CD81 molecule, also known as CD81 (Cluster of Differentiation 81), is a protein which in humans is encoded by the CD81gene. It is also known as 26 kDa cell surface protein, TAPA-1 (Target of the Antiproliferative Antibody 1), and Tetraspanin-28 (Tspan-28).
The gene is located on the Watson (plus) strand of the short arm of chromosome 11 (11p15.5). It is 20,103 bases in length and encodes a protein of 236 amino acids (predicted molecular weight 25.809 kDa).
The protein does not appear to be post translationally modified and has four transmembrane domains. Both the N-terminus and C-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 the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobicdomains. 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. This protein appears to promote muscle cell fusion and support myotube 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.
CD81 interacts directly with immunoglobulin superfamily member 8 (IGSF8,CD316) and CD36. It forms a signal transduction complex with CD19, CD21 and Leu-13 (CD225) on the surface of the B cell. On T cells CD81 associates with CD4 and CD8 and provides a costimulatory signal with CD3.
This protein plays a critical role in Hepatitis C attachment and/or cell entry by interacting with virus' E1/E2 glycoproteins heterodimer. The large extracellular loop(LEL) 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.
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. Engagement of CD81 lowers the signaling threshold required to trigger T-Cell\CD3 mediated proviral DNA in CD4+ T cells.
CD81 appears to play a role in the pathogenesis of influenza.
^Clark K.L.; Zeng Z.; Langford A.L.; Bowen S.M.; Todd S.C. (November 2001). "PGRL is a major CD81-associated protein on lymphocytes and distinguishes a new family of cell surface proteins". Journal of Immunology. 167 (9): 5115–5121. PMID11673522. doi:10.4049/jimmunol.167.9.5115.
^Bartosch B, Vitelli A, Granier C, Goujon C, Dubuisson J, Pascale S, Scarselli E, Cortese R, Nicosia A, Cosset FL (October 2003). "Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor". The Journal of Biological Chemistry. 278 (43): 41624–30. PMID12913001. doi:10.1074/jbc.M305289200.
^Silvie O, Rubinstein E, Franetich JF, Prenant M, Belnoue E, Rénia L, Hannoun L, Eling W, Levy S, Boucheix C, Mazier D (January 2003). "Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium yoelii sporozoite infectivity". Nat. Med. 9 (1): 93–6. PMID12483205. doi:10.1038/nm808.
^Tachibana I, Bodorova J, Berditchevski F, Zutter MM, Hemler ME (Nov 1997). "NAG-2, a novel transmembrane-4 superfamily (TM4SF) protein that complexes with integrins and other TM4SF proteins". J. Biol. Chem. 272 (46): 29181–9. PMID9360996. doi:10.1074/jbc.272.46.29181.
^Bradbury LE, Kansas GS, Levy S, Evans RL, Tedder TF (Nov 1992). "The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules". J. Immunol. 149 (9): 2841–50. PMID1383329.
^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. PMID7636191.
^ abHorváth G, Serru V, Clay D, Billard M, Boucheix C, Rubinstein E (Nov 1998). "CD19 is linked to the integrin-associated tetraspans CD9, CD81, and CD82". J. Biol. Chem. 273 (46): 30537–43. PMID9804823. doi:10.1074/jbc.273.46.30537.
^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. PMID8630057. doi:10.1006/bbrc.1996.0690.
^Charrin S, Le Naour F, Oualid M, Billard M, Faure G, Hanash SM, Boucheix C, Rubinstein E (Apr 2001). "The major CD9 and CD81 molecular partner. Identification and characterization of the complexes". J. Biol. Chem. 276 (17): 14329–37. PMID11278880. doi:10.1074/jbc.M011297200.
^Stipp CS, Orlicky D, Hemler ME (Feb 2001). "FPRP, a major, highly stoichiometric, highly specific CD81- and CD9-associated protein". J. Biol. Chem. 276 (7): 4853–62. PMID11087758. doi:10.1074/jbc.M009859200.
^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. PMID12036870. doi:10.1182/blood.V99.12.4413.
^Holzer M, Ziegler S, Albrecht B, Kronenberger B, Kaul A, Bartenschlager R, Kattner L, Klein CD, Hartmann RW (2008). "Identification of terfenadine as an inhibitor of human CD81-receptor HCV-E2 interaction: synthesis and structure optimization". Molecules. 13 (5): 1081–110. PMID18560330. doi:10.3390/molecules13051081.
Bradbury LE, Kansas GS, Levy S, et al. (1992). "The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules". J. Immunol. 149 (9): 2841–50. PMID1383329.
Andria ML, Hsieh CL, Oren R, et al. (1991). "Genomic organization and chromosomal localization of the TAPA-1 gene". J. Immunol. 147 (3): 1030–6. PMID1650385.
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. PMID8039242. doi:10.1006/cimm.1994.1212.
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. PMID8168850. doi:10.1007/BF00189229.
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. PMID8630057. doi:10.1006/bbrc.1996.0690.
Szöllósi J, Horejsí V, Bene L, et al. (1996). "Supramolecular complexes of MHC class I, MHC class II, CD20, and tetraspan molecules (CD53, CD81, and CD82) at the surface of a B cell line JY". J. Immunol. 157 (7): 2939–46. PMID8816400.
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): 2595–8. PMID9006891. doi:10.1074/jbc.272.5.2595.
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): 29174–80. PMID9360995. doi:10.1074/jbc.272.46.29174.
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): 29181–9. PMID9360996. doi:10.1074/jbc.272.46.29181.
Hu RJ, Lee MP, Connors TD, et al. (1998). "A 2.5-Mb transcript map of a tumor-suppressing subchromosomal transferable fragment from 11p15.5, and isolation and sequence analysis of three novel genes". Genomics. 46 (1): 9–17. PMID9403053. doi:10.1006/geno.1997.4981.