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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:
103.24 – 103.38 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 CD30,[4] CD27,[5][6] Lymphotoxin beta receptor,[7][8][9] Nucleoporin 62,[10] CD40,[11][12][13][14] TNFSF14,[15] RANK,[16][17] Caspase 3[18][19] and TANK.[20][21]


  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. ^ Ansieau, S; Scheffrahn I, Mosialos G, Brand H, Duyster J, Kaye K, Harada J, Dougall B, Hübinger G, Kieff E, Herrmann F, Leutz A, Gruss H J (November 1996). "Tumor necrosis factor receptor-associated factor (TRAF)-1, TRAF-2, and TRAF-3 interact in vivo with the CD30 cytoplasmic domain; TRAF-2 mediates CD30-induced nuclear factor kappa B activation". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 93 (24): 14053–8. doi:10.1073/pnas.93.24.14053. ISSN 0027-8424. PMC 19493. PMID 8943059.  (Retracted. If this is intentional, please replace {{Retracted}} with {{Retracted|intentional=yes}}.)
  5. ^ 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. (UNITED STATES) 161 (9): 4753–9. ISSN 0022-1767. PMID 9794406. 
  6. ^ Akiba, H; Nakano H, Nishinaka S, Shindo M, Kobata T, Atsuta M, Morimoto C, Ware C F, Malinin N L, 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. (UNITED STATES) 273 (21): 13353–8. doi:10.1074/jbc.273.21.13353. ISSN 0021-9258. PMID 9582383. 
  7. ^ VanArsdale, T L; VanArsdale S L; Force W R; Walter B N; Mosialos G; Kieff E; Reed J C; Ware C F (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. (UNITED STATES) 94 (6): 2460–5. doi:10.1073/pnas.94.6.2460. ISSN 0027-8424. PMC 20110. PMID 9122217. 
  8. ^ Wu, M Y; Wang P Y; Han S H; Hsieh S L (April 1999). "The cytoplasmic domain of the lymphotoxin-beta receptor mediates cell death in HeLa cells". J. Biol. Chem. (UNITED STATES) 274 (17): 11868–73. doi:10.1074/jbc.274.17.11868. ISSN 0021-9258. PMID 10207006. 
  9. ^ Marsters, S A; Ayres T M; Skubatch M; Gray C L; 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. (UNITED STATES) 272 (22): 14029–32. doi:10.1074/jbc.272.22.14029. ISSN 0021-9258. PMID 9162022. 
  10. ^ Gamper, C; van Eyndhoven W G; Schweiger E; Mossbacher M; Koo B; Lederman S (2000). "TRAF-3 interacts with p62 nucleoporin, a component of the nuclear pore central plug that binds classical NLS-containing import complexes". Mol. Immunol. (ENGLAND) 37 (1–2): 73–84. doi:10.1016/S0161-5890(00)00015-8. ISSN 0161-5890. PMID 10781837. 
  11. ^ 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. (UNITED STATES) 96 (4): 1234–9. doi:10.1073/pnas.96.4.1234. ISSN 0027-8424. PMC 15446. PMID 9990007. 
  12. ^ Hu, H M; O'Rourke K; Boguski M S; Dixit V M (December 1994). "A novel RING finger protein interacts with the cytoplasmic domain of CD40". J. Biol. Chem. (UNITED STATES) 269 (48): 30069–72. ISSN 0021-9258. PMID 7527023. 
  13. ^ Ni, C Z; Welsh K; Leo E; Chiou C K; Wu H; Reed J C; Ely K R (September 2000). "Molecular basis for CD40 signaling mediated by TRAF3". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (19): 10395–9. doi:10.1073/pnas.97.19.10395. ISSN 0027-8424. PMC 27035. PMID 10984535. 
  14. ^ Roy, N; Deveraux Q L; Takahashi R; Salvesen G S; Reed J C (December 1997). "The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases". EMBO J. (ENGLAND) 16 (23): 6914–25. doi:10.1093/emboj/16.23.6914. ISSN 0261-4189. PMC 1170295. PMID 9384571. 
  15. ^ Kuai, Jun; Nickbarg Elliott; Wooters Joe; Qiu Yongchang; Wang Jack; Lin Lih-Ling (April 2003). "Endogenous association of TRAF2, TRAF3, cIAP1, and Smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis". J. Biol. Chem. (United States) 278 (16): 14363–9. doi:10.1074/jbc.M208672200. ISSN 0021-9258. PMID 12571250. 
  16. ^ Galibert, L; Tometsko M E; Anderson D M; Cosman D; Dougall W C (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. (UNITED STATES) 273 (51): 34120–7. doi:10.1074/jbc.273.51.34120. ISSN 0021-9258. PMID 9852070. 
  17. ^ 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 (January 1999). "Receptor activator of NF-kappaB recruits multiple TRAF family adaptors and activates c-Jun N-terminal kinase". FEBS Lett. (NETHERLANDS) 443 (3): 297–302. doi:10.1016/S0014-5793(98)01731-1. ISSN 0014-5793. PMID 10025951. 
  18. ^ Lee, Z H; Lee S E; Kwack K; Yeo W; Lee T H; Bae S S; Suh P G; Kim H H (March 2001). "Caspase-mediated cleavage of TRAF3 in FasL-stimulated Jurkat-T cells". J. Leukoc. Biol. (United States) 69 (3): 490–6. ISSN 0741-5400. PMID 11261798. 
  19. ^ Leo, E; Deveraux Q L; Buchholtz C; Welsh K; Matsuzawa S; Stennicke H R; Salvesen G S; Reed J C (March 2001). "TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis". J. Biol. Chem. (United States) 276 (11): 8087–93. doi:10.1074/jbc.M009450200. ISSN 0021-9258. PMID 11098060. 
  20. ^ Bouwmeester, Tewis; Bauch Angela, Ruffner Heinz, Angrand Pierre-Olivier, Bergamini Giovanna, Croughton Karen, Cruciat Cristina, Eberhard Dirk, Gagneur Julien, Ghidelli Sonja, Hopf Carsten, Huhse Bettina, Mangano Raffaella, Michon Anne-Marie, Schirle Markus, Schlegl Judith, Schwab Markus, Stein Martin A, Bauer Andreas, Casari Georg, Drewes Gerard, Gavin Anne-Claude, Jackson David B, Joberty Gerard, Neubauer Gitte, Rick Jens, Kuster Bernhard, Superti-Furga Giulio (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. (England) 6 (2): 97–105. doi:10.1038/ncb1086. ISSN 1465-7392. PMID 14743216. 
  21. ^ Rothe, M; Xiong J; Shu H B; Williamson K; Goddard A; Goeddel D V (August 1996). "I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated signal transduction". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 93 (16): 8241–6. doi:10.1073/pnas.93.16.8241. ISSN 0027-8424. PMC 38654. PMID 8710854. 

Further reading[edit]