Q9Y653 (GPR56_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
G-protein coupled receptor 56

Alternative name(s):
Protein TM7XN1

Gene names

Name:	GPR56
Synonyms:	TM7LN4, TM7XN1
ORF Names:	UNQ540/PRO1083

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	693 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	Could be involved in cell-cell interactions.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Widely distributed with highest levels found in thyroid gland, brain and heart. Expressed in a great number of tumor cells.
Post-translational modification	The endogenous protein is proteolytically cleaved into 2 subunits, an extracellular subunit and a seven-transmembrane subunit. Ref.12
Involvement in disease	Polymicrogyria, bilateral frontoparietal (BFPP) [MIM:606854]: A malformation of the cortex in which the brain surface is irregular and characterized by an excessive number of small gyri with abnormal lamination, most severe in the frontoparietal regions. BFPP clinical manifestations include developmental and psychomotor delay, cerebellar and pyramidal signs, truncal ataxia, seizures, hyperreflexia. Polymicrogyria is a heterogeneous disorder, considered to be the result of postmigratory abnormal cortical organization. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13
Sequence similarities	Belongs to the G-protein coupled receptor 2 family. LN-TM7 subfamily. Contains 1 GPS domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	brain development Inferred from mutant phenotype Ref.13. Source: GDB cell adhesion Inferred from direct assay PubMed 15674329. Source: GDB cell-cell signaling Traceable author statement Ref.1. Source: ProtInc neuropeptide signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	G-protein coupled receptor activity Traceable author statement PubMed 15004227. Source: GDB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y653-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9Y653-2)

