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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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

BioCyciZFISH:G66-30680-MONOMER.
ReactomeiR-HSA-3296197. Hydroxycarboxylic acid-binding receptors.
R-HSA-373076. Class A/1 (Rhodopsin-like receptors).
R-HSA-418594. 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
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:24827. HCAR2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 33ExtracellularSequence analysisAdd BLAST33
Transmembranei34 – 54Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini55 – 63CytoplasmicSequence analysis9
Transmembranei64 – 84Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini85 – 102ExtracellularSequence analysisAdd BLAST18
Transmembranei103 – 123Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini124 – 142CytoplasmicSequence analysisAdd BLAST19
Transmembranei143 – 163Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini164 – 192ExtracellularSequence analysisAdd BLAST29
Transmembranei193 – 213Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini214 – 229CytoplasmicSequence analysisAdd BLAST16
Transmembranei230 – 250Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini251 – 273ExtracellularSequence analysisAdd BLAST23
Transmembranei274 – 294Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini295 – 363CytoplasmicSequence analysisAdd BLAST69

GO - Cellular componenti

  • cell junction Source: HPA
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi338442.
OpenTargetsiENSG00000182782.
PharmGKBiPA165961843.

Chemistry databases

ChEMBLiCHEMBL3785.
DrugBankiDB00627. Niacin.
GuidetoPHARMACOLOGYi312.

Polymorphism and mutation databases

BioMutaiHCAR2.
DMDMi74762622.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000696031 – 363Hydroxycarboxylic acid receptor 2Add BLAST363

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi100 ↔ 177PROSITE-ProRule annotation
Modified residuei328PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

MaxQBiQ8TDS4.
PaxDbiQ8TDS4.
PRIDEiQ8TDS4.

PTM databases

PhosphoSitePlusiQ8TDS4.

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

BgeeiENSG00000182782.
CleanExiHS_GPR109A.
GenevisibleiQ8TDS4. HS.

Organism-specific databases

HPAiHPA028660.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000375066.

Chemistry databases

BindingDBiQ8TDS4.

Structurei

3D structure databases

ProteinModelPortaliQ8TDS4.
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

eggNOGiENOG410IKI5. Eukaryota.
ENOG4110VUM. LUCA.
GeneTreeiENSGT00510000046798.
InParanoidiQ8TDS4.
KOiK08402.
OMAiRAINFIM.
OrthoDBiEOG091G0AN6.
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_049400187Q → R.Corresponds to variant rs676770dbSNPEnsembl.1
Natural variantiVAR_049401198F → L.Corresponds to variant rs676823dbSNPEnsembl.1
Natural variantiVAR_038713311R → C.1 PublicationCorresponds to variant rs7314976dbSNPEnsembl.1
Natural variantiVAR_038714317M → I.1 PublicationCorresponds to variant rs28682471dbSNPEnsembl.1

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.2. human.

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000375066.

Chemistry databases

BindingDBiQ8TDS4.
ChEMBLiCHEMBL3785.
DrugBankiDB00627. Niacin.
GuidetoPHARMACOLOGYi312.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSitePlusiQ8TDS4.

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.2. human.

Organism-specific databases

CTDi338442.
DisGeNETi338442.
GeneCardsiHCAR2.
HGNCiHGNC:24827. HCAR2.
HPAiHPA028660.
MIMi609163. gene.
neXtProtiNX_Q8TDS4.
OpenTargetsiENSG00000182782.
PharmGKBiPA165961843.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKI5. Eukaryota.
ENOG4110VUM. LUCA.
GeneTreeiENSGT00510000046798.
InParanoidiQ8TDS4.
KOiK08402.
OMAiRAINFIM.
OrthoDBiEOG091G0AN6.
TreeFamiTF330775.

Enzyme and pathway databases

BioCyciZFISH:G66-30680-MONOMER.
ReactomeiR-HSA-3296197. Hydroxycarboxylic acid-binding receptors.
R-HSA-373076. Class A/1 (Rhodopsin-like receptors).
R-HSA-418594. G alpha (i) signalling events.

Miscellaneous databases

GenomeRNAii338442.
PROiQ8TDS4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182782.
CleanExiHS_GPR109A.
GenevisibleiQ8TDS4. HS.

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...

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: November 2, 2016
This is version 120 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

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 one 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.