DNA topoisomerase 2-alpha

Function

Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand. May play a role in regulating the period length of BMAL1 transcriptional oscillation (By similarity).

Classification

Family (Pfam)

PF00204 DNA_gyraseB, PF00521 DNA_topoisoIV, PF08070 DTHCT, PF02518 HATPase_c, PF01751 Toprim, PF16898 TOPRIM_C

InterPro

DNA_Topoisomerase_II, DTHCT, HATPase_C_sf, HATPase_dom, Ribosomal_Su5_D2-typ_SF, Ribsml_uS5_D2-typ_fold_subgr, Topo_IIA, Topo_IIA-like_dom_sf, Topo_IIA_A/C_ab, Topo_IIA_A_a_sf, Topo_IIA_B_C, Topo_IIA_bsu_dom2, Topo_IIA_dom_A, TopoII_euk, TopoIIA_CS, TOPRIM_C, TOPRIM_dom, TOPRIM_TopoII

Functional cluster

Central Metabolic Enzymes (KARI/Glycolysis)

Experimental structures · PDB · 15

• 1ZXM X-ray 1.87A
• 1ZXN X-ray 2.51A
• 4FM9 X-ray 2.90A
• 4R1F X-ray 2.51A
• 5GWK X-ray 3.15A
• 5NNE X-ray 1.15A
• 6ZY5 EM 3.60A
• 6ZY6 EM 4.10A
• 6ZY7 EM 4.64A
• 6ZY8 EM 7.40A
• 8W50 X-ray 2.67A
• 9BQ6 X-ray 1.90A
• … and 3 more

A predicted model is available from AlphaFold.

Gene Ontology · 33

• GO:0000775 chromosome, centromeric region
• GO:0000793 condensed chromosome
• GO:0005737 cytoplasm
• GO:0009330 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex
• GO:0005730 nucleolus
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0032991 protein-containing complex
• GO:1990904 ribonucleoprotein complex
• GO:0005524 ATP binding
• GO:0008094 ATP-dependent activity, acting on DNA
• GO:0003682 chromatin binding
• GO:0003677 DNA binding
• GO:0008301 DNA binding, bending
• GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity
• GO:0000287 magnesium ion binding
• GO:0046982 protein heterodimerization activity
• GO:0042803 protein homodimerization activity
• GO:0005080 protein kinase C binding
• GO:0003723 RNA binding
• GO:0043130 ubiquitin binding
• GO:0030263 apoptotic chromosome condensation
• GO:0006325 chromatin organization
• GO:0007059 chromosome segregation
• GO:0006974 DNA damage response
• GO:0006265 DNA topological change
• GO:0007143 female meiotic nuclear division
• GO:0043065 positive regulation of apoptotic process
• GO:0045870 positive regulation of single stranded viral RNA replication via double stranded DNA intermediate
• GO:0042752 regulation of circadian rhythm
• GO:0000712 resolution of meiotic recombination intermediates
• GO:0048511 rhythmic process
• GO:0000819 sister chromatid segregation

Drugs targeting this protein · 21

• VALRUBICIN inhibitor
• AMRUBICIN inhibitor
• DAUNORUBICIN CITRATE inhibitor
• ETOPOSIDE PHOSPHATE inhibitor
• DEXRAZOXANE HYDROCHLORIDE inhibitor
• IDARUBICIN HYDROCHLORIDE inhibitor
• MITOXANTRONE HYDROCHLORIDE inhibitor
• DAUNORUBICIN HYDROCHLORIDE inhibitor
• DEXRAZOXANE inhibitor
• DAUNORUBICIN inhibitor
• BERUBICIN HYDROCHLORIDE inhibitor
• BECATECARIN inhibitor
• ALDOXORUBICIN inhibitor
• PAZUFLOXACIN inhibitor
• C-1311 inhibitor
• DOXORUBICIN HYDROCHLORIDE inhibitor
• AMSACRINE inhibitor
• ETOPOSIDE inhibitor
• TENIPOSIDE inhibitor
• AMRUBICIN HYDROCHLORIDE inhibitor
• VOSAROXIN inhibitor

Related proteins · sequence + function similarity

• DNA topoisomerase 2-alpha 1.00
• DNA topoisomerase 2-alpha 1.00
• DNA topoisomerase 2-alpha 0.99
• DNA topoisomerase 2-alpha 0.99
• DNA topoisomerase 2-alpha 0.98
• DNA topoisomerase 2-beta 0.98
• DNA topoisomerase 2-beta 0.98
• DNA topoisomerase 2-beta 0.98
• DNA topoisomerase 2-beta 0.97
• DNA topoisomerase 2 0.97
• DNA topoisomerase 2 0.96
• DNA topoisomerase 2 0.94

Co-cited proteins · studied together in the literature

• DNA topoisomerase 2-beta 6 shared papers
• Histone-lysine N-methyltransferase SETMAR 2 shared papers
• F-box only protein 28 1 shared papers
• DNA topoisomerase 2 1 shared papers
• ATP-dependent DNA helicase Q5 1 shared papers
• Serine/threonine-protein kinase PLK3 1 shared papers
• Casein kinase I isoform delta 1 shared papers
• DNA gyrase subunit B 1 shared papers
• ATP-dependent RNA helicase A 2 shared papers
• COP9 signalosome complex subunit 5 1 shared papers
• Large tegument protein deneddylase 1 shared papers
• Phospholipid scramblase 1 1 shared papers

Literature · 51 cited papers

• The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans. Life. Sci Alliance · 2022
• The Epstein-Barr virus deubiquitinating enzyme BPLF1 regulates the activity of topoisomerase II during productive infection. PLoS Pathog. · 2021
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• Fbxo28 promotes mitotic progression and regulates topoisomerase IIalpha-dependent DNA decatenation. Cell Cycle · 2016
• Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin Dynamics. PLoS ONE · 2015
• SUMO-2 orchestrates chromatin modifiers in response to DNA damage. Cell Rep. · 2015
• System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel small ubiquitin-like modified target proteins and acceptor lysines relevant for genome stability. Mol. Cell. Proteomics · 2015
• Uncovering global SUMOylation signaling networks in a site-specific manner. Nat. Struct. Mol. Biol. · 2014
• Structure of the N-terminal Gyrase B fragment in complex with ADPPi reveals rigid-body motion induced by ATP hydrolysis. PLoS ONE · 2014
• Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli. Proc. Natl. Acad. Sci. U.S.A. · 2014
• GANP regulates recruitment of AID to immunoglobulin variable regions by modulating transcription and nucleosome occupancy. Nat. Commun. · 2013
• Taperin (c9orf75), a mutated gene in nonsyndromic deafness, encodes a vertebrate specific, nuclear localized protein phosphatase one alpha (PP1alpha) docking protein. Biol. Open · 2012
• … and 39 more in the literature graph