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WO2002016548A2 - Recepteur couple a une proteine g - Google Patents

Recepteur couple a une proteine g Download PDF

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Publication number
WO2002016548A2
WO2002016548A2 PCT/IB2001/001446 IB0101446W WO0216548A2 WO 2002016548 A2 WO2002016548 A2 WO 2002016548A2 IB 0101446 W IB0101446 W IB 0101446W WO 0216548 A2 WO0216548 A2 WO 0216548A2
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WO
WIPO (PCT)
Prior art keywords
protein
coupled receptor
seq
receptor
gene
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IB2001/001446
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English (en)
Japanese (ja)
Other versions
WO2002016548A3 (fr
WO2002016548A8 (fr
Inventor
Tatsuya Haga
Shigeki Takeda
Shigeki Mitaku
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Japan Science and Technology Agency
Original Assignee
Japan Science and Technology Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Japan Science and Technology Corp filed Critical Japan Science and Technology Corp
Priority to US10/343,650 priority Critical patent/US20040067499A1/en
Priority to CA002418130A priority patent/CA2418130A1/fr
Publication of WO2002016548A2 publication Critical patent/WO2002016548A2/fr
Publication of WO2002016548A3 publication Critical patent/WO2002016548A3/fr
Anticipated expiration legal-status Critical
Publication of WO2002016548A8 publication Critical patent/WO2002016548A8/fr
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/72—Receptors; Cell surface antigens; Cell surface determinants for hormones
    • C07K14/723—G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH receptor

