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Yorodumi- SASDBS3: Wild type RNF8 complexed with Ubc13 (C87K, K92A mutant) and Mms2:... -
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-Basic information
Entry | Database: SASBDB / ID: SASDBS3 |
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Sample | Wild type RNF8 complexed with Ubc13 (C87K, K92A mutant) and Mms2: conjugated to Ubiquitin
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Function / homology | Function and homology information error-free postreplication DNA repair / : / UBC13-MMS2 complex / ubiquitin conjugating enzyme complex / sperm DNA condensation / ubiquitin-protein transferase activator activity / positive regulation of protein K63-linked ubiquitination / DNA double-strand break processing / protein K6-linked ubiquitination / isotype switching ...error-free postreplication DNA repair / : / UBC13-MMS2 complex / ubiquitin conjugating enzyme complex / sperm DNA condensation / ubiquitin-protein transferase activator activity / positive regulation of protein K63-linked ubiquitination / DNA double-strand break processing / protein K6-linked ubiquitination / isotype switching / postreplication repair / positive regulation of double-strand break repair / DNA repair-dependent chromatin remodeling / positive regulation of intracellular signal transduction / E2 ubiquitin-conjugating enzyme / response to ionizing radiation / cell division site / negative regulation of transcription elongation by RNA polymerase II / ubiquitin conjugating enzyme activity / protein K63-linked ubiquitination / antiviral innate immune response / positive regulation of double-strand break repair via homologous recombination / signal transduction in response to DNA damage / protein autoubiquitination / protein K48-linked ubiquitination / regulation of DNA repair / interstrand cross-link repair / epigenetic regulation of gene expression / ubiquitin ligase complex / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / negative regulation of TORC1 signaling / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / positive regulation of DNA repair / Downregulation of ERBB4 signaling / APC-Cdc20 mediated degradation of Nek2A / PINK1-PRKN Mediated Mitophagy / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / Pexophagy / Regulation of innate immune responses to cytosolic DNA / InlA-mediated entry of Listeria monocytogenes into host cells / VLDLR internalisation and degradation / Downregulation of ERBB2:ERBB3 signaling / NF-kB is activated and signals survival / NRIF signals cell death from the nucleus / Regulation of PTEN localization / Activated NOTCH1 Transmits Signal to the Nucleus / Regulation of BACH1 activity / Translesion synthesis by REV1 / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by POLK / MAP3K8 (TPL2)-dependent MAPK1/3 activation / TICAM1, RIP1-mediated IKK complex recruitment / Downregulation of TGF-beta receptor signaling / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Translesion synthesis by POLI / Gap-filling DNA repair synthesis and ligation in GG-NER / Josephin domain DUBs / Regulation of activated PAK-2p34 by proteasome mediated degradation / InlB-mediated entry of Listeria monocytogenes into host cell / IKK complex recruitment mediated by RIP1 / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Autodegradation of Cdh1 by Cdh1:APC/C / TNFR1-induced NF-kappa-B signaling pathway / APC/C:Cdc20 mediated degradation of Securin / ubiquitin binding / Asymmetric localization of PCP proteins / TCF dependent signaling in response to WNT / SCF-beta-TrCP mediated degradation of Emi1 / AUF1 (hnRNP D0) binds and destabilizes mRNA / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / Regulation of NF-kappa B signaling / TNFR2 non-canonical NF-kB pathway / activated TAK1 mediates p38 MAPK activation / Assembly of the pre-replicative complex / Vpu mediated degradation of CD4 Similarity search - Function |
