CD63 antigen is a protein that, in humans, is encoded by the CD63gene.[5] CD63 is mainly associated with membranes of intracellular vesicles, although cell surface expression may be induced.
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]
^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. PMID12036870.
Mal G (2012). Investigation of cellular functions of tetraspanin CD63. Germany: LAP LAMBERT Academic Publishing (LAP), GmbH & Co. ISBN978-3-659-18758-2.
Horejsí V, Vlcek C (August 1991). "Novel structurally distinct family of leucocyte surface glycoproteins including CD9, CD37, CD53 and CD63". FEBS Letters. 288 (1–2): 1–4. doi:10.1016/0014-5793(91)80988-F. PMID1879540. S2CID26316623.
Berditchevski F (December 2001). "Complexes of tetraspanins with integrins: more than meets the eye". Journal of Cell Science. 114 (Pt 23): 4143–51. doi:10.1242/jcs.114.23.4143. PMID11739647.
Wang MX, Earley JJ, Shields JA, Donoso LA (March 1992). "An ocular melanoma-associated antigen. Molecular characterization". Archives of Ophthalmology. 110 (3): 399–404. doi:10.1001/archopht.1992.01080150097036. PMID1339263.
Hotta H, Miyamoto H, Hara I, Takahashi N, Homma M (May 1992). "Genomic structure of the ME491/CD63 antigen gene and functional analysis of the 5'-flanking regulatory sequences". Biochemical and Biophysical Research Communications. 185 (1): 436–42. doi:10.1016/S0006-291X(05)81004-6. PMID1599482.
Hotta H, Ross AH, Huebner K, Isobe M, Wendeborn S, Chao MV, Ricciardi RP, Tsujimoto Y, Croce CM, Koprowski H (June 1988). "Molecular cloning and characterization of an antigen associated with early stages of melanoma tumor progression". Cancer Research. 48 (11): 2955–62. PMID3365686.
Ross AH, Dietzschold B, Jackson DM, Earley JJ, Ghrist BD, Atkinson B, Koprowski H (November 1985). "Isolation and amino terminal sequencing of a novel melanoma-associated antigen". Archives of Biochemistry and Biophysics. 242 (2): 540–8. doi:10.1016/0003-9861(85)90241-3. PMID4062294.
Radford KJ, Thorne RF, Hersey P (May 1996). "CD63 associates with transmembrane 4 superfamily members, CD9 and CD81, and with beta 1 integrins in human melanoma". Biochemical and Biophysical Research Communications. 222 (1): 13–8. doi:10.1006/bbrc.1996.0690. PMID8630057.
Gwynn B, Eicher EM, Peters LL (July 1996). "Genetic localization of Cd63, a member of the transmembrane 4 superfamily, reveals two distinct loci in the mouse genome". Genomics. 35 (2): 389–91. doi:10.1006/geno.1996.0375. PMID8661157.
