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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

HCAR3 Gene

protein-coding   GIFtS: 47
GCID: GC12M123200

Hydroxycarboxylic Acid Receptor 3

(Previous name: G protein-coupled receptor 109B)
(Previous symbol: GPR109B)
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
Hydroxycarboxylic Acid Receptor 31 2     HM742 5
GPR109B1 2 3 5     PUMAG2 5
G Protein-Coupled Receptor 109B1 2     Puma-g2
Niacin Receptor 22 3     GTP-Binding Protein2
Nicotinic Acid Receptor 22 3     Hydroxy-Carboxylic Acid Receptor 32
HCA32 3     Putative Chemokine Receptor2
G-Protein Coupled Receptor 109B2 3     HM74B3
G-Protein Coupled Receptor HM742 3     NIACR23
G-Protein Coupled Receptor HM74B2 3     

External Ids:    HGNC: 168241   Entrez Gene: 88432   Ensembl: ENSG000002553987   OMIM: 6060395   UniProtKB: P490193   

Export aliases for HCAR3 gene to outside databases


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

GeneCards Summary for HCAR3 Gene: 
HCAR3 (hydroxycarboxylic acid receptor 3) is a protein-coding gene. Diseases associated with HCAR3 include distal hereditary motor neuropathy, type ii, and distal hereditary motor neuropathy, and among its related super-pathways are Class A/1 (Rhodopsin-like receptors) and Signaling by GPCR. GO annotations related to this gene include G-protein coupled purinergic nucleotide receptor activity and G-protein coupled receptor activity. An important paralog of this gene is HCAR1.

UniProtKB/Swiss-Prot: HCAR3_HUMAN, P49019
Function: Receptor for 3-OH-octanoid acid mediates a negative feedback regulation of adipocyte lipolysis to
counteract prolipolytic influences under conditions of physiological or pathological increases in beta-oxidation
rates. Acts as a low affinity receptor for nicotinic acid. This pharmacological effect requires nicotinic acid
doses that are much higher than those provided by a normal diet

summary for HCAR3 Gene:
Nicotinic acid receptors are a group of Gi/Go protein-coupled receptors that are currently divided into
GPR81, GPR109A and GPR109B subtypes. GPR109B receptors originated from a gene duplication of GPR109A and
have > 95% homology. All subtypes are widely expressed throughout adipose tissue and are found at lower
levels on macrophages, neutrophils, Langerhans cells and in the spleen. Nicotinic acid receptors are
involved in the inhibition of lipolysis. The human genes encoding these receptors are located on chromosome
12 (12q24.3).

Gene Wiki entry for HCAR3 (Niacin receptor 2) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000012.11  NC_018923.2  NT_009755.19  
Regulatory elements:
   Search SABiosciences Regulatory transcription factor binding sites for HCAR3
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidHCAR3 promoter sequence
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Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat HCAR3


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 12q24.31   Ensembl cytogenetic band:  12q24.31   HGNC cytogenetic band: 12q24.31

HCAR3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HCAR3 gene location

GeneLoc information about chromosome 12         GeneLoc Exon Structure

GeneLoc location for GC12M123200:  view genomic region     (about GC identifiers)

Start:
123,199,303 bp from pter      End:
123,201,439 bp from pter
Size:
2,137 bases      Orientation:
minus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: HCAR3_HUMAN, P49019 (See protein sequence)
Recommended Name: Hydroxycarboxylic acid receptor 3  
Size: 387 amino acids; 44478 Da
Subcellular location: Cell membrane; Multi-pass membrane protein
Secondary accessions: A8K4G5 B2R830 E9PI97 Q8NGE4

Explore the universe of human proteins at neXtProt for HCAR3: NX_P49019

HCAR3 Protein expression data from MOPED1, PaxDb2 and MAXQB3 : --

REFSEQ proteins: NP_006009.2  
ENSEMBL proteins: 
 ENSP00000436714  
Reactome Protein details: P49019
Human Recombinant Protein Products for HCAR3: 
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Gene Ontology (GO): 3 cellular component terms (GO ID links to tree view):    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0005886plasma membrane TAS--
GO:0005887integral to plasma membrane TAS7505609
GO:0016021integral to membrane ----