Biological species | Homo sapiens (human) |
Citation | Journal: J Biol Chem / Year: 2016 Title: RNF8 E3 Ubiquitin Ligase Stimulates Ubc13 E2 Conjugating Activity That Is Essential for DNA Double Strand Break Signaling and BRCA1 Tumor Suppressor Recruitment. Authors: 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 / Abstract: 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. |
Contact author |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Data source
SASBDB page | SASDBS3 |
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-Related structure data
-External links
Related items in Molecule of the Month |
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-Models
Model #466 | Type: mix / Software: MES-FoXS / Radius of dummy atoms: 1.90 A Search similar-shape structures of this assembly by Omokage search (details) |
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Model #467 | Type: mix / Software: MES-FoXS / Radius of dummy atoms: 1.90 A Search similar-shape structures of this assembly by Omokage search (details) |
Model #468 | Type: mix / Software: MES-FoXS / Radius of dummy atoms: 1.90 A Search similar-shape structures of this assembly by Omokage search (details) |
Model #469 | Type: mix / Software: MES-FoXS (MES-FoXS) / Radius of dummy atoms: 1.90 A Search similar-shape structures of this assembly by Omokage search (details) |
Model #470 | Type: mix / Software: MES-FoXS / Radius of dummy atoms: 1.90 A Search similar-shape structures of this assembly by Omokage search (details) |
-Sample
Sample | Name: Wild type RNF8 complexed with Ubc13 (C87K, K92A mutant) and Mms2: conjugated to Ubiquitin Entity id: 304 / 305 / 306 / 307 |
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Buffer | Name: HEPES / Concentration: 20.00 mM / pH: 6.8 / Composition: 200 mM NaCl, 0.01 mM, ZnSO4, and 1 mM DTT |
Entity #304 | Name: RNF8 / Type: protein / Description: E3 ubiquitin-protein ligase RNF8 / Formula weight: 17.618 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: O76064 Sequence: GPLGSPEFQE HWALMEELNR SKKDFEAIIQ AKNKELEQTK EEKEKMQAQK EEVLSHMNDV LENELQCIIC SEYFIEAVTL NCAHSFCSYC INEWMKRKIE CPICRKDIKS KTYSLVLDNC INKMVNNLSS EVKERRIVLI RERKAKRLF |
Entity #305 | Name: Ubc13 - C87K, K92A / Type: protein Description: Ubiquitin-conjugating enzyme E2 N double mutant (C87K, K92A) Formula weight: 17.89 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: P61088 Sequence: GPLGSPEFMA GLPRRIIKET QRLLAEPVPG IKAEPDESNA RYFHVVIAGP QDSPFEGGTF KLELFLPEEY PMAAPKVRFM TKIYHPNVDK LGRIKLDILA DKWSPALQIR TVLLSIQALL SAPNPDDPLA NDVAEQWKTN EAQAIETARA WTRLYAMNNI |
Entity #306 | Name: UBC / Type: protein / Description: Polyubiquitin-C / Formula weight: 8.565 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: P0CG48 Sequence: MQIFVKTLTG KTITLEVEPS DTIENVKAKI QDKEGIPPDQ QRLIFAGKQL EDGRTLSDYN IQKESTLHLV LRLRGG |
Entity #307 | Name: Mms2 (UBE2V2) / Type: protein / Description: Ubiquitin-conjugating enzyme E2 variant 2 / Formula weight: 17.147 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: Q15819 Sequence: GPLGSPEFMA VSTGVKVPRN FRLLEELEEG QKGVGDGTVS WGLEDDEDMT LTRWTGMIIG PPRTNYENRI YSLKVECGPK YPEAPPSVRF VTKINMNGIN NSSGMVDARS IPVLAKWQNS YSIKVVLQEL RRLMMSKENM KLPQPPEGQT YNN |
-Experimental information
Beam | Instrument name: Advanced Light Source (ALS) 12.3.1 (SIBYLS) City: Berkeley, CA / 国: USA / Type of source: X-ray synchrotron / Wavelength: 0.103 Å | ||||||||||||||||||||||||||||||
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Detector | Name: Pilatus 2M | ||||||||||||||||||||||||||||||
Scan | Title: RNF8/Ubc13 (C87K K92A)/Mms2/Ubiquitin complex / Measurement date: Sep 8, 2015 / Unit: 1/nm /
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Distance distribution function P(R) | Sofotware P(R): GNOM 5.0 / Number of points: 186 /
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Result | Type of curve: single_conc /
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