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TNF receptor-associated factor 3
Protein TRAF3 PDB 1flk.png
PDB rendering based on 1flk.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols TRAF3 ; CAP-1; CAP1; CD40bp; CRAF1; IIAE5; LAP1
External IDs OMIM601896 MGI108041 HomoloGene7981 GeneCards: TRAF3 Gene
RNA expression pattern
PBB GE TRAF3 208315 x at tn.png
More reference expression data
Species Human Mouse
Entrez 7187 22031
Ensembl ENSG00000131323 ENSMUSG00000021277
UniProt Q13114 Q60803
RefSeq (mRNA) NM_001199427 NM_001048206
RefSeq (protein) NP_001186356 NP_001273051
Location (UCSC) Chr 14:
102.78 – 102.91 Mb
Chr 12:
111.17 – 111.27 Mb
PubMed search [1] [2]

TNF receptor-associated factor 3 is a protein that in humans is encoded by the TRAF3 gene.[1][2]


The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from, members of the TNF receptor (TNFR) superfamily. This protein participates in the signal transduction of CD40, a TNFR family member important for the activation of the immune response. This protein is found to be a critical component of the lymphotoxin-beta receptor (LTbetaR) signaling complex, which induces NF-kappaB activation and cell death initiated by LTbeta ligation. Epstein-Barr virus encoded latent infection membrane protein-1 (LMP1) can interact with this and several other members of the TRAF family, which may be essential for the oncogenic effects of LMP1. Three alternatively spliced transcript variants encoding two distinct isoforms have been reported.[3]


TRAF3 has been shown to interact with:


