TRAF6_HUMAN
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 03-AUG-2022, entry version 235.
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 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 [47]
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 [48]
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 [49]
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 [50]
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 [51]
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 [52]
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 [53]
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 [54]
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 [55]
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 [56]
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 [57]
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 [58]
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 [59]
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 [60]
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 [61]
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 [62]
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 [63]
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 [64]
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 [65]
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 [66]
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 IKBKG, IRAK1, AKT1 and AKT2
CC (PubMed:11057907, PubMed:18347055, PubMed:19713527, PubMed:19465916).
CC Also mediates ubiquitination of free/unanchored polyubiquitin chain
CC that leads to MAP3K7 activation (PubMed:19675569). Leads to the
CC activation of NF-kappa-B and JUN (PubMed:16378096, PubMed:17135271).
CC Seems to also play a role in dendritic cells (DCs) maturation and/or
CC activation (By similarity). Represses c-Myb-mediated transactivation,
CC in B-lymphocytes (PubMed:18093978, PubMed:18758450). Adapter protein
CC that seems to play a role in signal transduction initiated via TNF
CC receptor, IL-1 receptor and IL-17 receptor (PubMed:8837778,
CC PubMed:19825828, PubMed:12140561). Regulates osteoclast differentiation
CC by mediating the activation of adapter protein complex 1 (AP-1) and NF-
CC kappa-B, in response to RANK-L stimulation (By similarity). Together
CC with MAP3K8, mediates CD40 signals that activate ERK in B-cells and
CC macrophages, and thus may play a role in the regulation of
CC immunoglobulin production (By similarity).
CC {ECO:0000250|UniProtKB:P70196, ECO:0000269|PubMed:11057907,
CC ECO:0000269|PubMed:12140561, ECO:0000269|PubMed:16378096,
CC ECO:0000269|PubMed:17135271, 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: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;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
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. Interacts with ZNF675.
CC Interacts with ARRB1 and ARRB2. Interacts with MAP3K7 and
CC TAB1/MAP3K7IP1; during IL-1 signaling. Interacts with UBE2N. Interacts
CC with TGFBR1, HDAC1 and RANGAP1. Interacts with AKT1, AKT2 and AKT3.
CC Interacts (via TRAF domains) with NUMBL (via C-terminal). Interacts
CC with RBCK1. Interacts with LIMD1 (via LIM domains) (By similarity).
CC Interacts with RSAD2/viperin (By similarity). Interacts (via C-
CC terminus) with EIF2AK2/PKR (via the kinase catalytic domain) (By
CC similarity). Interacts with ZFAND5. Interacts with IL1RL1. Interacts
CC with TRAFD1. Interacts with AJUBA. Interacts with MAVS/IPS1. Interacts
CC (via TRAF domains) with DYNC2I2 (via WD domains). Interacts with IFIT3
CC (via N-terminus). Interacts with TICAM2. Interacts with CARD14.
CC Interacts with CD40 and MAP3K8; the interaction is required for ERK
CC activation (By similarity). Interacts with TICAM1 and this interaction
CC is enhanced in the presence of WDFY1 (PubMed:25736436). Interacts with
CC TANK; this interaction increases in response to DNA damage
CC (PubMed:25861989). Interacts with USP10; this interaction increases in
CC response to DNA damage (PubMed:25861989). Interacts with ZC3H12A; this
CC interaction increases in response to DNA damage and is stimulated by
CC TANK (PubMed:25861989). Interacts with WDFY3 (By similarity). Interacts
CC with 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). {ECO:0000250|UniProtKB:P70196,
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 -!- 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=2; 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 Cytoplasm, 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). {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 -!- 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/";
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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 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 AlphaFoldDB; Q9Y4K3; -.
DR SMR; Q9Y4K3; -.
DR BioGRID; 113041; 391.
DR CORUM; Q9Y4K3; -.
DR DIP; DIP-27515N; -.
DR ELM; Q9Y4K3; -.
DR IntAct; Q9Y4K3; 124.
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; Q9Y4K3; -.
DR PeptideAtlas; Q9Y4K3; -.
DR PRIDE; Q9Y4K3; -.
DR ProteomicsDB; 86225; -.
DR Antibodypedia; 3895; 556 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 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; WMQKNNQ; -.
DR OrthoDB; 918518at2759; -.
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-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-975871; MyD88 cascade initiated on plasma membrane.
DR SignaLink; Q9Y4K3; -.
DR SIGNOR; Q9Y4K3; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 7189; 35 hits in 1121 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 157 other tissues.
DR Genevisible; Q9Y4K3; HS.
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: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:0031435; F:mitogen-activated protein kinase kinase kinase binding; IPI:UniProtKB.
DR GO; GO:0043422; F:protein kinase B binding; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB.
DR GO; GO:0031996; F:thioesterase binding; IPI:UniProtKB.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IPI:UniProtKB.
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; IPI:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; EXP:Reactome.
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:0045453; P:bone resorption; IEA:Ensembl.
DR GO; GO:0048468; P:cell development; IEA:Ensembl.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IMP:ARUK-UCL.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEA:UniProtKB-KW.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:MGI.
DR GO; GO:0002753; P:cytoplasmic pattern recognition receptor signaling pathway; TAS:Reactome.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; TAS:Reactome.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0097400; P:interleukin-17-mediated signaling pathway; IEA:Ensembl.
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:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
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:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:BHF-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
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:0046330; P:positive regulation of JNK cascade; IBA:GO_Central.
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:1901224; P:positive regulation of NIK/NF-kappaB signaling; IMP:ARUK-UCL.
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: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 I-kappaB kinase/NF-kappaB signaling; 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; IMP:UniProtKB.
DR GO; GO:0042088; P:T-helper 1 type immune response; IEA:Ensembl.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IBA:GO_Central.
DR CDD; cd03776; MATH_TRAF6; 1.
DR Gene3D; 2.60.210.10; -; 1.
DR Gene3D; 3.30.40.10; -; 3.
DR InterPro; IPR002083; MATH/TRAF_dom.
DR InterPro; IPR043211; TNF_rcpt-assoc_TRAF.
DR InterPro; IPR012227; TNF_rcpt-assoc_TRAF_met.
DR InterPro; IPR008974; TRAF-like.
DR InterPro; IPR027139; TRAF6.
DR InterPro; IPR037309; TRAF6_MATH.
DR InterPro; IPR041310; TRAF6_Z2.
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; PTHR10131; 1.
DR PANTHER; PTHR10131:SF131; PTHR10131:SF131; 1.
DR Pfam; PF18048; TRAF6_Z2; 1.
DR Pfam; PF02176; zf-TRAF; 1.
DR PIRSF; PIRSF015614; TRAF; 1.
DR SMART; SM00061; MATH; 1.
DR SMART; SM00184; RING; 1.
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.
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 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"
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 A-
FT 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 TRAF3IP2-
FT 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
