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Cd81

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Cd81

CD81 molecule

PDB rendering based on 1g8q.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; CVID6; S5.7; TAPA1; TSPAN28
External IDs ChEMBL: GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

CD81 molecule, also known as CD81 (Cluster of Differentiation 81), is a protein which in humans is encoded by the CD81 gene.[1][2] It is also known as 26 kDa cell surface protein, Target of the antiproliferative antibody 1 (TAPA-1) and Tetraspanin-28 (Tspan-28).

Contents

  • Gene 1
  • Function 2
  • Clinical significance 3
  • Interactions 4
    • Ligands 4.1
  • See also 5
  • References 6
  • Further reading 7
  • External links 8

Gene

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).[2]

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 gene is expressed in hemopoietic, endothelial and epithelial cells. It is absent from erythrocytes, platelets and neutrophils.

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. 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.[1]

The tetraspanin family includes CD9, CD37, CD53, CD63, CD81 (this protein), CD82 and CD151.

CD81 interacts directly with immunoglobulin superfamily member 8 (IGSF8,[3] CD316) and CD36. It forms a signal transduction complex with CD19, CD21 and Leu-13 (CD225) on the surface of the B cell.[4] On T cells CD81 associates with CD4 and CD8 and provides a costimulatory signal with CD3.[4]

Clinical significance

This protein plays a critical role in Hepatitis C attachment and/or cell entry by interacting with virus' E1/E2 glycoproteins heterodimer.[5] 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.[6]

It also appears to play a role in liver invasion by Plasmodium species.[7] CD81 is required for Plasmodium vivax sporozoite entry into human hepatocytes and for Plasmodium yoelii sporozoite entry into murine hepatocytes.[8]

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.[9] Engagement of CD81 lowers the signaling threshold required to trigger T-Cell\CD3 mediated proviral DNA in CD4+ T cells.[10]

CD81 appears to play a role in the pathogeneis of influenza.[11]

Interactions

CD81 has been shown to interact with TSPAN4,[12] CD19,[13][14][15] CD9,[15][16] PTGFRN,[17][18] CD117[19] and CD29.[20][21]

Ligands

Benzyl salicylate[22] and terfenadine[23] have been shown to bind to CD81.

