GPR68 (G protein-coupled receptor 68)

2008-12-01   Yan Xu  

Department of Obstetrics, Gynecology, Indiana University School of Medicine, 975 W. Walnut St IB355A, Indianapolis, IN 46202, USA

Identity

HGNC
GPR68
LOCATION
14q32.11
IMAGE
Atlas Image
LEGEND
Picture from Entrez Gene.
LOCUSID
8111
ALIAS
AI2A6,GPR12A,OGR1
FUSION GENES
Show Gene Fusions

DNA/RNA

Note

GPR68 (OGR1) is a proton sensing receptor. Its physiological role need to be further investigated.
Atlas Image
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.

Proteins

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

Entity name
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).

Article Bibliography

Pubmed IDLast YearTitleAuthors
164903452006Sphingosylphosphorylcholine enhances calcium entry in thyroid FRO cells by a mechanism dependent on protein kinase C.Afrasiabi E et al
74984591995Cloning, sequencing and tissue distribution of two related G protein-coupled receptor candidates expressed prominently in human lung tissue.An S et al
188473312009Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1.Frick KK et al
177205332007Nociceptors of dorsal root ganglion express proton-sensing G-protein-coupled receptors.Huang CW et al
184857122008Extracellular acidification elicits spatially and temporally distinct Ca2+ signals.Huang WC et al
162973402005Two ligands for a GPCR, proton vs lysolipid.Im DS et al
175761692007RGS18 acts as a negative regulator of osteoclastogenesis by modulating the acid-sensing OGR1/NFAT signaling pathway.Iwai K et al
152589162004Novel clusters of receptors for sphingosine-1-phosphate, sphingosylphosphorylcholine, and (lyso)-phosphatidic acid: new receptors for "old" ligands.Kostenis E et al
129551482003Proton-sensing G-protein-coupled receptors.Ludwig MG et al
170789252007Lysophospholipid receptors: signalling, pharmacology and regulation by lysophospholipid metabolism.Meyer zu Heringdorf D et al
162107762005Sphingosylphosphorylcholine antagonizes proton-sensing ovarian cancer G-protein-coupled receptor 1 (OGR1)-mediated inositol phosphate production and cAMP accumulation.Mogi C et al
179642362008Extracellular acidification enhances osteoclast survival through an NFAT-independent, protein kinase C-dependent pathway.Pereverzev A et al
156650782005Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells.Radu CG et al
171188002006Receptors for protons or lipid messengers or both?Seuwen K et al
177282152007Ovarian cancer G protein-coupled receptor 1, a new metastasis suppressor gene in prostate cancer.Singh LS et al
160143262005Proton-sensing and lysolipid-sensitive G-protein-coupled receptors: a novel type of multi-functional receptors.Tomura H et al
183025042008Cyclooxygenase-2 expression and prostaglandin E2 production in response to acidic pH through OGR1 in a human osteoblastic cell line.Tomura H et al
86611591996Identification of human OGR1, a novel G protein-coupled receptor that maps to chromosome 14.Xu Y et al
167879162006Expression of and role for ovarian cancer G-protein-coupled receptor 1 (OGR1) during osteoclastogenesis.Yang M et al
170232022006Homo- and hetero-dimerization of LPA/S1P receptors, OGR1 and GPR4.Zaslavsky A et al

Other Information

Locus ID:

NCBI: 8111
MIM: 601404
HGNC: 4519
Ensembl: ENSG00000119714

Variants:

dbSNP: 8111
ClinVar: 8111
TCGA: ENSG00000119714
COSMIC: GPR68

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000119714ENST00000529102E9PNU7
ENSG00000119714ENST00000531499Q15743
ENSG00000119714ENST00000535815Q15743
ENSG00000119714ENST00000650645Q15743

Expression (GTEx)

0
5
10
15
20
25
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Pathways

PathwaySourceExternal ID
Signal TransductionREACTOMER-HSA-162582
Signaling by GPCRREACTOMER-HSA-372790
GPCR ligand bindingREACTOMER-HSA-500792
Class A/1 (Rhodopsin-like receptors)REACTOMER-HSA-373076
GPCR downstream signalingREACTOMER-HSA-388396
G alpha (q) signalling eventsREACTOMER-HSA-416476
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907

References

Pubmed IDYearTitleCitations
387614532024A novel mutation in GPR68 causes hypomaturation amelogenesis imperfecta.0
387614532024A novel mutation in GPR68 causes hypomaturation amelogenesis imperfecta.0
365038122023Expression of GPR-68 in Human Corneal and Conjunctival Epithelium. Possible indicator and mediator of attrition associated inflammation at the ocular surface.1
380774172023pH-sensing G protein-coupled orphan receptor GPR68 is expressed in human cartilage and correlates with degradation of extracellular matrix during OA progression.0
365038122023Expression of GPR-68 in Human Corneal and Conjunctival Epithelium. Possible indicator and mediator of attrition associated inflammation at the ocular surface.1
380774172023pH-sensing G protein-coupled orphan receptor GPR68 is expressed in human cartilage and correlates with degradation of extracellular matrix during OA progression.0
351633452022pH-Sensing G Protein-Coupled Receptor OGR1 (GPR68) Expression and Activation Increases in Intestinal Inflammation and Fibrosis.5
356239132022GPR-68 in human lacrimal gland. Detection and possible role in the pathogenesis of dry eye disease.1
351633452022pH-Sensing G Protein-Coupled Receptor OGR1 (GPR68) Expression and Activation Increases in Intestinal Inflammation and Fibrosis.5
356239132022GPR-68 in human lacrimal gland. Detection and possible role in the pathogenesis of dry eye disease.1
334789382021The evolution and mechanism of GPCR proton sensing.23
334789382021The evolution and mechanism of GPCR proton sensing.23
322799932020A missense mutation of Leu74Pro of OGR1 found in familial amelogenesis imperfecta actually causes the loss of the pH-sensing mechanism.6
323580682020CRISPR-addressable yeast strains with applications in human G protein-coupled receptor profiling and synthetic biology.9
329487832020Expression profiles of proton-sensing G-protein coupled receptors in common skin tumors.9

Citation

Yan Xu

GPR68 (G protein-coupled receptor 68)

Atlas Genet Cytogenet Oncol Haematol. 2008-12-01

Online version: http://atlasgeneticsoncology.org/gene/40745/gpr68