TNF receptor-associated factor 6

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityⁱ

• S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. EC:2.3.2.27

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• histone deacetylase binding Source: UniProtKB <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • Ref.46

    "Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification."
    Pham L.V., Zhou H.J., Lin-Lee Y.C., Tamayo A.T., Yoshimura L.C., Fu L., Darnay B.G., Ford R.J.
    J. Biol. Chem. 283:5081-5089(2008) [PubMed] [Europe PMC] [Abstract]

    Cited for: SUBCELLULAR LOCATION, FUNCTION, SUMOYLATION AT LYS-124; LYS-142 AND LYS-453, UBIQUITINATION, INTERACTION WITH HDAC1 AND RANGAP1, MUTAGENESIS OF LYS-124; LYS-142 AND LYS-453.
• identical protein binding Source: IntActInferred from physical interactionⁱ
  • Ref.62

    "E2 interaction and dimerization in the crystal structure of TRAF6."
    Yin Q., Lin S.C., Lamothe B., Lu M., Lo Y.C., Hura G., Zheng L., Rich R.L., Campos A.D., Myszka D.G., Lenardo M.J., Darnay B.G., Wu H.
    Nat. Struct. Mol. Biol. 16:658-666(2009) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 50-211 IN COMPLEXES WITH ZINC IONS AND UBE2N, SUBUNIT, FUNCTION, AUTOUBIQUITINATION, MUTAGENESIS OF ASP-57; CYS-70; ILE-72; LEU-74; ARG-88; PHE-118; PHE-122 AND LYS-124, ZINC-FINGER.
  • "Toward an understanding of the protein interaction network of the human liver."
    Wang J., Huo K., Ma L., Tang L., Li D., Huang X., Yuan Y., Li C., Wang W., Guan W., Chen H., Jin C., Wei J., Zhang W., Yang Y., Liu Q., Zhou Y., Zhang C.

    , Wu Z., Xu W., Zhang Y., Liu T., Yu D., Zhang Y., Chen L., Zhu D., Zhong X., Kang L., Gan X., Yu X., Ma Q., Yan J., Zhou L., Liu Z., Zhu Y., Zhou T., He F., Yang X.
    Mol. Syst. Biol. 7:536-536(2011) [PubMed] [Europe PMC] [Abstract]
  • "Systematic analysis of dimeric E3-RING interactions reveals increased combinatorial complexity in human ubiquitination networks."
    Woodsmith J., Jenn R.C., Sanderson C.M.
    Mol. Cell Proteomics 11:M111.016162-M111.016162(2012) [PubMed] [Europe PMC] [Abstract]
  • "A proteome-scale map of the human interactome network."
    Rolland T., Tasan M., Charloteaux B., Pevzner S.J., Zhong Q., Sahni N., Yi S., Lemmens I., Fontanillo C., Mosca R., Kamburov A., Ghiassian S.D., Yang X., Ghamsari L., Balcha D., Begg B.E., Braun P., Brehme M.

    , Broly M.P., Carvunis A.R., Convery-Zupan D., Corominas R., Coulombe-Huntington J., Dann E., Dreze M., Dricot A., Fan C., Franzosa E., Gebreab F., Gutierrez B.J., Hardy M.F., Jin M., Kang S., Kiros R., Lin G.N., Luck K., MacWilliams A., Menche J., Murray R.R., Palagi A., Poulin M.M., Rambout X., Rasla J., Reichert P., Romero V., Ruyssinck E., Sahalie J.M., Scholz A., Shah A.A., Sharma A., Shen Y., Spirohn K., Tam S., Tejeda A.O., Trigg S.A., Twizere J.C., Vega K., Walsh J., Cusick M.E., Xia Y., Barabasi A.L., Iakoucheva L.M., Aloy P., De Las Rivas J., Tavernier J., Calderwood M.A., Hill D.E., Hao T., Roth F.P., Vidal M.
    Cell 159:1212-1226(2014) [PubMed] [Europe PMC] [Abstract]
  • "Pooled-matrix protein interaction screens using Barcode Fusion Genetics."
    Yachie N., Petsalaki E., Mellor J.C., Weile J., Jacob Y., Verby M., Ozturk S.B., Li S., Cote A.G., Mosca R., Knapp J.J., Ko M., Yu A., Gebbia M., Sahni N., Yi S., Tyagi T., Sheykhkarimli D.

