Q9BXC0 (HCAR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hydroxycarboxylic acid receptor 1

Alternative name(s):
G-protein coupled receptor 104
G-protein coupled receptor 81

Gene names

Name:	HCAR1
Synonyms:	GPR104, GPR81, HCA1
ORF Names:	FKSG80

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	346 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a receptor for L-lactate and mediates its anti-lipolytic effect through a G(i)-protein-mediated pathway. Ref.2
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Expressed abundantly in brown and white fat. It also detectable at lower levels in liver, kidney, skeletal muscle, brain and pituitary. Not detected in frontal, temporal and occipital lobes of the cortex, basal forebrain, caudate nucleus, nucleus accumbens and hippocampus. Ref.1 Ref.2
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	response to estradiol stimulus Inferred from direct assay PubMed 15831516. Source: BHF-UCL
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	G-protein coupled receptor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 346	346	Hydroxycarboxylic acid receptor 1		PRO_0000069586
Regions
	Topological domain	1 – 21	21	Extracellular Potential
	Transmembrane	22 – 42	21	Helical; Name=1; Potential
	Topological domain	43 – 49	7	Cytoplasmic Potential
	Transmembrane	50 – 70	21	Helical; Name=2; Potential
	Topological domain	71 – 89	19	Extracellular Potential
	Transmembrane	90 – 110	21	Helical; Name=3; Potential
	Topological domain	111 – 130	20	Cytoplasmic Potential
	Transmembrane	131 – 151	21	Helical; Name=4; Potential
	Topological domain	152 – 182	31	Extracellular Potential
	Transmembrane	183 – 203	21	Helical; Name=5; Potential
	Topological domain	204 – 220	17	Cytoplasmic Potential
	Transmembrane	221 – 241	21	Helical; Name=6; Potential
	Topological domain	242 – 261	20	Extracellular Potential
	Transmembrane	262 – 281	20	Helical; Name=7; Potential
	Topological domain	282 – 346	65	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	3	1	N-linked (GlcNAc...) Potential
	Disulfide bond	88 ↔ 165		By similarity
Natural variations
	Natural variant	43	1	H → Q. Ref.8 Corresponds to variant rs35292336 [ dbSNP | Ensembl ].		VAR_025151
	Natural variant	253	1	D → E. Ref.8		VAR_025152
	Natural variant	253	1	D → H. Corresponds to variant rs36124671 [ dbSNP | Ensembl ].		VAR_061218
Experimental info
	Mutagenesis	99	1	R → A: Diminishes the response to L-lactate. Ref.2
	Mutagenesis	233	1	Y → A: Diminishes the response to L-lactate. Ref.2
	Mutagenesis	240	1	R → A: Diminishes the response to L-lactate. Ref.2
	Mutagenesis	267	1	T → A: Diminishes the response to L-lactate. Ref.2
	Sequence conflict	38	1	C → Y in AAH95506. Ref.11
	Sequence conflict	113	1	R → K in AAH66883. Ref.11
	Sequence conflict	187	1	M → I in AAH95506. Ref.11
	Sequence conflict	213	1	A → T in AAH95506. Ref.11
	Sequence conflict	222	1	I → T in AAH95506. Ref.11

