O15354 (GPR37_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Probable G-protein coupled receptor 37

Alternative name(s):
Endothelin B receptor-like protein 1
Short name=ETBR-LP-1
Parkin-associated endothelin receptor-like receptor
Short name=PAELR

Gene names

Name:

GPR37

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	613 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Orphan receptor. May have a unique functional role in the central nervous system. Ref.2 Ref.4
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.7 Ref.8
Subcellular location	Cell membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.9.
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.9
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Endoplasmic reticulum Membrane
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement Ref.3. Source: ProtInc
Molecular_function	G-protein coupled receptor activity Traceable author statement Ref.3. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Potential
	Chain	27 – 613	587	Probable G-protein coupled receptor 37		PRO_0000012799
Regions
	Topological domain	27 – 265	239	Extracellular Potential
	Transmembrane	266 – 286	21	Helical; Name=1; Potential
	Topological domain	287 – 299	13	Cytoplasmic Potential
	Transmembrane	300 – 320	21	Helical; Name=2; Potential
	Topological domain	321 – 335	15	Extracellular Potential
	Transmembrane	336 – 356	21	Helical; Name=3; Potential
	Topological domain	357 – 379	23	Cytoplasmic Potential
	Transmembrane	380 – 400	21	Helical; Name=4; Potential
	Topological domain	401 – 443	43	Extracellular Potential
	Transmembrane	444 – 464	21	Helical; Name=5; Potential
	Topological domain	465 – 493	29	Cytoplasmic Potential
	Transmembrane	494 – 514	21	Helical; Name=6; Potential
	Topological domain	515 – 531	17	Extracellular Potential
	Transmembrane	532 – 552	21	Helical; Name=7; Potential
	Topological domain	553 – 613	61	Cytoplasmic Potential
	Compositional bias	563 – 568	6	Poly-Cys
Amino acid modifications
	Glycosylation	36	1	N-linked (GlcNAc...) Potential
	Glycosylation	222	1	N-linked (GlcNAc...) Potential
	Glycosylation	239	1	N-linked (GlcNAc...) Potential
	Disulfide bond	334 ↔ 419		By similarity
Experimental info
	Sequence conflict	93	1	G → D in AAC51281. Ref.3
	Sequence conflict	106	1	A → T in AAC51281. Ref.3
	Sequence conflict	118	1	G → V in AAC51281. Ref.3
	Sequence conflict	160	1	G → V in AAC51281. Ref.3
	Sequence conflict	182	1	W → C in AAC51281. Ref.3
	Sequence conflict	231	1	E → D in AAC51281. Ref.3
	Sequence conflict	284	1	C → S in AAB70008. Ref.2
	Sequence conflict	304	1	A → V in AAC51281. Ref.3
	Sequence conflict	329	1	L → V in AAC51281. Ref.3
	Sequence conflict	503 – 504	2	FC → LG in AAC51281. Ref.3
	Sequence conflict	598	1	T → A in AAC51281. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	O15354 [UniParc]. Last modified January 1, 1999. Version 2. Checksum: 5A1AB269ED63E765	FASTA	613	67,114
	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

References

	« Hide 'large scale' referencesShow '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. , 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]	"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.
[7]	"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.
[8]	"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.
[9]	"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.
+	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. BC040007 mRNA. Translation: AAH40007.1.
IPI	IPI00006166.
PIR	JC5501.
RefSeq	NP_005293.1. NM_005302.3.
UniGene	Hs.731392.
3D structure databases
ProteinModelPortal	O15354.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000306449.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	O15354.
Proteomic databases
PaxDb	O15354.
PRIDE	O15354.
Protocols and materials databases
DNASU	2861.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000303921; ENSP00000306449; ENSG00000170775.
GeneID	2861.
KEGG	hsa:2861.
UCSC	uc003vli.3. human.
Organism-specific databases
CTD	2861.
GeneCards	GC07M124386.
HGNC	HGNC:4494. GPR37.
MIM	602583. gene.
neXtProt	NX_O15354.
PharmGKB	PA28882.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG291459.
HOGENOM	HOG000252922.
HOVERGEN	HBG051808.
InParanoid	O15354.
KO	K04243.
OMA	IQRRSRD.
OrthoDB	EOG4B5P5H.
PhylomeDB	O15354.
Gene expression databases
ArrayExpress	O15354.
Bgee	O15354.
CleanEx	HS_GPR37.
Genevestigator	O15354.
GermOnline	ENSG00000170775. Homo sapiens.
Family and domain databases
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR003909. GPR37_orph. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR01421. GPR37ORPHANR.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. False negative. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	2861.
NextBio	11281.
SOURCE	Search...

Entry information

Entry name

GPR37_HUMAN

Accession

Primary (citable) accession number: O15354
Secondary accession number(s): O00348, O14768, Q8TD39

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	January 1, 1999
Last modified:	May 1, 2013
This is version 114 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.