ID TRAF6_HUMAN Reviewed; 522 AA. AC Q9Y4K3; A6NKI7; A8KAB3; D3DR16; Q8NEH5; DT 09-MAY-2003, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 27-MAR-2024, entry version 244. DE RecName: Full=TNF receptor-associated factor 6; DE EC=2.3.2.27; DE AltName: Full=E3 ubiquitin-protein ligase TRAF6; DE AltName: Full=Interleukin-1 signal transducer; DE AltName: Full=RING finger protein 85; DE AltName: Full=RING-type E3 ubiquitin transferase TRAF6 {ECO:0000305}; GN Name=TRAF6; Synonyms=RNF85; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INTERACTION WITH IRAK1. RX PubMed=8837778; DOI=10.1038/383443a0; RA Cao Z., Xiong J., Takeuchi M., Kurama T., Goeddel D.V.; RT "TRAF6 is a signal transducer for interleukin-1."; RL Nature 383:443-446(1996). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG SeattleSNPs variation discovery resource; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP INTERACTION WITH MAP3K14. RX PubMed=9020361; DOI=10.1038/385540a0; RA Malinin N.L., Boldin M.P., Kovalenko A.V., Wallach D.; RT "MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL- RT 1."; RL Nature 385:540-544(1997). RN [8] RP INTERACTION WITH IRAK2. RX PubMed=9374458; DOI=10.1126/science.278.5343.1612; RA Muzio M., Ni J., Feng P., Dixit V.M.; RT "IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 RT signaling."; RL Science 278:1612-1615(1997). RN [9] RP INTERACTION WITH RIPK2. RX PubMed=9642260; DOI=10.1074/jbc.273.27.16968; RA McCarthy J.V., Ni J., Dixit V.M.; RT "RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase."; RL J. Biol. Chem. 273:16968-16975(1998). RN [10] RP INTERACTION WITH TNFRSF11A. RX PubMed=9774460; DOI=10.1074/jbc.273.43.28355; RA Wong B.R., Josien R., Lee S.Y., Vologodskaia M., Steinman R.M., Choi Y.; RT "The TRAF family of signal transducers mediates NF-kappaB activation by the RT TRANCE receptor."; RL J. Biol. Chem. 273:28355-28359(1998). RN [11] RP INTERACTION WITH TNFRSF5. RX PubMed=9432981; DOI=10.1084/jem.187.2.237; RA Kashiwada M., Shirakata Y., Inoue J., Nakano H., Okazaki K., Okumura K., RA Yamamoto T., Nagaoka H., Takemori T.; RT "Tumor necrosis factor receptor-associated factor 6 (TRAF6) stimulates RT extracellular signal-regulated kinase (ERK) activity in CD40 signaling RT along a ras-independent pathway."; RL J. Exp. Med. 187:237-244(1998). RN [12] RP INTERACTION WITH MAP3K5. RX PubMed=9774977; DOI=10.1016/s1097-2765(00)80283-x; RA Nishitoh H., Saitoh M., Mochida Y., Takeda K., Nakano H., Rothe M., RA Miyazono K., Ichijo H.; RT "ASK1 is essential for JNK/SAPK activation by TRAF2."; RL Mol. Cell 2:389-395(1998). RN [13] RP INTERACTION WITH MAP3K1. RX PubMed=10346818; DOI=10.1101/gad.13.10.1297; RA Baud V., Liu Z.-G., Bennett B., Suzuki N., Xia Y., Karin M.; RT "Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 RT is sufficient for JNK and IKK activation and target gene induction via an RT amino-terminal effector domain."; RL Genes Dev. 13:1297-1308(1999). RN [14] RP INTERACTION WITH NGFR. RX PubMed=9915784; DOI=10.1074/jbc.274.5.2597; RA Khursigara G., Orlinick J.R., Chao M.V.; RT "Association of the p75 neurotrophin receptor with TRAF6."; RL J. Biol. Chem. 274:2597-2600(1999). RN [15] RP INTERACTION WITH IRAK3. RX PubMed=10383454; DOI=10.1074/jbc.274.27.19403; RA Wesche H., Gao X., Li X., Kirschning C.J., Stark G.R., Cao Z.; RT "IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated RT kinase (IRAK) family."; RL J. Biol. Chem. 274:19403-19410(1999). RN [16] RP INTERACTION WITH NGFR. RX PubMed=10514511; DOI=10.1074/jbc.274.42.30202; RA Ye X., Mehlen P., Rabizadeh S., VanArsdale T., Zhang H., Shin H., RA Wang J.J.L., Leo E., Zapata J.M., Hauser C.A., Reed J.C., Bredesen D.E.; RT "TRAF family proteins interact with the common neurotrophin receptor and RT modulate apoptosis induction."; RL J. Biol. Chem. 274:30202-30208(1999). RN [17] RP INTERACTION WITH TNFRSF11A AND CSK. RX PubMed=10635328; DOI=10.1016/s1097-2765(00)80232-4; RA Wong B.R., Besser D., Kim N., Arron J.R., Vologodskaia M., Hanafusa H., RA Choi Y.; RT "TRANCE, a TNF family member, activates Akt/PKB through a signaling complex RT involving TRAF6 and c-Src."; RL Mol. Cell 4:1041-1049(1999). RN [18] RP INTERACTION WITH MAP3K7 AND TAB1. RX PubMed=10094049; DOI=10.1038/18465; RA Ninomiya-Tsuji J., Kishimoto K., Hiyama A., Inoue J., Cao Z., Matsumoto K.; RT "The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase RT cascade in the IL-1 signalling pathway."; RL Nature 398:252-256(1999). RN [19] RP INTERACTION WITH MAP3K5. RX PubMed=10523862; DOI=10.1038/sj.onc.1202975; RA Hoeflich K.P., Yeh W.C., Yao Z., Mak T.W., Woodgett J.R.; RT "Mediation of TNF receptor-associated factor effector functions by RT apoptosis signal-regulating kinase-1 (ASK1)."; RL Oncogene 18:5814-5820(1999). RN [20] RP INTERACTION WITH UBE2V1, AND FUNCTION AS AN E3 UBIQUITIN LIGASE. RX PubMed=11057907; DOI=10.1016/s0092-8674(00)00126-4; RA Deng L., Wang C., Spencer E., Yang L., Braun A., You J., Slaughter C., RA Pickart C., Chen Z.J.; RT "Activation of the IkappaB kinase complex by TRAF6 requires a dimeric RT ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain."; RL Cell 103:351-361(2000). RN [21] RP INTERACTION WITH TDP2. RX PubMed=10764746; DOI=10.1074/jbc.m000531200; RA Pype S., Declercq W., Ibrahimi A., Michiels C., Van Rietschoten J.G.I., RA Dewulf N., de Boer M., Vandenabeele P., Huylebroeck D., Remacle J.E.; RT "TTRAP, a novel protein that associates with CD40, tumor necrosis factor RT (TNF) receptor-75 and TNF receptor-associated factors (TRAFs), and that RT inhibits nuclear factor-kappa B activation."; RL J. Biol. Chem. 275:18586-18593(2000). RN [22] RP INTERACTION WITH TNFRSF17. RX PubMed=10908663; DOI=10.1073/pnas.160213497; RA Shu H.-B., Johnson H.; RT "B cell maturation protein is a receptor for the tumor necrosis factor RT family member TALL-1."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9156-9161(2000). RN [23] RP INTERACTION WITH TAX1BP1. RX PubMed=10920205; DOI=10.1073/pnas.170279097; RA Ling L., Goeddel D.V.; RT "T6BP, a TRAF6-interacting protein involved in IL-1 signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9567-9572(2000). RN [24] RP UBIQUITINATION. RX PubMed=11460167; DOI=10.1038/35085597; RA Wang C., Deng L., Hong M., Akkaraju G.R., Inoue J., Chen Z.J.; RT "TAK1 is a ubiquitin-dependent kinase of MKK and IKK."; RL Nature 412:346-351(2001). RN [25] RP INTERACTION WITH TRAF3IP2. RX PubMed=12459498; DOI=10.1016/s0014-5793(02)03688-8; RA Kanamori M., Kai C., Hayashizaki Y., Suzuki H.; RT "NF-kappaB activator Act1 associates with IL-1/Toll pathway adapter RT molecule TRAF6."; RL FEBS Lett. 532:241-246(2002). RN [26] RP INTERACTION WITH ZNF675. RX PubMed=11751921; DOI=10.1074/jbc.m110964200; RA Shin J.N., Kim I., Lee J.S., Koh G.Y., Lee Z.H., Kim H.