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GPR68 (G protein-coupled receptor 68)

Written2008-12Yan Xu
Department of Obstetrics, Gynecology, Indiana University School of Medicine, 975 W. Walnut St IB355A, Indianapolis, IN 46202, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)OGR1
HGNC (Hugo) GPR68
LocusID (NCBI) 8111
Atlas_Id 40745
Location 14q32.11  [Link to chromosome band 14q32]
Location_base_pair Starts at 91698876 and ends at 91710852 bp from pter ( according to hg19-Feb_2009)  [Mapping GPR68.png]
 
  Picture from Entrez Gene.
Fusion genes
(updated 2016)
DPY19L3 (19q13.11) / GPR68 (14q32.11)NUMB (14q24.2) / GPR68 (14q32.11)
Note GPR68 (OGR1) is a G protein-coupled receptor (GPCR), which share high homology with other three GPCRs (TDAG8, G2A and GPR4). OGR1, as well as TDAG8, G2A and GPR4, has been shown to be proton-sensing GPCRs. In particular, OGR1 has been shown to be a proton-sensing receptor in bone. OGR1 is expressed in osteoclasts and osteoblasts, where it mediates acid-induced signaling pathways via G(q/11) protein, phospholipase C, IP(3) formation, and subsequent Ca2+ release from thapsigargin-sensitive stores. Acidic pH has been shown to induce cyclooxygenase-2 (COX-2) induction and prostaglandin E2 (PGE2) production, resulting in stimulation of bone calcium release and osteoclastogenesis. OGR1 family receptors can also mediate effects of several phospholipids. However, whether the lipid regulation is specific to these receptors is still under debate.

DNA/RNA

Note GPR68 (OGR1) is a proton sensing receptor. Its physiological role need to be further investigated.
 
  Picture from Entrez Gene.
Description The open reading frame of GPR68 is encoded by a single exon (1095 bp) located at chromosome 14q31.
Transcription GPR68 transcripts of ~3.0 kb in human.

Protein

Description Size: 365 amino acids.
Expression GPR68 is expressed in blood; bone; brain; connective tissue; embryonic tissue; eye; heart, intestine; lung; pancreas; placenta; peripheral blood leukocyte, prostate; skin; stomach; thymus; uterus; chondrosarcoma; leukemia; normal; pancreatic cancer; small intestine, soft tissue/muscle tissue tumor; spleen, stomach tumor; testis, uterine tumor; embryo; fetus; adult.
Localisation Cell membrane
Function Osteoclastogenesis
Homology OGR1, GPR4, G2A, and TDAG8 share 40% to 50% homology with each other and seem to form a family of GPCRs. GPCRs form homo- and hetero-dimers or -oligomers. Although GPR4 and OGR1 share more than 50% homology, GPR4 forms strong homo- and hetero-dimers with LPA and S1P receptors, but OGR1 forms very weak homo-dimer and relatively weak hetero-dimers with other receptors.

Implicated in

Note
  
Entity Prostate cancer
Note Down regulated in metastatic prostate cancer.
Oncogenesis OGR1 is down regulated in metastatic prostate cancer tissues and over-expression OGR1 in prostate cancer cells suppress tumor metastasis. Thus, OGR1 has been considered as a tumor metastasis suppressor genes for prostate cancer (Singh et al., 2007).
  

Bibliography

Sphingosylphosphorylcholine enhances calcium entry in thyroid FRO cells by a mechanism dependent on protein kinase C.
Afrasiabi E, Blom T, Ekokoski E, Tuominen RK, Tornquist K.
Cell Signal. 2006 Oct;18(10):1671-8.
PMID 16490345
 
Cloning, sequencing and tissue distribution of two related G protein-coupled receptor candidates expressed prominently in human lung tissue.
An S, Tsai C, Goetzl EJ.
FEBS Lett. 1995 Nov 13;375(1-2):121-4.
PMID 7498459
 
