CD81

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

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.

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

CD81 interacts directly with immunoglobulin superfamily member 8 (IGSF8,{{cite journal |author1=Clark K.L. |author2=Zeng Z. |author3=Langford A.L. |author4=Bowen S.M. |author5=Todd S.C. | title = PGRL is a major CD81-associated protein on lymphocytes and distinguishes a new family of cell surface proteins | journal = Journal of Immunology | volume = 167 | issue = 9 | pages = 5115–5121 |date=November 2001 | pmid = 11673522 | doi = 10.4049/jimmunol.167.9.5115| doi-access =free }} CD316) and CD36. It forms a signal transduction complex with CD19, CD21 and Leu-13 (CD225) on the surface of the B cell.{{cite journal|title=CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in the immune system.|journal=Annu Rev Immunol |pmid=9597125|doi=10.1146/annurev.immunol.16.1.89|volume=16|year=1998|pages=89–109|vauthors=Levy S, Todd SC, Maecker HT }} 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.{{cite journal |vauthors=Bartosch B, Vitelli A, Granier C, Goujon C, Dubuisson J, Pascale S, Scarselli E, Cortese R, Nicosia A, Cosset FL | title = Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor | journal = The Journal of Biological Chemistry | volume = 278 | issue = 43 | pages = 41624–30 |date=October 2003 | pmid = 12913001 | doi = 10.1074/jbc.M305289200 | doi-access = free }} 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.{{cite journal |vauthors=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 | title = Structure-function analysis of hepatitis C virus envelope-CD81 binding | journal = J. Virol. | volume = 74 | issue = 10 | pages = 4824–30 |date=May 2000 | pmid = 10775621 | pmc = 112005 | doi = 10.1128/jvi.74.10.4824-4830.2000}}

It also appears to play a role in liver invasion by Plasmodium species.{{cite journal |vauthors=Yalaoui S, Zougbédé S, Charrin S, Silvie O, Arduise C, Farhati K, Boucheix C, Mazier D, Rubinstein E, Froissard P | title = Hepatocyte Permissiveness to Plasmodium Infection Is Conveyed by a Short and Structurally Conserved Region of the CD81 Large Extracellular Domain | journal = PLOS Pathogens | volume = 4 | issue = 2 | pages = e1000010 |date=February 2008 | pmid = 18389082 | pmc = 2279262 | doi = 10.1371/journal.ppat.1000010 | doi-access = free }} CD81 is required for Plasmodium vivax sporozoite entry into human hepatocytes and for Plasmodium yoelii sporozoite entry into murine hepatocytes.{{cite journal |vauthors=Silvie O, Rubinstein E, Franetich JF, Prenant M, Belnoue E, Rénia L, Hannoun L, Eling W, Levy S, Boucheix C, Mazier D | title = Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium yoelii sporozoite infectivity | journal = Nat. Med. | volume = 9 | issue = 1 | pages = 93–6 |date=January 2003 | pmid = 12483205 | doi = 10.1038/nm808 | s2cid = 6290736 }}

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.{{cite journal |vauthors=Grigorov B, Attuil-Audenis V, Perugi F, Nedelec M, Watson S, Pique C, Darlix JL, Conjeaud H, Muriaux D | title = A role for CD81 on the late steps of HIV-1 replication in a chronically infected T cell line | journal = Retrovirology | volume = 6 | pages = 28 | year = 2009 | pmid = 19284574 | pmc = 2657109 | doi = 10.1186/1742-4690-6-28 | doi-access = free }} Engagement of CD81 lowers the signaling threshold required to trigger T-Cell\CD3 mediated proviral DNA in CD4+ T cells.{{cite journal |vauthors=Tardif MR, Tremblay MJ | title = 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 | journal = J. Virol. | volume = 79 | issue = 7 | pages = 4316–28 |date=April 2005 | pmid = 15767432 | pmc = 1061526 | doi = 10.1128/JVI.79.7.4316-4328.2005 }}

CD81 appears to play a role in the pathogenesis of influenza.{{cite journal |vauthors=He J, Sun E, Bujny MV, Kim D, Davidson MW, Zhuang X | title = Dual Function of CD81 in Influenza Virus Uncoating and Budding | journal = PLOS Pathog. | volume = 9 | issue = 10 | pages = e1003701 |date=October 2013 | pmid = 24130495 | doi = 10.1371/journal.ppat.1003701 | pmc=3795033 | doi-access = free }}

