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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 | 330 | 1p36.11 | GPR3 | G protein-coupled receptor 3 | |
| Mouse | 7 | 330 | 4 D2.3 | Gpr3 | G-protein coupled receptor 3 | |
| Rat | 7 | 329 | 5q36 | Gpr3 | G protein-coupled receptor 3 | |
| Previous and Unofficial Names |
| Gpcr21 | GPCR3 | ACCA orphan receptor | adenylate cyclase constitutive activator | G protein-coupled receptor R4 | Gpcr20 |
| Database Links |
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| Specialist databases | |
| GPCRdb | gpr3_human (Hs), gpr3_mouse (Mm), gpr3_rat (Rn) |
| Other databases | |
| Alphafold | P46089 (Hs), P35413 (Mm), Q8K1Q3 (Rn) |
| ChEMBL Target | CHEMBL4523856 (Hs) |
| Ensembl Gene | ENSG00000181773 (Hs), ENSMUSG00000049649 (Mm), ENSRNOG00000009540 (Rn) |
| Entrez Gene | 2827 (Hs), 14748 (Mm), 266769 (Rn) |
| Human Protein Atlas | ENSG00000181773 (Hs) |
| KEGG Gene | hsa:2827 (Hs), mmu:14748 (Mm), rno:266769 (Rn) |
| OMIM | 600241 (Hs) |
| Pharos | P46089 (Hs) |
| RefSeq Nucleotide | NM_005281 (Hs), NM_008154 (Mm), NM_153727 (Rn) |
| RefSeq Protein | NP_005272 (Hs), NP_032180 (Mm), NP_714949 (Rn) |
| UniProtKB | P46089 (Hs), P35413 (Mm), Q8K1Q3 (Rn) |
| Wikipedia | GPR3 (Hs) |
| Natural/Endogenous Ligands |
| sphingosine 1-phosphate |
| Comments: Proposed ligand, single publication |
Download all structure-activity data for this target as a CSV file 
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proposed ligand (sphingosine 1-phosphate), supported by one publication [7], this result was not repeated in β-arrestin assay [10] and so the GPR3 is still recognised as an orphan. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gs family | Adenylyl cyclase stimulation |
| Comments: When expressed transiently in HEK293 cells, gpr3 confers constitutive activation of adenylate cyclase (AC) similar in amplitude to that seen with fully activated Gαs-coupled receptors | |
| References: 1 | |
| Expression Datasets |
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| Physiological Functions
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| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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| Biologically Significant Variants
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| General Comments |
| A study suggests that GPR3 normal function is involved in the modulation of behavioral responses to stress [8]. |
1. Eggerickx D, Denef JF, Labbe O, Hayashi Y, Refetoff S, Vassart G, Parmentier M, Libert F. (1995) Molecular cloning of an orphan G-protein-coupled receptor that constitutively activates adenylate cyclase. Biochem J, 309 ( Pt 3): 837-43. [PMID:7639700]
2. Ledent C, Demeestere I, Blum D, Petermans J, Hämäläinen T, Smits G, Vassart G. (2005) Premature ovarian aging in mice deficient for Gpr3. Proc Natl Acad Sci USA, 102 (25): 8922-6. [PMID:15956199]
3. Mehlmann LM, Saeki Y, Tanaka S, Brennan TJ, Evsikov AV, Pendola FL, Knowles BB, Eppig JJ, Jaffe LA. (2004) The Gs-linked receptor GPR3 maintains meiotic arrest in mammalian oocytes. Science, 306 (5703): 1947-50. [PMID:15591206]
4. Ruiz-Medina J, Ledent C, Valverde O. (2011) GPR3 orphan receptor is involved in neuropathic pain after peripheral nerve injury and regulates morphine-induced antinociception. Neuropharmacology, 61 (1-2): 43-50. [PMID:21352831]
5. Tanaka S, Shaikh IM, Chiocca EA, Saeki Y. (2009) The Gs-linked receptor GPR3 inhibits the proliferation of cerebellar granule cells during postnatal development. PLoS ONE, 4 (6): e5922. [PMID:19526062]
6. Thathiah A, Spittaels K, Hoffmann M, Staes M, Cohen A, Horré K, Vanbrabant M, Coun F, Baekelandt V, Delacourte A, Fischer DF, Pollet D, De Strooper B, Merchiers P. (2009) The orphan G protein-coupled receptor 3 modulates amyloid-beta peptide generation in neurons. Science, 323: 946-951. [PMID:19213921]
7. Uhlenbrock K, Gassenhuber H, Kostenis E. (2002) Sphingosine 1-phosphate is a ligand of the human gpr3, gpr6 and gpr12 family of constitutively active G protein-coupled receptors. Cell Signal, 14: 941-953. [PMID:12220620]
8. Valverde O, Célérier E, Baranyi M, Vanderhaeghen P, Maldonado R, Sperlagh B, Vassart G, Ledent C. (2009) GPR3 receptor, a novel actor in the emotional-like responses. PLoS ONE, 4 (3): e4704. [PMID:19259266]
9. Ye C, Zhang Z, Wang Z, Hua Q, Zhang R, Xie X. (2014) Identification of a novel small-molecule agonist for human G protein-coupled receptor 3. J Pharmacol Exp Ther, 349 (3): 437-43. [PMID:24633425]
10. Yin H, Chu A, Li W, Wang B, Shelton F, Otero F, Nguyen DG, Caldwell JS, Chen YA. (2009) Lipid G protein-coupled receptor ligand identification using beta-arrestin PathHunter assay. J Biol Chem, 284: 12328-12338. [PMID:19286662]
