| Post Translational Modifications | The N-terminus is cleaved by ADAM10 metalloproteinase.mediating limited proteolysis leading to the release of receptor ectodomain by shedding. In addition, cleaved by FURIN between Arg-54 and Asp-55. Ubiquitinated by PRKN in the presence of UBE2E1 and UBE2L3 in the endoplasmic reticulum. The unfolded form is specifically ubiquitinated by SYVN1, which promotes its proteasomal degradation and prevents neuronal cell death. |
| Function | G-protein-coupled receptor that plays a role in several physiological pathways such as resolution of inflammatory pain and oligodendrocyte differentiation. Acts as a receptor for several ligands including prosaposin, osteocalcin or neuroprotectin D1. Ligand binding induces endocytosis, followed by an ERK phosphorylation cascade. Acts as a receptor for osteocalcin (OCN) to regulate oligodendrocyte differentiation and central nervous system myelination. Mechanistically, plays a negative role in oligodendrocyte differentiation and myelination during development via activation of the ERK1/2 signaling pathway. Therefore, regulates the stability of myelin or resistance of myelin itself to demyelination. Upon activation by neuroprotectin D1 (NPD1), promotes the activation of phagocytosis in macrophages as well as the shift in cytokine release toward an anti-inflammatory profile, and thus helps to reverse inflammatory pain. In addition, the increased macrophage phagocytosis mediates protection against sepsis upon pathogen infection. Additionally, extracellular vesicles derived from efferocyte express prosaposin, which binds to macrophage GPR37 to increase expression of the efferocytosis receptor TIM4 via an ERK-AP1-dependent signaling axis, leading to increased macrophage efferocytosis efficiency and accelerated resolution of inflammation. May also act as a maturation factor of LRP6, protecting LRP6 from the endoplasmic reticulum (ER)-associated protein degradation (ERAD) and thereby promoting the Wnt/beta-catenin signaling pathway. |
| Protein Name | Prosaposin Receptor Gpr37Endothelin B Receptor-Like Protein 1Etbr-Lp-1G-Protein Coupled Receptor 37Parkin-Associated Endothelin Receptor-Like ReceptorPaelr |
| Database Links | Reactome: R-HSA-375276Reactome: R-HSA-418594 |
| Cellular Localisation | Cell ProjectionDendriteSynapseCell MembraneMulti-Pass Membrane ProteinEndoplasmic Reticulum Membrane |
| Alternative Protein Names | Prosaposin Receptor Gpr37 proteinEndothelin B Receptor-Like Protein 1 proteinEtbr-Lp-1 proteinG-Protein Coupled Receptor 37 proteinParkin-Associated Endothelin Receptor-Like Receptor proteinPaelr proteinGPR37 protein |
Information sourced from Uniprot.org