    , Roth J.F., Wong C., Musa L., Snider J., Liu Y.C., Yu H., Braun P., Stagljar I., Hao T., Calderwood M.A., Pelletier L., Aloy P., Hill D.E., Vidal M., Roth F.P.
    Mol. Syst. Biol. 12:863-863(2016) [PubMed] [Europe PMC] [Abstract]
• mitogen-activated protein kinase kinase kinase binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.18

    "The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway."
    Ninomiya-Tsuji J., Kishimoto K., Hiyama A., Inoue J., Cao Z., Matsumoto K.
    Nature 398:252-256(1999) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH MAP3K7 AND TAB1.
• protein kinase B binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.51

    "The E3 ligase TRAF6 regulates Akt ubiquitination and activation."
    Yang W.-L., Wang J., Chan C.-H., Lee S.-W., Campos A.D., Lamothe B., Hur L., Grabiner B.C., Lin X., Darnay B.G., Lin H.-K.
    Science 325:1134-1138(2009) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• protein kinase binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.51

    "The E3 ligase TRAF6 regulates Akt ubiquitination and activation."
    Yang W.-L., Wang J., Chan C.-H., Lee S.-W., Campos A.D., Lamothe B., Hur L., Grabiner B.C., Lin X., Darnay B.G., Lin H.-K.
    Science 325:1134-1138(2009) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• protein N-terminus binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.32

    "Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling."
    Sato S., Sugiyama M., Yamamoto M., Watanabe Y., Kawai T., Takeda K., Akira S.
    J. Immunol. 171:4304-4310(2003) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH TICAM1.
• thioesterase binding Source: UniProtKBInferred from physical interactionⁱ
  • "A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains."
    Zapata J.M., Pawlowski K., Haas E., Ware C.F., Godzik A., Reed J.C.
    J. Biol. Chem. 276:24242-24252(2001) [PubMed] [Europe PMC] [Abstract]
• tumor necrosis factor receptor binding Source: UniProtKBInferred from physical interactionⁱ
  • "A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis."
    Wiley S.R., Cassiano L., Lofton T., Davis-Smith T., Winkles J.A., Lindner V., Liu H., Daniel T.O., Smith C.A., Fanslow W.C.
    Immunity 15:837-846(2001) [PubMed] [Europe PMC] [Abstract]
• ubiquitin conjugating enzyme binding Source: MGI <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • Ref.55

    "SASH1 is a scaffold molecule in endothelial TLR4 signaling."
    Dauphinee S.M., Clayton A., Hussainkhel A., Yang C., Park Y.J., Fuller M.E., Blonder J., Veenstra T.D., Karsan A.
    J. Immunol. 191:892-901(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH SASH1.
• ubiquitin protein ligase activity Source: Ensembl
• ubiquitin protein ligase binding Source: UniProtKBInferred from physical interactionⁱ
  • "A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains."
    Zapata J.M., Pawlowski K., Haas E., Ware C.F., Godzik A., Reed J.C.
    J. Biol. Chem. 276:24242-24252(2001) [PubMed] [Europe PMC] [Abstract]
• ubiquitin-protein transferase activity Source: UniProtKBInferred from direct assayⁱ
  • "The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes."
    Sun L., Deng L., Ea C.-K., Xia Z.-P., Chen Z.J.
    Mol. Cell 14:289-301(2004) [PubMed] [Europe PMC] [Abstract]
  • Ref.44

    "Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation."
    Lamothe B., Besse A., Campos A.D., Webster W.K., Wu H., Darnay B.G.
    J. Biol. Chem. 282:4102-4112(2007) [PubMed] [Europe PMC] [Abstract]