Definitions

  • 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.
  • G protein-coupled receptor 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.
  • 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.
  • ligand targeting R a ligand targeting R.
  • ⁇ 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.
  • GPCR-specific ligand such as agonist-ian gonist.
  • not all of the GPCR is disclosed.
  • SOSUI http://sosui.proteome.bio.tuat.ac.jp/sosuiframe0.html
  • SOSUI 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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 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.
  • 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 is 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 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 constitu
  • n any integer from 52 to 322
  • 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.
  • 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.
  • 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)
  • 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
  • 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 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.
  • 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.
  • 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 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 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).
  • the present invention relates to a method for screening a promoting or inhibiting substance (claim 40).
  • 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.
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • GPCR genes are based on their DNA sequence information.
  • a human gene library and a human cDNA library are used.
  • 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.
  • 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.
  • SEQ ID NO: 2 n any integer from 3333 to 347
  • 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.
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • a single-chain antibody preparation method (US Pat. No. 4,946,778) can be applied.
  • 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).
  • 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
  • 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.
  • 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.
  • 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 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.
  • the method of F. Pietri-Rouxel (Eur. J. Biochei., 247, 1174-1179, 1997) and the like can be used.
  • 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.
  • 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.
  • 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 include, but are not limited to, non-human animals such as egrets and rodents such as mice and rats.
  • 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.
  • 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.
  • 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.
  • 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.
  • electroporation electroporation
  • GANC ganciclovir
  • a heterozygous mouse 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.
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the protein / peptide expressing cells 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.
  • 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.
  • 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.
  • 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.
  • ORFs open reading frames
  • 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 ⁇ 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 novel GPCR gene obtained by the above BLAST search was analyzed using an amino acid sequence.
  • 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.
  • the ORF 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.
  • SEQ ID NO: 2 n-1 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
  • (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.
  • 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)]
  • 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
  • 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
  • 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
  • GALS MOUSE GAL AN IN RECEPTOR TYPE 2 (AF042784); 109/299 (36%)
  • 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%)
  • PROBABLE G PROTEIN-COUPLED RECEPTOR (D43633); 125/312 (403 ⁇ 4) 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
  • G-protein coupled receptor SALPR G-protein coupled receptor SALPR; somatostatin and angiotens in-l ike
  • G- protein coupled receptor SALPR (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 (273 ⁇ 4)
  • 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)]
  • 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;
  • 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)]
  • 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;
  • 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;
  • 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)]
  • 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
  • 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)]
  • SEQ ID NO: 6 2 [TM 1; 17-39 (S), TM 2; 67-89 (P), TM3; 101-123 (S), TM4; 135-157 (P), TM5;
  • 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)]
  • 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;
  • SEQ ID NO: 70 [TM 1; 5-27 (P), TM 2; 55-76 (STM 3; 85-107 ( ⁇ ), ⁇ 4; 1 26-148 (S) , TM5; 164-186 (P), TM6; 2667-289 (P), TM7; 304-
  • 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)]
  • EDG6 putative G- Protein coupled receptor
  • 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
  • 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
  • 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)]
  • 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;
  • 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%)
  • 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)]
  • beta3- adrenergic receptor (AF109930); 39/120 (323 ⁇ 4)
  • 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)]
  • 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;
  • 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
  • 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
  • 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)]
  • 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)]
  • 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)]
  • 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
  • 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
  • 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
  • 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%)
  • 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
  • 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
  • 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
  • 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: 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)]
  • 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)]
  • 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;
  • 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 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;
  • 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)]
  • putative G-protein coupled receptor RAlc 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: 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;
  • 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)]
  • 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)]
  • 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;
  • 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;
  • 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
  • olfactory receptor-like protein C0R3 'beta L17432
  • 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)]
  • 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
  • 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
  • olfactory receptor Homo sapiens
  • 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
  • olfactory receptor P2 [Mus musculus] (AF247657); 194/302 (64%) SEQ ID NO: 2 3 4 [ ⁇ 1; 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) ]