The sequence of this isoform differs from the canonical sequence as follows:
     429-434: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Ref.10
	Chain	26 – 693	668	G-protein coupled receptor 56		PRO_0000012880
Regions
	Topological domain	26 – 402	377	Extracellular Potential
	Transmembrane	403 – 423	21	Helical; Name=1; Potential
	Topological domain	424 – 448	25	Cytoplasmic Potential
	Transmembrane	449 – 469	21	Helical; Name=2; Potential
	Topological domain	470 – 476	7	Extracellular Potential
	Transmembrane	477 – 497	21	Helical; Name=3; Potential
	Topological domain	498 – 518	21	Cytoplasmic Potential
	Transmembrane	519 – 539	21	Helical; Name=4; Potential
	Topological domain	540 – 576	37	Extracellular Potential
	Transmembrane	577 – 597	21	Helical; Name=5; Potential
	Topological domain	598 – 609	12	Cytoplasmic Potential
	Transmembrane	610 – 630	21	Helical; Name=6; Potential
	Topological domain	631 – 636	6	Extracellular Potential
	Transmembrane	637 – 657	21	Helical; Name=7; Potential
	Topological domain	658 – 693	36	Cytoplasmic Potential
	Domain	343 – 394	52	GPS
Sites
	Site	382 – 383	2	Cleavage; by autocatalysis Probable
Amino acid modifications
	Glycosylation	39	1	N-linked (GlcNAc...) Potential
	Glycosylation	148	1	N-linked (GlcNAc...) Potential
	Glycosylation	171	1	N-linked (GlcNAc...) Potential
	Glycosylation	234	1	N-linked (GlcNAc...) Potential
	Glycosylation	303	1	N-linked (GlcNAc...) Potential
	Glycosylation	324	1	N-linked (GlcNAc...) Potential
	Glycosylation	341	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	429 – 434	6	Missing in isoform 2.		VSP_035068
	Natural variant	38	1	R → W in BFPP. Ref.13		VAR_026242
	Natural variant	88	1	Y → C in BFPP. Ref.13		VAR_026243
	Natural variant	91	1	C → S in BFPP. Ref.13		VAR_026244
	Natural variant	281	1	S → R. Ref.1 Ref.2 Corresponds to variant rs1801257 [ dbSNP | Ensembl ].		VAR_017910
	Natural variant	306	1	Q → H. Ref.1 Ref.2 Ref.6 Ref.9 Corresponds to variant rs1801255 [ dbSNP | Ensembl ].		VAR_017911
	Natural variant	346	1	C → S in BFPP. Ref.13		VAR_026245
	Natural variant	493	1	M → T. Corresponds to variant rs17379472 [ dbSNP | Ensembl ].		VAR_049457
	Natural variant	527	1	P → L. Corresponds to variant rs16958679 [ dbSNP | Ensembl ].		VAR_049458
	Natural variant	565	1	R → W in BFPP. Ref.13		VAR_026246
Experimental info
	Mutagenesis	381	1	H → S: Abolishes cleavage. Ref.12
	Mutagenesis	383	1	T → G: Abolishes cleavage. Ref.12
	Sequence conflict	678	1	S → C in AAD30545. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 15, 2004. Version 2. Checksum: 801C8E62666A5155	FASTA	693	77,738
	10 20 30 40 50 60 MTPQSLLQTT LFLLSLLFLV QGAHGRGHRE DFRFCSQRNQ THRSSLHYKP TPDLRISIEN 70 80 90 100 110 120 SEEALTVHAP FPAAHPASRS FPDPRGLYHF CLYWNRHAGR LHLLYGKRDF LLSDKASSLL 130 140 150 160 170 180 CFQHQEESLA QGPPLLATSV TSWWSPQNIS LPSAASFTFS FHSPPHTAAH NASVDMCELK 190 200 210 220 230 240 RDLQLLSQFL KHPQKASRRP SAAPASQQLQ SLESKLTSVR FMGDMVSFEE DRINATVWKL 250 260 270 280 290 300 QPTAGLQDLH IHSRQEEEQS EIMEYSVLLP RTLFQRTKGR SGEAEKRLLL VDFSSQALFQ 310 320 330 340 350 360 DKNSSQVLGE KVLGIVVQNT KVANLTEPVV LTFQHQLQPK NVTLQCVFWV EDPTLSSPGH 370 380 390 400 410 420 WSSAGCETVR RETQTSCFCN HLTYFAVLMV SSVEVDAVHK HYLSLLSYVG CVVSALACLV 430 440 450 460 470 480 TIAAYLCSRV PLPCRRKPRD YTIKVHMNLL LAVFLLDTSF LLSEPVALTG SEAGCRASAI 490 500 510 520 530 540 FLHFSLLTCL SWMGLEGYNL YRLVVEVFGT YVPGYLLKLS AMGWGFPIFL VTLVALVDVD 550 560 570 580 590 600 NYGPIILAVH RTPEGVIYPS MCWIRDSLVS YITNLGLFSL VFLFNMAMLA TMVVQILRLR 610 620 630 640 650 660 PHTQKWSHVL TLLGLSLVLG LPWALIFFSF ASGTFQLVVL YLFSIITSFQ GFLIFIWYWS 670 680 690 MRLQARGGPS PLKSNSDSAR LPISSGSTSS SRI
	Isoform 2 [UniParc]. Checksum: BB8712796ED1B99B	FASTA	687	77,072
	10 20 30 40 50 60 MTPQSLLQTT LFLLSLLFLV QGAHGRGHRE DFRFCSQRNQ THRSSLHYKP TPDLRISIEN 70 80 90 100 110 120 SEEALTVHAP FPAAHPASRS FPDPRGLYHF CLYWNRHAGR LHLLYGKRDF LLSDKASSLL 130 140 150 160 170 180 CFQHQEESLA QGPPLLATSV TSWWSPQNIS LPSAASFTFS FHSPPHTAAH NASVDMCELK 190 200 210 220 230 240 RDLQLLSQFL KHPQKASRRP SAAPASQQLQ SLESKLTSVR FMGDMVSFEE DRINATVWKL 250 260 270 280 290 300 QPTAGLQDLH IHSRQEEEQS EIMEYSVLLP RTLFQRTKGR SGEAEKRLLL VDFSSQALFQ 310 320 330 340 350 360 DKNSSQVLGE KVLGIVVQNT KVANLTEPVV LTFQHQLQPK NVTLQCVFWV EDPTLSSPGH 370 380 390 400 410 420 WSSAGCETVR RETQTSCFCN HLTYFAVLMV SSVEVDAVHK HYLSLLSYVG CVVSALACLV 430 440 450 460 470 480 TIAAYLCSRR KPRDYTIKVH MNLLLAVFLL DTSFLLSEPV ALTGSEAGCR ASAIFLHFSL 490 500 510 520 530 540 LTCLSWMGLE GYNLYRLVVE VFGTYVPGYL LKLSAMGWGF PIFLVTLVAL VDVDNYGPII 550 560 570 580 590 600 LAVHRTPEGV IYPSMCWIRD SLVSYITNLG LFSLVFLFNM AMLATMVVQI LRLRPHTQKW 610 620 630 640 650 660 SHVLTLLGLS LVLGLPWALI FFSFASGTFQ LVVLYLFSII TSFQGFLIFI WYWSMRLQAR 670 680 GGPSPLKSNS DSARLPISSG STSSSRI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"GPR56, a novel secretin-like human G-protein-coupled receptor gene." Liu M., Parker R.M.C., Darby K., Eyre H.J., Copeland N.G., Crawford J., Gilbert D.J., Sutherland G.R., Jenkins N.A., Herzog H. Genomics 55:296-305(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS ARG-281 AND HIS-306.
