P49019 (HCAR3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hydroxycarboxylic acid receptor 3

Alternative name(s):
G-protein coupled receptor 109B
G-protein coupled receptor HM74
G-protein coupled receptor HM74B
Niacin receptor 2
Nicotinic acid receptor 2

Gene names

Name:	HCAR3
Synonyms:	GPR109B, HCA3, HM74B, NIACR2

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	387 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for 3-OH-octanoid acid mediates a negative feedback regulation of adipocyte lipolysis to counteract prolipolytic influences under conditions of physiological or pathological increases in beta-oxidation rates. Acts as a low affinity receptor for nicotinic acid. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet. Ref.6 Ref.7
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Expression largely restricted to adipose tissue and spleen. Ref.6
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
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	G-protein coupled purinergic nucleotide receptor activity Inferred from electronic annotation. Source: InterPro G-protein coupled receptor activity Traceable author statement PubMed 9205127. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 387	387	Hydroxycarboxylic acid receptor 3		PRO_0000069604
Regions
	Topological domain	1 – 28	28	Extracellular Potential
	Transmembrane	29 – 50	22	Helical; Name=1; Potential
	Topological domain	51 – 63	13	Cytoplasmic Potential
	Transmembrane	64 – 85	22	Helical; Name=2; Potential
	Topological domain	86 – 102	17	Extracellular Potential
	Transmembrane	103 – 123	21	Helical; Name=3; Potential
	Topological domain	124 – 142	19	Cytoplasmic Potential
	Transmembrane	143 – 163	21	Helical; Name=4; Potential
	Topological domain	164 – 194	31	Extracellular Potential
	Transmembrane	195 – 209	15	Helical; Name=5; Potential
	Topological domain	210 – 236	27	Cytoplasmic Potential
	Transmembrane	237 – 256	20	Helical; Name=6; Potential
	Topological domain	257 – 273	17	Extracellular Potential
	Transmembrane	274 – 298	25	Helical; Name=7; Potential
	Topological domain	299 – 387	89	Cytoplasmic Potential
Amino acid modifications
	Disulfide bond	100 ↔ 177		By similarity
Natural variations
	Natural variant	173	1	P → T. Ref.4 Corresponds to variant rs1798192 [ dbSNP | Ensembl ].		VAR_038715
	Natural variant	198	1	L → F. Ref.4 Corresponds to variant rs17884481 [ dbSNP | Ensembl ].		VAR_038716
	Natural variant	253	1	R → H. Ref.4		VAR_038717
	Natural variant	317	1	M → I. Ref.4		VAR_038718
	Natural variant	346	1	M → I. Ref.4 Corresponds to variant rs56308926 [ dbSNP | Ensembl ].		VAR_038719
	Natural variant	350	1	G → S. Ref.4		VAR_038720
Experimental info
	Mutagenesis	111	1	R → A: Abrogates completely the activation by OH-octanoid acid. Ref.7
	Sequence conflict	94	1	K → N in BAA01721. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P49019 [UniParc]. Last modified December 6, 2005. Version 2. Checksum: 26433C855E85EC81	FASTA	387	44,496
	10 20 30 40 50 60 MNRHHLQDHF LEIDKKNCCV FRDDFIAKVL PPVLGLEFIF GLLGNGLALW IFCFHLKSWK 70 80 90 100 110 120 SSRIFLFNLA VADFLLIICL PFVMDYYVRR SDWKFGDIPC RLVLFMFAMN RQGSIIFLTV 130 140 150 160 170 180 VAVDRYFRVV HPHHALNKIS NWTAAIISCL LWGITVGLTV HLLKKKLLIQ NGPANVCISF 190 200 210 220 230 240 SICHTFRWHE AMFLLEFLLP LGIILFCSAR IIWSLRQRQM DRHAKIKRAI TFIMVVAIVF 250 260 270 280 290 300 VICFLPSVVV RIRIFWLLHT SGTQNCEVYR SVDLAFFITL SFTYMNSMLD PVVYYFSSPS 310 320 330 340 350 360 FPNFFSTLIN RCLQRKMTGE PDNNRSTSVE LTGDPNKTRG APEALMANSG EPWSPSYLGP 370 380 TSNNHSKKGH CHQEPASLEK QLGCCIE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte chemotactic peptide receptors." Nomura H., Nielsen B.W., Matsushima K. Int. Immunol. 5:1239-1249(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Monocyte.
[2]	"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].
[3]	"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: Neutrophil.
[4]	SeattleSNPs variation discovery resource Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-173; PHE-198; HIS-253; ILE-317; ILE-346 AND SER-350.
[5]	"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]. Tissue: Pancreas.
[6]	"Molecular identification of high and low affinity receptors for nicotinic acid." Wise A., Foord S.M., Fraser N.J., Barnes A.A., Elshourbagy N., Eilert M., Ignar D.M., Murdock P.R., Steplewski K., Green A., Brown A.J., Dowell S.J., Szekeres P.G., Hassall D.G., Marshall F.H., Wilson S., Pike N.B. J. Biol. Chem. 278:9869-9874(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, CHARACTERIZATION.
[7]	"Deorphanization of GPR109B as a receptor for the beta-oxidation intermediate 3-OH-octanoic acid and its role in the regulation of lipolysis." Ahmed K., Tunaru S., Langhans C.-D., Hanson J., Michalski C.W., Koelker S., Jones P.M., Okun J.G., Offermanns S. J. Biol. Chem. 284:21928-21933(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ARG-111.
[8]	"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	D10923 mRNA. Translation: BAA01721.1. AB065865 Genomic DNA. Translation: BAC06083.1. AK290930 mRNA. Translation: BAF83619.1. AK313212 mRNA. Translation: BAG36027.1. EU293604 Genomic DNA. Translation: ABX64359.1. BC047891 mRNA. Translation: AAH47891.1.
IPI	IPI00025628.
PIR	I69202.
RefSeq	NP_006009.2. NM_006018.2.
UniGene	Hs.458425.
3D structure databases
ProteinModelPortal	P49019.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49019. 1 interaction.
Protein family/group databases
GPCRDB	Search...
Polymorphism databases
DMDM	83302831.
Proteomic databases
PRIDE	P49019.
Protocols and materials databases
DNASU	8843.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	8843.
KEGG	hsa:8843.
Organism-specific databases
CTD	8843.
GeneCards	GC12M123200.
H-InvDB	HIX0036803.
HGNC	HGNC:16824. HCAR3.
HPA	HPA028660.
MIM	606039. gene.
neXtProt	NX_P49019.
PharmGKB	PA165512827.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG051680.
InParanoid	P49019.
KO	K08402.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
CleanEx	HS_GPR109B.
Genevestigator	P49019.
GermOnline	ENSG00000182442. Homo sapiens.
Family and domain databases
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR002286. P2_purnocptor. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR01157. P2YPURNOCPTR.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P49019.
ChEMBL	CHEMBL4421.
DrugBank	DB04843. Mepenzolate. DB00627. Niacin.
GenomeRNAi	8843.
NextBio	33198.
SOURCE	Search...

Entry information

Entry name

HCAR3_HUMAN

Accession

Primary (citable) accession number: P49019
Secondary accession number(s): A8K4G5, B2R830, Q8NGE4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	December 6, 2005
Last modified:	May 1, 2013
This is version 118 of the entry and version 2 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.