HCAR1_HUMAN
ID HCAR1_HUMAN Reviewed; 346 AA.
AC Q9BXC0; B2R9X4; Q3Y5J3; Q4VBN1; Q6NXU5;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Hydroxycarboxylic acid receptor 1;
DE AltName: Full=G-protein coupled receptor 104;
DE AltName: Full=G-protein coupled receptor 81;
GN Name=HCAR1; Synonyms=GPR104, GPR81, HCA1; ORFNames=FKSG80;
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 [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=11574155; DOI=10.1016/s0378-1119(01)00651-5;
RA Lee D.K., Nguyen T., Lynch K.R., Cheng R., Vanti W.B., Arkhitko O.,
RA Lewis T., Evans J.F., George S.R., O'Dowd B.F.;
RT "Discovery and mapping of ten novel G protein-coupled receptor genes.";
RL Gene 275:83-91(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS
RP OF ARG-99; TYR-233; ARG-240 AND THR-267.
RX PubMed=19047060; DOI=10.1074/jbc.m806409200;
RA Liu C., Wu J., Zhu J., Kuei C., Yu J., Shelton J., Sutton S.W., Li X.,
RA Yun S.J., Mirzadegan T., Mazur C., Kamme F., Lovenberg T.W.;
RT "Lactate inhibits lipolysis in fat cells through activation of an orphan G-
RT protein-coupled receptor, GPR81.";
RL J. Biol. Chem. 284:2811-2822(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Wang Y.-G., Gong L.;
RT "Molecular cloning of FKSG80, a novel gene encoding a putative chemokine
RT receptor.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RA King M.M., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
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 [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-43 AND GLU-253.
RG SeattleSNPs variation discovery resource;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [12]
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 receptor for L-lactate and mediates its anti-
CC lipolytic effect through a G(i)-protein-mediated pathway.
CC {ECO:0000269|PubMed:19047060}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed abundantly in brown and white fat. It
CC also detectable at lower levels in liver, kidney, skeletal muscle,
CC brain and pituitary. Not detected in frontal, temporal and occipital
CC lobes of the cortex, basal forebrain, caudate nucleus, nucleus
CC accumbens and hippocampus. {ECO:0000269|PubMed:11574155,
CC ECO:0000269|PubMed:19047060}.
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/gpr81/";
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DR EMBL; AF411110; AAL26481.1; -; Genomic_DNA.
DR EMBL; EU809458; ACJ03844.1; -; mRNA.
DR EMBL; AF345568; AAK29071.1; -; mRNA.
DR EMBL; AB065866; BAC06084.1; -; Genomic_DNA.
DR EMBL; AY507143; AAR92485.1; -; mRNA.
DR EMBL; AK313955; BAG36671.1; -; mRNA.
DR EMBL; AB083631; BAB89344.1; -; Genomic_DNA.
DR EMBL; DQ157221; AAZ67915.1; -; Genomic_DNA.
DR EMBL; AC026333; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471054; EAW98337.1; -; Genomic_DNA.
DR EMBL; BC066881; AAH66881.1; -; mRNA.
DR EMBL; BC066882; AAH66882.1; -; mRNA.
DR EMBL; BC066883; AAH66883.1; -; mRNA.
DR EMBL; BC067484; AAH67484.1; -; mRNA.
DR EMBL; BC095506; AAH95506.1; -; mRNA.
DR CCDS; CCDS9236.1; -.
DR RefSeq; NP_115943.1; NM_032554.3.
DR AlphaFoldDB; Q9BXC0; -.
DR SMR; Q9BXC0; -.
DR BioGRID; 118073; 29.
DR IntAct; Q9BXC0; 1.
DR STRING; 9606.ENSP00000389255; -.
DR BindingDB; Q9BXC0; -.
DR ChEMBL; CHEMBL1075101; -.
DR GuidetoPHARMACOLOGY; 311; -.
DR TCDB; 9.A.14.13.4; the g-protein-coupled receptor (gpcr) family.
DR GlyGen; Q9BXC0; 1 site.
DR PhosphoSitePlus; Q9BXC0; -.
DR BioMuta; HCAR1; -.
DR DMDM; 47117701; -.
DR jPOST; Q9BXC0; -.
DR MassIVE; Q9BXC0; -.
DR PaxDb; Q9BXC0; -.
DR PeptideAtlas; Q9BXC0; -.
DR PRIDE; Q9BXC0; -.
DR ProteomicsDB; 79402; -.
DR Antibodypedia; 19185; 360 antibodies from 32 providers.
DR DNASU; 27198; -.
DR Ensembl; ENST00000432564.3; ENSP00000389255.1; ENSG00000196917.6.
