<i>GPR63</i> | Class A Orphans | IUPHAR/BPS Guide to PHARMACOLOGY

GPR63

Target id: 112

Nomenclature: GPR63

Family: Class A Orphans

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for GPR63 in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 419 6q16.1-q16.3 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
PSP24-2 | PSP24B | PSP24beta
Database Links
Specialist databases
GPCRDB gpr63_human (Hs), gpr63_mouse (Mm)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
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

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
dioleoylphosphatidic acid Hs Full agonist 6.3 pEC50 5
pEC50 6.3 (EC50 5x10-7 M) [5]
dihydrosphingosine 1-phosphate Hs Full agonist 6.2 pEC50 5
pEC50 6.2 (EC50 6.8x10-7 M) [5]
sphingosine 1-phosphate 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
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

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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]

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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
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: 
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

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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: 435-446. [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]

Contributors

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How to cite this page

Anthony P. Davenport, Stephen Alexander, Joanna L. Sharman, Adam J. Pawson, Helen E. Benson, Amy E. Monaghan, Wen Chiy Liew, Chido Mpamhanga, Jim Battey, Richard V. Benya, Robert T. Jensen, Sadashiva Karnik, Evi Kostenis, Eliot Spindel, Laura Storjohann, Kalyan Tirupula, Tom I. Bonner, Richard Neubig, Jean-Philippe Pin, Michael Spedding, Anthony Harmar.
Class A Orphans: GPR63. Last modified on 15/07/2015. Accessed on 15/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=112.