    Cited for: MUTAGENESIS OF CYS-70 AND LYS-124, UBIQUITINATION AT LYS-124, FUNCTION.
  • Ref.51

    "The E3 ligase TRAF6 regulates Akt ubiquitination and activation."
    Yang W.-L., Wang J., Chan C.-H., Lee S.-W., Campos A.D., Lamothe B., Hur L., Grabiner B.C., Lin X., Darnay B.G., Lin H.-K.
    Science 325:1134-1138(2009) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• zinc ion binding Source: InterPro

GO - Biological processⁱ

• activation of MAPK activity Source: Reactome
• activation of NF-kappaB-inducing kinase activity Source: UniProtKB <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes."
    Sun L., Deng L., Ea C.-K., Xia Z.-P., Chen Z.J.
    Mol. Cell 14:289-301(2004) [PubMed] [Europe PMC] [Abstract]
• activation of protein kinase activity Source: UniProtKBInferred from direct assayⁱ
  • Ref.44

    "Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation."
    Lamothe B., Besse A., Campos A.D., Webster W.K., Wu H., Darnay B.G.
    J. Biol. Chem. 282:4102-4112(2007) [PubMed] [Europe PMC] [Abstract]

    Cited for: MUTAGENESIS OF CYS-70 AND LYS-124, UBIQUITINATION AT LYS-124, FUNCTION.
• antigen processing and presentation of exogenous peptide antigen via MHC class II Source: Ensembl
• bone resorption Source: Ensembl
• cell development Source: Ensembl
• cellular response to cytokine stimulus Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Brain endothelial miR-146a negatively modulates T-cell adhesion through repressing multiple targets to inhibit NF-kappaB activation."
    Wu D., Cerutti C., Lopez-Ramirez M.A., Pryce G., King-Robson J., Simpson J.E., van der Pol S.M., Hirst M.C., de Vries H.E., Sharrack B., Baker D., Male D.K., Michael G.J., Romero I.A.
    J. Cereb. Blood Flow Metab. 35:412-423(2015) [PubMed] [Europe PMC] [Abstract]
• cellular response to DNA damage stimulus Source: UniProtKB-KW
• cellular response to lipopolysaccharide Source: MGIInferred from direct assayⁱ
  • Ref.55

    "SASH1 is a scaffold molecule in endothelial TLR4 signaling."
    Dauphinee S.M., Clayton A., Hussainkhel A., Yang C., Park Y.J., Fuller M.E., Blonder J., Veenstra T.D., Karsan A.
    J. Immunol. 191:892-901(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH SASH1.
• Fc-epsilon receptor signaling pathway Source: Reactome
• I-kappaB kinase/NF-kappaB signaling Source: Reactome
• interleukin-1-mediated signaling pathway Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• in utero embryonic development Source: Ensembl
• JNK cascade Source: Reactome
• membrane protein intracellular domain proteolysis Source: Reactome
• MyD88-dependent toll-like receptor signaling pathway Source: Reactome
• myeloid dendritic cell differentiation Source: Ensembl
• negative regulation of apoptotic process Source: Reactome
• negative regulation of transcription, DNA-templated Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.46

    "Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification."
    Pham L.V., Zhou H.J., Lin-Lee Y.C., Tamayo A.T., Yoshimura L.C., Fu L., Darnay B.G., Ford R.J.
    J. Biol. Chem. 283:5081-5089(2008) [PubMed] [Europe PMC] [Abstract]

    Cited for: SUBCELLULAR LOCATION, FUNCTION, SUMOYLATION AT LYS-124; LYS-142 AND LYS-453, UBIQUITINATION, INTERACTION WITH HDAC1 AND RANGAP1, MUTAGENESIS OF LYS-124; LYS-142 AND LYS-453.
• negative regulation of transcription by RNA polymerase II Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.46

