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Q8K209 (GPR56_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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:
G-protein coupled receptor 56
Alternative name(s):
Serpentine receptor cyt28

Cleaved into the following 2 chains:

  1. GPR56 N-terminal fragment
    Short name=GPR56 NT
    Short name=GPR56(N)
    Alternative name(s):
    GPR56 extracellular subunit
    GPR56 subunit alpha
  2. GPR56 C-terminal fragment
    Short name=GPR56 CT
    Short name=GPR56(C)
    Alternative name(s):
    GPR56 seven-transmembrane subunit
    Short name=GPR56 7TM
    GPR56 subunit beta
Gene names
Name:Gpr56
Synonyms:Cyt28
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length687 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in cell adhesion and probably in cell-cell interactions. Regulates the migration of neural precursor cells. Receptor for collagen III/Col3a1 in the developing brain and involved in regulation of cortical development, specifically in maintenance of the pial basemant membrane integrity and in cortical lamination. Binding to the Col3a1 ligand inhibits neuronal migration and activates the RhoA pathway by coupling to Gna13 and possibly Gna12. Ref.5 Ref.6 Ref.7 Ref.8

Enzyme regulation

GPR56 NT is proposed to inhibit receptor signaling; its interactions with extracellular ligands and /or homophilic GPR56 NT interactions may relieve the inhibition By similarity.

Subunit structure

Predominantly non-covalently linked heterodimer of the N-terminal and the C-terminal fragment. GPR56 NT self-associates in a trans-trans manner; the homophilic interaction enhances receptor signaling. GPR56 CT interacts with ARRB2; the interaction is impaired by GPR56 NT. Part of a GPCR-tetraspanin complex at least consisting of GPR56, CD81, eventually CD9, and GNA11 in which CD81 is enhancing the association of GPR56 with GNA11 By similarity. Ref.4

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.4.

GPR56 N-terminal fragment: Secreted Ref.4.

Tissue specificity

Expressed in neural progenitor cells in fetal forbrain. Expressed in migrating neurons. Expressed in radial glial endfeet (at protein level). Ref.8

Post-translational modification

Autoproteolytically cleaved into 2 fragments; the large extracellular N-terminal fragment and the membroune-bound C-terminal fragment predominantly remain associated and non-covalently linked. Ref.9

N-glycosylated. Th secreted GPR56 N-terminal fragment is heavily glycosylated. Ref.4

Ubiquitinated. Undergoes polyubiquitination upon activation By similarity.

Disruption phenotype

Cobblestone-like cortical malformation with defective pial basement membrane (BM), abnormal anchorage of radial glial endfeet, mislocalized Cajal-Retzius cells and neuronal overmigration. Severe malformation of the rostral cerebellum that develops perinatally. Granule cells from the rostral region show loss of adhesion to extracellular matrix molecules of the pial basement membrane. Ref.5 Ref.7

Sequence similarities

Belongs to the G-protein coupled receptor 2 family. LN-TM7 subfamily.

Contains 1 GPS domain.

Ontologies

Keywords
   Biological processCell adhesion
Differentiation
   Cellular componentCell membrane
Membrane
Secreted
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
G-protein coupled receptor
Receptor
Transducer
   PTMGlycoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRho protein signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

cell adhesion

Inferred from electronic annotation. Source: UniProtKB-KW

cerebral cortex radial glia guided migration

Inferred from mutant phenotype Ref.5. Source: UniProtKB

layer formation in cerebral cortex

Inferred from mutant phenotype Ref.5. Source: UniProtKB

negative regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of neuron migration

Inferred from mutant phenotype Ref.5. Source: UniProtKB

neuropeptide signaling pathway

Inferred from electronic annotation. Source: InterPro

positive regulation of Rho protein signal transduction

Inferred from mutant phenotype Ref.8. Source: UniProtKB

positive regulation of cell adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase C signaling

Inferred from sequence or structural similarity. Source: UniProtKB

vascular endothelial growth factor production

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentextracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

glial limiting end-foot

Inferred from direct assay Ref.5. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionG-protein coupled receptor activity

Inferred from mutant phenotype Ref.8. Source: UniProtKB

collagen binding

Inferred from direct assay Ref.8. Source: UniProtKB

extracellular matrix binding

Inferred from direct assay Ref.5. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Chain26 – 687662G-protein coupled receptor 56
PRO_0000012882
Chain26 – ?382357GPR56 N-terminal fragment
PRO_0000423090
Chain?383 – 687305GPR56 C-terminal fragment
PRO_0000423091

