<i>GPR75</i> | Class A Orphans | IUPHAR/BPS Guide to PHARMACOLOGY

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GPR75

Target not currently curated in GtoImmuPdb

Target id: 115

Nomenclature: GPR75

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

This receptor has a proposed ligand; see the Latest Pairings page for more information.

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 540 2p16 GPR75 G protein-coupled receptor 75 6
Mouse 7 540 11 A4 Gpr75 G protein-coupled receptor 75
Rat 7 540 14q22 Gpr75 G protein-coupled receptor 75
Previous and Unofficial Names
WI-31133 | WI31133
Database Links
Specialist databases
GPCRDB gpr75_human (Hs), gpr75_mouse (Mm), d3z826_rat (Rn)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
CCL5 {Sp: Human}
Comments: CCL5 was reported to be an agonist of GPR75 by Ignatov et al. [1] but the pairing could not be repeated in a recent β-arrestin assay [5].

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CCL5 {Sp: Human} Hs Full agonist 9.6 pEC50 1
pEC50 9.6 (EC50 2.6x10-10 M) [1]
Agonist Comments
Agonist data obtained from a luciferase reporter gene assay [1].
Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Comments:  CCL5 was reported to induce pertussis toxin-insensitive signalling, and dose dependent IP3 formation and Ca2+ mobilisation [1,3].
References:  1
Tissue Distribution
Retinal pigment epithelium, brain
Species:  Human
Technique:  Northern blot
References:  6
Retina
Species:  Human
Technique:  RT-PCR
References:  4
Brain, heart
Expression level:  High
Species:  Mouse
Technique:  RT-PCR
References:  1
Skeletal muscle
Expression level:  Low
Species:  Mouse
Technique:  RT-PCR
References:  1
Photoreceptor inner segments and outer plexiform layer
Species:  Mouse
Technique:  Northern blot
References:  6
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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Clinically-Relevant Mutations and Pathophysiology Comments
Six potential pathogenic variants have been identified to associate GPR75 with genetic predisposition to age-related macular degeneration [4].
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  S348R
Global MAF (%):  1
Subpopulation MAF (%):  AFR: 2
Minor allele count:  T=0.005/11
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession: 
Validation:  1000 Genomes, Frequency
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  A116T
Global MAF (%):  2
Subpopulation MAF (%):  AFR|AMR|EUR: 1|4|3
Minor allele count:  T=0.019/41
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession: 
Validation:  1000 Genomes, Frequency, Multiple observations
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  C160G
Global MAF (%):  1
Subpopulation MAF (%):  AFR: 4
Minor allele count:  C=0.010/22
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession: 
Validation:  1000 Genomes, Frequency
Type:  Naturally occurring SNP
Species:  Human
Amino acid change:  E195D
Comment on frequency:  Low frequency (<10% of all tested populations)
SNP accession: 
General Comments
CCL5 mediated pertussis toxin-insensitive signalling is neuroprotective, promoting survival of hippocampal cell lines following insult with amyloid-beta peptide, indicating a role for GPR75 in Alzheimer's disease [2].

References

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1. Ignatov A, Robert J, Gregory-Evans C, Schaller HC. (2006) RANTES stimulates Ca2+ mobilization and inositol trisphosphate (IP3) formation in cells transfected with G protein-coupled receptor 75. Br. J. Pharmacol., 149 (5): 490-7. [PMID:17001303]

2. Pease JE. (2006) Tails of the unexpected - an atypical receptor for the chemokine RANTES/CCL5 expressed in brain. Br. J. Pharmacol., 149 (5): 460-2. [PMID:17001302]

3. Pease JE. (2011) Targeting chemokine receptors in allergic disease. Biochem. J., 434 (1): 11-24. [PMID:21269275]

4. Sauer CG, White K, Stöhr H, Grimm T, Hutchinson A, Bernstein PS, Lewis RA, Simonelli F, Pauleikhoff D, Allikmets R, Weber BH. (2001) Evaluation of the G protein coupled receptor-75 (GPR75) in age related macular degeneration. Br J Ophthalmol, 85 (8): 969-75. [PMID:11466257]

5. Southern C, Cook JM, Neetoo-Isseljee Z, Taylor DL, Kettleborough CA, Merritt A, Bassoni DL, Raab WJ, Quinn E, Wehrman TS et al.. (2013) Screening β-Arrestin Recruitment for the Identification of Natural Ligands for Orphan G-Protein-Coupled Receptors. J Biomol Screen, 18 (5): 599-609. [PMID:23396314]

6. Tarttelin EE, Kirschner LS, Bellingham J, Baffi J, Taymans SE, Gregory-Evans K, Csaky K, Stratakis CA, Gregory-Evans CY. (1999) Cloning and characterization of a novel orphan G-protein-coupled receptor localized to human chromosome 2p16. Biochem. Biophys. Res. Commun., 260 (1): 174-80. [PMID:10381362]

Contributors

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