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P49019

- HCAR3_HUMAN

UniProt

P49019 - HCAR3_HUMAN

Protein

Hydroxycarboxylic acid receptor 3

Gene

HCAR3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 134 (01 Oct 2014)
      Sequence version 3 (26 Jun 2013)
      Previous versions | rss
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    Functioni

    Receptor for 3-OH-octanoid acid mediates a negative feedback regulation of adipocyte lipolysis to counteract prolipolytic influences under conditions of physiological or pathological increases in beta-oxidation rates. Acts as a low affinity receptor for nicotinic acid. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet.2 Publications

    GO - Molecular functioni

    1. G-protein coupled receptor activity Source: ProtInc

    GO - Biological processi

    1. G-protein coupled receptor signaling pathway Source: ProtInc

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Enzyme and pathway databases

    ReactomeiREACT_163785. Hydroxycarboxylic acid-binding receptors.
    REACT_19231. G alpha (i) signalling events.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Hydroxycarboxylic acid receptor 3
    Alternative name(s):
    G-protein coupled receptor 109B
    G-protein coupled receptor HM74
    G-protein coupled receptor HM74B
    Niacin receptor 2
    Nicotinic acid receptor 2
    Gene namesi
    Name:HCAR3
    Synonyms:GPR109B, HCA3, HM74B, NIACR2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:16824. HCAR3.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of plasma membrane Source: ProtInc
    2. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi111 – 1111R → A: Abrogates completely the activation by OH-octanoid acid. 1 Publication

    Organism-specific databases

    PharmGKBiPA165512827.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 387387Hydroxycarboxylic acid receptor 3PRO_0000069604Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi100 ↔ 177PROSITE-ProRule annotation

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    PRIDEiP49019.

    Expressioni

    Tissue specificityi

    Expression largely restricted to adipose tissue and spleen.1 Publication

    Gene expression databases

    CleanExiHS_GPR109B.
    GenevestigatoriP49019.

    Organism-specific databases

    HPAiHPA028660.

    Interactioni

    Protein-protein interaction databases

    IntActiP49019. 1 interaction.

    Structurei

    3D structure databases

    ProteinModelPortaliP49019.
    SMRiP49019. Positions 30-311.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 2828ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini51 – 6313CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini86 – 10217ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini124 – 14219CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini164 – 19431ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini210 – 23627CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini257 – 27317ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini299 – 38789CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei29 – 5022Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei64 – 8522Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei103 – 12321Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei143 – 16321Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei195 – 20915Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei237 – 25620Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei274 – 29825Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    HOVERGENiHBG051680.
    InParanoidiP49019.
    KOiK08402.
    OMAiTANVCIS.
    OrthoDBiEOG7R56SR.
    PhylomeDBiP49019.
    TreeFamiTF330775.

    Family and domain databases

    Gene3Di1.20.1070.10. 1 hit.
    InterProiIPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    IPR028017. HCAR2/3_rcpt.
    [Graphical view]
    PANTHERiPTHR24231:SF0. PTHR24231:SF0. 1 hit.
    PfamiPF00001. 7tm_1. 1 hit.
    [Graphical view]
    PRINTSiPR00237. GPCRRHODOPSN.
    PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P49019-1 [UniParc]FASTAAdd to Basket

    « Hide

    MNRHHLQDHF LEIDKKNCCV FRDDFIAKVL PPVLGLEFIF GLLGNGLALW    50
    IFCFHLKSWK SSRIFLFNLA VADFLLIICL PFVMDYYVRR SDWKFGDIPC 100
    RLVLFMFAMN RQGSIIFLTV VAVDRYFRVV HPHHALNKIS NWTAAIISCL 150
    LWGITVGLTV HLLKKKLLIQ NGTANVCISF SICHTFRWHE AMFLLEFFLP 200
    LGIILFCSAR IIWSLRQRQM DRHAKIKRAI TFIMVVAIVF VICFLPSVVV 250
    RIHIFWLLHT SGTQNCEVYR SVDLAFFITL SFTYMNSMLD PVVYYFSSPS 300
    FPNFFSTLIN RCLQRKITGE PDNNRSTSVE LTGDPNKTRG APEALIANSG 350
    EPWSPSYLGP TSNNHSKKGH CHQEPASLEK QLGCCIE 387
    Length:387
    Mass (Da):44,478
    Last modified:June 26, 2013 - v3
    Checksum:i887BA427B6134A3F
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti94 – 941K → N in BAA01721. (PubMed:7505609)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti173 – 1731T → P.4 Publications
    Corresponds to variant rs1798192 [ dbSNP | Ensembl ].
    VAR_038715
    Natural varianti198 – 1981F → L.4 Publications
    Corresponds to variant rs17884481 [ dbSNP | Ensembl ].
    VAR_038716
    Natural varianti253 – 2531H → R.4 Publications
    VAR_038717
    Natural varianti317 – 3171I → M.4 Publications
    VAR_038718
    Natural varianti346 – 3461I → M.4 Publications
    Corresponds to variant rs56308926 [ dbSNP | Ensembl ].
    VAR_038719
    Natural varianti350 – 3501G → S.
    VAR_038720

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D10923 mRNA. Translation: BAA01721.1.
    AB065865 Genomic DNA. Translation: BAC06083.1.
    AK290930 mRNA. Translation: BAF83619.1.
    AK313212 mRNA. Translation: BAG36027.1.
    EU293604 Genomic DNA. Translation: ABX64359.1.
    AC026333 Genomic DNA. No translation available.
    BC047891 mRNA. Translation: AAH47891.1.
    CCDSiCCDS53842.1.
    PIRiI69202.
    RefSeqiNP_006009.2. NM_006018.2.
    UniGeneiHs.458425.

