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Target not currently curated in GtoImmuPdb

Target id: 101

Nomenclature: GPR34

Family: Class A Orphans

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 7 381 Xp11.4 GPR34 G protein-coupled receptor 34 12
Mouse 7 375 X A1.1 Gpr34 G protein-coupled receptor 34 12
Rat 7 373 Xq12 Gpr34 G protein-coupled receptor 34 9
Database Links Click here for help
Specialist databases
GPCRdb gpr34_human (Hs), gpr34_mouse (Mm), q6xce7_rat (Rn)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Natural/Endogenous Ligands Click here for help
Comments: Proposed ligand in several publications but not replicated in a recent study based on β-arrestin recruitment [13].

Download all structure-activity data for this target as a CSV file go icon to follow link

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
lysophosphatidylserine Small molecule or natural product Ligand is endogenous in the given species Mm Agonist 7.3 pEC50 15
pEC50 7.3 (EC50 4.9x10-8 M) [15]
lysophosphatidylserine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 6.6 – 6.9 pEC50 8,15
pEC50 6.6 – 6.9 (EC50 2.7x10-7 – 1.29x10-7 M) [8,15]
View species-specific agonist tables
Agonist Comments
One study suggests that lyso-PS has only a random agonistic activity at some GPR34 orthologues and the search for the endogenous agonist should consider additional chemical entities [11].
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
YL-365 Small molecule or natural product Hs Antagonist 7.8 pIC50 1
pIC50 7.8 (IC50 1.7x10-8 M) [1]
Antagonist Comments
Aminoethyl-carbamoyl ATP has been identified as an antagonist of carp GPR34, indicating ligand promiscuity with non-lipid compounds [11].
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Phospholipase A2 stimulation
Comments:  LysoPS induces a dose-dependent increase in ERK activation in CHO/hGPR34 cells [15].
References:  8,14
Tissue Distribution Click here for help
Mast cells, placenta, spleen, thymus, ovary
Species:  Human
Technique:  RT-PCR
References:  15
Heart, brain, placenta, skeletal muscle, pancreas, spleen, thymus, prostate, testis, ovary, lung, liver, small intestine, colon, peripheral blood
Species:  Human
Technique:  Northern Blot
References:  5,12
Brain (caudate, frontal cortex, putamen, thalamus, hypothalamus, pons), liver, adipose tissue, placenta, uterus, fetal liver/spleen, retina, tonsillar germinal center B cells
Species:  Human
Technique:  Northern blot
References:  9
Species:  Human
Technique:  In situ hybridisation, Microarray analysis
References:  4
Mast cells, spleen, lung, splenic B and T cells
Species:  Mouse
Technique:  RT-PCR
References:  15
Heart, brain, spleen, lung, kidney, liver, testis
Species:  Mouse
Technique:  Northern blot
References:  12
Frontal cortex, cortex, striatum, midbrain, hippocampus, medulla pons, cerebellum, spleen
Species:  Rat
Technique:  Northern blot
References:  9
Mast cells, spleen, macrophages
Species:  Rat
Technique:  RT-PCR
References:  15
Primary olfactory cortex, supraoptic nucleus, nucleus of the lateral olfactory tract, suprachiasmatic nucleus, hippocampus, hypothalamic nuclei, anteroventral thalamic nucleus
Species:  Rat
Technique:  In situ hybridisation
References:  9
Tissue Distribution Comments
Ubiquitous expression of GPR34 has been verified by Northern Blot, qRT-PCR and microarray analysis, mediated by one promoter in humans and two promoters in rodents. In mice there is evidence for tissue specific expression of promoters [5].
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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Physiological Functions Click here for help
Mast cell degranulation in vitro
Species:  Human
Tissue:  Mast cells
References:  15
Physiological Functions Comments
Potential role for GPR34 in neuroinflammatory processes [4]. GPR34 mRNA has been identified as differentially expressed in melanoma metastasis [10].
Clinically-Relevant Mutations and Pathophysiology Comments
Putative candidate gene for ocular diseases mapped to the Xp11.4 region [7].

Chromosomal translocation (X;14)(p11.4;q32.33) in marginal zone lymphoma causes up-regulation of GPR34, as identified by qRT-PCR and immunohistochemistry [2].
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  N295S
Global MAF (%):  2
Subpopulation MAF (%):  AFR|AMR: 8|1
Minor allele count:  G=0.020/33
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession: 
Validation:  1000 Genomes, Frequency
General Comments
Different receptor isoforms may have different functions. GPR34 displays low allelic variability, but alternative initiation of translation [5]. Lysophosphatidylthreonine does not activate GPR34 suggesting an alternative receptor for mast cell degranulation [6]. Molecular modelling of binding site docking and mutagenesis indicates that GPR34 has the necessary conserved features of P2Y receptors [3].


