ID GPR37_HUMAN Reviewed; 613 AA. AC O15354; A4D0Y6; O00348; O14768; Q8TD39; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1999, sequence version 2. DT 13-FEB-2019, entry version 156. DE RecName: Full=Prosaposin receptor GPR37; DE AltName: Full=Endothelin B receptor-like protein 1; DE Short=ETBR-LP-1; DE AltName: Full=G-protein coupled receptor 37; DE AltName: Full=Parkin-associated endothelin receptor-like receptor; DE Short=PAELR; DE Flags: Precursor; GN Name=GPR37; 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 [GENOMIC DNA]. RC TISSUE=Brain; RX PubMed=9339362; DOI=10.1006/geno.1997.4900; RA Marazziti D., Golini E., Gallo A., Lombardi M.S., Matteoni R., RA Tocchini-Valentini G.P.; RT "Cloning of GPR37, a gene located on chromosome 7 encoding a putative RT G-protein-coupled peptide receptor, from a human frontal brain EST RT library."; RL Genomics 45:68-77(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY. RC TISSUE=Brain; RX PubMed=9526070; DOI=10.1016/S0169-328X(97)00336-7; RA Donohue P.J., Shapira H., Mantey S.A., Hampton L.L., Jensen R.T., RA Battey J.F.; RT "A human gene encodes a putative G protein-coupled receptor highly RT expressed in the central nervous system."; RL Brain Res. Mol. Brain Res. 54:152-160(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9144577; DOI=10.1006/bbrc.1997.6408; RA Zeng Z., Su K., Kyaw H., Li Y.; RT "A novel endothelin receptor type-B-like gene enriched in the brain."; RL Biochem. Biophys. Res. Commun. 233:559-567(1997). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INTERACTION WITH PRKN. RC TISSUE=Brain; RX PubMed=11439185; DOI=10.1016/S0092-8674(01)00407-X; RA Imai Y., Soda M., Inoue H., Hattori N., Mizuno Y., Takahashi R.; RT "An unfolded putative transmembrane polypeptide, which can lead to RT endoplasmic reticulum stress, is a substrate of Parkin."; RL Cell 105:891-902(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., RA Mural R.J., Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP INTERACTION WITH PRKN; STUB1 AND HSP70. RX PubMed=12150907; DOI=10.1016/S1097-2765(02)00583-X; RA Imai Y., Soda M., Hatakeyama S., Akagi T., Hashikawa T., Nakayama K., RA Takahashi R.; RT "CHIP is associated with Parkin, a gene responsible for familial RT Parkinson's disease, and enhances its ubiquitin ligase activity."; RL Mol. Cell 10:55-67(2002). RN [10] RP INTERACTION WITH PACRG. RX PubMed=14532270; DOI=10.1074/jbc.M309655200; RA Imai Y., Soda M., Murakami T., Shoji M., Abe K., Takahashi R.; RT "A product of the human gene adjacent to parkin is a component of Lewy RT bodies and suppresses Pael receptor-induced cell death."; RL J. Biol. Chem. 278:51901-51910(2003). RN [11] RP UBIQUITINATION, AND SUBCELLULAR LOCATION. RX PubMed=17059562; DOI=10.1111/j.1471-4159.2006.04155.x; RA Omura T., Kaneko M., Okuma Y., Orba Y., Nagashima K., Takahashi R., RA Fujitani N., Matsumura S., Hata A., Kubota K., Murahashi K., RA Uehara T., Nomura Y.; RT "A ubiquitin ligase HRD1 promotes the degradation of Pael receptor, a RT substrate of Parkin."; RL J. Neurochem. 99:1456-1469(2006). RN [12] RP FUNCTION. 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). CC -!- FUNCTION: Receptor for the neuroprotective and glioprotective CC factor prosaposin. Ligand binding induces endocytosis, followed by CC an ERK phosphorylation cascade. {ECO:0000269|PubMed:11439185, CC ECO:0000269|PubMed:23690594, ECO:0000269|PubMed:9526070}. CC -!- SUBUNIT: Forms a complex with PRKN, STUB1 and HSP70. The amount of CC STUB1 in the complex increases during ER stress. STUB1 promotes CC the dissociation of HSP70 from PRKN, thus facilitating PRKN- CC mediated GPR37 ubiquitination. Interacts with PACRG. CC {ECO:0000269|PubMed:11439185, ECO:0000269|PubMed:12150907, CC ECO:0000269|PubMed:14532270}. CC -!