CD81 molecule, also known asCD81 (Cluster ofDifferentiation81), is aprotein which in humans is encoded by theCD81gene.[5][6] It is also known as 26 kDa cell surface protein, TAPA-1 (Target of theAntiproliferativeAntibody 1), and Tetraspanin-28 (Tspan-28).
The gene is located on the plus strand of the short arm ofchromosome 11 (11p15.5). It is 20,103 bases in length and encodes a protein of 236amino acids (predicted molecular weight 25.809kDa).[6]
The protein does not appear to be post translationally modified and has four transmembrane domains. Both theN-terminus andC-terminus lie on the intracellular side of the membrane.
The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as thetetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of fourhydrophobicdomains. The proteins mediatesignal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surfaceglycoprotein that is known to complex withintegrins. This protein appears to promote muscle cell fusion and supportmyotube maintenance. Also it may be involved in signal transduction. This gene is localized in the tumor-suppressor gene region and thus it is a candidate gene for malignancies.[5]
CD81 interacts directly with immunoglobulin superfamily member 8 (IGSF8,[7]CD316) andCD36. It forms a signal transduction complex withCD19,CD21 and Leu-13 (CD225) on the surface of theB cell.[8] OnT cells CD81 associates withCD4 andCD8 and provides a costimulatory signal withCD3.[8]
This protein plays a critical role inHepatitis C attachment and/or cell entry by interacting with virus' E1/E2 glycoproteins heterodimer.[9] The large extracellular loop of CD81 binds the hepatitis E2 glycoprotein dimer. HCV-E2 and CD81 binding Kd is 1.8 nM. HCV-E2 engaged CD81 is only 30% internalized after 12hr, suggesting CD81 may be primarily an attachment receptor for HCV.[10]
HIV gag proteins use tetraspanin enriched microdomains (containing minimally CD81, CD82, CD63) as a platform for virion assembly and release. Purified HIV produced by MOLT\HIV cells contains CD81. Anti-CD81 antibodies downregulate HIV production 3 fold, however the CD81 protein free virus is more infectious.[13] Engagement of CD81 lowers the signaling threshold required to trigger T-Cell\CD3 mediated proviral DNA in CD4+ T cells.[14]
CD81 appears to play a role in the pathogenesis of influenza.[15]
^abLevy S, Todd SC, Maecker HT (1998). "CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in the immune system".Annu Rev Immunol.16:89–109.doi:10.1146/annurev.immunol.16.1.89.PMID9597125.
^Imai T, Kakizaki M, Nishimura M, Yoshie O (Aug 1995). "Molecular analyses of the association of CD4 with two members of the transmembrane 4 superfamily, CD81 and CD82".J. Immunol.155 (3):1229–39.doi:10.4049/jimmunol.155.3.1229.PMID7636191.S2CID32942467.
^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".Biochem. Biophys. Res. Commun.222 (1):13–8.Bibcode:1996BBRC..222...13R.doi:10.1006/bbrc.1996.0690.PMID8630057.
^Anzai N; 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.99 (12):4413–21.doi:10.1182/blood.V99.12.4413.PMID12036870.
Berditchevski F (2002). "Complexes of tetraspanins with integrins: more than meets the eye".J. Cell Sci.114 (Pt 23):4143–51.doi:10.1242/jcs.114.23.4143.PMID11739647.
Nagira M, Imai T, Ishikawa I, et al. (1994). "Mouse homologue of C33 antigen (CD82), a member of the transmembrane 4 superfamily: complementary DNA, genomic structure, and expression".Cell. Immunol.157 (1):144–57.doi:10.1006/cimm.1994.1212.PMID8039242.
Virtaneva KI, Emi N, Marken JS, et al. (1994). "Chromosomal localization of three human genes coding for A15, L6, and S5.7 (TAPA1): all members of the transmembrane 4 superfamily of proteins".Immunogenetics.39 (5):329–34.doi:10.1007/BF00189229.PMID8168850.S2CID22971645.
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):13–8.Bibcode:1996BBRC..222...13R.doi:10.1006/bbrc.1996.0690.PMID8630057.
