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Gene Review

TRAF5  -  TNF receptor-associated factor 5

Homo sapiens

Synonyms: MGC:39780, RING finger protein 84, RNF84
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Disease relevance of TRAF5


High impact information on TRAF5

  • Our data suggest that this distinction is due to an inability of the TRAF domain of TRAF5 to bind the TIM of Cardif [3].
  • Moreover, in vitro Ig production of traf5(-/-) B cells stimulated with anti-CD40 plus IL-4 was reduced substantially [4].
  • CD27-mediated costimulatory signal also was impaired in traf5(-/-) T cells [4].
  • Targeted disruption of Traf5 gene causes defects in CD40- and CD27-mediated lymphocyte activation [4].
  • In vitro binding assays revealed that TRAF5 associates with the cytoplasmic tail of CD40, but not with the cytoplasmic tail of tumor receptor factor receptor type 2, which associates with TRAF2 [5].

Biological context of TRAF5

  • Furthermore, transfection experiments with RANK and its deletion mutants in human embryonic 293 cells revealed that the TRAF6-binding region (340-358), but not the TRAF2 or TRAF5-binding region, is necessary and sufficient for RANK-induced NF-kappaB activation [6].
  • The TRAF5 gene was mapped to the human chromosome 1q32.3-q41 [7].
  • Human TNF receptor-associated factor 5 (TRAF5): cDNA cloning, expression and assignment of the TRAF5 gene to chromosome 1q32 [8].
  • A cDNA encoding the human homolog of the tumor necrosis factor receptor-associated factor 5 (TRAF5) protein has been molecularly cloned from a cDNA library of Human Daudi B cell line [7].
  • TRAF5 was determined to bind to the C-terminal 11 amino acids and the other TRAF members to a region N-terminal to the TRAF5 binding site [9].

Anatomical context of TRAF5

  • Although KMH2 showed weak expression, the remaining HD cell lines also lacked TRAF5 protein [10].
  • Expression of TRAF2 and TRAF5 mRNA was demonstrated in T- and B-cell lines that express CD30 [11].
  • In sum, our studies indicate that TRAF5 plays a crucial role in GITR-induced signaling pathways that augment T cell activation [12].
  • Expression analysis showed that, among the tissues examined, TRAF5 was strongly expressed in spleen and bursa of Fabricius, while among the cell lines examined, it was maximally expressed in IN24 [13].

Associations of TRAF5 with chemical compounds

  • Full-length TRAF3 and TRAF5 formed hetero-oligomers, presumably through their predicted isoleucine zippers [14].
  • Cisplatin upregulated the expression of both death and decoy TRAIL receptors, as well as of TRAF5 and -6, downregulated the anti-apoptotic proteins, Bcl-2, and induced activation of caspases-3, -8 and -9 [15].

Regulatory relationships of TRAF5

  • Dominant-negative TRAF2 and TRAF5 suppressed cytoplasmic aggregation along with constitutive NF-kappa B activation in H-RS cell lines [16].
  • Cross-linking of LTbetaR is able to recruit TRAF3 and TRAF5 to activate ASK1, whereas its activity is inhibited by free radical scavenger carboxyfullerenes [17].

Other interactions of TRAF5

  • TRAF5, a novel tumor necrosis factor receptor-associated factor family protein, mediates CD40 signaling [5].
  • TRAF6 also complexed to the C-region in addition to several regions N-terminal to the TRAF2 and TRAF5 association sites [18].
  • Analysis of TRANCE-R deletion mutants suggested that the TRAF2 and TRAF5 interaction sites were restricted to the C-terminal 93 amino acids (C-region) [18].
  • The association of CD30v with signal-transducing proteins, tumor necrosis factor receptor-associated factor (TRAF) 2, and TRAF5 was demonstrated by coimmunoprecipitation analysis, as was demonstrated for authentic CD30 protein [19].
  • ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5 [20].