-H.; RT "A novel zinc finger protein that inhibits osteoclastogenesis and the RT function of tumor necrosis factor receptor-associated factor 6."; RL J. Biol. Chem. 277:8346-8353(2002). RN [27] RP INTERACTION WITH IRAK4. RX PubMed=11960013; DOI=10.1073/pnas.082100399; RA Li S., Strelow A., Fontana E.J., Wesche H.; RT "IRAK4: a novel member of the IRAK family with the properties of an IRAK- RT kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 99:5567-5572(2002). RN [28] RP INTERACTION WITH PELI1. RX PubMed=12496252; DOI=10.1074/jbc.m212112200; RA Jiang Z., Johnson H.J., Nie H., Qin J., Bird T.A., Li X.; RT "Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through RT its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK- RT tumor necrosis factor receptor-associated factor 6 (TRAF6) complex."; RL J. Biol. Chem. 278:10952-10956(2003). RN [29] RP INTERACTION WITH PELI1 AND PELI2. RX PubMed=12804775; DOI=10.1016/s0014-5793(03)00533-7; RA Jensen L.E., Whitehead A.S.; RT "Pellino2 activates the mitogen activated protein kinase pathway."; RL FEBS Lett. 545:199-202(2003). RN [30] RP INTERACTION WITH TICAM2. RX PubMed=12721283; DOI=10.1074/jbc.m303451200; RA Bin L.-H., Xu L.-G., Shu H.-B.; RT "TIRP, a novel Toll/interleukin-1 receptor (TIR) domain-containing adapter RT protein involved in TIR signaling."; RL J. Biol. Chem. 278:24526-24532(2003). RN [31] RP INTERACTION WITH PELI3. RX PubMed=12874243; DOI=10.4049/jimmunol.171.3.1500; RA Jensen L.E., Whitehead A.S.; RT "Pellino3, a novel member of the Pellino protein family, promotes RT activation of c-Jun and Elk-1 and may act as a scaffolding protein."; RL J. Immunol. 171:1500-1506(2003). RN [32] RP INTERACTION WITH TICAM1. RX PubMed=14530355; DOI=10.4049/jimmunol.171.8.4304; RA Sato S., Sugiyama M., Yamamoto M., Watanabe Y., Kawai T., Takeda K., RA Akira S.; RT "Toll/IL-1 receptor domain-containing adapter inducing IFN-beta (TRIF) RT associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, RT and activates two distinct transcription factors, NF-kappa B and IFN- RT regulatory factor-3, in the Toll-like receptor signaling."; RL J. Immunol. 171:4304-4310(2003). RN [33] RP INTERACTION WITH TICAM1. RX PubMed=14739303; DOI=10.1074/jbc.m311629200; RA Han K.J., Su X., Xu L.-G., Bin L.H., Zhang J., Shu H.-B.; RT "Mechanisms of the TRIF-induced interferon-stimulated response element and RT NF-kappaB activation and apoptosis pathways."; RL J. Biol. Chem. 279:15652-15661(2004). RN [34] RP INTERACTION WITH ZFAND5. RX PubMed=14754897; DOI=10.1074/jbc.m309491200; RA Huang J., Teng L., Li L., Liu T., Li L., Chen D., Xu L.-G., Zhai Z., RA Shu H.-B.; RT "ZNF216 is an A20-like and IkappaB kinase gamma-interacting inhibitor of RT NFkappaB activation."; RL J. Biol. Chem. 279:16847-16853(2004). RN [35] RP INTERACTION WITH EIF2AK2. RX PubMed=15121867; DOI=10.1128/mcb.24.10.4502-4512.2004; RA Gil J., Garcia M.A., Gomez-Puertas P., Guerra S., Rullas J., Nakano H., RA Alcami J., Esteban M.; RT "TRAF family proteins link PKR with NF-kappa B activation."; RL Mol. Cell. Biol. 24:4502-4512(2004). RN [36] RP INTERACTION WITH TICAM1. RX PubMed=14982987; DOI=10.1073/pnas.0308496101; RA Jiang Z., Mak T.W., Sen G., Li X.; RT "Toll-like receptor 3-mediated activation of NF-kappaB and IRF3 diverges at RT Toll-IL-1 receptor domain-containing adapter inducing IFN-beta."; RL Proc. Natl. Acad. Sci. U.S.A. 101:3533-3538(2004). RN [37] RP INTERACTION WITH MAVS. RX PubMed=16125763; DOI=10.1016/j.cell.2005.08.012; RA Seth R.B., Sun L., Ea C.-K., Chen Z.J.; RT "Identification and characterization of MAVS, a mitochondrial antiviral RT signaling protein that activates NF-kappaB and IRF 3."; RL Cell 122:669-682(2005). RN [38] RP INTERACTION WITH IL1RL1. RX PubMed=16286016; DOI=10.1016/j.immuni.2005.09.015; RA Schmitz J., Owyang A., Oldham E., Song Y., Murphy E., McClanahan T.K., RA Zurawski G., Moshrefi M., Qin J., Li X., Gorman D.M., Bazan J.F., RA Kastelein R.A.; RT "IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor- RT related protein ST 2 and induces T helper type 2-associated cytokines."; RL Immunity 23:479-490(2005). RN [39] RP INTERACTION WITH TRAFD1. RX PubMed=16221674; DOI=10.1074/jbc.m508221200; RA Mashima R., Saeki K., Aki D., Minoda Y., Takaki H., Sanada T., RA Kobayashi T., Aburatani H., Yamanashi Y., Yoshimura A.; RT "FLN29, a novel interferon- and LPS-inducible gene acting as a negative RT regulator of toll-like receptor signaling."; RL J. Biol. Chem. 280:41289-41297(2005). RN [40] RP INTERACTION WITH MAVS. RX PubMed=16153868; DOI=10.1016/j.molcel.2005.08.014; RA Xu L.-G., Wang Y.-Y., Han K.-J., Li L.-Y., Zhai Z., Shu H.-B.; RT "VISA is an adapter protein required for virus-triggered IFN-beta RT Signaling."; RL Mol. Cell 19:727-740(2005). RN [41] RP INTERACTION WITH AJUBA. RX PubMed=15870274; DOI=10.1128/mcb.25.10.4010-4022.2005; RA Feng Y., Longmore G.D.; RT "The LIM protein Ajuba influences interleukin-1-induced NF-kappaB RT activation by affecting the assembly and activity of the protein kinase RT Czeta/p62/TRAF6 signaling complex."; RL Mol. Cell. Biol. 25:4010-4022(2005). RN [42] RP FUNCTION IN TRANSCRIPTIONAL ACTIVATION OF NF-KAPPA-B AND JUN, AND RP INTERACTION WITH ARRB1 AND ARRB2. RX PubMed=16378096; DOI=10.1038/ni1294; RA Wang Y., Tang Y., Teng L., Wu Y., Zhao X., Pei G.; RT "Association of beta-arrestin and TRAF6 negatively regulates Toll-like RT receptor-interleukin 1 receptor signaling."; RL Nat. Immunol. 7:139-147(2006). RN [43] RP IDENTIFICATION IN COMPLEX WITH IRAK1; IRAK4; MYD88 AND PELI1. RX PubMed=16951688; DOI=10.1038/ni1383; RA Choi K.C., Lee Y.S., Lim S., Choi H.K., Lee C.H., Lee E.K., Hong S., RA Kim I.H., Kim S.J., Park S.H.; RT "Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor RT signaling through direct interaction with the adapter Pellino-1."; RL Nat. Immunol. 