (U56420); 146/310 (47%) SEQ ID NO: 3 10 [TM 1; 11-33 (S), TM 2; 42-64 (P), TM 3; 75-97 (S), TM4; 106-128 (S), TM5; 151-173 (S), TM6; 188-210 (S), TM7; 214-236 (P), TM8; 24 9-2 7 0 (S)]

olfactory receptor P2 [Mus musculus] (AF247657); 276/315 (87¾) SEQ ID NO: 3 12 [TM 1; 15-37 (S), TM 2; 53-75 (S), TM 3; 8 4-10 6 (S), TM4; 10 9-13 1 (P), TM 5; 16 1-18 3 (P), TM 6; 19 6-2 18 (P) ]

olfactory receptor [Homo sapiens] (AF065870); 246/284 (86%) SEQ ID NO: 3 14 [TM 1; 26-48 (P), TM 2; 60-82 (S), TM 3; 9 9-12 0 (P), TM4; 14-1 64 (S), TM 5; 17 4-19 5 (S), TM 6; 20 2-24 (P), TM 7 237-258 (P), TM8; 271-292 (S)]

dJ80I19.1 (ol factory receptor-1 ike protein (hs6Ml-l)) [Homo sapiens] (AL022727); 136/305 (44%)

SEQ ID NO: 3 16 [TM 1; 10-32 (S), TM 2; 46-68 (P), TM 3; 80-102 (P), TM4; 1 17-1 39 (P), TM 5;

1 5 7-1 7 9 (P), TM 6; 2 2 2-244 (P), TM 7; 2 5 9-2 8 1 (P)]

odorant receptor S19 [Mus musculus] (AF121976); 168/291 (57%) SEQ ID NO: 3 18 [TM 1; 2-24 (S), TM 2; 45-67 (P), TM 3; 7 2-94 (P), TM 4; 1 1 9 1 1 4 1 (S), TM 5; 1 7 0-1 9 2 (P), TM 6; 2 2 1-243 (P), TM 7 2 6 0-

2 8 2 (P), TM8; 2 8 8-3 10 (S)]

odorant receptor S19 [Mus musculus] (AF121976); 163/280 (58%) SEQ ID NO: 32 0 [TM 1; 36-58 (P), TM 2; 65-86 (S), TM3; 93-115 (P), TM4; 134-156 (S), TM5;

1 95-2 17 (P), TM 6; 23 6-25 7 (S)]

ol factory r eceptor-1 ike protein [Homo sapiens] (L35475); 280/316

(88%)

SEQ ID NO: 3 2 2 [TM 1; 28-50 (P), TM 2; 96-118 (P), TM 3; 14 1-16 3 (S), TM 4; 1 76 — 198 (S), TM5; 207-229 (P), TM6; 239-260 (S), TM7; 273-294 (S)]

ol factory receptor G3 [Mus musculus] (AF102535); 187/223 (83%) SEQ ID NO: 3 24 [TM 1; 4-26 (P), TM 2; 54-76 (S), TM 3; 84-106 (P), TM4; 144-166 (P), TM5; 189-211 (S), TM6; 214—235 (S)]

odorant receptor S25 [Mus musculus] (AF121977); 180/251 (71%) SEQ ID NO: 32 [TM 1; 34-56 (P), TM 2; 97-1-1 9 (P), TM 3; 14 0-16 2 (P), TM4; 17 3-19 5 (S), TM 5; 20 22-23 (P), TM 6; 26 6-28 8 (S)]

odorant receptor S25 [Mus musculus] (AF121977); 189/310 (60%) SEQ ID NO: 328 [TMl; 33-55 (P), TM2; 98—120 (P), TM 3; 14 2-16 4 (S), TM4; 204-2 26 (P), TM 5; 23 9-26 1 (S), TM 6; 27 1-29 3 ( S)]

olfactory receptor P2 [Mus musculus] (AF247657); 158/309 (51%) SEQ ID NO: 33 0 [TM 1; 19-41 (P), TM 2; 61-83 (P), TM 3 955-1117 (P), TM4; 141-163 (P), TM5; 201-223 (PTM6; 230-260 (S), TM 7; 27 2-29 3 (S)]

odorant receptor [Mus musculus] (X92969); 156/310 (50%) SEQ ID NO: 33 2 [TM 1; 1-23 (S), TM 2; 33-55 (P), TM 3; 83-105 (S), TM4; 1 18-13 9 (P), TM 5;

166-188 (P), TM6; 226-248 (P), TM7; 260

-2 82 (S), TM 8; 29 2-3 1 3 (S)]

HGMP07J [Homo sapiens]> gi I 228481 Iprf I 11804351Colfactory receptor HGMP07J [Homo sapiens] (X64995); 168/308 (54%)

SEQ ID NO: 3 3 4 [TM 1; 33-55 (P), TM 2; 104 _ 126 (P), TM 3; 144-167 (S) TM4; 200 -229 (P), TM 5;

24 3-26 5 (P), TM 6; 27 6-29 8 (P)]

olfactory receptor 17 [Mus musculus] (AF106007); 181/311 (58%) SEQ ID NO: 33 [TM 1; 20-42 (P), TM 2; 63-85 (P), TM 3; 9 6-1 18 (P), TM4; 14 5-16 7 (S), TM 5;

203-225 (P), TM 6; 238-259 (S), TM 7; 272

-2 9 3 (S)]

HGMP07J [Homo sapiens]> gi I 228481 Iprf I 11804351Colfactory receptor HGMP07J [Homo sapiens] (X64995); 160/300 (53%)

SEQ ID NO: 33 8 [TM 1; 25-47 (P), TM 2; 61-83 (S)> TM 3; 100-122 (P), TM4; 144-16 6 (P), TM5; 198-220 (P), TM6; 236-258 (S), TM7; 269-291 (S)]

odorant receptor MORI 8 [Mus musculus] (AB030895); 181/302 (59¾) SEQ ID NO: 34 0 [TM 1; 1-23 (S TM 2; 25-47 (P), TM 3; 59- 8 1 (P), TM4; 92-1 14 (S), TM 5; 1

3—165 (S), TM6; 204-226 (P), TM7; 2337-259 (S), TM8; 2667-289 (S) ]

odorant receptor A16 [Mus musculus] (AB030896); 170/297 (57¾) SEQ ID NO: 342 [TM 1; 23-45 (P), TM 2; 85-107 (S), TM 3; 136-158 (P), TM4; 17 1- 19 3 (P), TM 5; 19 6-21 (P TM 6; 230-25 2 (P), TM 7; 25 9-28 1 (S)]

odorant receptor M0R18 [Mus musculus] (AB030895); 184/297 (61%) SEQ ID NO: 344 [TM 1; 4-26 (P), TM 2; 29-51 (P), TM 3; 8 7-109 (P), TM4; 132-154 (P), TM5; 200-222 (P) TM6; 229-250 (S)]

olfactory receptor [Mus musculus] (AJ251154); 188/308 (61%) SEQ ID NO: 34 6 [TM 1; 10-32 (S), TM 2; 42-64 (P), TM 3; 7 6-98 (S), TM4; 1 15-1 3 7 (S), TM 5; 1

56-177 (S), TM 6; 2 16-238 (S), TM 7; 254-276 (S), TM 8; 288-309 (S) ]

01 factory receptor 1 ike protein C0R3 'beta [Gal lus gal lus] (L17432); 167/314 (53¾)

SEQ ID NO: 34 8 [TM 1; 2-23 (S), TM 2; 29-51 (S), TM 3; 67-89 (S), TM 4; 102-124 (P), TM 5; 1

6 1-18 3 (S), TM 6; 2 09-2 3 1 (S), TM 7; 2 3 7-

2 5 9 (S)]

olfactory receptor [Homo sapiens] (Y10529); 193/270 (71%) SEQ ID NO: 350 [TM 1; 38-60 (P), TM 2; 81-103 (S). TM 3 1 1 1-1 3 3 (P), TM4; 1 54-1 76 (S), TM 5; 2 1 8-2 4 0 (P), TM 6; 2 54-2 7 6 (P) , TM 7; 288-309 (S)]

ol factory receptor [Mus musculus domes t icus] (AF073987); 183/216 (84%) SEQ ID NO: 35 2 [TM 1; 1-23 (S), TM 2; 30-52 (P), TM 3; 64-86 (P), TM 4; 103-125 ( S), TM5; 144-165 (P), TM6; 208-230 (P), TM7; 242-264 (S), TM8; 276- 2 9 7 (S)]

odorant receptor S18 [Mus musculus] (AF121975); 219/305 (71%) SEQ ID NO: 35 4 [TM 1; 38-60 (P), TM 2; 71-93 (P), TM 3 ; 107-129 (S), TM4; 152-174 (S), TM5; 213-235 (P), TM6; 248-270 (S) , TM 7; 280

-3 0 2 (S)]

odorant receptor S19 [Mus musculus] (AF121976); 163/288 (56%) SEQ ID NO: 35 6 [TM1; 28-50 (P), TM2; 72-94 (S), TM3; 1 1 2-1 3 4 (P), TM4; 14 1-16 3 (S), TM 5; 2 21-2 43 (P), TM 6; 28 6-30 8 (P ), TM7; 326-1347 (S), TM8; 357-379 (S)]

olfactory receptor C6 [Mus musculus] (AF102523); 138/308 (441) SEQ ID NO: 358 [TM1; 29-51 (P), TM2; 66-88 (P), TM3; 106-128 (S) TM4; 132-154 (P), TM5; 197-219 (P), TM6; 234-255 (S), TM 7; 2 6 7

-2 8 9 (S)]

olfactory receptor C6 [Mus musculus] (AF102523); 140/310 (45%) SEQ ID NO: 360 [TM 1; 1-23 (S), TM 2; 28-50 (S), TM 3; 6 4-8 6 (P), TM4; 10 0-1 2 2 (P), TM 5; 16 6-1 8 8 (P), TM 6; 2 0 1-2 2 2 (S)]

olfactory receptor C6 [Mus musculus] (AF102523); 100/215 (46%) SEQ ID NO: 36 2 [TM 1; 32-54 (P), TM 2; 105-127 (P). TM 3; 144-166 (Ρ) TM4; 185-207 (S), TM5; 2 1 0-2 3 1 (P), TM 6; 2 4 1-2 6 3 (S), TM 7; 2 7 2

