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Gene Review

CD82  -  CD82 molecule

Homo sapiens

Synonyms: 4F9, C33, C33 antigen, CD82 antigen, GR15, ...
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Disease relevance of CD82


Psychiatry related information on CD82

  • Similar to R3 peptide, R2 peptide also plays an important role in the formation of neurofibrillary tangles (NFTs) which is one of the two main biological characteristics of Alzheimer's disease (AD) [4].
  • Combined with significant age and gender relations, this implies a risk of underdiagnosed depression, if the EORTC QLQ C33 is used as the only instrument to screen for psychological distress in cancer patients [5].

High impact information on CD82

  • These results provide direct evidence that DARC is essential for the function of CD82 as a suppressor of metastasis [6].
  • Downregulation of KAI1 has been found to be clinically associated with metastatic progression in a variety of cancers, whereas overexpression of CD82 specifically suppresses tumor metastasis in various animal models [6].
  • Expression of this gene, designated KAI1, was reduced in human cell lines derived from metastatic prostate tumors [7].
  • KAI1 is evolutionarily conserved, is expressed in many human tissues, and encodes a member of a structurally distinct family of leukocyte surface glycoproteins [7].
  • The virus-containing vacuoles were also labeled with antibodies against LAMP-1, CD81, and CD82, which were also incorporated into the viral envelope [8].

Chemical compound and disease context of CD82

  • The expression of CD82 and CD63 was analysed by reverse transcriptase-PCR (RT-PCR) and immunohistochemistry in benign goiter (n=12) and 75 primary thyroid carcinoma tissue specimens (PTC: 33, FTC: 24, UTC: 18) out of which 36 were non-metastasized primary tumors and 39 were metastasized tumors (regional lymph node and/or distant metastases) [3].
  • To understand the basis of this association, we generated site-directed mutations in the various domains of CD82 and used coimmunoprecipitation and colocalization approaches to examine interactions with HTLV-1 MA [9].
  • The structure of the KAI1 large extracellular domain was modeled based on the solved crystal structure of the extracellular domain of another tetraspanin superfamily protein member, CD81 (hepatitis C virus envelope E2 glycoprotein receptor) [10].
  • Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissues from 53 bronchogenic adenocarcinomas and 51 squamous cell carcinomas using monoclonal antibodies against PTEN, nm23H-1, and KAI-1 proteins [11].
  • In 15 patients with metastatic disease who had failed androgen ablation therapy, more than 90% of the primary prostatic cancers had downregulation, with 60% having no KAI1 protein expression [12].

Biological context of CD82

  • Our data suggest that high KAII/CD82 gene expression by tumors of the lung may be associated with a good prognosis [1].
  • This down-regulation indicates that the diminished cell adhesiveness of CD82-expressing Du145 cells on laminin likely resulted from less cell surface expression of alpha6 integrins [13].
  • Although the physiological relevance of this change is unknown, in vitro data show that ectopically expressed CD82/KAI-1 can suppress tumor cell migration, a process underlying the dissemination of tumor cells in vivo [5] [14].
  • We further found that CD82 significantly inhibited cell adhesion on laminin 1 [13].
  • After CD82 is expressed in Du145 cells, this cellular morphogenesis was abolished, indicating a functional cross-talk between CD82 and alpha6 integrins [13].

Anatomical context of CD82

  • Multivariate analysis with the Cox regression model indicated that KAII/CD82 positivity correlated best with the overall survival rate, except for lymph node status [1].
  • CD82, member of the tetra-span-transmembrane protein family, is a costimulatory protein for T cell activation [15].
  • Here we demonstrate that two other tetraspans, CD82 and the early B cell marker CD9, are coimmunoprecipitated with CD19 from Brij97 lysates of B cell lines [16].
  • CD82, tetra-span-transmembrane protein, is a regulated transducing molecule on U937 monocytic cell line [17].
  • We have previously shown that CD82 membrane expression is up-regulated during differentiation of human monocytes [17].

