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P41731 (CD63_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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:
CD63 antigen
Alternative name(s):
CD_antigen=CD63
Gene names
Name:Cd63
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length238 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Functions as cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activation of AKT, FAK/PTK2 and MAP kinases. Promotes cell survival, reorganization of the actin cytoskeleton, cell adhesion, spreading and migration, via its role in the activation of AKT and FAK/PTK2. Plays a role in VEGFA signaling via its role in regulating the internalization of KDR/VEGFR2. Plays a role in intracellular vesicular transport processes, and is required for normal trafficking of the PMEL luminal domain that is essential for the development and maturation of melanocytes. Plays a role in the adhesion of leukocytes onto endothelial cells via its role in the regulation of SELP trafficking. May play a role in mast cell degranulation in response to Ms4a2/FceRI stimulation, but not in mast cell degranulation in response to other stimuli. Ref.3 Ref.5 Ref.6 Ref.7 Ref.8

Subunit structure

Interacts with TIMP1 and ITGB1 and recruits TIMP1 to ITGB1. Interacts with CD9. Identified in a complex with CD9 and ITGB3. Interacts with PMEL. Interacts with KDR/VEGFR2; identified in a complex with ITGB1 and KDR/VEGFR2 and is required to recruit KDR to ITGB1 complexes By similarity.

Subcellular location

Cell membrane; Multi-pass membrane protein By similarity. Lysosome membrane; Multi-pass membrane protein. Late endosome membrane; Multi-pass membrane protein. Endosomemultivesicular body By similarity. Melanosome By similarity. Note: Also found in Weibel-Palade bodies of endothelial cells. Located in platelet dense granules. Detected in a subset of pre-melanosomes. Detected on intralumenal vesicles (ILVs) within multivesicular bodies By similarity. Ref.3 Ref.8

Tissue specificity

Ubiquitous. Strongly expressed in kidney. Detected in spleen, bone marrow, peripheral blood mononuclear cells and macrophages.

Post-translational modification

Palmitoylated at a low, basal level in unstimulated platelets. The level of palmitoylation increases when platelets are activated by thrombin (in vitro) By similarity.

Disruption phenotype

No visible phenotype. Mutant mice are viable and fertile, but display impaired water homeostasis, with increased urinary flow, increased water intake, reduced urine osmolality and increased fecal water content. Mice display inclusions in the principal cells in the renal collecting duct (Ref.3). Mutant mice display variable graying of their coat color and a dramatic reduction in the number of melanosomes in the retinal pigment epithelium (Ref.6). According to Ref.5, mutant mice display a defect in the Selp-dependent attachment of leukocytes to endothelial cells. According to Ref.8, mast cells from mutant mice show decreased degranulation and decreased release of TNF in response to Ms4a2/FceRI stimulation, but no difference in mast cell degranulation in response to other stimuli and no change in the release of IL6 and leukotriene C4. Ref.3 Ref.5 Ref.6 Ref.7 Ref.8

Sequence similarities

Belongs to the tetraspanin (TM4SF) family.

Ontologies

Keywords
   Biological processProtein transport
Transport
   Cellular componentCell membrane
Endosome
Lysosome
Membrane
   DomainTransmembrane
Transmembrane helix
   PTMGlycoprotein
Lipoprotein
Palmitate
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell migration

Inferred from sequence or structural similarity. Source: UniProtKB

cell-matrix adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

cellular protein localization

Inferred from sequence orthology PubMed 15647390. Source: MGI

endosome to melanosome transport

Inferred from sequence or structural similarity. Source: UniProtKB

pigment cell differentiation

Inferred from mutant phenotype Ref.6. Source: UniProtKB

pigment granule maturation

Inferred from sequence or structural similarity. Source: UniProtKB

pigmentation

Inferred from mutant phenotype Ref.6. Source: UniProtKB

positive regulation of integrin-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of receptor internalization

Inferred from sequence or structural similarity. Source: UniProtKB

protein transport

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of rubidium ion transport

Inferred from sequence orthology PubMed 15647390. Source: MGI

regulation of vascular endothelial growth factor signaling pathway

Inferred from mutant phenotype Ref.7. Source: UniProtKB

   Cellular_componentcell surface

Inferred from electronic annotation. Source: Ensembl

endosome membrane

Inferred from sequence orthology PubMed 15229288. Source: MGI

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

intrinsic component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

late endosome

Inferred from direct assay PubMed 14668490. Source: MGI

late endosome membrane

Inferred from sequence or structural similarity. Source: UniProtKB

lysosomal membrane

Inferred from sequence or structural similarity. Source: UniProtKB

lysosome

Inferred from direct assay PubMed 14668490. Source: MGI

melanosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

multivesicular body, internal vesicle

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionprotein binding

Inferred from physical interaction PubMed 15647390. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 238237CD63 antigen
PRO_0000219217

Regions

Topological domain2 – 1110Cytoplasmic Potential
Transmembrane12 – 3221Helical; Potential
Topological domain33 – 5119Extracellular Potential
Transmembrane52 – 7221Helical; Potential
Topological domain73 – 819Cytoplasmic Potential
Transmembrane82 – 10221Helical; Potential
Topological domain103 – 203101Extracellular Potential
Transmembrane204 – 22421Helical; Potential
Topological domain225 – 23814Cytoplasmic Potential

