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GPR75

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Target id: 115

Nomenclature: GPR75

Family: Class A Orphans with emerging pharmacology

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

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 7 540 2p16.2 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 Click here for help
WI-31133 | WI31133
Database Links Click here for help
Specialist databases
GPCRdb gpr75_human (Hs), gpr75_mouse (Mm), d3z826_rat (Rn)
Other databases
Alphafold O95800 (Hs), Q6X632 (Mm), D3Z826 (Rn)
ChEMBL Target CHEMBL4523861 (Hs)
Ensembl Gene ENSG00000119737 (Hs), ENSMUSG00000043999 (Mm), ENSRNOG00000022176 (Rn)
Entrez Gene 10936 (Hs), 237716 (Mm), 498434 (Rn)
Human Protein Atlas ENSG00000119737 (Hs)
KEGG Gene hsa:10936 (Hs), mmu:237716 (Mm), rno:498434 (Rn)
OMIM 606704 (Hs)
Pharos O95800 (Hs)
RefSeq Nucleotide NM_006794 (Hs), NM_175490 (Mm), NM_001109096 (Rn)
RefSeq Protein NP_006785 (Hs), NP_780699 (Mm), NP_001102566 (Rn)
UniProtKB O95800 (Hs), Q6X632 (Mm), D3Z826 (Rn)
Wikipedia GPR75 (Hs)
Natural/Endogenous Ligands Click here for help
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 go icon to follow link

Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CCL5 {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Immunopharmacology Ligand 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 Click here for help
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 Click here for help
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 Click here for help

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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 Click here for help
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:  rs138373994
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:  VAR_033471, rs34000641
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:  VAR_033472, rs35349235
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:  rs1127767
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]

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