- INTERACTION: CC P29274:ADORA2A; NbExp=3; IntAct=EBI-15639515, EBI-2902702; CC Q9UBS5:GABBR1; NbExp=2; IntAct=EBI-15639515, EBI-724156; CC Q13639:HTR4; NbExp=5; IntAct=EBI-15639515, EBI-6656425; CC P08195:SLC3A2; NbExp=3; IntAct=EBI-15639515, EBI-702356; CC Q01959:SLC6A3; NbExp=2; IntAct=EBI-15639515, EBI-6661445; CC Q9NX61:TMEM161A; NbExp=2; IntAct=EBI-15639515, EBI-6138599; CC Q9H313:TTYH1; NbExp=2; IntAct=EBI-15639515, EBI-20793786; CC O95070:YIF1A; NbExp=2; IntAct=EBI-15639515, EBI-2799703; CC Q5BJH7:YIF1B; NbExp=2; IntAct=EBI-15639515, EBI-11288011; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17059562}; CC Multi-pass membrane protein {ECO:0000269|PubMed:17059562}. CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:17059562}; CC Multi-pass membrane protein {ECO:0000269|PubMed:17059562}. CC -!- TISSUE SPECIFICITY: Expressed in brain and spinal cord, and at CC lower levels in testis, placenta and liver, but no detectable CC expression observed in any other tissue. When overexpressed in CC cells, tends to become insoluble and unfolded. Accumulation of the CC unfolded protein may lead to dopaminergic neuronal death in CC juvenile Parkinson disease (PDJ). {ECO:0000269|PubMed:9526070}. CC -!- PTM: Ubiquitinated by PRKN in the presence of UBE2E1 and UBE2L3 in CC the endoplasmic reticulum. The unfolded form is specifically CC ubiquitinated by SYVN1, which promotes its proteasomal degradation CC and prevents neuronal cell death. {ECO:0000269|PubMed:17059562}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. 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; Y12476; CAA73080.1; -; Genomic_DNA. DR EMBL; Y12477; CAA73080.1; JOINED; Genomic_DNA. DR EMBL; AF017262; AAB70008.1; -; mRNA. DR EMBL; U87460; AAC51281.1; -; mRNA. DR EMBL; AF502281; AAM18625.2; -; mRNA. DR EMBL; AC004925; AAD08853.1; -; Genomic_DNA. DR EMBL; CH236947; EAL24325.1; -; Genomic_DNA. DR EMBL; CH471070; EAW83613.1; -; Genomic_DNA. DR EMBL; BC040007; AAH40007.1; -; mRNA. DR CCDS; CCDS5792.1; -. DR PIR; JC5501; JC5501. DR RefSeq; NP_005293.1; NM_005302.3. DR UniGene; Hs.406094; -. DR UniGene; Hs.731392; -. DR ProteinModelPortal; O15354; -. DR BioGrid; 109119; 27. DR DIP; DIP-60954N; -. DR IntAct; O15354; 45. DR MINT; O15354; -. DR STRING; 9606.ENSP00000306449; -. DR GuidetoPHARMACOLOGY; 103; -. DR TCDB; 9.A.14.13.20; the g-protein-coupled receptor (gpcr) family. DR iPTMnet; O15354; -. DR PhosphoSitePlus; O15354; -. DR BioMuta; GPR37; -. DR EPD; O15354; -. DR PaxDb; O15354; -. DR PeptideAtlas; O15354; -. DR PRIDE; O15354; -. DR ProteomicsDB; 48607; -. DR DNASU; 2861; -. DR Ensembl; ENST00000303921; ENSP00000306449; ENSG00000170775. DR GeneID; 2861; -. DR KEGG; hsa:2861; -. DR UCSC; uc003vli.5; human. DR CTD; 2861; -. DR DisGeNET; 2861; -. DR EuPathDB; HostDB:ENSG00000170775.2; -. DR GeneCards; GPR37; -. DR HGNC; HGNC:4494; GPR37. DR HPA; HPA042903; -. DR HPA; HPA068009; -. DR MIM; 602583; gene. DR neXtProt; NX_O15354; -. DR OpenTargets; ENSG00000170775; -. DR PharmGKB; PA28882; -. DR eggNOG; KOG3656; Eukaryota. DR eggNOG; ENOG410XRW9; LUCA. DR GeneTree; ENSGT00940000153565; -. DR HOGENOM; HOG000252922; -. DR HOVERGEN; HBG051808; -. DR InParanoid; O15354; -. DR KO; K04243; -. DR OMA; SDLYYWP; -. DR OrthoDB; 947117at2759; -. DR PhylomeDB; O15354; -. DR TreeFam; TF331292; -. DR Reactome; R-HSA-375276; Peptide ligand-binding receptors. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR SIGNOR; O15354; -. DR GeneWiki; GPR37; -. DR GenomeRNAi; 2861; -. DR PRO; PR:O15354; -. DR Proteomes; UP000005640; Chromosome 7. DR Bgee; ENSG00000170775; Expressed in 149 organ(s), highest expression level in Brodmann (1909) area 46. DR Genevisible; O15354; HS. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IDA:ParkinsonsUK-UCL. DR GO; GO:0043235; C:receptor complex; IDA:MGI. DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:ParkinsonsUK-UCL. DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0004930; F:G protein-coupled receptor activity; TAS:ProtInc. DR GO; GO:0031072; F:heat shock protein binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0030544; F:Hsp70 protein binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0042277; F:peptide binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0036505; F:prosaposin receptor activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IDA:ParkinsonsUK-UCL. DR GO; GO:0042416; P:dopamine biosynthetic process; IEA:Ensembl. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome. DR GO; GO:0031987; P:locomotion involved in locomotory behavior; IEA:Ensembl. DR GO; GO:1903206; P:negative regulation of hydrogen peroxide-induced cell death; ISS:ParkinsonsUK-UCL. DR GO; GO:0045964; P:positive regulation of dopamine metabolic process; 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; Complete proteome; Disulfide bond; KW Endoplasmic reticulum; G-protein coupled receptor; Glycoprotein; KW Membrane; Receptor; Reference proteome; Signal; Transducer; KW Transmembrane; Transmembrane helix; Ubl conjugation. FT SIGNAL 1 26 {ECO:0000255}. FT CHAIN 27 613 Prosaposin receptor GPR37. FT /FTId=PRO_0000012799. FT TOPO_DOM 27 265 Extracellular. {ECO:0000255}. FT TRANSMEM 266 286 Helical; Name=1. {ECO:0000255}. FT TOPO_DOM 287 299 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 300 320 Helical; Name=2. {ECO:0000255}. FT TOPO_DOM 321 335 Extracellular. {ECO:0000255}. FT TRANSMEM 336 356 Helical; Name=3. {ECO:0000255}. FT TOPO_DOM 357 379 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 380 400 Helical; Name=4. {ECO:0000255}. FT TOPO_DOM 401 443 Extracellular. {ECO:0000255}. FT TRANSMEM 444 464 Helical; Name=5. {ECO:0000255}. FT TOPO_DOM 465 493 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 494 514 Helical; Name=6. {ECO:0000255}. FT TOPO_DOM 515 531 Extracellular. {ECO:0000255}. FT TRANSMEM 532 552 Helical; Name=7. {ECO:0000255}. FT TOPO_DOM 553 613 Cytoplasmic. {ECO:0000255}. FT COMPBIAS 563 568 Poly-Cys. FT CARBOHYD 36 36 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 222 222 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 239 239 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 334 419 {ECO:0000255|PROSITE-ProRule:PRU00521}. FT CONFLICT 93 93 G -> D (in Ref. 3; AAC51281). FT {ECO:0000305}. FT CONFLICT 106 106 A -> T (in Ref. 3; AAC51281). FT {ECO:0000305}. FT CONFLICT 118 118 G -> V (in Ref. 3; AAC51281). FT {ECO:0000305}. FT CONFLICT 160 160 G -> V (in Ref. 3; AAC51281). FT {ECO:0000305}. FT CONFLICT 182 182 W -> C (in Ref. 3; AAC51281). FT {ECO:0000305}. FT CONFLICT 231 231 E -> D (in Ref. 3; AAC51281). FT {ECO:0000305}. FT CONFLICT 284 284 C -> S (in Ref. 2; AAB70008). FT {ECO:0000305}. FT CONFLICT 304 304 A -> V (in Ref. 3; AAC51281). FT {ECO:0000305}. FT CONFLICT 329 329 L -> V (in Ref. 3; AAC51281). FT {ECO:0000305}. FT CONFLICT 503 504 FC -> LG (in Ref. 3; AAC51281). FT {ECO:0000305}. FT CONFLICT 598 598 T -> A (in Ref. 3; AAC51281). FT {ECO:0000305}. SQ SEQUENCE 613 AA; 67114 MW; 5A1AB269ED63E765 CRC64; MRAPGALLAR MSRLLLLLLL KVSASSALGV APASRNETCL GESCAPTVIQ RRGRDAWGPG NSARDVLRAR APREEQGAAF LAGPSWDLPA APGRDPAAGR GAEASAAGPP GPPTRPPGPW RWKGARGQEP SETLGRGNPT ALQLFLQISE EEEKGPRGAG ISGRSQEQSV KTVPGASDLF YWPRRAGKLQ GSHHKPLSKT ANGLAGHEGW TIALPGRALA QNGSLGEGIH EPGGPRRGNS TNRRVRLKNP FYPLTQESYG AYAVMCLSVV IFGTGIIGNL AVMCIVCHNY YMRSISNSLL ANLAFWDFLI IFFCLPLVIF HELTKKWLLE DFSCKIVPYI EVASLGVTTF TLCALCIDRF RAATNVQMYY EMIENCSSTT AKLAVIWVGA LLLALPEVVL RQLSKEDLGF SGRAPAERCI IKISPDLPDT IYVLALTYDS ARLWWYFGCY FCLPTLFTIT CSLVTARKIR KAEKACTRGN KRQIQLESQM NCTVVALTIL YGFCIIPENI CNIVTAYMAT GVSQQTMDLL NIISQFLLFF KSCVTPVLLF CLCKPFSRAF MECCCCCCEE CIQKSSTVTS DDNDNEYTTE LELSPFSTIR REMSTFASVG THC //