[English] 日本語
Yorodumi
- PDB-9sqy: Cryo-EM structure of the ARISC(E33A)-RAP80:K63-Ub7 complex (Compo... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9sqy
TitleCryo-EM structure of the ARISC(E33A)-RAP80:K63-Ub7 complex (Composite map)
Components
  • (BRCA1-A complex subunit ...) x 2
  • (BRISC and BRCA1-A complex member ...) x 2
  • Lys-63-specific deubiquitinase BRCC36
  • Ubiquitin
KeywordsHYDROLASE / Deubiquitylating enzymes / JAMM/MPN family / ubiquitin chains / DNA damage repair
Function / homology
Function and homology information


peroxisome signal sequence receptor activity / BRISC complex / Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases / response to vitamin B6 / BRCA1-A complex / attachment of spindle microtubules to kinetochore / ubiquitin-modified histone reader activity / nuclear ubiquitin ligase complex / tumor necrosis factor receptor binding / mitotic G2/M transition checkpoint ...peroxisome signal sequence receptor activity / BRISC complex / Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases / response to vitamin B6 / BRCA1-A complex / attachment of spindle microtubules to kinetochore / ubiquitin-modified histone reader activity / nuclear ubiquitin ligase complex / tumor necrosis factor receptor binding / mitotic G2/M transition checkpoint / response to X-ray / K63-linked polyubiquitin modification-dependent protein binding / metal-dependent deubiquitinase activity / response to ionizing radiation / regulation of DNA damage checkpoint / protein K63-linked deubiquitination / K63-linked deubiquitinase activity / mitotic G2 DNA damage checkpoint signaling / polyubiquitin modification-dependent protein binding / DNA repair-dependent chromatin remodeling / mitotic spindle assembly / positive regulation of NLRP3 inflammasome complex assembly / protein deubiquitination / enzyme regulator activity / ubiquitin ligase complex / Maturation of protein E / Maturation of protein E / regulation of DNA repair / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Prevention of phagosomal-lysosomal fusion / Endosomal Sorting Complex Required For Transport (ESCRT) / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / Negative regulation of FLT3 / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / Constitutive Signaling by NOTCH1 HD Domain Mutants / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1,TRAF6-dependent induction of TAK1 complex / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / positive regulation of DNA repair / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / Downregulation of ERBB4 signaling / APC-Cdc20 mediated degradation of Nek2A / Regulation of FZD by ubiquitination / p75NTR recruits signalling complexes / InlA-mediated entry of Listeria monocytogenes into host cells / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / NF-kB is activated and signals survival / TRAF6-mediated induction of TAK1 complex within TLR4 complex / Regulation of pyruvate metabolism / Pexophagy / PD-L1(CD274) glycosylation and translocation to plasma membrane / NRIF signals cell death from the nucleus / Downregulation of ERBB2:ERBB3 signaling / Regulation of PTEN localization / Regulation of innate immune responses to cytosolic DNA / cellular response to ionizing radiation / VLDLR internalisation and degradation / Activated NOTCH1 Transmits Signal to the Nucleus / Translesion synthesis by REV1 / TICAM1, RIP1-mediated IKK complex recruitment / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA / Translesion synthesis by POLK / Regulation of BACH1 activity / InlB-mediated entry of Listeria monocytogenes into host cell / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / MAP3K8 (TPL2)-dependent MAPK1/3 activation / Translesion synthesis by POLI / Downregulation of TGF-beta receptor signaling / Josephin domain DUBs / Gap-filling DNA repair synthesis and ligation in GG-NER / IKK complex recruitment mediated by RIP1 / PINK1-PRKN Mediated Mitophagy / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / TNFR1-induced NF-kappa-B signaling pathway / Regulation of activated PAK-2p34 by proteasome mediated degradation / TCF dependent signaling in response to WNT / activated TAK1 mediates p38 MAPK activation / Regulation of NF-kappa B signaling / Maturation of DENV proteins / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / NOTCH3 Activation and Transmission of Signal to the Nucleus / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Regulation of signaling by CBL / Negative regulators of DDX58/IFIH1 signaling / Asymmetric localization of PCP proteins / Negative regulation of FGFR3 signaling / Ubiquitin-dependent degradation of Cyclin D
Similarity search - Function
BRCA1-A complex subunit RAP80 / RAP80, N-terminal / RAP80 N-terminal ubiquitin interaction motif / BRISC and BRCA1-A complex member 1 / FAM175 family, BRCA1-A complex, Abraxas 1 subunit / BRCA1-A complex subunit BRE / Brain and reproductive organ-expressed protein (BRE) / Brcc36 isopeptidase / BRCC36, C-terminal helical domain / BRCC36 C-terminal helical domain ...BRCA1-A complex subunit RAP80 / RAP80, N-terminal / RAP80 N-terminal ubiquitin interaction motif / BRISC and BRCA1-A complex member 1 / FAM175 family, BRCA1-A complex, Abraxas 1 subunit / BRCA1-A complex subunit BRE / Brain and reproductive organ-expressed protein (BRE) / Brcc36 isopeptidase / BRCC36, C-terminal helical domain / BRCC36 C-terminal helical domain / FAM175 family / BRCA1-A complex subunit Abraxas 1 MPN domain / Ubiquitin-interacting motif. / Rad18, zinc finger UBZ4-type / Zinc finger UBZ4-type profile. / : / Ubiquitin interacting motif / Ubiquitin-interacting motif (UIM) domain profile. / JAB1/Mov34/MPN/PAD-1 ubiquitin protease / JAB/MPN domain / JAB1/MPN/MOV34 metalloenzyme domain / MPN domain / MPN domain profile. / von Willebrand factor A-like domain superfamily / : / Ubiquitin domain signature. / Ubiquitin conserved site / Ubiquitin domain / Ubiquitin family / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Ubiquitin-like domain superfamily
Similarity search - Domain/homology
Polyubiquitin-C / Lys-63-specific deubiquitinase BRCC36 / BRCA1-A complex subunit Abraxas 1 / BRCA1-A complex subunit RAP80 / BRISC and BRCA1-A complex member 1 / BRISC and BRCA1-A complex member 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.92 Å
AuthorsFoglizzo, M. / Zeqiraj, E.
Funding support United Kingdom, 4items
OrganizationGrant numberCountry
Biotechnology and Biological Sciences Research Council (BBSRC)BB/Z51522X/1 United Kingdom
Wellcome Trust222531/Z/21/Z United Kingdom
Medical Research Council (MRC, United Kingdom)MR/T029471/1 United Kingdom
Wellcome Trust221524/Z/20/Z United Kingdom
CitationJournal: Nat Commun / Year: 2026
Title: Mechanism of K63-linked polyubiquitin recognition and cleavage by the BRCA1-A complex.
Authors: Martina Foglizzo / Arindam Datta / Oksana Degtjarik / Hirunika Perera / Jordan Liburd / Upasana M Sykora / Sri Ranjani Ganji / Gemma Wildsmith / Francesca Chandler / Lisa J Campbell / ...Authors: Martina Foglizzo / Arindam Datta / Oksana Degtjarik / Hirunika Perera / Jordan Liburd / Upasana M Sykora / Sri Ranjani Ganji / Gemma Wildsmith / Francesca Chandler / Lisa J Campbell / Antonio N Calabrese / Roger A Greenberg / Elton Zeqiraj /
Abstract: Deubiquitylases modulate cellular processes by removing monoubiquitin or cleaving polyubiquitin chains. The ARISC-RAP80 complex partners with BRCA1-BARD1 to form the BRCA1-A supercomplex, which ...Deubiquitylases modulate cellular processes by removing monoubiquitin or cleaving polyubiquitin chains. The ARISC-RAP80 complex partners with BRCA1-BARD1 to form the BRCA1-A supercomplex, which recognises K63-linked ubiquitin chains at DNA damage sites. ARISC-RAP80 contains multiple ubiquitin-binding sites, yet how these influence recognition and cleavage of K63-polyubiquitylated substrates remains unknown. We discover that a composite three-subunit interface allows ARISC-RAP80 to position K63-linked polyubiquitin chains in its catalytic site. Substrate recognition is further supported by RAP80 and non-catalytic ubiquitin-binding sites that impose a compact conformation on K63-polyubiquitylated substrates. This mechanism exploits the inherent flexibility of long ubiquitin chains and differs considerably from other deubiquitylases. Structure-guided mutageneses validate ubiquitin chain interactions, and cell-based assays demonstrate a functional role of the observed interfaces in chromatin recruitment. Our findings define mechanisms of polyubiquitin chain decoding and cleavage by ARISC-RAP80, linking ubiquitin reading and erasing functions to BRCA1-A mediated DNA damage responses.
History
DepositionSep 23, 2025Deposition site: PDBE / Processing site: PDBE
Revision 1.0Aug 5, 2026Provider: repository / Type: Initial release
Revision 1.0Aug 5, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Aug 5, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Aug 5, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Aug 26, 2026Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name / _em_admin.last_update
Revision 1.1Aug 26, 2026Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Database references / Experimental summary / Data content type: EM metadata / EM metadata / EM metadata / Category: citation / citation_author / em_admin
Data content type: EM metadata / EM metadata ...EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata / EM metadata
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name / _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
D: BRCA1-A complex subunit Abraxas 1
E: BRISC and BRCA1-A complex member 2
F: BRISC and BRCA1-A complex member 2
G: BRISC and BRCA1-A complex member 1
H: BRISC and BRCA1-A complex member 1
I: BRCA1-A complex subunit RAP80
J: BRCA1-A complex subunit RAP80
K: Ubiquitin
L: Ubiquitin
M: Ubiquitin
N: Ubiquitin
O: Ubiquitin
P: Ubiquitin
C: BRCA1-A complex subunit Abraxas 1
A: Lys-63-specific deubiquitinase BRCC36
B: Lys-63-specific deubiquitinase BRCC36
hetero molecules


Theoretical massNumber of molelcules
Total (without water)546,08418
Polymers545,95416
Non-polymers1312
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

