HCAR2_RAT
ID HCAR2_RAT Reviewed; 360 AA.
AC Q80Z39;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Hydroxycarboxylic acid receptor 2;
DE AltName: Full=G-protein coupled receptor 109;
DE AltName: Full=G-protein coupled receptor 109A;
DE AltName: Full=G-protein coupled receptor HM74;
DE AltName: Full=Niacin receptor 1;
DE AltName: Full=Nicotinic acid receptor;
DE AltName: Full=Protein PUMA-G;
GN Name=Hcar2; Synonyms=Gpr109, Gpr109a, Gpr109b, Niacr1, Pumag;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=12646212; DOI=10.1016/s0006-291x(03)00342-5;
RA Soga T., Kamohara M., Takasaki J., Matsumoto S., Saito T., Ohishi T.,
RA Hiyama H., Matsuo A., Matsushime H., Furuichi K.;
RT "Molecular identification of nicotinic acid receptor.";
RL Biochem. Biophys. Res. Commun. 303:364-369(2003).
RN [2]
RP FUNCTION, 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 [3]
RP FUNCTION.
RX PubMed=19141678; DOI=10.1152/ajpendo.91004.2008;
RA Plaisance E.P., Lukasova M., Offermanns S., Zhang Y., Cao G., Judd R.L.;
RT "Niacin stimulates adiponectin secretion through the GPR109A receptor.";
RL Am. J. Physiol. 296:E549-E558(2009).
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:12522134,
CC ECO:0000269|PubMed:12646212, ECO:0000269|PubMed:19141678}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in adipose tissue, lung and spleen.
CC {ECO:0000269|PubMed:12522134, ECO:0000269|PubMed:12646212}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AB103062; BAC58009.1; -; mRNA.
DR RefSeq; NP_852141.1; NM_181476.1.
DR AlphaFoldDB; Q80Z39; -.
DR SMR; Q80Z39; -.
DR STRING; 10116.ENSRNOP00000036057; -.
DR BindingDB; Q80Z39; -.
DR ChEMBL; CHEMBL4731; -.
DR DrugCentral; Q80Z39; -.
DR GuidetoPHARMACOLOGY; 312; -.
DR iPTMnet; Q80Z39; -.
DR PhosphoSitePlus; Q80Z39; -.
DR PaxDb; Q80Z39; -.
DR Ensembl; ENSRNOT00000032249; ENSRNOP00000036057; ENSRNOG00000026653.
DR GeneID; 353250; -.
DR KEGG; rno:353250; -.
DR UCSC; RGD:727952; rat.
DR CTD; 338442; -.
DR RGD; 727952; Hcar2.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00990000203619; -.
DR HOGENOM; CLU_009579_8_2_1; -.
DR InParanoid; Q80Z39; -.
DR OMA; KWDWKFG; -.
DR OrthoDB; 903658at2759; -.
DR PhylomeDB; Q80Z39; -.
DR TreeFam; TF330775; -.
DR Reactome; R-RNO-3296197; Hydroxycarboxylic acid-binding receptors.
DR Reactome; R-RNO-373076; Class A/1 (Rhodopsin-like receptors).
DR Reactome; R-RNO-418594; G alpha (i) signalling events.
DR PRO; PR:Q80Z39; -.
DR Proteomes; UP000002494; Chromosome 12.
DR Bgee; ENSRNOG00000026653; Expressed in spleen and 12 other tissues.
DR Genevisible; Q80Z39; RN.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; ISO:RGD.
DR GO; GO:0005525; F:GTP binding; ISO:RGD.
DR GO; GO:0070553; F:nicotinic acid receptor activity; IDA:UniProtKB.
DR GO; GO:0001614; F:purinergic nucleotide receptor activity; ISO:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; IDA:UniProtKB.
DR GO; GO:0001781; P:neutrophil apoptotic process; ISO:RGD.
DR GO; GO:0070165; P:positive regulation of adiponectin secretion; IDA:UniProtKB.
DR GO; GO:0033031; P:positive regulation of neutrophil apoptotic process; ISS: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..360
FT /note="Hydroxycarboxylic acid receptor 2"
FT /id="PRO_0000069606"
FT TOPO_DOM 1..30
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 31..51
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 52..60
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 61..81
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 82..98
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 99..119
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 120..140
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 141..161
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 162..189
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 190..210
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 211..226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 227..247
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 248..270
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 271..291
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 292..360
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 320..360
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 325
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9EP66"
FT DISULFID 97..174
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ SEQUENCE 360 AA; 41459 MW; 975BDEBCA448A6C5 CRC64;
MSKQNHFLVI NGKNCCVFRD ENIAKVLPPV LGLEFVFGLL GNGLALWIFC FHLKSWKSSR
IFLFNLAVAD FLLIICLPFL TDNYVQNWDW RFGSIPCRVM LFMLAMNRQG SIIFLTVVAV
DRYFRVVHPH HFLNKISNRT AAIISCFLWG ITIGLTVHLL YTDMMTRNGD ANLCSSFSIC
YTFRWHDAMF LLEFFLPLGI ILFCSGRIIW SLRQRQMDRH VKIKRAINFI MVVAIVFVIC
FLPSVAVRIR IFWLLYKHNV RNCDIYSSVD LAFFTTLSFT YMNSMLDPVV YYFSSPSFPN
FFSTCINRCL RRKTLGEPDN NRSTSVELTG DPSTIRSIPG ALMTDPSEPG SPPYLASTSR
