HCAR2_HUMAN
ID HCAR2_HUMAN Reviewed; 363 AA.
AC Q8TDS4; A0PJL5; A7LGG3;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Hydroxycarboxylic acid receptor 2;
DE AltName: Full=G-protein coupled receptor 109A;
DE AltName: Full=G-protein coupled receptor HM74A;
DE AltName: Full=Niacin receptor 1;
DE AltName: Full=Nicotinic acid receptor;
GN Name=HCAR2; Synonyms=GPR109A, HCA2, HM74A, NIACR1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND CHARACTERIZATION.
RX PubMed=12522134; DOI=10.1074/jbc.m210695200;
RA Wise A., Foord S.M., Fraser N.J., Barnes A.A., Elshourbagy N., Eilert M.,
RA Ignar D.M., Murdock P.R., Steplewski K., Green A., Brown A.J., Dowell S.J.,
RA Szekeres P.G., Hassall D.G., Marshall F.H., Wilson S., Pike N.B.;
RT "Molecular identification of high and low affinity receptors for nicotinic
RT acid.";
RL J. Biol. Chem. 278:9869-9874(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12044878; DOI=10.1016/s0014-5793(02)02775-8;
RA Takeda S., Kadowaki S., Haga T., Takaesu H., Mitaku S.;
RT "Identification of G protein-coupled receptor genes from the human genome
RT sequence.";
RL FEBS Lett. 520:97-101(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S.,
RA Tsutsumi S., Aburatani H., Asai K., Akiyama Y.;
RT "Genome-wide discovery and analysis of human seven transmembrane helix
RT receptor genes.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CYS-311 AND ILE-317.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=17932499; DOI=10.1038/sj.cdd.4402238;
RA Kostylina G., Simon D., Fey M.F., Yousefi S., Simon H.U.;
RT "Neutrophil apoptosis mediated by nicotinic acid receptors (GPR109A).";
RL Cell Death Differ. 15:134-142(2008).
RN [7]
RP NOMENCLATURE.
RX PubMed=21454438; DOI=10.1124/pr.110.003301;
RA Offermanns S., Colletti S.L., Lovenberg T.W., Semple G., Wise A.,
RA Ijzerman A.P.;
RT "International union of basic and clinical pharmacology. LXXXII:
RT nomenclature and classification of hydroxy-carboxylic acid receptors
RT (GPR81, GPR109A, and GPR109B).";
RL Pharmacol. Rev. 63:269-290(2011).
CC -!- FUNCTION: Acts as a high affinity receptor for both nicotinic acid
CC (also known as niacin) and (D)-beta-hydroxybutyrate and mediates
CC increased adiponectin secretion and decreased lipolysis through G(i)-
CC protein-mediated inhibition of adenylyl cyclase. This pharmacological
CC effect requires nicotinic acid doses that are much higher than those
CC provided by a normal diet. Mediates nicotinic acid-induced apoptosis in
CC mature neutrophils. Receptor activation by nicotinic acid results in
CC reduced cAMP levels which may affect activity of cAMP-dependent protein
CC kinase A and phosphorylation of target proteins, leading to neutrophil
CC apoptosis. The rank order of potency for the displacement of nicotinic
CC acid binding is 5-methyl pyrazole-3-carboxylic acid = pyridine-3-acetic
CC acid > acifran > 5-methyl nicotinic acid = acipimox >> nicotinuric acid
CC = nicotinamide. {ECO:0000269|PubMed:17932499}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17932499};
CC Multi-pass membrane protein {ECO:0000269|PubMed:17932499}.
CC -!- TISSUE SPECIFICITY: Expression largely restricted to adipose tissue and
CC spleen. Expressed on mature neutrophils but not on immature neutrophils
CC or eosinophils. {ECO:0000269|PubMed:12522134,
CC ECO:0000269|PubMed:17932499}.
CC -!- DEVELOPMENTAL STAGE: Expression in neutrophils occurs in the late
CC terminal differentiation phase. {ECO:0000269|PubMed:17932499}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/gpr109a/";
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DR EMBL; AY148884; AAN71621.1; -; mRNA.
DR EMBL; AB083632; BAB89345.1; -; Genomic_DNA.
DR EMBL; AB065876; BAC06094.1; -; Genomic_DNA.
DR EMBL; EU012026; ABS29270.1; -; Genomic_DNA.
DR EMBL; BC027965; AAH27965.1; -; mRNA.
DR EMBL; BC056419; AAH56419.1; -; mRNA.
DR CCDS; CCDS9235.1; -.
DR RefSeq; NP_808219.1; NM_177551.3.
DR AlphaFoldDB; Q8TDS4; -.
DR SMR; Q8TDS4; -.
DR STRING; 9606.ENSP00000375066; -.
DR BindingDB; Q8TDS4; -.
DR ChEMBL; CHEMBL3785; -.
DR DrugBank; DB00257; Clotrimazole.
DR DrugBank; DB08949; Inositol nicotinate.
DR DrugBank; DB00627; Niacin.
DR DrugCentral; Q8TDS4; -.
DR GuidetoPHARMACOLOGY; 312; -.
