|RNA expression pattern|
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.
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).
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. Recent work by other groups suggests that CD63 functions as an “adaptor”, controlling the functions of interacting proteins such as integrins, by inducing their internalisation. Our findings indicate that CD63 glycosylation status can affect this role (2).
- "Entrez Gene: CD63 CD63 molecule".
- 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. ISSN 0006-4971. PMID 12036870.
- 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. ISSN 0022-1767. PMID 9759843.
Gorakh Mal (2012). Investigation of cellular functions of tetraspanin CD63. ISBN 978-3-659-18758-2; Publishers: LAP LAMBERT Academic Publishing (LAP), GmbH & Co., Germany.
- Horejsí V, Vlcek C (1991). "Novel structurally distinct family of leucocyte surface glycoproteins including CD9, CD37, CD53 and CD63". FEBS Lett. 288 (1–2): 1–4. doi:10.1016/0014-5793(91)80988-F. PMID 1879540.
- Berditchevski F (2002). "Complexes of tetraspanins with integrins: more than meets the eye". J. Cell. Sci. 114 (Pt 23): 4143–51. PMID 11739647.
- Wang MX, Earley JJ, Shields JA, Donoso LA (1992). "An ocular melanoma-associated antigen. Molecular characterization". Arch. Ophthalmol. 110 (3): 399–404. PMID 1339263.
- 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. PMID 1599482.
- 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. PMID 1993697.
- 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. PMID 2171551.
- 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. PMID 2516848.
- 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. PMID 3365686.
- 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. PMID 4062294.
- 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. PMID 7629079.
- Nishibori M, Cham B, McNicol A et al. (1993). "The protein CD63 is in platelet dense granules, is deficient in a patient with Hermansky-Pudlak syndrome, and appears identical to granulophysin". J. Clin. Invest. 91 (4): 1775–1782. doi:10.1172/JCI116388. PMC 288158. PMID 7682577.
- 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. PMID 8630057.
- 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. PMID 8661157.
- 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. PMID 8757325.
- 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. PMID 8871662.
- 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. PMID 9006891.
- 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. PMID 9111230.
- 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. PMID 9360995.
- 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. PMID 9360996.