9ht6

Structural highlights

Function

CD82_HUMAN Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling (PubMed:19497983). Participates thereby in diverse biological functions such as cell signal transduction, adhesion, migration and protein trafficking. Acts as a attenuator of EGF signaling, facilitating ligand-induced endocytosis of the receptor and its subsequent desensitization (PubMed:10985391, PubMed:35538033). Mechanistically, modulates ligand-induced ubiquitination and trafficking of EGFR via E3 ligase CBL phosphorylation by PKC (PubMed:23897813). Increases cell-matrix adhesion by regulating the membrane organization of integrin alpha4/ITA4 (PubMed:24623721, PubMed:8757325). Modulates adhesion and suppresses cell migration through other integrins such as the alpha6/ITGA6 and beta1/ITGB1 (PubMed:15557282, PubMed:17560548). Decreases cell-associated plasminogen activation by interfering with the interaction between urokinase-type plasminogen activator/PLAU and its receptor PLAUR (PubMed:15677461). Associates with CD4 or CD8 and delivers costimulatory signals for the TCR/CD3 pathway. Plays a role in TLR9 trafficking to acidified CpG-containing compartments by controlling interaction between TLR9 and VAMP3 and subsequent myddosome assembly (By similarity). Inhibits LPS-induced inflammatory response by preventing binding of LPS to TLR4 on the cell surface (PubMed:36945827). Plays a role in the activation of macrophages into anti-inflammatory phenotypes (By similarity). Independently of Toll-like receptor (TLR) signaling, is recruited to pathogen-containing phagosomes prior to fusion with lysosomes and thereby participates in antigen presentation (By similarity). Also acts to control angiogenesis and switch angiogenic milieu to quiescent state by binding and sequestering VEGFA and PDGFB to inhibit the signaling they trigger via their respective cell surface receptor (PubMed:34530889).[UniProtKB:P40237]^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]}

References

1. ↑ Odintsova E, Sugiura T, Berditchevski F. Attenuation of EGF receptor signaling by a metastasis suppressor, the tetraspanin CD82/KAI-1. Curr Biol. 2000 Aug 24;10(16):1009-12. PMID:10985391 doi:10.1016/s0960-9822(00)00652-7
2. ↑ Zhang XA, Lane WS, Charrin S, Rubinstein E, Liu L. EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells. Cancer Res. 2003 May 15;63(10):2665-74 PMID:12750295
3. ↑ He B, Liu L, Cook GA, Grgurevich S, Jennings LK, Zhang XA. Tetraspanin CD82 attenuates cellular morphogenesis through down-regulating integrin alpha6-mediated cell adhesion. J Biol Chem. 2005 Feb 4;280(5):3346-54. PMID:15557282 doi:10.1074/jbc.M406680200
4. ↑ Bass R, Werner F, Odintsova E, Sugiura T, Berditchevski F, Ellis V. Regulation of urokinase receptor proteolytic function by the tetraspanin CD82. J Biol Chem. 2005 Apr 15;280(15):14811-8. PMID:15677461 doi:10.1074/jbc.M414189200
5. ↑ Xu C, Zhang YH, Thangavel M, Richardson MM, Liu L, Zhou B, Zheng Y, Ostrom RS, Zhang XA. CD82 endocytosis and cholesterol-dependent reorganization of tetraspanin webs and lipid rafts. FASEB J. 2009 Oct;23(10):3273-88. PMID:19497983 doi:10.1096/fj.08-123414
6. ↑ Odintsova E, van Niel G, Conjeaud H, Raposo G, Iwamoto R, Mekada E, Berditchevski F. Metastasis suppressor tetraspanin CD82/KAI1 regulates ubiquitylation of epidermal growth factor receptor. J Biol Chem. 2013 Sep 6;288(36):26323-26334. PMID:23897813 doi:10.1074/jbc.M112.439380
7. ↑ Termini CM, Cotter ML, Marjon KD, Buranda T, Lidke KA, Gillette JM. The membrane scaffold CD82 regulates cell adhesion by altering α4 integrin stability and molecular density. Mol Biol Cell. 2014 May;25(10):1560-73. PMID:24623721 doi:10.1091/mbc.E13-11-0660
8. ↑ Bu J, Zhong W, Li M, He S, Zhang M, Zhang Y, Li Y. CD82 palmitoylation site mutations at Cys5+Cys74 affect EGFR internalization and metabolism through recycling pathway. Acta Biochim Biophys Sin (Shanghai). 2022 Mar 25;54(3):400-408. PMID:35538033 doi:10.3724/abbs.2022011
9. ↑ Lee H, Han JH, An K, Kang YJ, Hwangbo H, Heo JH, Choi BH, Kim JJ, Kim SR, Lee SY, Hur J. Recombinant human KAI1/CD82 attenuates M1 macrophage polarization on LPS-stimulated RAW264.7 cells via blocking TLR4/JNK/NF-κB signal pathway. BMB Rep. 2023 Jun;56(6):359-364. PMID:36945827 doi:10.5483/BMBRep.2022-0189
10. ↑ Mannion BA, Berditchevski F, Kraeft SK, Chen LB, Hemler ME. Transmembrane-4 superfamily proteins CD81 (TAPA-1), CD82, CD63, and CD53 specifically associated with integrin alpha 4 beta 1 (CD49d/CD29). J Immunol. 1996 Sep 1;157(5):2039-47 PMID:8757325