-2 9 4 (S)]

HsOLFl [Homo sapiens] (U56420); 161/310 (51%)

SEQ ID NO: 364 [TM 1; 19-41 (P), TM 2; 61-83 (S), TM 3; 90-112 (P), TM4; 1 16-13 8 (S), TM 5;

1 4 5-1 6 7 (S), TM 6; 1 7 9-2 0 1 (S), TM 7; 2 1 0 1 2 3 2 (P), TM 8; 2 7 0-2 9 2 ( S)]

HsOLFl [Homo sapiens] (U56420); 168/307 (54%)

SEQ ID NO: 36 6 [TM 1; 19-41 (S), TM 2; 60-82 (S), TM 3; 99-121 (S), TM4; 140-1 6 2 (P), TM 5;

206-227 (P), TM6; 243-264 (S), TM7; 273

-2 9 3 (S)]

CfOLF2 [Canis familiaris] (U53680); 175/308 (56%)

SEQ ID NO: 36 8 [TM1; 29-51 (P), TM2; 101-123 (P), TM3; 144-166 (S), TM4; 206 -2 27 (P), TM 5; 240-26 2 (S), TM 6; 27 3-295 (S)]

olfactory receptor 0R93Ch [Pan troglodytes] (AF045577); 162/313 (51¾)

SEQ ID NO: 37 0 [TM 1; 23-45 (P), TM 2; 66-87 (S), TM 3; 94-116 (S), TM4; 133-15 5 (S), TM5; 200-222 (P), TM6; 246-268 (S), TM7; 276

-2 9 8 (S)]

CfOLFl [Canis familiaris] (U53679); 153/299 (51%)

SEQ ID NO: 37 2 [TM 1; 41 _ 63 (P), TM 2; 102-124 (S), TM 3; 137-159 (P), TM 4; -229 (P), TM5; 246-268 (P), TM6; 278—300 (P)] HsOLFl [Homo sapiens] (U56420); 173/306 (56%)

SEQ ID NO: 3 7 4 [TM 1; 7-29 (S), TM 2; 32-53 (P), TM 3; 60-82 (S), TM 4; 100-122 (S), TM5; 144-166 (P), TM6; 200-222 (P), TM7; 235-257 (S)]

similar to rat ol factory receptor 0R18; similar to S29710 (PID: g423702) [Homo sapiens] (AC004908); 220/311 (70%)

SEQ ID NO: 37 6 [TM 1; 1-23 (S), TM 2; 28-50 (P), TM 3; 59-81 (S), TM4; 95-1 17 ( P), TM5; 142-164 (P), TM6; 206-228 (P), TM7; 230-260 (P)]

similar to rat ol factory receptor 0R18; similar to S29710

(PID: g423702) [Homo sapiens] (AC004908); 225/291 (77%)

SEQ ID NO: 378 [TM1; 9-31 (S), TM2; 123-145 (P), TM3; 148-170 (S), TM4; 192 -2 14 (S), TM 5; 23 6-25 8 (P), TM 6; 2995-3 17 (P), TM 7; 334 — 35 5 (P), TM 8; 367-389 (S)]

olfactory receptor 0R18-rat (S29710); 204/302 (67%)

SEQ ID NO: 38 0 [TM 1; 9-31 (S), TM 2; 34-56 (P), TM 3; 62-84 (S), TM 4; 971 19 (S), TM5; 144-166 (S), TM6; 205-227 (P), TM7; 242-263 (P), TM8; 275-2 9 6 (P)]

olfactory receptor 4 [Gallus gallus] (X94744); 173/303 (57%) SEQ ID NO: 38 2 [TM 1; 20-42 (S), TM 2; 62-84 (S), TM 3; 9 5-1 17 (S), TM4; 14 6-16 8 (S), TM 5; 205-2 26 (P), TM 6; 23 7-25 9 (S) , TM 7; 2 6 8 -290 (S)]

odorant receptor M0R83 [Mus musculus] (AB030894); 156/304 (51%) SEQ ID NO: 38 4 [TM1; 22-44 (P), TM2; 62-84 (S), TM3; 9 8-12 0 (S), TM4; 144-16 6 (P), TM 5; 19 7-2 19 (P), TM 6; 23 7-25 (S), TM 7; 26 9-29 1 (S)]

odorant receptor M0R83 [Mus musculus] (Class 30894); 159/304 (52%) SEQ ID NO: 38 6 [TM 1; 49-71 (P), TM 2; 77-99 (S), TM 3; 120-142 (P), TM4; 173-195 (S), TM5; 221-243 (P), TM6; 260-282 (P ), TM 7; 2 89-3 1 1 (P)]

MOR 3 'Betal [Mus musculus] (AF133300); 188/310 (60%)

SEQ ID NO: 38 8 [TM 1; 17-39 (P), TM 2; 50-72 (S), TM 3; 82-104 (P), TM 4; 13 4-15 6 (S), TM 5; 167-189 (S), TM 6; 196-17-17 (P), TM 7; 2 24

-2 4 5 (S)]

olfactory receptor P2 [Mus musculus] (AF247657); 226/296 (76%) SEQ ID NO: 39 0 [TM 1; 19-41 (P), TM 2; 61-83 (P), TM 3 94-1 16 (P), TM4; 1 36-158 (P), TM 5; 178-200 (S), TM 6; 207-229 (P ), TM 7; 2 7 3

-2 95 (S)]

olfactory receptor P2 [Mus musculus] (AF247657); 170/304 (55¾) SEQ ID NO: 39 2 [TM 1; 27-49 (P), TM 2; 62-84 (P) TM 3; 9 5-117 (P), TM4; 135-157 (P), TM5; 177-199 (S), TM6; 207-229 (P)> TM 7; 2 7 3

-2 95 (S)] ol factory receptor P2 [Mus musculus] (AF247657); 164/304 (53%) SEQ ID NO: 39 4 [TM 1; 30-52 (P), TM 2; 74-96 (P), TM 3 13 7-15 7 (P), TM4; 18 3-205 (S), TM 5; 25 58-28 0 (P), TM 6; 32 0-34 1 (S )]

taste bud receptor protein TB 567 [Rat tus norvegicus] (U50948); 235/307 (76%)

SEQ ID NO: 39 6 [TM 1; 24-46 (P), TM 2; 56-78 (S), TM 3; 94-116 (S), TM4; 1 2 9-1 5 1 (P), TM5; 207-229 (P), TM6; 241-263 (S), TM7; 272-292 (P)]

olfactory receptor 0R14-rat (S29709); 256/304 (84%)

SEQ ID NO: 39 8 [TM 1; 28-50 (P), TM 2; 98-120 (P) TM 3; 127-149 (P), TM4; 203- 2 25 (P) TM 5; 24 9-27 1 (S), TM 6; 274-295 (S)]

olfactory receptor 0R14-rat (S29709); 234/299 (78%)

SEQ ID NO: 400 [TM 1; 32-54 (P), TM 2; 57-79 (P), TM 3; 92-114 (P), TM4; 122-15 1 (P), TM5; 201-2-3 (P), TM6; 237-259 (S)]

olfactory receptor 0R14-rat (S29709); 189/302 (62¾)

SEQ ID NO: 40 2 [TM 1; 30-52 (P), TM 2; 62-84 (S), TM 3; 94-116 (P), TM4; 133-159 (P), TM5; 203-225 (P), TM6; 238-259 (S), TM7; 272-293 (S)]

olfactory receptor [Rattus norvegicus] (X80671); 210/305 (68%) SEQ ID NO: 04 [TM 1; 26-48 (P), TM 2; 94-1 16 (S) TM 3; 1 2 9—15 1 (S), TM4; 18 1—203 (P), TM 5; 2 0 8-2 2 9 (P), TM 6; 240-- 2 62 (S), TM 7; 2 7 1

-2 9 2 (S)]

olfactory receptor 0R14-rat (S29709); 201/300 (67%)

SEQ ID NO: 40 6 [TM 1; 28-50 (P), TM 2; 63-85 (S), TM 3 '; 93-115 (P), TM4; 130- 15 2 (P), TM 5; 202-224 (P), TM 6; 23 8—25 9 (P)]

olfactory receptor [Rattus norvegicus] (X80671); 247/302 (81%) SEQ ID NO: 40 [TM 1; 1-21 (S), TM 2; 40-62 (P), TM 3; 9 8-120 (P), TM4; 23-245 (P), TM5; 260-282 (S), TM6; 290-31 (S)]

taste bud receptor protein TB 641 [Rat tus norvegicus] (U50949); 185/297 (62%)

SEQ ID NO: 4 1 0 [TM 1; 20-42 (P), TM 2; 200-222 (P) TM 3; 23 9-26 1 (P), TM4; 26 9- 290 (S), TM5; 304-326 (P), TM6; 331-1352 (P), TM7; 358

-3 7 2 (S)]

taste bud receptor protein TB 641 [Rat tus norvegicus] (U50949); 170/302 (56%)

SEQ ID NO: 4 1 2 [TM 1; 1-23 (S), TM 2; 26-48 (S), TM 3; 110-13 2 (S), TM4; 13 7-15 8 (P), TM5; 170-192 (P), TM6; 198-220 (S)]

taste bud receptor protein TB 641 [Rat tus. norvegicus] (U50949); 140/234 (59%)

SEQ ID NO: 4 1 4 [TM 1; 3-25 (S), TM 2; 30-52 (P), TM 3; 63-85 (S), TM 4; 180-202 (S), TM5; 205-226 (P), TM6; 239-261 (P), TM7; 266- 2 8 8 (S)]

taste bud receptor protein TB 641 [Rat tus norvegi cus] (U50949); 165/299 (55¾)

SEQ ID NO: 4 16 [TM 1; 6-28 (S), TM 2; 41-63 (S), TM 3; 102-124 (P), TM 4; 142-1 6 4 (P), TM 5;

1 7 0-1 9 2 (S), TM 6; 1 9 8—2 2 0 (S)]

olfactory receptor 0R18-rat (S29710); 154/209 (73%)