  • 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) ]
  • 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 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
  • 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
  • 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)]
  • 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
  • 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;
  • olfactory receptor Homo sapiens
  • 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;
  • 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
  • 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) ]
  • 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;
  • olfactory receptor Homo sapiens (Z98744); 160/250 (643 ⁇ 4) 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;
  • 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),
  • 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;
  • 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;
  • 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
  • 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 (873 ⁇ 4) 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
  • 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;
  • 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-
  • 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;
  • 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;
  • HGMP07J [Homo sapiens]> gi I 228481 Iprf I 11804351Colfactory receptor HGMP07J [Homo sapiens] (X64995); 168/308 (54%)
  • 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;
  • HGMP07J [Homo sapiens]> gi I 228481 Iprf I 11804351Colfactory receptor HGMP07J [Homo sapiens] (X64995); 160/300 (53%)
  • odorant receptor MORI 8 [Mus musculus] (AB030895); 181/302 (593 ⁇ 4) 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
  • odorant receptor A16 [Mus musculus] (AB030896); 170/297 (573 ⁇ 4) 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
  • 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
  • olfactory receptor Homo sapiens [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
  • 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
  • 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 ( ⁇ ) 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
  • HsOLFl Homo sapiens
  • 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 (513 ⁇ 4)
  • 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)]
  • 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 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)]
  • 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
  • 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
  • olfactory receptor P2 [Mus musculus] (AF247657); 170/304 (553 ⁇ 4) 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
  • 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)]
  • 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
  • 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)]
  • 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)]
  • 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)]
  • 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;
  • 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;
  • HsOLFl Homo sapiens
  • 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
  • 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
  • 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;
  • 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 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 )]
  • 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)]
  • 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
  • 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;
  • 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 (513 ⁇ 4) 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
  • HsOLFl Homo sapiens
  • 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;
  • 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 [ ⁇ 1; 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
  • 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
  • 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 )]
  • 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
  • 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 )]
  • 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;
  • 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;
  • olfactory receptor P2 [Mus musculus] (AF247657); 130/305 (423 ⁇ 4) 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;
  • 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;
  • 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)]
  • 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) '
  • 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
  • dJ80I19.7 (olfactory receptor-1 ike protein (hs6Ml-3)) [Homo sapiens] (AL022727); 174/304 (57%)
  • 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
  • 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;
  • 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;
  • 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
  • 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 [ ⁇ 1; 43-65 (P), TM2; 1 17-1 39 (S).
  • ol factory protein [Rattus norvegicus] (M64377); 174/311 (553 ⁇ 4) 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
  • 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 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
  • 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
  • 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 (683 ⁇ 4) 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;
  • 0L1 receptor [Rattus norvegicus] (L34074); 120/270 (443 ⁇ 4) 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
  • 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
  • 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)]
  • 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
  • olfactory receptor [Mus musculus] (AJ251155); 179/306 (583 ⁇ 4) 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
  • 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)]
  • HGMP07J [Homo sapiens]> gi 1228481 Iprf I 11804351 Colfactory receptor HGMP07J [Homo sapiens] (X64995); 119/261 (45%)
  • 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;
  • olfactory receptor [Mus musculus] (M84005); 182/305 (593 ⁇ 4) 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) ]
  • 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
  • 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)]
  • 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)]
  • 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)]
  • 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 ( ⁇ ) '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)]
  • 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
  • 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)]
  • 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
  • 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;
  • 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
  • HGMP07J [Homo sapiens] ⁇ gi 1228481 Iprf I 11804351 C olfactory receptor HGMP07J [Homo sapiens] (X64995); 165/308 (53%)
  • 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;
  • olfactory receptor Gorilla gorilla
  • AF101764 olfactory receptor 135/306
  • 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;
  • olfactory receptor [Mus musculus] (AJ251155); 157/309 (503 ⁇ 4) 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
  • 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
  • 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)]
  • 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)]
  • 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)]
  • 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)]
  • 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)]
  • 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)]
  • 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)]
  • 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.
  • a GPCR protein 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.
  • 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.

