G37L1_MOUSE
ID G37L1_MOUSE Reviewed; 481 AA.
AC Q99JG2; O88313; Q80UB9; Q99JG1;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=G-protein coupled receptor 37-like 1;
DE AltName: Full=Endothelin B receptor-like protein 2;
DE Short=ETBR-LP-2;
DE Flags: Precursor;
GN Name=Gpr37l1; Synonyms=Etbrlp2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=BALB/cJ; TISSUE=Liver;
RA Marazziti D., Golini E., Magrelli A., Matteoni R., Tocchini-Valentini G.P.;
RT "Genomic analysis of GPR37 and related orphan G-protein coupled receptor
RT genes highly expressed in the mammalian brain.";
RL Curr. Genomics 2:253-260(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 28-481.
RC STRAIN=C57BL/6J; TISSUE=Hippocampus;
RA Matsuo N., Kawamoto S., Matsubara K., Okubo K.;
RT "Cloning of a cDNA encoding a novel G-protein coupled receptor uniquely
RT expressed in the adult brain.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 256-454.
RX PubMed=12679517; DOI=10.1073/pnas.0230374100;
RA Vassilatis D.K., Hohmann J.G., Zeng H., Li F., Ranchalis J.E.,
RA Mortrud M.T., Brown A., Rodriguez S.S., Weller J.R., Wright A.C.,
RA Bergmann J.E., Gaitanaris G.A.;
RT "The G protein-coupled receptor repertoires of human and mouse.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:4903-4908(2003).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-471 AND THR-479, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, INTERACTION WITH PTCH1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=24062445; DOI=10.1073/pnas.1314819110;
RA Marazziti D., Di Pietro C., Golini E., Mandillo S., La Sala G.,
RA Matteoni R., Tocchini-Valentini G.P.;
RT "Precocious cerebellum development and improved motor functions in mice
RT lacking the astrocyte cilium-, patched 1-associated Gpr37l1 receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:16486-16491(2013).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, CLEAVAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=27072655; DOI=10.1126/scisignal.aad1089;
RA Coleman J.L., Ngo T., Schmidt J., Mrad N., Liew C.K., Jones N.M.,
RA Graham R.M., Smith N.J.;
RT "Metalloprotease cleavage of the N terminus of the orphan G protein-coupled
RT receptor GPR37L1 reduces its constitutive activity.";
RL Sci. Signal. 9:RA36-RA36(2016).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=28688853; DOI=10.1016/j.nbd.2017.07.006;
RA Giddens M.M., Wong J.C., Schroeder J.P., Farrow E.G., Smith B.M., Owino S.,
RA Soden S.E., Meyer R.C., Saunders C., LePichon J.B., Weinshenker D.,
RA Escayg A., Hall R.A.;
RT "GPR37L1 modulates seizure susceptibility: Evidence from mouse studies and
RT analyses of a human GPR37L1 variant.";
RL Neurobiol. Dis. 106:181-190(2017).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=29625592; DOI=10.1186/s13293-018-0173-y;
RA Coleman J.L.J., Mouat M.A., Wu J., Jancovski N., Bassi J.K., Chan A.Y.,
RA Humphreys D.T., Mrad N., Yu Z.Y., Ngo T., Iismaa S., Dos Remedios C.G.,
RA Feneley M.P., Allen A.M., Graham R.M., Smith N.J.;
RT "Orphan receptor GPR37L1 contributes to the sexual dimorphism of central
RT cardiovascular control.";
RL Biol. Sex Differ. 9:14-14(2018).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=28795439; DOI=10.1002/glia.23198;
RA Jolly S., Bazargani N., Quiroga A.C., Pringle N.P., Attwell D.,
RA Richardson W.D., Li H.;
RT "G protein-coupled receptor 37-like 1 modulates astrocyte glutamate
RT transporters and neuronal NMDA receptors and is neuroprotective in
RT ischemia.";
RL Glia 66:47-61(2018).
CC -!- FUNCTION: G-protein coupled receptor (PubMed:27072655). Has been shown
CC to bind the neuroprotective and glioprotective factor prosaposin
CC (PSAP), leading to endocytosis followed by an ERK phosphorylation
CC cascade (By similarity). However, other studies have shown that
CC prosaposin does not increase activity (By similarity). It has been
CC suggested that GPR37L1 is a constitutively active receptor which
CC signals through the guanine nucleotide-binding protein G(s) subunit
CC alpha (By similarity). Participates in the regulation of postnatal
CC cerebellar development by modulating the Shh pathway (PubMed:24062445).