    "Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification."
    Pham L.V., Zhou H.J., Lin-Lee Y.C., Tamayo A.T., Yoshimura L.C., Fu L., Darnay B.G., Ford R.J.
    J. Biol. Chem. 283:5081-5089(2008) [PubMed] [Europe PMC] [Abstract]

    Cited for: SUBCELLULAR LOCATION, FUNCTION, SUMOYLATION AT LYS-124; LYS-142 AND LYS-453, UBIQUITINATION, INTERACTION WITH HDAC1 AND RANGAP1, MUTAGENESIS OF LYS-124; LYS-142 AND LYS-453.
• neural tube closure Source: Ensembl
• nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
• odontogenesis of dentin-containing tooth Source: Ensembl
• ossification Source: UniProtKB-KW
• osteoclast differentiation Source: Ensembl
• positive regulation of apoptotic process Source: Reactome
• positive regulation of DNA-binding transcription factor activity Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "TAK1-dependent activation of AP-1 and c-Jun N-terminal kinase by receptor activator of NF-kappaB."
    Lee S.W., Han S.I., Kim H.H., Lee Z.H.
    J. Biochem. Mol. Biol. 35:371-376(2002) [PubMed] [Europe PMC] [Abstract]
• positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKBInferred from direct assayⁱ
  • Ref.44

    "Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation."
    Lamothe B., Besse A., Campos A.D., Webster W.K., Wu H., Darnay B.G.
    J. Biol. Chem. 282:4102-4112(2007) [PubMed] [Europe PMC] [Abstract]

    Cited for: MUTAGENESIS OF CYS-70 AND LYS-124, UBIQUITINATION AT LYS-124, FUNCTION.
• positive regulation of interleukin-12 biosynthetic process Source: Ensembl
• positive regulation of interleukin-2 production Source: UniProtKBInferred from mutant phenotypeⁱ
  • "The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes."
    Sun L., Deng L., Ea C.-K., Xia Z.-P., Chen Z.J.
    Mol. Cell 14:289-301(2004) [PubMed] [Europe PMC] [Abstract]
• positive regulation of interleukin-6 biosynthetic process Source: Ensembl
• positive regulation of JNK cascade Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of JUN kinase activity Source: BHF-UCLInferred from direct assayⁱ
  • Ref.26

    "A novel zinc finger protein that inhibits osteoclastogenesis and the function of tumor necrosis factor receptor-associated factor 6."
    Shin J.N., Kim I., Lee J.S., Koh G.Y., Lee Z.H., Kim H.-H.
    J. Biol. Chem. 277:8346-8353(2002) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH ZNF675.
• positive regulation of leukocyte adhesion to vascular endothelial cell Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Brain endothelial miR-146a negatively modulates T-cell adhesion through repressing multiple targets to inhibit NF-kappaB activation."
    Wu D., Cerutti C., Lopez-Ramirez M.A., Pryce G., King-Robson J., Simpson J.E., van der Pol S.M., Hirst M.C., de Vries H.E., Sharrack B., Baker D., Male D.K., Michael G.J., Romero I.A.
    J. Cereb. Blood Flow Metab. 35:412-423(2015) [PubMed] [Europe PMC] [Abstract]
• positive regulation of lipopolysaccharide-mediated signaling pathway Source: Ensembl
• positive regulation of NF-kappaB transcription factor activity Source: UniProtKBInferred from direct assayⁱ
  • "A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains."
    Zapata J.M., Pawlowski K., Haas E., Ware C.F., Godzik A., Reed J.C.
    J. Biol. Chem. 276:24242-24252(2001) [PubMed] [Europe PMC] [Abstract]
  • Ref.42

