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Protein

Hydroxycarboxylic acid receptor 2

Gene

HCAR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processApoptosis

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000182782.7
HGNCiHGNC:24827 HCAR2
MIMi609163 gene
neXtProtiNX_Q8TDS4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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

EPDiQ8TDS4
MaxQBiQ8TDS4
PaxDbiQ8TDS4
PeptideAtlasiQ8TDS4
PRIDEiQ8TDS4
ProteomicsDBi74335

PTM databases

iPTMnetiQ8TDS4
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 Expressed in 74 organ(s), highest expression level in blood
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
OMAiDTFRWHE
OrthoDBiEOG091G0AN6
TreeFamiTF330775

Family and domain databases

InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR028017 HCAR2/3_rcpt
PANTHERiPTHR24231:SF0 PTHR24231:SF0, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

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 dbSNP:rs676770Ensembl.1
Natural variantiVAR_049401198F → L. Corresponds to variant dbSNP:rs676823Ensembl.1
Natural variantiVAR_038713311R → C1 PublicationCorresponds to variant dbSNP:rs7314976Ensembl.1
Natural variantiVAR_038714317M → I1 PublicationCorresponds to variant dbSNP:rs2454727Ensembl.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

Similar proteinsi

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

iPTMnetiQ8TDS4
PhosphoSitePlusiQ8TDS4

Polymorphism and mutation databases

BioMutaiHCAR2
DMDMi74762622

Proteomic databases

EPDiQ8TDS4
MaxQBiQ8TDS4
PaxDbiQ8TDS4
PeptideAtlasiQ8TDS4
PRIDEiQ8TDS4
ProteomicsDBi74335

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
EuPathDBiHostDB:ENSG00000182782.7
GeneCardsiHCAR2
HGNCiHGNC:24827 HCAR2
HPAiHPA028660
MIMi609163 gene
neXtProtiNX_Q8TDS4
OpenTargetsiENSG00000182782
PharmGKBiPA165961843
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKI5 Eukaryota
ENOG4110VUM LUCA
GeneTreeiENSGT00510000046798
InParanoidiQ8TDS4
KOiK08402
OMAiDTFRWHE
OrthoDBiEOG091G0AN6
TreeFamiTF330775

Enzyme and pathway databases

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
PROiPR:Q8TDS4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182782 Expressed in 74 organ(s), highest expression level in blood
CleanExiHS_GPR109A
GenevisibleiQ8TDS4 HS

Family and domain databases

InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR028017 HCAR2/3_rcpt
PANTHERiPTHR24231:SF0 PTHR24231:SF0, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHCAR2_HUMAN
AccessioniPrimary (citable) accession number: Q8TDS4
Secondary accession number(s): A0PJL5, A7LGG3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: June 1, 2002
Last modified: November 7, 2018
This is version 130 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  6. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
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Main funding by: National Institutes of Health

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