[2]	"TM7XN1, a novel human EGF-TM7 like protein, detected with mRNA differential display using human melanoma cell lines with different metastatic potential." Zendman A.J.W., Cornelissen I.M.H.A., Weidle U.H., Ruiter D.J., van Muijen G.N.P. FEBS Lett. 446:292-298(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS ARG-281 AND HIS-306.
[3]	Kaighin V.A., Martin A.L., Aronstam R.S. Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[4]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"Genome-wide discovery and analysis of human seven transmembrane helix receptor genes." Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., Tsutsumi S., Aburatani H., Asai K., Akiyama Y. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT HIS-306.
[7]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.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. , 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].
[9]	"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] (ISOFORM 1), VARIANT HIS-306. Tissue: Placenta.
[10]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-40.
[11]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[12]	"A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis." Arac D., Boucard A.A., Bolliger M.F., Nguyen J., Soltis S.M., Sudhof T.C., Brunger A.T. EMBO J. 31:1364-1378(2012) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING, MUTAGENESIS OF HIS-381 AND THR-383.
[13]	"G protein-coupled receptor-dependent development of human frontal cortex." Piao X., Hill R.S., Bodell A., Chang B.S., Basel-Vanagaite L., Straussberg R., Dobyns W.B., Qasrawi B., Winter R.M., Innes A.M., Voit T., Ross M.E., Michaud J.L., Descarie J.-C., Barkovich A.J., Walsh C.A. Science 303:2033-2036(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS BFPP TRP-38; CYS-88; SER-91; SER-346 AND TRP-565.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF106858 mRNA. Translation: AAD30545.1. AJ011001 mRNA. Translation: CAB37294.1. EU432119 mRNA. Translation: ABY87918.1. AY358400 mRNA. Translation: AAQ88766.1. AB065909 Genomic DNA. Translation: BAC06124.1. BT007311 mRNA. Translation: AAP35975.1. AC018552 Genomic DNA. No translation available. CH471092 Genomic DNA. Translation: EAW82939.1. CH471092 Genomic DNA. Translation: EAW82940.1. BC008770 mRNA. Translation: AAH08770.1.
IPI	IPI00397949. IPI00412420.
RefSeq	NP_001139242.1. NM_001145770.1. NP_001139243.1. NM_001145771.1. NP_001139244.1. NM_001145772.1. NP_001139246.1. NM_001145774.1. NP_005673.3. NM_005682.5. NP_958932.1. NM_201524.2. NP_958933.1. NM_201525.2.
UniGene	Hs.513633.
3D structure databases
ProteinModelPortal	Q9Y653.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y653. 1 interaction.
STRING	9606.ENSP00000369018.
Protein family/group databases
MEROPS	S63.011.
GPCRDB	Search...
PTM databases
PhosphoSite	Q9Y653.
Polymorphism databases
DMDM	45476992.
Proteomic databases
PaxDb	Q9Y653.
PRIDE	Q9Y653.
Protocols and materials databases
DNASU	9289.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000379696; ENSP00000369018; ENSG00000205336. ENST00000388812; ENSP00000373464; ENSG00000205336. ENST00000388813; ENSP00000373465; ENSG00000205336. ENST00000456916; ENSP00000398034; ENSG00000205336. ENST00000538815; ENSP00000444415; ENSG00000205336. ENST00000540164; ENSP00000444911; ENSG00000205336. ENST00000562558; ENSP00000456620; ENSG00000205336. ENST00000562631; ENSP00000455351; ENSG00000205336. ENST00000567835; ENSP00000456794; ENSG00000205336. ENST00000568908; ENSP00000457456; ENSG00000205336. ENST00000568909; ENSP00000455215; ENSG00000205336.
GeneID	9289.
KEGG	hsa:9289.
UCSC	uc002ema.1. human. uc002emc.2. human.
Organism-specific databases
CTD	9289.
GeneCards	GC16P057653.
HGNC	HGNC:4512. GPR56.
HPA	HPA046065.
MIM	604110. gene. 606854. phenotype.
neXtProt	NX_Q9Y653.
Orphanet	101070. Bilateral frontoparietal polymicrogyria.
PharmGKB	PA28901.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG290113.
HOVERGEN	HBG051814.
InParanoid	Q9Y653.
KO	K08450.
OMA	WGFPIFL.
Gene expression databases
ArrayExpress	Q9Y653.
Bgee	Q9Y653.
CleanEx	HS_GPR56.
Genevestigator	Q9Y653.
GermOnline	ENSG00000205336. Homo sapiens.
Family and domain databases
InterPro	IPR017981. GPCR_2-like. IPR003910. GPCR_2_orphan_rcpt_GPR56. IPR000832. GPCR_2_secretin-like. IPR000203. GPS_dom. [Graphical view]
Pfam	PF00002. 7tm_2. 1 hit. PF01825. GPS. 1 hit. [Graphical view]
PRINTS	PR00249. GPCRSECRETIN. PR01422. GPR56ORPHANR.
SMART	SM00303. GPS. 1 hit. [Graphical view]
PROSITE	PS00650. G_PROTEIN_RECEP_F2_2. False negative. PS50261. G_PROTEIN_RECEP_F2_4. 1 hit. PS50221. GPS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	GPR56. human.
GenomeRNAi	9289.
NextBio	34805.
SOURCE	Search...

Entry information

Entry name

GPR56_HUMAN

Accession

Primary (citable) accession number: Q9Y653
Secondary accession number(s): A6NIT7 , A6NJV9, B0M0K4, O95966, Q8NGB3, Q96HB4

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2004
Last sequence update:	March 15, 2004
Last modified:	May 1, 2013
This is version 120 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.