Metabolic Acidosis Increases Intracellular Calcium in Bone Cells Through Activation of the Proton Receptor OGR1.
Frick KK, Krieger NS, Nehrke K, Bushinsky DA.
J Bone Miner Res. 2008 Oct 10. [Epub ahead of print]
PMID 18847331
 
Nociceptors of dorsal root ganglion express proton-sensing G-protein-coupled receptors.
Huang CW, Tzeng JN, Chen YJ, Tsai WF, Chen CC, Sun WH.
Mol Cell Neurosci. 2007 Oct;36(2):195-210.
PMID 17720533
 
Extracellular acidification elicits spatially and temporally distinct Ca2+ signals.
Huang WC, Swietach P, Vaughan-Jones RD, Ansorge O, Glitsch MD.
Curr Biol. 2008 May 20;18(10):781-5.
PMID 18485712
 
Two ligands for a GPCR, proton vs lysolipid.
Im DS.
Acta Pharmacol Sin. 2005 Dec;26(12):1435-41.
PMID 16297340
 
RGS18 acts as a negative regulator of osteoclastogenesis by modulating the acid-sensing OGR1/NFAT signaling pathway.
Iwai K, Koike M, Ohshima S, Miyatake K, Uchiyama Y, Saeki Y, Ishii M.
J Bone Miner Res. 2007 Oct;22(10):1612-20.
PMID 17576169
 
Novel clusters of receptors for sphingosine-1-phosphate, sphingosylphosphorylcholine, and (lyso)-phosphatidic acid: new receptors for "old" ligands.
Kostenis E.
J Cell Biochem. 2004 Aug 1;92(5):923-36.
PMID 15258916
 
Proton-sensing G-protein-coupled receptors.
Ludwig MG, Vanek M, Guerini D, Gasser JA, Jones CE, Junker U, Hofstetter H, Wolf RM, Seuwen K.
Nature. 2003 Sep 4;425(6953):93-8.
PMID 12955148
 
Lysophospholipid receptors: signalling, pharmacology and regulation by lysophospholipid metabolism.
Meyer zu Heringdorf D, Jakobs KH.
Biochim Biophys Acta. 2007 Apr;1768(4):923-40.
PMID 17078925
 
Sphingosylphosphorylcholine antagonizes proton-sensing ovarian cancer G-protein-coupled receptor 1 (OGR1)-mediated inositol phosphate production and cAMP accumulation.
Mogi C, Tomura H, Tobo M, Wang JQ, Damirin A, Kon J, Komachi M, Hashimoto K, Sato K, Okajima F.
J Pharmacol Sci. 2005 Oct;99(2):160-7.
PMID 16210776
 
Extracellular acidification enhances osteoclast survival through an NFAT-independent, protein kinase C-dependent pathway.
Pereverzev A, Komarova SV, Korcok J, Armstrong S, Tremblay GB, Dixon SJ, Sims SM.
Bone. 2008 Jan;42(1):150-61.
PMID 17964236
 
Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells.
Radu CG, Nijagal A, McLaughlin J, Wang L, Witte ON.
Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1632-7.
PMID 15665078
 
Receptors for protons or lipid messengers or both?
Seuwen K, Ludwig MG, Wolf RM.
J Recept Signal Transduct Res. 2006;26(5-6):599-610.
PMID 17118800
 
Ovarian cancer G protein-coupled receptor 1, a new metastasis suppressor gene in prostate cancer.
Singh LS, Berk M, Oates R, Zhao Z, Tan H, Jiang Y, Zhou A, Kirmani K, Steinmetz R, Lindner D, Xu Y.
J Natl Cancer Inst. 2007 Sep 5;99(17):1313-27.
PMID 17728215
 
Proton-sensing and lysolipid-sensitive G-protein-coupled receptors: a novel type of multi-functional receptors.
Tomura H, Mogi C, Sato K, Okajima F.
Cell Signal. 2005 Dec;17(12):1466-76.
PMID 16014326
 
