O15354 · GPR37_HUMAN
- ProteinProsaposin receptor GPR37
- GeneGPR37
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids613 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
G-protein-coupled receptor that plays a role in several physiological pathways such as resolution of inflammatory pain and oligodendrocyte differentiation (By similarity).
Acts as a receptor for several ligands including prosaposin, osteocalcin or neuroprotectin D1. Ligand binding induces endocytosis, followed by an ERK phosphorylation cascade (PubMed:11439185, PubMed:23690594).
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 (By similarity).
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 (PubMed:28341812).
Acts as a receptor for several ligands including prosaposin, osteocalcin or neuroprotectin D1. Ligand binding induces endocytosis, followed by an ERK phosphorylation cascade (PubMed:11439185, PubMed:23690594).
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 (By similarity).
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 (PubMed:28341812).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 54-55 | Cleavage; by FURIN | ||||
Sequence: RD | ||||||
Site | 167-168 | Cleavage | ||||
Sequence: EQ |
GO annotations
Keywords
- Molecular function
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameProsaposin receptor GPR37
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO15354
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 27-265 | Extracellular | ||||
Sequence: ALGVAPASRNETCLGESCAPTVIQRRGRDAWGPGNSARDVLRARAPREEQGAAFLAGPSWDLPAAPGRDPAAGRGAEASAAGPPGPPTRPPGPWRWKGARGQEPSETLGRGNPTALQLFLQISEEEEKGPRGAGISGRSQEQSVKTVPGASDLFYWPRRAGKLQGSHHKPLSKTANGLAGHEGWTIALPGRALAQNGSLGEGIHEPGGPRRGNSTNRRVRLKNPFYPLTQESYGAYAVM | ||||||
Transmembrane | 266-286 | Helical; Name=1 | ||||
Sequence: CLSVVIFGTGIIGNLAVMCIV | ||||||
Topological domain | 287-299 | Cytoplasmic | ||||
Sequence: CHNYYMRSISNSL | ||||||
Transmembrane | 300-320 | Helical; Name=2 | ||||
Sequence: LANLAFWDFLIIFFCLPLVIF | ||||||
Topological domain | 321-335 | Extracellular | ||||
Sequence: HELTKKWLLEDFSCK | ||||||
Transmembrane | 336-356 | Helical; Name=3 | ||||
Sequence: IVPYIEVASLGVTTFTLCALC | ||||||
Topological domain | 357-379 | Cytoplasmic | ||||
Sequence: IDRFRAATNVQMYYEMIENCSST | ||||||
Transmembrane | 380-400 | Helical; Name=4 | ||||
Sequence: TAKLAVIWVGALLLALPEVVL | ||||||
Topological domain | 401-443 | Extracellular | ||||
Sequence: RQLSKEDLGFSGRAPAERCIIKISPDLPDTIYVLALTYDSARL | ||||||
Transmembrane | 444-464 | Helical; Name=5 | ||||
Sequence: WWYFGCYFCLPTLFTITCSLV | ||||||
Topological domain | 465-493 | Cytoplasmic | ||||
Sequence: TARKIRKAEKACTRGNKRQIQLESQMNCT | ||||||
Transmembrane | 494-514 | Helical; Name=6 | ||||
Sequence: VVALTILYGFCIIPENICNIV | ||||||
Topological domain | 515-531 | Extracellular | ||||
Sequence: TAYMATGVSQQTMDLLN | ||||||
Transmembrane | 532-552 | Helical; Name=7 | ||||
Sequence: IISQFLLFFKSCVTPVLLFCL | ||||||
Topological domain | 553-613 | Cytoplasmic | ||||
Sequence: CKPFSRAFMECCCCCCEECIQKSSTVTSDDNDNEYTTELELSPFSTIRREMSTFASVGTHC |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 54 | Strong increase of full-length receptor abundance at the cell surface. | ||||
Sequence: R → A | ||||||
Mutagenesis | 558 | Strong loss of interaction with MUPP1 resulting in dendritic alteration. | ||||
Sequence: R → Q |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 768 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, glycosylation, disulfide bond, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Signal | 1-26 | UniProt | |||||
Sequence: MRAPGALLARMSRLLLLLLLKVSASS | |||||||
Chain | PRO_0000012799 | 27-613 | UniProt | Prosaposin receptor GPR37 | |||
Sequence: ALGVAPASRNETCLGESCAPTVIQRRGRDAWGPGNSARDVLRARAPREEQGAAFLAGPSWDLPAAPGRDPAAGRGAEASAAGPPGPPTRPPGPWRWKGARGQEPSETLGRGNPTALQLFLQISEEEEKGPRGAGISGRSQEQSVKTVPGASDLFYWPRRAGKLQGSHHKPLSKTANGLAGHEGWTIALPGRALAQNGSLGEGIHEPGGPRRGNSTNRRVRLKNPFYPLTQESYGAYAVMCLSVVIFGTGIIGNLAVMCIVCHNYYMRSISNSLLANLAFWDFLIIFFCLPLVIFHELTKKWLLEDFSCKIVPYIEVASLGVTTFTLCALCIDRFRAATNVQMYYEMIENCSSTTAKLAVIWVGALLLALPEVVLRQLSKEDLGFSGRAPAERCIIKISPDLPDTIYVLALTYDSARLWWYFGCYFCLPTLFTITCSLVTARKIRKAEKACTRGNKRQIQLESQMNCTVVALTILYGFCIIPENICNIVTAYMATGVSQQTMDLLNIISQFLLFFKSCVTPVLLFCLCKPFSRAFMECCCCCCEECIQKSSTVTSDDNDNEYTTELELSPFSTIRREMSTFASVGTHC | |||||||
Glycosylation | 36 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 222 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Glycosylation | 239 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 334↔419 | UniProt | |||||
Sequence: CKIVPYIEVASLGVTTFTLCALCIDRFRAATNVQMYYEMIENCSSTTAKLAVIWVGALLLALPEVVLRQLSKEDLGFSGRAPAERC | |||||||
Modified residue (large scale data) | 594 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 598 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
The N-terminus is cleaved by ADAM10 metalloproteinase; mediating limited proteolysis leading to the release of receptor ectodomain by shedding (PubMed:26869225, PubMed:34042202).