CD81 has been shown to interact with TSPAN4,{{cite journal |vauthors=Tachibana I, Bodorova J, Berditchevski F, Zutter MM, Hemler ME | title = NAG-2, a novel transmembrane-4 superfamily (TM4SF) protein that complexes with integrins and other TM4SF proteins | journal = J. Biol. Chem. | volume = 272 | issue = 46 | pages = 29181–9 |date=Nov 1997 | pmid = 9360996 | doi = 10.1074/jbc.272.46.29181 | doi-access = free }} CD19,{{cite journal |vauthors=Bradbury LE, Kansas GS, Levy S, Evans RL, Tedder TF | title = The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules | journal = J. Immunol. | volume = 149 | issue = 9 | pages = 2841–50 |date=Nov 1992 | doi = 10.4049/jimmunol.149.9.2841 | pmid = 1383329 | s2cid = 23655762 | doi-access = free }}{{cite journal |vauthors=Imai T, Kakizaki M, Nishimura M, Yoshie O | title = Molecular analyses of the association of CD4 with two members of the transmembrane 4 superfamily, CD81 and CD82 | journal = J. Immunol. | volume = 155 | issue = 3 | pages = 1229–39 |date=Aug 1995 | doi = 10.4049/jimmunol.155.3.1229 | pmid = 7636191 | s2cid = 32942467 }}{{cite journal |vauthors=Horváth G, Serru V, Clay D, Billard M, Boucheix C, Rubinstein E | title = CD19 is linked to the integrin-associated tetraspans CD9, CD81, and CD82 | journal = J. Biol. Chem. | volume = 273 | issue = 46 | pages = 30537–43 |date=Nov 1998 | pmid = 9804823 | doi = 10.1074/jbc.273.46.30537 | doi-access = free }} CD9,{{cite journal |vauthors=Radford KJ, Thorne RF, Hersey P | title = CD63 associates with transmembrane 4 superfamily members, CD9 and CD81, and with beta 1 integrins in human melanoma | journal = Biochem. Biophys. Res. Commun. | volume = 222 | issue = 1 | pages = 13–8 |date=May 1996 | pmid = 8630057 | doi = 10.1006/bbrc.1996.0690 }} PTGFRN,{{cite journal |vauthors=Charrin S, Le Naour F, Oualid M, Billard M, Faure G, Hanash SM, Boucheix C, Rubinstein E | title = The major CD9 and CD81 molecular partner. Identification and characterization of the complexes | journal = J. Biol. Chem. | volume = 276 | issue = 17 | pages = 14329–37 |date=Apr 2001 | pmid = 11278880 | doi = 10.1074/jbc.M011297200 | doi-access = free }}{{cite journal |vauthors=Stipp CS, Orlicky D, Hemler ME | title = FPRP, a major, highly stoichiometric, highly specific CD81- and CD9-associated protein | journal = J. Biol. Chem. | volume = 276 | issue = 7 | pages = 4853–62 |date=Feb 2001 | pmid = 11087758 | doi = 10.1074/jbc.M009859200 | doi-access = free }} CD117{{cite journal |author1=Anzai N |author2=Lee Younghee |author3=Youn Byung-S |author4=Fukuda Seiji |author5=Kim Young-June |author6=Mantel Charlie |author7=Akashi Makoto |author8=Broxmeyer Hal E | title = C-kit associated with the transmembrane 4 superfamily proteins constitutes a functionally distinct subunit in human hematopoietic progenitors | journal = Blood | volume = 99 | issue = 12 | pages = 4413–21 |date=Jun 2002 | pmid = 12036870 | doi = 10.1182/blood.V99.12.4413 }} and CD29.{{cite journal |vauthors=Serru V, Le Naour F, Billard M, Azorsa DO, Lanza F, Boucheix C, Rubinstein E | title = Selective tetraspan-integrin complexes (CD81/alpha4beta1, CD151/alpha3beta1, CD151/alpha6beta1) under conditions disrupting tetraspan interactions | journal = Biochem. J. | volume = 340 | issue = Pt 1 | pages = 103–11 |date=May 1999 | pmid = 10229664 | pmc = 1220227 | doi = 10.1042/0264-6021:3400103 }}{{cite journal |author1=Mazzocca A |author2=Carloni Vinicio |author3=Sciammetta Silvia |author4=Cordella Claudia |author5=Pantaleo Pietro |author6=Caldini Anna |author7=Gentilini Paolo |author8=Pinzani Massimo | title = Expression of transmembrane 4 superfamily (TM4SF) proteins and their role in hepatic stellate cell motility and wound healing migration | journal = J. Hepatol. | volume = 37 | issue = 3 | pages = 322–30 |date=Sep 2002 | pmid = 12175627 | doi = 10.1016/S0168-8278(02)00175-7 }}