DR iPTMnet; Q8TDS4; -.
DR PhosphoSitePlus; Q8TDS4; -.
DR BioMuta; HCAR2; -.
DR DMDM; 74762622; -.
DR EPD; Q8TDS4; -.
DR jPOST; Q8TDS4; -.
DR MassIVE; Q8TDS4; -.
DR MaxQB; Q8TDS4; -.
DR PaxDb; Q8TDS4; -.
DR PeptideAtlas; Q8TDS4; -.
DR PRIDE; Q8TDS4; -.
DR ProteomicsDB; 74335; -.
DR Antibodypedia; 19187; 203 antibodies from 29 providers.
DR DNASU; 338442; -.
DR Ensembl; ENST00000328880.6; ENSP00000375066.2; ENSG00000182782.8.
DR GeneID; 338442; -.
DR KEGG; hsa:338442; -.
DR MANE-Select; ENST00000328880.6; ENSP00000375066.2; NM_177551.4; NP_808219.1.
DR UCSC; uc001ucx.2; human.
DR CTD; 338442; -.
DR DisGeNET; 338442; -.
DR GeneCards; HCAR2; -.
DR HGNC; HGNC:24827; HCAR2.
DR HPA; ENSG00000182782; Tissue enhanced (esophagus).
DR MIM; 609163; gene.
DR neXtProt; NX_Q8TDS4; -.
DR OpenTargets; ENSG00000182782; -.
DR PharmGKB; PA165961843; -.
DR VEuPathDB; HostDB:ENSG00000182782; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00990000203619; -.
DR HOGENOM; CLU_009579_8_2_1; -.
DR InParanoid; Q8TDS4; -.
DR OMA; MNWHHPQ; -.
DR OrthoDB; 903658at2759; -.
DR PhylomeDB; Q8TDS4; -.
DR TreeFam; TF330775; -.
DR PathwayCommons; Q8TDS4; -.
DR Reactome; R-HSA-3296197; Hydroxycarboxylic acid-binding receptors.
DR Reactome; R-HSA-373076; Class A/1 (Rhodopsin-like receptors).
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SIGNOR; Q8TDS4; -.
DR BioGRID-ORCS; 338442; 11 hits in 1058 CRISPR screens.
DR GenomeRNAi; 338442; -.
DR Pharos; Q8TDS4; Tclin.
DR PRO; PR:Q8TDS4; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q8TDS4; protein.
DR Bgee; ENSG00000182782; Expressed in blood and 88 other tissues.
DR ExpressionAtlas; Q8TDS4; baseline and differential.
DR Genevisible; Q8TDS4; HS.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0070553; F:nicotinic acid receptor activity; ISS:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; ISS:UniProtKB.
DR GO; GO:0001781; P:neutrophil apoptotic process; IDA:UniProtKB.
DR GO; GO:0070165; P:positive regulation of adiponectin secretion; ISS:UniProtKB.
DR GO; GO:0033031; P:positive regulation of neutrophil apoptotic process; IDA:UniProtKB.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR028017; HCAR2/3_rcpt.
DR PANTHER; PTHR46048:SF5; PTHR46048:SF5; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cell membrane; Disulfide bond; G-protein coupled receptor;
KW Membrane; Phosphoprotein; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..363
FT /note="Hydroxycarboxylic acid receptor 2"
FT /id="PRO_0000069603"
FT TOPO_DOM 1..33
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 34..54
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 55..63
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 64..84
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 85..102
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 103..123
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 124..142
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 143..163
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 164..192
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 193..213
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 214..229
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 230..250
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 251..273
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 274..294
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 295..363
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 319..363
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 319..334
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 328
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9EP66"
FT DISULFID 100..177
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 187
FT /note="Q -> R (in dbSNP:rs676770)"
FT /id="VAR_049400"
FT VARIANT 198
FT /note="F -> L (in dbSNP:rs676823)"
FT /id="VAR_049401"
FT VARIANT 311
FT /note="R -> C (in dbSNP:rs7314976)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_038713"
FT VARIANT 317
FT /note="M -> I (in dbSNP:rs2454727)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_038714"
SQ SEQUENCE 363 AA; 41850 MW; C4B0EEC9CCB81D56 CRC64;
MNRHHLQDHF LEIDKKNCCV FRDDFIVKVL PPVLGLEFIF GLLGNGLALW IFCFHLKSWK
SSRIFLFNLA VADFLLIICL PFLMDNYVRR WDWKFGDIPC RLMLFMLAMN RQGSIIFLTV
VAVDRYFRVV HPHHALNKIS NRTAAIISCL LWGITIGLTV HLLKKKMPIQ NGGANLCSSF
SICHTFQWHE AMFLLEFFLP LGIILFCSAR IIWSLRQRQM DRHAKIKRAI TFIMVVAIVF
VICFLPSVVV RIRIFWLLHT SGTQNCEVYR SVDLAFFITL SFTYMNSMLD PVVYYFSSPS
FPNFFSTLIN RCLQRKMTGE PDNNRSTSVE LTGDPNKTRG APEALMANSG EPWSPSYLGP
TSP
