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Q8TDS4

- HCAR2_HUMAN

UniProt

Q8TDS4 - HCAR2_HUMAN

Protein

Hydroxycarboxylic acid receptor 2

Gene

HCAR2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 106 (01 Oct 2014)
      Sequence version 1 (01 Jun 2002)
      Previous versions | rss
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    Functioni

    Acts as a high affinity receptor for both nicotinic acid (also known as niacin) and (D)-beta-hydroxybutyrate and mediates increased adiponectin secretion and decreased lipolysis through G(i)-protein-mediated inhibition of adenylyl cyclase. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet. Mediates nicotinic acid-induced apoptosis in mature neutrophils. Receptor activation by nicotinic acid results in reduced cAMP levels which may affect activity of cAMP-dependent protein kinase A and phosphorylation of target proteins, leading to neutrophil apoptosis. The rank order of potency for the displacement of nicotinic acid binding is 5-methyl pyrazole-3-carboxylic acid = pyridine-3-acetic acid > acifran > 5-methyl nicotinic acid = acipimox >> nicotinuric acid = nicotinamide.1 Publication

    GO - Molecular functioni

    1. nicotinic acid receptor activity Source: UniProtKB

    GO - Biological processi

    1. negative regulation of lipid catabolic process Source: UniProtKB
    2. neutrophil apoptotic process Source: UniProtKB
    3. positive regulation of adiponectin secretion Source: UniProtKB
    4. positive regulation of neutrophil apoptotic process Source: UniProtKB

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Keywords - Biological processi

    Apoptosis

    Enzyme and pathway databases

    ReactomeiREACT_14828. Class A/1 (Rhodopsin-like receptors).
    REACT_163785. Hydroxycarboxylic acid-binding receptors.
    REACT_19231. G alpha (i) signalling events.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Hydroxycarboxylic acid receptor 2
    Alternative name(s):
    G-protein coupled receptor 109A
    G-protein coupled receptor HM74A
    Niacin receptor 1
    Nicotinic acid receptor
    Gene namesi
    Name:HCAR2
    Synonyms:GPR109A, HCA2, HM74A, NIACR1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:24827. HCAR2.

    Subcellular locationi

    Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW
    2. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA165961843.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 363363Hydroxycarboxylic acid receptor 2PRO_0000069603Add
    BLAST

    Amino acid modifications

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

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    MaxQBiQ8TDS4.
    PaxDbiQ8TDS4.
    PRIDEiQ8TDS4.

    PTM databases

    PhosphoSiteiQ8TDS4.

    Expressioni

    Tissue specificityi

    Expression largely restricted to adipose tissue and spleen. Expressed on mature neutrophils but not on immature neutrophils or eosinophils.2 Publications

    Developmental stagei

    Expression in neutrophils occurs in the late terminal differentiation phase.1 Publication

    Gene expression databases

    BgeeiQ8TDS4.
    CleanExiHS_GPR109A.
    GenevestigatoriQ8TDS4.

    Organism-specific databases

    HPAiHPA028660.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000375066.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8TDS4.
    SMRiQ8TDS4. Positions 38-332.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3333ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini55 – 639CytoplasmicSequence Analysis
    Topological domaini85 – 10218ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini124 – 14219CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini164 – 19229ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini214 – 22916CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini251 – 27323ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini295 – 36369CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei34 – 5421Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei64 – 8421Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei103 – 12321Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei143 – 16321Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei193 – 21321Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei230 – 25021Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei274 – 29421Helical; 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

    eggNOGiNOG148880.
    InParanoidiQ8TDS4.
    KOiK08402.
    OMAiRAINFIM.
    OrthoDBiEOG7R56SR.
    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.

    Q8TDS4-1 [UniParc]FASTAAdd to Basket

    « Hide

    MNRHHLQDHF LEIDKKNCCV FRDDFIVKVL PPVLGLEFIF GLLGNGLALW    50
    IFCFHLKSWK SSRIFLFNLA VADFLLIICL PFLMDNYVRR WDWKFGDIPC 100
    RLMLFMLAMN RQGSIIFLTV VAVDRYFRVV HPHHALNKIS NRTAAIISCL 150
    LWGITIGLTV HLLKKKMPIQ NGGANLCSSF SICHTFQWHE AMFLLEFFLP 200
    LGIILFCSAR IIWSLRQRQM DRHAKIKRAI TFIMVVAIVF VICFLPSVVV 250
    RIRIFWLLHT SGTQNCEVYR SVDLAFFITL SFTYMNSMLD PVVYYFSSPS 300
    FPNFFSTLIN RCLQRKMTGE PDNNRSTSVE LTGDPNKTRG APEALMANSG 350
    EPWSPSYLGP TSP 363
    Length:363
    Mass (Da):41,850
    Last modified:June 1, 2002 - v1
    Checksum:iC4B0EEC9CCB81D56
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti187 – 1871Q → R.
    Corresponds to variant rs676770 [ dbSNP | Ensembl ].
    VAR_049400
    Natural varianti198 – 1981F → L.
    Corresponds to variant rs676823 [ dbSNP | Ensembl ].
    VAR_049401
    Natural varianti311 – 3111R → C.1 Publication
    Corresponds to variant rs7314976 [ dbSNP | Ensembl ].
    VAR_038713
    Natural varianti317 – 3171M → I.1 Publication
    Corresponds to variant rs28682471 [ dbSNP | Ensembl ].
    VAR_038714

