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Q8TDS4 (HCAR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length363 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 363363Hydroxycarboxylic acid receptor 2
PRO_0000069603

Regions

Topological domain1 – 3333Extracellular Potential
Transmembrane34 – 5421Helical; Name=1; Potential
Topological domain55 – 639Cytoplasmic Potential
Transmembrane64 – 8421Helical; Name=2; Potential
Topological domain85 – 10218Extracellular Potential
Transmembrane103 – 12321Helical; Name=3; Potential
Topological domain124 – 14219Cytoplasmic Potential
Transmembrane143 – 16321Helical; Name=4; Potential
Topological domain164 – 19229Extracellular Potential
Transmembrane193 – 21321Helical; Name=5; Potential
Topological domain214 – 22916Cytoplasmic Potential
Transmembrane230 – 25021Helical; Name=6; Potential
Topological domain251 – 27323Extracellular Potential
Transmembrane274 – 29421Helical; Name=7; Potential
Topological domain295 – 36369Cytoplasmic Potential

Amino acid modifications

Disulfide bond100 ↔ 177 By similarity

Natural variations

Natural variant1871Q → R.
Corresponds to variant rs676770 [ dbSNP | Ensembl ].
VAR_049400
Natural variant1981F → L.
Corresponds to variant rs676823 [ dbSNP | Ensembl ].
VAR_049401
Natural variant3111R → C. Ref.4
Corresponds to variant rs7314976 [ dbSNP | Ensembl ].
VAR_038713
Natural variant3171M → I. Ref.4
Corresponds to variant rs28682471 [ dbSNP | Ensembl ].
VAR_038714

Sequences

Sequence LengthMass (Da)Tools
Q8TDS4 [UniParc].

Last modified June 1, 2002. Version 1.
Checksum: C4B0EEC9CCB81D56

FASTA36341,850
        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 

« Hide

References

« Hide '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

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.
CCDSCCDS9235.1.
RefSeqNP_808219.1. NM_177551.3.
UniGeneHs.524812.

3D structure databases

ProteinModelPortalQ8TDS4.
SMRQ8TDS4. Positions 38-332.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000375066.

Chemistry

BindingDBQ8TDS4.
ChEMBLCHEMBL3785.
DrugBankDB04843. Mepenzolate.
DB00627. Niacin.
GuidetoPHARMACOLOGY312.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ8TDS4.

Polymorphism databases

DMDM74762622.

Proteomic databases

MaxQBQ8TDS4.
PaxDbQ8TDS4.
PRIDEQ8TDS4.

Protocols and materials databases

DNASU338442.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000328880; ENSP00000375066; ENSG00000182782.
GeneID338442.
KEGGhsa:338442.
UCSCuc001ucx.1. human.

Organism-specific databases

CTD338442.
GeneCardsGC12M123187.
HGNCHGNC:24827. HCAR2.
HPAHPA028660.
MIM609163. gene.
neXtProtNX_Q8TDS4.
PharmGKBPA165961843.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG148880.
InParanoidQ8TDS4.
KOK08402.
OMARAINFIM.
OrthoDBEOG7R56SR.
TreeFamTF330775.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeQ8TDS4.
CleanExHS_GPR109A.
GenevestigatorQ8TDS4.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR028017. HCAR2/3_rcpt.
[Graphical view]
PANTHERPTHR24231:SF0. PTHR24231:SF0. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi338442.
NextBio97016.
PROQ8TDS4.
SOURCESearch...

Entry information

Entry nameHCAR2_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries