ID CD81_HUMAN Reviewed; 236 AA. AC P60033; P18582; Q5U0J6; DT 21-NOV-2003, integrated into UniProtKB/Swiss-Prot. DT 21-NOV-2003, sequence version 1. DT 27-MAR-2024, entry version 184. DE RecName: Full=CD81 antigen; DE AltName: Full=26 kDa cell surface protein TAPA-1 {ECO:0000303|PubMed:1695320}; DE AltName: Full=Target of the antiproliferative antibody 1 {ECO:0000303|PubMed:1695320}; DE AltName: Full=Tetraspanin-28; DE Short=Tspan-28; DE AltName: CD_antigen=CD81 {ECO:0000303|PubMed:8766544}; GN Name=CD81 {ECO:0000303|PubMed:8766544, ECO:0000312|HGNC:HGNC:1701}; GN Synonyms=TAPA1 {ECO:0000303|PubMed:1695320}, TSPAN28; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION. RX PubMed=1695320; DOI=10.1128/mcb.10.8.4007-4015.1990; RA Oren R., Takahashi S., Doss C., Levy R., Levy S.; RT "TAPA-1, the target of an antiproliferative antibody, defines a new family RT of transmembrane proteins."; RL Mol. Cell. Biol. 10:4007-4015(1990). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., RA Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., RA Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., RA Nickerson D.A.; RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP INTERACTION WITH IFITM1, AND SUBCELLULAR LOCATION. RX PubMed=2398277; RA Takahashi S., Doss C., Levy S., Levy R.; RT "TAPA-1, the target of an antiproliferative antibody, is associated on the RT cell surface with the Leu-13 antigen."; RL J. Immunol. 145:2207-2213(1990). RN [7] RP TOPOLOGY. RX PubMed=1860863; DOI=10.1016/s0021-9258(18)98728-4; RA Levy S., Nguyen V.Q., Andria M.L., Takahashi S.; RT "Structure and membrane topology of TAPA-1."; RL J. Biol. Chem. 266:14597-14602(1991). RN [8] RP IDENTIFICATION IN A COMPLEX WITH CR2; CD19 AND IFITM1, AND SUBCELLULAR RP LOCATION. RX PubMed=1383329; RA Bradbury L.E., Kansas G.S., Levy S., Evans R.L., Tedder T.F.; RT "The CD19/CD21 signal transducing complex of human B lymphocytes includes RT the target of antiproliferative antibody-1 and Leu-13 molecules."; RL J. Immunol. 149:2841-2850(1992). RN [9] RP FUNCTION, INTERACTION WITH IFITM1, AND INTERACTION WITH HLA-DR. RX PubMed=8409388; RA Schick M.R., Levy S.; RT "The TAPA-1 molecule is associated on the surface of B cells with HLA-DR RT molecules."; RL J. Immunol. 151:4090-4097(1993). RN [10] RP FUNCTION. RX PubMed=8766544; DOI=10.1002/eji.1830260706; RA Secrist H., Levy S., DeKruyff R.H., Umetsu D.T.; RT "Ligation of TAPA-1 (CD81) or major histocompatibility complex class II in RT co-cultures of human B and T lymphocytes enhances interleukin-4 synthesis RT by antigen-specific CD4+ T cells."; RL Eur. J. Immunol. 26:1435-1442(1996). RN [11] RP INTERACTION WITH IGSF8. RX PubMed=11504738; DOI=10.1074/jbc.m107338200; RA Stipp C.S., Kolesnikova T.V., Hemler M.E.; RT "EWI-2 is a major CD9 and CD81 partner and member of a novel Ig protein RT subfamily."; RL J. Biol. Chem. 276:40545-40554(2001). RN [12] RP INTERACTION WITH HCV E1/E2 ENVELOPE HETERODIMER (MICROBIAL INFECTION). RX PubMed=12913001; DOI=10.1074/jbc.m305289200; RA Bartosch B., Vitelli A., Granier C., Goujon C., Dubuisson J., Pascale S., RA Scarselli E., Cortese R., Nicosia A., Cosset F.-L.; RT "Cell entry of hepatitis C virus requires a set of co-receptors that RT include the CD81 tetraspanin and the SR-B1 scavenger receptor."; RL J. Biol. Chem. 278:41624-41630(2003). RN [13] RP FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH CD9. RX PubMed=12796480; DOI=10.1083/jcb.200212031; RA Takeda Y., Tachibana I., Miyado K., Kobayashi M., Miyazaki T., RA Funakoshi T., Kimura H., Yamane H., Saito Y., Goto H., Yoneda T., RA Yoshida M., Kumagai T., Osaki T., Hayashi S., Kawase I., Mekada E.; RT "Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear RT phagocytes."; RL J. Cell Biol. 161:945-956(2003). RN [14] RP INTERACTION WITH HCV E1/E2 ENVELOPE HETERODIMER (MICROBIAL INFECTION). RX PubMed=12970454; DOI=10.1128/jvi.77.19.10677-10683.2003; RA Cocquerel L., Kuo C.-C., Dubuisson J., Levy S.; RT "CD81-dependent binding of hepatitis C virus E1E2 heterodimers."; RL J. Virol. 