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 31-JUL-2019, entry version 149. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT genes."; RL Gene 275:83-91(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND RP MUTAGENESIS 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 RT orphan G-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 RT chemokine 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 RT sequenced by 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 RT genome 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., RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., RA 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., RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., RA 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., RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., RA Kucherlapati R., Weinstock G., 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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. CC It also detectable at lower levels in liver, kidney, skeletal CC muscle, brain and pituitary. Not detected in frontal, temporal and CC occipital lobes of the cortex, basal forebrain, caudate nucleus, CC nucleus 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 BioGrid; 118073; 5. 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 PhosphoSitePlus; Q9BXC0; -. DR BioMuta; HCAR1; -. DR DMDM; 47117701; -. DR jPOST; Q9BXC0; -. DR PaxDb; Q9BXC0; -. DR PeptideAtlas; Q9BXC0; -. DR PRIDE; Q9BXC0; -. DR ProteomicsDB; 79402; -. DR DNASU; 27198; -. DR Ensembl; ENST00000432564; ENSP00000389255; ENSG00000196917. DR GeneID; 27198; -. DR KEGG; hsa:27198; -. DR UCSC; uc001ucz.4; human. DR CTD; 27198; -. DR DisGeNET; 27198; -. DR GeneCards; HCAR1; -. DR HGNC; HGNC:4532; HCAR1. DR MIM; 606923; gene. DR neXtProt; NX_Q9BXC0; -. DR OpenTargets; ENSG00000196917; -. DR PharmGKB; PA28925; -. DR eggNOG; ENOG410IKI5; Eukaryota. DR eggNOG; ENOG4110VUM; LUCA. DR GeneTree; ENSGT00950000182614; -. DR InParanoid; Q9BXC0; -. DR KO; K08401; -. DR OMA; QLEFFLP; -. DR OrthoDB; 856254at2759; -. DR PhylomeDB; Q9BXC0; -. DR TreeFam; TF330775; -. DR Reactome; R-HSA-3296197; Hydroxycarboxylic acid-binding receptors. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR GeneWiki; GPR81; -. DR GenomeRNAi; 27198; -. DR PRO; PR:Q9BXC0; -. DR Proteomes; UP000005640; Chromosome 12. DR Bgee; ENSG00000196917; Expressed in 56 organ(s), highest expression level in thoracic mammary gland. DR Genevisible; Q9BXC0; HS. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome. 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; Complete proteome; Disulfide bond; KW G-protein coupled receptor; Glycoprotein; Membrane; Polymorphism; KW Receptor; Reference proteome; Transducer; Transmembrane; KW Transmembrane helix. FT CHAIN 1 346 Hydroxycarboxylic acid receptor 1. FT /FTId=PRO_0000069586. FT TOPO_DOM 1 21 Extracellular. {ECO:0000255}. FT TRANSMEM 22 42 Helical; Name=1. {ECO:0000255}. FT TOPO_DOM 43 49 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 50 70 Helical; Name=2. {ECO:0000255}. FT TOPO_DOM 71 89 Extracellular. {ECO:0000255}. FT TRANSMEM 90 110 Helical; Name=3. {ECO:0000255}. FT TOPO_DOM 111 130 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 131 151 Helical; Name=4. {ECO:0000255}. FT TOPO_DOM 152 182 Extracellular. {ECO:0000255}. FT TRANSMEM 183 203 Helical; Name=5. {ECO:0000255}. FT TOPO_DOM 204 220 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 221 241 Helical; Name=6. {ECO:0000255}. FT TOPO_DOM 242 261 Extracellular. {ECO:0000255}. FT TRANSMEM 262 281 Helical; Name=7. {ECO:0000255}. FT TOPO_DOM 282 346 Cytoplasmic. {ECO:0000255}. FT CARBOHYD 3 3 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 88 165 {ECO:0000255|PROSITE-ProRule:PRU00521}. FT VARIANT 43 43 H -> Q (in dbSNP:rs35292336). FT {ECO:0000269|Ref.8}. FT /FTId=VAR_025151. FT VARIANT 253 253 D -> E. {ECO:0000269|Ref.8}. FT /FTId=VAR_025152. FT VARIANT 253 253 D -> H (in dbSNP:rs36124671). FT /FTId=VAR_061218. FT MUTAGEN 99 99 R->A: Diminishes the response to L- FT lactate. {ECO:0000269|PubMed:19047060}. FT MUTAGEN 233 233 Y->A: Diminishes the response to L- FT lactate. {ECO:0000269|PubMed:19047060}. FT MUTAGEN 240 240 R->A: Diminishes the response to L- FT lactate. {ECO:0000269|PubMed:19047060}. FT MUTAGEN 267 267 T->A: Diminishes the response to L- FT lactate. {ECO:0000269|PubMed:19047060}. FT CONFLICT 38 38 C -> Y (in Ref. 11; AAH95506). FT {ECO:0000305}. FT CONFLICT 113 113 R -> K (in Ref. 11; AAH66883). FT {ECO:0000305}. FT CONFLICT 187 187 M -> I (in Ref. 11; AAH95506). FT {ECO:0000305}. FT CONFLICT 213 213 A -> T (in Ref. 11; AAH95506). FT {ECO:0000305}. FT CONFLICT 222 222 I -> T (in Ref. 11; AAH95506). FT {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 //