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O15354 (GPR37_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Prosaposin receptor GPR37
Alternative name(s):
Endothelin B receptor-like protein 1
Short name=ETBR-LP-1
G-protein coupled receptor 37
Parkin-associated endothelin receptor-like receptor
Short name=PAELR
Gene names
Name:GPR37
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length613 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for the neuroprotective and glioprotective factor prosaposin. Ligand binding induces endocytosis, followed by an ERK phosphorylation cascade. Ref.2 Ref.4 Ref.12

Subunit structure

Forms a complex with PARK2, STUB1 and HSP70. The amount of STUB1 in the complex increases during ER stress. STUB1 promotes the dissociation of HSP70 from PARK2, thus facilitating PARK2-mediated GPR37 ubiquitination. Interacts with PACRG. Ref.4 Ref.9 Ref.10

Subcellular location

Cell membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.11.

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). Ref.2

Post-translational modification

Ubiquitinated by PARK2 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. Ref.11

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Potential
Chain27 – 613587Prosaposin receptor GPR37
PRO_0000012799

Regions

Topological domain27 – 265239Extracellular Potential
Transmembrane266 – 28621Helical; Name=1; Potential
Topological domain287 – 29913Cytoplasmic Potential
Transmembrane300 – 32021Helical; Name=2; Potential
Topological domain321 – 33515Extracellular Potential
Transmembrane336 – 35621Helical; Name=3; Potential
Topological domain357 – 37923Cytoplasmic Potential
Transmembrane380 – 40021Helical; Name=4; Potential
Topological domain401 – 44343Extracellular Potential
Transmembrane444 – 46421Helical; Name=5; Potential
Topological domain465 – 49329Cytoplasmic Potential
Transmembrane494 – 51421Helical; Name=6; Potential
Topological domain515 – 53117Extracellular Potential
Transmembrane532 – 55221Helical; Name=7; Potential
Topological domain553 – 61361Cytoplasmic Potential
Compositional bias563 – 5686Poly-Cys

Amino acid modifications

Glycosylation361N-linked (GlcNAc...) Potential
Glycosylation2221N-linked (GlcNAc...) Potential
Glycosylation2391N-linked (GlcNAc...) Potential
Disulfide bond334 ↔ 419 By similarity

Experimental info

Sequence conflict931G → D in AAC51281. Ref.3
Sequence conflict1061A → T in AAC51281. Ref.3
Sequence conflict1181G → V in AAC51281. Ref.3
Sequence conflict1601G → V in AAC51281. Ref.3
Sequence conflict1821W → C in AAC51281. Ref.3
Sequence conflict2311E → D in AAC51281. Ref.3
Sequence conflict2841C → S in AAB70008. Ref.2
Sequence conflict3041A → V in AAC51281. Ref.3
Sequence conflict3291L → V in AAC51281. Ref.3
Sequence conflict503 – 5042FC → LG in AAC51281. Ref.3
Sequence conflict5981T → A in AAC51281. Ref.3

Sequences

Sequence LengthMass (Da)Tools
O15354 [UniParc].

Last modified January 1, 1999. Version 2.
Checksum: 5A1AB269ED63E765

FASTA61367,114
        10         20         30         40         50         60 
MRAPGALLAR MSRLLLLLLL KVSASSALGV APASRNETCL GESCAPTVIQ RRGRDAWGPG 

        70         80         90        100        110        120 
NSARDVLRAR APREEQGAAF LAGPSWDLPA APGRDPAAGR GAEASAAGPP GPPTRPPGPW 

       130        140        150        160        170        180 
RWKGARGQEP SETLGRGNPT ALQLFLQISE EEEKGPRGAG ISGRSQEQSV KTVPGASDLF 

       190        200        210        220        230        240 
YWPRRAGKLQ GSHHKPLSKT ANGLAGHEGW TIALPGRALA QNGSLGEGIH EPGGPRRGNS 

       250        260        270        280        290        300 
TNRRVRLKNP FYPLTQESYG AYAVMCLSVV IFGTGIIGNL AVMCIVCHNY YMRSISNSLL 

       310        320        330        340        350        360 
ANLAFWDFLI IFFCLPLVIF HELTKKWLLE DFSCKIVPYI EVASLGVTTF TLCALCIDRF 

       370        380        390        400        410        420 
RAATNVQMYY EMIENCSSTT AKLAVIWVGA LLLALPEVVL RQLSKEDLGF SGRAPAERCI 

       430        440        450        460        470        480 
IKISPDLPDT IYVLALTYDS ARLWWYFGCY FCLPTLFTIT CSLVTARKIR KAEKACTRGN 

       490        500        510        520        530        540 
KRQIQLESQM NCTVVALTIL YGFCIIPENI CNIVTAYMAT GVSQQTMDLL NIISQFLLFF 

