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Gene and Protein Information  |
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| 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 |
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| Specialist databases | |
| GPCRdb | gpr34_human (Hs), gpr34_mouse (Mm), q6xce7_rat (Rn) |
| Other databases | |
| Alphafold | Q9UPC5 (Hs), Q9R1K6 (Mm), Q6XCE7 (Rn) |
| ChEMBL Target | CHEMBL3562165 (Hs), CHEMBL1075291 (Mm), CHEMBL1075235 (Rn) |
| Ensembl Gene | ENSG00000171659 (Hs), ENSMUSG00000040229 (Mm), ENSRNOG00000039759 (Rn) |
| Entrez Gene | 2857 (Hs), 23890 (Mm), 554353 (Rn) |
| Human Protein Atlas | ENSG00000171659 (Hs) |
| KEGG Gene | hsa:2857 (Hs), mmu:23890 (Mm), rno:554353 (Rn) |
| OMIM | 300241 (Hs) |
| Pharos | Q9UPC5 (Hs) |
| RefSeq Nucleotide | NM_005300 (Hs), NM_011823 (Mm), NM_001024925 (Rn) |
| RefSeq Protein | NP_005291 (Hs), NP_035953 (Mm), NP_001020096 (Rn) |
| UniProtKB | Q9UPC5 (Hs), Q9R1K6 (Mm), Q6XCE7 (Rn) |
| Wikipedia | GPR34 (Hs) |
| Natural/Endogenous Ligands |
| lysophosphatidylserine |
| 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 
| Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||
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| 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
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| 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
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| 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 |
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| Physiological Functions
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| 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
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| 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]. |
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]