77:10677-10683(2003). RN [15] RP FUNCTION (MICROBIAL INFECTION), AND TISSUE SPECIFICITY. RX PubMed=12483205; DOI=10.1038/nm808; RA Silvie O., Rubinstein E., Franetich J.F., Prenant M., Belnoue E., Renia L., RA Hannoun L., Eling W., Levy S., Boucheix C., Mazier D.; RT "Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium RT yoelii sporozoite infectivity."; RL Nat. Med. 9:93-96(2003). RN [16] RP PTM, AND FUNCTION. RX PubMed=15161911; DOI=10.1074/jbc.m404410200; RA Cherukuri A., Carter R.H., Brooks S., Bornmann W., Finn R., Dowd C.S., RA Pierce S.K.; RT "B cell signaling is regulated by induced palmitoylation of CD81."; RL J. Biol. Chem. 279:31973-31982(2004). RN [17] RP INTERACTION WITH ADGRG1 AND GNA11. RX PubMed=15004227; DOI=10.1091/mbc.e03-12-0886; RA Little K.D., Hemler M.E., Stipp C.S.; RT "Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact RT cells: central role of CD81 in facilitating GPR56-Galpha q/11 RT association."; RL Mol. Biol. Cell 15:2375-2387(2004). RN [18] RP FUNCTION, AND INTERACTION WITH CD19. RX PubMed=16449649; DOI=10.1128/mcb.26.4.1373-1385.2006; RA Shoham T., Rajapaksa R., Kuo C.C., Haimovich J., Levy S.; RT "Building of the tetraspanin web: distinct structural domains of CD81 RT function in different cellular compartments."; RL Mol. Cell. Biol. 26:1373-1385(2006). RN [19] RP FUNCTION (MICROBIAL INFECTION), SUBUNIT, SUBCELLULAR LOCATION, AND RP INTERACTION WITH CLDN1; CLDN6 AND CLDN9. RX PubMed=20375010; DOI=10.1074/jbc.m110.104836; RA Harris H.J., Davis C., Mullins J.G., Hu K., Goodall M., Farquhar M.J., RA Mee C.J., McCaffrey K., Young S., Drummer H., Balfe P., McKeating J.A.; RT "Claudin association with CD81 defines hepatitis C virus entry."; RL J. Biol. Chem. 285:21092-21102(2010). RN [20] RP INVOLVEMENT IN CVID6, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=20237408; DOI=10.1172/jci39748; RA van Zelm M.C., Smet J., Adams B., Mascart F., Schandene L., Janssen F., RA Ferster A., Kuo C.-C., Levy S., van Dongen J.J.M., van der Burg M.; RT "CD81 gene defect in humans disrupts CD19 complex formation and leads to RT antibody deficiency."; RL J. Clin. Invest. 120:1265-1274(2010). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [22] RP INTERACTION WITH CD53 AND SCIMP. RX PubMed=21930792; DOI=10.1128/mcb.05817-11; RA Draber P., Vonkova I., Stepanek O., Hrdinka M., Kucova M., Skopcova T., RA Otahal P., Angelisova P., Horejsi V., Yeung M., Weiss A., Brdicka T.; RT "SCIMP, a transmembrane adapter protein involved in major RT histocompatibility complex class II signaling."; RL Mol. Cell. Biol. 31:4550-4562(2011). RN [23] RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH CLDN1. RX PubMed=21516087; DOI=10.1038/nm.2341; RA Lupberger J., Zeisel M.B., Xiao F., Thumann C., Fofana I., Zona L., RA Davis C., Mee C.J., Turek M., Gorke S., Royer C., Fischer B., Zahid M.N., RA Lavillette D., Fresquet J., Cosset F.L., Rothenberg S.M., Pietschmann T., RA Patel A.H., Pessaux P., Doffoel M., Raffelsberger W., Poch O., RA McKeating J.A., Brino L., Baumert T.F.; RT "EGFR and EphA2 are host factors for hepatitis C virus entry and possible RT targets for antiviral therapy."; RL Nat. Med. 17:589-595(2011). RN [24] RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=22307619; DOI=10.1073/pnas.1121307109; RA Sagi Y., Landrigan A., Levy R., Levy S.; RT "Complementary costimulation of human T-cell subpopulations by cluster of RT differentiation 28 (CD28) and CD81."; RL Proc. Natl. Acad. Sci. U.S.A. 109:1613-1618(2012). RN [25] RP FUNCTION, INTERACTION WITH CD247, INTERACTION WITH ICAM1, AND INTERACTION RP WITH CD9. RX PubMed=23858057; DOI=10.1128/mcb.00302-13; RA Rocha-Perugini V., Zamai M., Gonzalez-Granado J.M., Barreiro O., Tejera E., RA Yanez-Mo M., Caiolfa V.R., Sanchez-Madrid F.; RT "CD81 controls sustained T cell activation signaling and defines the RT maturation stages of cognate immunological synapses."; RL Mol. Cell. Biol. 33:3644-3658(2013). RN [26] RP FUNCTION, INTERACTION WITH IFITM1, AND SUBCELLULAR LOCATION. RX PubMed=26354436; DOI=10.1074/jbc.m115.657346; RA Narayana S.K., Helbig K.J., McCartney E.M., Eyre N.S., Bull R.A., RA Eltahla A., Lloyd A.R., Beard M.R.; RT "The Interferon-induced Transmembrane Proteins, IFITM1, IFITM2, and IFITM3 RT Inhibit Hepatitis C Virus Entry."; RL J. Biol. Chem. 290:25946-25959(2015). RN [27] RP INTERACTION WITH INTEGRIN ITGAV:ITGB3, AND MUTAGENESIS OF LYS-116; ILE-119; RP LYS-121; LYS-124; PHE-126; LYS-144; LYS-148; PHE-186 AND LYS-187. RX PubMed=27993971; DOI=10.1042/bcj20160998; RA Yu J., Lee C.Y., Changou C.A., Cedano-Prieto D.M., Takada Y.K., Takada Y.; RT "The CD9, CD81, and CD151 EC2 domains bind to the classical RGD-binding RT site of integrin alphavbeta3."; RL Biochem. J. 474:589-596(2017). RN [28] RP FUNCTION, FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH SAMHD1. RX PubMed=28871089; DOI=10.1038/s41564-017-0019-0; RA Rocha-Perugini V., Suarez H., Alvarez S., Lopez-Martin S., Lenzi G.M., RA Vences-Catalan F., Levy S., Kim B., Munoz-Fernandez M.A., RA Sanchez-Madrid F., Yanez-Mo M.; RT "CD81 association with SAMHD1 enhances HIV-1 reverse transcription by RT increasing dNTP levels."; RL Nat. Microbiol. 2:1513-1522(2017). RN [29] {ECO:0007744|PDB:1G8Q} RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 113-202. RX PubMed=11226150; DOI=10.1093/emboj/20.1.12; RA Kitadokoro K., Bordo D., Galli G., Petracca R., Falugi F., Abrignani S., RA Grandi G., Bolognesi M.; RT "CD81 extracellular domain 3D structure: insight into the tetraspanin RT superfamily structural motifs."; RL EMBO J. 20:12-18(2001). RN [30] {ECO:0007744|PDB:1IV5} RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 113-201. RX PubMed=12437138; DOI=10.1515/bc.2002.164; RA Kitadokoro K., Ponassi M., Galli G., Petracca R., Falugi F., Grandi G., RA Bolognesi M.; RT "Subunit association and conformational flexibility in the head subdomain RT of human CD81 large extracellular loop."; RL Biol. Chem. 383:1447-1452(2002). RN [31] {ECO:0007744|PDB:3X0E} RP X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 113-202, FUNCTION (MICROBIAL RP INFECTION), INTERACTION WITH HCV ENVELOPE PROTEIN E2 (MICROBIAL INFECTION), RP DISULFIDE BONDS, AND MUTAGENESIS OF GLU-188 AND ASP-196. RX PubMed=26116703; DOI=10.1096/fj.15-272880; RA Yang W., Zhang M., Chi X., Liu X., Qin B., Cui S.; RT "An intramolecular bond at cluster of differentiation 81 ectodomain is RT important for hepatitis C virus entry."; RL FASEB J. 29:4214-4226(2015). RN [32] {ECO:0007744|PDB:5TCX} RP X-RAY CRYSTALLOGRAPHY (2.96 ANGSTROMS), FUNCTION, TOPOLOGY, DISULFIDE RP BONDS, CHOLESTEROL BINDING, DOMAIN, AND MUTAGENESIS OF GLU-219. RX PubMed=27881302; DOI=10.1016/j.cell.2016.09.056; RA Zimmerman B., Kelly B., McMillan B.J., Seegar T.C.M., Dror R.O., RA Kruse A.C., Blacklow S.C.; RT "Crystal Structure of a Full-Length Human Tetraspanin Reveals a RT Cholesterol-Binding Pocket."; RL Cell 167:1041-1051.E11(2016). RN [33] {ECO:0007744|PDB:5M2C, ECO:0007744|PDB:5M33, ECO:0007744|PDB:5M3D, ECO:0007744|PDB:5M3T, ECO:0007744|PDB:5M4R} RP X-RAY CRYSTALLOGRAPHY (1.28 ANGSTROMS) OF 113-201, AND DISULFIDE BONDS. RX PubMed=27916518; DOI=10.1016/j.str.2016.11.003; RA Cunha E.S., Sfriso P., Rojas A.L., Roversi P., Hospital A., Orozco M., RA Abrescia N.G.A.; RT "Mechanism of Structural Tuning of the Hepatitis C Virus Human Cellular RT Receptor CD81 Large Extracellular Loop."; RL Structure 25:53-65(2017). CC -!- FUNCTION: Structural component of specialized membrane microdomains CC known as tetraspanin-enriched microdomains (TERMs), which act as CC platforms for receptor clustering and signaling. Essential for CC trafficking and compartmentalization of CD19 receptor on the surface of CC activated B cells (PubMed:20237408, PubMed:27881302, PubMed:16449649). CC Upon initial encounter with microbial pathogens, enables the assembly CC of CD19-CR2/CD21 and B cell receptor (BCR) complexes at signaling CC TERMs, lowering the threshold dose of antigen required to trigger B CC cell clonal expansion and antibody production (PubMed:15161911, CC PubMed:20237408). In T cells, facilitates the localization of CD247/CD3 CC zeta at antigen-induced synapses with B cells, providing for CC costimulation and polarization toward T helper type 2 phenotype CC (PubMed:22307619, PubMed:23858057, PubMed:8766544). Present in MHC CC class II compartments, may also play a role in antigen presentation CC (PubMed:8409388, PubMed:8766544). Can act both as positive and negative CC regulator of homotypic or heterotypic cell-cell fusion processes. CC Positively regulates sperm-egg fusion and may be involved in acrosome CC reaction (By similarity). In myoblasts, associates with CD9 and PTGFRN CC and inhibits myotube fusion during muscle regeneration (By similarity). CC In macrophages, associates with CD9 and beta-1 and beta-2 integrins, CC and prevents macrophage fusion into multinucleated giant cells CC specialized in ingesting complement-opsonized large particles CC (PubMed:12796480). Also prevents the fusion of mononuclear cell CC progenitors into osteoclasts in charge of bone resorption (By CC similarity). May regulate the compartmentalization of enzymatic CC activities. In T cells, defines the subcellular localization of dNTPase CC SAMHD1 and permits its degradation by the proteasome, thereby CC controlling intracellular dNTP levels (PubMed:28871089). Also involved CC in cell adhesion and motility. Positively regulates integrin-mediated CC adhesion of macrophages, particularly relevant for the inflammatory CC response in the lung (By similarity). {ECO:0000250|UniProtKB:P35762, CC ECO:0000269|PubMed:12796480, ECO:0000269|PubMed:15161911, CC ECO:0000269|PubMed:16449649, ECO:0000269|PubMed:20237408, CC ECO:0000269|PubMed:22307619, ECO:0000269|PubMed:23858057, CC ECO:0000269|PubMed:27881302, ECO:0000269|PubMed:28871089, CC ECO:0000269|PubMed:8409388, ECO:0000269|PubMed:8766544}. CC -!- FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C CC virus (HCV) in hepatocytes. Association with CLDN1 and the CLDN1-CD81 CC receptor complex is essential for HCV entry into host cell. CC {ECO:0000269|PubMed:20375010, ECO:0000269|PubMed:21516087, CC ECO:0000269|PubMed:26116703, ECO:0000269|PubMed:26354436}. CC -!- FUNCTION: (Microbial infection) Involved in SAMHD1-dependent CC restriction of HIV-1 replication. May support early replication of both CC R5- and X4-tropic HIV-1 viruses in T cells, likely via proteasome- CC dependent degradation of SAMHD1. {ECO:0000269|PubMed:28871089}. CC -!- FUNCTION: (Microbial infection) Specifically required for Plasmodium CC falciparum infectivity of hepatocytes, controlling sporozoite entry CC into hepatocytes via the parasitophorous vacuole and subsequent CC parasite differentiation to exoerythrocytic forms. CC {ECO:0000269|PubMed:12483205}. CC -!- SUBUNIT: Homodimer (PubMed:20375010). Part of a complex composed of CC CD19, CR2/CD21, CD81 and IFITM1/CD225 in the membrane of mature B CC cells. Interacts (via the second extracellular domain) with CD19; this CC interaction is initiated early during biosynthesis in the ER and CC enables trafficking of only properly folded CD19 (PubMed:16449649, CC PubMed:1383329). Part of a complex that includes MHC class II/HLA-DR CC molecules and IFITM1 (PubMed:8409388). Interacts with IFITM1 CC (PubMed:2398277, PubMed:26354436). Interacts with IFITM2 and IFITM3 (By CC similarity). Part of integrin-tetraspanin complex composed of CD9, CC CD81, beta-1 and beta-2 integrins in the membrane of CC monocyte/macrophages (PubMed:12796480). Interacts (via the second CC extracellular domain) with integrin ITGAV:ITGB3 (PubMed:27993971). CC Interacts with CD247/CD3 zeta, ICAM1 and CD9 at the immune synapse on T CC cell membrane (PubMed:23858057). Part of a GPCR-tetraspanin complex CC consisting at least of ADGRG1, CD81, possibly CD9, and GNA11 in which CC CD81 enhances the association of ADGRG1 with GNA11 (PubMed:15004227). CC Part of a complex composed of CD9, CD81, PTGFRN and IGSF8 (By CC similarity). Interacts directly with IGSF8 (PubMed:11504738). Interacts CC with CD53 and SCIMP (PubMed:21930792). Interacts with SAMHD1 (via its CC C-terminus) (PubMed:28871089). Interacts with glypican GPC3 and with CC the transcriptional repressor HHEX; binding to GPC3 decreases the CC availability of free CD81 for binding to HHEX, resulting in nuclear CC translocation of HHEX and transcriptional repression (By similarity). CC Interacts with CLDN1 (PubMed:20375010, PubMed:21516087). Interacts with CC CLDN6 and CLDN9 (PubMed:20375010). {ECO:0000250|UniProtKB:P35762, CC ECO:0000269|PubMed:12796480, ECO:0000269|PubMed:1383329, CC ECO:0000269|PubMed:16449649, ECO:0000269|PubMed:20375010, CC ECO:0000269|PubMed:23858057, ECO:0000269|PubMed:2398277, CC ECO:0000269|PubMed:26354436, ECO:0000269|PubMed:28871089, CC ECO:0000269|PubMed:8409388}. CC -!