+データを開く
-基本情報
登録情報 | データベース: SASBDB / ID: SASDBS3 |
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試料 | Wild type RNF8 complexed with Ubc13 (C87K, K92A mutant) and Mms2: conjugated to Ubiquitin
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機能・相同性 | 機能・相同性情報 error-free postreplication DNA repair / UBC13-MMS2 complex / ubiquitin conjugating enzyme complex / ubiquitin-protein transferase activator activity / sperm DNA condensation / positive regulation of protein K63-linked ubiquitination / DNA double-strand break processing / protein K6-linked ubiquitination / isotype switching / postreplication repair ...error-free postreplication DNA repair / UBC13-MMS2 complex / ubiquitin conjugating enzyme complex / ubiquitin-protein transferase activator activity / sperm DNA condensation / positive regulation of protein K63-linked ubiquitination / DNA double-strand break processing / protein K6-linked ubiquitination / isotype switching / postreplication repair / positive regulation of intracellular signal transduction / positive regulation of double-strand break repair / DNA repair-dependent chromatin remodeling / response to ionizing radiation / E2 ubiquitin-conjugating enzyme / negative regulation of transcription elongation by RNA polymerase II / ubiquitin conjugating enzyme activity / protein K63-linked ubiquitination / positive regulation of double-strand break repair via homologous recombination / signal transduction in response to DNA damage / protein autoubiquitination / protein K48-linked ubiquitination / interstrand cross-link repair / regulation of DNA repair / ubiquitin ligase complex / antiviral innate immune response / Maturation of protein E / negative regulation of TORC1 signaling / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / FLT3 signaling by CBL mutants / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Prevention of phagosomal-lysosomal fusion / Glycogen synthesis / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / Endosomal Sorting Complex Required For Transport (ESCRT) / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / TICAM1,TRAF6-dependent induction of TAK1 complex / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Regulation of FZD by ubiquitination / TICAM1-dependent activation of IRF3/IRF7 / NOTCH2 Activation and Transmission of Signal to the Nucleus / p75NTR recruits signalling complexes / APC/C:Cdc20 mediated degradation of Cyclin B / VLDLR internalisation and degradation / Downregulation of ERBB4 signaling / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / APC-Cdc20 mediated degradation of Nek2A / positive regulation of DNA repair / Regulation of innate immune responses to cytosolic DNA / NF-kB is activated and signals survival / InlA-mediated entry of Listeria monocytogenes into host cells / epigenetic regulation of gene expression / Regulation of pyruvate metabolism / Downregulation of ERBB2:ERBB3 signaling / NRIF signals cell death from the nucleus / Pexophagy / Activated NOTCH1 Transmits Signal to the Nucleus / Regulation of PTEN localization / Regulation of BACH1 activity / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / TICAM1, RIP1-mediated IKK complex recruitment / Translesion synthesis by REV1 / MAP3K8 (TPL2)-dependent MAPK1/3 activation / Translesion synthesis by POLK / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Downregulation of TGF-beta receptor signaling / Translesion synthesis by POLI / IKK complex recruitment mediated by RIP1 / Regulation of activated PAK-2p34 by proteasome mediated degradation / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / Gap-filling DNA repair synthesis and ligation in GG-NER / Josephin domain DUBs / InlB-mediated entry of Listeria monocytogenes into host cell / PINK1-PRKN Mediated Mitophagy / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / ubiquitin binding / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / TNFR1-induced NF-kappa-B signaling pathway / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / SCF-beta-TrCP mediated degradation of Emi1 / Regulation of NF-kappa B signaling / Asymmetric localization of PCP proteins / TCF dependent signaling in response to WNT / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / AUF1 (hnRNP D0) binds and destabilizes mRNA / activated TAK1 mediates p38 MAPK activation / TNFR2 non-canonical NF-kB pathway / Regulation of signaling by CBL 類似検索 - 分子機能 |
生物種 | Homo sapiens (ヒト) |