Amino acid modifications

Glycosylation1161N-linked (GlcNAc...) Potential
Glycosylation1301N-linked (GlcNAc...) Ref.4
Glycosylation1501N-linked (GlcNAc...) Potential
Glycosylation1721N-linked (GlcNAc...) Potential

Sequences

Sequence LengthMass (Da)Tools
P41731 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: B57E47B31E13EED8

FASTA23825,767
        10         20         30         40         50         60 
MAVEGGMKCV KFLLYVLLLA FCACAVGLIA IGVAVQVVLK QAITHETTAG SLLPVVIIAV 

        70         80         90        100        110        120 
GAFLFLVAFV GCCGACKENY CLMITFAIFL SLIMLVEVAV AIAGYVFRDQ VKSEFNKSFQ 

       130        140        150        160        170        180 
QQMQNYLKDN KTATILDKLQ KENNCCGASN YTDWENIPGM AKDRVPDSCC INITVGCGND 

       190        200        210        220        230 
FKESTIHTQG CVETIAIWLR KNILLVAAAA LGIAFVEVLG IIFSCCLVKS IRSGYEVM 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of the murine homologue of CD63/ME491 and detection of its strong expression in the kidney and activated macrophages."
Miyamoto M., Homma M., Hotta H.
Biochim. Biophys. Acta 1217:312-316(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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].
Strain: FVB/N.
Tissue: Colon and Mammary gland.
[3]"Deficiency of the tetraspanin CD63 associated with kidney pathology but normal lysosomal function."
Schroder J., Lullmann-Rauch R., Himmerkus N., Pleines I., Nieswandt B., Orinska Z., Koch-Nolte F., Schroder B., Bleich M., Saftig P.
Mol. Cell. Biol. 29:1083-1094(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, FUNCTION.
[4]"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-130.
[5]"CD63 is an essential cofactor to leukocyte recruitment by endothelial P-selectin."
Doyle E.L., Ridger V., Ferraro F., Turmaine M., Saftig P., Cutler D.F.
Blood 118:4265-4273(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[6]"The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis."
van Niel G., Charrin S., Simoes S., Romao M., Rochin L., Saftig P., Marks M.S., Rubinstein E., Raposo G.
Dev. Cell 21:708-721(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MELANOCYTE DEVELOPMENT, DISRUPTION PHENOTYPE.
[7]"Tetraspanin CD63 promotes vascular endothelial growth factor receptor 2-beta1 integrin complex formation, thereby regulating activation and downstream signaling in endothelial cells in vitro and in vivo."
Tugues S., Honjo S., Konig C., Padhan N., Kroon J., Gualandi L., Li X., Barkefors I., Thijssen V.L., Griffioen A.W., Claesson-Welsh L.
J. Biol. Chem. 288:19060-19071(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[8]"The tetraspanin CD63 is required for efficient IgE-mediated mast cell degranulation and anaphylaxis."
Kraft S., Jouvin M.H., Kulkarni N., Kissing S., Morgan E.S., Dvorak A.M., Schroder B., Saftig P., Kinet J.P.
J. Immunol. 191:2871-2878(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D16432 mRNA. Translation: BAA03904.1.
BC008108 mRNA. Translation: AAH08108.1.
BC012212 mRNA. Translation: AAH12212.1.
BC083161 mRNA. Translation: AAH83161.1.
CCDSCCDS24297.1.
PIRS43511.
RefSeqNP_001036045.1. NM_001042580.1.
NP_001269895.1. NM_001282966.1.
NP_031679.1. NM_007653.3.
UniGeneMm.371552.
Mm.416079.

3D structure databases

ProteinModelPortalP41731.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP41731. 2 interactions.

PTM databases

PhosphoSiteP41731.

Proteomic databases

MaxQBP41731.
PaxDbP41731.
PRIDEP41731.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000026407; ENSMUSP00000026407; ENSMUSG00000025351.
ENSMUST00000105229; ENSMUSP00000100862; ENSMUSG00000025351.
GeneID12512.
KEGGmmu:12512.
UCSCuc007hou.1. mouse.

Organism-specific databases

CTD967.
MGIMGI:99529. Cd63.

Phylogenomic databases

eggNOGNOG268658.
HOVERGENHBG107306.
InParanoidP41731.
KOK06497.
OMAVTQGCGI.
OrthoDBEOG73BVDM.
TreeFamTF316345.

Gene expression databases

ArrayExpressP41731.
BgeeP41731.
CleanExMM_CD63.
GenevestigatorP41731.

Family and domain databases

InterProIPR000301. Tetraspanin.
IPR018499. Tetraspanin/Peripherin.
IPR018503. Tetraspanin_CS.
IPR008952. Tetraspanin_EC2.
[Graphical view]
PfamPF00335. Tetraspannin. 1 hit.
[Graphical view]
PIRSFPIRSF002419. Tetraspanin. 1 hit.
PRINTSPR00259. TMFOUR.
SUPFAMSSF48652. SSF48652. 1 hit.
PROSITEPS00421. TM4_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio281496.
PROP41731.
SOURCESearch...

Entry information

Entry nameCD63_MOUSE
AccessionPrimary (citable) accession number: P41731
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 111 of the entry and version 2 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