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.
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.
A recent investigation showed that expression of CD63 positively correlates with the invasiveness of ovarian cancer.
In cell biology, CD63 is often used as a marker for multivesicular bodies, which are enriched with CD63.
^Anzai, Naoyuki; Lee Younghee; Youn Byung-S; Fukuda Seiji; Kim Young-June; Mantel Charlie; Akashi Makoto; Broxmeyer Hal E (Jun 2002). "C-kit associated with the transmembrane 4 superfamily proteins constitutes a functionally distinct subunit in human hematopoietic progenitors". Blood. United States. 99 (12): 4413–4421. doi:10.1182/blood.V99.12.4413. ISSN0006-4971. PMID12036870.
^Hammond, C; Denzin L K; Pan M; Griffith J M; Geuze H J; Cresswell P (Oct 1998). "The tetraspan protein CD82 is a resident of MHC class II compartments where it associates with HLA-DR, -DM, and -DO molecules". J. Immunol. UNITED STATES. 161 (7): 3282–91. ISSN0022-1767. PMID9759843.
Gorakh Mal (2012). Investigation of cellular functions of tetraspanin CD63. ISBN978-3-659-18758-2; Publishers: LAP LAMBERT Academic Publishing (LAP), GmbH & Co., Germany.
Hotta H, Miyamoto H, Hara I, et al. (1992). "Genomic structure of the ME491/CD63 antigen gene and functional analysis of the 5'-flanking regulatory sequences". Biochem. Biophys. Res. Commun. 185 (1): 436–442. doi:10.1016/S0006-291X(05)81004-6. PMID1599482.
Metzelaar MJ, Wijngaard PL, Peters PJ, et al. (1991). "CD63 antigen. A novel lysosomal membrane glycoprotein, cloned by a screening procedure for intracellular antigens in eukaryotic cells". J. Biol. Chem. 266 (5): 3239–45. PMID1993697.
Rapp G, Freudenstein J, Klaudiny J, et al. (1990). "Characterization of three abundant mRNAs from human ovarian granulosa cells". DNA Cell Biol. 9 (7): 479–485. doi:10.1089/dna.1990.9.479. PMID2171551.
Hotta H, Takahashi N, Homma M (1990). "Transcriptional enhancement of the human gene encoding for a melanoma-associated antigen (ME491) in association with malignant transformation". Jpn. J. Cancer Res. 80 (12): 1186–91. doi:10.1111/j.1349-7006.1989.tb01653.x. PMID2516848.
Hotta H, Ross AH, Huebner K, et al. (1988). "Molecular cloning and characterization of an antigen associated with early stages of melanoma tumor progression". Cancer Res. 48 (11): 2955–62. PMID3365686.
Ross AH, Dietzschold B, Jackson DM, et al. (1985). "Isolation and amino terminal sequencing of a novel melanoma-associated antigen". Arch. Biochem. Biophys. 242 (2): 540–548. doi:10.1016/0003-9861(85)90241-3. PMID4062294.
Berditchevski F, Bazzoni G, Hemler ME (1995). "Specific association of CD63 with the VLA-3 and VLA-6 integrins". J. Biol. Chem. 270 (30): 17784–17790. doi:10.1074/jbc.270.30.17784. PMID7629079.
Radford KJ, Thorne RF, Hersey P (1996). "CD63 associates with transmembrane 4 superfamily members, CD9 and CD81, and with beta 1 integrins in human melanoma". Biochem. Biophys. Res. Commun. 222 (1): 13–18. doi:10.1006/bbrc.1996.0690. PMID8630057.
Gwynn B, Eicher EM, Peters LL (1996). "Genetic localization of Cd63, a member of the transmembrane 4 superfamily, reveals two distinct loci in the mouse genome". Genomics. 35 (2): 389–391. doi:10.1006/geno.1996.0375. PMID8661157.
Mannion BA, Berditchevski F, Kraeft SK, et al. (1996). "Transmembrane-4 superfamily proteins CD81 (TAPA-1), CD82, CD63, and CD53 specifically associated with integrin alpha 4 beta 1 (CD49d/CD29)". J. Immunol. 157 (5): 2039–47. PMID8757325.
Skubitz KM, Campbell KD, Iida J, Skubitz AP (1996). "CD63 associates with tyrosine kinase activity and CD11/CD18, and transmits an activation signal in neutrophils". J. Immunol. 157 (8): 3617–26. PMID8871662.
Berditchevski F, Tolias KF, Wong K, et al. (1997). "A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase". J. Biol. Chem. 272 (5): 2595–2598. doi:10.1074/jbc.272.5.2595. PMID9006891.
Sincock PM, Mayrhofer G, Ashman LK (1997). "Localization of the transmembrane 4 superfamily (TM4SF) member PETA-3 (CD151) in normal human tissues: comparison with CD9, CD63, and alpha5beta1 integrin". J. Histochem. Cytochem. 45 (4): 515–25. doi:10.1177/002215549704500404. PMID9111230.
Berditchevski F, Chang S, Bodorova J, Hemler ME (1997). "Generation of monoclonal antibodies to integrin-associated proteins. Evidence that alpha3beta1 complexes with EMMPRIN/basigin/OX47/M6". J. Biol. Chem. 272 (46): 29174–29180. doi:10.1074/jbc.272.46.29174. PMID9360995.
Tachibana I, Bodorova J, Berditchevski F, et al. (1997). "NAG-2, a novel transmembrane-4 superfamily (TM4SF) protein that complexes with integrins and other TM4SF proteins". J. Biol. Chem. 272 (46): 29181–29189. doi:10.1074/jbc.272.46.29181. PMID9360996.