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

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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
RefSeq Nucleotide
RefSeq Protein
Natural/Endogenous Ligands
Comments: Proposed ligand, single publication

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

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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.


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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: 3714-3725. [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]


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How to cite this page

Stephen P.H. Alexander, Jim Battey, Helen E. Benson, Richard V. Benya, Tom I. Bonner, Anthony P. Davenport, Satoru Eguchi, Anthony Harmar, Nick Holliday, Robert T. Jensen, Sadashiva Karnik, Evi Kostenis, Wen Chiy Liew, Amy E. Monaghan, Chido Mpamhanga, Richard Neubig, Adam J. Pawson, Jean-Philippe Pin, Joanna L. Sharman, Michael Spedding, Eliot Spindel, Leigh Stoddart, Laura Storjohann, Walter (Wally) Thomas, Kalyan Tirupula, Patrick Vanderheyden.
Class A Orphans: GPR31. Last modified on 30/06/2015. Accessed on 20/07/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=98.