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY148884 mRNA. Translation: AAN71621.1.
    AB083632 Genomic DNA. Translation: BAB89345.1.
    AB065876 Genomic DNA. Translation: BAC06094.1.
    EU012026 Genomic DNA. Translation: ABS29270.1.
    BC027965 mRNA. Translation: AAH27965.1.
    BC056419 mRNA. Translation: AAH56419.1.
    CCDSiCCDS9235.1.
    RefSeqiNP_808219.1. NM_177551.3.
    UniGeneiHs.524812.

    Genome annotation databases

    EnsembliENST00000328880; ENSP00000375066; ENSG00000182782.
    GeneIDi338442.
    KEGGihsa:338442.
    UCSCiuc001ucx.1. human.

    Polymorphism databases

    DMDMi74762622.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY148884 mRNA. Translation: AAN71621.1 .
    AB083632 Genomic DNA. Translation: BAB89345.1 .
    AB065876 Genomic DNA. Translation: BAC06094.1 .
    EU012026 Genomic DNA. Translation: ABS29270.1 .
    BC027965 mRNA. Translation: AAH27965.1 .
    BC056419 mRNA. Translation: AAH56419.1 .
    CCDSi CCDS9235.1.
    RefSeqi NP_808219.1. NM_177551.3.
    UniGenei Hs.524812.

    3D structure databases

    ProteinModelPortali Q8TDS4.
    SMRi Q8TDS4. Positions 38-332.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000375066.

    Chemistry

    BindingDBi Q8TDS4.
    ChEMBLi CHEMBL3785.
    DrugBanki DB04843. Mepenzolate.
    DB00627. Niacin.
    GuidetoPHARMACOLOGYi 312.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei Q8TDS4.

    Polymorphism databases

    DMDMi 74762622.

    Proteomic databases

    MaxQBi Q8TDS4.
    PaxDbi Q8TDS4.
    PRIDEi Q8TDS4.

    Protocols and materials databases

    DNASUi 338442.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000328880 ; ENSP00000375066 ; ENSG00000182782 .
    GeneIDi 338442.
    KEGGi hsa:338442.
    UCSCi uc001ucx.1. human.

    Organism-specific databases

    CTDi 338442.
    GeneCardsi GC12M123187.
    HGNCi HGNC:24827. HCAR2.
    HPAi HPA028660.
    MIMi 609163. gene.
    neXtProti NX_Q8TDS4.
    PharmGKBi PA165961843.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG148880.
    InParanoidi Q8TDS4.
    KOi K08402.
    OMAi RAINFIM.
    OrthoDBi EOG7R56SR.
    TreeFami TF330775.

    Enzyme and pathway databases

    Reactomei REACT_14828. Class A/1 (Rhodopsin-like receptors).
    REACT_163785. Hydroxycarboxylic acid-binding receptors.
    REACT_19231. G alpha (i) signalling events.

    Miscellaneous databases

    GenomeRNAii 338442.
    NextBioi 97016.
    PROi Q8TDS4.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q8TDS4.
    CleanExi HS_GPR109A.
    Genevestigatori Q8TDS4.

    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. Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, CHARACTERIZATION.
    2. "Identification of G protein-coupled receptor genes from the human genome sequence."
      Takeda S., Kadowaki S., Haga T., Takaesu H., Mitaku S.
      FEBS Lett. 520:97-101(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "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].
    4. SeattleSNPs variation discovery resource
      Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-311 AND ILE-317.
    5. "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].
      Tissue: Pancreas.
    6. "Neutrophil apoptosis mediated by nicotinic acid receptors (GPR109A)."
      Kostylina G., Simon D., Fey M.F., Yousefi S., Simon H.U.
      Cell Death Differ. 15:134-142(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    7. "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 nameiHCAR2_HUMAN
    AccessioniPrimary (citable) accession number: Q8TDS4
    Secondary accession number(s): A0PJL5, A7LGG3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 6, 2005
    Last sequence update: June 1, 2002
    Last modified: October 1, 2014
    This is version 106 of the entry and version 1 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