Nomenclature: GPR34

Family: Class A Orphans

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 381 Xp11.4-p11.3 GPR34 G protein-coupled receptor 34 11
Mouse 7 375 X A1.3 Gpr34 G protein-coupled receptor 34 11
Rat 7 373 Xq12 Gpr34 G protein-coupled receptor 34 8
Previous and Unofficial Names
GPR34
GPR34_predicted
G protein-coupled receptor 34
G-protein-coupled receptor GPR34
G-protein-coupled receptor GPR34 (predicted)
probable G-protein coupled receptor 34
Database Links
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Natural/Endogenous Ligands
lysophosphatidylserine
Comments: Proposed ligand in several publications but not replicated in a recent study based on β-arrestin recruitment [12].
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
lysophosphatidylserine Mm Agonist 7.31 pEC50 14
pEC50 7.31 (EC50 4.9x10-8 M) [14]
lysophosphatidylserine Hs Full agonist 6.57 – 6.89 pEC50 7,14
pEC50 6.57 – 6.89 (EC50 2.7x10-7 – 1.29x10-7 M) [7,14]
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 [10].
Antagonist Comments
Aminoethyl-carbamoyl ATP has been identified as an antagonist of carp GPR34, indicating ligand promiscuity with non-lipid compounds [10].
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Phospholipase A2 stimulation
Comments:  LysoPS induces a dose-dependent increase in ERK activation in CHO/hGPR34 cells [14].
References:  7,13
Tissue Distribution
Mast cells, placenta, spleen, thymus, ovary
Species:  Human
Technique:  RT-PCR
References:  14
Heart, brain, placenta, skeletal muscle, pancreas, spleen, thymus, prostate, testis, ovary, lung, liver, small intestine, colon, peripheral blood
Species:  Human
Technique:  Northern Blot
References:  4,11
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:  8
Microglia
Species:  Human
Technique:  In situ hybridisation, Microarray analysis
References:  3
Mast cells, spleen, lung, splenic B and T cells
Species:  Mouse
Technique:  RT-PCR
References:  14
Heart, brain, spleen, lung, kidney, liver, testis
Species:  Mouse
Technique:  Northern blot
References:  11
Frontal cortex, cortex, striatum, midbrain, hippocampus, medulla pons, cerebellum, spleen
Species:  Rat
Technique:  Northern blot
References:  8
Mast cells, spleen, macrophages
Species:  Rat
Technique:  RT-PCR
References:  14
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:  8
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 [4].
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
Mast cell degranulation in vitro
Species:  Human
Tissue:  Mast cells
References:  14
Physiological Functions Comments
Potential role for GPR34 in neuroinflammatory processes [3]. GPR34 mRNA has been identified as differentially expressed in melanoma metastasis [9].
Clinically-Relevant Mutations and Pathophysiology Comments
Putative candidate gene for ocular diseases mapped to the Xp11.4 region [6].

Chromosomal translocation (X;14)(p11.4;q32.33) in marginal zone lymphoma causes up-regulation of GPR34, as identified by qRT-PCR and immunohistochemistry [1].
Biologically Significant Variants
Type:  SNP
Species:  Human
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 [4]. Lysophosphatidylthreonine does not activate GPR34 suggesting an alternative receptor for mast cell degranulation [5]. Molecular modelling of binding site docking and mutagenesis indicates that GPR34 has the necessary conserved features of P2Y receptors [2].

REFERENCES

1. 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. Haematologica97 (2): 184-8. [PMID:22058210]

2. 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]

3. Bédard A, Tremblay P, Chernomoretz A, Vallières L. (2007) Identification of genes preferentially expressed by microglia and upregulated during cuprizone-induced inflammation. Glia55 (8): 777-89. [PMID:17285589]

4. Engemaier E, Römpler H, Schöneberg T, Schulz A. (2006) Genomic and supragenomic structure of the nucleotide-like G-protein-coupled receptor GPR34. Genomics87 (2): 254-64. [PMID:16338117]

5. 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]

6. 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]

7. 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]

8. 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. Genomics56 (1): 12-21. [PMID:10036181]

9. Qin Y, Verdegaal EM, Siderius M, Bebelman JP, Smit MJ, Leurs R, Willemze R, Tensen CP, Osanto S. (2010) 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,  [Epub ahead of print]. [PMID:20880198]

10. 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]

11. 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. Acta1446 (1-2): 57-70. [PMID:10395919]

12. 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 Screen18 (5): 599-609. [PMID:23396314]

13. Sugo T, Mori M. (2008) Another ligand fishing for G protein-coupled receptor 14. Discovery of urotensin II-related peptide in the rat brain. Peptides29 (5): 809-12. [PMID:17628210]

14. 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]

To cite this database page, please use the following:

Anthony P. Davenport, Stephen Alexander, Joanna L. Sharman, Adam J. Pawson, Helen E. Benson, Amy E. Monaghan, Wen Chiy Liew, Chido Mpamhanga, Jim Battey, Richard V. Benya, Robert T. Jensen, Sadashiva Karnik, Evi Kostenis, Eliot Spindel, Laura Storjohann, Kalyan Tirupula, Tom I. Bonner, Richard Neubig, Jean-Philippe Pin, Michael Spedding, Anthony Harmar.
Class A Orphans: GPR34. Last modified on 26/11/2013. Accessed on 22/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=101.

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