Analytical, diagnostic and therapeutic context of TRAF5


  1. Activation of TRAF5 and TRAF6 signal cascades negatively regulates the latent replication origin of Epstein-Barr virus through p38 mitogen-activated protein kinase. Shirakata, M., Imadome, K.I., Okazaki, K., Hirai, K. J. Virol. (2001) [Pubmed]
  2. Ethanol potentiates HIV-1 gp120-induced apoptosis in human neurons via both the death receptor and NMDA receptor pathways. Chen, W., Tang, Z., Fortina, P., Patel, P., Addya, S., Surrey, S., Acheampong, E.A., Mukhtar, M., Pomerantz, R.J. Virology (2005) [Pubmed]
  3. Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif. Saha, S.K., Pietras, E.M., He, J.Q., Kang, J.R., Liu, S.Y., Oganesyan, G., Shahangian, A., Zarnegar, B., Shiba, T.L., Wang, Y., Cheng, G. EMBO J. (2006) [Pubmed]
  4. Targeted disruption of Traf5 gene causes defects in CD40- and CD27-mediated lymphocyte activation. Nakano, H., Sakon, S., Koseki, H., Takemori, T., Tada, K., Matsumoto, M., Munechika, E., Sakai, T., Shirasawa, T., Akiba, H., Kobata, T., Santee, S.M., Ware, C.F., Rennert, P.D., Taniguchi, M., Yagita, H., Okumura, K. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  5. TRAF5, a novel tumor necrosis factor receptor-associated factor family protein, mediates CD40 signaling. Ishida, T.K., Tojo, T., Aoki, T., Kobayashi, N., Ohishi, T., Watanabe, T., Yamamoto, T., Inoue, J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  6. Activation of NF-kappaB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-kappaB-inducing kinase. Identification of a novel TRAF6 interaction motif. Darnay, B.G., Ni, J., Moore, P.A., Aggarwal, B.B. J. Biol. Chem. (1999) [Pubmed]
  7. Cloning and characterization of a cDNA encoding the human homolog of tumor necrosis factor receptor-associated factor 5 (TRAF5). Mizushima, S., Fujita, M., Ishida, T., Azuma, S., Kato, K., Hirai, M., Otsuka, M., Yamamoto, T., Inoue, J. Gene (1998) [Pubmed]
  8. Human TNF receptor-associated factor 5 (TRAF5): cDNA cloning, expression and assignment of the TRAF5 gene to chromosome 1q32. Nakano, H., Shindo, M., Yamada, K., Yoshida, M.C., Santee, S.M., Ware, C.F., Jenkins, N.A., Gilbert, D.J., Yagita, H., Copeland, N.C., Okumura, K. Genomics (1997) [Pubmed]
  9. Receptor activator of NF-kappaB recruits multiple TRAF family adaptors and activates c-Jun N-terminal kinase. Kim, H.H., Lee, D.E., Shin, J.N., Lee, Y.S., Jeon, Y.M., Chung, C.H., Ni, J., Kwon, B.S., Lee, Z.H. FEBS Lett. (1999) [Pubmed]
  10. Expression of the tumor necrosis factor receptor-associated factors (TRAFs) 1 and 2 is a characteristic feature of Hodgkin and Reed-Sternberg cells. Izban, K.F., Ergin, M., Martinez, R.L., Alkan, S. Mod. Pathol. (2000) [Pubmed]
  11. Tumor necrosis factor receptor-associated factor (TRAF) 5 and TRAF2 are involved in CD30-mediated NFkappaB activation. Aizawa, S., Nakano, H., Ishida, T., Horie, R., Nagai, M., Ito, K., Yagita, H., Okumura, K., Inoue, J., Watanabe, T. J. Biol. Chem. (1997) [Pubmed]
  12. Tumor necrosis factor receptor (TNFR)-associated factor 5 is a critical intermediate of costimulatory signaling pathways triggered by glucocorticoid-induced TNFR in T cells. Esparza, E.M., Lindsten, T., Stockhausen, J.M., Arch, R.H. J. Biol. Chem. (2006) [Pubmed]
  13. Molecular study on chicken tumor necrosis factor receptor-II and tumor necrosis factor receptor-associated factor-5. Abdalla, S.A., Horiuchi, H., Furusawa, S., Matsuda, H. Vet. Immunol. Immunopathol. (2004) [Pubmed]
  14. CD40-tumor necrosis factor receptor-associated factor (TRAF) interactions: regulation of CD40 signaling through multiple TRAF binding sites and TRAF hetero-oligomerization. Pullen, S.S., Miller, H.G., Everdeen, D.S., Dang, T.T., Crute, J.J., Kehry, M.R. Biochemistry (1998) [Pubmed]
  15. Physiological and molecular effects of Apo2L/TRAIL and cisplatin in ovarian carcinoma cell lines. Siervo-Sassi, R.R., Marrangoni, A.M., Feng, X., Naoumova, N., Winans, M., Edwards, R.P., Lokshin, A. Cancer Lett. (2003) [Pubmed]
  16. Cytoplasmic aggregation of TRAF2 and TRAF5 proteins in the Hodgkin-Reed-Sternberg cells. Horie, R., Watanabe, T., Ito, K., Morisita, Y., Watanabe, M., Ishida, T., Higashihara, M., Kadin, M., Watanabe, T. Am. J. Pathol. (2002) [Pubmed]
  17. The role of apoptosis signal-regulating kinase 1 in lymphotoxin-beta receptor-mediated cell death. Chen, M.C., Hwang, M.J., Chou, Y.C., Chen, W.H., Cheng, G., Nakano, H., Luh, T.Y., Mai, S.C., Hsieh, S.L. J. Biol. Chem. (2003) [Pubmed]
  18. The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE receptor. Wong, B.R., Josien, R., Lee, S.Y., Vologodskaia, M., Steinman, R.M., Choi, Y. J. Biol. Chem. (1998) [Pubmed]
  19. Frequent expression of the variant CD30 in human malignant myeloid and lymphoid neoplasms. Horie, R., Gattei, V., Ito, K., Imajo-Ohmi, S., Tange, T., Miyauchi, J., Pinto, A., Degan, M., De Iuliis, A., Tassan Mazzocco, F., Rossi, F.M., Higashihara, M., Watanabe, T. Am. J. Pathol. (1999) [Pubmed]
  20. ATAR, a novel tumor necrosis factor receptor family member, signals through TRAF2 and TRAF5. Hsu, H., Solovyev, I., Colombero, A., Elliott, R., Kelley, M., Boyle, W.J. J. Biol. Chem. (1997) [Pubmed]
  21. CD40-mediated signaling in monocytic cells: up-regulation of tumor necrosis factor receptor-associated factor mRNAs and activation of mitogen-activated protein kinase signaling pathways. Pearson, L.L., Castle, B.E., Kehry, M.R. Int. Immunol. (2001) [Pubmed]
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