    "Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling."
    Wang Y., Tang Y., Teng L., Wu Y., Zhao X., Pei G.
    Nat. Immunol. 7:139-147(2006) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION IN TRANSCRIPTIONAL ACTIVATION OF NF-KAPPA-B AND JUN, INTERACTION WITH ARBB1 AND ARBB2.
• positive regulation of NIK/NF-kappaB signaling Source: ARUK-UCLInferred from mutant phenotypeⁱ
  • "Brain endothelial miR-146a negatively modulates T-cell adhesion through repressing multiple targets to inhibit NF-kappaB activation."
    Wu D., Cerutti C., Lopez-Ramirez M.A., Pryce G., King-Robson J., Simpson J.E., van der Pol S.M., Hirst M.C., de Vries H.E., Sharrack B., Baker D., Male D.K., Michael G.J., Romero I.A.
    J. Cereb. Blood Flow Metab. 35:412-423(2015) [PubMed] [Europe PMC] [Abstract]
• positive regulation of osteoclast differentiation Source: UniProtKBInferred from direct assayⁱ
  • Ref.44

    "Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation."
    Lamothe B., Besse A., Campos A.D., Webster W.K., Wu H., Darnay B.G.
    J. Biol. Chem. 282:4102-4112(2007) [PubMed] [Europe PMC] [Abstract]

    Cited for: MUTAGENESIS OF CYS-70 AND LYS-124, UBIQUITINATION AT LYS-124, FUNCTION.
• positive regulation of protein ubiquitination Source: BHF-UCL <p>Non-traceable Author Statement</p> <p>Used for statements in the abstract, introduction or discussion of a paper that cannot be traced back to another publication.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#nas">GO evidence code guide</a></p> Non-traceable author statementⁱ
  • "Activation of interferon regulatory factor 5 by site specific phosphorylation."
    Chang Foreman H.C., Van Scoy S., Cheng T.F., Reich N.C.
    PLoS ONE 7:E33098-E33098(2012) [PubMed] [Europe PMC] [Abstract]
• positive regulation of smooth muscle cell proliferation Source: Ensembl
• positive regulation of T cell cytokine production Source: UniProtKBInferred from mutant phenotypeⁱ
  • "The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes."
    Sun L., Deng L., Ea C.-K., Xia Z.-P., Chen Z.J.
    Mol. Cell 14:289-301(2004) [PubMed] [Europe PMC] [Abstract]
• positive regulation of T cell proliferation Source: Ensembl
• positive regulation of transcription by RNA polymerase II Source: BHF-UCLInferred from direct assayⁱ
  • Ref.26

    "A novel zinc finger protein that inhibits osteoclastogenesis and the function of tumor necrosis factor receptor-associated factor 6."
    Shin J.N., Kim I., Lee J.S., Koh G.Y., Lee Z.H., Kim H.-H.
    J. Biol. Chem. 277:8346-8353(2002) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH ZNF675.
• positive regulation of transcription regulatory region DNA binding Source: BHF-UCLInferred from direct assayⁱ
  • Ref.26

    "A novel zinc finger protein that inhibits osteoclastogenesis and the function of tumor necrosis factor receptor-associated factor 6."
    Shin J.N., Kim I., Lee J.S., Koh G.Y., Lee Z.H., Kim H.-H.
    J. Biol. Chem. 277:8346-8353(2002) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH ZNF675.
• protein autoubiquitination Source: UniProtKBInferred from direct assayⁱ
  • Ref.44

    "Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation."
    Lamothe B., Besse A., Campos A.D., Webster W.K., Wu H., Darnay B.G.
    J. Biol. Chem. 282:4102-4112(2007) [PubMed] [Europe PMC] [Abstract]

    Cited for: MUTAGENESIS OF CYS-70 AND LYS-124, UBIQUITINATION AT LYS-124, FUNCTION.
  • Ref.46

    "Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification."
    Pham L.V., Zhou H.J., Lin-Lee Y.C., Tamayo A.T., Yoshimura L.C., Fu L., Darnay B.G., Ford R.J.
    J. Biol. Chem. 283:5081-5089(2008) [PubMed] [Europe PMC] [Abstract]