SEQ ID NO: 4 18 [TM 1; 26-48 (S), TM 2; 99 _ 1 2 1 (P)-TM 3; 14 1-16 3 (P), TM 4; 204-2 26 (P), TM5; 235-25 (P), TM6; 267-1829 (S), TM7: 305-227 (P)

odorant receptor A16 [Mus musculus] (AB030896); 164/286 (57%) SEQ ID NO: 4 20 [TM 1; 33-55 (P), TM 2; 70-92 (S), TM 3 ; 103-125 (P), TM4; 209—231 (P), TM5; 247-269 (S), TM6; 278-300 (S) ]

olfactory receptor 4 [Gallus gallus] (X94744); 159/306 (51%) SEQ ID NO: 42 [TM 1; 6-28 (S), TM 2; 31-52 (P), TM 3; 9 1-11 3 (P), TM4; 13 7-15 9 (S), TM 5;

2 0 1-2 2 3 (P), TM 6; 2 3 9-2 6 1 (S), TM 7; 2 7 0-2 9 2 (S)]

olfactory receptor OR93Ch [Pan troglodytes] (AF045577); 166/305 (54%)

SEQ ID NO: 4 2 4 [TM 1; 24-46 (P), TM 2; 9-12 0 (P). TM 3; 13 7-15 9 (P), TM 4; 204-2 2 5 (P), TM 5; 2 3 7-2 5 8 (S), TM 6; 2 7 0-2 9 1 (S)]

HsOLFl [Homo sapiens] (U56420); 154/301 (51%) SEQ ID NO: 4 26 [TM 1; 17-39 (S), TM 2; 72-94 (S), TM 3; 13 4-156 (P), TM 4; 203-2 2 4 (P), TM 5; 2 38-260 (P), TM 6; 26 9-29 1 (S)]

olfactory receptor 2 [Gallus gallus] (X94742); 155/307 (50%) SEQ ID NO: 42 8 [TM 1; 26-48 (P), TM 2; 55-77 (S), TM 3; 8 1-10 3 (S), TM4; 14 1-16 3 (P), TM 5; 19 7-2 19 (P), TM 6; 23 8-26 0 (P) , TM 7; 2 6 8

-2 90 (S)]

olfactory receptor 0R18-rat (S29710); 193/299 (64%)

SEQ ID NO: 4 30 [TM 1; 35-57 (S), TM 2; 96-118 (S) TM 3; 130-152 (P), TM4; 156 _ 1 7 8 (S), TM 5; 19 3-2 15 (P), TM 6; 23 9-26 1 (P), TM 7; 26 6

-288 (S), TM8; 294-315 (S)]

olfactory receptor 0R18-rat (S29710); 213/304 (70%)

SEQ ID NO: 4 3 2 [TM 1; 10-32 (S), TM 2; 63-85 (P), TM 3; 101-123 (S), TM4; 158- 180 (P) TM5; 194-216 (P), TM6; 229-249 (S)]

01 factory receptor [Rattus norvegicus] (AF010293); 198/263 (75%) SEQ ID NO: 4 3 4 [TM 1; 16-38 (P), TM 2; 56-78 (S), TM 3 86-108 (P), TM4; 139-161 (P), TM5; 197-219 (P), TM6; 238-260 (S ), TM 7; 27 0-29 1 (S)]

olfactory protein [Rattus norvegicus] (M64378); 142/294 (48%) SEQ ID NO: 4 36 [TM 1; 8-30 (P), TM 2; 60-82 (S), TM 3; 9 3-115 (P), TM4; 139-16-11 (P), TM5;

203-225 (P), TM 6; 268-290 (S)] olfactory receptor C6 [Mus musculus] (AF102523); 149/312 (47%) SEQ ID NO: 4 38 [TM 1; 21-43 (P), TM 2; 89-111 (S), TM 3; 132-154 (S), TM4; 199—221 (P), TM5; 239-260 (S), TM6; 269-291 ( S)]

olfactory receptor 2 [Gallus gallus] (X94742); 148/304 (481) SEQ ID NO: 44 0 [TM 1; 34-56 (P), TM 2; 62-84 (P), TM 3; 8 8- 110 (S), TM4; 206-228 (P), TM5; 238-260 (P), TM6; 270-291 (S)]

olfactory receptor 2 [Gallus gallus] (X94742); 158/307 (51%) SEQ ID NO: 44 2 [TM 1; 23-45 (S), TM 2; 76-98 (S), TM 3; 134-156 (S), TM4; 199—221 (P), TM5; 240-261 (S), TM6; 270—291 (P)]

olfactory receptor 4 [Gallus gallus] (X94744); 171/301 (56%) SEQ ID NO: 444 [TM 1; 3-25 (S), TM 2; 37-59 (S), TM 3; 7 8 -100 (P), TM4; 147-169 (P), TM5; 184-206 (P), TM6; 211-235 (S)]

olfactory receptor OR93Ch [Pan troglodytes] (AF045577); 134/245 (54¾)

SEQ ID NO: 446 [TM 1; 8-30 (P), TM 2; 33-54 (P), TM 3; 95-117 (S), TM 4; 126-148 ( P), TM5; 2 0 8 2 3 0 (P) TM6; 2 71-2 9 3 (S)]

olfactory receptor 4 [Gallus gallus] (X94744); 149/304 (49%) SEQ ID NO: 44 8 [TM 1; 57-79 (P), TM 2; 96 _ 1 18 (S). TM 3 131-155 (S), TM4; 205-227 (S), TM5; 2337-259 (P), TM6; 274-295 (S )]

taste bud receptor protein TB 641 [Rat tus norvegicus] (U50949); 173/298 (58%)

SEQ ID NO: 450 [TM1; 19-41 (P), TM2; 62-84 (P), TM3; 95-117 (P), TM4; 141--16 3 (P), TM5; 202-224 (P), TM6; 240-261 (P), TM7; 272-294 (S)]

olfactory receptor C6 [Mus musculus] (AF102523); 152/300 (50%) SEQ ID NO: 45 2 [TM l; 31-53 (P), TM 2; 95 _ 1 17 (P) TM 3 125-147 (P), TM4; 180-202 (S), TM5; 208-229 (P), TM6; 238-260 ( S), TM 7; 2 72-2 94 (P)]

olfactory receptor [Rattus norvegicus] (X80671); 193/301 (64%) SEQ ID NO: 45 [TM 1; 2-24 (S), TM 2; 29-51 (S), TM 3; 59 -8 1 (S), TM4; 107-129 (S), TM5; 169-190 (P), TM6; 201-223 (P)]

odorant receptor M0R83 [Mus musculus] (AB030894); 156/269 (57%) SEQ ID NO: 45 6 [TM 1; 1-21 (S), TM 2; 40-62 (P), TM 3; 9 8-12 0 (P), TM4; 2 3-2 4 5 (P), TM 5; 2 5 9-2 8 1 (S), TM 6; 2 9 8-3 2 0 (P)]

tas te bud receptor protein TB 641 [Rat tus norvegicus] (U50949); 154/249 (61%)

SEQ ID NO: 45 8 [TM 1; 25-47 (P), TM 2; 55-77 (S), TM 3; 97-119 (S), TM4; 140-16 2 (S), TM5; 200-222 (P), TM6; 230-258 (S)]

olfactory receptor 4 [Gallus gallus] (X94744); 153/303 (50%) SEQ ID NO: 460 [TM 1; 1-17 (S), TM 2; 27-49 (S), TM 3; 6 7-89 (P), TM4; 102-124 (P), TM5; 1 74-196 (S), TM 6; 208-230 (P), TM 7; 238-260 (S)]

olfactory receptor [Homo sapiens] (Y10529); 185/261 (70%) SEQ ID NO: 46 2 [TM 1; 1-20 (S), TM 2; 57-79 (P), TM 3; 8 9 11 1 1 (S), TM4; 12 2-144 (P) TM 5;

1 56-1 78 (P), TM 6; 2 24-2 46 (P)]

olfactory receptor 4 [Gallus gallus] (X94744); 122/229 (53%) SEQ ID NO: 46 4 [TM 1; 32-54 (S), TM 2; 92-114 (P) TM 3 140-162 (S), TM4; 197-219 (S), TM5; 238-260 (S), TM6; 272-293 (P)]

olfactory receptor 0R93Gib [Hylobates lar] (AF045580); 160/309 (51¾) SEQ ID No. 4 6 6 [TM 1; 1-23 (S), TM 2; 33-55 (S), TM 3; 6 9-91 (P), TM4; 150-171 (P), TM5; 1

8 2-204 (P), TM 6; 2 1 1-2 3 3 (S)]

HsOLFl [Homo sapiens] (U56420); 147/247 (59%)

SEQ ID NO: 46 8 [TM 1; 26-48 (P), TM 2; 94 _ 1 16 (P) TM 3; 13 6-158 (P), TM 4; 180- 20 2 (S), TM 5;

2 09-2 3 1 (P), TM 6; 2 3 8-2 6 0 (S), TM 7; 2 7 1-2 9 2 (P)]

olfactory receptor 4 [Gallus gallus] (X94744); 170/307 (55%) SEQ ID NO: 47 0 [TM 1; 7-29 (P), TM 2; 35-57 (S) TM 3; 7 0-92 (S), TM4; 184-205 (P), TM5; 213-235 (S), TM6; 2427-268 (P))]

olfactory receptor OR93Gib [Hylobates lar] (AF045580); 151/283 (53%) SEQ ID NO: 47 2 [TM 1; 19-41 (P), TM 2; 56-78 (S), TM 3 104-126 (P), TM4; 144-166 (P), TM5; 203-224 (P), TM6; 2337-259 (P), TM7; 269-291 (P)]

odorant receptor M0R83 [Mus musculus] (AB030894); 160/306 (52%) SEQ ID NO: 47 4 [ΤΜ1; 27-49 (P), TM 2; 144-164 (S), TM 3 172-193 (S), TM4; 205-226 (P), TM5; 242-264 (P), TM6; 268-290 (S )]

odorant receptor M0R83 [Mus musculus] (AB030894); 170/308 (55%) SEQ ID NO: 47 6 [TM 1; 37-59 (P), TM 2; 108-130 (S), TM 3; 153-175 (P), TM4; 188-210 (P), TM5; 214-235 (P), TM6; 251-273 (P), TM 7; 2 7 8