       550        560        570        580        590        600 
KSCVTPVLLF CLCKPFSRAF MECCCCCCEE CIQKSSTVTS DDNDNEYTTE LELSPFSTIR 

       610 
REMSTFASVG THC 

« Hide

References

« Hide 'large scale' references
[1]"Cloning of GPR37, a gene located on chromosome 7 encoding a putative G-protein-coupled peptide receptor, from a human frontal brain EST library."
Marazziti D., Golini E., Gallo A., Lombardi M.S., Matteoni R., Tocchini-Valentini G.P.
Genomics 45:68-77(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Brain.
[2]"A human gene encodes a putative G protein-coupled receptor highly expressed in the central nervous system."
Donohue P.J., Shapira H., Mantey S.A., Hampton L.L., Jensen R.T., Battey J.F.
Brain Res. Mol. Brain Res. 54:152-160(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
Tissue: Brain.
[3]"A novel endothelin receptor type-B-like gene enriched in the brain."
Zeng Z., Su K., Kyaw H., Li Y.
Biochem. Biophys. Res. Commun. 233:559-567(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin."
Imai Y., Soda M., Inoue H., Hattori N., Mizuno Y., Takahashi R.
Cell 105:891-902(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH PARK2.
Tissue: Brain.
[5]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[9]"CHIP is associated with Parkin, a gene responsible for familial Parkinson's disease, and enhances its ubiquitin ligase activity."
Imai Y., Soda M., Hatakeyama S., Akagi T., Hashikawa T., Nakayama K., Takahashi R.
Mol. Cell 10:55-67(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PARK2; STUB1 AND HSP70.
[10]"A product of the human gene adjacent to parkin is a component of Lewy bodies and suppresses Pael receptor-induced cell death."
Imai Y., Soda M., Murakami T., Shoji M., Abe K., Takahashi R.
J. Biol. Chem. 278:51901-51910(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PACRG.
[11]"A ubiquitin ligase HRD1 promotes the degradation of Pael receptor, a substrate of Parkin."
Omura T., Kaneko M., Okuma Y., Orba Y., Nagashima K., Takahashi R., Fujitani N., Matsumura S., Hata A., Kubota K., Murahashi K., Uehara T., Nomura Y.
J. Neurochem. 99:1456-1469(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, SUBCELLULAR LOCATION.
[12]"GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin."
Meyer R.C., Giddens M.M., Schaefer S.A., Hall R.A.
Proc. Natl. Acad. Sci. U.S.A. 110:9529-9534(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y12476, Y12477 Genomic DNA. Translation: CAA73080.1.
AF017262 mRNA. Translation: AAB70008.1.
U87460 mRNA. Translation: AAC51281.1.
AF502281 mRNA. Translation: AAM18625.2.
AC004925 Genomic DNA. Translation: AAD08853.1.
CH236947 Genomic DNA. Translation: EAL24325.1.
CH471070 Genomic DNA. Translation: EAW83613.1.
BC040007 mRNA. Translation: AAH40007.1.
CCDSCCDS5792.1.
PIRJC5501.
RefSeqNP_005293.1. NM_005302.3.
UniGeneHs.406094.
Hs.731392.

3D structure databases

ProteinModelPortalO15354.
SMRO15354. Positions 240-565.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109119. 14 interactions.
STRING9606.ENSP00000306449.

Chemistry

GuidetoPHARMACOLOGY103.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteO15354.

Proteomic databases

PaxDbO15354.
PRIDEO15354.

Protocols and materials databases

DNASU2861.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000303921; ENSP00000306449; ENSG00000170775.
GeneID2861.
KEGGhsa:2861.
UCSCuc003vli.4. human.

Organism-specific databases

CTD2861.
GeneCardsGC07M124386.
HGNCHGNC:4494. GPR37.
MIM602583. gene.
neXtProtNX_O15354.
PharmGKBPA28882.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG291459.
HOGENOMHOG000252922.
HOVERGENHBG051808.
InParanoidO15354.
KOK04243.
OMAIQRRSRD.
OrthoDBEOG79SDX9.
PhylomeDBO15354.
TreeFamTF331292.

Gene expression databases

ArrayExpressO15354.
BgeeO15354.
CleanExHS_GPR37.
GenevestigatorO15354.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR003909. GPR37_orph.
[Graphical view]
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR01421. GPR37ORPHANR.
PROSITEPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGPR37.
GenomeRNAi2861.
NextBio11281.
PROO15354.
SOURCESearch...

Entry information

Entry nameGPR37_HUMAN
AccessionPrimary (citable) accession number: O15354
Secondary accession number(s): A4D0Y6 expand/collapse secondary AC list , O00348, O14768, Q8TD39
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: January 1, 1999
Last modified: July 9, 2014
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries