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Protein

Hydroxycarboxylic acid receptor 2

Gene

Hcar2

Organism
Mus musculus (Mouse)
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.1 Publication

GO - Molecular functioni

  • GTP binding Source: MGI
  • nicotinic acid receptor activity Source: UniProtKB
  • purinergic nucleotide receptor activity Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

ReactomeiR-MMU-3296197. Hydroxycarboxylic acid-binding receptors.
R-MMU-373076. Class A/1 (Rhodopsin-like receptors).
R-MMU-418594. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Hydroxycarboxylic acid receptor 2
Alternative name(s):
G-protein coupled receptor 109
G-protein coupled receptor 109A
G-protein coupled receptor HM74
Niacin receptor 1
Nicotinic acid receptor
Protein PUMA-G
Gene namesi
Name:Hcar2
Synonyms:Gpr109, Gpr109a, Gpr109b, Niacr1, Pumag
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1933383. Hcar2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3030ExtracellularSequence analysisAdd
BLAST
Transmembranei31 – 5121Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini52 – 609CytoplasmicSequence analysis
Transmembranei61 – 8121Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini82 – 9817ExtracellularSequence analysisAdd
BLAST
Transmembranei99 – 11921Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini120 – 14021CytoplasmicSequence analysisAdd
BLAST
Transmembranei141 – 16121Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini162 – 18928ExtracellularSequence analysisAdd
BLAST
Transmembranei190 – 21021Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini211 – 22616CytoplasmicSequence analysisAdd
BLAST
Transmembranei227 – 24721Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini248 – 27023ExtracellularSequence analysisAdd
BLAST
Transmembranei271 – 29121Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini292 – 36069CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cell junction Source: MGI
  • integral component of membrane Source: MGI
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Niacin administration has no effect on serum adiponectin levels in contrast to wild-type mice where levels are decreased.1 Publication

Chemistry

ChEMBLiCHEMBL4420.
GuidetoPHARMACOLOGYi312.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 360360Hydroxycarboxylic acid receptor 2PRO_0000069605Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi97 ↔ 174PROSITE-ProRule annotation
Modified residuei325 – 3251PhosphoserineCombined sources

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

MaxQBiQ9EP66.
PaxDbiQ9EP66.
PRIDEiQ9EP66.

PTM databases

iPTMnetiQ9EP66.
PhosphoSiteiQ9EP66.

Expressioni

Tissue specificityi

Expressed in lungs, spleen, heart, skeletal muscle and adipose tissue.2 Publications

Inductioni

By interferon-gamma in macrophages.1 Publication

Gene expression databases

BgeeiQ9EP66.
CleanExiMM_GPR109A.
ExpressionAtlasiQ9EP66. baseline and differential.
GenevisibleiQ9EP66. MM.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000054104.

Chemistry

BindingDBiQ9EP66.

Structurei

3D structure databases

ProteinModelPortaliQ9EP66.
SMRiQ9EP66. Positions 27-302.
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.
InParanoidiQ9EP66.
KOiK08402.
OMAiRAINFIM.
OrthoDBiEOG7R56SR.
PhylomeDBiQ9EP66.
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.

Q9EP66-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSKSDHFLVI NGKNCCVFRD ENIAKVLPPV LGLEFVFGLL GNGLALWIFC
60 70 80 90 100
FHLKSWKSSR IFLFNLAVAD FLLIICLPFL TDNYVHNWDW RFGGIPCRVM
110 120 130 140 150
LFMLAMNRQG SIIFLTVVAV DRYFRVVHPH HFLNKISNRT AAIISCFLWG
160 170 180 190 200
LTIGLTVHLL YTNMMTKNGE AYLCSSFSIC YNFRWHDAMF LLEFFLPLAI
210 220 230 240 250
ILFCSGRIIW SLRQRQMDRH AKIKRAINFI MVVAIVFIIC FLPSVAVRIR
260 270 280 290 300
IFWLLYKYNV RNCDIYSSVD LAFFTTLSFT YMNSMLDPVV YYFSSPSFPN
310 320 330 340 350
FFSTCINRCL RKKTLGEPDN NRSTSVELTG DPSTTRSIPG ALMADPSEPG
360
SPPYLASTSR
Length:360
Mass (Da):41,401
Last modified:March 1, 2001 - v1
Checksum:iCCCE52A2475777FC
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ300198 mRNA. Translation: CAC17790.1.
AJ300199 Genomic DNA. Translation: CAC17791.1.
AK150795 mRNA. Translation: BAE29858.1.
CCDSiCCDS19668.1.
RefSeqiNP_109626.1. NM_030701.3.
UniGeneiMm.440567.
Mm.486809.