Benzyl salicylate{{cite journal |vauthors=Rajesh S, Sridhar P, Tews BA, Fénéant L, Cocquerel L, Ward DG, Berditchevski F, Overduin M | title = Structural basis of ligand interactions of the large extracellular domain of tetraspanin CD81 | journal = J Virol | volume = 86| issue = 18| pages = 9606–16|date=June 2012 | pmid = 22740401 | doi = 10.1128/JVI.00559-12 | pmc=3446547}} and terfenadine{{cite journal |vauthors=Holzer M, Ziegler S, Albrecht B, Kronenberger B, Kaul A, Bartenschlager R, Kattner L, Klein CD, Hartmann RW | title = Identification of terfenadine as an inhibitor of human CD81-receptor HCV-E2 interaction: synthesis and structure optimization | journal = Molecules | volume = 13 | issue = 5 | pages = 1081–110 | year = 2008 | pmid = 18560330 | pmc = 6245452 | doi = 10.3390/molecules13051081| doi-access = free }} have been shown to bind to CD81.

• Cluster of differentiation

{{reflist|35em}}

{{refbegin |35em}}

• {{cite journal | author=Berditchevski F |title=Complexes of tetraspanins with integrins: more than meets the eye |journal=J. Cell Sci. |volume=114 |issue= Pt 23 |pages= 4143–51 |year= 2002 |doi=10.1242/jcs.114.23.4143 |pmid= 11739647 }}
• {{cite journal | author=Ye J |title=Reliance of Host Cholesterol Metabolic Pathways for the Life Cycle of Hepatitis C Virus |journal=PLOS Pathog. |volume=3 |issue= 8 |pages= e108 |year= 2007 |pmid= 17784784 |doi= 10.1371/journal.ppat.0030108 | pmc=1959368 |doi-access=free }}
• {{cite journal |vauthors=Bradbury LE, Kansas GS, Levy S |title=The CD19/CD21 signal transducing complex of human B lymphocytes includes the target of antiproliferative antibody-1 and Leu-13 molecules |journal=J. Immunol. |volume=149 |issue= 9 |pages= 2841–50 |year= 1992 |doi=10.4049/jimmunol.149.9.2841 |pmid= 1383329 |s2cid=23655762 |display-authors=etal|doi-access=free }}
• {{cite journal |vauthors=Andria ML, Hsieh CL, Oren R |title=Genomic organization and chromosomal localization of the TAPA-1 gene |journal=J. Immunol. |volume=147 |issue= 3 |pages= 1030–6 |year= 1991 |doi=10.4049/jimmunol.147.3.1030 |pmid= 1650385 |s2cid=31032048 |display-authors=etal}}
• {{cite journal |vauthors=Oren R, Takahashi S, Doss C |title=TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins |journal=Mol. Cell. Biol. |volume=10 |issue= 8 |pages= 4007–15 |year= 1990 |pmid= 1695320 |doi= 10.1128/MCB.10.8.4007| pmc=360911 |display-authors=etal}}
• {{cite journal |vauthors=Levy S, Nguyen VQ, Andria ML, Takahashi S |title=Structure and membrane topology of TAPA-1 |journal=J. Biol. Chem. |volume=266 |issue= 22 |pages= 14597–602 |year= 1991 |doi=10.1016/S0021-9258(18)98728-4 |pmid= 1860863 |doi-access=free }}
• {{cite journal |vauthors=Takahashi S, Doss C, Levy S, Levy R |title=TAPA-1, the target of an antiproliferative antibody, is associated on the cell surface with the Leu-13 antigen |journal=J. Immunol. |volume=145 |issue= 7 |pages= 2207–13 |year= 1990 |doi=10.4049/jimmunol.145.7.2207 |pmid= 2398277 |s2cid=30999229 |doi-access=free }}
• {{cite journal |vauthors=Matsumoto AK, Martin DR, Carter RH |title=Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes |journal=J. Exp. Med. |volume=178 |issue= 4 |pages= 1407–17 |year= 1993 |pmid= 7690834 |doi=10.1084/jem.178.4.1407 | pmc=2191213 |display-authors=etal}}
• {{cite journal |vauthors=Nagira M, Imai T, Ishikawa I |title=Mouse homologue of C33 antigen (CD82), a member of the transmembrane 4 superfamily: complementary DNA, genomic structure, and expression |journal=Cell. Immunol. |volume=157 |issue= 1 |pages= 144–57 |year= 1994 |pmid= 8039242 |doi= 10.1006/cimm.1994.1212 |display-authors=etal}}
