TRAF4

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.[4][5][6]

TRAF4
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTRAF4, CART1, MLN62, RNF83, TNF receptor associated factor 4
External IDsOMIM: 602464 MGI: 1202880 HomoloGene: 3173 GeneCards: TRAF4
Gene location (Human)
Chr.Chromosome 17 (human)[1]
Band17q11.2Start28,744,005 bp[1]
End28,750,956 bp[1]
RNA expression pattern


More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

9618

22032

Ensembl

ENSG00000076604

ENSMUSG00000017386

UniProt

Q9BUZ4

Q61382

RefSeq (mRNA)

NM_004295
NM_145751

NM_009423

RefSeq (protein)

NP_004286

NP_033449

Location (UCSC)Chr 17: 28.74 – 28.75 Mbn/a
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

TRAF4 is a member of the TNF receptor associated factor (TRAF) family, a family of scaffold proteins.[7] 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.[8]

Protein interactions

TRAF4 has been shown to interact with neurotrophin receptor, p75 (NTR/NTSR1),[9][10] 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.[6]

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 [11] However, in malignant B cells TRAF4 can facilitate NFkB activation by the CD40 ligand provided by T cells, and in this context serves as an oncogene.[12] In this context TRAF4 levels are regulated by a MYC - miR-29 axis.

References

  1. GRCh38: Ensembl release 89: ENSG00000076604 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. 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.
  5. 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.
  6. "Entrez Gene: TRAF4 TNF receptor-associated factor 4".
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. Sharma S, Pavlasova GM, Seda V, Cerna KA, Vojackova E, Filip D, Ondrisova L, Sandova V, Kostalova L, Zeni PF, Borsky M, Oppelt J, Liskova K, Kren L, Janikova A, Pospisilova S, Fernandes SM, Shehata M, Rassenti LZ, Jaeger U, Doubek M, Davids MS, Brown JR, Mayer J, Kipps TJ, Mraz M (December 2020). "miR-29 Modulates CD40 Signaling in Chronic Lymphocytic Leukemia by Targeting TRAF4: an Axis Affected by BCR inhibitors". Blood. doi:10.1182/blood.2020005627 (inactive 2021-01-20). PMID 33171493.CS1 maint: DOI inactive as of January 2021 (link)

Further reading


This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.