Genome annotation databases

EnsembliENSMUST00000057145; ENSMUSP00000054104; ENSMUSG00000045502.
GeneIDi80885.
KEGGimmu:80885.
UCSCiuc008zop.3. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ300198 mRNA. Translation: CAC17790.1.
AJ300199 Genomic DNA. Translation: CAC17791.1.
AK150795 mRNA. Translation: BAE29858.1.
CCDSiCCDS19668.1.
RefSeqiNP_109626.1. NM_030701.3.
UniGeneiMm.440567.
Mm.486809.

3D structure databases

ProteinModelPortaliQ9EP66.
SMRiQ9EP66. Positions 27-302.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000054104.

Chemistry

BindingDBiQ9EP66.
ChEMBLiCHEMBL4420.
GuidetoPHARMACOLOGYi312.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ9EP66.
PhosphoSiteiQ9EP66.

Proteomic databases

MaxQBiQ9EP66.
PaxDbiQ9EP66.
PRIDEiQ9EP66.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000057145; ENSMUSP00000054104; ENSMUSG00000045502.
GeneIDi80885.
KEGGimmu:80885.
UCSCiuc008zop.3. mouse.

Organism-specific databases

CTDi338442.
MGIiMGI:1933383. Hcar2.

Phylogenomic databases

eggNOGiENOG410IKI5. Eukaryota.
ENOG4110VUM. LUCA.
GeneTreeiENSGT00510000046798.
InParanoidiQ9EP66.
KOiK08402.
OMAiRAINFIM.
OrthoDBiEOG7R56SR.
PhylomeDBiQ9EP66.
TreeFamiTF330775.

Enzyme and pathway databases

ReactomeiR-MMU-3296197. Hydroxycarboxylic acid-binding receptors.
R-MMU-373076. Class A/1 (Rhodopsin-like receptors).
R-MMU-418594. G alpha (i) signalling events.

Miscellaneous databases

NextBioi350203.
PROiQ9EP66.
SOURCEiSearch...

Gene expression databases

BgeeiQ9EP66.
CleanExiMM_GPR109A.
ExpressionAtlasiQ9EP66. baseline and differential.
GenevisibleiQ9EP66. MM.

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. "PUMA-G, an IFN-gamma-inducible gene in macrophages is a novel member of the seven transmembrane spanning receptor superfamily."
    Schaub A., Fuetterer A., Pfeffer K.
    Eur. J. Immunol. 31:3714-3725(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], INDUCTION, TISSUE SPECIFICITY.
    Strain: 129/SvJ and C57BL/6.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Bone marrow.
  3. Cited for: TISSUE SPECIFICITY.
  4. Cited for: FUNCTION.
  5. "Niacin stimulates adiponectin secretion through the GPR109A receptor."
    Plaisance E.P., Lukasova M., Offermanns S., Zhang Y., Cao G., Judd R.L.
    Am. J. Physiol. 296:E549-E558(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-325, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brown adipose tissue and Spleen.

Entry informationi

Entry nameiHCAR2_MOUSE
AccessioniPrimary (citable) accession number: Q9EP66
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: March 1, 2001
Last modified: February 17, 2016
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. 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.