Top ▲

GtoPdb is requesting financial support from commercial users. Please see our sustainability page for more information.

GPR63

Click here for help

Target id: 112

Nomenclature: GPR63

Family: Class A Orphans with emerging pharmacology

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 419 6q16.1 GPR63 G protein-coupled receptor 63 3-5
Mouse 7 425 4 A3 Gpr63 G protein-coupled receptor 63 3
Rat 7 425 5q21 Gpr63 G protein-coupled receptor 63
Previous and Unofficial Names Click here for help
PSP24-2 | PSP24B | PSP24beta
Database Links Click here for help
Specialist databases
GPCRdb gpr63_human (Hs), gpr63_mouse (Mm)
Other databases
Alphafold Q9BZJ6 (Hs), Q9EQQ3 (Mm)
ChEMBL Target CHEMBL4523916 (Hs)
Ensembl Gene ENSG00000112218 (Hs), ENSMUSG00000040372 (Mm), ENSRNOG00000007675 (Rn)
Entrez Gene 81491 (Hs), 81006 (Mm), 297952 (Rn)
Human Protein Atlas ENSG00000112218 (Hs)
KEGG Gene hsa:81491 (Hs), mmu:81006 (Mm), rno:297952 (Rn)
OMIM 606915 (Hs)
Pharos Q9BZJ6 (Hs)
RefSeq Nucleotide NM_030784 (Hs), NM_030733 (Mm), NM_001106640 (Rn)
RefSeq Protein NP_110411 (Hs), NP_109658 (Mm), NP_001100110 (Rn)
UniProtKB Q9BZJ6 (Hs), Q9EQQ3 (Mm)
Wikipedia GPR63 (Hs)
Natural/Endogenous Ligands Click here for help
dihydrosphingosine 1-phosphate
dioleoylphosphatidic acid
sphingosine 1-phosphate
Comments: Proposed ligand, single publication

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
dioleoylphosphatidic acid Small molecule or natural product Ligand is endogenous in the given species Hs Full agonist 6.3 pEC50 5
⤷ pEC50 6.3 (EC50 5x10-7 M) [5]
dihydrosphingosine 1-phosphate Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 6.2 pEC50 5
⤷ pEC50 6.2 (EC50 6.8x10-7 M) [5]
sphingosine 1-phosphate Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 6.1 – 6.2 pEC50 5
⤷ pEC50 6.1 – 6.2 (EC50 8x10-7 – 6.6x10-7 M) [5]
Agonist Comments
Yin et al. evaluated receptor/ligand pairing using an arrestin assay system but there was no hit detected for GPR63 [6].
Tissue Distribution Click here for help
Frontal cortex, thalamus, caudate, hypothalamus, midbrain
Species:  Human
Technique:  Northern blot
References:  4
High expression in brain, especially in the thalamus and the caudate nucleus, and peripheral tissues such as thymus, stomach and small intestine. Lower expression in kidney, spleen, pancreas and heart.
Species:  Human
Technique:  RT-PCR
References:  5
Brain, neuroendocrine cells, testicular cells
Species:  Mouse
Technique:  Northern blot
References:  3
Neuronal cell
Species:  Rat
Technique:  Northern blot
References:  3
Tissue Distribution Comments
Expression of GPR63 was not detected in the liver when examined by Northern blot analysis [4].
Expression Datasets Click here for help

Show »

Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

There should be a chart of expression data here, you may need to enable JavaScript!
Physiological Functions Comments
GPR63 is highly expressed in neuronal cells and the expression remains constant from the early embryonic stages to adulthood, suggesting the important roles of GPR63 in neuronal functions [3]. High expression of GPR63 in thalamus, caudate, stomach and small intestine may imply a role of GPR63 in central or peripheral control of feeding behaviour [5].
Gene Expression and Pathophysiology Comments
A 1.5Mb deletion in chromosome 6q16.1, including GPR63, is associated with autistic features including speech delay [1].
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  V21M
Global MAF (%):  2
Subpopulation MAF (%):  AMR|EUR: 2|4
Minor allele count:  T=0.019/42
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession:  VAR_049396, rs35358396
Validation:  1000 Genomes, Frequency
General Comments
Proposed ligands (sphingosine 1-phosphate and dioleoylphosphatidic acid), supported by one publication [5], but not replicated in [6]. Unlike Xenopus GPR63, mammalian GPR63 is not responsive to lysophosphatidic acid (LPA) [2].

References

Show »

1. Derwińska K, Bernaciak J, Wiśniowiecka-Kowalnik B, Obersztyn E, Bocian E, Stankiewicz P. (2009) Autistic features with speech delay in a girl with an approximately 1.5-Mb deletion in 6q16.1, including GPR63 and FUT9. Clin Genet, 75 (2): 199-202. [PMID:18717687]

2. Kawasawa Y, Kume K, Izumi T, Shimizu T. (2000) Mammalian PSP24s (alpha and beta isoforms) are not responsive to lysophosphatidic acid in mammalian expression systems. Biochem Biophys Res Commun, 276 (3): 957-64. [PMID:11027575]

3. Kawasawa Y, Kume K, Nakade S, Haga H, Izumi T, Shimizu T. (2000) Brain-specific expression of novel G-protein-coupled receptors, with homologies to Xenopus PSP24 and human GPR45. Biochem Biophys Res Commun, 276 (3): 952-6. [PMID:11027574]

4. Lee DK, George SR, Cheng R, Nguyen T, Liu Y, Brown M, Lynch KR, O'Dowd BF. (2001) Identification of four novel human G protein-coupled receptors expressed in the brain. Brain Res Mol Brain Res, 86 (1-2): 13-22. [PMID:11165367]

5. Niedernberg A, Tunaru S, Blaukat A, Ardati A, Kostenis E. (2003) Sphingosine 1-phosphate and dioleoylphosphatidic acid are low affinity agonists for the orphan receptor GPR63. Cell Signal, 15 (4): 435-46. [PMID:12618218]

6. Yin H, Chu A, Li W, Wang B, Shelton F, Otero F, Nguyen DG, Caldwell JS, Chen YA. (2009) Lipid G protein-coupled receptor ligand identification using beta-arrestin PathHunter assay. J Biol Chem, 284: 12328-12338. [PMID:19286662]

How to cite this page