- SUBUNIT: (Microbial infection) Plays a critical role in HCV attachment CC and/or cell entry by interacting with HCV E1/E2 glycoproteins CC heterodimer. {ECO:0000269|PubMed:12913001, ECO:0000269|PubMed:12970454, CC ECO:0000269|PubMed:26116703}. CC -!- INTERACTION: CC P60033; O14672: ADAM10; NbExp=9; IntAct=EBI-712921, EBI-1536151; CC P60033; PRO_0000029067 [O14672]: ADAM10; NbExp=2; IntAct=EBI-712921, EBI-21222747; CC P60033; Q13520: AQP6; NbExp=3; IntAct=EBI-712921, EBI-13059134; CC P60033; Q10589: BST2; NbExp=3; IntAct=EBI-712921, EBI-2476339; CC P60033; Q7Z7G2: CPLX4; NbExp=3; IntAct=EBI-712921, EBI-18013275; CC P60033; Q15125: EBP; NbExp=3; IntAct=EBI-712921, EBI-3915253; CC P60033; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-712921, EBI-781551; CC P60033; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-712921, EBI-18304435; CC P60033; P35212: GJA4; NbExp=3; IntAct=EBI-712921, EBI-6918707; CC P60033; Q5T7V8: GORAB; NbExp=3; IntAct=EBI-712921, EBI-3917143; CC P60033; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-712921, EBI-13345167; CC P60033; Q8TED1: GPX8; NbExp=3; IntAct=EBI-712921, EBI-11721746; CC P60033; Q14739: LBR; NbExp=3; IntAct=EBI-712921, EBI-1055147; CC P60033; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-712921, EBI-2820517; CC P60033; Q96PE7: MCEE; NbExp=3; IntAct=EBI-712921, EBI-10292326; CC P60033; Q9Y676: MRPS18B; NbExp=3; IntAct=EBI-712921, EBI-750085; CC P60033; O14524-2: NEMP1; NbExp=3; IntAct=EBI-712921, EBI-10969203; CC P60033; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-712921, EBI-716063; CC P60033; Q9NR31: SAR1A; NbExp=3; IntAct=EBI-712921, EBI-3920694; CC P60033; Q8WTV0: SCARB1; NbExp=4; IntAct=EBI-712921, EBI-78657; CC P60033; Q5VUM1: SDHAF4; NbExp=3; IntAct=EBI-712921, EBI-16769525; CC P60033; Q9BXS9-3: SLC26A6; NbExp=3; IntAct=EBI-712921, EBI-12814225; CC P60033; Q16623: STX1A; NbExp=3; IntAct=EBI-712921, EBI-712466; CC P60033; Q8WY91: THAP4; NbExp=3; IntAct=EBI-712921, EBI-726691; CC P60033; Q9Y320: TMX2; NbExp=3; IntAct=EBI-712921, EBI-6447886; CC P60033; Q9NSU2-1: TREX1; NbExp=3; IntAct=EBI-712921, EBI-16746122; CC P60033; PRO_0000037570 [P27958]; Xeno; NbExp=11; IntAct=EBI-712921, EBI-6904269; CC P60033; PRO_0000045596 [Q99IB8]; Xeno; NbExp=2; IntAct=EBI-712921, EBI-6901449; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1383329, CC ECO:0000269|PubMed:1695320, ECO:0000269|PubMed:20237408, CC ECO:0000269|PubMed:22307619, ECO:0000269|PubMed:2398277, CC ECO:0000269|PubMed:26354436}; Multi-pass membrane protein CC {ECO:0000255}. Basolateral cell membrane {ECO:0000269|PubMed:20375010}; CC Multi-pass membrane protein {ECO:0000255}. Note=Associates with CLDN1 CC and the CLDN1-CD81 complex localizes to the basolateral cell membrane. CC {ECO:0000269|PubMed:20375010}. CC -!- TISSUE SPECIFICITY: Expressed on B cells (at protein level) CC (PubMed:20237408). Expressed in hepatocytes (at protein level) CC (PubMed:12483205). Expressed in monocytes/macrophages (at protein CC level) (PubMed:12796480). Expressed on both naive and memory CD4- CC positive T cells (at protein level) (PubMed:22307619). CC {ECO:0000269|PubMed:12483205, ECO:0000269|PubMed:12796480, CC ECO:0000269|PubMed:20237408, ECO:0000269|PubMed:22307619}. CC -!- DOMAIN: Binds cholesterol in a cavity lined by the transmembrane spans. CC {ECO:0000269|PubMed:27881302}. CC -!- PTM: Not glycosylated. {ECO:0000305}. CC -!- PTM: Likely constitutively palmitoylated at low levels. Protein CC palmitoylation is up-regulated upon coligation of BCR and CD9-C2R-CD81 CC complexes in lipid rafts. {ECO:0000269|PubMed:15161911}. CC -!