    Genome annotation databases

    EnsembliENST00000528880; ENSP00000436714; ENSG00000255398.
    GeneIDi8843.
    KEGGihsa:8843.

    Polymorphism databases

    DMDMi519668680.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D10923 mRNA. Translation: BAA01721.1 .
    AB065865 Genomic DNA. Translation: BAC06083.1 .
    AK290930 mRNA. Translation: BAF83619.1 .
    AK313212 mRNA. Translation: BAG36027.1 .
    EU293604 Genomic DNA. Translation: ABX64359.1 .
    AC026333 Genomic DNA. No translation available.
    BC047891 mRNA. Translation: AAH47891.1 .
    CCDSi CCDS53842.1.
    PIRi I69202.
    RefSeqi NP_006009.2. NM_006018.2.
    UniGenei Hs.458425.

    3D structure databases

    ProteinModelPortali P49019.
    SMRi P49019. Positions 30-311.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    IntActi P49019. 1 interaction.

    Chemistry

    BindingDBi P49019.
    ChEMBLi CHEMBL4421.
    DrugBanki DB04843. Mepenzolate.
    DB00627. Niacin.
    GuidetoPHARMACOLOGYi 313.

    Protein family/group databases

    GPCRDBi Search...

    Polymorphism databases

    DMDMi 519668680.

    Proteomic databases

    PRIDEi P49019.

    Protocols and materials databases

    DNASUi 8843.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000528880 ; ENSP00000436714 ; ENSG00000255398 .
    GeneIDi 8843.
    KEGGi hsa:8843.

    Organism-specific databases

    CTDi 8843.
    GeneCardsi GC12M123200.
    H-InvDB HIX0036803.
    HGNCi HGNC:16824. HCAR3.
    HPAi HPA028660.
    MIMi 606039. gene.
    neXtProti NX_P49019.
    PharmGKBi PA165512827.
    GenAtlasi Search...

    Phylogenomic databases

    HOVERGENi HBG051680.
    InParanoidi P49019.
    KOi K08402.
    OMAi TANVCIS.
    OrthoDBi EOG7R56SR.
    PhylomeDBi P49019.
    TreeFami TF330775.

    Enzyme and pathway databases

    Reactomei REACT_163785. Hydroxycarboxylic acid-binding receptors.
    REACT_19231. G alpha (i) signalling events.

    Miscellaneous databases

    GenomeRNAii 8843.
    NextBioi 33198.
    PROi P49019.
    SOURCEi Search...

    Gene expression databases

    CleanExi HS_GPR109B.
    Genevestigatori P49019.

    Family and domain databases

    Gene3Di 1.20.1070.10. 1 hit.
    InterProi IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    IPR028017. HCAR2/3_rcpt.
    [Graphical view ]
    PANTHERi PTHR24231:SF0. PTHR24231:SF0. 1 hit.
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00237. GPCRRHODOPSN.
    PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte chemotactic peptide receptors."
      Nomura H., Nielsen B.W., Matsushima K.
      Int. Immunol. 5:1239-1249(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS PRO-173; LEU-198; ARG-253; MET-317 AND MET-346.
      Tissue: Monocyte.
    2. "Genome-wide discovery and analysis of human seven transmembrane helix receptor genes."
      Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., Tsutsumi S., Aburatani H., Asai K., Akiyama Y.
      Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PRO-173; LEU-198; ARG-253; MET-317 AND MET-346.
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS PRO-173; LEU-198; ARG-253; MET-317 AND MET-346.
      Tissue: Neutrophil.
    4. SeattleSNPs variation discovery resource
      Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    5. "The finished DNA sequence of human chromosome 12."
      Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
      , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
      Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS PRO-173; LEU-198; ARG-253; MET-317 AND MET-346.
      Tissue: Pancreas.
    7. Cited for: FUNCTION, TISSUE SPECIFICITY, CHARACTERIZATION.
    8. "Deorphanization of GPR109B as a receptor for the beta-oxidation intermediate 3-OH-octanoic acid and its role in the regulation of lipolysis."
      Ahmed K., Tunaru S., Langhans C.-D., Hanson J., Michalski C.W., Koelker S., Jones P.M., Okun J.G., Offermanns S.
      J. Biol. Chem. 284:21928-21933(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF ARG-111.
    9. "International union of basic and clinical pharmacology. LXXXII: nomenclature and classification of hydroxy-carboxylic acid receptors (GPR81, GPR109A, and GPR109B)."
      Offermanns S., Colletti S.L., Lovenberg T.W., Semple G., Wise A., Ijzerman A.P.
      Pharmacol. Rev. 63:269-290(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: NOMENCLATURE.

    Entry informationi

    Entry nameiHCAR3_HUMAN
    AccessioniPrimary (citable) accession number: P49019
    Secondary accession number(s): A8K4G5
    , B2R830, E9PI97, Q8NGE4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: June 26, 2013
    Last modified: October 1, 2014
    This is version 134 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. 7-transmembrane G-linked receptors
      List of 7-transmembrane G-linked receptor entries
    2. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3