<i>GPR31</i> | Class A Orphans | IUPHAR/BPS Guide to PHARMACOLOGY

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GPR31

Target not currently curated in GtoImmuPdb

Target id: 98

Nomenclature: GPR31

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

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 319 6q27 GPR31 G protein-coupled receptor 31 7
Mouse 7 319 17 A1 Gpr31c G protein-coupled receptor 31, D17Leh66c region
Rat 7 319 1q11 Gpr31 G protein-coupled receptor 31
Previous and Unofficial Names
12-HETER | HETER1 | hydroxyeicosatetraenoic (HETE) acid receptor 1 | 12-(S)-HETE acid receptor | G protein-coupled receptor 31, D17Leh66c region
Database Links
Specialist databases
GPCRDB gpr31_human (Hs), gpr31_mouse (Mm)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
12S-HETE
Comments: Proposed ligand, single publication

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
12S-[3H]HETE Mm Agonist 8.3 pKd 2
pKd 8.3 (Kd 4.87x10-9 M) [2]
12S-HETE Mm Full agonist 9.6 pEC50 2
pEC50 9.6 (EC50 2.8x10-10 M) [2]
Agonist Comments
12-(S)-HETE is a 12-lipoxygenase metabolite of arachidonic acid, which produces a number of cellular responses including cytoskeletal remodeling to facilitate cell chemotaxis and secretion of proteinases and vascular endothelial growth factor leading to an angiogenic response. 12-(S)-HETE treatment of cancer cells alsoenhanced the expression of integrins and fibronectin,which prolong cell survival. GPR31 displayed high affinity binding for tritiated 12-(S)-HETE (Kd = 5 nM) and unlabeled 12-(S)-HETE stimulated GTPγS coupling in the membranes of GPR31-transfected cells, with an EC50 of 0.28 nM [2]. In concordance, GPR31 is phylogenetically closest to the OXE receptor (for which the ligand is 5-oxo-6,8,11,14-eicosatetraenoic acid) [1].

Unlabelled 12S-HETE effectively replaces the radioactive ligand bound to receptors, whereas 12R-HETE is unable to replace GPR31 bound 12S-[3H]HETE suggesting stereospecific binding [2].
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
Comments:  12S-HETE/GPR31 mediated ERK1/2 activation is inhibited by pertussis toxin, suggesting the involvement of Gi/o heterotrimeric G proteins [2]
References:  2
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
Thought to exert an effect on innate immunity through cytokine IFN-γ [4], [6].
Physiological Consequences of Altering Gene Expression Comments
Knockdown of GPR31 using shRNA in transfected CHO cells diminishes specific binding of 12S-[3H]HETE [2].
Clinically-Relevant Mutations and Pathophysiology Comments
Dominantly inherited cutaneous small-vessel lymphocytic vasculitis maps to chromosome 6q26-q27, making GPR31 (which also maps to the linked region) a plausible candidate for the disease based on biological function [6].
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  H91R
Global MAF (%):  1
Subpopulation MAF (%):  AFR: 4
Minor allele count:  T=0.009/20
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession: 
Validation:  1000 Genomes, HapMap, Frequency
Biologically Significant Variant Comments
An in-frame 210-bp deletion in GPR31 is observed in the mouse t complex responder locus responsible for transmission ratio distortion of mouse t haplotypes [5].
General Comments
Clone AK036897 holds 50% identity with human GPR31 indicating that it may be a murine paralog of the receptor. However it is too short to encode a putative GPCR structure, indicating that the cDNA is likely to be a partial fragment [3]. 12S-[3H]HETE has been shown to bind to the BLT2 receptor with much lower affinity than that of GPR31.

References

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1. Gloriam DE, Fredriksson R, Schiöth HB. (2007) The G protein-coupled receptor subset of the rat genome. BMC Genomics, 8: 338. [PMID:17892602]

2. Guo Y, Zhang W, Giroux C, Cai Y, Ekambaram P, Dilly AK, Hsu A, Zhou S, Maddipati KR, Liu J et al.. (2011) Identification of the orphan G protein-coupled receptor GPR31 as a receptor for 12-(S)-hydroxyeicosatetraenoic acid. J. Biol. Chem., 286 (39): 33832-40. [PMID:21712392]

3. Kawasawa Y, McKenzie LM, Hill DP, Bono H, Yanagisawa M, RIKEN GER Group, GSL Members. (2003) G protein-coupled receptor genes in the FANTOM2 database. Genome Res., 13 (6B): 1466-77. [PMID:12819145]

4. Schaub A, Fütterer A, Pfeffer K. (2001) PUMA-G, an IFN-gamma-inducible gene in macrophages is a novel member of the seven transmembrane spanning receptor superfamily. Eur. J. Immunol., 31 (12): 3714-25. [PMID:11745392]

5. Schimenti JC. (1999) ORFless, intronless, and mutant transcription units in the mouse t complex responder (Tcr) locus. Mamm. Genome, 10 (10): 969-76. [PMID:10501965]

6. Sellick GS, Coleman RJ, Webb EL, Chow J, Bevan S, Rosbotham JL, Houlston RS. (2005) Dominantly inherited cutaneous small-vessel lymphocytic vasculitis maps to chromosome 6q26-q27. Hum. Genet., 118 (1): 82-6. [PMID:16133183]

7. Zingoni A, Rocchi M, Storlazzi CT, Bernardini G, Santoni A, Napolitano M. (1997) Isolation and chromosomal localization of GPR31, a human gene encoding a putative G protein-coupled receptor. Genomics, 42 (3): 519-23. [PMID:9205127]

Contributors

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