- DISEASE: Immunodeficiency, common variable, 6 (CVID6) [MIM:613496]: A CC primary immunodeficiency characterized by antibody deficiency, CC hypogammaglobulinemia, recurrent bacterial infections and an inability CC to mount an antibody response to antigen. The defect results from a CC failure of B-cell differentiation and impaired secretion of CC immunoglobulins; the numbers of circulating B-cells is usually in the CC normal range, but can be low. {ECO:0000269|PubMed:20237408}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the tetraspanin (TM4SF) family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M33680; AAA36663.1; -; mRNA. DR EMBL; BT019507; AAV38314.1; -; mRNA. DR EMBL; BT019508; AAV38315.1; -; mRNA. DR EMBL; EF064749; ABK41932.1; -; Genomic_DNA. DR EMBL; AC129929; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC124057; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC002978; AAH02978.1; -; mRNA. DR EMBL; BC093047; AAH93047.1; -; mRNA. DR CCDS; CCDS7734.1; -. DR PIR; A35649; A35649. DR RefSeq; NP_001284578.1; NM_001297649.1. DR RefSeq; NP_004347.1; NM_004356.3. DR PDB; 1G8Q; X-ray; 1.60 A; A/B=113-201. DR PDB; 1IV5; X-ray; 2.60 A; A/B=113-201. DR PDB; 3X0E; X-ray; 1.84 A; A/B=113-202. DR PDB; 5DFV; X-ray; 2.80 A; A/B=112-201. DR PDB; 5DFW; X-ray; 2.33 A; A=112-201. DR PDB; 5M2C; X-ray; 1.96 A; A/B=112-201. DR PDB; 5M33; X-ray; 1.28 A; A/B=113-201. DR PDB; 5M3D; X-ray; 2.38 A; A/B/C/D=112-201. DR PDB; 5M3T; X-ray; 2.02 A; A/B=112-201. DR PDB; 5M4R; X-ray; 3.10 A; A/B/C/D/E=112-201. DR PDB; 5TCX; X-ray; 2.96 A; A=2-236. DR PDB; 6EJG; X-ray; 2.82 A; A/B=112-202. DR PDB; 6EJM; X-ray; 2.15 A; A/B=112-202. DR PDB; 6EK2; X-ray; 2.65 A; A/B=112-201. DR PDB; 6U9S; X-ray; 2.40 A; C/F=112-200. DR PDB; 7JIC; EM; 3.80 A; B=2-236. DR PDBsum; 1G8Q; -. DR PDBsum; 1IV5; -. DR PDBsum; 3X0E; -. DR PDBsum; 5DFV; -. DR PDBsum; 5DFW; -. DR PDBsum; 5M2C; -. DR PDBsum; 5M33; -. DR PDBsum; 5M3D; -. DR PDBsum; 5M3T; -. DR PDBsum; 5M4R; -. DR PDBsum; 5TCX; -. DR PDBsum; 6EJG; -. DR PDBsum; 6EJM; -. DR PDBsum; 6EK2; -. DR PDBsum; 6U9S; -. DR PDBsum; 7JIC; -. DR AlphaFoldDB; P60033; -. DR BMRB; P60033; -. DR EMDB; EMD-22344; -. DR SMR; P60033; -. DR BioGRID; 107413; 292. DR CORUM; P60033; -. DR IntAct; P60033; 295. DR MINT; P60033; -. DR STRING; 9606.ENSP00000263645; -. DR BindingDB; P60033; -. DR ChEMBL; CHEMBL1075180; -. DR TCDB; 8.A.40.1.1; the tetraspanin (tetraspanin) family. DR GlyGen; P60033; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P60033; -. DR PhosphoSitePlus; P60033; -. DR SwissPalm; P60033; -. DR BioMuta; CD81; -. DR DMDM; 38503376; -. DR EPD; P60033; -. DR jPOST; P60033; -. DR MassIVE; P60033; -. DR MaxQB; P60033; -. DR PaxDb; 9606-ENSP00000263645; -. DR PeptideAtlas; P60033; -. DR ProteomicsDB; 57182; -. DR Pumba; P60033; -. DR ABCD; P60033; 10 sequenced antibodies. DR Antibodypedia; 1570; 1485 antibodies from 47 providers. DR DNASU; 975; -. DR Ensembl; ENST00000263645.10; ENSP00000263645.5; ENSG00000110651.13. DR GeneID; 975; -. DR KEGG; hsa:975; -. DR MANE-Select; ENST00000263645.10; ENSP00000263645.5; NM_004356.4; NP_004347.1. DR UCSC; uc001lwf.2; human. DR AGR; HGNC:1701; -. DR CTD; 975; -. DR DisGeNET; 975; -. DR GeneCards; CD81; -. DR HGNC; HGNC:1701; CD81. DR HPA; ENSG00000110651; Low tissue specificity. DR MalaCards; CD81; -. DR MIM; 186845; gene. DR MIM; 613496; phenotype. DR neXtProt; NX_P60033; -. DR OpenTargets; ENSG00000110651; -. DR Orphanet; 1572; Common variable immunodeficiency. DR PharmGKB; PA26240; -. DR VEuPathDB; HostDB:ENSG00000110651; -. DR eggNOG; KOG3882; Eukaryota. DR GeneTree; ENSGT00940000158805; -. DR HOGENOM; CLU_055524_10_0_1; -. DR InParanoid; P60033; -. DR OMA; HETLSCC; -. DR OrthoDB; 2964111at2759; -. DR PhylomeDB; P60033; -. DR TreeFam; TF352895; -. DR PathwayCommons; P60033; -. DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell. DR Reactome; R-HSA-977606; Regulation of Complement cascade. DR SignaLink; P60033; -. DR BioGRID-ORCS; 975; 22 hits in 1154 CRISPR screens. DR ChiTaRS; CD81; human. DR EvolutionaryTrace; P60033; -. DR GeneWiki; CD81; -. DR GenomeRNAi; 975; -. DR Pharos; P60033; Tchem. DR PRO; PR:P60033; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P60033; Protein. DR Bgee; ENSG00000110651; Expressed in stromal cell of endometrium and 213 other cell types or tissues. DR ExpressionAtlas; P60033; baseline and differential. DR GO; GO:0009925; C:basal plasma membrane; IDA:ARUK-UCL. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0001772; C:immunological synapse; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0097197; C:tetraspanin-enriched microdomain; IDA:UniProtKB. DR GO; GO:0031982; C:vesicle; IDA:UniProtKB. DR GO; GO:0015485; F:cholesterol binding; IDA:UniProtKB. DR GO; GO:0005178; F:integrin binding; IDA:UniProtKB. DR GO; GO:0042289; F:MHC class II protein binding; IDA:UniProtKB. DR GO; GO:0023026; F:MHC class II protein complex binding; HDA:UniProtKB. DR GO; GO:1990459; F:transferrin receptor binding; IPI:BHF-UCL. DR GO; GO:0001618; F:virus receptor activity; IMP:UniProtKB. DR GO; GO:0035783; P:CD4-positive, alpha-beta T cell costimulation; IDA:UniProtKB. DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; ISS:UniProtKB. DR GO; GO:0002455; P:humoral immune response mediated by circulating immunoglobulin; IMP:UniProtKB. DR GO; GO:0001771; P:immunological synapse formation; IMP:UniProtKB. DR GO; GO:0034238; P:macrophage fusion; IDA:UniProtKB. DR GO; GO:0014905; P:myoblast fusion involved in skeletal muscle regeneration; ISS:UniProtKB. DR GO; GO:0072675; P:osteoclast fusion; ISS:UniProtKB. DR GO; GO:1905676; P:positive regulation of adaptive immune memory response; IMP:UniProtKB. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IDA:AgBase. DR GO; GO:0050861; P:positive regulation of B cell receptor signaling pathway; IMP:UniProtKB. DR GO; GO:2000563; P:positive regulation of CD4-positive, alpha-beta T cell proliferation; IDA:UniProtKB. DR GO; GO:0002863; P:positive regulation of inflammatory response to antigenic stimulus; ISS:UniProtKB. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB. DR GO; GO:1904352; P:positive regulation of protein catabolic process in the vacuole; IMP:BHF-UCL. DR GO; GO:0070863; P:positive regulation of protein exit from endoplasmic reticulum; IMP:UniProtKB. DR GO; GO:1903911; P:positive regulation of receptor clustering; IDA:UniProtKB. DR GO; GO:2001190; P:positive regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell; IDA:UniProtKB. DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; IMP:UniProtKB. DR GO; GO:2000553; P:positive regulation of T-helper 2 cell cytokine production; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:BHF-UCL. DR GO; GO:0061462; P:protein localization to lysosome; IMP:BHF-UCL. DR GO; GO:0072659; P:protein localization to plasma membrane; IDA:UniProtKB. DR GO; GO:0031623; P:receptor internalization; ISS:UniProtKB. DR GO; GO:1905521; P:regulation of macrophage migration; ISS:UniProtKB. DR GO; GO:0031647; P:regulation of protein stability; IMP:BHF-UCL. DR CDD; cd03151; CD81_like_LEL; 1. DR Gene3D; 1.10.1450.10; Tetraspanin; 1. DR InterPro; IPR018499; Tetraspanin/Peripherin. DR InterPro; IPR000301; Tetraspanin_animals. DR InterPro; IPR018503; Tetraspanin_CS. DR InterPro; IPR008952; Tetraspanin_EC2_sf. DR PANTHER; PTHR19282:SF214; CD81 ANTIGEN; 1. DR PANTHER; PTHR19282; TETRASPANIN; 1. DR Pfam; PF00335; Tetraspanin; 1. DR PIRSF; PIRSF002419; Tetraspanin; 1. DR PRINTS; PR00259; TMFOUR. DR SUPFAM; SSF48652; Tetraspanin; 1. DR PROSITE; PS00421; TM4_1; 1. DR Genevisible; P60033; HS. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Cell membrane; Disulfide bond; KW Host cell receptor for virus entry; Host-virus interaction; Immunity; KW Lipid-binding; Membrane; Receptor; Reference proteome; Transmembrane; KW Transmembrane helix. FT CHAIN 1..236 FT /note="CD81 antigen" FT /id="PRO_0000219221" FT TOPO_DOM 1..12 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:27881302, FT ECO:0000305|PubMed:1860863" FT TRANSMEM 13..33 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:27881302" FT TOPO_DOM 34..63 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:27881302" FT TRANSMEM 64..84 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:27881302" FT TOPO_DOM 85..89 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:27881302" FT TRANSMEM 90..112 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:27881302" FT TOPO_DOM 113..201 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:27881302" FT TRANSMEM 202..224 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:27881302" FT TOPO_DOM 225..236 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:27881302, FT ECO:0000305|PubMed:1860863" FT BINDING 219 