DR GeneID; 27198; -.
DR KEGG; hsa:27198; -.
DR MANE-Select; ENST00000432564.3; ENSP00000389255.1; NM_032554.4; NP_115943.1.
DR UCSC; uc001ucz.4; human.
DR CTD; 27198; -.
DR DisGeNET; 27198; -.
DR GeneCards; HCAR1; -.
DR HGNC; HGNC:4532; HCAR1.
DR HPA; ENSG00000196917; Group enriched (breast, parathyroid gland).
DR MIM; 606923; gene.
DR neXtProt; NX_Q9BXC0; -.
DR OpenTargets; ENSG00000196917; -.
DR PharmGKB; PA28925; -.
DR VEuPathDB; HostDB:ENSG00000196917; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT00990000203619; -.
DR HOGENOM; CLU_009579_8_2_1; -.
DR InParanoid; Q9BXC0; -.
DR OMA; LMESHLC; -.
DR OrthoDB; 903658at2759; -.
DR PhylomeDB; Q9BXC0; -.
DR TreeFam; TF330775; -.
DR PathwayCommons; Q9BXC0; -.
DR Reactome; R-HSA-3296197; Hydroxycarboxylic acid-binding receptors.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; Q9BXC0; -.
DR BioGRID-ORCS; 27198; 12 hits in 1059 CRISPR screens.
DR ChiTaRS; HCAR1; human.
DR GeneWiki; GPR81; -.
DR GenomeRNAi; 27198; -.
DR Pharos; Q9BXC0; Tchem.
DR PRO; PR:Q9BXC0; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9BXC0; protein.
DR Bgee; ENSG00000196917; Expressed in omental fat pad and 65 other tissues.
DR ExpressionAtlas; Q9BXC0; baseline and differential.
DR Genevisible; Q9BXC0; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; IEA:Ensembl.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR028016; HCAR1_rcpt.
DR PANTHER; PTHR46048:SF3; PTHR46048:SF3; 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; Glycoprotein;
KW Membrane; Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..346
FT /note="Hydroxycarboxylic acid receptor 1"
FT /id="PRO_0000069586"
FT TOPO_DOM 1..21
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 22..42
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 43..49
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 50..70
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 71..89
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 90..110
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 111..130
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 131..151
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 152..182
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 183..203
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 204..220
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 221..241
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 242..261
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..281
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 282..346
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 3
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 88..165
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 43
FT /note="H -> Q (in dbSNP:rs35292336)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_025151"
FT VARIANT 253
FT /note="D -> E"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_025152"
FT VARIANT 253
FT /note="D -> H (in dbSNP:rs36124671)"
FT /id="VAR_061218"
FT MUTAGEN 99
FT /note="R->A: Diminishes the response to L-lactate."
FT /evidence="ECO:0000269|PubMed:19047060"
FT MUTAGEN 233
FT /note="Y->A: Diminishes the response to L-lactate."
FT /evidence="ECO:0000269|PubMed:19047060"
FT MUTAGEN 240
FT /note="R->A: Diminishes the response to L-lactate."
FT /evidence="ECO:0000269|PubMed:19047060"
FT MUTAGEN 267
FT /note="T->A: Diminishes the response to L-lactate."
FT /evidence="ECO:0000269|PubMed:19047060"
FT CONFLICT 38
FT /note="C -> Y (in Ref. 11; AAH95506)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="R -> K (in Ref. 11; AAH66883)"
FT /evidence="ECO:0000305"
FT CONFLICT 187
FT /note="M -> I (in Ref. 11; AAH95506)"
FT /evidence="ECO:0000305"
FT CONFLICT 213
FT /note="A -> T (in Ref. 11; AAH95506)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="I -> T (in Ref. 11; AAH95506)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 346 AA; 39295 MW; E0DB114EEB3A47A5 CRC64;
MYNGSCCRIE GDTISQVMPP LLIVAFVLGA LGNGVALCGF CFHMKTWKPS TVYLFNLAVA
DFLLMICLPF RTDYYLRRRH WAFGDIPCRV GLFTLAMNRA GSIVFLTVVA ADRYFKVVHP
HHAVNTISTR VAAGIVCTLW ALVILGTVYL LLENHLCVQE TAVSCESFIM ESANGWHDIM
FQLEFFMPLG IILFCSFKIV WSLRRRQQLA RQARMKKATR FIMVVAIVFI TCYLPSVSAR
LYFLWTVPSS ACDPSVHGAL HITLSFTYMN SMLDPLVYYF SSPSFPKFYN KLKICSLKPK
QPGHSKTQRP EEMPISNLGR RSCISVANSF QSQSDGQWDP HIVEWH