Associations of CD82 with chemical compounds

  • Finally, the internalization of cell surface integrin alpha6 is significantly enhanced upon CD82 expression [13].
  • The present study addresses phenotypic changes in Chinese hamster ovary mutant cell line ldlD deficient in UDP-Glc 4-epimerase and expressing CD82 or CD9 by cDNA transfection [18].
  • In contrast, mutations of conserved amino acids in the inner loop of CD82 or of palmitoylated cysteines that flank the inner loop diminished CD82 association with MA [9].
  • Second, all functional effects linked to CD82 engagement, such as adhesion to culture plates, formation of actin bundles and early events of tyrosine phosphorylation, are abolished, or strongly reduced, by cholesterol depletion [19].
  • Expression of CD82 causes a significant increase in the amount of EGFR and ErbB2 in the light fractions of the sucrose gradient [20].
  • (iii) In contrast, YTS1 cells, lacking CD82, displayed HGF-independent activation of Met tyrosine kinase and high cell motility [21].

Physical interactions of CD82

  • Expression of CD9, C63 and CD151 was found to be coupled whereas CD82 was expressed independently [22].
  • CD82 could be coprecipitated with both mature and beta 2-microglobulin (beta 2m)-free heavy chains of MHC-I from CHAPS extracts [23].

Regulatory relationships of CD82


Other interactions of CD82

  • No relationship was found between MRP-1 expression and KAI1 expression [27].
  • Moreover, we assessed the prognostic value of evaluating the expressions of MRP-1, KAI1, and ME491 simultaneously in NSCLCs [27].
  • In cells expressing CD82/KAI-1, the initial activation of EGFR is not affected, but subsequent desensitization of EGF-induced signaling occurs more rapidly [14].
  • These associations were confirmed by the cocapping of CD19 with CD9 or CD82 [16].
  • Molecular analyses of the association of CD4 with two members of the transmembrane 4 superfamily, CD81 and CD82 [28].

Analytical, diagnostic and therapeutic context of CD82


  1. Correlation of KAI1/CD82 gene expression with good prognosis in patients with non-small cell lung cancer. Adachi, M., Taki, T., Ieki, Y., Huang, C.L., Higashiyama, M., Miyake, M. Cancer Res. (1996) [Pubmed]
  2. Expression of tetra-spans transmembrane family (CD9, CD37, CD53, CD63, CD81 and CD82) in normal and neoplastic human keratinocytes: an association of CD9 with alpha 3 beta 1 integrin. Okochi, H., Kato, M., Nashiro, K., Yoshie, O., Miyazono, K., Furue, M. Br. J. Dermatol. (1997) [Pubmed]
  3. CD82, and CD63 in thyroid cancer. Chen, Z., Mustafa, T., Trojanowicz, B., Brauckhoff, M., Gimm, O., Schmutzler, C., Köhrle, J., Holzhausen, H.J., Kehlen, A., Klonisch, T., Finke, R., Dralle, H., Hoang-Vu, C. Int. J. Mol. Med. (2004) [Pubmed]
  4. Copper binding properties of a tau peptide associated with Alzheimer's disease studied by CD, NMR, and MALDI-TOF MS. Ma, Q., Li, Y., Du, J., Liu, H., Kanazawa, K., Nemoto, T., Nakanishi, H., Zhao, Y. Peptides (2006) [Pubmed]
  5. Anxiety and depression in cancer patients: relation between the Hospital Anxiety and Depression Scale and the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire. Skarstein, J., Aass, N., Fosså, S.D., Skovlund, E., Dahl, A.A. Journal of psychosomatic research. (2000) [Pubmed]
  6. Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression. Bandyopadhyay, S., Zhan, R., Chaudhuri, A., Watabe, M., Pai, S.K., Hirota, S., Hosobe, S., Tsukada, T., Miura, K., Takano, Y., Saito, K., Pauza, M.E., Hayashi, S., Wang, Y., Mohinta, S., Mashimo, T., Iiizumi, M., Furuta, E., Watabe, K. Nat. Med. (2006) [Pubmed]
  7. KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2. Dong, J.T., Lamb, P.W., Rinker-Schaeffer, C.W., Vukanovic, J., Ichikawa, T., Isaacs, J.T., Barrett, J.C. Science (1995) [Pubmed]
  8. Infectious HIV-1 assembles in late endosomes in primary macrophages. Pelchen-Matthews, A., Kramer, B., Marsh, M. J. Cell Biol. (2003) [Pubmed]
  9. The Inner Loop of Tetraspanins CD82 and CD81 Mediates Interactions with Human T Cell Lymphotrophic Virus Type 1 Gag Protein. Mazurov, D., Heidecker, G., Derse, D. J. Biol. Chem. (2007) [Pubmed]
  10. KAI1, a prostate metastasis suppressor: prediction of solvated structure and interactions with binding partners; integrins, cadherins, and cell-surface receptor proteins. Bienstock, R.J., Barrett, J.C. Mol. Carcinog. (2001) [Pubmed]
  11. Co-downregulation of PTEN, KAI-1, and nm23-H1 tumor/metastasis suppressor proteins in non-small cell lung cancer. Goncharuk, V.N., del-Rosario, A., Kren, L., Anwar, S., Sheehan, C.E., Carlson, J.A., Ross, J.S. Annals of diagnostic pathology. (2004) [Pubmed]
  12. Down-regulation of the KAI1 metastasis suppressor gene during the progression of human prostatic cancer infrequently involves gene mutation or allelic loss. Dong, J.T., Suzuki, H., Pin, S.S., Bova, G.S., Schalken, J.A., Isaacs, W.B., Barrett, J.C., Isaacs, J.T. Cancer Res. (1996) [Pubmed]
  13. Tetraspanin CD82 attenuates cellular morphogenesis through down-regulating integrin alpha6-mediated cell adhesion. He, B., Liu, L., Cook, G.A., Grgurevich, S., Jennings, L.K., Zhang, X.A. J. Biol. Chem. (2005) [Pubmed]
  14. Attenuation of EGF receptor signaling by a metastasis suppressor, the tetraspanin CD82/KAI-1. Odintsova, E., Sugiura, T., Berditchevski, F. Curr. Biol. (2000) [Pubmed]
  15. CD82, member of the tetra-span-transmembrane protein family, is a costimulatory protein for T cell activation. Lebel-Binay, S., Lagaudrière, C., Fradelizi, D., Conjeaud, H. J. Immunol. (1995) [Pubmed]
  16. CD19 is linked to the integrin-associated tetraspans CD9, CD81, and CD82. Horváth, G., Serru, V., Clay, D., Billard, M., Boucheix, C., Rubinstein, E. J. Biol. Chem. (1998) [Pubmed]
  17. CD82, tetra-span-transmembrane protein, is a regulated transducing molecule on U937 monocytic cell line. Lebel-Binay, S., Lagaudrière, C., Fradelizi, D., Conjeaud, H. J. Leukoc. Biol. (1995) [Pubmed]
