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Open data
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Basic information
| Entry | Database: PDB / ID: 7cun | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Title | The structure of human Integrator-PP2A complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Keywords | TRANSCRIPTION / Integrator-PP2A complex / phosphatase | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Function / homology | Function and homology informationU2 snRNA 3'-end processing / meiotic spindle elongation / Integration of energy metabolism / snRNA 3'-end processing / PP2A-mediated dephosphorylation of key metabolic factors / RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity / MASTL Facilitates Mitotic Progression / protein phosphatase type 2A complex / protein serine/threonine phosphatase complex ...U2 snRNA 3'-end processing / meiotic spindle elongation / Integration of energy metabolism / snRNA 3'-end processing / PP2A-mediated dephosphorylation of key metabolic factors / RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity / MASTL Facilitates Mitotic Progression / protein phosphatase type 2A complex / protein serine/threonine phosphatase complex / regulation of meiotic cell cycle process involved in oocyte maturation / peptidyl-threonine dephosphorylation / mitotic sister chromatid separation / meiotic sister chromatid cohesion, centromeric / snRNA processing / INTAC complex / RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity / FAR/SIN/STRIPAK complex / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / Inhibition of replication initiation of damaged DNA by RB1/E2F1 / female meiotic nuclear division / regulation of transcription elongation by RNA polymerase II / protein phosphatase regulator activity / GABA receptor binding / integrator complex / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / protein antigen binding / ERKs are inactivated / Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / Initiation of Nuclear Envelope (NE) Reformation / 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 / RNA polymerase II transcription initiation surveillance / Co-stimulation by CD28 / regulation of growth / Disassembly of the destruction complex and recruitment of AXIN to the membrane / negative regulation of epithelial to mesenchymal transition / inner cell mass cell proliferation / Co-inhibition by CTLA4 / Platelet sensitization by LDL / protein-serine/threonine phosphatase / negative regulation of glycolytic process through fructose-6-phosphate / positive regulation of NLRP3 inflammasome complex assembly / ERK/MAPK targets / protein serine/threonine phosphatase activity / mesoderm development / vascular endothelial cell response to oscillatory fluid shear stress / T cell homeostasis / regulation of cell differentiation / phosphoprotein phosphatase activity / regulation of microtubule polymerization / regulation of G1/S transition of mitotic cell cycle / RNA polymerase II transcribes snRNA genes / lateral plasma membrane / chromosome, centromeric region / DARPP-32 events / negative regulation of hippo signaling / protein dephosphorylation / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Cyclin A/B1/B2 associated events during G2/M transition / spindle assembly / protein localization to chromatin / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / embryo implantation / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Mitotic Prometaphase / Recruitment of mitotic centrosome proteins and complexes / RNA endonuclease activity / EML4 and NUDC in mitotic spindle formation / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / Recruitment of NuMA to mitotic centrosomes / protein tyrosine phosphatase activity / Anchoring of the basal body to the plasma membrane / Resolution of Sister Chromatid Cohesion / DNA damage checkpoint signaling / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / AURKA Activation by TPX2 / cellular response to ionizing radiation / meiotic cell cycle / chromosome segregation / negative regulation of transforming growth factor beta receptor signaling pathway / RAF activation / Spry regulation of FGF signaling / RHO GTPases Activate Formins / negative regulation of canonical Wnt signaling pathway / Degradation of beta-catenin by the destruction complex / PKR-mediated signaling / response to lead ion / tau protein binding / spindle pole / Negative regulation of MAPK pathway / Cyclin D associated events in G1 Similarity search - Function | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Authors | Zheng, H. / Qi, Y. / Liu, W. / Li, J. / Wang, J. / Xu, Y. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Citation | Journal: Science / Year: 2020Title: Identification of Integrator-PP2A complex (INTAC), an RNA polymerase II phosphatase. Authors: Hai Zheng / Yilun Qi / Shibin Hu / Xuan Cao / Congling Xu / Zhinang Yin / Xizi Chen / Yan Li / Weida Liu / Jie Li / Jiawei Wang / Gang Wei / Kaiwei Liang / Fei Xavier Chen / Yanhui Xu / ![]() Abstract: The 14-subunit metazoan-specific Integrator contains an endonuclease that cleaves nascent RNA transcripts. Here, we identified a complex containing Integrator and protein phosphatase 2A core enzyme ...The 14-subunit metazoan-specific Integrator contains an endonuclease that cleaves nascent RNA transcripts. Here, we identified a complex containing Integrator and protein phosphatase 2A core enzyme (PP2A-AC), termed INTAC. The 3.5-angstrom-resolution structure reveals that nine human Integrator subunits and PP2A-AC assemble into a cruciform-shaped central scaffold formed by the backbone and shoulder modules, with the phosphatase and endonuclease modules flanking the opposite sides. As a noncanonical PP2A holoenzyme, the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 and thus regulates transcription. Our study extends the function of PP2A to transcriptional regulation and reveals how dual enzymatic activities-RNA cleavage and RNA polymerase II dephosphorylation-are structurally and functionally integrated into the INTAC complex. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Structure visualization
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| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 7cun.cif.gz | 1.3 MB | Display | PDBx/mmCIF format |
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| PDB format | pdb7cun.ent.gz | 1 MB | Display | PDB format |
| PDBx/mmJSON format | 7cun.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Summary document | 7cun_validation.pdf.gz | 877.4 KB | Display | wwPDB validaton report |
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| Full document | 7cun_full_validation.pdf.gz | 959.7 KB | Display | |
| Data in XML | 7cun_validation.xml.gz | 179.9 KB | Display | |
| Data in CIF | 7cun_validation.cif.gz | 289.8 KB | Display | |
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cu/7cun ftp://data.pdbj.org/pub/pdb/validation_reports/cu/7cun | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 30473MC M: map data used to model this data C: citing same article ( |
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| Similar structure data |
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Assembly
| Deposited unit | ![]()
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Components
-Integrator complex subunit ... , 9 types, 9 molecules ABDEFGHIK
| #1: Protein | 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 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q8N201 |
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| #2: Protein | 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 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q9H0H0 |
| #3: Protein | 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 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q96HW7 |
| #4: Protein | 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 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q6P9B9 |
| #5: Protein | 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 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q9UL03 |
| #6: Protein | 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 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q9NVH2 |
| #7: Protein | 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 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q75QN2 |
| #8: Protein | 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 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q9NV88 |
| #9: Protein | 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 / Cell line (production host): HEK293 / Production host: Homo sapiens (human)References: UniProt: Q5TA45, Hydrolases; Acting on ester bonds; Endoribonucleases producing 3'-phosphomonoesters |
-Protein , 3 types, 3 molecules PQU
| #10: Protein | Mass: 66034.883 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P30153 |
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| #11: Protein | Mass: 35636.152 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human)References: UniProt: P67775, protein-serine/threonine phosphatase |
| #12: Protein | Mass: 50570.449 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) |
-Non-polymers , 2 types, 4 molecules 


| #13: Chemical | | #14: Chemical | |
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-Details
| Has ligand of interest | N |
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| Has protein modification | Y |
| Sequence details | For chain U, the density of UNK residues is too cracked or discontinuous to assign fitable sequence. |
-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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| Buffer solution | pH: 7.4 | ||||||||||||||||||||||||||||||
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
| Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: FEI TITAN KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD |
| Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
| Software | Name: PHENIX / Version: 1.16_3549: / Classification: refinement | ||||||||||||||||||||||||
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| EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
| CTF correction | Type: NONE | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 68378 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
| Displacement parameters | Biso mean: 47.99 Å2 | ||||||||||||||||||||||||
| Refine LS restraints |
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Homo sapiens (human)
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