HCAR3_HUMAN
ID HCAR3_HUMAN Reviewed; 387 AA.
AC P49019; A8K4G5; B2R830; E9PI97; Q8NGE4;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2013, sequence version 3.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Hydroxycarboxylic acid receptor 3;
DE AltName: Full=G-protein coupled receptor 109B;
DE AltName: Full=G-protein coupled receptor HM74;
DE AltName: Full=G-protein coupled receptor HM74B;
DE AltName: Full=Niacin receptor 2;
DE AltName: Full=Nicotinic acid receptor 2;
GN Name=HCAR3; Synonyms=GPR109B, HCA3, HM74B, NIACR2;
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], AND VARIANTS PRO-173; LEU-198; ARG-253; MET-317
RP AND MET-346.
RC TISSUE=Monocyte;
RX PubMed=7505609; DOI=10.1093/intimm/5.10.1239;
RA Nomura H., Nielsen B.W., Matsushima K.;
RT "Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte
RT chemotactic peptide receptors.";
RL Int. Immunol. 5:1239-1249(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PRO-173; LEU-198; ARG-253;
RP MET-317 AND MET-346.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS PRO-173; LEU-198;
RP ARG-253; MET-317 AND MET-346.
RC TISSUE=Neutrophil;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS PRO-173; LEU-198;
RP ARG-253; MET-317 AND MET-346.
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 [7]
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 [8]
RP FUNCTION, AND MUTAGENESIS OF ARG-111.
RX PubMed=19561068; DOI=10.1074/jbc.m109.019455;
RA Ahmed K., Tunaru S., Langhans C.-D., Hanson J., Michalski C.W., Koelker S.,
RA Jones P.M., Okun J.G., Offermanns S.;
RT "Deorphanization of GPR109B as a receptor for the beta-oxidation
RT intermediate 3-OH-octanoic acid and its role in the regulation of
RT lipolysis.";
RL J. Biol. Chem. 284:21928-21933(2009).
RN [9]
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: Receptor for 3-OH-octanoid acid mediates a negative feedback
CC regulation of adipocyte lipolysis to counteract prolipolytic influences
CC under conditions of physiological or pathological increases in beta-
CC oxidation rates. Acts as a low affinity receptor for nicotinic acid.
CC This pharmacological effect requires nicotinic acid doses that are much
CC higher than those provided by a normal diet.
CC {ECO:0000269|PubMed:12522134, ECO:0000269|PubMed:19561068}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expression largely restricted to adipose tissue and
CC spleen. {ECO:0000269|PubMed:12522134}.
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/gpr109b/";
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DR EMBL; D10923; BAA01721.1; -; mRNA.
DR EMBL; AB065865; BAC06083.1; -; Genomic_DNA.
DR EMBL; AK290930; BAF83619.1; -; mRNA.
DR EMBL; AK313212; BAG36027.1; -; mRNA.
DR EMBL; EU293604; ABX64359.1; -; Genomic_DNA.
DR EMBL; AC026333; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC047891; AAH47891.1; -; mRNA.
DR CCDS; CCDS53842.1; -.
DR PIR; I69202; I69202.
DR RefSeq; NP_006009.2; NM_006018.2.
DR AlphaFoldDB; P49019; -.
DR SMR; P49019; -.
DR IntAct; P49019; 1.
DR STRING; 9606.ENSP00000436714; -.
DR BindingDB; P49019; -.
DR ChEMBL; CHEMBL4421; -.
DR DrugBank; DB08949; Inositol nicotinate.
DR DrugBank; DB00627; Niacin.
DR DrugCentral; P49019; -.
DR GuidetoPHARMACOLOGY; 313; -.
DR iPTMnet; P49019; -.
DR PhosphoSitePlus; P49019; -.
DR BioMuta; HCAR3; -.
DR DMDM; 519668680; -.
DR EPD; P49019; -.
DR jPOST; P49019; -.
DR MassIVE; P49019; -.
DR MaxQB; P49019; -.
DR PaxDb; P49019; -.
DR PeptideAtlas; P49019; -.
DR PRIDE; P49019; -.
DR ProteomicsDB; 20737; -.
DR ProteomicsDB; 55956; -.
DR Antibodypedia; 53056; 203 antibodies from 26 providers.
DR DNASU; 8843; -.
DR Ensembl; ENST00000528880.3; ENSP00000436714.2; ENSG00000255398.3.
