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- PDB-8yjb: Cryo-EM structure of the human DSS1-INTAC complex -

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Basic information

Entry
Database: PDB / ID: 8yjb
TitleCryo-EM structure of the human DSS1-INTAC complex
Components
  • (Integrator complex subunit ...) x 9
  • (Serine/threonine-protein phosphatase 2A ...) x 2
  • 26S proteasome complex subunit DSS1
KeywordsTRANSCRIPTION / DSS1 / Integrator / INTAC
Function / homology
Function and homology information


U2 snRNA 3'-end processing / meiotic spindle elongation / Integration of energy metabolism / PP2A-mediated dephosphorylation of key metabolic factors / snRNA 3'-end processing / MASTL Facilitates Mitotic Progression / regulation of meiotic cell cycle process involved in oocyte maturation / mitotic sister chromatid separation / protein phosphatase type 2A complex / protein serine/threonine phosphatase complex ...U2 snRNA 3'-end processing / meiotic spindle elongation / Integration of energy metabolism / PP2A-mediated dephosphorylation of key metabolic factors / snRNA 3'-end processing / MASTL Facilitates Mitotic Progression / regulation of meiotic cell cycle process involved in oocyte maturation / mitotic sister chromatid separation / protein phosphatase type 2A complex / protein serine/threonine phosphatase complex / peptidyl-threonine dephosphorylation / meiotic sister chromatid cohesion, centromeric / snRNA processing / peptidyl-serine dephosphorylation / FAR/SIN/STRIPAK complex / : / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / female meiotic nuclear division / Inhibition of replication initiation of damaged DNA by RB1/E2F1 / Impaired BRCA2 translocation to the nucleus / Impaired BRCA2 binding to SEM1 (DSS1) / regulation of transcription elongation by RNA polymerase II / GABA receptor binding / protein phosphatase regulator activity / protein antigen binding / integrator complex / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / ERKs are inactivated / Initiation of Nuclear Envelope (NE) Reformation / Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters / Beta-catenin phosphorylation cascade / Signaling by GSK3beta mutants / CTNNB1 S33 mutants aren't phosphorylated / CTNNB1 S37 mutants aren't phosphorylated / CTNNB1 S45 mutants aren't phosphorylated / CTNNB1 T41 mutants aren't phosphorylated / proteasome regulatory particle, lid subcomplex / Co-stimulation by CD28 / regulation of growth / Disassembly of the destruction complex and recruitment of AXIN to the membrane / Regulation of ornithine decarboxylase (ODC) / Proteasome assembly / Homologous DNA Pairing and Strand Exchange / Defective homologous recombination repair (HRR) due to BRCA1 loss of function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function / Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function / Cross-presentation of soluble exogenous antigens (endosomes) / Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) / negative regulation of epithelial to mesenchymal transition / Resolution of D-loop Structures through Holliday Junction Intermediates / inner cell mass cell proliferation / Somitogenesis / Co-inhibition by CTLA4 / protein serine/threonine phosphatase activity / Platelet sensitization by LDL / histone H2AXS140 phosphatase activity / RNA polymerase II CTD heptapeptide repeat Y1 phosphatase activity / RNA polymerase II CTD heptapeptide repeat T4 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity / MAP kinase serine/threonine phosphatase activity / calmodulin-dependent protein phosphatase activity / Impaired BRCA2 binding to RAD51 / myosin phosphatase activity / protein-serine/threonine phosphatase / negative regulation of glycolytic process through fructose-6-phosphate / positive regulation of NLRP3 inflammasome complex assembly / ERK/MAPK targets / T cell homeostasis / mesoderm development / vascular endothelial cell response to oscillatory fluid shear stress / regulation of cell differentiation / regulation of G1/S transition of mitotic cell cycle / Presynaptic phase of homologous DNA pairing and strand exchange / phosphoprotein phosphatase activity / RNA polymerase II transcribes snRNA genes / chromosome, centromeric region / DARPP-32 events / positive regulation of protein serine/threonine kinase activity / lateral plasma membrane / negative regulation of hippo signaling / proteasome assembly / mRNA export from nucleus / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Cyclin A/B1/B2 associated events during G2/M transition / spindle assembly / protein dephosphorylation / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / protein tyrosine phosphatase activity / embryo implantation / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / RNA endonuclease activity / Recruitment of mitotic centrosome proteins and complexes
Similarity search - Function
