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Hydroxycarboxylic acid receptor 2 (G-protein coupled receptor 109A) (G-protein coupled receptor HM74A) (Niacin receptor 1) (Nicotinic acid receptor)

 HCAR2_HUMAN             Reviewed;         363 AA.
Q8TDS4; A0PJL5; A7LGG3;
06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
01-JUN-2002, sequence version 1.
31-JAN-2018, entry version 127.
RecName: Full=Hydroxycarboxylic acid receptor 2;
AltName: Full=G-protein coupled receptor 109A;
AltName: Full=G-protein coupled receptor HM74A;
AltName: Full=Niacin receptor 1;
AltName: Full=Nicotinic acid receptor;
Name=HCAR2; Synonyms=GPR109A, HCA2, HM74A, NIACR1;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND CHARACTERIZATION.
PubMed=12522134; DOI=10.1074/jbc.M210695200;
Wise A., Foord S.M., Fraser N.J., Barnes A.A., Elshourbagy N.,
Eilert M., Ignar D.M., Murdock P.R., Steplewski K., Green A.,
Brown A.J., Dowell S.J., Szekeres P.G., Hassall D.G., Marshall F.H.,
Wilson S., Pike N.B.;
"Molecular identification of high and low affinity receptors for
nicotinic acid.";
J. Biol. Chem. 278:9869-9874(2003).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=12044878; DOI=10.1016/S0014-5793(02)02775-8;
Takeda S., Kadowaki S., Haga T., Takaesu H., Mitaku S.;
"Identification of G protein-coupled receptor genes from the human
genome sequence.";
FEBS Lett. 520:97-101(2002).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S.,
Tsutsumi S., Aburatani H., Asai K., Akiyama Y.;
"Genome-wide discovery and analysis of human seven transmembrane helix
receptor genes.";
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CYS-311 AND ILE-317.
SeattleSNPs variation discovery resource;
Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Pancreas;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
STAGE.
PubMed=17932499; DOI=10.1038/sj.cdd.4402238;
Kostylina G., Simon D., Fey M.F., Yousefi S., Simon H.U.;
"Neutrophil apoptosis mediated by nicotinic acid receptors
(GPR109A).";
Cell Death Differ. 15:134-142(2008).
[7]
NOMENCLATURE.
PubMed=21454438; DOI=10.1124/pr.110.003301;
Offermanns S., Colletti S.L., Lovenberg T.W., Semple G., Wise A.,
Ijzerman A.P.;
"International union of basic and clinical pharmacology. LXXXII:
nomenclature and classification of hydroxy-carboxylic acid receptors
(GPR81, GPR109A, and GPR109B).";
Pharmacol. Rev. 63:269-290(2011).
-!- FUNCTION: 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. {ECO:0000269|PubMed:17932499}.
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17932499};
Multi-pass membrane protein {ECO:0000269|PubMed:17932499}.
-!- TISSUE SPECIFICITY: Expression largely restricted to adipose
tissue and spleen. Expressed on mature neutrophils but not on
immature neutrophils or eosinophils. {ECO:0000269|PubMed:12522134,
ECO:0000269|PubMed:17932499}.
-!- DEVELOPMENTAL STAGE: Expression in neutrophils occurs in the late
terminal differentiation phase. {ECO:0000269|PubMed:17932499}.
-!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
{ECO:0000255|PROSITE-ProRule:PRU00521}.
-!- WEB RESOURCE: Name=SeattleSNPs;
URL="http://pga.gs.washington.edu/data/gpr109a/";
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; AY148884; AAN71621.1; -; mRNA.
EMBL; AB083632; BAB89345.1; -; Genomic_DNA.
EMBL; AB065876; BAC06094.1; -; Genomic_DNA.
EMBL; EU012026; ABS29270.1; -; Genomic_DNA.
EMBL; BC027965; AAH27965.1; -; mRNA.
EMBL; BC056419; AAH56419.1; -; mRNA.
CCDS; CCDS9235.1; -.
RefSeq; NP_808219.1; NM_177551.3.
UniGene; Hs.524812; -.
ProteinModelPortal; Q8TDS4; -.
STRING; 9606.ENSP00000375066; -.
BindingDB; Q8TDS4; -.
ChEMBL; CHEMBL3785; -.
DrugBank; DB00627; Niacin.
GuidetoPHARMACOLOGY; 312; -.
iPTMnet; Q8TDS4; -.
PhosphoSitePlus; Q8TDS4; -.
BioMuta; HCAR2; -.
DMDM; 74762622; -.
EPD; Q8TDS4; -.
MaxQB; Q8TDS4; -.
PaxDb; Q8TDS4; -.
PeptideAtlas; Q8TDS4; -.
PRIDE; Q8TDS4; -.
DNASU; 338442; -.