7:1057-1065(2006). RN [44] RP MUTAGENESIS OF CYS-70 AND LYS-124, UBIQUITINATION AT LYS-124, AND FUNCTION. RX PubMed=17135271; DOI=10.1074/jbc.m609503200; RA Lamothe B., Besse A., Campos A.D., Webster W.K., Wu H., Darnay B.G.; RT "Site-specific Lys-63-linked tumor necrosis factor receptor-associated RT factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase RT activation."; RL J. Biol. Chem. 282:4102-4112(2007). RN [45] RP INTERACTION WITH RBCK1. RX PubMed=17449468; DOI=10.1074/jbc.m701913200; RA Tian Y., Zhang Y., Zhong B., Wang Y.Y., Diao F.C., Wang R.P., Zhang M., RA Chen D.Y., Zhai Z.H., Shu H.B.; RT "RBCK1 negatively regulates tumor necrosis factor- and interleukin-1- RT triggered NF-kappaB activation by targeting TAB2/3 for degradation."; RL J. Biol. Chem. 282:16776-16782(2007). RN [46] RP FUNCTION, AND INTERACTION WITH TAX1BP1. RX PubMed=17703191; DOI=10.1038/sj.emboj.7601823; RA Shembade N., Harhaj N.S., Liebl D.J., Harhaj E.W.; RT "Essential role for TAX1BP1 in the termination of TNF-alpha-, IL-1- and RT LPS-mediated NF-kappaB and JNK signaling."; RL EMBO J. 26:3910-3922(2007). RN [47] RP SUBCELLULAR LOCATION, FUNCTION, SUMOYLATION AT LYS-124; LYS-142 AND RP LYS-453, UBIQUITINATION, INTERACTION WITH HDAC1 AND RANGAP1, AND RP MUTAGENESIS OF LYS-124; LYS-142 AND LYS-453. RX PubMed=18093978; DOI=10.1074/jbc.m706307200; RA Pham L.V., Zhou H.J., Lin-Lee Y.C., Tamayo A.T., Yoshimura L.C., Fu L., RA Darnay B.G., Ford R.J.; RT "Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid RT cells negatively regulates c-Myb-mediated transactivation through small RT ubiquitin-related modifier-1 modification."; RL J. Biol. Chem. 283:5081-5089(2008). RN [48] RP FUNCTION IN UBIQUITINATION OR IRAK1. RX PubMed=18347055; DOI=10.1128/mcb.02098-07; RA Conze D.B., Wu C.J., Thomas J.A., Landstrom A., Ashwell J.D.; RT "Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 RT receptor- and toll-like receptor-mediated NF-kappaB activation."; RL Mol. Cell. Biol. 28:3538-3547(2008). RN [49] RP FUNCTION, INTERACTION WITH TGFBR1, AND UBIQUITINATION. RX PubMed=18758450; DOI=10.1038/ncb1780; RA Sorrentino A., Thakur N., Grimsby S., Marcusson A., von Bulow V., RA Schuster N., Zhang S., Heldin C.H., Landstrom M.; RT "The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor RT kinase-independent manner."; RL Nat. Cell Biol. 10:1199-1207(2008). RN [50] RP INTERACTION WITH DYNC2I2. RX PubMed=19521662; DOI=10.1007/s00018-009-0059-6; RA Gao D., Wang R., Li B., Yang Y., Zhai Z., Chen D.Y.; RT "WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced RT NF-kappaB activation pathway."; RL Cell. Mol. Life Sci. 66:2573-2584(2009). RN [51] RP FUNCTION, AND UBIQUITINATION. RX PubMed=19675569; DOI=10.1038/nature08247; RA Xia Z.-P., Sun L., Chen X., Pineda G., Jiang X., Adhikari A., Zeng W., RA Chen Z.J.; RT "Direct activation of protein kinases by unanchored polyubiquitin chains."; RL Nature 461:114-119(2009). RN [52] RP FUNCTION. RX PubMed=19713527; DOI=10.1126/science.1175065; RA Yang W.-L., Wang J., Chan C.-H., Lee S.-W., Campos A.D., Lamothe B., RA Hur L., Grabiner B.C., Lin X., Darnay B.G., Lin H.-K.; RT "The E3 ligase TRAF6 regulates Akt ubiquitination and activation."; RL Science 325:1134-1138(2009). RN [53] RP FUNCTION, UBIQUITINATION AT LYS-124, MUTAGENESIS OF CYS-70 AND LYS-124, AND RP INTERACTION WITH IL17RA AND TRAF3IP2. RX PubMed=19825828; DOI=10.1126/scisignal.2000382; RA Liu C., Qian W., Qian Y., Giltiay N.V., Lu Y., Swaidani S., Misra S., RA Deng L., Chen Z.J., Li X.; RT "Act1, a U-box E3 ubiquitin ligase for IL-17 signaling."; RL Sci. Signal. 2:ra63-ra63(2009). RN [54] RP INTERACTION WITH NUMBL. RX PubMed=20079715; DOI=10.1016/j.bbrc.2010.01.037; RA Zhou L., Ma Q., Shi H., Huo K.; RT "NUMBL interacts with TRAF6 and promotes the degradation of TRAF6."; RL Biochem. Biophys. Res. Commun. 392:409-414(2010). RN [55] RP INTERACTION WITH TOMM70. RX PubMed=20628368; DOI=10.1038/cr.2010.103; RA Liu X.Y., Wei B., Shi H.X., Shan Y.F., Wang C.; RT "Tom70 mediates activation of interferon regulatory factor 3 on RT mitochondria."; RL Cell Res. 20:994-1011(2010). RN [56] RP INTERACTION WITH CARD14. RX PubMed=21302310; DOI=10.1002/jcp.22667; RA Scudiero I., Zotti T., Ferravante A., Vessichelli M., Vito P., Stilo R.; RT "Alternative splicing of CARMA2/CARD14 transcripts generates protein RT variants with differential effect on NF-kappaB activation and endoplasmic RT reticulum stress-induced cell death."; RL J. Cell. Physiol. 226:3121-3131(2011). RN [57] RP INTERACTION WITH IFIT3. RX PubMed=21813773; DOI=10.4049/jimmunol.1100963; RA Liu X.Y., Chen W., Wei B., Shan Y.F., Wang C.; RT "IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging RT MAVS and TBK1."; RL J. Immunol. 187:2559-2568(2011). RN [58] RP INTERACTION WITH SASH1. RX PubMed=23776175; DOI=10.4049/jimmunol.1200583; RA Dauphinee S.M., Clayton A., Hussainkhel A., Yang C., Park Y.J., RA Fuller M.E., Blonder J., Veenstra T.D., Karsan A.; RT "SASH1 is a scaffold molecule in endothelial TLR4 signaling."; RL J. Immunol. 191:892-901(2013). RN [59] RP INTERACTION WITH AMBRA1. RX PubMed=23524951; DOI=10.1038/ncb2708; RA Nazio F., Strappazzon F., Antonioli M., Bielli P., Cianfanelli V., RA Bordi M., Gretzmeier C., Dengjel J., Piacentini M., Fimia G.M., Cecconi F.; RT "mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self- RT association and function through AMBRA1 and TRAF6."; RL Nat. Cell Biol. 15:406-416(2013). RN [60] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP CYS-70. RX PubMed=23514740; DOI=10.4049/jimmunol.1202742; RA Xie J.J., Liang J.Q., Diao L.H., Altman A., Li Y.; RT "TNFR-associated factor 6 regulates TCR signaling via interaction with and RT modification of LAT adapter."; RL J. Immunol. 190:4027-4036(2013). RN [61] RP SUBCELLULAR LOCATION, AND DEUBIQUITINATION BY EPSTEIN-BARR VIRUS PROTEIN RP BPLF1 (MICROBIAL INFECTION). RX PubMed=24586164; DOI=10.1371/journal.ppat.1003960; RA van Gent M., Braem S.G., de Jong A., Delagic N., Peeters J.G., Boer I.G., RA Moynagh P.N., Kremmer E., Wiertz E.J., Ovaa H., Griffin B.D., Ressing M.E.; RT "Epstein-Barr virus large tegument protein BPLF1 contributes to innate RT immune evasion through interference with toll-like receptor signaling."; RL PLoS Pathog. 10:e1003960-e1003960(2014). RN [62] RP UBIQUITINATION, AND INTERACTION WITH LRRC19. RX PubMed=25026888; DOI=10.1038/ncomms5434; RA Su X., Min S., Cao S., Yan H., Zhao Y., Li H., Chai L., Mei S., Yang J., RA Zhang Y., Zhang Z., Liu F., Sun W., Che Y., Yang R.; RT "LRRC19 expressed in the kidney induces TRAF2/6-mediated signals to prevent RT infection by uropathogenic bacteria."; RL Nat. Commun. 