HCAR3 for ontologies           About GeneDecksing



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(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section
HGNC Gene Families: 
HCAR: GPCR / Class A : Hydroxy-carboxylic acid receptors

IUPHAR Guide to PHARMACOLOGY protein family classification: HCA3 receptor 
Hydroxycarboxylic acid receptors

3 InterPro protein domains:
 IPR017452 GPCR_Rhodpsn_7TM
 IPR000276 GPCR_Rhodpsn
 IPR002286 purinergic_P2Y_rcpt

Graphical View of Domain Structure for InterPro Entry P49019

ProtoNet protein and cluster: P49019

UniProtKB/Swiss-Prot: HCAR3_HUMAN, P49019
Similarity: Belongs to the G-protein coupled receptor 1 family


HCAR3 for domains           About GeneDecksing


(According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
About This Section

Molecular Function:

     UniProtKB/Swiss-Prot Summary: HCAR3_HUMAN, P49019
Function: Receptor for 3-OH-octanoid acid mediates a negative feedback regulation of adipocyte lipolysis to
counteract prolipolytic influences under conditions of physiological or pathological increases in beta-oxidation
rates. Acts as a low affinity receptor for nicotinic acid. This pharmacological effect requires nicotinic acid
doses that are much higher than those provided by a normal diet

     Gene Ontology (GO): 2 molecular function terms (GO ID links to tree view):    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0004930G-protein coupled receptor activity IEA--
GO:0045028G-protein coupled purinergic nucleotide receptor activity ----
     
HCAR3 for ontologies           About GeneDecksing


Animal Models:
   inGenious Targeting Laboratory - Custom generated mouse model solutions for HCAR3 
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miRNA
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SwitchGear 3'UTR luciferase reporter plasmidHCAR3 3' UTR sequence
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(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene).
About This Section

SuperPaths for HCAR3 About                                                                                                See pathways by source

SuperPathContained pathways About
1Class A/1 (Rhodopsin-like receptors)
Class A/1 (Rhodopsin-like receptors)0.71
G alpha (i) signalling events0.46
GPCR ligand binding0.71
GPCRs, Class A Rhodopsin-like0.41
2Signaling by GPCR
Signaling by GPCR0.90
Signal Transduction0.55
GPCR downstream signaling0.90
3Hydroxycarboxylic acid-binding receptors
Hydroxycarboxylic acid-binding receptors

Pathways by source                                                                                                                                                                 See SuperPaths
Show all pathways


1 BioSystems Pathway for HCAR3
    GPCRs, Class A Rhodopsin-like

5/7        Reactome Pathways for HCAR3 (see all 7)
    GPCR downstream signaling
Signal Transduction
Signaling by GPCR
G alpha (i) signalling events
GPCR ligand binding



HCAR3 for pathways           About GeneDecksing

Interactions:

    Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for HCAR3

Gene Ontology (GO): 1 biological process term (GO ID links to tree view):    About this table

GO IDQualified GO termEvidencePubMed IDs
GO:0007186G-protein coupled receptor signaling pathway TAS7505609

HCAR3 for ontologies           About GeneDecksing



(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

HCAR3 for compounds           About GeneDecksing

Browse Small Molecules at EMD Millipore
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Compounds for HCAR3 available from Tocris Bioscience    About this table
CompoundAction CAS #
AcifranHypolipidemic agent; agonist for the GPR109A (HM74A) and GPR109B receptors[72420-38-3]
IBC 293Selective agonist for the GPR109B (HM74) receptor. Antilipolytic[306935-41-1]

10/12 IUPHAR Ligands for HCAR3 (HCA3 receptor) (see all 12)    About this table 
LigandTypeActionAffinityPubmed IDs
compound 6o [PMID:19524438]
AgonistFull agonist8.5219524438
4-(n-propyl)amino-3-nitrobenzoic acid
AgonistFull agonist7.5217931863
5-methyl-?ae5-(5-meth?aeylthiophe?aen-3-yl)-4?ae-oxo-4,5-?aedihydrofu?aeran-2-car?aeboxylic a?aecid
AgonistFull agonist6.717358052
nicotinic acid
AgonistFull agonist4 - 6.5212522134
1-isopropylbenzotriazole-5-carboxylic acid
AgonistFull agonist6.416480258
D-kynurenine
AgonistFull agonist5.5819237584
2-hydroxyoctanoic acid
AgonistFull agonist5.419561068
5-ethyl-4-oxo-5-phenyl-4,5-dihydro-furan-2-carboxylic acid
AgonistFull agonist5.317358052
acifran
AgonistFull agonist4.7 - 5.215929991 12522134 16389067 17358052
3-hydroxyoctanoic acid
AgonistFull agonist5.119561068