• {{cite journal |vauthors=Virtaneva KI, Emi N, Marken JS |title=Chromosomal localization of three human genes coding for A15, L6, and S5.7 (TAPA1): all members of the transmembrane 4 superfamily of proteins |journal=Immunogenetics |volume=39 |issue= 5 |pages= 329–34 |year= 1994 |pmid= 8168850 |doi=10.1007/BF00189229 |s2cid=22971645 |display-authors=etal}}
• {{cite journal |vauthors=Radford KJ, Thorne RF, Hersey P |title=CD63 associates with transmembrane 4 superfamily members, CD9 and CD81, and with beta 1 integrins in human melanoma |journal=Biochem. Biophys. Res. Commun. |volume=222 |issue= 1 |pages= 13–8 |year= 1996 |pmid= 8630057 |doi= 10.1006/bbrc.1996.0690 }}
• {{cite journal |vauthors=Szöllósi J, Horejsí V, Bene L |title=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 |journal=J. Immunol. |volume=157 |issue= 7 |pages= 2939–46 |year= 1996 |doi=10.4049/jimmunol.157.7.2939 |pmid= 8816400 |s2cid=18389389 |display-authors=etal|doi-access=free }}
• {{cite journal |vauthors=Berditchevski F, Tolias KF, Wong K |title=A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase |journal=J. Biol. Chem. |volume=272 |issue= 5 |pages= 2595–8 |year= 1997 |pmid= 9006891 |doi=10.1074/jbc.272.5.2595 |display-authors=etal|doi-access=free }}
• {{cite journal |vauthors=Berditchevski F, Chang S, Bodorova J, Hemler ME |title=Generation of monoclonal antibodies to integrin-associated proteins. Evidence that alpha3beta1 complexes with EMMPRIN/basigin/OX47/M6 |journal=J. Biol. Chem. |volume=272 |issue= 46 |pages= 29174–80 |year= 1997 |pmid= 9360995 |doi=10.1074/jbc.272.46.29174 |doi-access=free }}
• {{cite journal |vauthors=Tachibana I, Bodorova J, Berditchevski F |title=NAG-2, a novel transmembrane-4 superfamily (TM4SF) protein that complexes with integrins and other TM4SF proteins |journal=J. Biol. Chem. |volume=272 |issue= 46 |pages= 29181–9 |year= 1997 |pmid= 9360996 |doi=10.1074/jbc.272.46.29181 |display-authors=etal|doi-access=free }}
• {{cite journal |vauthors=Hu RJ, Lee MP, Connors TD |title=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 |journal=Genomics |volume=46 |issue= 1 |pages= 9–17 |year= 1998 |pmid= 9403053 |doi= 10.1006/geno.1997.4981 |display-authors=etal|doi-access=free }}
• {{cite journal |vauthors=Pileri P, Uematsu Y, Campagnoli S |title=Binding of hepatitis C virus to CD81 |journal=Science |volume=282 |issue= 5390 |pages= 938–41 |year= 1998 |pmid= 9794763 |doi=10.1126/science.282.5390.938 |bibcode=1998Sci...282..938P |display-authors=etal}}
• {{cite journal |vauthors=Serru V, Le Naour F, Billard M |title=Selective tetraspan-integrin complexes (CD81/alpha4beta1, CD151/alpha3beta1, CD151/alpha6beta1) under conditions disrupting tetraspan interactions |journal=Biochem. J. |volume=340 |issue= Pt 1|pages= 103–11 |year= 1999 |pmid= 10229664 |doi=10.1042/0264-6021:3400103 | pmc=1220227 |display-authors=etal}}
• {{cite journal |vauthors=Tachibana I, Hemler ME |title=Role of Transmembrane 4 Superfamily (Tm4sf) Proteins Cd9 and Cd81 in Muscle Cell Fusion and Myotube Maintenance |journal=J. Cell Biol. |volume=146 |issue= 4 |pages= 893–904 |year= 1999 |pmid= 10459022 |doi=10.1083/jcb.146.4.893 | pmc=2156130 }}
• {{cite journal |vauthors=Higginbottom A, Quinn ER, Kuo CC |title=Identification of Amino Acid Residues in CD81 Critical for Interaction with Hepatitis C Virus Envelope Glycoprotein E2 |journal=J. Virol. |volume=74 |issue= 8 |pages= 3642–9 |year= 2000 |pmid= 10729140 |doi=10.1128/JVI.74.8.3642-3649.2000 | pmc=111874 |display-authors=etal}}

{{refend}}

• {{MeshName|CD81+protein,+human}}
• {{UCSC gene info|CD81}}

{{PDB Gallery|geneid=975}}

{{Clusters of differentiation}}

{{Immunoglobulin superfamily immune receptors}}

{{Other cell membrane proteins}}

{{NLM content}}

{{DEFAULTSORT:Cd81}}

Category:Clusters of differentiation