CC Regulates baseline blood pressure in females and protects against
CC cardiovascular stress in males (PubMed:29625592). Mediates inhibition
CC of astrocyte glutamate transporters and reduction in neuronal N-methyl-
CC D-aspartate receptor activity (PubMed:28795439).
CC {ECO:0000250|UniProtKB:O60883, ECO:0000269|PubMed:24062445,
CC ECO:0000269|PubMed:27072655, ECO:0000269|PubMed:28795439,
CC ECO:0000269|PubMed:29625592}.
CC -!- SUBUNIT: Interacts with the PTCH1 receptor.
CC {ECO:0000269|PubMed:24062445}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24062445,
CC ECO:0000269|PubMed:27072655}; Multi-pass membrane protein
CC {ECO:0000255}. Cell projection, cilium membrane
CC {ECO:0000269|PubMed:24062445}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Associates with the basal membrane of Bergmann glia
CC cell primary cilia. {ECO:0000269|PubMed:24062445}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain but not in heart or
CC kidney (at protein level) (PubMed:29625592). In the brain, highly
CC expressed in cerebellar Bergmann glia (at protein level)
CC (PubMed:24062445, PubMed:29625592). Detected in the hippocampus but not
CC in the brain stem or neocortex (at protein level) (PubMed:29625592). In
CC several key cardiovascular centers of the central nervous system
CC including the caudal and rostral ventrolateral medulla, the nucleus of
CC the solitary tract, and the A5 nucleus, detected close to, but not
CC within, tyrosine hydroxylase-positive catecholaminergic neurons (at
CC protein level) (PubMed:29625592). Expressed in astrocytes in both gray
CC and white matter and is also detected throughout the brain in some
CC oligodendrocyte precursors (PubMed:28795439).
CC {ECO:0000269|PubMed:24062445, ECO:0000269|PubMed:28795439,
CC ECO:0000269|PubMed:29625592}.
CC -!- DEVELOPMENTAL STAGE: At postnatal day 1, not detectable in any brain
CC area examined but at postnatal day 8, strongly expressed in both
CC astrocytes and oligodendrocyte precursors (OPs). At postnatal day 15
CC and during adulthood, expression in astrocytes and OPs remains at high
CC levels. {ECO:0000269|PubMed:28795439}.
CC -!- DOMAIN: The N-terminal region is required for constitutive signal
CC transduction. {ECO:0000250|UniProtKB:O60883}.
CC -!- PTM: Undergoes metalloprotease-mediated cleavage which reduces its
CC constitutive activity. {ECO:0000269|PubMed:27072655}.
CC -!- PTM: Ubiquitinated. {ECO:0000250|UniProtKB:O60883}.
CC -!- DISRUPTION PHENOTYPE: Premature down-regulation of proliferation of
CC cerebellar granule neuron precursors in postnatal mice, precocious
CC maturation of Bergmann glia and Purkinje neurons, precocious juvenile
CC motor abilities, and improved adult motor learning and coordination
CC (PubMed:24062445). Early activation of the Shh pathway with increased
CC levels of Shh, Smo and Ptch1 earlier in postnatal development than in
CC wild-type mice (PubMed:24062445). Increased aortic diastolic, mean
CC arterial and pulse pressures in females but not in males
CC (PubMed:29625592). Males develop exacerbated left ventricular
CC hypertrophy and evidence of heart failure when challenged with short-
CC term angiotensin-2 infusion while females are protected from cardiac
CC fibrosis (PubMed:29625592). Increased susceptibility to induced
CC seizures (PubMed:28688853). Reduced signaling in the cerebellum as
CC indicated by significantly less cAMP production (PubMed:27072655). No
CC effect on the input resistance or resting potential of astrocytes or
CC neurons (PubMed:28795439). Neuronal death is increased by 40% in an in
CC vitro model of ischemia (PubMed:28795439).
CC {ECO:0000269|PubMed:24062445, ECO:0000269|PubMed:27072655,
CC ECO:0000269|PubMed:28688853, ECO:0000269|PubMed:28795439,
CC ECO:0000269|PubMed:29625592}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- CAUTION: Has been reported to act as a receptor for prosaposin (PSAP).
CC However, it has also been shown that prosaposin does not increase
CC activity. It has been suggested that GPR37L1 is a constitutively active
CC receptor. {ECO:0000250|UniProtKB:O60883}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA32062.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AJ306537; CAC34842.1; -; Genomic_DNA.
DR EMBL; AJ306538; CAC34843.1; -; Genomic_DNA.
DR EMBL; AB016602; BAA32062.1; ALT_INIT; mRNA.
DR EMBL; AY255561; AAO85073.1; -; mRNA.
DR CCDS; CCDS48371.1; -.
DR RefSeq; NP_602320.2; NM_134438.3.
