ID G37L1_HUMAN Reviewed; 481 AA. AC O60883; B2R7M9; Q5SXP7; Q86VP7; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 02-NOV-2010, sequence version 2. DT 13-FEB-2019, entry version 156. 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 Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT ASP-90. RC TISSUE=Brain; RX PubMed=9539149; DOI=10.1016/S0014-5793(98)00170-7; RA Valdenaire O., Giller T., Breu V., Ardati A., Schweizer A., RA Richards J.G.; RT "A new family of orphan G protein-coupled receptors predominantly RT expressed in the brain."; RL FEBS Lett. 424:193-196(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-90. RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cerebellum; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-91. 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP GLYCOSYLATION AT THR-79; THR-85; SER-86; THR-95 AND THR-107, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=23234360; DOI=10.1021/pr300963h; RA Halim A., Ruetschi U., Larson G., Nilsson J.; RT "LC-MS/MS characterization of O-glycosylation sites and glycan RT structures of human cerebrospinal fluid glycoproteins."; RL J. Proteome Res. 12:573-584(2013). RN [7] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=23690594; DOI=10.1073/pnas.1219004110; RA Meyer R.C., Giddens M.M., Schaefer S.A., Hall R.A.; RT "GPR37 and GPR37L1 are receptors for the neuroprotective and RT glioprotective factors prosaptide and prosaposin."; RL Proc. Natl. Acad. Sci. U.S.A. 110:9529-9534(2013). RN [8] RP FUNCTION, CLEAVAGE, AND DOMAIN. 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- RT coupled receptor GPR37L1 reduces its constitutive activity."; RL Sci. Signal. 9:RA36-RA36(2016). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION, VARIANT ASN-349, AND RP CHARACTERIZATION OF VARIANT ASN-349. 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., RA Owino S., Soden S.E., Meyer R.C., Saunders C., LePichon J.B., RA Weinshenker D., Escayg A., Hall R.A.; RT "GPR37L1 modulates seizure susceptibility: Evidence from mouse studies RT and analyses of a human GPR37L1 variant."; RL Neurobiol. Dis. 106:181-190(2017). CC -!- FUNCTION: G-protein coupled receptor (PubMed:27072655). Has been CC shown to bind the neuroprotective and glioprotective factor CC prosaposin (PSAP), leading to endocytosis followed by an ERK CC phosphorylation cascade (PubMed:23690594). However, other studies CC have shown that prosaposin does not increase activity CC (PubMed:27072655, PubMed:28688853). It has been suggested that CC GPR37L1 is a constitutively active receptor which signals through CC the guanine nucleotide-binding protein G(s) subunit alpha CC (PubMed:27072655). Participates in the regulation of postnatal CC cerebellar development by modulating the Shh pathway (By CC similarity). Regulates baseline blood pressure in females and CC protects against cardiovascular stress in males (By similarity). CC Mediates inhibition of astrocyte glutamate transporters and CC reduction in neuronal N-methyl-D-aspartate receptor activity (By CC similarity). {ECO:0000250|UniProtKB:Q99JG2, CC ECO:0000269|PubMed:23690594, ECO:0000269|PubMed:27072655, CC ECO:0000269|PubMed:28688853}. CC -!- SUBUNIT: Interacts with the PTCH1 receptor. CC {ECO:0000250|UniProtKB:Q99JG2}. CC -!- INTERACTION: CC P42785:PRCP; NbExp=2; IntAct=EBI-2927498, EBI-2803892; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28688853}; CC Multi-pass membrane protein {ECO:0000255}. Cell projection, cilium CC membrane {ECO:0000250|UniProtKB:Q99JG2}; Multi-pass membrane CC protein {ECO:0000255}. Note=Associates with the basal membrane of CC Bergmann glia cell primary cilia. {ECO:0000250|UniProtKB:Q99JG2}. CC -!