1 Novoseek inferred chemical compound relationship for HCAR3 gene    About this table
Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
niacin 84.6 19 16386710 (4), 12563315 (3), 15580557 (2), 19237584 (2) (see all 7)

Search CenterWatch for drugs/clinical trials and news about HCAR3

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for HCAR3 gene: 
NM_006018.2  

Unigene Cluster for HCAR3:

Hydroxycarboxylic acid receptor 3
Hs.458425  [show with all ESTs]
Unigene Representative Sequence: NM_006018
1 Ensembl transcript including schematic representation, and UCSC links where relevant:
ENST00000528880(uc001ucy.4)
miRNA
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hsa-miR-203 hsa-miR-141 hsa-miR-204 hsa-miR-200a hsa-miR-1208 hsa-miR-211
SwitchGear 3'UTR luciferase reporter plasmidHCAR3 3' UTR sequence
Inhib. RNA
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Additional mRNA sequence: 

AK290930.1 AK313212.1 BC038955.1 BC047891.1 D10923.1 

2 DOTS entries:

DT.410471  DT.100787462 

24/68 AceView cDNA sequences (see all 68):

BM008116 AL545172 BM980688 AW449521 AL546894 AW081241 NM_177551 N62053 
CD364466 BU684103 BE718299 BC063461 BC056419 BU146785 T29786 AY148884 
AW264883 AW088065 AL545140 BF091320 AL698846 BI837965 BV205727 BM918711 

GeneLoc Exon Structure


(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

HCAR3 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>2/3
CGAP TAG: CTGGACCCCG
HCAR3 Expression
About this image


Genevestigator expression for HCAR3

SOURCE GeneReport for Unigene cluster: Hs.458425

UniProtKB/Swiss-Prot: HCAR3_HUMAN, P49019
Tissue specificity: Expression largely restricted to adipose tissue and spleen

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In Situ
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(Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of chordates.

Orthologs for HCAR3 gene from 1/7 species (see all 7)    About this table
Organism Taxonomic
classification
Gene Description Human
Similarity
Orthology
Type
Details
zebrafish
(Danio rerio)
Actinopterygii gpr81-31 GPR81-like protein 3 52.61(n)
43.2(a)
  100148539  XM_001921202.3  XP_001921237.2 
        Species with no ortholog for HCAR3

ENSEMBL Gene Tree for HCAR3 (if available)
TreeFam Gene Tree for HCAR3 (if available)

(Paralogs according to 1HomoloGene,
2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
About This Section
Paralogs for HCAR3 gene
HCAR12  OXER12  GPR312  GPR202  HCAR22  
16 SIMAP similar genes for HCAR3 using alignment to 1 protein entry:     HCAR3_HUMAN:
HCAR2    HCAR1    OXER1    GPR31    CMKLR1    LPAR6
P2RY5    LPAR4    CYSLTR1    CYSLTR2    GPR35    KPG_011
GPR17    KPG_007    P2RY1    OXGR1

