TRAF4

TNF receptor-associated factor 4
Rendering based on PDB 2EOD​.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2EOD​, 2YUC​, 3ZJB​, 4K8U​, 4M4E​
Identifiers
Symbols	TRAF4 ; CART1; MLN62; RNF83
External IDs	OMIM: 602464 MGI: 1202880 HomoloGene: 3173 GeneCards: TRAF4 Gene
Gene ontology Molecular function • DNA binding • ubiquitin-protein transferase activity • tumor necrosis factor receptor binding • protein binding • zinc ion binding • protein kinase binding • ubiquitin protein ligase binding • thioesterase binding • WW domain binding Cellular component • nucleus • cytoplasm • cytoskeleton • plasma membrane • bicellular tight junction • perinuclear region of cytoplasm Biological process • apoptotic process • signal transduction • activation of NF-kappaB-inducing kinase activity • respiratory gaseous exchange • protein ubiquitination • respiratory tube development • regulation of apoptotic process • positive regulation of protein kinase activity • positive regulation of JNK cascade • positive regulation of protein homodimerization activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
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

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

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]

References

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. "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

• Bradley JR, Pober JS (2001). "Tumor necrosis factor receptor-associated factors (TRAFs)". Oncogene 20 (44): 6482–91. doi:10.1038/sj.onc.1204788. PMID 11607847.
• Masson R, Régnier CH, Chenard MP, et al. (1998). "Tumor necrosis factor receptor associated factor 4 (TRAF4) expression pattern during mouse development". Mech. Dev. 71 (1–2): 187–91. doi:10.1016/S0925-4773(97)00192-5. PMID 9507120.
• Zapata JM, Pawlowski K, Haas E, et al. (2001). "A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains". J. Biol. Chem. 276 (26): 24242–52. doi:10.1074/jbc.M100354200. PMID 11279055.
• Régnier CH, Masson R, Kedinger V, et al. (2002). "Impaired neural tube closure, axial skeleton malformations, and tracheal ring disruption in TRAF4-deficient mice". Proc. Natl. Acad. Sci. U.S.A. 99 (8): 5585–90. doi:10.1073/pnas.052124799. PMC 122813. PMID 11943846.
• Xu YC, Wu RF, Gu Y, et al. (2002). "Involvement of TRAF4 in oxidative activation of c-Jun N-terminal kinase". J. Biol. Chem. 277 (31): 28051–7. doi:10.1074/jbc.M202665200. PMID 12023963.
• Glauner H, Siegmund D, Motejadded H, et al. (2002). "Intracellular localization and transcriptional regulation of tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4)". Eur. J. Biochem. 269 (19): 4819–29. doi:10.1046/j.1432-1033.2002.03180.x. PMID 12354113.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Sax JK, El-Deiry WS (2003). "Identification and characterization of the cytoplasmic protein TRAF4 as a p53-regulated proapoptotic gene". J. Biol. Chem. 278 (38): 36435–44. doi:10.1074/jbc.M303191200. PMID 12788948.
• Fleckenstein DS, Dirks WG, Drexler HG, Quentmeier H (2003). "Tumor necrosis factor receptor-associated factor (TRAF) 4 is a new binding partner for the p70S6 serine/threonine kinase". Leuk. Res. 27 (8): 687–94. doi:10.1016/S0145-2126(02)00325-9. PMID 12801526.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Ma BY, Mikolajczak SA, Danesh A, et al. (2005). "The expression and the regulatory role of OX40 and 4-1BB heterodimer in activated human T cells". Blood 106 (6): 2002–10. doi:10.1182/blood-2004-04-1622. PMID 15941918.
• Takeshita F, Ishii KJ, Kobiyama K, et al. (2005). "TRAF4 acts as a silencer in TLR-mediated signaling through the association with TRAF6 and TRIF". Eur. J. Immunol. 35 (8): 2477–85. doi:10.1002/eji.200526151. PMID 16052631.
• Abell AN, Johnson GL (2006). "MEKK4 is an effector of the embryonic TRAF4 for JNK activation". J. Biol. Chem. 280 (43): 35793–6. doi:10.1074/jbc.C500260200. PMID 16157600.