-3 0 0 (S)]

odorant receptor M0R83 [Mus musculus] (AB030894); 168/297 (56%) SEQ ID NO: 47 8 [TM 1; 29-51 (P), TM 2; 58-80 (S), TM 3; 1 4 1-16 3 (P), TM4; 17 7-19 9 (P), TM 5; 205-2 26 (P), TM 6; 23 9-26 1 (P ), TM 7; 2 7 1

-2 9 3 (S)]

odorant receptor M0R83 [Mus musculus] (AB030894); 159/300 (53%) SEQ ID NO: 48 0 [TM 1; 30-52 (P), TM 2; 95—117 (S), TM 3 149-171 (S), TM4; 197-219 (P), TM5; 241-263 (P), TM6; 268-290 (P )]

similar to rat ol factory receptor 0R18; similar to S29710 (PID: g423702) [Homo sapiens] (AC004908); 167/312 (53%)

SEQ ID NO: 48 2 [TM 1; 23-45 (P), TM 2; 58-80 (S), TM 3; 96-18 (S), TM4; 14 1-16 3 (S), TM5; 200-222 (P), TM6; 245-267 (S), TM7; 270

-2 9 2 (S)] CfOLFl [Canis familiaris] (U53679); 149/310 (48%)

SEQ ID NO: 4 8 4 [TM 1; 29-50 (P), TM 2; 60-82 (S), TM 3; 95-1 17 (P), TM4; 13 4-1 56 (S), TM5; 203-225 (P), TM6; 238-259 (S), TM7; 274-294 (S)]

olfactory receptor P2 [Mus musculus] (AF247657); 144/307 (46%) SEQ ID NO: 48 6 [TM 1; 26-48 (S), TM 2; 88-110 (P), TM 3 136-158 (S), TM4; 194—216 (P), TM5; 231-253 (P), TM6; 259-281 (S )]

similar to rat ol factory receptor 0R18; similar to S29710 (PID: g423702) [Homo sapiens] (AC004908); 177/296 (59%)

SEQ ID NO: 4 8 8 [TM 1; 30-52 (P), TM 2; 70-92 (S), TM 3; 106-128 (S), TM4; 146-1 6 8 (P), TM 5; 19 6-2 18 (P), TM 6; 23 9-26 1 (S), TM 7; 27 0-29 2 (S)]

odorant receptor S46 [Mus musculus] (AF121979); 188/304 (61%) SEQ ID NO: 490 [TM1; 25-47 (P), TM2; 53-75 (S), TM3; 15 0-17 2 (S), TM4; 19 9-22 1 (P), TM 5; 23 5-25 7 (P), TM 6; 26 9-29 1 (S )]

odorant receptor MORI 8 [Mus musculus] (AB030895); 193/301 (64%) SEQ ID NO: 49 2 [TM 1; 6-28 (S), TM 2; 30-51 (S), TM 3 105-127 (P), TM4; 138—160 (P), TM5; 169-91 (S), TM6; 199-221 ( P), TM7; 235-257 (P), TM8; 266-288 (S)]

odorant receptor A16 [Mus musculus] (AB030896); 184/302 (60%) SEQ ID NO: 49 4 CTM l; 24-46 (P), TM 2; 57-79 (S), TM3; 108-130 (S), TM4; 144-167 (S), TM5;

1 7 7-1 9 9 (S), TM 6; 2 9-2 3 1 (P), TM 7; 2 3 9-2 6 1 (S)> TM 8; 2 7 0-2 9 2 ( P)]

odorant receptor SI [Mus musculus] (AF121972); 129/297 (43%) SEQ ID NO: 49 6 [TM 1; 74-96 (P), TM 2; 1 26-1 48 (S) TM 3; 169-19-1 (P), TM4; 206—228 (P), TM5;

234-255 (P), TM6; 266-288 (P), TM7; 297-319 (P)]

olfactory receptor P2 [Mus musculus] (AF247657); 130/305 (42¾) SEQ ID NO: 498 [TM1; 48-70 (P), TM2; 73-95 (S), TM3; 9 9-12 1 (S), TM4; 13 0-15 1 (S), TM 5;

162-24-184 (P), TM6; 222-244 (P), TM7; 254-275 (P), TM8; 284-306 (S) ]

chick olfactory receptor 7 [Gallus gallus] (Z79586); 130/303 (42%) SEQ ID NO: 500 [TM 1; 8-30 (P), TM 2; 34-56 (P), TM 3 82-104 (S), TM4; 140-162 (P), TM5;

240-224 (P), TM6; 240-261 (P), TM7; 269-291 (S)]

odorant receptor SI [Mus musculus] (AF121972); 143/307 (46%) SEQ ID NO: 50 2 [TM 1; 1-23 (S), TM 2; 42-64 (S), TM 3; 8 4-106 (P), TM4; 148-169 (P), TM5; 184-205 (S), TM6; 213-235 (S)]

olfactory receptor E6 [Mus musculus] (AF102528); 155/223 (69%) SEQ ID NO: 50 4 [TM 1; 2-24 (S), TM 2; 40-62 (S), TM 3; 80-102 (P), TM4; 144-166 (P), TM5; 181-202 (S), TM6; 214-235 (S)] olfactory receptor [Rattus norvegicus] (X80671); 127/243 (52%) SEQ ID NO: 50 [TM1; 1-23 (P), TM2; 27-49 (P), TM3; 6 5-87 (S), TM4; 89-111 (P), TM5; 156-178 (P), TM6; 194-215 (P), TM7; 2 2 7-2 4 9 (S)]

olfactory receptor [Gorilla gorilla] (AF101764); 93/214 (43%) SEQ ID NO: 50 [TM 1; 11-33 (P), TM 2; 49-71 (S), TM 3; 80-102 (S), TM4; 128-150 (S), TM5; 193-215 (P), TM6; 225-247 (P) , TM7; 254-276 (S)]

olfactory receptor P2 [Mus musculus] (AF247657); 128/290 (44%) SEQ ID NO: 5 10 [TM 1; 18-40 (P), TM 2; 56-78 (P), TM 3; 9 1-11 3 (S), TM4; 125-147 (S), TM5; 200-222 (P), TM6; 242-264 (S), TM7 ; 26 9-29 1 (S)]

ol factory recept or-1 ike protein [Rat tus norvegicus] (AF029357); 129/300 (43%)

SEQ ID NO: 5 1 2 [TM 1; 25-47 (P), TM 2; 55-77 (S), TM 3; 93-115 (P), TM4; 124-1 46 (S), TM5; 206-228 (P), TM6; 237-259 (P), TM7; 270-291 (S)]

olfactory receptor [Gorilla gorilla] (AF101764); 125/302 (411) SEQ ID NO: 51 4 [TM 1; 8-30 (S), TM 2; 32-51 (P), TM 3; 63 -85 (S), TM4; 94-116 (S), TM5; 141-163 (P), TM6; 201-223 (P), TM7; 244 -26 6 (S), TM 8; 27 2-29 3 (S)] ol factory receptor-1 ike protein [Rattus norvegicus] (AF029357); 131/297 (44) '

SEQ ID NO: 5 16 [TM 1; 26-48 (P), TM 2; 53-75 (S), TM 3; 96-18 (S), TM4; 13 5-1 5 7 (P), TM 5; 198-220 (P), TM 6; 24 1-26 3 (S), TM 7; 27 0-291 (S)]

gustatory receptor 43 [Rattus norvegicus] (AB038167); 265/311 (85%) SEQ ID NO: 5 18 [TM1; 31-52 (P), TM2; 62-84 (S), TM3; 9 9-12 1 (P), TM4; 144-16 6 (S), TM 5; 22-2 24 (P), TM 6; 23 6-25 8 (P), TM 7; 2 7 1

-2 9 2 (S)]

dJ80I19.7 (olfactory receptor-1 ike protein (hs6Ml-3)) [Homo sapiens] (AL022727); 174/304 (57%)

SEQ ID NO: 52 0 [TM 1; 8-30 (P), TM 2; 79-101 (P), TM 3; 128-150 (S), TM 4; 18 6- 2 08 (P), TM 5; 2 6-2 4 7 (S), TM 6; 2 5 7-2 7 7 (S)]

gustatory receptor 43 [Rattus norvegicus] (AB038167); 169/283 (59%) SEQ ID NO: 5 2 2 [TM 1; 32-54 (P), TM 2; 56-78 (S), TM 3; 9 1-11 3 (S), TM4; 14 2-1 64 (S), TM 5; 205-2 27 (P), TM 6; 2 38-260 (S), TM 7; 2 7 2

-2 94 (S)]

olfactory protein [Rattus norvegicus] (M64377); 161/303 (53%) SEQ ID NO: 52 4 [TM 1; 1-22 (S), TM 2; 29-51 (S), TM 3; 1 0 1-12 3 (P), TM4; 17 2-19 4 (P), TM 5; 2 13-2 35 (S), TM 6; 23 9-26 1 (S) ]

olfactory protein [Rattus norvegicus] (M64392); 165/268 (61%) SEQ ID NO: 5 2 6 [TM 1; 28-50 (P), TM 2; 61-83 (S TM 3; 103-125 (P), TM 4; 140-1 6 2 (P), TM 5; 20 2-2 24 (P), TM 6; 23 7—25 9 (P)]

olfactory protein [Rattus norvegicus] (M64377); 161/305 (52%) SEQ ID NO: 528 [TM1; 27-49 (P), TM2; 63-85 (S), TM3; 9 1-1 13 (S), TM4; 14 1-163 (S), TM 5;

177-199 (S), TM6; 206-228 (P), TM7; 240

-26 2 (S), TM 8; 27 0-29 2 (S)]

olfactory receptor [Pan troglodytes] (AF101741); 195/307 (63%) SEQ ID NO: 5 30 [TM 1; 2-24 (S), TM 2; 31-53 (S), TM 3; 6 5-87 (S), TM4; 109—131 (S), TM5; 169—191 (P), TM6; 209—226 (S)]

olfactory receptor [Mus musculus] (AJ251154); 190/285 (66%) SEQ ID NO: 53 2 [TM 1; 33-55 (P), TM 2; 98 _ 120 (S) TM 3; 132-25-154 (S), TM4; 175-197 (S), TM5;

205-227 (P), TM6; 237-258 (P), TM7; 278

-2 9 9 (S)]

olfactory factor 0R37 one rat (S29711); 244/304 (80%)