5:4434-4434(2014). RN [63] RP FUNCTION. RX PubMed=25907557; DOI=10.1074/jbc.m115.646422; RA Yang Y., Wu S., Wang Y., Pan S., Lan B., Liu Y., Zhang L., Leng Q., RA Chen D., Zhang C., He B., Cao Y.; RT "The Us3 Protein of Herpes Simplex Virus 1 Inhibits T Cell Signaling by RT Confining Linker for Activation of T Cells (LAT) Activation via TRAF6 RT Protein."; RL J. Biol. Chem. 290:15670-15678(2015). RN [64] RP INTERACTION WITH TICAM1. RX PubMed=25736436; DOI=10.15252/embr.201439637; RA Hu Y.H., Zhang Y., Jiang L.Q., Wang S., Lei C.Q., Sun M.S., Shu H.B., RA Liu Y.; RT "WDFY1 mediates TLR3/4 signaling by recruiting TRIF."; RL EMBO Rep. 16:447-455(2015). RN [65] RP INTERACTION WITH TANK; USP10 AND ZC3H12A, AND DEUBIQUITINATION BY USP10. RX PubMed=25861989; DOI=10.1074/jbc.m115.643767; RA Wang W., Huang X., Xin H.B., Fu M., Xue A., Wu Z.H.; RT "TRAF family member-associated NF-kappaB activator (TANK) inhibits RT genotoxic nuclear factor kappaB activation by facilitating deubiquitinase RT USP10-dependent deubiquitination of TRAF6 ligase."; RL J. Biol. Chem. 290:13372-13385(2015). RN [66] RP INTERACTION WITH TRIM13. RX PubMed=28087809; DOI=10.1124/mol.116.106716; RA Huang B., Baek S.H.; RT "Trim13 potentiates toll-like receptor 2-mediated nuclear factor kappaB RT activation via K29-linked polyubiquitination of tumor necrosis factor RT receptor-associated factor 6."; RL Mol. Pharmacol. 91:307-316(2017). RN [67] RP FUNCTION, AND INTERACTION WITH CRBN. RX PubMed=31620128; DOI=10.3389/fimmu.2019.02203; RA Kim M.J., Min Y., Shim J.H., Chun E., Lee K.Y.; RT "CRBN Is a Negative Regulator of Bactericidal Activity and Autophagy RT Activation Through Inhibiting the Ubiquitination of ECSIT and BECN1."; RL Front. Immunol. 10:2203-2203(2019). RN [68] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 347-506 OF APOPROTEIN AND IN RP COMPLEXES WITH TNFRSF5 AND TNFRSF11A PEPTIDES, FUNCTION, AND SUBUNIT. RX PubMed=12140561; DOI=10.1038/nature00888; RA Ye H., Arron J.R., Lamothe B., Cirilli M., Kobayashi T., Shevde N.K., RA Segal D., Dzivenu O.K., Vologodskaia M., Yim M., Du K., Singh S., RA Pike J.W., Darnay B.G., Choi Y., Wu H.; RT "Distinct molecular mechanism for initiating TRAF6 signalling."; RL Nature 418:443-447(2002). RN [69] RP STRUCTURE BY NMR OF 63-124 IN COMPLEX WITH ZINC IONS, AND INTERACTION WITH RP UBE2N. RX PubMed=17327397; DOI=10.1110/ps.062358007; RA Mercier P., Lewis M.J., Hau D.D., Saltibus L.F., Xiao W., Spyracopoulos L.; RT "Structure, interactions, and dynamics of the RING domain from human RT TRAF6."; RL Protein Sci. 16:602-614(2007). RN [70] RP STRUCTURE BY NMR OF 43-128. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the RING domain of the human TNF receptor-associated RT factor 6 protein."; RL Submitted (MAR-2008) to the PDB data bank. RN [71] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 50-211 IN COMPLEXES WITH ZINC IONS RP AND UBE2N, SUBUNIT, FUNCTION, AUTOUBIQUITINATION, MUTAGENESIS OF ASP-57; RP CYS-70; ILE-72; LEU-74; ARG-88; PHE-118; PHE-122 AND LYS-124, AND RP ZINC-FINGER. RX PubMed=19465916; DOI=10.1038/nsmb.1605; RA Yin Q., Lin S.C., Lamothe B., Lu M., Lo Y.C., Hura G., Zheng L., Rich R.L., RA Campos A.D., Myszka D.G., Lenardo M.J., Darnay B.G., Wu H.; RT "E2 interaction and dimerization in the crystal structure of TRAF6."; RL Nat. Struct. Mol. Biol. 16:658-666(2009). CC -!- FUNCTION: E3 ubiquitin ligase that, together with UBE2N and UBE2V1, CC mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains CC conjugated to proteins, such as ECSIT, IKBKG, IRAK1, AKT1 and AKT2 CC (PubMed:31620128, PubMed:11057907, PubMed:18347055, PubMed:19713527, CC PubMed:19465916). Also mediates ubiquitination of free/unanchored CC polyubiquitin chain that leads to MAP3K7 activation (PubMed:19675569). CC Leads to the activation of NF-kappa-B and JUN (PubMed:16378096, CC PubMed:17135271, PubMed:17703191). Seems to also play a role in CC dendritic cells (DCs) maturation and/or activation (By similarity). CC Represses c-Myb-mediated transactivation, in B-lymphocytes CC (PubMed:18093978, PubMed:18758450). Adapter protein that seems to play CC a role in signal transduction initiated via TNF receptor, IL-1 receptor CC and IL-17 receptor (PubMed:8837778, PubMed:19825828, PubMed:12140561). CC Regulates osteoclast differentiation by mediating the activation of CC adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L CC stimulation (By similarity). Together with MAP3K8, mediates CD40 CC signals that activate ERK in B-cells and macrophages, and thus may play CC a role in the regulation of immunoglobulin production (By similarity). CC Participates also in the TCR signaling by ubiquitinating LAT CC (PubMed:25907557, PubMed:23514740). {ECO:0000250|UniProtKB:P70196, CC ECO:0000269|PubMed:11057907, ECO:0000269|PubMed:12140561, CC ECO:0000269|PubMed:16378096, ECO:0000269|PubMed:17135271, CC ECO:0000269|PubMed:17703191, ECO:0000269|PubMed:18093978, CC ECO:0000269|PubMed:18347055, ECO:0000269|PubMed:18758450, CC ECO:0000269|PubMed:19465916, ECO:0000269|PubMed:19675569, CC ECO:0000269|PubMed:19713527, ECO:0000269|PubMed:19825828, CC ECO:0000269|PubMed:23514740, ECO:0000269|PubMed:25907557, CC ECO:0000269|PubMed:31620128, ECO:0000269|PubMed:8837778}. CC -!- CATALYTIC ACTIVITY: CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:23514740}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:23514740}. CC -!- SUBUNIT: Homotrimer. Homooligomer. N-terminal region is dimeric while CC C-terminal region is trimeric; maybe providing a mode of CC oligomerization. Upon IL1B treatment, forms a complex with PELI1, CC IRAK1, IRAK4 and MYD88; this complex recruits MAP3K7/TAK1, TAB1 and CC TAB2 to mediate NF-kappa-B activation. Direct binding of SMAD6 to PELI1 CC prevents the complex formation and hence negatively regulates IL1R-TLR CC signaling and eventually NF-kappa-B-mediated gene expression. Binds to CC TNFRSF5/CD40 and TNFRSF11A/RANK. Associates with NGFR, TNFRSF17, IRAK2, CC IRAK3, RIPK2, MAP3K1, MAP3K5, MAP3K14, CSK, TRAF, TRAF-interacting CC protein TRIP and TNF receptor associated protein TDP2. Interacts with CC IL17R. Interacts with SQSTM1 bridging NTRK1 and NGFR. Forms a ternary CC complex with SQSTM1 and PRKCZ (By similarity). Interacts with PELI2 and CC PELI3. Binds UBE2V1. Interacts with TAX1BP1; this interaction mediates CC deubiquitination of TRAF6 and inhibition of NF-kappa-B activation CC (PubMed:10920205, PubMed:17703191). Interacts with ZNF675. Interacts CC with ARRB1 and ARRB2. Interacts with MAP3K7 and TAB1/MAP3K7IP1; during CC IL-1 signaling. Interacts with UBE2N. Interacts with TGFBR1, HDAC1 and CC RANGAP1. Interacts with AKT1, AKT2 and AKT3. Interacts (via TRAF CC domains) with NUMBL (via