    Cited for: SUBCELLULAR LOCATION, FUNCTION, SUMOYLATION AT LYS-124; LYS-142 AND LYS-453, UBIQUITINATION, INTERACTION WITH HDAC1 AND RANGAP1, MUTAGENESIS OF LYS-124; LYS-142 AND LYS-453.
• protein deubiquitination Source: Reactome
• protein K63-linked ubiquitination Source: UniProtKBInferred from direct assayⁱ
  • Ref.51

    "The E3 ligase TRAF6 regulates Akt ubiquitination and activation."
    Yang W.-L., Wang J., Chan C.-H., Lee S.-W., Campos A.D., Lamothe B., Hur L., Grabiner B.C., Lin X., Darnay B.G., Lin H.-K.
    Science 325:1134-1138(2009) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• protein polyubiquitination Source: UniProtKBInferred from direct assayⁱ
  • "The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes."
    Sun L., Deng L., Ea C.-K., Xia Z.-P., Chen Z.J.
    Mol. Cell 14:289-301(2004) [PubMed] [Europe PMC] [Abstract]
  • Ref.50

    "Direct activation of protein kinases by unanchored polyubiquitin chains."
    Xia Z.-P., Sun L., Chen X., Pineda G., Jiang X., Adhikari A., Zeng W., Chen Z.J.
    Nature 461:114-119(2009) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, UBIQUITINATION.
• regulation of I-kappaB kinase/NF-kappaB signaling Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• regulation of immunoglobulin secretion Source: Ensembl
• response to interleukin-1 Source: UniProtKBInferred from direct assayⁱ
  • Ref.44

    "Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation."
    Lamothe B., Besse A., Campos A.D., Webster W.K., Wu H., Darnay B.G.
    J. Biol. Chem. 282:4102-4112(2007) [PubMed] [Europe PMC] [Abstract]

    Cited for: MUTAGENESIS OF CYS-70 AND LYS-124, UBIQUITINATION AT LYS-124, FUNCTION.
• stimulatory C-type lectin receptor signaling pathway Source: Reactome
• T cell receptor signaling pathway Source: UniProtKBInferred from mutant phenotypeⁱ
  • "The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes."
    Sun L., Deng L., Ea C.-K., Xia Z.-P., Chen Z.J.
    Mol. Cell 14:289-301(2004) [PubMed] [Europe PMC] [Abstract]
• T-helper 1 type immune response Source: Ensembl
• toll-like receptor 9 signaling pathway Source: Reactome
• toll-like receptor signaling pathway Source: Reactome
• tumor necrosis factor-mediated signaling pathway Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

Mutagenesis

Organism-specific databases

Miscellaneous databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityⁱ

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• histone deacetylase binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.46

    "Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid cells negatively regulates c-Myb-mediated transactivation through small ubiquitin-related modifier-1 modification."
    Pham L.V., Zhou H.J., Lin-Lee Y.C., Tamayo A.T., Yoshimura L.C., Fu L., Darnay B.G., Ford R.J.
    J. Biol. Chem. 283:5081-5089(2008) [PubMed] [Europe PMC] [Abstract]

    Cited for: SUBCELLULAR LOCATION, FUNCTION, SUMOYLATION AT LYS-124; LYS-142 AND LYS-453, UBIQUITINATION, INTERACTION WITH HDAC1 AND RANGAP1, MUTAGENESIS OF LYS-124; LYS-142 AND LYS-453.
• identical protein binding Source: IntActInferred from physical interactionⁱ
  • Ref.62

    "E2 interaction and dimerization in the crystal structure of TRAF6."
    Yin Q., Lin S.C., Lamothe B., Lu M., Lo Y.C., Hura G., Zheng L., Rich R.L., Campos A.D., Myszka D.G., Lenardo M.J., Darnay B.G., Wu H.
    Nat. Struct. Mol. Biol. 16:658-666(2009) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 50-211 IN COMPLEXES WITH ZINC IONS AND UBE2N, SUBUNIT, FUNCTION, AUTOUBIQUITINATION, MUTAGENESIS OF ASP-57; CYS-70; ILE-72; LEU-74; ARG-88; PHE-118; PHE-122 AND LYS-124, ZINC-FINGER.
  • "Toward an understanding of the protein interaction network of the human liver."
    Wang J., Huo K., Ma L., Tang L., Li D., Huang X., Yuan Y., Li C., Wang W., Guan W., Chen H., Jin C., Wei J., Zhang W., Yang Y., Liu Q., Zhou Y., Zhang C.