SEQ ID NO: 5 3 4 [TM 1; 2-24 (S), TM 2; 31-53 (S), TM 3; 65-87 (S), TM 4; 109-13 1 (S), TM5; 171-193 (P), TM6; 208-226 (P)]

olfactory receptor [Mus musculus] (AJ251154); 197/285 (69%) SEQ ID NO: 536 [TM1; 1-23 (S), TM2; 57-79 (P), TM3; 1 28-150 (S), TM4; 169-191 (S), TM5; 206-228 (P), TM6; 237-259 (P) , TM 7; 2 6 7

-28 8 (P), TM8; 30 5-3 2 7 (S)] ol factory factor OR37 one rat (S29711); 259/304 (85%)

SEQ ID NO: 538 [TM1; 8-30 (P), TM2; 56-78 (S),

TM3; 81-103 (S), TM4; 107-129 (S), TM5;

1 4 8-17 0 (P), TM 6; 17 7-1 9 9 (P), TM 7; 203-2 25 (P)]

olfactory receptor [Mus musculus] (AJ251154); 166/283 (581) SEQ ID NO: 54 0 [TM 1; 24-46 (P), TM 2; 62-84 (S), TM 3; 101 -12 3 (S), TM4; 13 7-15 9 (S), TM 5; 17 1-19 3 (S), TM 6; 20 7-2 29 (P), TM 7; 2 3 7 1 2 5 8 (P), TM 8; 2 7 4-2 9 6 (S)]

olfactory receptor [Mus musculus] (AJ251154); 219/319 (68%) SEQ ID NO: 54 2 [ΤΜ1; 43-65 (P), TM2; 1 17-1 39 (S).

TM3; 152-174 (P), TM4; 214-236 (P), TM5;

2 5 3-2 7 4 (S), TM 6; 2 8 6-3 0 6 (S)]

ol factory protein [Rattus norvegicus] (M64377); 174/311 (55¾) SEQ ID NO: 544 [TM 1; 39-61 (P), TM 2; 1 16-138 (P). TM 3; 15 2-17 4 (P), TM4; 2 14-2 36 (P), TM 5; 25 3-274 (P), TM 6; 284-306 (S)]

ol factory receptor [Homo sapiens] (AJ003147); 171/308 (55%) SEQ ID NO: 54 6 [TM1; 33-55 (P), TM2; 68-90 (P), TM3; 100-122 (S), TM4; 144-165 (S), TM5: 208-230 (P), TM6; 244-266 (S) , TM 7; 27 9-29 8 (S)]

HGMP07J [Homo sapiens]> gi | 2284811 pr f I 11804351C olfactory receptor HGMP07J [Homo sapiens] (X64995); 143/297 (48%)

SEQ ID NO: 54 8 [TM 1; 17-39 (P), TM 2; 70-92 (S), TM3; 98-120 (P) TM4; 144-167 (P), TM5; 202-224 (P), TM6; 238-259 (S)]

olfactory receptor OR93Gib [Hylobates lar] (AF045580); 149/309 (48%) SEQ ID NO: 550 [TM 1; 1-19 (S), TM 2; 27-49 (P), TM 3; 1 0 3-1 2 5 (S), TM4; 1 3 9-1 6 1 (P), TM 5; 2 0 1-2 2 3 (P), TM 6; 2 3 7-2 5 8 (S) ]

olfactory factor 0R37-rat (S29711); 148/305 (48%)

SEQ ID NO: 55 2 [TM 1; 33-54 (P), TM 2; 60-82 (P), TM 3; 95-117 (P), TM4; 133-15 5 (S), TM5; 202-224 (P), TM6; 239-261 (P), TM7; 273

-2 9 4 (S)]

olfactory receptor E3 [Mus musculus] (AF102527); 159/223 (71%) SEQ ID NO: 55 4 [TM 1; 19-41 (S), TM 2; 49—71 (P), TM 3 8 1-10 3 (S), TM4; 12 1-14 3 (P), TM 5; 16 3-18 5 (S), TM 6; 2 16-2 3 8 (P ), TM7; 260-1282 (S), TM8; 294-314 (S)]

olfactory receptor E3 [Mus musculus] (AF102527); 168/223 (75) SEQ ID NO: 55 6 [TM 1; 33-55 (P), TM 2; 65—87 (P), TM 3; 1 0 1-1 2 3 (S), TM 4; 1 49-1 7 1 (P), TM 5; 2 0 8-2 3 0 (P), TM 6; 242-2 64 (P), TM 7; 2 7 7

-298 (S), TM8; 320-342 (P)]

olfactory receptor E3 [Mus musculus] (AF102527); 128/223 (57%) SEQ ID NO: 55-8 [TM1; 4-26 (S), TM2; 34-56 (S), TM3; 6 2-84 (S), TM4; 16 5-18 7 (P), TM 5; 204-2 26 (P), TM 6; 23 5-25 7 (S)]

olfactory receptor E3 [Mus musculus] (AF102527); 147/223 (65%) SEQ ID NO: 560 [TM1; 25-47 (P), TM2; 57-79 (S), TM3; 93-115 (P), TM4; 134-156 (S), TM5; 201-223 (S), TM6; 234-256 (S), TM7; 269-291 (S)]

olfactory receptor [Gorilla gorilla] (AF101764); 128/301 (42%) SEQ ID NO: 56 2 [TM 1; 34 _ 55 (P), TM 2; 101-123 (S), TM 3; 144-166 (S), TM4; 208-230 (P), TM5; 244-266 (P), TM6; 275-297 (S) ]

olfactory receptor E3 [Mus musculus] (AF102527); 152/223 (68%) SEQ ID NO: 56 4 [TM 1; 35-57 (P), TM 2; 95-117 (S), TM 3; 14 2-16 4 (P), TM4; 17 0 _ 19 2 (S), TM 5; 20 7-22 (P), TM 6; 23 8-26 0 (P)]

ol factory receptor [Mus musculus] (AJ251155); 256/312 (82%) SEQ ID NO: 56 6 [TM 1; 19-41 (P), TM 2; 61-83 (P), TM 3 95-117 (S), TM4; 141-163 (S), TM5; 201-223 (P) TM6; 230-260 (S) ]

HGMP07J [Homo sapiens]> gi 1228481 | prf I 11804351Colfactory receptor HGMP07J [Homo sapiens] (X64995); 157/309 (50¾)

SEQ ID NO: 5 6 8 [TM 1; 24-46 (P), TM 2; 57-79 (S), TM 3; 92-114 (S), TM4; 14 1-16 3 (P), TM5; 202-224 (P), TM6; 239-261 (S), TM7; 268-290 (S)]

olfactory protein [Rattus norvegicus] (M64378); 208/304 (68¾) SEQ ID NO: 57 0 [TM 1; 63-85 (P), TM 2; 98-120 (S), TM3; 1 4 5-16 7 (S), TM4; 17 9-21 (S), TM 5; 243-265 (P), TM 6; 28 1-302 (S)] 01 factory receptor [Mus musculus] (M84005); 191/305 (62%) SEQ ID NO: 5 7 2 [TM 1; 13-35 (S), TM 2; 59-81 (S), TM 3 ; 102-124 (S), TM4; 166-188 (P), TM5;

2 0 1-2 2 3 (S), TM 6; 2 3 7-2 5 7 (S)]

0L1 receptor [Rattus norvegicus] (L34074); 120/270 (44¾) SEQ ID NO: 5 74 [TM 1; 15-37 (S), TM 2; 52-74 (S), TM 3; 9- 1 2 1 (S), TM 4; 16 2-18 4 (P), TM 5; 19 5-2 16 (S), TM 6; 2 27-2 49 (S), TM 7; 2 5 2

-2 74 (P), TM 8; 27 7-29 9 (P)]

olfactory receptor G7 [Mus musculus] (AF102537); 133/223 (59%) SEQ ID NO: 57 6 [TM 1; 19-41 (P), TM 2; 57-79 (S), TM 3 94-16-16 (S), TM4; 139-16-11 (S), TM5; 2022-224 (P), TM6; 240-260 (S), TM 7; 2 7 6

-2 9 8 (S)]

olfactory receptor P2 [Mus musculus] (AF247657); 135/301 (44%) SEQ ID NO: 57 8 [TM 1; 28-50 (P), TM 2; 62-84 (S), TM 3; 9 8-12 0 (P), TM4; 144-16 6 (P), TM 5; 2 09-2 31 (S), TM 6; 242-264 (P)]

01 factory protein [Rattus norvegicus] (M64377); 175/309 (56%) SEQ ID NO: 580 [TM1; 1-23 (S), TM2; 51-73 (P),

TM 3; 1 19-14 1 (S), TM4; 16 6-18 7 (S), TM 5;

204-226 (S), TM6; 235-257 (P), TM7; 272

-2 9 4 (S)]

CfOLF2 [Canis f ami 1 i ar is] (U53680); 168/293 (57¾)

SEQ ID NO: 58 2 [TM 1; 32-54 (P), TM 2; 94-1 16 (S) TM 3; 144-16 7 (P), TM 4; 200-22 2 (P), TM 5; 24 6-26 8 (S), TM 6; 27 0-29 2 (S)]

olfactory receptor [Pan troglodytes] (AF101741); 184/307 (59%) SEQ ID NO: 58 4 [TM 1; 55-77 (P), TM 2; 91 1 1 1 3 (S), TM 3 124-146 (P), TM4; 172-194 (S), TM5; 209-231 (P), TM6; 238—260 ( P), TM 7; 2 65

-2 8 7 (P), TM 8; 2 98-3 2 0 (S)]

olfactory receptor [Mus musculus] (AJ251155); 179/306 (58¾) SEQ ID NO: 58 6 [TM 1; 27-49 (P), TM 2; 87-109 (P), TM 3; 1 26-148 (S), TM4; 153-175 (S), TM5; 202-224 (P), TM6; 239-260 (S ), TM 7; 2 7 2

-2 9 4 (S)]

olfactory receptor [Rattus norvegicus] (X80671); 151/300 (50%) SEQ ID NO: 58 8 [TM 1; 28-50 (P), TM 2; 98-120 (P), TM 3 140-162 (P), TM4; 206-227 (P), TM5; 240-262 (S), TM6; 271-293 (S)]

olfactory receptor OR93Ch [Pan troglodytes] (AF045577); 161/304 (52%)