In addition, cleaved by FURIN between Arg-54 and Asp-55 (PubMed:34042202).
In addition, cleaved by FURIN between Arg-54 and Asp-55 (PubMed:34042202).
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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in brain and spinal cord, and at lower levels in testis, placenta and liver, but no detectable expression observed in any other tissue. When overexpressed in cells, tends to become insoluble and unfolded. Accumulation of the unfolded protein may lead to dopaminergic neuronal death in juvenile Parkinson disease (PDJ).
Gene expression databases
Organism-specific databases
Interaction
Subunit
Forms a complex with PRKN, STUB1 and HSP70. The amount of STUB1 in the complex increases during ER stress. STUB1 promotes the dissociation of HSP70 from PRKN, thus facilitating PRKN-mediated GPR37 ubiquitination. Interacts with PACRG. Interacts with MPDZ (PubMed:25977097).
Interacts with CNTNAP2 (PubMed:25977097).
Interacts with LRP6; this interaction promotes LRP6 maturation (PubMed:28341812).
Interacts with CNTNAP2 (PubMed:25977097).
Interacts with LRP6; this interaction promotes LRP6 maturation (PubMed:28341812).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 80-138 | Disordered | ||||
Sequence: FLAGPSWDLPAAPGRDPAAGRGAEASAAGPPGPPTRPPGPWRWKGARGQEPSETLGRGN | ||||||
Region | 152-172 | Disordered | ||||
Sequence: EEKGPRGAGISGRSQEQSVKT |
Sequence similarities
Belongs to the G-protein coupled receptor 1 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Protein family/group databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length613
- Mass (Da)67,114
- Last updated1999-01-01 v2
- Checksum5A1AB269ED63E765
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 93 | in Ref. 3; AAC51281 | ||||
Sequence: G → D | ||||||
Sequence conflict | 106 | in Ref. 3; AAC51281 | ||||
Sequence: A → T | ||||||
Sequence conflict | 118 | in Ref. 3; AAC51281 | ||||
Sequence: G → V | ||||||
Sequence conflict | 160 | in Ref. 3; AAC51281 | ||||
Sequence: G → V | ||||||
Sequence conflict | 182 | in Ref. 3; AAC51281 | ||||
Sequence: W → C | ||||||
Sequence conflict | 231 | in Ref. 3; AAC51281 | ||||
Sequence: E → D | ||||||
Sequence conflict | 284 | in Ref. 2; AAB70008 | ||||
Sequence: C → S | ||||||
Sequence conflict | 304 | in Ref. 3; AAC51281 | ||||
Sequence: A → V | ||||||
Sequence conflict | 329 | in Ref. 3; AAC51281 | ||||
Sequence: L → V | ||||||
Sequence conflict | 503-504 | in Ref. 3; AAC51281 | ||||
Sequence: FC → LG | ||||||
Sequence conflict | 598 | in Ref. 3; AAC51281 | ||||
Sequence: T → A |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Y12476 EMBL· GenBank· DDBJ | CAA73080.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
Y12477 EMBL· GenBank· DDBJ | CAA73080.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF017262 EMBL· GenBank· DDBJ | AAB70008.1 EMBL· GenBank· DDBJ | mRNA | ||
U87460 EMBL· GenBank· DDBJ | AAC51281.1 EMBL· GenBank· DDBJ | mRNA | ||
AF502281 EMBL· GenBank· DDBJ | AAM18625.2 EMBL· GenBank· DDBJ | mRNA | ||
AC004925 EMBL· GenBank· DDBJ | AAD08853.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH236947 EMBL· GenBank· DDBJ | EAL24325.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471070 EMBL· GenBank· DDBJ | EAW83613.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC040007 EMBL· GenBank· DDBJ | AAH40007.1 EMBL· GenBank· DDBJ | mRNA |