C-terminal). Interacts with RBCK1. Interacts CC with LIMD1 (via LIM domains) (By similarity). Interacts with CC RSAD2/viperin (By similarity). Interacts (via C-terminus) with CC EIF2AK2/PKR (via the kinase catalytic domain) (By similarity). CC Interacts with ZFAND5. Interacts with IL1RL1. Interacts with TRAFD1. CC Interacts with AJUBA. Interacts with MAVS/IPS1. Interacts (via TRAF CC domains) with DYNC2I2 (via WD domains). Interacts with IFIT3 (via N- CC terminus). Interacts with TICAM2. Interacts with CARD14. Interacts with CC CD40 and MAP3K8; the interaction is required for ERK activation (By CC similarity). Interacts with TICAM1 and this interaction is enhanced in CC the presence of WDFY1 (PubMed:25736436). Interacts with TANK; this CC interaction increases in response to DNA damage (PubMed:25861989). CC Interacts with USP10; this interaction increases in response to DNA CC damage (PubMed:25861989). Interacts with ZC3H12A; this interaction CC increases in response to DNA damage and is stimulated by TANK CC (PubMed:25861989). Interacts with WDFY3 (By similarity). Interacts with CC TRIM13 (PubMed:28087809). Interacts with GPS2 (By similarity). CC Interacts (via C-terminus) with SASH1 (PubMed:23776175). Interacts with CC LRRC19 (PubMed:25026888). Interacts with IL17RA and TRAF3IP2. Interacts CC with TOMM70 (PubMed:20628368). Interacts with AMBRA1; interaction is CC required to mediate 'Lys-63'-linked ubiquitination of ULK1 CC (PubMed:23524951). Interacts with CRBN; this interaction inhibits TLR4- CC mediated signaling by preventing TRAF6-mediated ubiquitination of ECSIT CC (PubMed:31620128). {ECO:0000250|UniProtKB:P70196, CC ECO:0000269|PubMed:10920205, ECO:0000269|PubMed:17703191, CC ECO:0000269|PubMed:19825828, ECO:0000269|PubMed:20628368, CC ECO:0000269|PubMed:23524951, ECO:0000269|PubMed:23776175, CC ECO:0000269|PubMed:25026888, ECO:0000269|PubMed:25736436, CC ECO:0000269|PubMed:25861989, ECO:0000269|PubMed:28087809, CC ECO:0000269|PubMed:31620128}. CC -!- INTERACTION: CC Q9Y4K3; Q9C0C7-3: AMBRA1; NbExp=2; IntAct=EBI-359276, EBI-16042318; CC Q9Y4K3; Q8IWQ3-3: BRSK2; NbExp=3; IntAct=EBI-359276, EBI-13085322; CC Q9Y4K3; P25942: CD40; NbExp=2; IntAct=EBI-359276, EBI-525714; CC Q9Y4K3; Q9HAV5: EDA2R; NbExp=2; IntAct=EBI-359276, EBI-526033; CC Q9Y4K3; Q8WWZ3: EDARADD; NbExp=5; IntAct=EBI-359276, EBI-2949647; CC Q9Y4K3; P14778: IL1R1; NbExp=2; IntAct=EBI-359276, EBI-525905; CC Q9Y4K3; Q8NA54: IQUB; NbExp=3; IntAct=EBI-359276, EBI-10220600; CC Q9Y4K3; P51617: IRAK1; NbExp=3; IntAct=EBI-359276, EBI-358664; CC Q9Y4K3; O43187: IRAK2; NbExp=3; IntAct=EBI-359276, EBI-447733; CC Q9Y4K3; Q9Y616: IRAK3; NbExp=3; IntAct=EBI-359276, EBI-447690; CC Q9Y4K3; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-359276, EBI-739832; CC Q9Y4K3; Q9UDY8: MALT1; NbExp=5; IntAct=EBI-359276, EBI-1047372; CC Q9Y4K3; O43318: MAP3K7; NbExp=2; IntAct=EBI-359276, EBI-358684; CC Q9Y4K3; Q7Z434: MAVS; NbExp=4; IntAct=EBI-359276, EBI-995373; CC Q9Y4K3; P50222: MEOX2; NbExp=3; IntAct=EBI-359276, EBI-748397; CC Q9Y4K3; Q8N3F0: MTURN; NbExp=3; IntAct=EBI-359276, EBI-11980301; CC Q9Y4K3; Q96DC9: OTUB2; NbExp=3; IntAct=EBI-359276, EBI-746259; CC Q9Y4K3; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-359276, EBI-742388; CC Q9Y4K3; Q9UNA4: POLI; NbExp=3; IntAct=EBI-359276, EBI-741774; CC Q9Y4K3; P54725: RAD23A; NbExp=3; IntAct=EBI-359276, EBI-746453; CC Q9Y4K3; Q9BVN2-2: RUSC1; NbExp=2; IntAct=EBI-359276, EBI-6257338; CC Q9Y4K3; P04271: S100B; NbExp=3; IntAct=EBI-359276, EBI-458391; CC Q9Y4K3; Q9NYA1: SPHK1; NbExp=2; IntAct=EBI-359276, EBI-985303; CC Q9Y4K3; Q13501: SQSTM1; NbExp=4; IntAct=EBI-359276, EBI-307104; CC Q9Y4K3; P43405-2: SYK; NbExp=3; IntAct=EBI-359276, EBI-25892332; CC Q9Y4K3; Q9NYJ8: TAB2; NbExp=3; IntAct=EBI-359276, EBI-358708; CC Q9Y4K3; Q86VP1: TAX1BP1; NbExp=8; IntAct=EBI-359276, EBI-529518; CC Q9Y4K3; Q96CG3: TIFA; NbExp=6; IntAct=EBI-359276, EBI-740711; CC Q9Y4K3; Q9UKE5: TNIK; NbExp=3; IntAct=EBI-359276, EBI-1051794; CC Q9Y4K3; Q13077: TRAF1; NbExp=17; IntAct=EBI-359276, EBI-359224; CC Q9Y4K3; Q12933: TRAF2; NbExp=9; IntAct=EBI-359276, EBI-355744; CC Q9Y4K3; O43734: TRAF3IP2; NbExp=4; IntAct=EBI-359276, EBI-744798; CC Q9Y4K3; O00463: TRAF5; NbExp=15; IntAct=EBI-359276, EBI-523498; CC Q9Y4K3; Q9Y4K3: TRAF6; NbExp=11; IntAct=EBI-359276, EBI-359276; CC Q9Y4K3; P0CG48: UBC; NbExp=3; IntAct=EBI-359276, EBI-3390054; CC Q9Y4K3; P51668: UBE2D1; NbExp=2; IntAct=EBI-359276, EBI-743540; CC Q9Y4K3; P62837: UBE2D2; NbExp=5; IntAct=EBI-359276, EBI-347677; CC Q9Y4K3; P61077: UBE2D3; NbExp=2; IntAct=EBI-359276, EBI-348268; CC Q9Y4K3; P61088: UBE2N; NbExp=8; IntAct=EBI-359276, EBI-1052908; CC Q9Y4K3; Q9HAC8: UBTD1; NbExp=3; IntAct=EBI-359276, EBI-745871; CC Q9Y4K3; O94888: UBXN7; NbExp=3; IntAct=EBI-359276, EBI-1993627; CC Q9Y4K3; P09936: UCHL1; NbExp=3; IntAct=EBI-359276, EBI-714860; CC Q9Y4K3; O75385: ULK1; NbExp=2; IntAct=EBI-359276, EBI-908831; CC Q9Y4K3; O75604: USP2; NbExp=3; IntAct=EBI-359276, EBI-743272; CC Q9Y4K3; Q8N1B4: VPS52; NbExp=6; IntAct=EBI-359276, EBI-2799833; CC Q9Y4K3; P61964: WDR5; NbExp=2; IntAct=EBI-359276, EBI-540834; CC Q9Y4K3; P07947: YES1; NbExp=6; IntAct=EBI-359276, EBI-515331; CC Q9Y4K3; Q5VVQ6: YOD1; NbExp=5; IntAct=EBI-359276, EBI-2510804; CC Q9Y4K3; P24278: ZBTB25; NbExp=3; IntAct=EBI-359276, EBI-739899; CC Q9Y4K3; Q8TD23: ZNF675; NbExp=4; IntAct=EBI-359276, EBI-528190; CC Q9Y4K3; Q9UGI0: ZRANB1; NbExp=4; IntAct=EBI-359276, EBI-527853; CC Q9Y4K3; Q9QZH6: Ecsit; Xeno; NbExp=2; IntAct=EBI-359276, EBI-527020; CC Q9Y4K3; P07174: Ngfr; Xeno; NbExp=2; IntAct=EBI-359276, EBI-1038810; CC Q9Y4K3; P10221: UL37; Xeno; NbExp=3; IntAct=EBI-359276, EBI-6880600; CC Q9Y4K3; Q01220: VACWR178; Xeno; NbExp=2; IntAct=EBI-359276, EBI-3863691; CC Q9Y4K3; Q8V2D1; Xeno; NbExp=3; IntAct=EBI-359276, EBI-8622036; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18093978, CC ECO:0000269|PubMed:23514740, ECO:0000269|PubMed:24586164}. Cytoplasm, CC cell cortex {ECO:0000269|PubMed:18093978}. Nucleus CC {ECO:0000269|PubMed:18093978}. Lipid droplet CC {ECO:0000250|UniProtKB:P70196}. Note=Found in the nuclei of some CC aggressive B-cell lymphoma cell lines as well as in the nuclei of both CC resting and activated T- and B-lymphocytes. Found in punctate nuclear CC body protein complexes. Ubiquitination may occur in the cytoplasm and CC sumoylation in the nucleus. RSAD2/viperin recruits it to the lipid CC droplet (By similarity). {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, placenta, lung, liver, CC skeletal muscle, kidney and pancreas. CC -!