DR GeneID; 8843; -.
DR KEGG; hsa:8843; -.
DR MANE-Select; ENST00000528880.3; ENSP00000436714.2; NM_006018.3; NP_006009.2.
DR UCSC; uc001ucy.4; human.
DR CTD; 8843; -.
DR DisGeNET; 8843; -.
DR GeneCards; HCAR3; -.
DR HGNC; HGNC:16824; HCAR3.
DR HPA; ENSG00000255398; Tissue enhanced (bone marrow, esophagus, lymphoid tissue).
DR MIM; 606039; gene.
DR neXtProt; NX_P49019; -.
DR OpenTargets; ENSG00000255398; -.
DR PharmGKB; PA165512827; -.
DR VEuPathDB; HostDB:ENSG00000255398; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00990000203619; -.
DR HOGENOM; CLU_009579_8_2_1; -.
DR InParanoid; P49019; -.
DR OMA; KWDWKFG; -.
DR OrthoDB; 903658at2759; -.
DR PhylomeDB; P49019; -.
DR TreeFam; TF330775; -.
DR PathwayCommons; P49019; -.
DR Reactome; R-HSA-3296197; Hydroxycarboxylic acid-binding receptors.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P49019; -.
DR BioGRID-ORCS; 8843; 10 hits in 1022 CRISPR screens.
DR GenomeRNAi; 8843; -.
DR Pharos; P49019; Tchem.
DR PRO; PR:P49019; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P49019; protein.
DR Bgee; ENSG00000255398; Expressed in blood and 77 other tissues.
DR Genevisible; P49019; HS.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0070553; F:nicotinic acid receptor activity; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
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 Cell membrane; Disulfide bond; G-protein coupled receptor; Membrane;
KW Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..387
FT /note="Hydroxycarboxylic acid receptor 3"
FT /id="PRO_0000069604"
FT TOPO_DOM 1..28
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 29..50
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 51..63
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 64..85
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 86..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..194
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 195..209
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 210..236
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 237..256
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 257..273
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 274..298
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 299..387
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 319..343
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 DISULFID 100..177
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 173
FT /note="T -> P (in dbSNP:rs1798192)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:7505609,
FT ECO:0000269|Ref.2"
FT /id="VAR_038715"
FT VARIANT 198
FT /note="F -> L (in dbSNP:rs17884481)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:7505609,
FT ECO:0000269|Ref.2"
FT /id="VAR_038716"
FT VARIANT 253
FT /note="H -> R (in dbSNP:rs118091133)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:7505609,
FT ECO:0000269|Ref.2"
FT /id="VAR_038717"
FT VARIANT 317
FT /note="I -> M (in dbSNP:rs116821988)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:7505609,
FT ECO:0000269|Ref.2"
FT /id="VAR_038718"
FT VARIANT 346
FT /note="I -> M (in dbSNP:rs1696351)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:7505609,
FT ECO:0000269|Ref.2"
FT /id="VAR_038719"
FT VARIANT 350
FT /note="G -> S (in dbSNP:rs201835480)"
FT /id="VAR_038720"
FT MUTAGEN 111
FT /note="R->A: Abrogates completely the activation by OH-
FT octanoid acid."
FT /evidence="ECO:0000269|PubMed:19561068"
FT CONFLICT 94
FT /note="K -> N (in Ref. 1; BAA01721)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 387 AA; 44478 MW; 887BA427B6134A3F CRC64;
MNRHHLQDHF LEIDKKNCCV FRDDFIAKVL PPVLGLEFIF GLLGNGLALW IFCFHLKSWK
SSRIFLFNLA VADFLLIICL PFVMDYYVRR SDWKFGDIPC RLVLFMFAMN RQGSIIFLTV
VAVDRYFRVV HPHHALNKIS NWTAAIISCL LWGITVGLTV HLLKKKLLIQ NGTANVCISF
SICHTFRWHE AMFLLEFFLP LGIILFCSAR IIWSLRQRQM DRHAKIKRAI TFIMVVAIVF
VICFLPSVVV RIHIFWLLHT SGTQNCEVYR SVDLAFFITL SFTYMNSMLD PVVYYFSSPS
FPNFFSTLIN RCLQRKITGE PDNNRSTSVE LTGDPNKTRG APEALIANSG EPWSPSYLGP
TSNNHSKKGH CHQEPASLEK QLGCCIE