    , Wu Z., Xu W., Zhang Y., Liu T., Yu D., Zhang Y., Chen L., Zhu D., Zhong X., Kang L., Gan X., Yu X., Ma Q., Yan J., Zhou L., Liu Z., Zhu Y., Zhou T., He F., Yang X.
    Mol. Syst. Biol. 7:536-536(2011) [PubMed] [Europe PMC] [Abstract]
  • "Systematic analysis of dimeric E3-RING interactions reveals increased combinatorial complexity in human ubiquitination networks."
    Woodsmith J., Jenn R.C., Sanderson C.M.
    Mol. Cell Proteomics 11:M111.016162-M111.016162(2012) [PubMed] [Europe PMC] [Abstract]
  • "A proteome-scale map of the human interactome network."
    Rolland T., Tasan M., Charloteaux B., Pevzner S.J., Zhong Q., Sahni N., Yi S., Lemmens I., Fontanillo C., Mosca R., Kamburov A., Ghiassian S.D., Yang X., Ghamsari L., Balcha D., Begg B.E., Braun P., Brehme M.

    , Broly M.P., Carvunis A.R., Convery-Zupan D., Corominas R., Coulombe-Huntington J., Dann E., Dreze M., Dricot A., Fan C., Franzosa E., Gebreab F., Gutierrez B.J., Hardy M.F., Jin M., Kang S., Kiros R., Lin G.N., Luck K., MacWilliams A., Menche J., Murray R.R., Palagi A., Poulin M.M., Rambout X., Rasla J., Reichert P., Romero V., Ruyssinck E., Sahalie J.M., Scholz A., Shah A.A., Sharma A., Shen Y., Spirohn K., Tam S., Tejeda A.O., Trigg S.A., Twizere J.C., Vega K., Walsh J., Cusick M.E., Xia Y., Barabasi A.L., Iakoucheva L.M., Aloy P., De Las Rivas J., Tavernier J., Calderwood M.A., Hill D.E., Hao T., Roth F.P., Vidal M.
    Cell 159:1212-1226(2014) [PubMed] [Europe PMC] [Abstract]
  • "Pooled-matrix protein interaction screens using Barcode Fusion Genetics."
    Yachie N., Petsalaki E., Mellor J.C., Weile J., Jacob Y., Verby M., Ozturk S.B., Li S., Cote A.G., Mosca R., Knapp J.J., Ko M., Yu A., Gebbia M., Sahni N., Yi S., Tyagi T., Sheykhkarimli D.

    , Roth J.F., Wong C., Musa L., Snider J., Liu Y.C., Yu H., Braun P., Stagljar I., Hao T., Calderwood M.A., Pelletier L., Aloy P., Hill D.E., Vidal M., Roth F.P.
    Mol. Syst. Biol. 12:863-863(2016) [PubMed] [Europe PMC] [Abstract]
• mitogen-activated protein kinase kinase kinase binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.18

    "The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway."
    Ninomiya-Tsuji J., Kishimoto K., Hiyama A., Inoue J., Cao Z., Matsumoto K.
    Nature 398:252-256(1999) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH MAP3K7 AND TAB1.
• protein kinase B binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.51

    "The E3 ligase TRAF6 regulates Akt ubiquitination and activation."
    Yang W.-L., Wang J., Chan C.-H., Lee S.-W., Campos A.D., Lamothe B., Hur L., Grabiner B.C., Lin X., Darnay B.G., Lin H.-K.
    Science 325:1134-1138(2009) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• protein kinase binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.51

