ID   GPR37_RAT               Reviewed;         603 AA.
AC   Q9QYC6;
DT   11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 141.
DE   RecName: Full=Prosaposin receptor GPR37;
DE   AltName: Full=G-protein coupled receptor 37;
DE   AltName: Full=G-protein coupled receptor CNS1;
DE   Flags: Precursor;
GN   Name=Gpr37;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC   TISSUE=Hypothalamus;
RX   PubMed=10350639; DOI=10.1016/s0169-328x(99)00092-3;
RA   Leng N., Gu G., Simerly R.B., Spindel E.R.;
RT   "Molecular cloning and characterization of two putative G protein-coupled
RT   receptors which are highly expressed in the central nervous system.";
RL   Brain Res. Mol. Brain Res. 69:73-83(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
CC   -!- FUNCTION: G-protein-coupled receptor that plays a role in several
CC       physiological pathways such as resolution of inflammatory pain and
CC       oligodendrocyte differentiation (By similarity). Acts as a receptor for
CC       several ligands including prosaposin, osteocalcin or neuroprotectin D1.
CC       Ligand binding induces endocytosis, followed by an ERK phosphorylation
CC       cascade (By similarity). Acts as a receptor for osteocalcin (OCN) to
CC       regulate oligodendrocyte differentiation and central nervous system
CC       myelination. Mechanistically, plays a negative role in oligodendrocyte
CC       differentiation and myelination during development via activation of
CC       the ERK1/2 signaling pathway. Therefore, regulates the stability of
CC       myelin or resistance of myelin itself to demyelination. Upon activation
CC       by neuroprotectin D1 (NPD1), promotes the activation of phagocytosis in
CC       macrophages as well as the shift in cytokine release toward an anti-
CC       inflammatory profile, and thus helps to reverse inflammatory pain. In
CC       addition, the increased macrophage phagocytosis mediates protection
CC       against sepsis upon pathogen infection. Additionally, extracellular
CC       vesicles derived from efferocyte express prosaposin, which binds to
CC       macrophage GPR37 to increase expression of the efferocytosis receptor
CC       TIM4 via an ERK-AP1-dependent signaling axis, leading to increased
CC       macrophage efferocytosis efficiency and accelerated resolution of
CC       inflammation (By similarity). May also act as a maturation factor of
CC       LRP6, protecting LRP6 from the endoplasmic reticulum (ER)-associated
CC       protein degradation (ERAD) and thereby promoting the Wnt/beta-catenin
CC       signaling pathway (By similarity). {ECO:0000250|UniProtKB:O15354,
CC       ECO:0000250|UniProtKB:Q9QY42}.
CC   -!- SUBUNIT: Forms a complex with PRKN, STUB1 and HSP70. The amount of
CC       STUB1 in the complex increases during ER stress. STUB1 promotes the
CC       dissociation of HSP70 from PRKN, thus facilitating PRKN-mediated GPR37
CC       ubiquitination. Interacts with PACRG (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cell projection, dendrite
CC       {ECO:0000250|UniProtKB:O15354}. Synapse {ECO:0000250|UniProtKB:O15354}.
CC       Cell membrane {ECO:0000250|UniProtKB:O15354}; Multi-pass membrane
CC       protein {ECO:0000250|UniProtKB:O15354}. Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:O15354}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:O15354}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in the brain. High levels of
CC       expression were seen in fiber tracts such as the corpus callosum,
CC       anterior commissure, fornix, internal capsule, cerebral peduncles, and
CC       stria terminalis. Additionally, moderate levels of expression were seen
CC       in the pyramidal tracts and cerebellar peduncles, as well as in the
CC       spinal tract of the trigeminal nerve and the spinal fasciculi.
CC       {ECO:0000269|PubMed:10350639}.
CC   -!- PTM: The N-terminus is cleaved by ADAM10 metalloproteinase; mediating
CC       limited proteolysis leading to the release of receptor ectodomain by
CC       shedding. In addition, cleaved by FURIN between Arg-53 and Asp-54.
CC       {ECO:0000250|UniProtKB:O15354}.
CC   -!- PTM: Ubiquitinated by PRKN in the presence of UBE2E1 and UBE2L3 in the
CC       endoplasmic reticulum. The unfolded form is specifically ubiquitinated
CC       by SYVN1, which promotes its proteasomal degradation and prevents
CC       neuronal cell death. {ECO:0000250|UniProtKB:O15354}.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR   EMBL; AF087946; AAD54655.1; -; mRNA.
DR   EMBL; BC087728; AAH87728.1; -; mRNA.
DR   RefSeq; NP_476549.1; NM_057201.1.
DR   AlphaFoldDB; Q9QYC6; -.
DR   SMR; Q9QYC6; -.
DR   STRING; 10116.ENSRNOP00000003593; -.
DR   GlyCosmos; Q9QYC6; 3 sites, No reported glycans.
DR   GlyGen; Q9QYC6; 3 sites.
DR   PhosphoSitePlus; Q9QYC6; -.
DR   PaxDb; 10116-ENSRNOP00000003593; -.
DR   Ensembl; ENSRNOT00000003593.7; ENSRNOP00000003593.4; ENSRNOG00000002524.7.
DR   Ensembl; ENSRNOT00055036212; ENSRNOP00055029422; ENSRNOG00055021199.
DR   Ensembl; ENSRNOT00060031435; ENSRNOP00060025506; ENSRNOG00060018313.
DR   Ensembl; ENSRNOT00065042331; ENSRNOP00065034633; ENSRNOG00065024650.
DR   GeneID; 117549; -.
DR   KEGG; rno:117549; -.
DR   UCSC; RGD:619848; rat.