-
BRCA1-A complex subunit ... , 2 types, 4 molecules DCIJ

#1: Protein BRCA1-A complex subunit Abraxas 1 / Coiled-coil domain-containing protein 98 / Protein FAM175A


Mass: 50623.969 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ABRAXAS1, ABRA1, CCDC98, FAM175A, UNQ496/PRO1013 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q6UWZ7
#4: Protein BRCA1-A complex subunit RAP80 / Receptor-associated protein 80 / Retinoid X receptor-interacting protein 110 / Ubiquitin ...Receptor-associated protein 80 / Retinoid X receptor-interacting protein 110 / Ubiquitin interaction motif-containing protein 1


Mass: 80243.945 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: UIMC1, RAP80, RXRIP110 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q96RL1

-
BRISC and BRCA1-A complex member ... , 2 types, 4 molecules EFGH

#2: Protein BRISC and BRCA1-A complex member 2 / BRCA1-A complex subunit BRE / BRCA1/BRCA2-containing complex subunit 45 / Brain and reproductive ...BRCA1-A complex subunit BRE / BRCA1/BRCA2-containing complex subunit 45 / Brain and reproductive organ-expressed protein


Mass: 43721.602 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BABAM2, BRCC45, BRE / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9NXR7
#3: Protein BRISC and BRCA1-A complex member 1 / Mediator of RAP80 interactions and targeting subunit of 40 kDa / New component of the BRCA1-A complex


Mass: 36594.930 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BABAM1, C19orf62, MERIT40, NBA1, HSPC142 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q9NWV8

-
Protein , 2 types, 8 molecules KLMNOPAB

#5: Protein
Ubiquitin / Polyubiquitin-C


Mass: 8576.831 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: UBC / Production host: Escherichia coli (E. coli) / References: UniProt: P0CG48
#6: Protein Lys-63-specific deubiquitinase BRCC36 / BRCA1-A complex subunit BRCC36 / BRCA1/BRCA2-containing complex subunit 3 / BRCA1/BRCA2-containing ...BRCA1-A complex subunit BRCC36 / BRCA1/BRCA2-containing complex subunit 3 / BRCA1/BRCA2-containing complex subunit 36 / BRISC complex subunit BRCC36


Mass: 36061.883 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRCC3, BRCC36, C6.1A, CXorf53 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P46736, Hydrolases; Acting on peptide bonds (peptidases); Omega peptidases

-
Non-polymers , 1 types, 2 molecules

#7: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn / Feature type: SUBJECT OF INVESTIGATION

-
Details

Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: ARISC(E33A)-RAP80 in complex with K63-linked ubiquitin chains
Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT
Molecular weightValue: 0.207 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
21Spodoptera frugiperda (fall armyworm)7108
41Escherichia coli (E. coli)562
Buffer solutionpH: 7.3
Buffer component
IDConc.NameFormulaBuffer-ID
125 mM2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acidHEPES1
2150 mMSodium chlorideNaCl1
31 mMTris(2-carboxyethyl)phosphineTCEP1
SpecimenConc.: 0.6 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Details: Freshly purified ARISC(E33A)-RAP80 (at 0.6 mg/mL) was mixed with 1.5-fold molar excess of K63-linked heptaUb (Ub7) chains, and incubated in the presence of 0.025% (v/v) glutaraldehyde (Sigma- ...Details: Freshly purified ARISC(E33A)-RAP80 (at 0.6 mg/mL) was mixed with 1.5-fold molar excess of K63-linked heptaUb (Ub7) chains, and incubated in the presence of 0.025% (v/v) glutaraldehyde (Sigma-Aldrich) at room temperature for 4 min. The cross-linking reaction was then quenched by the addition of 100 mM Tris-HCl pH 7.5 prior to cryo-EM grids preparation.
Specimen supportDetails: UltraAuFoil R1.2/1.3 300-mesh grids (Quantifoil Micro Tools GmbH) were glow-discharged for 1 min at 12 mA and 0.38 mBar pressure using a PELCO easiGlow system (Ted Pella).
Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: UltrAuFoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K
Details: blot force = 1 N; blot time = 6 s; waiting time = 27 s

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal magnification: 165000 X / Nominal defocus max: 3000 nm / Nominal defocus min: 900 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingAverage exposure time: 3.4 sec. / Electron dose: 45.5 e/Å2 / Film or detector model: TFS FALCON 4i (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 10649
EM imaging opticsEnergyfilter name: TFS Selectris / Energyfilter slit width: 10 eV / Phase plate: VOLTA PHASE PLATE

-
Processing

EM software
IDNameVersionCategory
1crYOLOv1.6.1particle selection
4cryoSPARCv4.5.3CTF correction
7UCSF ChimeraXv1.6.1model fitting
9PHENIX1.21.1_5286:model refinement
10cryoSPARCv4.5.3initial Euler assignment
11cryoSPARCv4.5.3final Euler assignment
12cryoSPARCv4.5.3classification
13cryoSPARCv4.5.33D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 789840
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 2.92 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 214650 / Num. of class averages: 1 / Symmetry type: POINT

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more