Cyclooxygenase-2 expression and prostaglandin E2 production in response to acidic pH through OGR1 in a human osteoblastic cell line.
Tomura H, Wang JQ, Liu JP, Komachi M, Damirin A, Mogi C, Tobo M, Nochi H, Tamoto K, Im DS, Sato K, Okajima F.
J Bone Miner Res. 2008 Jul;23(7):1129-39.
PMID 18302504
 
Identification of human OGR1, a novel G protein-coupled receptor that maps to chromosome 14.
Xu Y, Casey G.
Genomics. 1996 Jul 15;35(2):397-402.
PMID 8661159
 
Expression of and role for ovarian cancer G-protein-coupled receptor 1 (OGR1) during osteoclastogenesis.
Yang M, Mailhot G, Birnbaum MJ, MacKay CA, Mason-Savas A, Odgren PR.
J Biol Chem. 2006 Aug 18;281(33):23598-605.
PMID 16787916
 
Homo- and hetero-dimerization of LPA/S1P receptors, OGR1 and GPR4.
Zaslavsky A, Singh LS, Tan H, Ding H, Liang Z, Xu Y.
Biochim Biophys Acta. 2006 Oct;1761(10):1200-12.
PMID 17023202
 

Citation

This paper should be referenced as such :
Xu, Y
GPR68 (G protein-coupled receptor 68)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(11):845-846.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/GPR68ID40745ch14q32.html