- TISSUE SPECIFICITY: Expressed in primary cortical astrocytes (at CC protein level) (PubMed:23690594). Expressed in the central nervous CC system (PubMed:9539149). {ECO:0000269|PubMed:23690594, CC ECO:0000269|PubMed:9539149}. CC -!- DOMAIN: The N-terminal region is required for constitutive signal CC transduction. {ECO:0000269|PubMed:27072655}. CC -!- PTM: O-glycosylated. {ECO:0000269|PubMed:23234360}. CC -!- PTM: Undergoes metalloprotease-mediated cleavage which reduces its CC constitutive activity. {ECO:0000269|PubMed:27072655}. CC -!- PTM: Ubiquitinated. {ECO:0000269|PubMed:28688853}. 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 CC (PSAP) (PubMed:23690594). However, it has also been shown that CC prosaposin does not increase activity (PubMed:27072655, CC PubMed:28688853). It has been suggested that GPR37L1 is a CC constitutively active receptor (PubMed:27072655). CC {ECO:0000269|PubMed:23690594, ECO:0000269|PubMed:27072655, CC ECO:0000269|PubMed:28688853}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; Y16280; CAA76153.1; -; mRNA. DR EMBL; AK313044; BAG35876.1; -; mRNA. DR EMBL; AK222639; BAD96359.1; -; mRNA. DR EMBL; AL592300; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC050334; AAH50334.1; -; mRNA. DR CCDS; CCDS1420.1; -. DR RefSeq; NP_004758.3; NM_004767.3. DR UniGene; Hs.132049; -. DR UniGene; Hs.604697; -. DR ProteinModelPortal; O60883; -. DR IntAct; O60883; 48. DR STRING; 9606.ENSP00000356251; -. DR BindingDB; O60883; -. DR ChEMBL; CHEMBL5892; -. DR GuidetoPHARMACOLOGY; 104; -. DR GlyConnect; 661; -. DR iPTMnet; O60883; -. DR PhosphoSitePlus; O60883; -. DR UniCarbKB; O60883; -. DR BioMuta; GPR37L1; -. DR PaxDb; O60883; -. DR PeptideAtlas; O60883; -. DR PRIDE; O60883; -. DR ProteomicsDB; 49649; -. DR Ensembl; ENST00000367282; ENSP00000356251; ENSG00000170075. DR GeneID; 9283; -. DR KEGG; hsa:9283; -. DR UCSC; uc001gxj.4; human. DR CTD; 9283; -. DR DisGeNET; 9283; -. DR EuPathDB; HostDB:ENSG00000170075.8; -. DR GeneCards; GPR37L1; -. DR H-InvDB; HIX0200009; -. DR HGNC; HGNC:14923; GPR37L1. DR HPA; HPA064454; -. DR MIM; 617630; gene. DR neXtProt; NX_O60883; -. DR OpenTargets; ENSG00000170075; -. DR PharmGKB; PA28883; -. DR eggNOG; KOG3656; Eukaryota. DR eggNOG; ENOG410XRW9; LUCA. DR GeneTree; ENSGT00940000153565; -. DR HOGENOM; HOG000252922; -. DR HOVERGEN; HBG051808; -. DR InParanoid; O60883; -. DR KO; K04244; -. DR OMA; TEMSSSI; -. DR OrthoDB; 568030at2759; -. DR PhylomeDB; O60883; -. DR TreeFam; TF331292; -. DR Reactome; R-HSA-375276; Peptide ligand-binding receptors. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR ChiTaRS; GPR37L1; human. DR GeneWiki; GPR37L1; -. DR GenomeRNAi; 9283; -. DR PRO; PR:O60883; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000170075; Expressed in 101 organ(s), highest expression level in medial globus pallidus. DR Genevisible; O60883; HS. DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0043235; C:receptor complex; IDA:MGI. DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0004930; F:G protein-coupled receptor activity; IDA:UniProtKB. DR GO; GO:0042277; F:peptide binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0036505; F:prosaposin receptor activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IDA:ParkinsonsUK-UCL. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome. DR GO; GO:0048712; P:negative regulation of astrocyte differentiation; IEA:Ensembl. DR GO; GO:1903206; P:negative regulation of hydrogen peroxide-induced cell death; ISS:ParkinsonsUK-UCL. DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl. DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IEA:Ensembl. DR GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; ISS:UniProtKB. DR GO; GO:0021940; P:positive regulation of cerebellar granule cell precursor proliferation; IEA:Ensembl. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:ParkinsonsUK-UCL. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR InterPro; IPR003909; GPR37_orph. 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; Complete proteome; Disulfide bond; KW G-protein coupled receptor; Glycoprotein; Membrane; Phosphoprotein; KW Polymorphism; Receptor; Reference proteome; Signal; Transducer; KW Transmembrane; Transmembrane helix; Ubl conjugation. FT SIGNAL 1 25 {ECO:0000255}. FT CHAIN 26 481 G-protein coupled receptor 37-like 1. FT /FTId=PRO_0000012796. FT TOPO_DOM 26 134 Extracellular. {ECO:0000255}. FT TRANSMEM 135 155 Helical; Name=1. {ECO:0000255}. FT TOPO_DOM 156 167 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 168 188 Helical; Name=2. {ECO:0000255}. FT TOPO_DOM 189 205 Extracellular. {ECO:0000255}. FT TRANSMEM 206 226 Helical; Name=3. {ECO:0000255}. FT TOPO_DOM 227 251 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 252 272 Helical; Name=4. {ECO:0000255}. FT TOPO_DOM 273 310 Extracellular. {ECO:0000255}. FT TRANSMEM 311 331 Helical; Name=5. {ECO:0000255}. FT TOPO_DOM 332 361 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 362 382 Helical; Name=6. {ECO:0000255}. FT TOPO_DOM 383 398 Extracellular. {ECO:0000255}. FT TRANSMEM 399 419 Helical; Name=7. {ECO:0000255}. FT TOPO_DOM 420 481 Cytoplasmic. {ECO:0000255}. FT COMPBIAS 418 439 Cys-rich. FT MOD_RES 471 471 Phosphoserine. FT {ECO:0000250|UniProtKB:Q99JG2}. FT MOD_RES 479 479 Phosphothreonine. FT {ECO:0000250|UniProtKB:Q99JG2}. FT CARBOHYD 79 79 O-linked (GalNAc...) threonine. FT {ECO:0000269|PubMed:23234360}. FT CARBOHYD 85 85 O-linked (GalNAc...) threonine. FT {ECO:0000269|PubMed:23234360}. FT CARBOHYD 86 86 O-linked (GalNAc...) serine. FT {ECO:0000269|PubMed:23234360}. FT CARBOHYD 95 95 O-linked (GalNAc...) threonine. FT {ECO:0000269|PubMed:23234360}. FT CARBOHYD 105 105 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 107 107 O-linked (GalNAc...) threonine. FT {ECO:0000269|PubMed:23234360}. FT DISULFID 203 286 {ECO:0000255|PROSITE-ProRule:PRU00521}. FT VARIANT 81 81 P -> A (in dbSNP:rs3795594). FT /FTId=VAR_047455. FT VARIANT 90 90 G -> D (in dbSNP:rs3795595). FT {ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:9539149}. FT /FTId=VAR_047456. FT VARIANT 91 91 K -> R (in dbSNP:rs17854616). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_047457. FT VARIANT 349 349 K -> N (found in siblings with a novel FT form of progressive myoclonus epilepsy; FT unknown pathological significance; no FT effect on expression levels, cell surface FT location, signaling activity or FT ubiquitination; dbSNP:rs372386575). FT {ECO:0000269|PubMed:28688853}. FT /FTId=VAR_080868. FT CONFLICT 204 204 R -> S (in Ref. 2; BAG35876). FT {ECO:0000305}. FT CONFLICT 433 433 C -> F (in Ref. 2; BAG35876). FT {ECO:0000305}. SQ SEQUENCE 481 AA; 52771 MW; EE9DFE0446E3AF24 CRC64; MRWLWPLAVS LAVILAVGLS RVSGGAPLHL GRHRAETQEQ QSRSKRGTED EEAKGVQQYV PEEWAEYPRP IHPAGLQPTK PLVATSPNPG KDGGTPDSGQ ELRGNLTGAP GQRLQIQNPL YPVTESSYSA YAIMLLALVV FAVGIVGNLS VMCIVWHSYY LKSAWNSILA SLALWDFLVL FFCLPIVIFN EITKQRLLGD VSCRAVPFME VSSLGVTTFS LCALGIDRFH VATSTLPKVR PIERCQSILA KLAVIWVGSM TLAVPELLLW QLAQEPAPTM GTLDSCIMKP SASLPESLYS LVMTYQNARM WWYFGCYFCL PILFTVTCQL VTWRVRGPPG RKSECRASKH EQCESQLNST VVGLTVVYAF CTLPENVCNI VVAYLSTELT RQTLDLLGLI NQFSTFFKGA ITPVLLLCIC RPLGQAFLDC CCCCCCEECG GASEASAANG SDNKLKTEVS SSIYFHKPRE SPPLLPLGTP C //