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TNF receptor-associated factor 4
Protein TRAF4 PDB 2EOD.png
Rendering based on PDB 2EOD.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols TRAF4 ; CART1; MLN62; RNF83
External IDs OMIM602464 MGI1202880 HomoloGene3173 GeneCards: TRAF4 Gene
RNA expression pattern
PBB GE TRAF4 202871 at tn.png
PBB GE TRAF4 211899 s at tn.png
More reference expression data
Species Human Mouse
Entrez 9618 22032
Ensembl ENSG00000076604 ENSMUSG00000017386
UniProt Q9BUZ4 Q61382
RefSeq (mRNA) NM_004295 NM_009423
RefSeq (protein) NP_004286 NP_033449
Location (UCSC) Chr 17:
28.74 – 28.75 Mb
Chr 11:
78.16 – 78.17 Mb
PubMed search [1] [2]

TNF receptor-associated factor 4 (TRAF4) also known as RING finger protein 83 (RNF83) is a protein that in humans is encoded by the TRAF4 gene.[1][2][3]

TRAF4 is a member of the TNF receptor associated factor (TRAF) family, a family of scaffold proteins.[4] TRAF proteins connect IL-1R/Toll and TNF receptors with signaling factors that lead to the activation of NF-κB and mitogen-activated protein kinases. However, TRAF4 is not known to interact with TNF receptors and its cellular functions are not well understood.[5]

Protein interactions[edit]

TRAF4 has been shown to interact with neurotrophin receptor, p75 (NTR/NTSR1),[6][7] and negatively regulate NTR induced cell death and NF-kappa B activation. This protein has been found to bind to p47phox, a cytosolic regulatory factor included in a multi-protein complex known as NAD(P)H oxidase. This protein thus, is thought to be involved in the oxidative activation of MAPK8/JNK. Alternatively spliced transcript variants have been observed but the full-length nature of only one has been determined.[3]

A recent report indicates that TRAF4 binds to NOD-Like Receptors NOD1 and NOD2, and specifically inhibits activation of NF-κB by the activated NOD2-RIP2 complex [8]


  1. ^ Regnier CH, Tomasetto C, Moog-Lutz C, Chenard MP, Wendling C, Basset P, Rio MC (Dec 1995). "Presence of a new conserved domain in CART1, a novel member of the tumor necrosis factor receptor-associated protein family, which is expressed in breast carcinoma". J Biol Chem 270 (43): 25715–21. doi:10.1074/jbc.270.43.25715. PMID 7592751. 
  2. ^ Tomasetto C, Regnier C, Moog-Lutz C, Mattei MG, Chenard MP, Lidereau R, Basset P, Rio MC (Jan 1996). "Identification of four novel human genes amplified and overexpressed in breast carcinoma and localized to the q11-q21.3 region of chromosome 17". Genomics 28 (3): 367–76. doi:10.1006/geno.1995.1163. PMID 7490069. 
  3. ^ a b "Entrez Gene: TRAF4 TNF receptor-associated factor 4". 
  4. ^ Wajant H, Henkler F, Scheurich P (June 2001). "The TNF-receptor-associated factor family: scaffold molecules for cytokine receptors, kinases and their regulators". Cell. Signal. 13 (6): 389–400. doi:10.1016/S0898-6568(01)00160-7. PMID 11384837. 
  5. ^ Kedinger V, Rio MC (2007). "TRAF4, the unique family member". Adv. Exp. Med. Biol. Advances in Experimental Medicine and Biology 597: 60–71. doi:10.1007/978-0-387-70630-6_5. ISBN 978-0-387-70629-0. PMID 17633017. 
  6. ^ Ye X, Mehlen P, Rabizadeh S, VanArsdale T, Zhang H, Shin H, Wang JJ, Leo E, Zapata J, Hauser CA, Reed JC, Bredesen DE (October 1999). "TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction". J. Biol. Chem. 274 (42): 30202–8. doi:10.1074/jbc.274.42.30202. PMID 10514511. 
  7. ^ Krajewska M, Krajewski S, Zapata JM, Van Arsdale T, Gascoyne RD, Berern K, McFadden D, Shabaik A, Hugh J, Reynolds A, Clevenger CV, Reed JC (June 1998). "TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues". Am. J. Pathol. 152 (6): 1549–61. PMC 1858434. PMID 9626059. 
  8. ^ Marinis JM, Homer CR, McDonald C, Abbott DW (2011). "A Novel Motif in the Crohn's Disease Susceptibility Protein, NOD2, Allows TRAF4 to Down-regulate Innate Immune Responses". J. Biol. Chem. 286 (3): 1938–1950. doi:10.1074/jbc.M110.189308. PMC 3023490. PMID 21097508. 

Further reading[edit]