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 24-JAN-2024, entry version 171. 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/"; 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; 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 GlyCosmos; Q9BXC0; 1 site, No reported glycans. DR GlyGen; Q9BXC0; 1 site. DR PhosphoSitePlus; Q9BXC0; -. DR BioMuta; HCAR1; -. DR DMDM; 47117701; -. DR jPOST; Q9BXC0; -. DR MassIVE; Q9BXC0; -. DR PaxDb; 9606-ENSP00000389255; -. DR PeptideAtlas; Q9BXC0; -. DR ProteomicsDB; 79402; -. DR Antibodypedia; 19185; 392 antibodies from 33 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 AGR; HGNC:4532; -. 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; RHRQWAF; -. DR OrthoDB; 5354998at2759; -. 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; 18 hits in 1137 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 primordial germ cell in gonad and 66 other cell types or tissues. DR ExpressionAtlas; Q9BXC0; baseline and differential. 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 CDD; cd15201; 7tmA_HCAR1-3; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR PANTHER; PTHR46048:SF3; HYDROXYCARBOXYLIC ACID RECEPTOR 1; 1. DR PANTHER; PTHR46048; HYDROXYCARBOXYLIC ACID RECEPTOR 2; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00237; GPCRRHODOPSN. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR Genevisible; Q9BXC0; HS. 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 //