Biology:TRAF4

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Generic protein structure example

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. "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. Dec 1995. doi:10.1074/jbc.270.43.25715. PMID 7592751. 
  2. "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. Jan 1996. doi:10.1006/geno.1995.1163. PMID 7490069. 
  3. 3.0 3.1 "Entrez Gene: TRAF4 TNF receptor-associated factor 4". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9618. 
  4. "The TNF-receptor-associated factor family: scaffold molecules for cytokine receptors, kinases and their regulators". Cell. Signal. 13 (6): 389–400. June 2001. doi:10.1016/S0898-6568(01)00160-7. PMID 11384837. 
  5. "TRAF4, the unique family member". Adv. Exp. Med. Biol.. Advances in Experimental Medicine and Biology 597: 60–71. 2007. doi:10.1007/978-0-387-70630-6_5. ISBN 978-0-387-70629-0. PMID 17633017. 
  6. "TRAF family proteins interact with the common neurotrophin receptor and modulate apoptosis induction". J. Biol. Chem. 274 (42): 30202–8. October 1999. doi:10.1074/jbc.274.42.30202. PMID 10514511. 
  7. "TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues". Am. J. Pathol. 152 (6): 1549–61. June 1998. PMID 9626059. 
  8. "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. 2011. doi:10.1074/jbc.M110.189308. PMID 21097508. 

Further reading