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Abstract

L'invention concerne un gène récepteur couplé à une protéine G (GPCR) permettant de trouver un mécanisme de transduction des signaux in vivo ou d'identifier une protéine cible de médicament et un procédé de recherche complète d'une protéine GPCR dans une base de données. Des cadres de lecture ouverts (ORF) contenant entre 250 et 1000 résidus d'aminoacides sont extraits des données génome d'origine humaine et des ORF provenant de séquences d'ADN répétées, des ORF contenant plusieurs aminoacides indéfinis et des ORF possédant un seul aminoacide dans un rapport d'au moins 20 % y sont exclus. Ensuite, les ORF contenant 6 à 8 domaines transmembranaires sont extraits au moyen de SOSUI. Parmi les ORF ainsi obtenus, un gène homologue comprenant un gène GPCR connu (de préférence, un gène démontrant la plus grande homologie avec un gène GPCR ou un gène associé à GPCR dans la recherche d'homologie) est recherché.
PCT/IB2001/001446 2000-08-04 2001-07-30 Recepteur couple a une proteine g Ceased WO2002016548A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US10/343,650 US20040067499A1 (en) 2000-08-04 2001-07-30 Novel g protein-coupled receptor
CA002418130A CA2418130A1 (fr) 2000-08-04 2001-07-30 Recepteur couple a une proteine g

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP2000-237818 2000-08-04
JP2000237818 2000-08-04
JP2001034434A JP2002112793A (ja) 2000-08-04 2001-02-09 新規ｇ蛋白質共役受容体
JP2001-34434 2001-02-09

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WO2002016548A2 true WO2002016548A2 (fr) 2002-02-28
WO2002016548A3 WO2002016548A3 (fr) 2002-06-27
WO2002016548A8 WO2002016548A8 (fr) 2003-02-27

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WO2003087362A1 (fr) * 2002-04-03 2003-10-23 Banyu Pharmaceutical Co., Ltd. Nouveau gene recepteur couple a la proteine g et proteine bg8
WO2004007716A1 (fr) * 2002-07-17 2004-01-22 Nihon University Procede pour isoler un gene gpcr et nouveau gene gpcr
US6838258B2 (en) 1999-10-05 2005-01-04 Agensys, Inc. G protein-coupled receptor up-regulated in prostate cancer and uses thereof
EP1442117A4 (fr) * 2001-10-12 2005-04-27 Univ California Recepteurs gastro-intestinaux chimiosensibles
US7056685B1 (en) 2002-11-05 2006-06-06 Amgen Inc. Receptor ligands and methods of modulating receptors
EP1553980A4 (fr) * 2002-04-01 2006-06-14 Agensys Inc Acide nucleique et proteine correspondante appelee 238p1b2 utile dans le traitement et la detection du cancer
EP1292827A4 (fr) * 2000-04-07 2006-07-12 Senomyx Inc Recepteurs gustatifs t2r et genes codant pour eux
EP1347052A4 (fr) * 2000-11-17 2006-07-19 Banyu Pharma Co Ltd Bg37, proteine du recepteur couple aux proteines g de liaison de guanosine triphosphate (gtp)
US7108991B2 (en) 1998-11-20 2006-09-19 Arena Pharmaceuticals, Inc. Human orphan G protein-coupled receptors
EP1612222A3 (fr) * 2000-09-22 2006-10-25 ChemCom S.A. Récepteurs olfactifs et de phéromones couplés à la protéine G
US7208280B2 (en) 1999-10-05 2007-04-24 Agensys, Inc. Nucleic acid and corresponding protein entitled 101P3A41 useful in treatment and detection of cancer
US7312086B2 (en) 2000-12-07 2007-12-25 Bristol-Myers Squibb Company Methods of diagnosing colon adenocarcinoma using the human g-protein coupled receptor hgprbmy23
US7314725B2 (en) 2001-07-20 2008-01-01 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Phenylthiocarbamide (PTC) taste receptor
US7361338B2 (en) 1999-10-05 2008-04-22 Agensys, Inc. Methods to inhibit growth of prostate cancer cells
US7553814B2 (en) 2002-04-01 2009-06-30 Agensys, Inc. 238P1B2 protein
US7579453B2 (en) 2003-06-19 2009-08-25 The United States Of America As Represented By The Secretary Of The Dapartment Of Health And Human Services Variants of human taste receptor genes
US7816492B2 (en) 1998-11-20 2010-10-19 Arena Pharmaceuticals, Inc. Human G protein-coupled receptors
USRE42190E1 (en) 1998-11-20 2011-03-01 Arena Pharmaceuticals, Inc. Method of identifying a compound for inhibiting or stimulating human G protein-coupled receptors
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DE10344799A1 (de) * 2003-09-26 2005-04-14 Ganymed Pharmaceuticals Ag Identifizierung von Oberflächen-assoziierten Antigenen für die Tumordiagnose und -therapie
US9141755B2 (en) 2010-08-26 2015-09-22 National Institute Of Biomedical Innovation Device and method for selecting genes and proteins