Domain of unknown function DUF3677 / Integrator complex subunit 2, metazoa / Integrator complex subunit 2 / Integrator complex subunit 7 / Integrator complex subunit 1 / : / : / : / : / : ...Domain of unknown function DUF3677 / Integrator complex subunit 2, metazoa / Integrator complex subunit 2 / Integrator complex subunit 7 / Integrator complex subunit 1 / : / : / : / : / : / : / Integrator complex subunit 1, RP2B-binding domain / Integrator complex subunit 2 / Integrator complex subunit 1, R3 domain / Integrator complex subunit 1, R4 domain / Integrator complex subunit 1, INTS2-binding domain / Integrator complex subunit 7, C-terminal domain / Integrator complex subunit 7, N-terminal / Integrator complex subunit 7 helical bundle / INTS6/SAGE1/DDX26B/CT45, C-terminal / : / INTS6/SAGE1/DDX26B/CT45 C-terminus / Integrator complex subunit 5, C-terminal / Integrator complex subunit 5, N-terminal / Integrator complex subunit 8 / Integrator complex subunit 5 / Integrator complex subunit 5 N-terminus / Integrator complex subunit 5 C-terminus / : / INTS4 8 helical bundle domain / Sister chromatid cohesion protein PDS5 protein / Integrator complex subunit 9 / : / Integrator IntS9, C-terminal domain / Integrator complex subunit 11, MBL-fold / : / Integrator IntS11, C-terminal domain / Metallo-beta-lactamase superfamily domain / : / : / : / Beta-Casp domain / Beta-Casp domain / Beta-Casp domain / Zn-dependent metallo-hydrolase, RNA specificity domain / Zn-dependent metallo-hydrolase RNA specificity domain / HEAT repeat / HEAT repeat / : / PPP2R1A-like HEAT repeat / Serine/threonine specific protein phosphatases signature. / Protein phosphatase 2A homologues, catalytic domain. / DSS1/SEM1 / DSS1/SEM1 family / DSS1_SEM1 / Serine/threonine-specific protein phosphatase/bis(5-nucleosyl)-tetraphosphatase / HEAT repeat profile. / HEAT, type 2 / von Willebrand factor type A domain / HEAT repeats / Calcineurin-like phosphoesterase domain, ApaH type / Calcineurin-like phosphoesterase / Metallo-dependent phosphatase-like / VWFA domain profile. / Metallo-beta-lactamase superfamily / Metallo-beta-lactamase / von Willebrand factor, type A / Ribonuclease Z/Hydroxyacylglutathione hydrolase-like / von Willebrand factor A-like domain superfamily / Armadillo-like helical / Tetratricopeptide-like helical domain superfamily / Armadillo-type fold
Similarity search - Domain/homology
: / Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform / 26S proteasome complex subunit SEM1 / Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform / Integrator complex subunit 11 / Integrator complex subunit 5 / Integrator complex subunit 8 / Integrator complex subunit 1 / Integrator complex subunit 4 / Integrator complex subunit 2 ...: / Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform / 26S proteasome complex subunit SEM1 / Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform / Integrator complex subunit 11 / Integrator complex subunit 5 / Integrator complex subunit 8 / Integrator complex subunit 1 / Integrator complex subunit 4 / Integrator complex subunit 2 / Integrator complex subunit 9 / Integrator complex subunit 7 / Integrator complex subunit 6
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.1 Å
AuthorsZheng, H. / Xu, Y. / Cheng, J.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: To Be Published
Title: Stabilization of Integrator/INTAC by the small but versatile DSS1 protein.
Authors: Xu, C. / Zhou, Q. / Zheng, H. / Song, A. / Zhao, W. / Xiong, Y. / Huang, Z. / Xu, Y. / Cheng, J. / Chen, F.X.
History
DepositionMar 1, 2024Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Mar 5, 2025Provider: repository / Type: Initial release
Revision 1.0Mar 5, 2025Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Mar 5, 2025Data content type: Additional map / Part number: 1 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0Mar 5, 2025Data content type: Additional map / Part number: 2 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0Mar 5, 2025Data content type: Additional map / Part number: 3 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0Mar 5, 2025Data content type: Additional map / Part number: 4 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0Mar 5, 2025Data content type: Additional map / Part number: 5 / Data content type: Additional map / Provider: repository / Type: Initial release
Revision 1.0Mar 5, 2025Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Mar 5, 2025Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
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Revision 1.0Mar 5, 2025Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Mar 5, 2025Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
0: 26S proteasome complex subunit DSS1
I: Integrator complex subunit 9
K: Integrator complex subunit 11
B: Integrator complex subunit 2
D: Integrator complex subunit 4
G: Integrator complex subunit 7
P: Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform
Q: Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
A: Integrator complex subunit 1
E: Integrator complex subunit 5
F: Integrator complex subunit 6
H: Integrator complex subunit 8
hetero molecules


