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target has curated data in GtoImmuPdb
Target id: 103
Nomenclature: GPR37
Family: Class A Orphans
This receptor has a proposed ligand; see the Latest Pairings page for more information.
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 | 613 | 7q31.33 | GPR37 | G protein-coupled receptor 37 | 21 |
| Mouse | 7 | 600 | 6 11.65 cM | Gpr37 | G protein-coupled receptor 37 | 9 |
| Rat | 7 | 603 | 4q22 | Gpr37 | G protein-coupled receptor 37 | |
| Previous and Unofficial Names |
| EDNRBL | EDNRLB | PAELR | hET(B)R-LP | G-protein coupled receptor CNS1 | parkin-associated endothelin B-like receptor | Endothelin B receptor-like protein 1 |
| Database Links |
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| Specialist databases | |
| GPCRdb | gpr37_human (Hs), gpr37_mouse (Mm), gpr37_rat (Rn) |
| Other databases | |
| Alphafold | O15354 (Hs), Q9QY42 (Mm), Q9QYC6 (Rn) |
| ChEMBL Target | CHEMBL4523862 (Hs) |
| Ensembl Gene | ENSG00000170775 (Hs), ENSMUSG00000039904 (Mm), ENSRNOG00000002524 (Rn) |
| Entrez Gene | 2861 (Hs), 14763 (Mm), 117549 (Rn) |
| Human Protein Atlas | ENSG00000170775 (Hs) |
| KEGG Gene | hsa:2861 (Hs), mmu:14763 (Mm), rno:117549 (Rn) |
| OMIM | 602583 (Hs) |
| Pharos | O15354 (Hs) |
| RefSeq Nucleotide | NM_005302 (Hs), NM_010338 (Mm), NM_057201 (Rn) |
| RefSeq Protein | NP_005293 (Hs), NP_034468 (Mm), NP_476549 (Rn) |
| UniProtKB | O15354 (Hs), Q9QY42 (Mm), Q9QYC6 (Rn) |
| Wikipedia | GPR37 (Hs) |
| Natural/Endogenous Ligands |
| prosaptide {Sp: Human} |
| prosaposin |
| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Although it was reported that mammalian tissues contain a peptide of identical amino acid sequence to Hydra head activator [2] and that head activator is an agonist of GPR37 [17], there is currently no evidence for the presence of a gene encoding this peptide in any sequenced genome. However, the C-terminal sequences of head activator and prosaptide are similar, which may explain the activity of head activator on GPR37 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Immunopharmacology Comments |
| GPR37 has been implicated in the resolution of inflammatory pain, at least in part via activation by the specialized proresolving mediator neuroprotectin D1 [1,16,22]. |
| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gi/Go family | Adenylyl cyclase inhibition |
| Comments: Pertussis toxin pre-treatment completely inhibited the ability of prosaptide to stimulate ERK phosphorylation in GPR37-transfected cells [13]. It has been reported that neuropeptide head activator signal transduction through GPR37 required Ca2+ influx through a channel of the transient receptor potential (TRP) family and activation of the Ca2+-dependent calmodulin kinase and phosphoinositide 3-kinase [17]. | |
| References: 17 | |
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| The mRNA level of GPR37 in rat striatum decreased within 2 hours after methamphetamine treatment [15]. The expression of GPR37 in MN9D cell line was upregulated after 0.5 hour of exposure to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+ and remained upregulated up to 48 hours [20]. | ||||||||
| Expression Datasets |
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| Functional Assays
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| Physiological Functions
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| Physiological Consequences of Altering Gene Expression
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| Physiological Consequences of Altering Gene Expression Comments | ||||||||||
| It is reported that overexpression of GPR37 led to aggregate formation, retention of the receptor in the cytoplasm and low survival rates of transfected cells [17]. | ||||||||||
| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Gene Expression and Pathophysiology Comments | |
| GPR37 has been reported to be a substrate for the ubiquitin ligase parkin, a gene product responsible for autosomal recessive juvenile Parkinsonism and to accumulate in the brains of patients with this condition [4], as well as in Lewy bodies in the brains of adult patients with Parkinson's disease [14]. Hypermethylation of GPR37 has been found in acute myeloid leukemia [18]. |
| General Comments |
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Proposed ligand (prosaposin), supported by one publication [13]. GPR37 has been reported to be a substrate for the ubiquitin ligase parkin, a gene product responsible for autosomal recessive juvenile Parkinsonism and to accumulate in the brains of patients with this condition [4]. |
1. Bang S, Xie YK, Zhang ZJ, Wang Z, Xu ZZ, Ji RR. (2018) GPR37 regulates macrophage phagocytosis and resolution of inflammatory pain. J Clin Invest, 128 (8): 3568-3582. [PMID:30010619]
2. Bodenmüller H, Schaller HC. (1981) Conserved amino acid sequence of a neuropeptide, the head activator, from coelenterates to humans. Nature, 293 (5833): 579-80. [PMID:7290191]