Ensembl; ENST00000328880; ENSP00000375066; ENSG00000182782.
GeneID; 338442; -.
KEGG; hsa:338442; -.
UCSC; uc001ucx.2; human.
CTD; 338442; -.
DisGeNET; 338442; -.
EuPathDB; HostDB:ENSG00000182782.7; -.
GeneCards; HCAR2; -.
HGNC; HGNC:24827; HCAR2.
HPA; HPA028660; -.
MIM; 609163; gene.
neXtProt; NX_Q8TDS4; -.
OpenTargets; ENSG00000182782; -.
PharmGKB; PA165961843; -.
eggNOG; ENOG410IKI5; Eukaryota.
eggNOG; ENOG4110VUM; LUCA.
GeneTree; ENSGT00510000046798; -.
InParanoid; Q8TDS4; -.
KO; K08402; -.
OMA; DTFRWHE; -.
OrthoDB; EOG091G0AN6; -.
TreeFam; TF330775; -.
Reactome; R-HSA-3296197; Hydroxycarboxylic acid-binding receptors.
Reactome; R-HSA-373076; Class A/1 (Rhodopsin-like receptors).
Reactome; R-HSA-418594; G alpha (i) signalling events.
GenomeRNAi; 338442; -.
PRO; PR:Q8TDS4; -.
Proteomes; UP000005640; Chromosome 12.
Bgee; ENSG00000182782; -.
CleanEx; HS_GPR109A; -.
Genevisible; Q8TDS4; HS.
GO; GO:0030054; C:cell junction; IDA:HPA.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
GO; GO:0070553; F:nicotinic acid receptor activity; ISS:UniProtKB.
GO; GO:0007186; P:G-protein coupled receptor signaling pathway; TAS:Reactome.
GO; GO:0050995; P:negative regulation of lipid catabolic process; ISS:UniProtKB.
GO; GO:0001781; P:neutrophil apoptotic process; IDA:UniProtKB.
GO; GO:0070165; P:positive regulation of adiponectin secretion; ISS:UniProtKB.
GO; GO:0033031; P:positive regulation of neutrophil apoptotic process; IDA:UniProtKB.
InterPro; IPR000276; GPCR_Rhodpsn.
InterPro; IPR017452; GPCR_Rhodpsn_7TM.
InterPro; IPR028017; HCAR2/3_rcpt.
PANTHER; PTHR24231:SF0; PTHR24231:SF0; 1.
Pfam; PF00001; 7tm_1; 1.
PRINTS; PR00237; GPCRRHODOPSN.
PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
1: Evidence at protein level;
Apoptosis; Cell membrane; Complete proteome; Disulfide bond;
G-protein coupled receptor; Membrane; Phosphoprotein; Polymorphism;
Receptor; Reference proteome; Transducer; Transmembrane;
Transmembrane helix.
CHAIN 1 363 Hydroxycarboxylic acid receptor 2.
/FTId=PRO_0000069603.
TOPO_DOM 1 33 Extracellular. {ECO:0000255}.
TRANSMEM 34 54 Helical; Name=1. {ECO:0000255}.
TOPO_DOM 55 63 Cytoplasmic. {ECO:0000255}.
TRANSMEM 64 84 Helical; Name=2. {ECO:0000255}.
TOPO_DOM 85 102 Extracellular. {ECO:0000255}.
TRANSMEM 103 123 Helical; Name=3. {ECO:0000255}.
TOPO_DOM 124 142 Cytoplasmic. {ECO:0000255}.
TRANSMEM 143 163 Helical; Name=4. {ECO:0000255}.
TOPO_DOM 164 192 Extracellular. {ECO:0000255}.
TRANSMEM 193 213 Helical; Name=5. {ECO:0000255}.
TOPO_DOM 214 229 Cytoplasmic. {ECO:0000255}.
TRANSMEM 230 250 Helical; Name=6. {ECO:0000255}.
TOPO_DOM 251 273 Extracellular. {ECO:0000255}.
TRANSMEM 274 294 Helical; Name=7. {ECO:0000255}.
TOPO_DOM 295 363 Cytoplasmic. {ECO:0000255}.
MOD_RES 328 328 Phosphoserine.
{ECO:0000250|UniProtKB:Q9EP66}.
DISULFID 100 177 {ECO:0000255|PROSITE-ProRule:PRU00521}.
VARIANT 187 187 Q -> R (in dbSNP:rs676770).
/FTId=VAR_049400.
VARIANT 198 198 F -> L (in dbSNP:rs676823).
/FTId=VAR_049401.
VARIANT 311 311 R -> C (in dbSNP:rs7314976).
{ECO:0000269|Ref.4}.
/FTId=VAR_038713.
VARIANT 317 317 M -> I (in dbSNP:rs2454727).
{ECO:0000269|Ref.4}.
/FTId=VAR_038714.
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


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