    "The E3 ligase TRAF6 regulates Akt ubiquitination and activation."
    Yang W.-L., Wang J., Chan C.-H., Lee S.-W., Campos A.D., Lamothe B., Hur L., Grabiner B.C., Lin X., Darnay B.G., Lin H.-K.
    Science 325:1134-1138(2009) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• protein N-terminus binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.32

    "Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling."
    Sato S., Sugiyama M., Yamamoto M., Watanabe Y., Kawai T., Takeda K., Akira S.
    J. Immunol. 171:4304-4310(2003) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH TICAM1.
• thioesterase binding Source: UniProtKBInferred from physical interactionⁱ
  • "A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains."
    Zapata J.M., Pawlowski K., Haas E., Ware C.F., Godzik A., Reed J.C.
    J. Biol. Chem. 276:24242-24252(2001) [PubMed] [Europe PMC] [Abstract]
• tumor necrosis factor receptor binding Source: UniProtKBInferred from physical interactionⁱ
  • "A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis."
    Wiley S.R., Cassiano L., Lofton T., Davis-Smith T., Winkles J.A., Lindner V., Liu H., Daniel T.O., Smith C.A., Fanslow W.C.
    Immunity 15:837-846(2001) [PubMed] [Europe PMC] [Abstract]
• ubiquitin conjugating enzyme binding Source: MGIInferred from direct assayⁱ
  • Ref.55

    "SASH1 is a scaffold molecule in endothelial TLR4 signaling."
    Dauphinee S.M., Clayton A., Hussainkhel A., Yang C., Park Y.J., Fuller M.E., Blonder J., Veenstra T.D., Karsan A.
    J. Immunol. 191:892-901(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH SASH1.
• ubiquitin protein ligase binding Source: UniProtKBInferred from physical interactionⁱ
  • "A diverse family of proteins containing tumor necrosis factor receptor-associated factor domains."
    Zapata J.M., Pawlowski K., Haas E., Ware C.F., Godzik A., Reed J.C.
    J. Biol. Chem. 276:24242-24252(2001) [PubMed] [Europe PMC] [Abstract]

Protein-protein interaction databases

Chemistry databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Domains and Repeats

Region

Coiled coil

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domainⁱ

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Zinc finger

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequenceⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

        10         20         30         40         50
MSLLNCENSC GSSQSESDCC VAMASSCSAV TKDDSVGGTA STGNLSSSFM 
        60         70         80         90        100
EEIQGYDVEF DPPLESKYEC PICLMALREA VQTPCGHRFC KACIIKSIRD 
       110        120        130        140        150
AGHKCPVDNE ILLENQLFPD NFAKREILSL MVKCPNEGCL HKMELRHLED 
       160        170        180        190        200
HQAHCEFALM DCPQCQRPFQ KFHINIHILK DCPRRQVSCD NCAASMAFED 
       210        220        230        240        250
KEIHDQNCPL ANVICEYCNT ILIREQMPNH YDLDCPTAPI PCTFSTFGCH 
       260        270        280        290        300
EKMQRNHLAR HLQENTQSHM RMLAQAVHSL SVIPDSGYIS EVRNFQETIH 
       310        320        330        340        350
QLEGRLVRQD HQIRELTAKM ETQSMYVSEL KRTIRTLEDK VAEIEAQQCN 
       360        370        380        390        400
GIYIWKIGNF GMHLKCQEEE KPVVIHSPGF YTGKPGYKLC MRLHLQLPTA 
       410        420        430        440        450
QRCANYISLF VHTMQGEYDS HLPWPFQGTI RLTILDQSEA PVRQNHEEIM 
       460        470        480        490        500
DAKPELLAFQ RPTIPRNPKG FGYVTFMHLE ALRQRTFIKD DTLLVRCEVS 
       510        520 
TRFDMGSLRR EGFQPRSTDA GV                               

Experimental Info

Sequence databases

Genome annotation databases

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

Protein family/group databases

PTM databases

Polymorphism and mutation databases