Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Hydroxycarboxylic acid receptor 2

Gene

HCAR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  1. nicotinic acid receptor activity Source: UniProtKB

GO - Biological processi

  1. negative regulation of lipid catabolic process Source: UniProtKB
  2. neutrophil apoptotic process Source: UniProtKB
  3. positive regulation of adiponectin secretion Source: UniProtKB
  4. positive regulation of neutrophil apoptotic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiREACT_14828. Class A/1 (Rhodopsin-like receptors).
REACT_163785. Hydroxycarboxylic acid-binding receptors.
REACT_19231. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
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 namesi
Name:HCAR2
Synonyms:GPR109A, HCA2, HM74A, NIACR1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:24827. HCAR2.

Subcellular locationi

  1. Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3333ExtracellularSequence AnalysisAdd
BLAST
Transmembranei34 – 5421Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini55 – 639CytoplasmicSequence Analysis
Transmembranei64 – 8421Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini85 – 10218ExtracellularSequence AnalysisAdd
BLAST
Transmembranei103 – 12321Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini124 – 14219CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei143 – 16321Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini164 – 19229ExtracellularSequence AnalysisAdd
BLAST
Transmembranei193 – 21321Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini214 – 22916CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei230 – 25021Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini251 – 27323ExtracellularSequence AnalysisAdd
BLAST
Transmembranei274 – 29421Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini295 – 36369CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA165961843.

Chemistry

DrugBankiDB00627. Niacin.

Polymorphism and mutation databases

BioMutaiHCAR2.
DMDMi74762622.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 363363Hydroxycarboxylic acid receptor 2PRO_0000069603Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi100 ↔ 177PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond

Proteomic databases

MaxQBiQ8TDS4.
PaxDbiQ8TDS4.
PRIDEiQ8TDS4.

PTM databases

PhosphoSiteiQ8TDS4.

Expressioni

Tissue specificityi

Expression largely restricted to adipose tissue and spleen. Expressed on mature neutrophils but not on immature neutrophils or eosinophils.2 Publications

Developmental stagei

Expression in neutrophils occurs in the late terminal differentiation phase.1 Publication

Gene expression databases

BgeeiQ8TDS4.
CleanExiHS_GPR109A.
GenevestigatoriQ8TDS4.

Organism-specific databases

HPAiHPA028660.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000375066.

Structurei

3D structure databases

ProteinModelPortaliQ8TDS4.
SMRiQ8TDS4. Positions 38-332.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG148880.
GeneTreeiENSGT00510000046798.
InParanoidiQ8TDS4.
KOiK08402.
OMAiRAINFIM.
OrthoDBiEOG7R56SR.
TreeFamiTF330775.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR028017. HCAR2/3_rcpt.
[Graphical view]
PANTHERiPTHR24231:SF0. PTHR24231:SF0. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8TDS4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNRHHLQDHF LEIDKKNCCV FRDDFIVKVL PPVLGLEFIF GLLGNGLALW
60 70 80 90 100
IFCFHLKSWK SSRIFLFNLA VADFLLIICL PFLMDNYVRR WDWKFGDIPC
110 120 130 140 150
RLMLFMLAMN RQGSIIFLTV VAVDRYFRVV HPHHALNKIS NRTAAIISCL
160 170 180 190 200
LWGITIGLTV HLLKKKMPIQ NGGANLCSSF SICHTFQWHE AMFLLEFFLP
210 220 230 240 250
LGIILFCSAR IIWSLRQRQM DRHAKIKRAI TFIMVVAIVF VICFLPSVVV
260 270 280 290 300
RIRIFWLLHT SGTQNCEVYR SVDLAFFITL SFTYMNSMLD PVVYYFSSPS
310 320 330 340 350
FPNFFSTLIN RCLQRKMTGE PDNNRSTSVE LTGDPNKTRG APEALMANSG
360
EPWSPSYLGP TSP
Length:363
Mass (Da):41,850
Last modified:June 1, 2002 - v1
Checksum:iC4B0EEC9CCB81D56
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti187 – 1871Q → R.
Corresponds to variant rs676770 [ dbSNP | Ensembl ].
VAR_049400
Natural varianti198 – 1981F → L.
Corresponds to variant rs676823 [ dbSNP | Ensembl ].
VAR_049401
Natural varianti311 – 3111R → C.1 Publication
Corresponds to variant rs7314976 [ dbSNP | Ensembl ].
VAR_038713
Natural varianti317 – 3171M → I.1 Publication
Corresponds to variant rs28682471 [ dbSNP | Ensembl ].
VAR_038714

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS9235.1.
RefSeqiNP_808219.1. NM_177551.3.
UniGeneiHs.524812.

Genome annotation databases

EnsembliENST00000328880; ENSP00000375066; ENSG00000182782.
GeneIDi338442.
KEGGihsa:338442.
UCSCiuc001ucx.1. human.

Polymorphism and mutation databases

BioMutaiHCAR2.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS9235.1.
RefSeqiNP_808219.1. NM_177551.3.
UniGeneiHs.524812.

3D structure databases

ProteinModelPortaliQ8TDS4.
SMRiQ8TDS4. Positions 38-332.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000375066.

Chemistry

BindingDBiQ8TDS4.
ChEMBLiCHEMBL3785.
DrugBankiDB00627. Niacin.
GuidetoPHARMACOLOGYi312.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiQ8TDS4.

Polymorphism and mutation databases

BioMutaiHCAR2.
DMDMi74762622.

Proteomic databases

MaxQBiQ8TDS4.
PaxDbiQ8TDS4.
PRIDEiQ8TDS4.

Protocols and materials databases

DNASUi338442.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000328880; ENSP00000375066; ENSG00000182782.
GeneIDi338442.
KEGGihsa:338442.
UCSCiuc001ucx.1. human.

Organism-specific databases

CTDi338442.
GeneCardsiGC12M123187.
HGNCiHGNC:24827. HCAR2.
HPAiHPA028660.
MIMi609163. gene.
neXtProtiNX_Q8TDS4.
PharmGKBiPA165961843.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG148880.
GeneTreeiENSGT00510000046798.
InParanoidiQ8TDS4.
KOiK08402.
OMAiRAINFIM.
OrthoDBiEOG7R56SR.
TreeFamiTF330775.

Enzyme and pathway databases

ReactomeiREACT_14828. Class A/1 (Rhodopsin-like receptors).
REACT_163785. Hydroxycarboxylic acid-binding receptors.
REACT_19231. G alpha (i) signalling events.

Miscellaneous databases

GenomeRNAii338442.
NextBioi97016.
PROiQ8TDS4.
SOURCEiSearch...

Gene expression databases

BgeeiQ8TDS4.
CleanExiHS_GPR109A.
GenevestigatoriQ8TDS4.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR028017. HCAR2/3_rcpt.
[Graphical view]
PANTHERiPTHR24231:SF0. PTHR24231:SF0. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. 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.

Entry informationi

Entry nameiHCAR2_HUMAN
AccessioniPrimary (citable) accession number: Q8TDS4
Secondary accession number(s): A0PJL5, A7LGG3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: June 1, 2002
Last modified: April 29, 2015
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.