3. Imai Y, Inoue H, Kataoka A, Hua-Qin W, Masuda M, Ikeda T, Tsukita K, Soda M, Kodama T, Fuwa T, Honda Y, Kaneko S, Matsumoto S, Wakamatsu K, Ito S, Miura M, Aosaki T, Itohara S, Takahashi R. (2007) Pael receptor is involved in dopamine metabolism in the nigrostriatal system. Neurosci Res, 59 (4): 413-25. [PMID:17889953]
4. Imai Y, Soda M, Inoue H, Hattori N, Mizuno Y, Takahashi R. (2001) An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell, 105 (7): 891-902. [PMID:11439185]
5. Ito J, Ito M, Nambu H, Fujikawa T, Tanaka K, Iwaasa H, Tokita S. (2009) Anatomical and histological profiling of orphan G-protein-coupled receptor expression in gastrointestinal tract of C57BL/6J mice. Cell Tissue Res, 338 (2): 257-69. [PMID:19763624]
6. Kitao Y, Imai Y, Ozawa K, Kataoka A, Ikeda T, Soda M, Nakimawa K, Kiyama H, Stern DM, Hori O, Wakamatsu K, Ito S, Itohara S, Takahashi R, Ogawa S. (2007) Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic reticulum stress and dopamine toxicity, which is enhanced under condition of parkin inactivation. Hum Mol Genet, 16 (1): 50-60. [PMID:17116640]
7. Marazziti D, Di Pietro C, Golini E, Mandillo S, Matteoni R, Tocchini-Valentini GP. (2009) Induction of macroautophagy by overexpression of the Parkinson's disease-associated GPR37 receptor. FASEB J, 23 (6): 1978-87. [PMID:19218498]
8. Marazziti D, Di Pietro C, Mandillo S, Golini E, Matteoni R, Tocchini-Valentini GP. (2011) Absence of the GPR37/PAEL receptor impairs striatal Akt and ERK2 phosphorylation, DeltaFosB expression, and conditioned place preference to amphetamine and cocaine. FASEB J, 25 (6): 2071-81. [PMID:21372109]
9. Marazziti D, Gallo A, Golini E, Matteoni R, Tocchini-Valentini GP. (1998) Molecular cloning and chromosomal localization of the mouse Gpr37 gene encoding an orphan G-protein-coupled peptide receptor expressed in brain and testis. Genomics, 53 (3): 315-24. [PMID:9799598]
10. Marazziti D, Golini E, Gallo A, Lombardi MS, Matteoni R, Tocchini-Valentini GP. (1997) Cloning of GPR37, a gene located on chromosome 7 encoding a putative G-protein-coupled peptide receptor, from a human frontal brain EST library. Genomics, 45 (1): 68-77. [PMID:9339362]
11. Marazziti D, Golini E, Mandillo S, Magrelli A, Witke W, Matteoni R, Tocchini-Valentini GP. (2004) Altered dopamine signaling and MPTP resistance in mice lacking the Parkinson's disease-associated GPR37/parkin-associated endothelin-like receptor. Proc Natl Acad Sci USA, 101 (27): 10189-94. [PMID:15218106]
12. Marazziti D, Mandillo S, Di Pietro C, Golini E, Matteoni R, Tocchini-Valentini GP. (2007) GPR37 associates with the dopamine transporter to modulate dopamine uptake and behavioral responses to dopaminergic drugs. Proc Natl Acad Sci USA, 104 (23): 9846-51. [PMID:17519329]
13. Meyer RC, Giddens MM, Schaefer SA, Hall RA. (2013) GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin. Proc Natl Acad Sci USA, 110 (23): 9529-34. [PMID:23690594]
14. Murakami T, Shoji M, Imai Y, Inoue H, Kawarabayashi T, Matsubara E, Harigaya Y, Sasaki A, Takahashi R, Abe K. (2004) Pael-R is accumulated in Lewy bodies of Parkinson's disease. Ann Neurol, 55 (3): 439-42. [PMID:14991825]
15. Nakahara T, Kuroki T, Ohta E, Kajihata T, Yamada H, Yamanaka M, Hashimoto K, Tsutsumi T, Hirano M, Uchimura H. (2003) Effect of the neurotoxic dose of methamphetamine on gene expression of parkin and Pael-receptors in rat striatum. Parkinsonism Relat Disord, 9 (4): 213-9. [PMID:12618056]
16. Qu L, Caterina MJ. (2018) Accelerating the reversal of inflammatory pain with NPD1 and its receptor GPR37. J Clin Invest, 128 (8): 3246-3249. [PMID:30010628]
17. Rezgaoui M, Süsens U, Ignatov A, Gelderblom M, Glassmeier G, Franke I, Urny J, Imai Y, Takahashi R, Schaller HC. (2006) The neuropeptide head activator is a high-affinity ligand for the orphan G-protein-coupled receptor GPR37. J Cell Sci, 119 (Pt 3): 542-9. [PMID:16443751]
18. Toyota M, Kopecky KJ, Toyota MO, Jair KW, Willman CL, Issa JP. (2001) Methylation profiling in acute myeloid leukemia. Blood, 97 (9): 2823-9. [PMID:11313277]
19. Wang HQ, Imai Y, Inoue H, Kataoka A, Iita S, Nukina N, Takahashi R. (2008) Pael-R transgenic mice crossed with parkin deficient mice displayed progressive and selective catecholaminergic neuronal loss. J Neurochem, 107 (1): 171-85. [PMID:18691389]
20. Wang J, Duhart HM, Xu Z, Patterson TA, Newport GD, Ali SF. (2008) Comparison of the time courses of selective gene expression and dopaminergic depletion induced by MPP+ in MN9D cells. Neurochem Int, 52 (6): 1037-43. [PMID:18069091]
21. Zeng Z, Su K, Kyaw H, Li Y. (1997) A novel endothelin receptor type-B-like gene enriched in the brain. Biochem Biophys Res Commun, 233 (2): 559-67. [PMID:9144577]
22. Zhang LY, Jia MR, Sun T. (2018) The roles of special proresolving mediators in pain relief. Rev Neurosci, 29 (6): 645-660. [PMID:29420307]