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WO2000005264A1 (fr) * 1998-07-23 2000-02-03 Takeda Chemical Industries, Ltd. Nouvelle proteine receptrice conjuguee a la proteine g et adn de cette derniere
JP2000050875A (ja) * 1998-08-07 2000-02-22 Kazusa Dna Kenkyusho 新規ｇ蛋白質共役型レセプター蛋白質およびそのｄｎａ

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US7816492B2 (en) 1998-11-20 2010-10-19 Arena Pharmaceuticals, Inc. Human G protein-coupled receptors
US7893235B2 (en) 1998-11-20 2011-02-22 Arena Pharmaceuticals, Inc. Nucleic acids encoding the GPCR, RUP3, and methods of use thereof
US7108991B2 (en) 1998-11-20 2006-09-19 Arena Pharmaceuticals, Inc. Human orphan G protein-coupled receptors
USRE42190E1 (en) 1998-11-20 2011-03-01 Arena Pharmaceuticals, Inc. Method of identifying a compound for inhibiting or stimulating human G protein-coupled receptors
US7208280B2 (en) 1999-10-05 2007-04-24 Agensys, Inc. Nucleic acid and corresponding protein entitled 101P3A41 useful in treatment and detection of cancer
US7795391B2 (en) 1999-10-05 2010-09-14 Agensys, Inc. Protein showing enhanced expression in cancer cells
US6838258B2 (en) 1999-10-05 2005-01-04 Agensys, Inc. G protein-coupled receptor up-regulated in prostate cancer and uses thereof
US8236510B2 (en) 1999-10-05 2012-08-07 Agensys, Inc. Protein showing enhanced expression in cancer cells
US7361338B2 (en) 1999-10-05 2008-04-22 Agensys, Inc. Methods to inhibit growth of prostate cancer cells
US7351583B2 (en) 1999-10-05 2008-04-01 Agensys, Inc. Antibodies to G protein-coupled receptor
US7968693B2 (en) 2000-04-07 2011-06-28 Senomyx, Inc. Human T2R51 nucleic acid sequences and polypeptides
US7816093B2 (en) 2000-04-07 2010-10-19 Senomyx, Inc. Assays for identifying human bitter taste modulators
US8030009B2 (en) 2000-04-07 2011-10-04 Senomyx, Inc. Human T2R67 taste receptor and related assays for identifying human bitter taste modulators
US7723051B2 (en) 2000-04-07 2010-05-25 Senomyx, Inc. HT2R75 taste receptor and related assays for identifying human bitter taste modulators
US8030468B2 (en) 2000-04-07 2011-10-04 Senomyx, Inc. Human T2R51 taste receptor nucleic acid sequences and polypeptides
US7396651B2 (en) 2000-04-07 2008-07-08 Senomyx, Inc. Binding assay employing human T2R taste receptors
EP1292827A4 (fr) * 2000-04-07 2006-07-12 Senomyx Inc Recepteurs gustatifs t2r et genes codant pour eux
US7736862B2 (en) 2000-04-07 2010-06-15 Senomyx, Inc. Human T2R63 receptor and related assays for identifying human bitter taste modulators
US7638289B2 (en) 2000-04-07 2009-12-29 Senomyx, Inc. Human T2R55 taste receptor and related assays for identifying human bitter taste modulators
US8153386B2 (en) 2000-04-07 2012-04-10 Senomyx, Inc. Human T2R64 taste receptor and related assays for identifying human bitter taste modulators
US7704698B2 (en) 2000-04-07 2010-04-27 Senomyx, Inc. Human T2R51 taste receptor and related assays for identifying bitter taste modulators
US9163074B2 (en) 2000-04-07 2015-10-20 Senomyx, Inc. Human T2R nucleic acid sequences
US7718383B2 (en) 2000-04-07 2010-05-18 Senomyx, Inc. Human T2R65 taste receptor and related assays for identifying human bitter taste modulators
US7785802B2 (en) 2000-04-07 2010-08-31 Senomyx, Inc. Human T2R71 receptor and related assays for identifying human bitter taste modulators
EP1612222A3 (fr) * 2000-09-22 2006-10-25 ChemCom S.A. Récepteurs olfactifs et de phéromones couplés à la protéine G
US7723046B2 (en) 2000-11-17 2010-05-25 Banyu Pharmaceutical Co., Ltd. Method of screening for a compound using guanosine triphosphate (GTP)-binding protein-coupled receptor protein, BG37
US7198914B2 (en) 2000-11-17 2007-04-03 Banyu Pharmaceutical Co., Ltd. Guanosine triphosphate (GTP)-binding protein-coupled receptor protein, BG37
US8076455B2 (en) 2000-11-17 2011-12-13 Merck Sharp & Dohme Corp. Guanosine triphosphate (GTP)-binding protein-coupled receptor protein, BG37
EP1347052A4 (fr) * 2000-11-17 2006-07-19 Banyu Pharma Co Ltd Bg37, proteine du recepteur couple aux proteines g de liaison de guanosine triphosphate (gtp)
US7713699B2 (en) 2000-12-07 2010-05-11 Bristol-Myers Squibb Company Methods of diagnosing colon adenocarcinoma using mRNA encoding the human g-protein coupled receptor, HGPRBMY23
US7312086B2 (en) 2000-12-07 2007-12-25 Bristol-Myers Squibb Company Methods of diagnosing colon adenocarcinoma using the human g-protein coupled receptor hgprbmy23
US7666601B2 (en) 2001-07-20 2010-02-23 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Phenylthiocarbamide (PTC) taste receptor
US8148082B2 (en) 2001-07-20 2012-04-03 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Phenylthiocarbamide (PTC) taste receptor
US7314725B2 (en) 2001-07-20 2008-01-01 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Phenylthiocarbamide (PTC) taste receptor
EP1442117A4 (fr) * 2001-10-12 2005-04-27 Univ California Recepteurs gastro-intestinaux chimiosensibles
US7553814B2 (en) 2002-04-01 2009-06-30 Agensys, Inc. 238P1B2 protein
US8003100B2 (en) 2002-04-01 2011-08-23 Agensys, Inc. Antibodies that bind to 238P1B2
US7749746B2 (en) 2002-04-01 2010-07-06 Agensys, Inc. Nucleic acid encoding 238P1B2 useful in detecting cancer
EP1553980A4 (fr) * 2002-04-01 2006-06-14 Agensys Inc Acide nucleique et proteine correspondante appelee 238p1b2 utile dans le traitement et la detection du cancer
WO2003087362A1 (fr) * 2002-04-03 2003-10-23 Banyu Pharmaceutical Co., Ltd. Nouveau gene recepteur couple a la proteine g et proteine bg8
WO2004007716A1 (fr) * 2002-07-17 2004-01-22 Nihon University Procede pour isoler un gene gpcr et nouveau gene gpcr
US7056685B1 (en) 2002-11-05 2006-06-06 Amgen Inc. Receptor ligands and methods of modulating receptors
US7579453B2 (en) 2003-06-19 2009-08-25 The United States Of America As Represented By The Secretary Of The Dapartment Of Health And Human Services Variants of human taste receptor genes
US8309701B2 (en) 2003-06-19 2012-11-13 The United States of America as represented by the Secrectary of the Department of Health and Human Services Variants of human taste receptor genes
US9783590B2 (en) 2003-06-19 2017-10-10 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Variants of human taste receptor genes
US8153635B2 (en) 2007-09-20 2012-04-10 Irm Llc Compounds and compositions as modulators of GPR119 activity
US8258156B2 (en) 2007-09-20 2012-09-04 Irm Llc Compounds and compositions as modulators of GPR119 activity

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