FT /ligand="cholesterol" FT /ligand_id="ChEBI:CHEBI:16113" FT /evidence="ECO:0000269|PubMed:27881302, FT ECO:0007744|PDB:5TCX" FT SITE 116 FT /note="Important for interaction with integrin" FT /evidence="ECO:0000269|PubMed:27993971" FT SITE 144 FT /note="Important for interaction with integrin" FT /evidence="ECO:0000269|PubMed:27993971" FT SITE 148 FT /note="Important for interaction with integrin" FT /evidence="ECO:0000269|PubMed:27993971" FT DISULFID 156..190 FT /evidence="ECO:0000269|PubMed:11226150, FT ECO:0000269|PubMed:12437138, ECO:0000269|PubMed:26116703, FT ECO:0000269|PubMed:27881302, ECO:0000269|PubMed:27916518, FT ECO:0007744|PDB:1G8Q, ECO:0007744|PDB:1IV5, FT ECO:0007744|PDB:3X0E, ECO:0007744|PDB:5DFV, FT ECO:0007744|PDB:5DFW, ECO:0007744|PDB:5M2C, FT ECO:0007744|PDB:5M33, ECO:0007744|PDB:5M3D, FT ECO:0007744|PDB:5M3T, ECO:0007744|PDB:5M4R, FT ECO:0007744|PDB:5TCX, ECO:0007744|PDB:6EJG, FT ECO:0007744|PDB:6EJM, ECO:0007744|PDB:6EK2" FT DISULFID 157..175 FT /evidence="ECO:0000269|PubMed:11226150, FT ECO:0000269|PubMed:12437138, ECO:0000269|PubMed:26116703, FT ECO:0000269|PubMed:27881302, ECO:0000269|PubMed:27916518, FT ECO:0007744|PDB:1G8Q, ECO:0007744|PDB:1IV5, FT ECO:0007744|PDB:3X0E, ECO:0007744|PDB:5DFV, FT ECO:0007744|PDB:5DFW, ECO:0007744|PDB:5M2C, FT ECO:0007744|PDB:5M33, ECO:0007744|PDB:5M3D, FT ECO:0007744|PDB:5M3T, ECO:0007744|PDB:5M4R, FT ECO:0007744|PDB:5TCX, ECO:0007744|PDB:6EJG, FT ECO:0007744|PDB:6EJM, ECO:0007744|PDB:6EK2" FT MUTAGEN 116 FT /note="K->E: Reduces binding to integrin." FT /evidence="ECO:0000269|PubMed:27993971" FT MUTAGEN 119 FT /note="I->A: No effect on integrin binding." FT /evidence="ECO:0000269|PubMed:27993971" FT MUTAGEN 121 FT /note="K->E: No effect on integrin binding." FT /evidence="ECO:0000269|PubMed:27993971" FT MUTAGEN 124 FT /note="K->E: No effect on integrin binding." FT /evidence="ECO:0000269|PubMed:27993971" FT MUTAGEN 126 FT /note="F->A: No effect on integrin binding." FT /evidence="ECO:0000269|PubMed:27993971" FT MUTAGEN 144 FT /note="K->E: Reduces binding to integrin; when associated FT with E-148." FT /evidence="ECO:0000269|PubMed:27993971" FT MUTAGEN 148 FT /note="K->E: Reduces binding to integrin; when associated FT with E-144." FT /evidence="ECO:0000269|PubMed:27993971" FT MUTAGEN 186 FT /note="F->A: No effect on integrin binding." FT /evidence="ECO:0000269|PubMed:27993971" FT MUTAGEN 187 FT /note="K->E: No effect on integrin binding." FT /evidence="ECO:0000269|PubMed:27993971" FT MUTAGEN 188 FT /note="E->K,Q: Strongly reduced affinity for HCV protein FT E2; when associated with E-196." FT /evidence="ECO:0000269|PubMed:26116703" FT MUTAGEN 188 FT /note="E->K: Mildly reduced affinity for HCV protein E2." FT /evidence="ECO:0000269|PubMed:26116703" FT MUTAGEN 196 FT /note="D->E: Strongly reduced affinity for HCV protein E2; FT when associated with K-188 or Q-188." FT /evidence="ECO:0000269|PubMed:26116703" FT MUTAGEN 196 FT /note="D->K,Q,R: Strongly reduced affinity for HCV protein FT E2." FT /evidence="ECO:0000269|PubMed:26116703" FT MUTAGEN 219 FT /note="E->A,Q: Reduced affinity for cholesterol binding." FT /evidence="ECO:0000269|PubMed:27881302" FT HELIX 10..36 FT /evidence="ECO:0007829|PDB:5TCX" FT HELIX 57..80 FT /evidence="ECO:0007829|PDB:5TCX" FT HELIX 81..84 FT /evidence="ECO:0007829|PDB:5TCX" FT HELIX 113..115 FT /evidence="ECO:0007829|PDB:6U9S" FT HELIX 116..136 FT /evidence="ECO:0007829|PDB:5M33" FT HELIX 141..154 FT /evidence="ECO:0007829|PDB:5M33" FT STRAND 158..160 FT /evidence="ECO:0007829|PDB:5M3D" FT HELIX 163..165 FT /evidence="ECO:0007829|PDB:5M33" FT HELIX 166..171 FT /evidence="ECO:0007829|PDB:5M33" FT HELIX 172..174 FT /evidence="ECO:0007829|PDB:5M2C" FT HELIX 181..185 FT /evidence="ECO:0007829|PDB:5M33" FT HELIX 190..199 FT /evidence="ECO:0007829|PDB:5M33" FT HELIX 202..230 FT /evidence="ECO:0007829|PDB:5TCX" SQ SEQUENCE 236 AA; 25809 MW; EB9BD7671AC91B4A CRC64; MGVEGCTKCI KYLLFVFNFV FWLAGGVILG VALWLRHDPQ TTNLLYLELG DKPAPNTFYV GIYILIAVGA VMMFVGFLGC YGAIQESQCL LGTFFTCLVI LFACEVAAGI WGFVNKDQIA KDVKQFYDQA LQQAVVDDDA NNAKAVVKTF HETLDCCGSS TLTALTTSVL KNNLCPSGSN IISNLFKEDC HQKIDDLFSG KLYLIGIAAI VVAVIMIFEM ILSMVLCCGI RNSSVY //