Regions

Topological domain26 – 402377Extracellular Potential
Transmembrane403 – 42321Helical; Name=1; Potential
Topological domain424 – 44219Cytoplasmic Potential
Transmembrane443 – 46321Helical; Name=2; Potential
Topological domain464 – 4718Extracellular Potential
Transmembrane472 – 49221Helical; Name=3; Potential
Topological domain493 – 51220Cytoplasmic Potential
Transmembrane513 – 53321Helical; Name=4; Potential
Topological domain534 – 57037Extracellular Potential
Transmembrane571 – 59121Helical; Name=5; Potential
Topological domain592 – 60312Cytoplasmic Potential
Transmembrane604 – 62421Helical; Name=6; Potential
Topological domain625 – 6306Extracellular Potential
Transmembrane631 – 65121Helical; Name=7; Potential
Topological domain652 – 68736Cytoplasmic Potential
Domain343 – 39452GPS

Sites

Site382 – 3832Cleavage; by autocatalysis By similarity

Amino acid modifications

Glycosylation391N-linked (GlcNAc...) Ref.4
Glycosylation1481N-linked (GlcNAc...) Ref.4
Glycosylation1711N-linked (GlcNAc...) Ref.4
Glycosylation2341N-linked (GlcNAc...) Ref.4
Glycosylation3031N-linked (GlcNAc...) Ref.4
Glycosylation3241N-linked (GlcNAc...) Ref.4
Glycosylation3411N-linked (GlcNAc...) Ref.4

Experimental info

Mutagenesis381R → Q or W: Reduced cell surface localization. Ref.9
Mutagenesis881Y → C: Reduced cell surface localization. Ref.9
Mutagenesis911C → S: Reduced cell surface localization. Ref.9
Mutagenesis3461C → S: Abolishes proteolytic cleavage and cell surface localization. Ref.4
Mutagenesis3491W → S: Abolishes proteolytic cleavage and cell surface localization. Ref.4
Sequence conflict6431F → Y in AAF00617. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q8K209 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: B5315D70B66C9A9A

FASTA68777,255
        10         20         30         40         50         60 
MAVQVLRQMV YFLLSLFSLV QGAHSGSPRE DFRFCGQRNQ TQQSTLHYDQ SSEPHIFVWN 

        70         80         90        100        110        120 
TEETLTIRAP FLAAPDIPRF FPEPRGLYHF CLYWSRHTGR LHLRYGKHDY LLSSQASRLL 

       130        140        150        160        170        180 
CFQKQEQSLK QGAPLIATSV SSWQIPQNTS LPGAPSFIFS FHNAPHKVSH NASVDMCDLK 

       190        200        210        220        230        240 
KELQQLSRYL QHPQKAAKRP TAAFISQQLQ SLESKLTSVS FLGDTLSFEE DRVNATVWKL 

       250        260        270        280        290        300 
PPTAGLEDLH IHSQKEEEQS EVQAYSLLLP RAVFQQTRGR RRDDAKRLLV VDFSSQALFQ 

       310        320        330        340        350        360 
DKNSSQVLGE KVLGIVVQNT KVTNLSDPVV LTFQHQPQPK NVTLQCVFWV EDPASSSTGS 

       370        380        390        400        410        420 
WSSAGCETVS RDTQTSCLCN HLTYFAVLMV SSTEVEATHK HYLTLLSYVG CVISALACVF 

       430        440        450        460        470        480 
TIAAYLCSRR KSRDYTIKVH MNLLSAVFLL DVSFLLSEPV ALTGSEAACR TSAMFLHFSL 

       490        500        510        520        530        540 
LACLSWMGLE GYNLYRLVVE VFGTYVPGYL LKLSIVGWGF PVFLVTLVAL VDVNNYGPII 

       550        560        570        580        590        600 
LAVRRTPERV TYPSMCWIRD SLVSYVTNLG LFSLVFLFNL AMLATMVVQI LRLRPHSQNW 

       610        620        630        640        650        660 
PHVLTLLGLS LVLGLPWALV FFSFASGTFQ LVILYLFSII TSFQGFLIFL WYWSMRFQAQ 