Theoretical massNumber of molelcules
Total (without water)1,167,33616
Polymers1,167,09512
Non-polymers2414
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Protein , 1 types, 1 molecules 0

#1: Protein 26S proteasome complex subunit DSS1 / Deleted in split hand/split foot protein 1 / Split hand/foot deleted protein 1 / Split hand/foot ...Deleted in split hand/split foot protein 1 / Split hand/foot deleted protein 1 / Split hand/foot malformation type 1 protein


Mass: 8284.611 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SHFM1, DSS1, SHFDG1 / Production host: Homo sapiens (human) / References: UniProt: P60896

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Integrator complex subunit ... , 9 types, 9 molecules IKBDGAEFH

#2: Protein Integrator complex subunit 9 / Int9 / Protein related to CPSF subunits of 74 kDa / RC-74


Mass: 73891.219 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: INTS9, RC74 / Production host: Homo sapiens (human) / References: UniProt: Q9NV88
#3: Protein Integrator complex subunit 11 / Int11 / Cleavage and polyadenylation-specific factor 3-like protein / CPSF3-like protein / Protein ...Int11 / Cleavage and polyadenylation-specific factor 3-like protein / CPSF3-like protein / Protein related to CPSF subunits of 68 kDa / RC-68


Mass: 67756.562 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: INTS11, CPSF3L, RC68 / Production host: Homo sapiens (human)
References: UniProt: Q5TA45, Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters
#4: Protein Integrator complex subunit 2 / Int2


Mass: 134451.625 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: INTS2, KIAA1287 / Production host: Homo sapiens (human) / References: UniProt: Q9H0H0
#5: Protein Integrator complex subunit 4 / Int4


Mass: 108306.758 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: INTS4, MSTP093 / Production host: Homo sapiens (human) / References: UniProt: Q96HW7
#6: Protein Integrator complex subunit 7 / Int7


Mass: 106952.617 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: INTS7, C1orf73 / Production host: Homo sapiens (human) / References: UniProt: Q9NVH2
#9: Protein Integrator complex subunit 1 / Int1


Mass: 244574.922 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: INTS1, KIAA1440, UNQ1821/PRO3434 / Production host: Homo sapiens (human) / References: UniProt: Q8N201
#10: Protein Integrator complex subunit 5 / Int5


Mass: 108115.227 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: INTS5, KIAA1698 / Production host: Homo sapiens (human) / References: UniProt: Q6P9B9
#11: Protein Integrator complex subunit 6 / Int6 / DBI-1 / Protein DDX26 / Protein deleted in cancer 1 / DICE1


Mass: 100527.078 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: INTS6, DBI1, DDX26, DDX26A / Production host: Homo sapiens (human) / References: UniProt: Q9UL03
#12: Protein Integrator complex subunit 8 / Int8 / Protein kaonashi-1


Mass: 113219.859 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: INTS8, C8orf52 / Production host: Homo sapiens (human) / References: UniProt: Q75QN2

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Serine/threonine-protein phosphatase 2A ... , 2 types, 2 molecules PQ

#7: Protein Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform / Medium tumor antigen-associated 61 kDa protein / PP2A subunit A isoform PR65-alpha / PP2A subunit A ...Medium tumor antigen-associated 61 kDa protein / PP2A subunit A isoform PR65-alpha / PP2A subunit A isoform R1-alpha


Mass: 65378.344 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PPP2R1A / Production host: Homo sapiens (human) / References: UniProt: P30153
#8: Protein Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform / PP2A-alpha / Replication protein C / RP-C


Mass: 35636.152 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PPP2CA / Production host: Homo sapiens (human)
References: UniProt: P67775, protein-serine/threonine phosphatase

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Non-polymers , 2 types, 4 molecules

#13: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#14: Chemical ChemComp-MN / MANGANESE (II) ION


Mass: 54.938 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mn

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Details

Has ligand of interestN
Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

ComponentName: DSS1-INTAC-PEC / Type: COMPLEX / Entity ID: #1-#12 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: GOLD / Grid type: Quantifoil R1.2/1.3
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1500 nm
Specimen holderCryogen: NITROGEN
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

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Processing

EM software
IDNameCategory
1Gautomatchparticle selection
2SerialEMimage acquisition
4RELIONCTF correction
7Cootmodel fitting
10RELIONinitial Euler assignment
11RELIONfinal Euler assignment
13RELION3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 587397
3D reconstructionResolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 43790 / Symmetry type: POINT
Atomic model buildingProtocol: RIGID BODY FIT
Atomic model buildingPDB-ID: 7YCX

7ycx


Accession code: 7YCX / Source name: PDB / Type: experimental model

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