External links

Nomenclature
HGNC (Hugo)GPR68   4519
Cards
AtlasGPR68ID40745ch14q32
Entrez_Gene (NCBI)GPR68  8111  G protein-coupled receptor 68
AliasesGPR12A; OGR1
GeneCards (Weizmann)GPR68
Ensembl hg19 (Hinxton)ENSG00000119714 [Gene_View]  chr14:91698876-91710852 [Contig_View]  GPR68 [Vega]
Ensembl hg38 (Hinxton)ENSG00000119714 [Gene_View]  chr14:91698876-91710852 [Contig_View]  GPR68 [Vega]
ICGC DataPortalENSG00000119714
TCGA cBioPortalGPR68
AceView (NCBI)GPR68
Genatlas (Paris)GPR68
WikiGenes8111
SOURCE (Princeton)GPR68
Genetics Home Reference (NIH)GPR68
Genomic and cartography
GoldenPath hg19 (UCSC)GPR68  -     chr14:91698876-91710852 -  14q31   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)GPR68  -     14q31   [Description]    (hg38-Dec_2013)
EnsemblGPR68 - 14q31 [CytoView hg19]  GPR68 - 14q31 [CytoView hg38]
Mapping of homologs : NCBIGPR68 [Mapview hg19]  GPR68 [Mapview hg38]
OMIM601404   
Gene and transcription
Genbank (Entrez)AY615372 BC067470 BC067471 BC067472 BC069592
RefSeq transcript (Entrez)NM_001177676 NM_003485
RefSeq genomic (Entrez)NC_000014 NC_018925 NT_026437 NW_004929393
Consensus coding sequences : CCDS (NCBI)GPR68
Cluster EST : UnigeneHs.8882 [ NCBI ]
CGAP (NCI)Hs.8882
Alternative Splicing GalleryENSG00000119714
Gene ExpressionGPR68 [ NCBI-GEO ]   GPR68 [ EBI - ARRAY_EXPRESS ]   GPR68 [ SEEK ]   GPR68 [ MEM ]
Gene Expression Viewer (FireBrowse)GPR68 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)8111
GTEX Portal (Tissue expression)GPR68
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ15743   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ15743  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ15743
Splice isoforms : SwissVarQ15743
PhosPhoSitePlusQ15743
Domaine pattern : Prosite (Expaxy)G_PROTEIN_RECEP_F1_1 (PS00237)    G_PROTEIN_RECEP_F1_2 (PS50262)   
Domains : Interpro (EBI)GPCR_Rhodpsn    GPCR_Rhodpsn_7TM    OGR1_rcpt   
Domain families : Pfam (Sanger)7tm_1 (PF00001)   
Domain families : Pfam (NCBI)pfam00001   
Conserved Domain (NCBI)GPR68
DMDM Disease mutations8111
Blocks (Seattle)GPR68
SuperfamilyQ15743
Human Protein AtlasENSG00000119714
Peptide AtlasQ15743
HPRD03241
IPIIPI00976873   IPI00019433   
Protein Interaction databases
DIP (DOE-UCLA)Q15743
IntAct (EBI)Q15743
FunCoupENSG00000119714
BioGRIDGPR68
STRING (EMBL)GPR68
ZODIACGPR68
Ontologies - Pathways
QuickGOQ15743
Ontology : AmiGOG-protein coupled receptor activity  plasma membrane  integral component of plasma membrane  inflammatory response  G-protein coupled receptor signaling pathway  positive regulation of insulin secretion involved in cellular response to glucose stimulus  negative regulation of monocyte differentiation  cellular response to pH  positive regulation of osteoclast development  
Ontology : EGO-EBIG-protein coupled receptor activity  plasma membrane  integral component of plasma membrane  inflammatory response  G-protein coupled receptor signaling pathway  positive regulation of insulin secretion involved in cellular response to glucose stimulus  negative regulation of monocyte differentiation  cellular response to pH  positive regulation of osteoclast development  
REACTOMEQ15743 [protein]
REACTOME Pathways373076 [pathway]   416476 [pathway]   
NDEx NetworkGPR68
Atlas of Cancer Signalling NetworkGPR68
Wikipedia pathwaysGPR68
Orthology - Evolution
OrthoDB8111
GeneTree (enSembl)ENSG00000119714
Phylogenetic Trees/Animal Genes : TreeFamGPR68
HOVERGENQ15743
HOGENOMQ15743
Homologs : HomoloGeneGPR68
Homology/Alignments : Family Browser (UCSC)GPR68
Gene fusions - Rearrangements
Fusion : MitelmanDPY19L3/GPR68 [19q13.11/14q32.11]  [t(14;19)(q32;q13)]  
Fusion : MitelmanNUMB/GPR68 [14q24.2/14q32.11]  [t(14;14)(q24;q32)]  
Fusion: TCGADPY19L3 19q13.11 GPR68 14q32.11 SKCM
Fusion: TCGANUMB 14q24.2 GPR68 14q32.11 LUSC
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerGPR68 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)GPR68
dbVarGPR68
ClinVarGPR68
1000_GenomesGPR68 
Exome Variant ServerGPR68
ExAC (Exome Aggregation Consortium)GPR68 (select the gene name)
Genetic variants : HAPMAP8111
Genomic Variants (DGV)GPR68 [DGVbeta]
DECIPHER (Syndromes)14:91698876-91710852  ENSG00000119714
CONAN: Copy Number AnalysisGPR68 
Mutations
ICGC Data PortalGPR68 
TCGA Data PortalGPR68 
Broad Tumor PortalGPR68
OASIS PortalGPR68 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICGPR68  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDGPR68
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch GPR68
DgiDB (Drug Gene Interaction Database)GPR68
DoCM (Curated mutations)GPR68 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)GPR68 (select a term)
intoGenGPR68
NCG5 (London)GPR68
Cancer3DGPR68(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM601404   
Orphanet
MedgenGPR68
Genetic Testing Registry GPR68
NextProtQ15743 [Medical]
TSGene8111
GENETestsGPR68
Huge Navigator GPR68 [HugePedia]
snp3D : Map Gene to Disease8111
BioCentury BCIQGPR68
ClinGenGPR68
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD8111
Chemical/Pharm GKB GenePA28911
Clinical trialGPR68
Miscellaneous
canSAR (ICR)GPR68 (select the gene name)
Probes
Litterature
PubMed24 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineGPR68
EVEXGPR68
GoPubMedGPR68
iHOPGPR68
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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