GPR68
Target id: 114
Nomenclature: GPR68
Family: Class A Orphans
See the Latest Pairings page for more information.
Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Natural/Endogenous Ligands
- Rank order lists
- Agonists
- Antagonists
- Allosteric Modulators
- Immuno Process Associations
- Transduction Mechanisms
- Tissue Distribution
- Expression Datasets
- Physiological Functions
- Physiological Consequences of Altering Gene Expression
- Phenotypes, Alleles and Disease Models
- Gene Expression and Pathophysiology
- Biologically Significant Variants
- General Comments
- References
- Contributors
- How to cite this page
Gene and Protein Information  |
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| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 365 | 14q32.11 | GPR68 | G protein-coupled receptor 68 | 2,34 |
| Mouse | 7 | 365 | 12 E | Gpr68 | G protein-coupled receptor 68 | |
| Rat | 7 | 375 | 6q32 | Gpr68 | G protein-coupled receptor 68 | |
| Previous and Unofficial Names |
| GPR12A | Ovarian cancer G-protein coupled receptor 1 | sphingosylphosphorylcholine receptor | OGR1 |
| Database Links |
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| Specialist databases | |
| GPCRdb | ogr1_human (Hs), ogr1_mouse (Mm) |
| Other databases | |
| Alphafold | Q15743 (Hs), Q8BFQ3 (Mm) |
| ChEMBL Target | CHEMBL3713916 (Hs), CHEMBL4523380 (Mm) |
| Ensembl Gene | ENSG00000119714 (Hs), ENSMUSG00000047415 (Mm), ENSRNOG00000046309 (Rn) |
| Entrez Gene | 8111 (Hs), 238377 (Mm), 314386 (Rn) |
| Human Protein Atlas | ENSG00000119714 (Hs) |
| KEGG Gene | hsa:8111 (Hs), mmu:238377 (Mm), rno:314386 (Rn) |
| OMIM | 601404 (Hs) |
| Pharos | Q15743 (Hs) |
| RefSeq Nucleotide | NM_003485 (Hs), NM_175493 (Mm), NM_001108049 (Rn) |
| RefSeq Protein | NP_003476 (Hs), NP_780702 (Mm), NP_001101519 (Rn) |
| UniProtKB | Q15743 (Hs), Q8BFQ3 (Mm) |
| Wikipedia | GPR68 (Hs) |
| Natural/Endogenous Ligands |
| Protons |
| Endogenous ligand |
| Protons |
Download all structure-activity data for this target as a CSV file 
| Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Gpr68 was previously identified as a receptor for sphingosyl phosphorylcholine (SPC) [35], but the original publication has been retracted [39]. However, GPR4, GPR65, GPR68 and GPR132 are now thought to function as proton-sensing receptors detecting acidic pH [4,28]. SPC was later found to antagonise the proton-induced activation of the GPR68-mediated signalling pathways [21,28]. A family of 3,5-disubstituted isoxazoles (Isx) were identified as agonists of GPR68 [26]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonist Comments | ||
| It has been reported by Wang et al. that psychosine antagonises pH responses by GPR68 [32]. |
| Allosteric Modulators | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Immuno Process Associations | ||
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
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Gi/Go family Gq/G11 family |
Adenylyl cyclase inhibition Phospholipase C stimulation |
| References: 17,19,33,36 | |
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| GPR68 was expressed early during mouse osteoclast differentiation in vivo and in vitro [36]. GPR68 was strongly regulated in vivo after 2 days of colony stimulating factor-1 treatment [36]. High levels of GPR68 mRNA were detected by microarray, RT-PCR and immunoblotting when mouse bone marrow mononuclear cells and RAW 264.7 pre-osteoclast-like cells were treated with RANKL to induce osteoclast differentiation [13,36]. | ||||||||
| Expression Datasets |
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| Physiological Functions
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| Physiological Functions Comments | ||||||||
| GPR68 transiently increases intracellular calcium, mediates SPC-induced ERK1/2 activation and inhibits cellular proliferation [3]. GPR68 causes cAMP accumulation and inositol phosphate production upon stimulation by extracellular acidification [21]. | ||||||||
| Physiological Consequences of Altering Gene Expression
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| Physiological Consequences of Altering Gene Expression Comments | ||||||||||
| Knockout of GPR68 in mouse macrophages did not affect the acidic pH-induced inhibitory action on cytokine production [20]. | ||||||||||
| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Gene Expression and Pathophysiology Comments | |
| GPR68 expression was shown to be fivefold lower in metastatic prostate cancers than primary prostate cancers [15]. Gene expression of GPR68 is changed in ASIC3 knockout mice [8]. GPR68 has been reported as a novel metastasis suppressor gene for prostate cancer [17]. |
| Biologically Significant Variants
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| General Comments |
| GPR68 is fully activated at pH 6.8, but almost silent at pH 7.8 [18]. Several His residues that reside in the extracellular domain of GPR68 are shown to be responsible for the proton binding, pH-sensing activity of GPR68 [18]. GPR68 forms very weak homodimers and relatively weak heterodimers with other receptors (LPA and GPR4) [38]. GPR68 is coupled to IP3-mediated Cai signalling in osteoblasts [14]. |
References
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2. An S, Tsai C, Goetzl EJ. (1995) Cloning, sequencing and tissue distribution of two related G protein-coupled receptor candidates expressed prominently in human lung tissue. FEBS Lett, 375 (1-2): 121-4. [PMID:7498459]
3. Bektas M, Barak LS, Jolly PS, Liu H, Lynch KR, Lacana E, Suhr KB, Milstien S, Spiegel S. (2003) The G protein-coupled receptor GPR4 suppresses ERK activation in a ligand-independent manner. Biochemistry, 42 (42): 12181-91. [PMID:14567679]
4. Davenport AP, Alexander SP, Sharman JL, Pawson AJ, Benson HE, Monaghan AE, Liew WC, Mpamhanga CP, Bonner TI, Neubig RR et al.. (2013) International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands. Pharmacol Rev, 65 (3): 967-86. [PMID:23686350]
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