SEQ ID NO: 590 [TM 1; 11-33 (S), TM 2; 52-73 (S), TM 3; 98-120 (P), TM 4; 135-1 5 7 (S), TM 5; 16 3-18 4 (P), TM 6; 2 25-2 4 7 (S)]

HGMP07J [Homo sapiens]> gi 1228481 Iprf I 11804351 Colfactory receptor HGMP07J [Homo sapiens] (X64995); 119/261 (45%)

SEQ ID NO: 59 2 [TM 1; 1-23 (P), TM 2; 42-64 (S), TM 3; 76-98 (S), TM 4; 107-1 2 9 (P), TM 5; 13 7-15 8 (S), TM 6; 17 6-19 8 (S)]

olfactory receptor [Mus musculus] (AJ251154); 188/216 (87) SEQ ID NO: 59 4 [TM 1; 11-33 (P), TM 2; 47-69 (S), TM 3; 94-16 (P), TM4; 140-1 6 2 (P), TM 5;

168-189 (S), TM6; 195-208 (S)]

similar to mouse ol factory receptor 13; similar to P34984 (PID: g464305) [Homo sapiens] (AC005587); 126/208 (60%)

SEQ ID NO: 59 6 [TM1; 17-39 (P), TM2; 84-106 (P), TM3; 126-147 (S), TM4; 17 1 (S), TM 5;

2 0 1-2 2 3 (S), TM 6; 2 5 8-2 8 0 (P), TM 7; 2 9 8-3 2 0 (S), TM 8; 3 3 0-3 5 2 ( S)]

olfactory receptor [Mus musculus] (M84005); 182/305 (59¾) SEQ ID NO: 59 8 [TM 1; 16-38 (P), TM 2; 94 _ 1 16 (S), TM 3; 1 40-162 (P), TM4; 171-193 (S), TM5; 200-222 (P), TM6; 239-261 (S) ]

similar to mouse ol factory receptor 13; similar to P34984 (PID: g464305) [Homo sapiens] (AC005587); 183/251 (72%)

SEQ ID NO: 600 [TM 1; 32-54 (P), TM 2; 95 to 117 (P), TM 3; 139-161 (S), TM4; 196- 2 18 (P), TM 5; 24 2-26 4 (S), TM 6; 27 6-29 8 (S)]

Hs0LF3 [Homo sapiens] (U56421); 135/305 (44%)

SEQ ID NO: 62 [TM 1; 19-41 (P). TM 2; 61-83 (P), TM 3; 94-116 (S), TM4; 148-17 0 (P), TM 5; 180-202 (S), TM 6; 211-233 (P) TM 7; 211-262 (S), TM 8; 27 3-2 9 4 (S)]

R30385_l [Homo sapiens] (AC004510); 293/313 (93%)

SEQ ID NO: 6 4 [TM 1; 73-95 (S), TM 2; 146-168 (S), TM 3; 19 1-2-13 (S), TM 4; 24 5 -26 7 (P), TM 5; 2 9 1-3 1 2 (P), TM 6; 3 24-3 44 (S)]

olfactory receptor 4 [Gallus gal lus] (X94744); 169/310 (54%) SEQ ID NO: 06 [TM 1; 1-21 (S), TM 2; 45-67 (P), TM 3 73-95 (S), TM4; 106-128 (S), TM5; 161-183 (P), TM6; 223-245 (P) , TM7; 258—280 (S), TM8; 290-311 (S)]

odorant receptor SI [Mus musculus] (AF121972); 215/315 (68%) SEQ ID NO: 6 08 [TM 1; 41-63 (P), TM 2; 71-93 (S)> TM 3 105-127 (P), TM4; 149-171 (P), TM5; 216-38 (P), TM6; 249-271 (P) ), TM 7; 2 79-30 1 (S)]

odorant receptor SI [Mus musculus] (AF121972); 278/317 (87%) SEQ ID NO: 6 10 [TM 1; 29-50 (P), TM 2; 59-81 (P), TM 3 96-1118 (S), TM4; 144-166 (P), TM5; 203-224 (P), TM6; 240-262 (P), TM 7; 26 9-29 1 (S)]

odorant receptor M0R83 [Mus musculus] (AB030894); 167/308 (54%) SEQ ID NO: 6 1 2 [TM 1; 56-78 (S), TM 2; 97-119 (S) TM 3 136-158 (P), TM4; 184-206 (P), TM5; 239-261 (P), TM6; 278-299 (P S), TM 7; 3 10-3 3 1 (S)]

odorant receptor SI [Mus musculus] (AF121972); 195/293 (66%) SEQ ID NO: 6 14 [TM 1; 26-48 (P), TM 2; 608 2 (S), TM 3; 93-115 (S), TM4; 141-163 (P), TM5: 206-228 (P), TM6; 238—259 (S) , TM 7; 268-290 (S)] olfactory receptor C6 [Mus musculus] (AF102523); 148/299 (49%) SEQ ID NO: 6 16 [TM 1; 19-41 (S TM 2; 62-84 (S), TM 3; 10 0-122 (S), TM; 140—162 (P), TM5: 220-224 (P), TM6: 242-264 (S)]

BC62940-1 2 [Homo sapiens] (AC004659); 214/310 (69%)

SEQ ID NO: 6 18 [TM 1; 33-55 (P), TM 2; 64-86 (S), TM 3; 100-122 (S), TM 4; 1 37-1 59 (P), TM5; 207-229 (P), TM6; 245-267 (P), TM7; 273-295 (S)]

taste bud receptor protein TB 641 [Rat tus norvegi cus] (U50949); 270/310 (87%)

SEQ ID NO: 6 20 [TM 1; 3-25 (P), TM 2; 30-51 (S), TM 3; 53-74 (S), TM 4; 81-95 (S) , TM5; 101-122 (S), TM6; 144-166 (P), TM7; 183-205 (P), TM8; 214--2 3 5 (S)]

olfactory receptor [Callithrix jacchus] (AF127882); 200/216 (92%) SEQ ID NO: 62 2 [TM1; 3-25 (P), TM2; 30-51 (P), TM3; 54 -75 (S), TM4; 78-96 (S), TM5; 102-123 (S), TM6; 144-166 (P), TM7; 18 3-205 (PTM8; 2 14-2 3 5 (S)]

olfactory receptor [Eulemur rubr iventer] (AF127861); 200/216 (92%) SEQ ID NO: 6 2 4 [TM 1; 16-38 (P), TM 2; 94-116 (S), TM 3; 14 0-16 2 (P), TM4; 17 1-19 3 (S), TM 5; 200-22 (P), TM 6; 23 9-26 0 (P)]

similar to mouse olfactory receptor 13; similar to P34984 (PID: g464305) [Homo sapiens] (AC005587); 217/307 (70%) SEQ ID NO: 6 26 [TM 1; 1-23 (P), TM 2; 52-74 (P), TM 3; 120-142 (S), TM; 168-19 0 (P), TM 5; 230-25 1 (P), TM 6; 26 22-284 (P)]

odorant receptor MORI 8 [Mus musculus] (AB030895); 158/299 (52%) SEQ ID NO: 6 2 8 [TM 1; 27-49 (P), TM 2; 62-84 (S), TM 3 98-120 (S), TM4; 145-167 (P), TM5; 205-226 (P), TM6; 2337-259 ( P)]

odorant receptor MORI 8 [Mus musculus] (AB030895); 149/293 (50%) SEQ ID NO: 6 3 0 [TM 1; 39-61 (P), TM 2; 80-102 (S), TM3; 115-137 (P), TM4; 160-182 (P), TM5; 190-212 (S) TM6; 222-246 ( P), TM7; 261-283 (P), TM8; 2888-310 (P)]

similar to rat olfactory receptor 0R18; similar to S29710 (PID: g423702) [Homo sapiens] (AC004908); 164/302 (54%)

SEQ ID NO: 6 3 2 [TM 1; 31-53 (P), TM 2; 62-84 (S), TM 3; 101-123 (S), TM4; 133- 155 (S), TM5; 164-186 (S), TM6; 200-222 (P), TM7; 238-260 (P), TM8 2 68-290 (S)]

odorant receptor M0R83 [Mus musculus] (AB030894); 164/307 (53%) SEQ ID NO: 6 34 [TM 1; 27-49 (P), TM 2; 92-1 1 4 (Ρ) 'TM 3 133-155 (P), TM4; 200-222 (P), TM5; 2337-258 (S), TM6; 266-288 (S)]

odorant receptor M0R83 [Mus musculus] (AB030894); 262/306 (85%) SEQ ID NO: 636 [TM1; 5-27 (P), TM2; 33-55 (S), TM3; 5 9-8 1 (S), TM4; 8 3-10 5 (S), TM 5; 11 4-13 36 (S), TM 6; 144-16 6 (P), TM 7 1 8 0-2 0 1 (S), TM 8; 2 1 4—2 3 6 (S)]

taste bud receptor protein TB 641 [Rat tus norvegi cus] (U50949); 189/244 (77%)

SEQ ID NO: 6 3 8 [TM 1; 7-29 (S), TM 2; 67-89 (S), TM 3; 102-124 (P), TM4; 16 6-18 8 (S), TM5; 209-231 (P), TM6; 237-259 (S)]

BC319430_5 [Homo sapiens] (AC006271); 183/260 (70%)

SEQ ID NO: 640 [TM1; 20-42 (S), TM2; 46-67 (S), TM3; 72-94 (S), TM4; 1 15—137 (S) , TM5; 160-182 (P), TM6; 218-240 (P) TM7; 256-278 (S), TM8; 292-31 4 (S)]

odorant receptor SI [Mus musculus] (AF121972); 191/314 (60%) SEQ ID NO: 642 [TM 1; 2-24 (S), TM 2; 48-70 (P), TM 3; 1 16 -138 (S), TM4; 162-184 (P), TM5; 188-210 (S), TM6; 222-244 (S), TM7 2 6 3

-285 (S), TM8; 325-345 (P)]

0LF4 [Homo sapiens] (AC002988); 200/302 (66%)

SEQ ID NO: 644 [TM 1; 25-47 (P)> TM 2; 58-80 (S), TM 3; 100-122 (P), TM4; 142-16 4 (P), TM5; 933-215 (P), TM6; 241-262 (S), TM7; 272