HCAR3 for paralogs           About GeneDecksing



(SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

10/180 SNPs in HCAR3 are shown (see all 180)    About this table     
Genomic DataTranscription Related DataAllele Frequencies
SNP IDValidClinical
significance
Chr 12 posSequence#AA
Chg
TypeMore#Allele
freq
PopTotal
sample
More
----------
VAR_0387204
----see VAR_0387202 G S mis40--------
VAR_0387174
----see VAR_0387172 H R mis40--------
VAR_0387184
----see VAR_0387182 I M mis40--------
rs557760991,2
C,F--123198832(+) CAAGCA/GGCCGC 1 -- int12Minor allele frequency- G:0.25NA 4
rs22621941,2
C,F,A--123198921(-) CCTGAA/CGTAAG 1 -- int13Minor allele frequency- C:0.33NA 6
rs22569361,2
C,F,A--123198936(-) AAGGCA/GGGCAG 1 -- int15Minor allele frequency- G:0.30NA WA 10
rs1394128121,2
C--123199222(+) GGACAA/TAGTTA 1 -- int10--------
rs6312561,2
C,F,A,H--123199327(-) TACCAC/TTTCAA 1 -- ut313Minor allele frequency- T:0.33NA 6
rs1402888391,2
C--123199342(+) TTTGGC/TAAGTA 1 -- ut310--------
rs1503627891,2
C--123199392(+) CTCTAA/CCCGTG 1 -- ut310--------

HapMap Linkage Disequilibrium report for HCAR3 (123199303 - 123201439 bp)

Structural Variations
     Database of Genomic Variants (DGV) 3 variations for HCAR3:    About this table     
Variant IDTypeSubtypePubMed ID
nsv913CNV Insertion18451855
esv8582CNV Loss19470904
esv26589CNV Gain19812545

SABiosciences Cancer Mutation PCR Assays
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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section
OMIM gene information: 606039    OMIM disorders: --

4 diseases for HCAR3:    About MalaCards
distal hereditary motor neuropathy, type ii    distal hereditary motor neuropathy    neuropathy    schizophrenia


HCAR3 for disorders           About GeneDecksing


Export disorders for HCAR3 gene to outside databases

(in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
About This Section

PubMed articles for HCAR3 gene, integrated from 9 sources (see all 28):
(articles sorted by number of sources associating them with HCAR3)
    Utopia: connect your pdf to the dynamic
world of online information

  1. International union of basic and clinical pharmacology. LXXXII: nomenclature and classification of hydroxy-carboxylic acid receptors (GPR81, GPR109A, and GPR109B). (PubMed id 21454438)1, 2, 3 Offermanns S....Ijzerman A.P. (2011)
  2. Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte chemotactic peptide receptors. (PubMed id 7505609)1, 2, 3 Nomura H.... Matsushima K. (1993)
  3. Molecular identification of high and low affinity receptors for nicotinic acid. (PubMed id 12522134)1, 2, 9 Wise A.... Pike N.B. (2003)
  4. Deorphanization of GPR109B as a receptor for the beta-oxidation intermediate 3-OH-octanoic acid and its role in the regulation of lipolysis. (PubMed id 19561068)1, 2 Ahmed K.... Offermanns S. (2009)
  5. Nicotinic acid receptor agonists. (PubMed id 18983141)1, 3 Boatman P.D....Semple G. (2008)
  6. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S....Malek J. (2004)
  7. Isolation and chromosomal localization of GPR31, a human gene encoding a putative G protein-coupled receptor. (PubMed id 9205127)1, 3 Zingoni A....Napolitano M. (1997)
  8. Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor, GPR109B. (PubMed id 19237584)1, 9 Irukayama-Tomobe Y....Sakurai T. (2009)
  9. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. (PubMed id 12563315)1, 9 Tunaru S....Offermanns S. (2003)
  10. Activated human hydroxy-carboxylic acid receptor-3 sig nals to MAP kinase cascades via the PLC-dependent PKC and MMP-mediated EGFR path ways. (PubMed id 22289163)1 Zhou Q....Zhou N.M. (2012)

(in PubMed, OMIM, and NCBI Bookshelf)
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section
Entrez Gene: 8843 HGNC: 16824 AceView: GPR109A Ensembl:ENSG00000255398 euGenes: HUgn8843
ECgene: HCAR3 H-InvDB: HCAR3

(According to HUGE)
About This Section
  --

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section
NameDescription
PharmGKB entry for HCAR3 Pharmacogenomics, SNPs, Pathways
SeattleSNPshttp://pga.gs.washington.edu/data/gpr109b/

(Patent information from GeneIP,
Licensable technologies from WIS Yeda, Salk, Tufts,
IP news from LifeMap Sciences, Inc.)
About This Section
Patent Information for HCAR3 gene:
Search GeneIP for patents involving HCAR3

GeneCards and IP:
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