GPR68 (G protein-coupled receptor 68)

2008-12-01 Yan Xu Affiliation

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

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.

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).

Bibliography

Pubmed ID	Last Year	Title	Authors
16490345	2006	Sphingosylphosphorylcholine enhances calcium entry in thyroid FRO cells by a mechanism dependent on protein kinase C.	Afrasiabi E et al
7498459	1995	Cloning, sequencing and tissue distribution of two related G protein-coupled receptor candidates expressed prominently in human lung tissue.	An S et al
18847331	2009	Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1.	Frick KK et al
17720533	2007	Nociceptors of dorsal root ganglion express proton-sensing G-protein-coupled receptors.	Huang CW et al
18485712	2008	Extracellular acidification elicits spatially and temporally distinct Ca2+ signals.	Huang WC et al
16297340	2005	Two ligands for a GPCR, proton vs lysolipid.	Im DS et al
17576169	2007	RGS18 acts as a negative regulator of osteoclastogenesis by modulating the acid-sensing OGR1/NFAT signaling pathway.	Iwai K et al
15258916	2004	Novel clusters of receptors for sphingosine-1-phosphate, sphingosylphosphorylcholine, and (lyso)-phosphatidic acid: new receptors for "old" ligands.	Kostenis E et al
12955148	2003	Proton-sensing G-protein-coupled receptors.	Ludwig MG et al
17078925	2007	Lysophospholipid receptors: signalling, pharmacology and regulation by lysophospholipid metabolism.	Meyer zu Heringdorf D et al
16210776	2005	Sphingosylphosphorylcholine antagonizes proton-sensing ovarian cancer G-protein-coupled receptor 1 (OGR1)-mediated inositol phosphate production and cAMP accumulation.	Mogi C et al
17964236	2008	Extracellular acidification enhances osteoclast survival through an NFAT-independent, protein kinase C-dependent pathway.	Pereverzev A et al
15665078	2005	Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells.	Radu CG et al
17118800	2006	Receptors for protons or lipid messengers or both?	Seuwen K et al
17728215	2007	Ovarian cancer G protein-coupled receptor 1, a new metastasis suppressor gene in prostate cancer.	Singh LS et al
16014326	2005	Proton-sensing and lysolipid-sensitive G-protein-coupled receptors: a novel type of multi-functional receptors.	Tomura H et al
18302504	2008	Cyclooxygenase-2 expression and prostaglandin E2 production in response to acidic pH through OGR1 in a human osteoblastic cell line.	Tomura H et al
8661159	1996	Identification of human OGR1, a novel G protein-coupled receptor that maps to chromosome 14.	Xu Y et al
16787916	2006	Expression of and role for ovarian cancer G-protein-coupled receptor 1 (OGR1) during osteoclastogenesis.	Yang M et al
17023202	2006	Homo- 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 ID	Transcript ID	Uniprot
ENSG00000119714	ENST00000529102	E9PNU7
ENSG00000119714	ENST00000531499	Q15743
ENSG00000119714	ENST00000535815	Q15743
ENSG00000119714	ENST00000650645	Q15743

Expression (GTEx)

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

Pathway	Source	External ID
Signal Transduction	REACTOME	R-HSA-162582
Signaling by GPCR	REACTOME	R-HSA-372790
GPCR ligand binding	REACTOME	R-HSA-500792
Class A/1 (Rhodopsin-like receptors)	REACTOME	R-HSA-373076
GPCR downstream signaling	REACTOME	R-HSA-388396
G alpha (q) signalling events	REACTOME	R-HSA-416476
Gastrin-CREB signalling pathway via PKC and MAPK	REACTOME	R-HSA-881907

References

Pubmed ID	Year	Title	Citations
12955148	2003	Proton-sensing G-protein-coupled receptors.	182
15665078	2005	Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells.	60
29677517	2018	GPR68 Senses Flow and Is Essential for Vascular Physiology.	33
16087674	2005	Prostaglandin I(2) production and cAMP accumulation in response to acidic extracellular pH through OGR1 in human aortic smooth muscle cells.	32
20237496	2010	New genetic associations detected in a host response study to hepatitis B vaccine.	27
17728215	2007	Ovarian cancer G protein-coupled receptor 1, a new metastasis suppressor gene in prostate cancer.	22
18302504	2008	Cyclooxygenase-2 expression and prostaglandin E2 production in response to acidic pH through OGR1 in a human osteoblastic cell line.	18
29092903	2018	GPR68, a proton-sensing GPCR, mediates interaction of cancer-associated fibroblasts and cancer cells.	16
22508039	2012	The proton-activated G protein coupled receptor OGR1 acutely regulates the activity of epithelial proton transport proteins.	15
27693231	2016	Mutations in the pH-Sensing G-protein-Coupled Receptor GPR68 Cause Amelogenesis Imperfecta.	15

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-(g-protein-coupled-receptor-68)