CD63

CD63 antigen is a protein that, in humans, is encoded by the CD63 gene.[5] CD63 is mainly associated with membranes of intracellular vesicles, although cell surface expression may be induced.

CD63
Identifiers
AliasesCD63, LAMP-3, ME491, MLA1, OMA81H, TSPAN30, CD63 molecule
External IDsOMIM: 155740 MGI: 99529 HomoloGene: 37526 GeneCards: CD63
Orthologs
SpeciesHumanMouse
Entrez

967

12512

Ensembl

ENSG00000135404

ENSMUSG00000025351

UniProt

P08962

P41731

RefSeq (mRNA)

NM_001042580
NM_001282966
NM_007653

RefSeq (protein)

NP_001036045
NP_001269895
NP_031679

Location (UCSC)Chr 12: 55.73 – 55.73 MbChr 10: 128.74 – 128.75 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth, and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins. It may function as a blood platelet activation marker. Deficiency of this protein is associated with Hermansky-Pudlak Syndrome . Also this gene has been associated with tumor progression. The use of alternate polyadenylation sites has been found for this gene. Alternative splicing results in multiple transcript variants encoding different proteins.[5]

Allergy diagnosis

CD63 is a good marker for flow cytometric quantification of in vitro activated basophils for diagnosis of IgE-mediated allergy. The test is commonly designated as basophil activation test (BAT).

Research

Initially, deletion and point mutants were used to investigate the role of the C-terminus, which contains a putative lysosomal-targeting/internalisation motif (GYEVM). C-terminal mutants showed increased surface expression and decreased intracellular localisation relative to CD63Wt. Antibody induced internalisation was reduced in C-terminal deletion mutants and abolished in G→A and Y→A mutants, showing the crucial role of these residues in internalisation.

CD63 is extensively and variably glycosylated and the EC2 region contain three potential N-linked glycosylation sites (N130, N150, and N172). Mutants N130A and N150A were similar to hCD63Wt with respect to intracellular localisation and internalisation. However, the hCD63N172A mutant showed a mainly cell surface localisation and low internalisation. Expression of a mutant lacking all three glycosylation sites was very unstable. It was speculated that the reduced internalisation of CD63N172A might be due to changes in its interaction with cell surface molecules. Immunoprecipitation experiments showed some evidence of a protein (100kDa) associating with CD63N172A, but this was not consistent. However, an association between CD63Wt and β2 integrin (CD18) was shown by co-internalisation of these proteins. Interactions with CD63 may therefore affect the trafficking and function of β2 integrins.

In cell biology, CD63 is often used as a marker for multivesicular bodies, which in some cells are enriched with CD63,[6] as well as for extracellular vesicles released from either the multivesicular body or the plasma membrane.[7]

Interactions

CD63 has been shown to interact with CD117[8] and CD82.[9]

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000135404 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000025351 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: CD63 CD63 molecule".
  6. Piper RC, Katzmann DJ (2007). "Biogenesis and function of multivesicular bodies". Annual Review of Cell and Developmental Biology. 23: 519–47. doi:10.1146/annurev.cellbio.23.090506.123319. PMC 2911632. PMID 17506697.
  7. Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, et al. (2018). "Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines". Journal of Extracellular Vesicles. 7 (1): 1535750. doi:10.1080/20013078.2018.1535750. PMC 6322352. PMID 30637094.
  8. Anzai N, Lee Y, Youn BS, Fukuda S, Kim YJ, Mantel C, Akashi M, Broxmeyer HE (June 2002). "C-kit associated with the transmembrane 4 superfamily proteins constitutes a functionally distinct subunit in human hematopoietic progenitors". Blood. 99 (12): 4413–21. doi:10.1182/blood.V99.12.4413. PMID 12036870.
  9. Hammond C, Denzin LK, Pan M, Griffith JM, Geuze HJ, Cresswell P (October 1998). "The tetraspan protein CD82 is a resident of MHC class II compartments where it associates with HLA-DR, -DM, and -DO molecules". Journal of Immunology. 161 (7): 3282–91. PMID 9759843.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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