       670        680 
GGPSPLKNNS DSAKLPISSG STSSSRI 

« Hide

References

« Hide 'large scale' references
[1]"Identification of novel hematopoietic stem cell regulatory genes."
Phillips R.L., Ernst R.E., Dosil M., Wesley C.K., Moore K.A., Kingsley P.D., Sykes S., Palis J., Lemischka I.R.
Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C57BL/6.
Tissue: Liver.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Lung, Pituitary, Placenta and Spinal ganglion.
[3]"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].
[4]"Disease-associated mutations affect GPR56 protein trafficking and cell surface expression."
Jin Z., Tietjen I., Bu L., Liu-Yesucevitz L., Gaur S.K., Walsh C.A., Piao X.
Hum. Mol. Genet. 16:1972-1985(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, SUBCELLULAR LOCATION, GLYCOSYLATION AT ARG-38; ASN-39; TYR-88; CYS-91; ASN-148; ASN-171; ASN-234; ASN-303; ASN-324 AND ASN-341, MUTAGENESIS OF CYS-346 AND TRP-349.
[5]"GPR56 regulates pial basement membrane integrity and cortical lamination."
Li S., Jin Z., Koirala S., Bu L., Xu L., Hynes R.O., Walsh C.A., Corfas G., Piao X.
J. Neurosci. 28:5817-5826(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[6]"Orphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a G alpha 12/13 and Rho pathway."
Iguchi T., Sakata K., Yoshizaki K., Tago K., Mizuno N., Itoh H.
J. Biol. Chem. 283:14469-14478(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"GPR56-regulated granule cell adhesion is essential for rostral cerebellar development."
Koirala S., Jin Z., Piao X., Corfas G.
J. Neurosci. 29:7439-7449(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AND DISRUPTION PHENOTYPE.
[8]"G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination."
Luo R., Jeong S.J., Jin Z., Strokes N., Li S., Piao X.
Proc. Natl. Acad. Sci. U.S.A. 108:12925-12930(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, LIGAND-BINDING.
[9]"Disease-associated mutations prevent GPR56-collagen III interaction."
Luo R., Jin Z., Deng Y., Strokes N., Piao X.
PLoS ONE 7:E29818-E29818(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: LIGAND-BINDING, PROTEOLYTIC PROCESSING, MUTAGENESIS OF ARG-38; TYR-88 AND CYS-91.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF166382 mRNA. Translation: AAF00617.1.
AK087268 mRNA. Translation: BAC39835.1.
AK133678 mRNA. Translation: BAE21780.1.
AK141886 mRNA. Translation: BAE24871.1.
AK141894 mRNA. Translation: BAE24874.1.
AK167547 mRNA. Translation: BAE39613.1.
BC034678 mRNA. Translation: AAH34678.1.
RefSeqNP_001185823.1. NM_001198894.1.
NP_061370.2. NM_018882.3.
XP_006530755.1. XM_006530692.1.
XP_006530756.1. XM_006530693.1.
XP_006530757.1. XM_006530694.1.
XP_006530758.1. XM_006530695.1.
XP_006530759.1. XM_006530696.1.
XP_006530760.1. XM_006530697.1.
UniGeneMm.290834.

3D structure databases

ProteinModelPortalQ8K209.
SMRQ8K209. Positions 439-660.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ8K209. 1 interaction.
STRING10090.ENSMUSP00000090959.

Protein family/group databases

MEROPSS63.011.
GPCRDBSearch...

PTM databases

PhosphoSiteQ8K209.

Proteomic databases

PaxDbQ8K209.
PRIDEQ8K209.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000093271; ENSMUSP00000090959; ENSMUSG00000031785.
ENSMUST00000179619; ENSMUSP00000137520; ENSMUSG00000031785.
GeneID14766.
KEGGmmu:14766.
UCSCuc009mxl.2. mouse.

Organism-specific databases

CTD9289.
MGIMGI:1340051. Gpr56.

Phylogenomic databases

eggNOGNOG290113.
GeneTreeENSGT00750000117610.
HOGENOMHOG000015136.
HOVERGENHBG051814.
InParanoidQ8K209.
KOK08450.
OMAWGFPIFL.
OrthoDBEOG7XPZ55.
PhylomeDBQ8K209.
TreeFamTF321769.

Gene expression databases

BgeeQ8K209.
CleanExMM_GPR56.
GenevestigatorQ8K209.

Family and domain databases

InterProIPR017981. GPCR_2-like.
IPR003910. GPCR_2_orphan_rcpt_GPR56.
IPR000832. GPCR_2_secretin-like.
IPR000203. GPS.
[Graphical view]
PfamPF00002. 7tm_2. 1 hit.
PF01825. GPS. 1 hit.
[Graphical view]
PRINTSPR00249. GPCRSECRETIN.
PR01422. GPR56ORPHANR.
SMARTSM00303. GPS. 1 hit.
[Graphical view]
PROSITEPS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
PS50221. GPS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGPR56. mouse.
NextBio286855.
PROQ8K209.
SOURCESearch...

Entry information

Entry nameGPR56_MOUSE
AccessionPrimary (citable) accession number: Q8K209
Secondary accession number(s): Q3UR17, Q9QZT2
Entry history
Integrated into UniProtKB/Swiss-Prot: March 15, 2004
Last sequence update: October 1, 2002
Last modified: April 16, 2014
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries