HCAR2_MOUSE
ID HCAR2_MOUSE Reviewed; 360 AA.
AC Q9EP66;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 144.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], INDUCTION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=129/SvJ, and C57BL/6J;
RX PubMed=11745392;
RX DOI=10.1002/1521-4141(200112)31:12<3714::aid-immu3714>3.0.co;2-1;
RA Schaub A., Fuetterer A., Pfeffer K.;
RT "PUMA-G, an IFN-gamma-inducible gene in macrophages is a novel member of
RT the seven transmembrane spanning receptor superfamily.";
RL Eur. J. Immunol. 31:3714-3725(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP 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 [4]
RP FUNCTION.
RX PubMed=15929991; DOI=10.1074/jbc.c500213200;
RA Taggart A.K.P., Kero J., Gan X., Cai T.-Q., Cheng K., Ippolito M., Ren N.,
RA Kaplan R., Wu K., Wu T.-J., Jin L., Liaw C., Chen R., Richman J.,
RA Connolly D., Offermanns S., Wright S.D., Waters M.G.;
RT "(D)-beta-hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic
RT acid receptor PUMA-G.";
RL J. Biol. Chem. 280:26649-26652(2005).
RN [5]
RP DISRUPTION PHENOTYPE.
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).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-325, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. {ECO:0000269|PubMed:15929991}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in lungs, spleen, heart, skeletal muscle
CC and adipose tissue. {ECO:0000269|PubMed:11745392,
CC ECO:0000269|PubMed:12646212}.
CC -!- INDUCTION: By interferon-gamma in macrophages.
CC {ECO:0000269|PubMed:11745392}.
CC -!- DISRUPTION PHENOTYPE: Niacin administration has no effect on serum
CC adiponectin levels in contrast to wild-type mice where levels are
CC decreased. {ECO:0000269|PubMed:19141678}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ300198; CAC17790.1; -; mRNA.
DR EMBL; AJ300199; CAC17791.1; -; Genomic_DNA.
DR EMBL; AK150795; BAE29858.1; -; mRNA.
DR CCDS; CCDS19668.1; -.
DR RefSeq; NP_109626.1; NM_030701.3.
DR AlphaFoldDB; Q9EP66; -.
DR SMR; Q9EP66; -.
DR STRING; 10090.ENSMUSP00000054104; -.
DR BindingDB; Q9EP66; -.
DR ChEMBL; CHEMBL4420; -.
DR DrugCentral; Q9EP66; -.
DR GuidetoPHARMACOLOGY; 312; -.
DR iPTMnet; Q9EP66; -.
DR PhosphoSitePlus; Q9EP66; -.
DR jPOST; Q9EP66; -.
DR PaxDb; Q9EP66; -.
DR PRIDE; Q9EP66; -.
DR ProteomicsDB; 271495; -.
DR DNASU; 80885; -.
DR Ensembl; ENSMUST00000057145; ENSMUSP00000054104; ENSMUSG00000045502.
DR GeneID; 80885; -.
DR KEGG; mmu:80885; -.
DR UCSC; uc008zop.3; mouse.
DR CTD; 338442; -.
DR MGI; MGI:1933383; Hcar2.
DR VEuPathDB; HostDB:ENSMUSG00000045502; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00990000203619; -.
DR HOGENOM; CLU_009579_8_2_1; -.
DR InParanoid; Q9EP66; -.
DR OMA; KWDWKFG; -.
DR OrthoDB; 903658at2759; -.
DR PhylomeDB; Q9EP66; -.
DR TreeFam; TF330775; -.
DR Reactome; R-MMU-3296197; Hydroxycarboxylic acid-binding receptors.
DR Reactome; R-MMU-373076; Class A/1 (Rhodopsin-like receptors).
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR BioGRID-ORCS; 80885; 0 hits in 71 CRISPR screens.
DR PRO; PR:Q9EP66; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9EP66; protein.
DR Bgee; ENSMUSG00000045502; Expressed in granulocyte and 60 other tissues.
DR ExpressionAtlas; Q9EP66; baseline and differential.
DR Genevisible; Q9EP66; MM.
DR GO; GO:0030054; C:cell junction; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IDA:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IDA:MGI.
DR GO; GO:0005525; F:GTP binding; IDA:MGI.
DR GO; GO:0070553; F:nicotinic acid receptor activity; ISS:UniProtKB.
DR GO; GO:0001614; F:purinergic nucleotide receptor activity; IDA:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:MGI.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; ISS:UniProtKB.
DR GO; GO:0070165; P:positive regulation of adiponectin secretion; ISS: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 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_0000069605"
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 COMPBIAS 320..336
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 325
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT DISULFID 97..174
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ SEQUENCE 360 AA; 41401 MW; CCCE52A2475777FC CRC64;
MSKSDHFLVI NGKNCCVFRD ENIAKVLPPV LGLEFVFGLL GNGLALWIFC FHLKSWKSSR
IFLFNLAVAD FLLIICLPFL TDNYVHNWDW RFGGIPCRVM LFMLAMNRQG SIIFLTVVAV
DRYFRVVHPH HFLNKISNRT AAIISCFLWG LTIGLTVHLL YTNMMTKNGE AYLCSSFSIC
YNFRWHDAMF LLEFFLPLAI ILFCSGRIIW SLRQRQMDRH AKIKRAINFI MVVAIVFIIC
FLPSVAVRIR IFWLLYKYNV RNCDIYSSVD LAFFTTLSFT YMNSMLDPVV YYFSSPSFPN
FFSTCINRCL RKKTLGEPDN NRSTSVELTG DPSTTRSIPG ALMADPSEPG SPPYLASTSR