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1. A-González N, Castrillo A. (2011) Liver X receptors as regulators of macrophage inflammatory and metabolic pathways. Biochim Biophys Acta, 1812 (8): 982-94. [PMID:21193033]

2. Baens M, Finalet Ferreiro J, Tousseyn T, Urbankova H, Michaux L, de Leval L, Dierickx D, Wolter P, Sagaert X, Vandenberghe P et al.. (2012) t(X;14)(p11.4;q32.33) is recurrent in marginal zone lymphoma and up-regulates GPR34. Haematologica, 97 (2): 184-8. [PMID:22058210]

3. Bhatnagar S, Mishra S, Pathak R. (2011) Mining human genome for novel purinergic P2Y receptors: a sequence analysis and molecular modeling approach. J Recept Signal Transduct Res, 31 (1): 75-84. [PMID:21142848]

4. Bédard A, Tremblay P, Chernomoretz A, Vallières L. (2007) Identification of genes preferentially expressed by microglia and upregulated during cuprizone-induced inflammation. Glia, 55 (8): 777-89. [PMID:17285589]

5. Engemaier E, Römpler H, Schöneberg T, Schulz A. (2006) Genomic and supragenomic structure of the nucleotide-like G-protein-coupled receptor GPR34. Genomics, 87 (2): 254-64. [PMID:16338117]

6. Iwashita M, Makide K, Nonomura T, Misumi Y, Otani Y, Ishida M, Taguchi R, Tsujimoto M, Aoki J, Arai H et al.. (2009) Synthesis and evaluation of lysophosphatidylserine analogues as inducers of mast cell degranulation. Potent activities of lysophosphatidylthreonine and its 2-deoxy derivative. J Med Chem, 52 (19): 5837-63. [PMID:19743861]

7. Jacobi FK, Broghammer M, Pesch K, Zrenner E, Berger W, Meindl A, Pusch CM. (2000) Physical mapping and exclusion of GPR34 as the causative gene for congenital stationary night blindness type 1. Hum Genet, 107 (1): 89-91. [PMID:10982042]

8. Kitamura H, Makide K, Shuto A, Ikubo M, Inoue A, Suzuki K, Sato Y, Nakamura S, Otani Y, Ohwada T et al.. (2012) GPR34 is a receptor for lysophosphatidylserine with a fatty acid at the sn-2 position. J Biochem, 151 (5): 511-8. [PMID:22343749]

9. Marchese A, Sawzdargo M, Nguyen T, Cheng R, Heng HH, Nowak T, Im DS, Lynch KR, George SR, O'dowd BF. (1999) Discovery of three novel orphan G-protein-coupled receptors. Genomics, 56 (1): 12-21. [PMID:10036181]

10. Qin Y, Verdegaal EM, Siderius M, Bebelman JP, Smit MJ, Leurs R, Willemze R, Tensen CP, Osanto S. (2011) Quantitative expression profiling of G-protein-coupled receptors (GPCRs) in metastatic melanoma: the constitutively active orphan GPCR GPR18 as novel drug target. Pigment Cell Melanoma Res, 24 (1): 207-18. [PMID:20880198]

11. Ritscher L, Engemaier E, Stäubert C, Liebscher I, Schmidt P, Hermsdorf T, Römpler H, Schulz A, Schöneberg T. (2012) The ligand specificity of the G-protein-coupled receptor GPR34. Biochem J, 443 (3): 841-50. [PMID:22348703]

12. Schöneberg T, Schulz A, Grosse R, Schade R, Henklein P, Schultz G, Gudermann T. (1999) A novel subgroup of class I G-protein-coupled receptors. Biochim Biophys Acta, 1446 (1-2): 57-70. [PMID:10395919]

13. 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]

14. Sugo T, Mori M. (2008) Another ligand fishing for G protein-coupled receptor 14. Discovery of urotensin II-related peptide in the rat brain. Peptides, 29 (5): 809-12. [PMID:17628210]

15. Sugo T, Tachimoto H, Chikatsu T, Murakami Y, Kikukawa Y, Sato S, Kikuchi K, Nagi T, Harada M, Ogi K, Ebisawa M, Mori M. (2006) Identification of a lysophosphatidylserine receptor on mast cells. Biochem Biophys Res Commun, 341 (4): 1078-87. [PMID:16460680]


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