-2 9 3 (S)]

BC85395_3 [Homo sapiens] (AC005255); 201/302 (66%)

SEQ ID NO: 646 [TM 1; 19-1 (S), TM 2; 95-117 (P) TM 3; 144-165 (P), TM 4; 170-19 2 (S), TM5; 200-222 (S), TM6; 241-263 (S)]

BC85395 3 [Homo sapiens] (AC005255); 186/298 (62%) SEQ ID NO: 6 4 8 [TM 1; 27-49 (P), TM 2; 60-82 (S), TM 3; 100-122 (P), TM 4; 144-16 5 (P), TM 5; 2 10-2 32 (P), TM 6; 243-26 5 (S)]

olfactory receptor [Papio haraadryas] (AF127819); 204/216 (94%) SEQ ID NO: 650 [TM1; 34-56 (P), TM2; 62-84 (S), TM3; 98 -120 (P), TM4; 124-146 (S), TM5; 202-224 (P), TM6; 2337-259 (S), TM7 2 7 0

-2 9 2 (S)]

olfactory protein [Rattus norvegicus] (M64386); 177/308 (57%) SEQ ID NO: 65 2 [TM 1; 41-63 (S), TM 2; 82-104 (S). TM 3; 1 1 3—1 3 4 (S), TM4; 144—166 (P), TM 5;

1 8 1-2 0 3 (P), TM 6; 2 1 0—2 3 2 (S)]

HGMP07J [Homo sapiens]> gi 1228481 Iprf I 11804351Colfactory receptor HGMP07J [Homo sapiens] (X64995); 124/248 (50%)

SEQ ID NO: 65 4 [TM 1; 12-34 (P), TM 2; 45-67 (S), TM 3; 101-123 (S), TM4; 144-16 6 (S), TM 5; 19 7-2 19 (P), TM 6; 240-26 1 (S), TM 7; 27 2

-2 9 3 (S)]

HGMP07J [Homo sapiens]〉 gi 1228481 Iprf I 11804351 C olfactory receptor HGMP07J [Homo sapiens] (X64995); 165/308 (53%)

SEQ ID NO: 65 6 (TM 1; 28-50 (P), TM 2; 94 _ 1 16 (S) 'TM 3; 13 9-16 1 (S), TM 4; 203 -2 25 (P), TM 5;

23 9-26 0 (P), TM 6; 27 1-29 3 (S)]

olfactory receptor P2 [Mus musculus] (AF247657); 155/308 (50%) SEQ ID NO: 65 8 [TM 1; 51-73 (P), TM 2; 83-105 (P), TM 3; 156—178 (P), TM4; 202-224 (P), TM5; 2 29-250 (P), TM 6; 2 65-2 7 7 (P), TM 7; 2 92-3 1 4 (P)]

odorant receptor M0R83 [Mus musculus] (AB030894); 174/304 (57%) SEQ ID NO: 660 [TM 1; 1-23 (S), TM2; 50-72 (P), TM3; 8 1-10 3 (S), TM4; 1 13-13 5 (P), TM 5;

160-182 (S), TM6; 222-244 (P), TM7: 258-280 (S), TM8; 292-314 (S) ]

olfactory receptor [Gorilla gorilla] (AF101764); 135/306 (44%) SEQ ID NO: 62 (TM1; 23-45 (P), TM2; 60-82 (S), TM3; 9 8-12 0 (S), TM4; 13 9-16 1 (P) TM 5;

203-225 (P), TM6; 2337-259 (S), TM7; 271

-2 9 2 (S)]

ol factory receptor, family 12, subfamily D, member 2 (NP_039224); 205/306 (66%)

SEQ ID NO: 6 4 [TM 1; 7-29 (S), TM 2; 33-55 (S

TM 3; 95-1 17 (P), TM4; 14 1-16 3 (S), TM 5; 204-26 (P), TM 6; 240-26 2 (P ), TM 7; 2 7 2

-2 9 3 (S)]

olfactory receptor [Mus musculus] (AJ251155); 157/309 (50¾) SEQ ID NO: 66 6 [TM 1; 18-40 (P), TM 2; 55-77 (S), TM 3; 1 1 1-13 3 (P), TM 4; 142-16 4 (P), TM 5; 195-2-17 (P), TM 6; 24 6-26 8 (P), TM 7; 2 8 4

-3 0 5 (S)]

candidate taste receptor T2R7 (AF227133); 95/303 (31¾)

SEQ ID NO: 6 6 8 [TM 1; 8-30 (P), TM 2; 45-67 (S), TM 3; 97-1 19 (S), TM4; 1 28-15 0 (P), TM 5; 180-202 (P), TM 6; 228-250 (P), TM 7; 252

-27 3 (S), TM 8; 27 6-29 8 (S)]

candidate taste receptor T2R13 (AF227137); 140/307 (45%)

SEQ ID NO: 67 0 [TM 1; 7-29 (P), TM 2; 48-70 (S), TM 3; 99-120 (S), TM 4; (P), TM 5;

17 8-200 (P), TM 6; 2 27-24 9 (P)]

candidate taste receptor T2R13 (AF227137); 136/306 (44%)

SEQ ID NO: 67 2 [TM 1; 10-32 (P), TM 2; 42-64 (P), TM 3; 93-115 (S), TM 4; 1 26-1 48 (P), TM5; 182-204 (P), TM6; 235—257 (P)]

candidate taste receptor T2R7 (AF227133); 131/311 (42¾)

SEQ ID NO: 6 7 4 [TM 1; 19-41 (S), TM 2; 61-83 (S), TM 3; 108-130 (S), TM4; 1 38- 16 0 (P), TM 5; 195-2-17 (P), TM 6; 24 7-26 9 (P)]

candidate taste receptor T2R9 (AF227135); 101/307 (32¾)

SEQ ID NO: 676 [TM 1; 34-56 (P), TM 2; 75-97 (S), TM 3; 114-136 (P), TM4; 80 (P), TM 5;

209-231 (P), TM6; 262-284 (P), TM7; 286

-3 0 8 (S)]

taste receptor rT2R6 (AF240766); 100/291 (34%)

SEQ ID NO: 6 7 8 [TM 1; 34-56 (P), TM 2; 75-97 (S), TM 3; 114-13 36 (P), TM 4; 180 (P), TM5; 209-231 (P), TM6; 258-280 (P)]

candidate taste receptor T2R7 (AF227133); 103/310 (33¾)

SEQ ID NO: 6 80 [TM 1; 7-29 (P), TM 2; 94-116 (P), TM 3; 13 1-15 3 (P), TM 4; 18 2-2 0 4 (P) TM 5; 2 35-25 7 (P), TM 6; 26 7-28 9 (P), TM 7; 29 1-30 7 (S)]

taste receptor rT2R12 (AF240768); 214/307 (69%)

SEQ ID NO: 68 2 [TM 1; 8-30 (P), TM 2; 46-68 (P), TM 3; 91-113 (S), TM4; 1 28-15 0 (P), TM 5; 180-202 (P), TM 6; 229-25 1 (P)]

candidate taste receptor T2R13 (AF227137); 140/309 (45¾)

SEQ ID NO: 6 8 4 [TM 1; 8-30 (P), TM 2; 45-67 (P), TM 3; 90-11 (P), TM 4; 12 9-15 1 (P), TM5; 178-200 (P), TM6; 227-249 (P)]

candidate taste receptor T2R13 (AF227137); 116/246 (47%)

SEQ ID NO: 68 6 [TM 1; 7-29 (P), TM 2; 34-56 (P), TM 3; 61-83 (P), TM4; 1 16-1 38 ( P), TM5; 147-169 (P), TM6; 197-219 (P), TM7; 248-269 (P), TM8; 29 5-3 1 7 (S)]

candidate taste receptor T2R13 (AF227137); 131/292 (44¾)

SEQ ID NO: 68 8 [TM 1; 8-30 (P), TM 2; 45-67 (P), TM 3; 97-1 19 (P), TM 4; 1 26-1 48 (P), TM5; 178-200 (P), TM6; 230-251 (P), TM7; 267-289 (S)]

candidate taste receptor T2R13 (AF227137); 136/309 (44%)

SEQ ID NO: 69 0 [TM1; 8-30 (P), TM 2; 45-67 (P), TM 3; 97-119 (P), TM4; 128-15 0 (P), TM 5; 180-202 (P), TM 6; 2 9—2 5 1 (P)]

candidate taste receptor T2R13 (AF227137); 115/252 (45%)

SEQ ID NO: 692 [TM 1; 8-30 (P), TM 2; 46-68 (S), TM3; 999-121 (S), TM4; 128-150 (P), TM5; 184-206 (P), TM6; 229-125 (P)]

candidate taste receptor T2R13 (AF227137); 136/306 (44%)

SEQ ID NO: 694 [TM 1; 8-30 (P), TM 2; 45-67 (P), TM 3; 97-119 (S), TM4; 128-15 0 (P), TM 5;

17 8-200 (P), TM 6; 2 28-250 (P), T M 7; 27 6-298 (S)]

candidate taste receptor T2R13 (AF227137); 131/293 (44%) Industrial availability

According to the present invention, it was possible to comprehensively search a database for new GPCR genes and GPCR proteins, which enable discovery of in vivo signaling mechanisms and identification of novel drug target proteins. By using a GPCR protein, it becomes possible to screen for its endogenous ligands and the like. These GPCRs and their endogenous ligands can be used to study drugs acting on them, and to inherit the gene and its mutants. It is expected that it can be applied to new treatment methods, such as application to treatment. It is also expected to be applied to the development of new taste substances, bitter taste inhibitors, new odorants, and odor inhibitors as ligands for taste receptors and olfactory receptors. In addition, the discovery of new in vivo signaling mechanisms and the identification of novel drug target proteins can be expected through analysis of new GPCR genes.

Claims

The scope of the claims

1.Extract an open reading frame consisting of 200 to 150 amino acid residues containing 6 to 8 transmembrane regions from human-derived genomic information, and select from the obtained open reading frames. A method for searching for a G protein-coupled receptor gene and a Z or G protein-coupled receptor protein, which comprises searching for a gene having homology with a known G protein-coupled receptor gene.