  18. Motility inhibition and apoptosis are induced by metastasis-suppressing gene product CD82 and its analogue CD9, with concurrent glycosylation. Ono, M., Handa, K., Withers, D.A., Hakomori, S. Cancer Res. (1999) [Pubmed]
  19. Tetraspanin CD82 controls the association of cholesterol-dependent microdomains with the actin cytoskeleton in T lymphocytes: relevance to co-stimulation. Delaguillaumie, A., Harriague, J., Kohanna, S., Bismuth, G., Rubinstein, E., Seigneuret, M., Conjeaud, H. J. Cell. Sci. (2004) [Pubmed]
  20. Tetraspanin CD82 regulates compartmentalisation and ligand-induced dimerization of EGFR. Odintsova, E., Voortman, J., Gilbert, E., Berditchevski, F. J. Cell. Sci. (2003) [Pubmed]
  21. Ganglioside GM2-tetraspanin CD82 complex inhibits met and its cross-talk with integrins, providing a basis for control of cell motility through glycosynapse. Todeschini, A.R., Dos Santos, J.N., Handa, K., Hakomori, S.I. J. Biol. Chem. (2007) [Pubmed]
  22. Expression of tetraspanin adaptor proteins below defined threshold values is associated with in vitro invasiveness of mammary carcinoma cells. Sauer, G., Kurzeder, C., Grundmann, R., Kreienberg, R., Zeillinger, R., Deissler, H. Oncol. Rep. (2003) [Pubmed]
  23. The tetraspanin protein CD82 associates with both free HLA class I heavy chain and heterodimeric beta 2-microglobulin complexes. Lagaudrière-Gesbert, C., Lebel-Binay, S., Wiertz, E., Ploegh, H.L., Fradelizi, D., Conjeaud, H. J. Immunol. (1997) [Pubmed]
  24. Functional analysis of CD82 in the early phase of T cell activation: roles in cell adhesion and signal transduction. Shibagaki, N., Hanada, K., Yamaguchi, S., Yamashita, H., Shimada, S., Hamada, H. Eur. J. Immunol. (1998) [Pubmed]
  25. Overexpression of CD82 on human T cells enhances LFA-1 / ICAM-1-mediated cell-cell adhesion: functional association between CD82 and LFA-1 in T cell activation. Shibagaki, N., Hanada, K., Yamashita, H., Shimada, S., Hamada, H. Eur. J. Immunol. (1999) [Pubmed]
  26. Nuclear factor-kappaB-dependent expression of metastasis suppressor KAI1/CD82 gene in lung cancer cell lines expressing mutant p53. Shinohara, T., Miki, T., Nishimura, N., Nokihara, H., Hamada, H., Mukaida, N., Sone, S. Cancer Res. (2001) [Pubmed]
  27. Novel staging protocol for non-small-cell lung cancers according to MRP-1/CD9 and KAI1/CD82 gene expression. Adachi, M., Taki, T., Konishi, T., Huang, C.I., Higashiyama, M., Miyake, M. J. Clin. Oncol. (1998) [Pubmed]
  28. Molecular analyses of the association of CD4 with two members of the transmembrane 4 superfamily, CD81 and CD82. Imai, T., Kakizaki, M., Nishimura, M., Yoshie, O. J. Immunol. (1995) [Pubmed]
  29. Mouse homologue of C33 antigen (CD82), a member of the transmembrane 4 superfamily: complementary DNA, genomic structure, and expression. Nagira, M., Imai, T., Ishikawa, I., Uwabe, K.I., Yoshie, O. Cell. Immunol. (1994) [Pubmed]
  30. Regulation of urokinase receptor proteolytic function by the tetraspanin CD82. Bass, R., Werner, F., Odintsova, E., Sugiura, T., Berditchevski, F., Ellis, V. J. Biol. Chem. (2005) [Pubmed]
  31. The tetraspan protein CD82 is a resident of MHC class II compartments where it associates with HLA-DR, -DM, and -DO molecules. Hammond, C., Denzin, L.K., Pan, M., Griffith, J.M., Geuze, H.J., Cresswell, P. J. Immunol. (1998) [Pubmed]
  32. Role of tumor metastasis suppressor gene KAI1 in digestive tract carcinomas and cancer cells. Wu, Q., Ji, Y., Zhang, M.Q., Chen, Y.Q., Chen, F., Shi, D.L., Zheng, Z.H., Huang, Y.J., Su, W.J. Cell Tissue Res. (2003) [Pubmed]
  33. Metastasis-suppressor KAI1/CD82 induces homotypic aggregation of human prostate cancer cells through Src-dependent pathway. Jee, B., Jin, K., Hahn, J.H., Song, H.G., Lee, H. Exp. Mol. Med. (2003) [Pubmed]
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