  1. ^ Sato T, Irie S, Reed JC (February 1995). "A novel member of the TRAF family of putative signal transducing proteins binds to the cytosolic domain of CD40". FEBS Lett 358 (2): 113–8. doi:10.1016/0014-5793(94)01406-Q. PMID 7530216. 
  2. ^ Mosialos G, Birkenbach M, Yalamanchili R, VanArsdale T, Ware C, Kieff E (March 1995). "The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family". Cell 80 (3): 389–99. doi:10.1016/0092-8674(95)90489-1. PMID 7859281. 
  3. ^ "Entrez Gene: TRAF3 TNF receptor-associated factor 3". 
  4. ^ Yamamoto H, Kishimoto T, Minamoto S (November 1998). "NF-kappaB activation in CD27 signaling: involvement of TNF receptor-associated factors in its signaling and identification of functional region of CD27". J. Immunol. 161 (9): 4753–9. PMID 9794406. 
  5. ^ Akiba H, Nakano H, Nishinaka S, Shindo M, Kobata T, Atsuta M, Morimoto C, Ware CF, Malinin NL, Wallach D, Yagita H, Okumura K (May 1998). "CD27, a member of the tumor necrosis factor receptor superfamily, activates NF-kappaB and stress-activated protein kinase/c-Jun N-terminal kinase via TRAF2, TRAF5, and NF-kappaB-inducing kinase". J. Biol. Chem. 273 (21): 13353–8. doi:10.1074/jbc.273.21.13353. PMID 9582383. 
  6. ^ Tsukamoto N, Kobayashi N, Azuma S, Yamamoto T, Inoue J (February 1999). "Two differently regulated nuclear factor kappaB activation pathways triggered by the cytoplasmic tail of CD40". Proc. Natl. Acad. Sci. U.S.A. 96 (4): 1234–9. doi:10.1073/pnas.96.4.1234. PMC 15446. PMID 9990007. 
  7. ^ Hu HM, O'Rourke K, Boguski MS, Dixit VM (December 1994). "A novel RING finger protein interacts with the cytoplasmic domain of CD40". J. Biol. Chem. 269 (48): 30069–72. PMID 7527023. 
  8. ^ Ni CZ, Welsh K, Leo E, Chiou CK, Wu H, Reed JC, Ely KR (September 2000). "Molecular basis for CD40 signaling mediated by TRAF3". Proc. Natl. Acad. Sci. U.S.A. 97 (19): 10395–9. doi:10.1073/pnas.97.19.10395. PMC 27035. PMID 10984535. 
  9. ^ Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC (December 1997). "The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases". EMBO J. 16 (23): 6914–25. doi:10.1093/emboj/16.23.6914. PMC 1170295. PMID 9384571. 
  10. ^ Lee ZH, Lee SE, Kwack K, Yeo W, Lee TH, Bae SS, Suh PG, Kim HH (March 2001). "Caspase-mediated cleavage of TRAF3 in FasL-stimulated Jurkat-T cells". J. Leukoc. Biol. 69 (3): 490–6. PMID 11261798. 
  11. ^ Leo E, Deveraux QL, Buchholtz C, Welsh K, Matsuzawa S, Stennicke HR, Salvesen GS, Reed JC (March 2001). "TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis". J. Biol. Chem. 276 (11): 8087–93. doi:10.1074/jbc.M009450200. PMID 11098060. 
  12. ^ VanArsdale TL, VanArsdale SL, Force WR, Walter BN, Mosialos G, Kieff E, Reed JC, Ware CF (March 1997). "Lymphotoxin-beta receptor signaling complex: role of tumor necrosis factor receptor-associated factor 3 recruitment in cell death and activation of nuclear factor kappaB". Proc. Natl. Acad. Sci. U.S.A. 94 (6): 2460–5. doi:10.1073/pnas.94.6.2460. PMC 20110. PMID 9122217. 
  13. ^ Wu MY, Wang PY, Han SH, Hsieh SL (April 1999). "The cytoplasmic domain of the lymphotoxin-beta receptor mediates cell death in HeLa cells". J. Biol. Chem. 274 (17): 11868–73. doi:10.1074/jbc.274.17.11868. PMID 10207006. 
  14. ^ Marsters SA, Ayres TM, Skubatch M, Gray CL, Rothe M, Ashkenazi A (May 1997). "Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-kappaB and AP-1". J. Biol. Chem. 272 (22): 14029–32. doi:10.1074/jbc.272.22.14029. PMID 9162022. 
  15. ^ Gamper C, van Eyndhoven WG, Schweiger E, Mossbacher M, Koo B, Lederman S. "TRAF-3 interacts with p62 nucleoporin, a component of the nuclear pore central plug that binds classical NLS-containing import complexes". Mol. Immunol. 37 (1-2): 73–84. doi:10.1016/s0161-5890(00)00015-8. PMID 10781837. 
  16. ^ Galibert L, Tometsko ME, Anderson DM, Cosman D, Dougall WC (December 1998). "The involvement of multiple tumor necrosis factor receptor (TNFR)-associated factors in the signaling mechanisms of receptor activator of NF-kappaB, a member of the TNFR superfamily". J. Biol. Chem. 273 (51): 34120–7. doi:10.1074/jbc.273.51.34120. PMID 9852070. 
  17. ^ Kim HH, Lee DE, Shin JN, Lee YS, Jeon YM, Chung CH, Ni J, Kwon BS, Lee ZH (January 1999). "Receptor activator of NF-kappaB recruits multiple TRAF family adaptors and activates c-Jun N-terminal kinase". FEBS Lett. 443 (3): 297–302. doi:10.1016/s0014-5793(98)01731-1. PMID 10025951. 
  18. ^ Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216. 
  19. ^ Rothe M, Xiong J, Shu HB, Williamson K, Goddard A, Goeddel DV (August 1996). "I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated signal transduction". Proc. Natl. Acad. Sci. U.S.A. 93 (16): 8241–6. doi:10.1073/pnas.93.16.8241. PMC 38654. PMID 8710854. 
  20. ^ Kuai J, Nickbarg E, Wooters J, Qiu Y, Wang J, Lin LL (April 2003). "Endogenous association of TRAF2, TRAF3, cIAP1, and Smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis". J. Biol. Chem. 278 (16): 14363–9. doi:10.1074/jbc.M208672200. PMID 12571250. 

Further reading[edit]