DR AlphaFoldDB; Q99JG2; -.
DR SMR; Q99JG2; -.
DR STRING; 10090.ENSMUSP00000027682; -.
DR GlyGen; Q99JG2; 1 site.
DR iPTMnet; Q99JG2; -.
DR PhosphoSitePlus; Q99JG2; -.
DR SwissPalm; Q99JG2; -.
DR MaxQB; Q99JG2; -.
DR PaxDb; Q99JG2; -.
DR PeptideAtlas; Q99JG2; -.
DR PRIDE; Q99JG2; -.
DR ProteomicsDB; 267661; -.
DR Antibodypedia; 20649; 300 antibodies from 32 providers.
DR DNASU; 171469; -.
DR Ensembl; ENSMUST00000027682; ENSMUSP00000027682; ENSMUSG00000026424.
DR GeneID; 171469; -.
DR KEGG; mmu:171469; -.
DR UCSC; uc007csv.2; mouse.
DR CTD; 9283; -.
DR MGI; MGI:1928503; Gpr37l1.
DR VEuPathDB; HostDB:ENSMUSG00000026424; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01040000240430; -.
DR HOGENOM; CLU_029119_0_0_1; -.
DR InParanoid; Q99JG2; -.
DR OMA; QCERQLN; -.
DR OrthoDB; 568030at2759; -.
DR PhylomeDB; Q99JG2; -.
DR TreeFam; TF331292; -.
DR Reactome; R-MMU-375276; Peptide ligand-binding receptors.
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR BioGRID-ORCS; 171469; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q99JG2; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q99JG2; protein.
DR Bgee; ENSMUSG00000026424; Expressed in cerebellum lobe and 89 other tissues.
DR Genevisible; Q99JG2; MM.
DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; ISO:MGI.
DR GO; GO:0004930; F:G protein-coupled receptor activity; ISS:UniProtKB.
DR GO; GO:0042277; F:peptide binding; ISO:MGI.
DR GO; GO:0036505; F:prosaposin receptor activity; ISS:UniProtKB.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0060020; P:Bergmann glial cell differentiation; IMP:MGI.
DR GO; GO:0048712; P:negative regulation of astrocyte differentiation; IMP:MGI.
DR GO; GO:1903206; P:negative regulation of hydrogen peroxide-induced cell death; IMP:ParkinsonsUK-UCL.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IMP:MGI.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IMP:MGI.
DR GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; IMP:UniProtKB.
DR GO; GO:0021940; P:positive regulation of cerebellar granule cell precursor proliferation; IMP:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IGI:ParkinsonsUK-UCL.
DR GO; GO:0007224; P:smoothened signaling pathway; IMP:MGI.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR003909; GPR37_orph.
DR PANTHER; PTHR46216; PTHR46216; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01421; GPR37ORPHANR.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Disulfide bond; G-protein coupled receptor;
KW Glycoprotein; Membrane; Phosphoprotein; Receptor; Reference proteome;
KW Signal; Transducer; Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..481
FT /note="G-protein coupled receptor 37-like 1"
FT /id="PRO_0000012797"
FT TOPO_DOM 25..134
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 135..155
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 156..167
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 168..188
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 189..205
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 206..226
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 227..251
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 252..272
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 273..310
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 311..331
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 332..360
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 361..381
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 382..398
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 399..419
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 420..481
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 25..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 75..101
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 38..55
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 79..93
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 479
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 203..286
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
SQ SEQUENCE 481 AA; 52729 MW; D7CF26B83B7F6E8C CRC64;
MRWLWPLAVS LVVVLTVGLS GVSGAATSSL GGHRAKVQEQ QSRPRRGTKD EGPKEVQHYV
PEEWAEYPKP IHPAGLQPTK TLEATSPNPD KDGATPGNGQ ELRVNLTGTP SQRLQIQNPL
YPVTESSYSA YAIMLLALVV FAVGIVGNLS VMCIVWHSYY LKSAWNSILA SLALWDFLVL
FFCLPIVIFN EITKQRLLGD VSCRAVPFME VSSLGVTTFS LCALGIDRFH VATSTLPKVR
PIERCQSILA KLAVIWVGSM MLAVPELLLW QLAQEPAPTA GTVDSCIMKP SADLPESVYS
LVMTYQNARM WWYFGCYFCL PILFTVTCQL VTWRVRGPPG RKPECRAGRH EQCESQLNST
VVGLTVVYAF CTLPENVCNI VVAYLSTELT RQTLDLLGLI NQFSTFFKGA ITPVLLLCIC
RPLGQAFLDC CCCCCCEECG GASDSSATVS ADSKLKAEVS SSIYFHKPRE SPPLLPLGTP
C