See also

References

  1. ^ a b "Entrez Gene: CD81 CD81 molecule". 
  2. ^ a b Andria ML, Hsieh CL, Oren R, Francke U, Levy S (August 1991). "Genomic organization and chromosomal localization of the TAPA-1 gene". Journal of Immunology 147 (3): 1030–6.  
  3. ^ 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 (Baltimore, Md. : 1950) 167 (9): 5115–5121.  
  4. ^ a b Levy 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. 1998;16:89-109 16: 89–109.  
  5. ^ 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.  
  6. ^ Petracca R, Falugi F, Galli G, Norais N, Rosa D, Campagnoli S, Burgio V, Di Stasio E, Giardina B, Houghton M, Abrignani S, Grandi G (May 2000). "Structure-function analysis of hepatitis C virus envelope-CD81 binding". J. Virol. 74 (10): 4824–30.  
  7. ^ Yalaoui S, Zougbédé S, Charrin S, Silvie O, Arduise C, Farhati K, Boucheix C, Mazier D, Rubinstein E, Froissard P (February 2008). "Hepatocyte Permissiveness to Plasmodium Infection Is Conveyed by a Short and Structurally Conserved Region of the CD81 Large Extracellular Domain". PLoS Pathogens 4 (2): e1000010.  
  8. ^ 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.  
  9. ^ Grigorov B, Attuil-Audenis V, Perugi F, Nedelec M, Watson S, Pique C, Darlix JL, Conjeaud H, Muriaux D (2009). "A role for CD81 on the late steps of HIV-1 replication in a chronically infected T cell line". Retrovirology 6: 28.  
  10. ^ Tardif MR, Tremblay MJ (April 2005). "Tetraspanin CD81 provides a costimulatory signal resulting in increased human immunodeficiency virus type 1 gene expression in primary CD4+ T lymphocytes through NF-kappaB, NFAT, and AP-1 transduction pathways". J. Virol. 79 (7): 4316–28.  
  11. ^ He J, Sun E, Bujny MV, Kim D, Davidson MW, Zhuang X (October 2013). "Dual Function of CD81 in Influenza Virus Uncoating and Budding". PLoS Pathog. 9 (10): e1003701.  
  12. ^ Tachibana I, Bodorova J, Berditchevski F, Zutter M M, Hemler M E (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.  
  13. ^ Bradbury LE, Kansas G S, Levy S, Evans R L, Tedder T F (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.  
  14. ^ 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.  
  15. ^ a b Horváth 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.  
  16. ^ Radford KJ, Thorne R F, 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.  
  17. ^ Charrin S, Le Naour F, Oualid M, Billard M, Faure G, Hanash S M, 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.  
  18. ^ Stipp CS, Orlicky D, Hemler M E (Feb 2001). "FPRP, a major, highly stoichiometric, highly specific CD81- and CD9-associated protein". J. Biol. Chem. 276 (7): 4853–62.  
  19. ^ 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.  
  20. ^ Serru V, Le Naour F, Billard M, Azorsa D O, Lanza F, Boucheix C, Rubinstein E (May 1999). "Selective tetraspan-integrin complexes (CD81/alpha4beta1, CD151/alpha3beta1, CD151/alpha6beta1) under conditions disrupting tetraspan interactions". Biochem. J. 340 (Pt 1): 103–11.  
  21. ^ Mazzocca A, Carloni Vinicio, Sciammetta Silvia, Cordella Claudia, Pantaleo Pietro, Caldini Anna, Gentilini Paolo, Pinzani Massimo (Sep 2002). "Expression of transmembrane 4 superfamily (TM4SF) proteins and their role in hepatic stellate cell motility and wound healing migration". J. Hepatol. 37 (3): 322–30.  
  22. ^ Rajesh S, Sridhar P, Tews BA, Fénéant L, Cocquerel L, Ward DG, Berditchevski F, Overduin M (June 2012). "Structural basis of ligand interactions of the large extracellular domain of tetraspanin CD81". J Virol 86 (18): 9606–16.  
  23. ^ 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.  

Further reading

  • Berditchevski F (2002). "Complexes of tetraspanins with integrins: more than meets the eye". J. Cell. Sci. 114 (Pt 23): 4143–51.  
  • Ye J (2007). "Reliance of Host Cholesterol Metabolic Pathways for the Life Cycle of Hepatitis C Virus". PLoS Pathog. 3 (8): e108.  
  • 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.  
  • 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.  
  • Oren R, Takahashi S, Doss C, et al. (1990). "TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins". Mol. Cell. Biol. 10 (8): 4007–15.  
  • Levy S, Nguyen VQ, Andria ML, Takahashi S (1991). "Structure and membrane topology of TAPA-1". J. Biol. Chem. 266 (22): 14597–602.  
  • Takahashi S, Doss C, Levy S, Levy R (1990). "TAPA-1, the target of an antiproliferative antibody, is associated on the cell surface with the Leu-13 antigen". J. Immunol. 145 (7): 2207–13.  
  • Matsumoto AK, Martin DR, Carter RH, et al. (1993). "Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes". J. Exp. Med. 178 (4): 1407–17.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  
  • Pileri P, Uematsu Y, Campagnoli S, et al. (1998). "Binding of hepatitis C virus to CD81". Science 282 (5390): 938–41.  
  • Serru V, Le Naour F, Billard M, et al. (1999). "Selective tetraspan-integrin complexes (CD81/alpha4beta1, CD151/alpha3beta1, CD151/alpha6beta1) under conditions disrupting tetraspan interactions". Biochem. J. 340 (Pt 1): 103–11.  
  • Tachibana I, Hemler ME (1999). "Role of Transmembrane 4 Superfamily (Tm4sf) Proteins Cd9 and Cd81 in Muscle Cell Fusion and Myotube Maintenance". J. Cell Biol. 146 (4): 893–904.  
  • Higginbottom A, Quinn ER, Kuo CC, et al. (2000). "Identification of Amino Acid Residues in CD81 Critical for Interaction with Hepatitis C Virus Envelope Glycoprotein E2". J. Virol. 74 (8): 3642–9.  

External links

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