Q8TDS4 (HCAR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hydroxycarboxylic acid receptor 2

Alternative name(s):
G-protein coupled receptor 109A
G-protein coupled receptor HM74A
Niacin receptor 1
Nicotinic acid receptor

Gene names

Name:	HCAR2
Synonyms:	GPR109A, HCA2, HM74A, NIACR1

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

General annotation (Comments)

Function	Acts as a high affinity receptor for both nicotinic acid (also known as niacin) and (D)-beta-hydroxybutyrate and mediates increased adiponectin secretion and decreased lipolysis through G(i)-protein-mediated inhibition of adenylyl cyclase. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet. Mediates nicotinic acid-induced apoptosis in mature neutrophils. Receptor activation by nicotinic acid results in reduced cAMP levels which may affect activity of cAMP-dependent protein kinase A and phosphorylation of target proteins, leading to neutrophil apoptosis. The rank order of potency for the displacement of nicotinic acid binding is 5-methyl pyrazole-3-carboxylic acid = pyridine-3-acetic acid > acifran > 5-methyl nicotinic acid = acipimox >> nicotinuric acid = nicotinamide. Ref.6
Subcellular location	Cell membrane; Multi-pass membrane protein Ref.6.
Tissue specificity	Expression largely restricted to adipose tissue and spleen. Expressed on mature neutrophils but not on immature neutrophils or eosinophils. Ref.1 Ref.6
Developmental stage	Expression in neutrophils occurs in the late terminal differentiation phase. Ref.6
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of lipid catabolic process Inferred from sequence or structural similarity. Source: UniProtKB neutrophil apoptotic process Inferred from direct assay Ref.6. Source: UniProtKB positive regulation of adiponectin secretion Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of neutrophil apoptotic process Inferred from direct assay Ref.6. Source: UniProtKB
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay Ref.6. Source: UniProtKB
Molecular_function	G-protein coupled purinergic nucleotide receptor activity Inferred from electronic annotation. Source: InterPro nicotinic acid receptor activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 363	363	Hydroxycarboxylic acid receptor 2		PRO_0000069603
Regions
	Topological domain	1 – 33	33	Extracellular Potential
	Transmembrane	34 – 54	21	Helical; Name=1; Potential
	Topological domain	55 – 63	9	Cytoplasmic Potential
	Transmembrane	64 – 84	21	Helical; Name=2; Potential
	Topological domain	85 – 102	18	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 – 192	29	Extracellular Potential
	Transmembrane	193 – 213	21	Helical; Name=5; Potential
	Topological domain	214 – 229	16	Cytoplasmic Potential
	Transmembrane	230 – 250	21	Helical; Name=6; Potential
	Topological domain	251 – 273	23	Extracellular Potential
	Transmembrane	274 – 294	21	Helical; Name=7; Potential
	Topological domain	295 – 363	69	Cytoplasmic Potential
Amino acid modifications
	Modified residue	326	1	Phosphoserine By similarity
	Modified residue	327	1	Phosphothreonine By similarity
	Modified residue	328	1	Phosphoserine By similarity
	Disulfide bond	100 ↔ 177		By similarity
Natural variations
	Natural variant	187	1	Q → R. Corresponds to variant rs676770 [ dbSNP | Ensembl ].		VAR_049400
	Natural variant	198	1	F → L. Corresponds to variant rs676823 [ dbSNP | Ensembl ].		VAR_049401
	Natural variant	311	1	R → C. Ref.4 Corresponds to variant rs7314976 [ dbSNP | Ensembl ].		VAR_038713
	Natural variant	317	1	M → I. Ref.4 Corresponds to variant rs28682471 [ dbSNP | Ensembl ].		VAR_038714

Sequences

	Sequence		Length	Mass (Da)
	Q8TDS4 [UniParc]. Last modified June 1, 2002. Version 1. Checksum: C4B0EEC9CCB81D56	FASTA	363	41,850
	10 20 30 40 50 60 MNRHHLQDHF LEIDKKNCCV FRDDFIVKVL PPVLGLEFIF GLLGNGLALW IFCFHLKSWK 70 80 90 100 110 120 SSRIFLFNLA VADFLLIICL PFLMDNYVRR WDWKFGDIPC RLMLFMLAMN RQGSIIFLTV 130 140 150 160 170 180 VAVDRYFRVV HPHHALNKIS NRTAAIISCL LWGITIGLTV HLLKKKMPIQ NGGANLCSSF 190 200 210 220 230 240 SICHTFQWHE AMFLLEFFLP 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 TSP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, CHARACTERIZATION.
[2]	"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].
[3]	"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].
[4]	SeattleSNPs variation discovery resource Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CYS-311 AND ILE-317.
[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]	"Neutrophil apoptosis mediated by nicotinic acid receptors (GPR109A)." Kostylina G., Simon D., Fey M.F., Yousefi S., Simon H.U. Cell Death Differ. 15:134-142(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[7]	"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	AY148884 mRNA. Translation: AAN71621.1. AB083632 Genomic DNA. Translation: BAB89345.1. AB065876 Genomic DNA. Translation: BAC06094.1. EU012026 Genomic DNA. Translation: ABS29270.1. BC027965 mRNA. Translation: AAH27965.1. BC056419 mRNA. Translation: AAH56419.1.
IPI	IPI00157746.
RefSeq	NP_808219.1. NM_177551.3.
UniGene	Hs.524812.
3D structure databases
ProteinModelPortal	Q8TDS4.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000375066.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q8TDS4.
Polymorphism databases
DMDM	74762622.
Proteomic databases
PaxDb	Q8TDS4.
PRIDE	Q8TDS4.
Protocols and materials databases
DNASU	338442.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000328880; ENSP00000375066; ENSG00000182782.
GeneID	338442.
KEGG	hsa:338442.
UCSC	uc001ucx.1. human.
Organism-specific databases
CTD	338442.
GeneCards	GC12M123187.
HGNC	HGNC:24827. HCAR2.
HPA	HPA028660.
MIM	609163. gene.
neXtProt	NX_Q8TDS4.
PharmGKB	PA165961843.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG148880.
InParanoid	Q8TDS4.
KO	K08402.
OrthoDB	EOG495ZSR.
PhylomeDB	Q8TDS4.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	Q8TDS4.
CleanEx	HS_GPR109A.
Genevestigator	Q8TDS4.
GermOnline	ENSG00000182782. 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	Q8TDS4.
ChEMBL	CHEMBL3785.
DrugBank	DB04843. Mepenzolate. DB00627. Niacin.
GenomeRNAi	338442.
NextBio	97016.
SOURCE	Search...

Entry information

Entry name

HCAR2_HUMAN

Accession

Primary (citable) accession number: Q8TDS4
Secondary accession number(s): A0PJL5, A7LGG3

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 6, 2005
Last sequence update:	June 1, 2002
Last modified:	May 1, 2013
This is version 91 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.