Sequences

	Sequence		Length	Mass (Da)
	Q9BXC0 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: E0DB114EEB3A47A5	FASTA	346	39,295
	10 20 30 40 50 60 MYNGSCCRIE GDTISQVMPP LLIVAFVLGA LGNGVALCGF CFHMKTWKPS TVYLFNLAVA 70 80 90 100 110 120 DFLLMICLPF RTDYYLRRRH WAFGDIPCRV GLFTLAMNRA GSIVFLTVVA ADRYFKVVHP 130 140 150 160 170 180 HHAVNTISTR VAAGIVCTLW ALVILGTVYL LLENHLCVQE TAVSCESFIM ESANGWHDIM 190 200 210 220 230 240 FQLEFFMPLG IILFCSFKIV WSLRRRQQLA RQARMKKATR FIMVVAIVFI TCYLPSVSAR 250 260 270 280 290 300 LYFLWTVPSS ACDPSVHGAL HITLSFTYMN SMLDPLVYYF SSPSFPKFYN KLKICSLKPK 310 320 330 340 QPGHSKTQRP EEMPISNLGR RSCISVANSF QSQSDGQWDP HIVEWH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Discovery and mapping of ten novel G protein-coupled receptor genes." Lee D.K., Nguyen T., Lynch K.R., Cheng R., Vanti W.B., Arkhitko O., Lewis T., Evans J.F., George S.R., O'Dowd B.F. Gene 275:83-91(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[2]	"Lactate inhibits lipolysis in fat cells through activation of an orphan G-protein-coupled receptor, GPR81." Liu C., Wu J., Zhu J., Kuei C., Yu J., Shelton J., Sutton S.W., Li X., Yun S.J., Mirzadegan T., Mazur C., Kamme F., Lovenberg T.W. J. Biol. Chem. 284:2811-2822(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF ARG-99; TYR-233; ARG-240 AND THR-267.
[3]	"Molecular cloning of FKSG80, a novel gene encoding a putative chemokine receptor." Wang Y.-G., Gong L. Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Genome-wide discovery and analysis of human seven transmembrane helix receptor genes." Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., Tsutsumi S., Aburatani H., Asai K., Akiyama Y. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." King M.M., Aronstam R.S., Sharma S.V. Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Spleen.
[7]	"Identification of G protein-coupled receptor genes from the human genome sequence." Takeda S., Kadowaki S., Haga T., Takaesu H., Mitaku S. FEBS Lett. 520:97-101(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	SeattleSNPs variation discovery resource Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-43 AND GLU-253.
[9]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[12]	"International union of basic and clinical pharmacology. LXXXII: nomenclature and classification of hydroxy-carboxylic acid receptors (GPR81, GPR109A, and GPR109B)." Offermanns S., Colletti S.L., Lovenberg T.W., Semple G., Wise A., Ijzerman A.P. Pharmacol. Rev. 63:269-290(2011) [PubMed] [Europe PMC] [Abstract] Cited for: NOMENCLATURE.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF411110 Genomic DNA. Translation: AAL26481.1. EU809458 mRNA. Translation: ACJ03844.1. AF345568 mRNA. Translation: AAK29071.1. AB065866 Genomic DNA. Translation: BAC06084.1. AY507143 mRNA. Translation: AAR92485.1. AK313955 mRNA. Translation: BAG36671.1. AB083631 Genomic DNA. Translation: BAB89344.1. DQ157221 Genomic DNA. Translation: AAZ67915.1. AC026333 Genomic DNA. No translation available. CH471054 Genomic DNA. Translation: EAW98337.1. BC066881 mRNA. Translation: AAH66881.1. BC066882 mRNA. Translation: AAH66882.1. BC066883 mRNA. Translation: AAH66883.1. BC067484 mRNA. Translation: AAH67484.1. BC095506 mRNA. Translation: AAH95506.1.
IPI	IPI00000211.
RefSeq	NP_115943.1. NM_032554.3.
UniGene	Hs.610873. Hs.711001.
3D structure databases
ProteinModelPortal	Q9BXC0.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000349478.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q9BXC0.
Polymorphism databases
DMDM	47117701.
Proteomic databases
PaxDb	Q9BXC0.
PRIDE	Q9BXC0.
Protocols and materials databases
DNASU	27198.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000356987; ENSP00000349478; ENSG00000196917. ENST00000432564; ENSP00000389255; ENSG00000196917. ENST00000436083; ENSP00000409980; ENSG00000196917.
GeneID	27198.
KEGG	hsa:27198.
UCSC	uc001ucz.3. human.
Organism-specific databases
CTD	27198.
GeneCards	GC12M123104.
H-InvDB	HIX0026348.
HGNC	HGNC:4532. HCAR1.
MIM	606923. gene.
neXtProt	NX_Q9BXC0.
PharmGKB	PA28925.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG148165.
HOVERGEN	HBG051680.
InParanoid	Q9BXC0.
KO	K08401.
OMA	MFQLEFF.
OrthoDB	EOG495ZSR.
PhylomeDB	Q9BXC0.
Gene expression databases
Bgee	Q9BXC0.
CleanEx	HS_GPR81.
Genevestigator	Q9BXC0.
GermOnline	ENSG00000196917. Homo sapiens.
Family and domain databases
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1075101.
GenomeRNAi	27198.
NextBio	50062.
SOURCE	Search...

Entry information

Entry name

HCAR1_HUMAN

Accession

Primary (citable) accession number: Q9BXC0
Secondary accession number(s): B2R9X4 , Q3Y5J3, Q4VBN1, Q6NXU5

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 10, 2003
Last sequence update:	June 1, 2001
Last modified:	May 1, 2013
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.