- DOMAIN: The coiled coil domain mediates homo- and hetero- CC oligomerization. CC -!- DOMAIN: The MATH/TRAF domain binds to receptor cytoplasmic domains. CC -!- PTM: Sumoylated on Lys-124, Lys-142 and Lys-453 with SUMO1. CC {ECO:0000269|PubMed:18093978}. CC -!- PTM: Polyubiquitinated on Lys-124 by TRAF3IP2; after cell stimulation CC with IL17A (PubMed:19825828). Polyubiquitinated on Lys-124; after cell CC stimulation with IL1B or TGFB. This ligand-induced cell stimulation CC leads to dimerization/oligomerization of TRAF6 molecules, followed by CC auto-ubiquitination which involves UBE2N and UBE2V1 and leads to TRAF6 CC activation. This 'Lys-63' site-specific poly-ubiquitination appears to CC be associated with the activation of signaling molecules. Endogenous CC autoubiquitination occurs only for the cytoplasmic form. CC Deubiquitinated by USP10 in a TANK-dependent manner, leading to the CC negative regulation of NF-kappaB signaling upon DNA damage CC (PubMed:25861989). LRRC19 induces 'Lys-63' ubiquitination CC (PubMed:25026888). Ubiquitinated at Lys-319 by the SCF(FBXL2) complex, CC leading to its degradation by the proteasome (By similarity). CC {ECO:0000250|UniProtKB:P70196, ECO:0000269|PubMed:11460167, CC ECO:0000269|PubMed:17135271, ECO:0000269|PubMed:18093978, CC ECO:0000269|PubMed:18758450, ECO:0000269|PubMed:19465916, CC ECO:0000269|PubMed:19675569, ECO:0000269|PubMed:19825828, CC ECO:0000269|PubMed:25026888, ECO:0000269|PubMed:25861989}. CC -!- PTM: (Microbial infection) Deubiquitinated by Epstein-Barr virus BPLF1 CC on both 'Lys-48' and 'Lys-63'-linked ubiquitin chains; leading to NF- CC kappa-B signaling inhibition. {ECO:0000269|PubMed:24586164}. CC -!- SIMILARITY: Belongs to the TNF receptor-associated factor family. A CC subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/traf6/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U78798; AAB38751.1; -; mRNA. DR EMBL; AY228337; AAO38054.1; -; Genomic_DNA. DR EMBL; AK292978; BAF85667.1; -; mRNA. DR EMBL; AC009656; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC061999; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471064; EAW68119.1; -; Genomic_DNA. DR EMBL; CH471064; EAW68120.1; -; Genomic_DNA. DR EMBL; CH471064; EAW68122.1; -; Genomic_DNA. DR EMBL; BC031052; AAH31052.1; -; mRNA. DR CCDS; CCDS7901.1; -. DR PIR; S71821; S71821. DR RefSeq; NP_004611.1; NM_004620.3. DR RefSeq; NP_665802.1; NM_145803.2. DR PDB; 1LB4; X-ray; 2.40 A; A=348-504. DR PDB; 1LB5; X-ray; 2.40 A; A=347-504. DR PDB; 1LB6; X-ray; 1.80 A; A=347-504. DR PDB; 2ECI; NMR; -; A=50-128. DR PDB; 2JMD; NMR; -; A=67-124. DR PDB; 3HCS; X-ray; 2.20 A; A/B=50-211. DR PDB; 3HCT; X-ray; 2.10 A; A=50-159. DR PDB; 3HCU; X-ray; 2.60 A; A/C=50-159. DR PDB; 4Z8M; X-ray; 2.95 A; A/B=346-504. DR PDB; 5ZUJ; X-ray; 2.60 A; A=350-501. DR PDB; 6A33; X-ray; 2.10 A; A=350-501. DR PDB; 7L3L; X-ray; 2.80 A; B/D=52-158. DR PDB; 8HZ2; X-ray; 2.60 A; A/B=54-210. DR PDBsum; 1LB4; -. DR PDBsum; 1LB5; -. DR PDBsum; 1LB6; -. DR PDBsum; 2ECI; -. DR PDBsum; 2JMD; -. DR PDBsum; 3HCS; -. DR PDBsum; 3HCT; -. DR PDBsum; 3HCU; -. DR PDBsum; 4Z8M; -. DR PDBsum; 5ZUJ; -. DR PDBsum; 6A33; -. DR PDBsum; 7L3L; -. DR PDBsum; 8HZ2; -. DR AlphaFoldDB; Q9Y4K3; -. DR SMR; Q9Y4K3; -. DR BioGRID; 113041; 423. DR CORUM; Q9Y4K3; -. DR DIP; DIP-27515N; -. DR ELM; Q9Y4K3; -. DR IntAct; Q9Y4K3; 127. DR MINT; Q9Y4K3; -. DR STRING; 9606.ENSP00000433623; -. DR BindingDB; Q9Y4K3; -. DR ChEMBL; CHEMBL3588728; -. DR MoonDB; Q9Y4K3; Predicted. DR iPTMnet; Q9Y4K3; -. DR PhosphoSitePlus; Q9Y4K3; -. DR BioMuta; TRAF6; -. DR DMDM; 30580642; -. DR EPD; Q9Y4K3; -. DR jPOST; Q9Y4K3; -. DR MassIVE; Q9Y4K3; -. DR MaxQB; Q9Y4K3; -. DR PaxDb; 9606-ENSP00000433623; -. DR PeptideAtlas; Q9Y4K3; -. DR ProteomicsDB; 86225; -. DR Pumba; Q9Y4K3; -. DR Antibodypedia; 3895; 622 antibodies from 45 providers. DR DNASU; 7189; -. DR Ensembl; ENST00000348124.5; ENSP00000337853.5; ENSG00000175104.15. DR Ensembl; ENST00000526995.6; ENSP00000433623.1; ENSG00000175104.15. DR GeneID; 7189; -. DR KEGG; hsa:7189; -. DR MANE-Select; ENST00000526995.6; ENSP00000433623.1; NM_004620.4; NP_004611.1. DR UCSC; uc001mwq.3; human. DR AGR; HGNC:12036; -. DR CTD; 7189; -. DR DisGeNET; 7189; -. DR GeneCards; TRAF6; -. DR HGNC; HGNC:12036; TRAF6. DR HPA; ENSG00000175104; Low tissue specificity. DR MalaCards; TRAF6; -. DR MIM; 602355; gene. DR neXtProt; NX_Q9Y4K3; -. DR OpenTargets; ENSG00000175104; -. DR Orphanet; 1810; Autosomal dominant hypohidrotic ectodermal dysplasia. DR PharmGKB; PA36713; -. DR VEuPathDB; HostDB:ENSG00000175104; -. DR eggNOG; KOG0297; Eukaryota. DR GeneTree; ENSGT00940000155426; -. DR HOGENOM; CLU_021061_5_0_1; -. DR InParanoid; Q9Y4K3; -. DR OMA; FMHLQAL; -. DR OrthoDB; 2913784at2759; -. DR PhylomeDB; Q9Y4K3; -. DR TreeFam; TF321154; -. DR PathwayCommons; Q9Y4K3; -. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane. DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway. DR Reactome; R-HSA-168927; TICAM1, RIP1-mediated IKK complex recruitment. DR Reactome; R-HSA-193692; Regulated proteolysis of p75NTR. DR Reactome; R-HSA-202424; Downstream TCR signaling. DR Reactome; R-HSA-205043; NRIF signals cell death from the nucleus. DR Reactome; R-HSA-209543; p75NTR recruits signalling complexes. DR Reactome; R-HSA-209560; NF-kB is activated and signals survival. DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation. DR Reactome; R-HSA-445989; TAK1-dependent IKK and NF-kappa-B activation. DR Reactome; R-HSA-450302; activated TAK1 mediates p38 MAPK activation. DR Reactome; R-HSA-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1. DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases. DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-HSA-9014325; TICAM1,TRAF6-dependent induction of TAK1 complex. DR Reactome; R-HSA-9020702; Interleukin-1 signaling. DR Reactome; R-HSA-933541; TRAF6 mediated IRF7 activation. DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation. DR Reactome; R-HSA-937039; IRAK1 recruits IKK complex. DR Reactome; R-HSA-937041; IKK complex recruitment mediated by RIP1. DR Reactome; R-HSA-937042; IRAK2 mediated activation of TAK1 complex. DR Reactome; R-HSA-937072; TRAF6-mediated induction of TAK1 complex within TLR4 complex. DR Reactome; R-HSA-9645460; Alpha-protein kinase 1 signaling pathway. DR Reactome; R-HSA-9692916; SARS-CoV-1 activates/modulates innate immune responses. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR Reactome; R-HSA-975110; TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling. DR Reactome; R-HSA-975138; TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation. DR Reactome; R-HSA-975144; IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation. DR Reactome; R-HSA-975155; MyD88 dependent cascade initiated on endosome. DR Reactome; R-HSA-975163; IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation. DR Reactome; R-HSA-9758274; Regulation of NF-kappa B signaling. DR Reactome; R-HSA-975871; MyD88 cascade initiated on plasma membrane. DR SignaLink; Q9Y4K3; -. DR SIGNOR; Q9Y4K3; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 7189; 38 hits in 1201 CRISPR screens. DR ChiTaRS; TRAF6; human. DR EvolutionaryTrace; Q9Y4K3; -. DR GeneWiki; TRAF6; -. DR GenomeRNAi; 7189; -. DR Pharos; Q9Y4K3; Tbio. DR PRO; PR:Q9Y4K3; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q9Y4K3; Protein. DR Bgee; ENSG00000175104; Expressed in secondary oocyte and 158 other cell types or tissues. DR GO; GO:0035631; C:CD40 receptor complex; ISS:BHF-UCL. DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISS:BHF-UCL. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0010008; C:endosome membrane; TAS:Reactome. DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:UniProt. DR GO; GO:0005811; C:lipid droplet; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0043422; F:protein kinase B binding; IPI:UniProtKB. DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IEA:InterPro. DR GO; GO:0032813; F:tumor necrosis factor receptor superfamily binding; IBA:GO_Central. DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IDA:MGI. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; EXP:Reactome. DR GO; GO:0034450; F:ubiquitin-ubiquitin ligase activity; IDA:UniProt. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0007250; P:activation of NF-kappaB-inducing kinase activity; IMP:UniProtKB. DR GO; GO:0032147; P:activation of protein kinase activity; IDA:UniProtKB. DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; IEA:Ensembl. DR GO; GO:0140374; P:antiviral innate immune response; IDA:UniProt. DR GO; GO:0000045; P:autophagosome assembly; IDA:UniProt. DR GO; GO:0045453; P:bone resorption; IEA:Ensembl. DR GO; GO:0007249; P:canonical NF-kappaB signal transduction; IDA:UniProt. DR GO; GO:0071345; P:cellular response to cytokine stimulus; IMP:ARUK-UCL. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:MGI. DR GO; GO:0002753; P:cytoplasmic pattern recognition receptor signaling pathway; IDA:UniProt. DR GO; GO:0006974; P:DNA damage response; IEA:UniProtKB-KW. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0045087; P:innate immune response; IBA:GO_Central. DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; TAS:Reactome. DR GO; GO:0097400; P:interleukin-17-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0038173; P:interleukin-17A-mediated signaling pathway; IDA:UniProt. DR GO; GO:0038172; P:interleukin-33-mediated signaling pathway; IMP:UniProt. DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0043011; P:myeloid dendritic cell differentiation; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl. DR GO; GO:0038061; P:non-canonical NF-kappaB signal transduction; IDA:UniProt. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl. DR GO; GO:0001503; P:ossification; IEA:UniProtKB-KW. DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:UniProtKB. DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:BHF-UCL. DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IEA:Ensembl. DR GO; GO:0032743; P:positive regulation of interleukin-2 production; IMP:UniProtKB. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl. DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IDA:BHF-UCL. DR GO; GO:1904996; P:positive regulation of leukocyte adhesion to vascular endothelial cell; IMP:ARUK-UCL. DR GO; GO:0031666; P:positive regulation of lipopolysaccharide-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IDA:UniProtKB. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; NAS:BHF-UCL. DR GO; GO:0002726; P:positive regulation of T cell cytokine production; IMP:UniProtKB. DR GO; GO:0042102; P:positive regulation of T cell proliferation; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:2000679; P:positive regulation of transcription regulatory region DNA binding; IDA:BHF-UCL. DR GO; GO:0032481; P:positive regulation of type I interferon production; IEA:Ensembl. DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB. DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB. DR GO; GO:0042981; P:regulation of apoptotic process; IEA:InterPro. DR GO; GO:0043122; P:regulation of canonical NF-kappaB signal transduction; IBA:GO_Central. DR GO; GO:0002637; P:regulation of immunoglobulin production; IEA:Ensembl. DR GO; GO:0070555; P:response to interleukin-1; IDA:UniProtKB. DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; TAS:Reactome. DR GO; GO:0050852; P:T cell receptor signaling pathway; IDA:UniProt. DR GO; GO:0042088; P:T-helper 1 type immune response; IEA:Ensembl. DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome. DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IDA:UniProt. DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IBA:GO_Central. DR CDD; cd03776; MATH_TRAF6; 1. DR CDD; cd16643; mRING-HC-C3HC3D_TRAF6; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 3. DR IDEAL; IID00744; -. DR InterPro; IPR002083; MATH/TRAF_dom. DR InterPro; IPR012227; TNF_rcpt-assoc_TRAF_met. DR InterPro; IPR008974; TRAF-like. DR InterPro; IPR037309; TRAF6_MATH. DR InterPro; IPR027139; TRAF6_RING-HC. DR InterPro; IPR041310; TRAF6_Z2. DR InterPro; IPR049342; TRAF_MEP1_MATH_dom. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR InterPro; IPR001293; Znf_TRAF. DR PANTHER; PTHR10131; TNF RECEPTOR ASSOCIATED FACTOR; 1. DR PANTHER; PTHR10131:SF131; TNF RECEPTOR-ASSOCIATED FACTOR 6; 1. DR Pfam; PF21355; TRAF-mep_MATH; 1. DR Pfam; PF18048; TRAF6_Z2; 1. DR Pfam; PF13923; zf-C3HC4_2; 1. DR Pfam; PF02176; zf-TRAF; 1. DR PIRSF; PIRSF015614; TRAF; 1. DR SMART; SM00061; MATH; 1. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR SUPFAM; SSF49599; TRAF domain-like; 3. DR PROSITE; PS50144; MATH; 1. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. DR PROSITE; PS50145; ZF_TRAF; 2. DR Genevisible; Q9Y4K3; HS. PE 1: Evidence at protein level; KW 3D-structure; Coiled coil; Cytoplasm; DNA damage; Immunity; KW Isopeptide bond; Lipid droplet; Metal-binding; Nucleus; Osteogenesis; KW Reference proteome; Repeat; Transferase; Ubl conjugation; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..522 FT /note="TNF receptor-associated factor 6" FT /id="PRO_0000056407" FT DOMAIN 350..499 FT /note="MATH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00129" FT ZN_FING 70..109 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT ZN_FING 150..202 FT /note="TRAF-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00207" FT ZN_FING 203..259 FT /note="TRAF-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00207" FT REGION 1..354 FT /note="Interaction with TAX1BP1" FT /evidence="ECO:0000269|PubMed:10920205" FT REGION 355..522 FT /note="Interaction with TANK" FT /evidence="ECO:0000269|PubMed:25861989" FT COILED 288..348 FT /evidence="ECO:0000255" FT CROSSLNK 124 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT CROSSLNK 124 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin); alternate" FT /evidence="ECO:0000269|PubMed:17135271, FT ECO:0000269|PubMed:19825828" FT CROSSLNK 142 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:18093978" FT CROSSLNK 319 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P70196" FT CROSSLNK 453 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:18093978" FT MUTAGEN 57 FT /note="D->K: Loss of interaction with UBE2N." FT /evidence="ECO:0000269|PubMed:19465916" FT MUTAGEN 70 FT /note="C->A: Loss of ligase activity, autoubiquitination FT and signaling capacity." FT /evidence="ECO:0000269|PubMed:17135271, FT ECO:0000269|PubMed:19465916, ECO:0000269|PubMed:23514740" FT MUTAGEN 72 FT /note="I->D: Loss of interaction with UBE2N. Has no effect FT on TRAF3IP2-mediated 'Lys-63'-linked polyubiquitination." FT /evidence="ECO:0000269|PubMed:19465916, FT ECO:0000269|PubMed:19825828" FT MUTAGEN 74 FT /note="L->E,K: Loss of interaction with UBE2N." FT /evidence="ECO:0000269|PubMed:19465916" FT MUTAGEN 88 FT /note="R->A: Loss of TRAF6 homodimerization and impaired FT polyubiquitin synthesis. Loss of TRAF6 homodimerization and FT impaired polyubiquitin synthesis; when associated with FT A-122." FT /evidence="ECO:0000269|PubMed:19465916" FT MUTAGEN 118 FT /note="F->A: Loss of TRAF6 homodimerization and impaired FT polyubiquitin synthesis." FT /evidence="ECO:0000269|PubMed:19465916" FT MUTAGEN 118 FT /note="F->W: Partially impaired polyubiquitin synthesis." FT /evidence="ECO:0000269|PubMed:19465916" FT MUTAGEN 118 FT /note="F->Y: Partially impaired polyubiquitin synthesis." FT /evidence="ECO:0000269|PubMed:19465916" FT MUTAGEN 122 FT /note="F->A: Loss of TRAF6 homodimerization and partially FT impaired polyubiquitin synthesis. Loss of TRAF6 FT homodimerization and impaired polyubiquitin synthesis; when FT associated with A-88." FT /evidence="ECO:0000269|PubMed:19465916" FT MUTAGEN 124 FT /note="K->R: Loss of SUMO1-modification and c-myb-mediated FT transcriptional repressive activation. Loss of FT TRAF3IP2-mediated 'Lys-63'-linked polyubiquitination." FT /evidence="ECO:0000269|PubMed:17135271, FT ECO:0000269|PubMed:18093978, ECO:0000269|PubMed:19465916, FT ECO:0000269|PubMed:19825828" FT MUTAGEN 142 FT /note="K->R: Loss of SUMO1-modification and c-myb-mediated FT transcriptional repressive activation." FT /evidence="ECO:0000269|PubMed:18093978" FT MUTAGEN 453 FT /note="K->R: Loss of SUMO1-modification and c-myb-mediated FT transcriptional repressive activation." FT /evidence="ECO:0000269|PubMed:18093978" FT CONFLICT 12 FT /note="S -> F (in Ref. 6; AAH31052)" FT /evidence="ECO:0000305" FT STRAND 60..62 FT /evidence="ECO:0007829|PDB:3HCT" FT HELIX 66..68 FT /evidence="ECO:0007829|PDB:3HCT" FT TURN 71..73 FT /evidence="ECO:0007829|PDB:3HCT" FT STRAND 74..76 FT /evidence="ECO:0007829|PDB:7L3L" FT STRAND 78..82 FT /evidence="ECO:0007829|PDB:3HCT" FT TURN 84..86 FT /evidence="ECO:0007829|PDB:2ECI" FT STRAND 88..90 FT /evidence="ECO:0007829|PDB:3HCT" FT HELIX 91..101 FT /evidence="ECO:0007829|PDB:3HCT" FT TURN 106..108 FT /evidence="ECO:0007829|PDB:3HCT" FT HELIX 114..116 FT /evidence="ECO:0007829|PDB:3HCT" FT HELIX 121..128 FT /evidence="ECO:0007829|PDB:3HCT" FT STRAND 130..133 FT /evidence="ECO:0007829|PDB:3HCT" FT STRAND 135..138 FT /evidence="ECO:0007829|PDB:3HCU" FT STRAND 142..144 FT /evidence="ECO:0007829|PDB:3HCT" FT HELIX 145..147 FT /evidence="ECO:0007829|PDB:3HCT" FT HELIX 149..151 FT /evidence="ECO:0007829|PDB:3HCT" FT STRAND 153..155 FT /evidence="ECO:0007829|PDB:3HCT" FT STRAND 158..161 FT /evidence="ECO:0007829|PDB:3HCS" FT TURN 163..165 FT /evidence="ECO:0007829|PDB:3HCS" FT STRAND 168..170 FT /evidence="ECO:0007829|PDB:3HCS" FT HELIX 171..173 FT /evidence="ECO:0007829|PDB:3HCS" FT HELIX 174..180 FT /evidence="ECO:0007829|PDB:3HCS" FT STRAND 186..188 FT /evidence="ECO:0007829|PDB:3HCS" FT TURN 190..192 FT /evidence="ECO:0007829|PDB:3HCS" FT STRAND 195..197 FT /evidence="ECO:0007829|PDB:3HCS" FT HELIX 198..200 FT /evidence="ECO:0007829|PDB:3HCS" FT HELIX 201..205 FT /evidence="ECO:0007829|PDB:3HCS" FT STRAND 351..357 FT /evidence="ECO:0007829|PDB:1LB6" FT HELIX 360..368 FT /evidence="ECO:0007829|PDB:1LB6" FT STRAND 373..376 FT /evidence="ECO:0007829|PDB:1LB6" FT STRAND 380..385 FT /evidence="ECO:0007829|PDB:1LB6" FT STRAND 388..395 FT /evidence="ECO:0007829|PDB:1LB6" FT TURN 401..405 FT /evidence="ECO:0007829|PDB:1LB6" FT STRAND 406..414 FT /evidence="ECO:0007829|PDB:1LB6" FT HELIX 419..421 FT /evidence="ECO:0007829|PDB:1LB6" FT STRAND 428..434 FT /evidence="ECO:0007829|PDB:1LB6" FT HELIX 440..442 FT /evidence="ECO:0007829|PDB:6A33" FT STRAND 446..451 FT /evidence="ECO:0007829|PDB:1LB6" FT HELIX 457..459 FT /evidence="ECO:0007829|PDB:1LB6" FT STRAND 463..466 FT /evidence="ECO:0007829|PDB:1LB6" FT STRAND 468..478 FT /evidence="ECO:0007829|PDB:1LB6" FT HELIX 479..483 FT /evidence="ECO:0007829|PDB:1LB6" FT TURN 484..486 FT /evidence="ECO:0007829|PDB:6A33" FT STRAND 492..500 FT /evidence="ECO:0007829|PDB:1LB6" SQ SEQUENCE 522 AA; 59573 MW; 5AB9C255CCFEE749 CRC64; MSLLNCENSC GSSQSESDCC VAMASSCSAV TKDDSVGGTA STGNLSSSFM EEIQGYDVEF DPPLESKYEC PICLMALREA VQTPCGHRFC KACIIKSIRD AGHKCPVDNE ILLENQLFPD NFAKREILSL MVKCPNEGCL HKMELRHLED HQAHCEFALM DCPQCQRPFQ KFHINIHILK DCPRRQVSCD NCAASMAFED KEIHDQNCPL ANVICEYCNT ILIREQMPNH YDLDCPTAPI PCTFSTFGCH EKMQRNHLAR HLQENTQSHM RMLAQAVHSL SVIPDSGYIS EVRNFQETIH QLEGRLVRQD HQIRELTAKM ETQSMYVSEL KRTIRTLEDK VAEIEAQQCN GIYIWKIGNF GMHLKCQEEE KPVVIHSPGF YTGKPGYKLC MRLHLQLPTA QRCANYISLF VHTMQGEYDS HLPWPFQGTI RLTILDQSEA PVRQNHEEIM DAKPELLAFQ RPTIPRNPKG FGYVTFMHLE ALRQRTFIKD DTLLVRCEVS TRFDMGSLRR EGFQPRSTDA GV //