TRAF6

TRAF6
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTRAF6, MGC:3310, RNF85, TNF receptor associated factor 6
External IDsOMIM: 602355; MGI: 108072; HomoloGene: 3395; GeneCards: TRAF6; OMA:TRAF6 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

7189

22034

Ensembl

ENSG00000175104

ENSMUSG00000027164

UniProt

Q9Y4K3

P70196

RefSeq (mRNA)

NM_145803
NM_004620

NM_009424
NM_001303273

RefSeq (protein)

NP_004611
NP_665802

NP_001290202
NP_033450

Location (UCSC)Chr 11: 36.48 – 36.51 MbChr 2: 101.51 – 101.53 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

TRAF6 is a TRAF human protein.

Function

The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins are associated with, and mediate signal transduction from members of the TNF receptor superfamily. This protein mediates the signaling not only from the members of the TNF receptor superfamily, but also from the members of the Toll/IL-1 family. Signals from receptors such as CD40, TNFSF11/TRANCE/RANKL and IL-1 have been shown to be mediated by this protein. This protein also interacts with various protein kinases including IRAK1/IRAK, SRC and PKCzeta, which provides a link between distinct signaling pathways. This protein functions as a signal transducer in the NF-kappaB pathway that activates IkappaB kinase (IKK) in response to proinflammatory cytokines. The interaction of this protein with UBE2N/UBC13, and UBE2V1/UEV1A, which are ubiquitin conjugating enzymes catalyzing the formation of polyubiquitin chains, has been found to be required for IKK activation by this protein. Two alternatively spliced transcript variants encoding identical proteins have been reported.[5]

Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations

Interactions

TRAF6 has been shown to interact with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000175104 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027164 – Ensembl, May 2017
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  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: TRAF6 TNF receptor-associated factor 6".
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  19. ^ Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel DV (October 1996). "TRAF6 is a signal transducer for interleukin-1". Nature. 383 (6599): 443–6. Bibcode:1996Natur.383..443C. doi:10.1038/383443a0. PMID 8837778. S2CID 4269027.
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  22. ^ a b Ling L, Goeddel DV (August 2000). "T6BP, a TRAF6-interacting protein involved in IL-1 signaling". Proc. Natl. Acad. Sci. U.S.A. 97 (17): 9567–72. Bibcode:2000PNAS...97.9567L. doi:10.1073/pnas.170279097. PMC 16905. PMID 10920205.
  23. ^ a b c Takaesu G, Ninomiya-Tsuji J, Kishida S, Li X, Stark GR, Matsumoto K (April 2001). "Interleukin-1 (IL-1) receptor-associated kinase leads to activation of TAK1 by inducing TAB2 translocation in the IL-1 signaling pathway". Mol. Cell. Biol. 21 (7): 2475–84. doi:10.1128/MCB.21.7.2475-2484.2001. PMC 86880. PMID 11259596.
  24. ^ a b c Takaesu G, Kishida S, Hiyama A, Yamaguchi K, Shibuya H, Irie K, Ninomiya-Tsuji J, Matsumoto K (April 2000). "TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway". Mol. Cell. 5 (4): 649–58. doi:10.1016/s1097-2765(00)80244-0. PMID 10882101.
  25. ^ a b c Walsh MC, Kim GK, Maurizio PL, Molnar EE, Choi Y (2008). Unutmaz D (ed.). "TRAF6 autoubiquitination-independent activation of the NFkappaB and MAPK pathways in response to IL-1 and RANKL". PLOS ONE. 3 (12): e4064. Bibcode:2008PLoSO...3.4064W. doi:10.1371/journal.pone.0004064. PMC 2603309. PMID 19112497.
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  28. ^ a b Ma Q, Zhou L, Shi H, Huo K (June 2008). "NUMBL interacts with TAB2 and inhibits TNFalpha and IL-1beta-induced NF-kappaB activation". Cell. Signal. 20 (6): 1044–51. doi:10.1016/j.cellsig.2008.01.015. PMID 18299187.
  29. ^ Sorrentino A, Thakur N, Grimsby S, Marcusson A, von Bulow V, Schuster N, Zhang S, Heldin CH, Landström M (October 2008). "The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner". Nat. Cell Biol. 10 (10): 1199–207. doi:10.1038/ncb1780. PMID 18758450. S2CID 22984417.
  30. ^ a b Chen L, Dong W, Zou T, Ouyang L, He G, Liu Y, Qi Y (August 2008). "Protein phosphatase 4 negatively regulates LPS cascade by inhibiting ubiquitination of TRAF6". FEBS Lett. 582 (19): 2843–9. Bibcode:2008FEBSL.582.2843C. doi:10.1016/j.febslet.2008.07.014. PMID 18634786. S2CID 27700566.
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  33. ^ Darnay BG, Ni J, Moore PA, Aggarwal BB (March 1999). "Activation of NF-kappaB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-kappaB-inducing kinase. Identification of a novel TRAF6 interaction motif". J. Biol. Chem. 274 (12): 7724–31. doi:10.1074/jbc.274.12.7724. PMID 10075662.
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