DR   AGR; RGD:619848; -.
DR   CTD; 2861; -.
DR   RGD; 619848; Gpr37.
DR   eggNOG; KOG3656; Eukaryota.
DR   GeneTree; ENSGT01100000263518; -.
DR   HOGENOM; CLU_032138_1_0_1; -.
DR   InParanoid; Q9QYC6; -.
DR   OMA; HSRRWRT; -.
DR   OrthoDB; 4268515at2759; -.
DR   PhylomeDB; Q9QYC6; -.
DR   TreeFam; TF331292; -.
DR   Reactome; R-RNO-375276; Peptide ligand-binding receptors.
DR   Reactome; R-RNO-418594; G alpha (i) signalling events.
DR   PRO; PR:Q9QYC6; -.
DR   Proteomes; UP000002494; Chromosome 4.
DR   Bgee; ENSRNOG00000002524; Expressed in Ammon's horn and 19 other cell types or tissues.
DR   GO; GO:0009986; C:cell surface; ISO:RGD.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR   GO; GO:0043235; C:receptor complex; ISO:RGD.
DR   GO; GO:0045202; C:synapse; ISO:RGD.
DR   GO; GO:0000151; C:ubiquitin ligase complex; ISO:RGD.
DR   GO; GO:0008528; F:G protein-coupled peptide receptor activity; ISO:RGD.
DR   GO; GO:0031072; F:heat shock protein binding; ISO:RGD.
DR   GO; GO:0030544; F:Hsp70 protein binding; ISO:RGD.
DR   GO; GO:0042923; F:neuropeptide binding; ISO:RGD.
DR   GO; GO:0008188; F:neuropeptide receptor activity; ISO:RGD.
DR   GO; GO:0030165; F:PDZ domain binding; ISO:RGD.
DR   GO; GO:0042277; F:peptide binding; ISO:RGD.
DR   GO; GO:0036505; F:prosaposin receptor activity; ISO:RGD.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR   GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; ISO:RGD.
DR   GO; GO:0034614; P:cellular response to reactive oxygen species; ISO:RGD.
DR   GO; GO:0016358; P:dendrite development; ISO:RGD.
DR   GO; GO:0042416; P:dopamine biosynthetic process; ISO:RGD.
DR   GO; GO:0031987; P:locomotion involved in locomotory behavior; ISO:RGD.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; ISO:RGD.
DR   GO; GO:0045964; P:positive regulation of dopamine metabolic process; ISO:RGD.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR   CDD; cd15127; 7tmA_GPR37; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   InterPro; IPR003909; GPR37_orph.
DR   PANTHER; PTHR46216:SF3; PROSAPOSIN RECEPTOR GPR37; 1.
DR   PANTHER; PTHR46216; PROSAPOSIN RECEPTOR GPR37 FAMILY MEMBER; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR01421; GPR37ORPHANR.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR   Genevisible; Q9QYC6; RN.
PE   2: Evidence at transcript level;
KW   Cell membrane; Cell projection; Disulfide bond; Endoplasmic reticulum;
KW   G-protein coupled receptor; Glycoprotein; Membrane; Receptor;
KW   Reference proteome; Signal; Synapse; Transducer; Transmembrane;
KW   Transmembrane helix; Ubl conjugation.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000255"
FT   CHAIN           27..603
FT                   /note="Prosaposin receptor GPR37"
FT                   /id="PRO_0000012801"
FT   TOPO_DOM        27..255
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        256..276
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        277..289
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        290..310
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        311..325
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        326..346
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        347..369
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        370..390
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        391..433
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        434..454
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        455..483
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        484..504
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        505..521
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        522..542
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        543..603
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          39..232
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        56..80
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        127..141
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        148..177
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            53..54
FT                   /note="Cleavage; by FURIN"
FT                   /evidence="ECO:0000250|UniProtKB:O15354"
FT   SITE            164..165
FT                   /note="Cleavage"
FT                   /evidence="ECO:0000250|UniProtKB:O15354"
FT   CARBOHYD        36
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        212
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        229
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        324..409
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ   SEQUENCE   603 AA;  66961 MW;  87F3042B8267CEAD CRC64;
     MPAPGAPLSR TSRLLLLLLF KVSVSAALSF VPEPRNGTCL GESCSPLIPR RSRDAGGPRN
     SARDALRVHV PREKLEAEVR GATSWDLPPP RGGDTGVIEE AAASGPLGPP TKPPGAWRWK
     GAQGKEPSGH LGRREPTDSQ LFRQTSERGE MSSKRDEIPQ GSQEHSVKTE PEPRDLFYWP
     RKTGQLQGSH YRPSAVHEGR TLAPPGRALP QNGSADDWVP DQGGPRRGNS TNRRVRLKNP
     FYPLTQESYG AYAVMCLSVV IFGTGIIGNL AVMCIVCHNY YMRSISNSLL ANLAFWDFLI
     IFFCLPLVIF HELTKKWLLE DFSCKIVPYI EVASLGVTTF TLCALCIDRF RAATNVQMYY
     EMIENCSSTT AKLAVIWVGA LLLALPEVVL RQLSKEDLGF SGQAPAERCV IKISPDLPDT
     IYVLALTYDG ARLWWYFGCY FCLPTLFTIT CSLVTARKIR KAEKASTRGN KRQIHLESQM
     NCTVVALTIL YGFCIIPENI CNIVTAYMAT GVSQQTMDLL NIISQFLLFF KSCVTPVLLF
     CLCRPFSRAF MECCCCCCEE CIQKSSTVTS DDNDNEYTTE LELSPFSTIR REMSTFASVG
     THC
//