2. When extracting open reading frames, exclude open reading frames derived from DNA repeats, open reading frames containing many undefined amino acids, and open reading frames containing more than 20% of the same amino acids. The method for retrieving a G protein-coupled receptor gene and a Z or G protein-coupled receptor protein according to claim 1, characterized in that:

3. The G protein-coupled receptor according to claim 1 or 2, wherein the gene having homology with a known G protein-coupled receptor gene is a G protein-coupled receptor gene or a G protein-coupled receptor-related gene. Method for searching for somatic gene and Z or G protein-coupled receptor protein.

4. The method for searching for a G protein-coupled receptor gene and a Z or G protein-coupled receptor protein according to any one of claims 1 to 3, wherein the G protein-coupled receptor has an endogenous ligand.

5. The G protein-coupled receptor gene and Z according to claim 4, wherein the G protein-coupled receptor having an endogenous ligand is a G protein-coupled receptor other than an olfactory receptor and a taste receptor. Or a method for searching for a G protein-coupled receptor protein.

6. G protein-coupled receptor with endogenous ligand The method for retrieving a G protein-coupled receptor gene and / or a G protein-coupled receptor protein according to claim 4, which is a white matter-coupled receptor.

7. The G protein-coupled receptor gene and the Z or G protein-coupled receptor according to claim 4, wherein the G protein-coupled receptor having an endogenous ligand is a G protein-coupled receptor of a taste receptor. How to search for proteins.

8. A G protein-coupled receptor gene obtained by the method for searching for a G protein-coupled receptor gene and / or a G protein-coupled receptor protein according to any one of claims 1 to 7.

9. The following gene (a) or (b) encoding the G protein-coupled receptor protein _t (a) SEQ ID NO: 2 n (indicating any integer from 1 to 51) amino acid G protein-coupled receptor protein consisting of sequence

(b) consists of an amino acid sequence represented by SEQ ID NO: 2 n (where n is an integer from l to 51) in which one or several amino acids have been deleted, replaced or added G protein-coupled receptor protein 10 10. The nucleotide sequence shown in SEQ ID NO: 2 n _ l (indicating any integer from l to 51) or a complementary sequence thereof and a part or a part of these sequences DNA encoding a G protein-coupled receptor protein consisting of DNA inclusive.

1 1. A DNA which hybridizes with DNA constituting the gene according to claim 10 under stringent conditions and encodes a G protein-coupled receptor protein.

1 2. A gene encoding the following G protein-coupled receptor protein (a) or (b).

(a) a G protein-coupled receptor protein consisting of the amino acid sequence represented by SEQ ID NO: 2 n (n = any integer from 52 to 33 2)

(b) SEQ ID NO: 2 n (n = any integer from 52 to 33 2) G protein-coupled receptor protein _t comprising an amino acid sequence in which one or several amino acids have been deleted, replaced or added in the amino acid sequence shown in

1 3. The nucleotide sequence shown in SEQ ID NO: 2 n-1 (n = any integer from 52 to 332) or its complementary sequence, and DNA containing a part or all of these sequences DNA encoding a G protein-coupled receptor protein consisting of:

14. A DNA encoding the G protein-coupled receptor protein, which is eight-hybridized with DNA constituting the gene according to claim 13 under stringent conditions.

1 5. A gene encoding the following G protein-coupled receptor protein of (a) or (b).

(a) A G protein-coupled receptor protein consisting of the amino acid sequence represented by SEQ ID NO: 2 n (n is an integer from 33 to 34).

(b) In the amino acid sequence represented by SEQ ID NO: 2 n (where n is an integer from 33 to 34), one or several amino acids are deleted, substituted, or added. G protein-coupled receptor protein consisting of a sequence.

1 6. The nucleotide sequence shown in SEQ ID NO: 2 n _l (n is an integer from 33 to 34) or its complementary sequence, and a DN containing a part or all of these sequences DNA encoding G protein-coupled receptor protein consisting of A.

17. A DNA that hybridizes with the DNA constituting the gene according to claim 16 under stringent conditions and encodes a G protein-coupled receptor protein.

1 8. It is obtained by the method for searching for a G protein-coupled receptor gene and a Z or G protein-coupled receptor protein according to any one of claims 1 to 7.

9 G protein-coupled receptor protein.

1 9. A G protein-coupled receptor protein consisting of the amino acid sequence represented by SEQ ID NO: 2 n (n represents any integer from 1 to 51).

20. In the amino acid sequence represented by SEQ ID NO: 2 n (in which n represents any integer from 1 to 51), the amino acid sequence has one or several amino acids deleted, replaced or added. G protein-coupled receptor protein <

2 1. A G protein-coupled receptor protein consisting of the amino acid sequence represented by SEQ ID NO: 2 n (where n represents any integer from 52 to 32).

2 2. In the amino acid sequence represented by SEQ ID NO: 2 n (n = any integer from 52 to 32), one or several amino acids are deleted, substituted or added. G protein-coupled receptor protein.

2 3. A G protein-coupled receptor protein consisting of the amino acid sequence represented by SEQ ID NO: 2 n (where n represents an integer from 33 to 34).

24. Amino acid sequence represented by SEQ ID NO: 2 n (where n is an integer from 33 to 34) in which one or several amino acids are deleted, substituted or added A G protein-coupled receptor protein consisting of:

2 5. A partial peptide of a G protein-coupled receptor protein obtained by the method for searching for a G protein-coupled receptor gene and a Z or G protein-coupled receptor protein according to any one of claims 1 to 7.

26. The partial peptide according to claim 25, wherein the G protein-coupled receptor protein is the G protein-coupled receptor protein according to any one of claims 19 to 24.

2 7. A partial protein of the G protein-coupled receptor protein according to claim 18 or the G protein-coupled receptor protein according to claim 25, and a marker protein and Z Or a fusion protein or fusion peptide bound to a peptide tag.

28. The fusion protein according to claim 27, wherein the G protein-coupled receptor protein is the G protein-coupled receptor protein according to any one of claims 19 to 24.

29. A fei body which specifically binds to the G protein-coupled receptor protein according to claim 18.

30. The antibody according to claim 29, wherein the G protein-coupled receptor protein is the G protein-coupled receptor protein according to any one of claims 19 to 24.

31. A host cell comprising an expression system capable of expressing the G protein-coupled receptor protein according to claim 18.

32. The host cell according to claim 31, wherein the G protein-coupled receptor protein is the G protein-coupled receptor protein according to any one of claims 19 to 24. '

33. A non-human animal, wherein the function of the gene encoding the G protein-coupled receptor protein according to claim 18 is deficient on a chromosome or the protein is overexpressed.

34. The non-human animal according to claim 33, wherein the G protein-coupled receptor protein is the G protein-coupled receptor protein according to any one of claims 19 to 24.

35. The non-human animal according to claim 33 or 34, wherein the non-human animal is a mouse.

36. A G protein-coupled receptor protein according to any one of claims 18 to 24, a partial peptide according to claim 25 or 26, or a membrane of a cell expressing the protein or partial peptide, A substance that promotes or suppresses the function of a G protein-coupled receptor or a G protein, which is characterized by using a test substance. A method for screening a substance that promotes or suppresses the expression of a coupled receptor.

37. A G protein-coupled receptor protein according to any one of claims 18 to 24, a partial peptide according to claim 25 or 26, or a membrane of a cell expressing the protein or partial peptide. Screening method for a substance that promotes or suppresses the function of a G protein-coupled receptor or a substance that promotes or suppresses the expression of a G protein-coupled receptor, comprising using a test substance, and a test substance. .

38. Use of a test substance and a cell that expresses the G protein-coupled receptor protein according to any one of claims 18 to 24 or the partial peptide according to claim 25 or 26. A method for screening for a substance that promotes or suppresses the function of a G protein-coupled receptor or a substance that promotes or suppresses the expression of a G protein-coupled receptor.

39. The cell that expresses the G protein-coupled receptor protein according to any one of claims 18 to 24 or the partial peptide according to claim 25 or 26, wherein the cell expresses the G protein-coupled receptor protein according to claim 31 or 32. 39. A screening for a substance that promotes or suppresses the function of a G protein-coupled receptor or a substance that promotes or suppresses the expression of a G protein-coupled receptor according to any one of claims 36 to 38. Method.

40. Use of the non-human animal according to any one of claims 33 to 35 and a test substance, wherein the substance promotes or suppresses a function of a G protein-coupled receptor or a G protein-coupled receptor. A screening method for a substance that promotes or suppresses expression.

1. A G protein-coupled receptor function promoting or inhibiting substance or a G protein-coupled receptor expression promoting or inhibiting substance screening method according to any one of claims 36 to 40. G protein-coupled receptor function promoter or inhibitor or G protein-coupled receptor expression promotion Or inhibitors.

42. The method according to claim 41, wherein the substance that promotes or suppresses the function of a G protein-coupled receptor or the substance that promotes or suppresses the expression of a G protein-coupled receptor is a ligand of a G protein-coupled receptor. A substance that promotes or suppresses the function of a G protein-coupled receptor or a substance that promotes or suppresses the expression of a G protein-coupled receptor.

43. A pharmaceutical composition used for treating a patient in need of promoting the function or enhancing the expression of a G protein-coupled receptor, wherein the protein according to any one of claims 18 to 24 is used as an active ingredient. A pharmaceutical composition comprising the partial peptide according to claim 25 or 26, or a substance that promotes the function or expression of the G protein-coupled receptor according to claim 41 or 42.

44. A pharmaceutical composition used for treating a patient in need of suppression of the function or expression of a G protein-coupled receptor, wherein the protein according to any one of claims 18 to 24 as an active ingredient. A pharmaceutical composition comprising the partial peptide according to claim 25 or 26, or a substance that suppresses the function or expression of the G protein-coupled receptor according to claim 41 or 42.

45. A G protein-coupled receptor comprising comparing a DNA sequence encoding a G protein-coupled receptor protein in a sample with a DNA sequence encoding a protein according to any one of claims 18 to 24. A method for diagnosing a disease associated with body function or expression.

46. Diseases associated with the function or expression of a G protein-coupled receptor comprising all or part of the antisense strand of DNA or RNA encoding the protein according to any one of claims 18 to 24. Diagnostic probe.

47. A diagnostic agent for a disease associated with the function or expression of a G protein-coupled receptor, comprising the diagnostic probe according to claim 46 and / or the antibody according to claim 29 or 30.