引用 | ジャーナル: J Biol Chem / 年: 2016 タイトル: RNF8 E3 Ubiquitin Ligase Stimulates Ubc13 E2 Conjugating Activity That Is Essential for DNA Double Strand Break Signaling and BRCA1 Tumor Suppressor Recruitment. 著者: Curtis D Hodge / Ismail H Ismail / Ross A Edwards / Greg L Hura / Andrew T Xiao / John A Tainer / Michael J Hendzel / J N Mark Glover / 要旨: DNA double strand break (DSB) responses depend on the sequential actions of the E3 ubiquitin ligases RNF8 and RNF168 plus E2 ubiquitin-conjugating enzyme Ubc13 to specifically generate histone Lys-63- ...DNA double strand break (DSB) responses depend on the sequential actions of the E3 ubiquitin ligases RNF8 and RNF168 plus E2 ubiquitin-conjugating enzyme Ubc13 to specifically generate histone Lys-63-linked ubiquitin chains in DSB signaling. Here, we defined the activated RNF8-Ubc13∼ubiquitin complex by x-ray crystallography and its functional solution conformations by x-ray scattering, as tested by separation-of-function mutations imaged in cells by immunofluorescence. The collective results show that the RING E3 RNF8 targets E2 Ubc13 to DSB sites and plays a critical role in damage signaling by stimulating polyubiquitination through modulating conformations of ubiquitin covalently linked to the Ubc13 active site. Structure-guided separation-of-function mutations show that the RNF8 E2 stimulating activity is essential for DSB signaling in mammalian cells and is necessary for downstream recruitment of 53BP1 and BRCA1. Chromatin-targeted RNF168 rescues 53BP1 recruitment involved in non-homologous end joining but not BRCA1 recruitment for homologous recombination. These findings suggest an allosteric approach to targeting the ubiquitin-docking cleft at the E2-E3 interface for possible interventions in cancer and chronic inflammation, and moreover, they establish an independent RNF8 role in BRCA1 recruitment. |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-モデル
モデル #466 | タイプ: mix / ソフトウェア: MES-FoXS / ダミー原子の半径: 1.90 A Omokage検索でこの集合体の類似形状データを探す (詳細) |
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モデル #467 | タイプ: mix / ソフトウェア: MES-FoXS / ダミー原子の半径: 1.90 A Omokage検索でこの集合体の類似形状データを探す (詳細) |
モデル #468 | タイプ: mix / ソフトウェア: MES-FoXS / ダミー原子の半径: 1.90 A Omokage検索でこの集合体の類似形状データを探す (詳細) |
モデル #469 | タイプ: mix / ソフトウェア: MES-FoXS (MES-FoXS) / ダミー原子の半径: 1.90 A Omokage検索でこの集合体の類似形状データを探す (詳細) |
モデル #470 | タイプ: mix / ソフトウェア: MES-FoXS / ダミー原子の半径: 1.90 A Omokage検索でこの集合体の類似形状データを探す (詳細) |
-試料
試料 | 名称: Wild type RNF8 complexed with Ubc13 (C87K, K92A mutant) and Mms2: conjugated to Ubiquitin Entity id: 304 / 305 / 306 / 307 |
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バッファ | 名称: HEPES / 濃度: 20.00 mM / pH: 6.8 / 組成: 200 mM NaCl, 0.01 mM, ZnSO4, and 1 mM DTT |
要素 #304 | 名称: RNF8 / タイプ: protein / 記述: E3 ubiquitin-protein ligase RNF8 / 分子量: 17.618 / 分子数: 2 / 由来: Homo sapiens / 参照: UniProt: O76064 配列: GPLGSPEFQE HWALMEELNR SKKDFEAIIQ AKNKELEQTK EEKEKMQAQK EEVLSHMNDV LENELQCIIC SEYFIEAVTL NCAHSFCSYC INEWMKRKIE CPICRKDIKS KTYSLVLDNC INKMVNNLSS EVKERRIVLI RERKAKRLF |
要素 #305 | 名称: Ubc13 - C87K, K92A / タイプ: protein 記述: Ubiquitin-conjugating enzyme E2 N double mutant (C87K, K92A) 分子量: 17.89 / 分子数: 2 / 由来: Homo sapiens / 参照: UniProt: P61088 配列: GPLGSPEFMA GLPRRIIKET QRLLAEPVPG IKAEPDESNA RYFHVVIAGP QDSPFEGGTF KLELFLPEEY PMAAPKVRFM TKIYHPNVDK LGRIKLDILA DKWSPALQIR TVLLSIQALL SAPNPDDPLA NDVAEQWKTN EAQAIETARA WTRLYAMNNI |
要素 #306 | 名称: UBC / タイプ: protein / 記述: Polyubiquitin-C / 分子量: 8.565 / 分子数: 2 / 由来: Homo sapiens / 参照: UniProt: P0CG48 配列: MQIFVKTLTG KTITLEVEPS DTIENVKAKI QDKEGIPPDQ QRLIFAGKQL EDGRTLSDYN IQKESTLHLV LRLRGG |
要素 #307 | 名称: Mms2 (UBE2V2) / タイプ: protein / 記述: Ubiquitin-conjugating enzyme E2 variant 2 / 分子量: 17.147 / 分子数: 2 / 由来: Homo sapiens / 参照: UniProt: Q15819 配列: GPLGSPEFMA VSTGVKVPRN FRLLEELEEG QKGVGDGTVS WGLEDDEDMT LTRWTGMIIG PPRTNYENRI YSLKVECGPK YPEAPPSVRF VTKINMNGIN NSSGMVDARS IPVLAKWQNS YSIKVVLQEL RRLMMSKENM KLPQPPEGQT YNN |
-実験情報
ビーム | 設備名称: Advanced Light Source (ALS) 12.3.1 (SIBYLS) / 地域: Berkeley, CA / 国: USA / 線源: X-ray synchrotron / 波長: 0.103 Å | ||||||||||||||||||||||||||||||
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検出器 | 名称: Pilatus 2M | ||||||||||||||||||||||||||||||
スキャン | タイトル: RNF8/Ubc13 (C87K K92A)/Mms2/Ubiquitin complex / 測定日: 2015年9月8日 / 単位: 1/nm /
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距離分布関数 P(R) | ソフトウェア P(R): GNOM 5.0 / ポイント数: 186 /
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結果 | カーブのタイプ: single_conc /
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