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Gene Review

GPR37  -  G protein-coupled receptor 37 (endothelin...

Homo sapiens

Synonyms: EDNRBL, ETBR-LP-1, Endothelin B receptor-like protein 1, G-protein coupled receptor 37, PAELR, ...
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Disease relevance of GPR37


High impact information on GPR37


Psychiatry related information on GPR37

  • In the absence of Pael-R, overexpression of TRX in all neurons increased the level of locomotor activity in aged flies and extended the mean longevity by 15% [7].

Chemical compound and disease context of GPR37


Biological context of GPR37

  • The GPR37 genomic sequence was mapped to chromosome 7q31, and it was isolated upon screening of a chromosome 7-specific genomic library [8].
  • The GPR37 cDNA predicts a single open reading frame coding for a 613-amino-acid protein with seven hydrophobic transmembrane domains [8].
  • Although the ligand for the putative GPR37 receptor has not been identified, its deduced amino acid sequence shows a high degree of homology (approximately 40% in the transmembrane regions) with most mammalian peptide-specific G-protein-coupled receptors and particularly with the human endothelin-B, bombesin-BB1, and bombesin-BB2 receptors [8].
  • The GPR37 gene spans more than 25 kb and contains two exons and a single intron which interrupts the GPR37 cDNA within the sequence encoding the presumed third transmembrane domain [8].
  • A cDNA sequence encoding a putative peptide-specific G-protein-coupled receptor (GPR37) was isolated from a set of human brain frontal lobe expressed sequence tags [8].

Anatomical context of GPR37


Associations of GPR37 with chemical compounds

  • Parkin specifically ubiquitinates the unfolded Pael-R and promotes its degradation, resulting in suppression of cell death induced by the accumulation of unfolded Pael-R [1].
  • Electrophysiological recordings in frog oocytes and in mammalian cell lines as well as Ca(2+) mobilisation assays revealed nanomolar affinities of HA to GPR37 [11].
  • The predicted mouse GPR37 protein contains seven putative hydrophobic transmembrane domains, as well as a long (249 amino acid residues), arginine- and proline-rich amino-terminal extracellular domain, which is also a distinctive feature of the human GPR37 receptor [12].

Regulatory relationships of GPR37

  • Specific binding of radiolabeled ET-1 and ET-3 to membrane preparations and to intact cells expressing recombinant protein of hET(B)R-LP/HA did not show any significant difference of binding properties between cells transfected with plasmid DNA, hET(B)R-LP/HA/pcDNA1/Amp, and cells untransfected, including both COS7 cells and HEK293 cells [13].

Other interactions of GPR37


  1. Pael receptor, endoplasmic reticulum stress, and Parkinson's disease. Takahashi, R., Imai, Y. J. Neurol. (2003) [Pubmed]
  2. Suppressive effects of 4-phenylbutyrate on the aggregation of Pael receptors and endoplasmic reticulum stress. Kubota, K., Niinuma, Y., Kaneko, M., Okuma, Y., Sugai, M., Omura, T., Uesugi, M., Uehara, T., Hosoi, T., Nomura, Y. J. Neurochem. (2006) [Pubmed]
  3. 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. Kitao, Y., Imai, Y., Ozawa, K., Kataoka, A., Ikeda, T., Soda, M., Nakimawa, K., Kiyama, H., Stern, D.M., Hori, O., Wakamatsu, K., Ito, S., Itohara, S., Takahashi, R., Ogawa, S. Hum. Mol. Genet. (2007) [Pubmed]
  4. An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Imai, Y., Soda, M., Inoue, H., Hattori, N., Mizuno, Y., Takahashi, R. Cell (2001) [Pubmed]
  5. Parkin suppresses dopaminergic neuron-selective neurotoxicity induced by Pael-R in Drosophila. Yang, Y., Nishimura, I., Imai, Y., Takahashi, R., Lu, B. Neuron (2003) [Pubmed]
  6. Pael-R is accumulated in Lewy bodies of Parkinson's disease. Murakami, T., Shoji, M., Imai, Y., Inoue, H., Kawarabayashi, T., Matsubara, E., Harigaya, Y., Sasaki, A., Takahashi, R., Abe, K. Ann. Neurol. (2004) [Pubmed]
  7. Thioredoxin suppresses Parkin-associated endothelin receptor-like receptor-induced neurotoxicity and extends longevity in Drosophila. Umeda-Kameyama, Y., Tsuda, M., Ohkura, C., Matsuo, T., Namba, Y., Ohuchi, Y., Aigaki, T. J. Biol. Chem. (2007) [Pubmed]
  8. Cloning of GPR37, a gene located on chromosome 7 encoding a putative G-protein-coupled peptide receptor, from a human frontal brain EST library. Marazziti, D., Golini, E., Gallo, A., Lombardi, M.S., Matteoni, R., Tocchini-Valentini, G.P. Genomics (1997) [Pubmed]
  9. A product of the human gene adjacent to parkin is a component of Lewy bodies and suppresses Pael receptor-induced cell death. Imai, Y., Soda, M., Murakami, T., Shoji, M., Abe, K., Takahashi, R. J. Biol. Chem. (2003) [Pubmed]
  10. The pathological role of Pael-receptor/GPR37 in AR-JP. Takahahshi, R. Parkinsonism Relat. Disord. (2006) [Pubmed]
  11. The neuropeptide head activator is a high-affinity ligand for the orphan G-protein-coupled receptor GPR37. Rezgaoui, M., Süsens, U., Ignatov, A., Gelderblom, M., Glassmeier, G., Franke, I., Urny, J., Imai, Y., Takahashi, R., Schaller, H.C. J. Cell. Sci. (2006) [Pubmed]
  12. Molecular cloning and chromosomal localization of the mouse Gpr37 gene encoding an orphan G-protein-coupled peptide receptor expressed in brain and testis. Marazziti, D., Gallo, A., Golini, E., Matteoni, R., Tocchini-Valentini, G.P. Genomics (1998) [Pubmed]
  13. A novel endothelin receptor type-B-like gene enriched in the brain. Zeng, Z., Su, K., Kyaw, H., Li, Y. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
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