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MGP003172

UniProt Annotations

Entry Information

Gene Name	topoisomerase (DNA) II alpha 170kDa
Protein Entry	TOP2A_HUMAN
UniProt ID	P11388
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=4; Name=1; IsoId=P11388-1; Sequence=Displayed; Name=2; IsoId=P11388-2; Sequence=VSP_006531; Name=3; IsoId=P11388-3; Sequence=VSP_006529; Name=4; IsoId=P11388-4; Sequence=VSP_006530;
Catalytic Activity	ATP-dependent breakage, passage and rejoining of double-stranded DNA. {ECO:0000255\|PROSITE-ProRule:PRU00995, ECO:0000269\|PubMed:19222228, ECO:0000269\|PubMed:19697956}.
Cofactor	Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305\|PubMed:19222228, ECO:0000305\|PubMed:19697956, ECO:0000305\|PubMed:22323612, ECO:0000305\|PubMed:22841979}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000305\|PubMed:19222228, ECO:0000305\|PubMed:19697956, ECO:0000305\|PubMed:22323612, ECO:0000305\|PubMed:22841979}; Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000305\|PubMed:19222228, ECO:0000305\|PubMed:19697956, ECO:0000305\|PubMed:22323612, ECO:0000305\|PubMed:22841979}; Note=Binds two Mg(2+) per subunit. The magnesium ions form salt bridges with both the protein and the DNA. Can also accept other divalent metal cations, such as Mn(2+) or Ca(2+). {ECO:0000305\|PubMed:19222228, ECO:0000305\|PubMed:19697956, ECO:0000305\|PubMed:22323612, ECO:0000305\|PubMed:22841979};
Enzyme Regulation	Specifically inhibited by the intercalating agent amsacrine.
Function	Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity). {ECO:0000250\|UniProtKB:Q01320, ECO:0000269\|PubMed:18790802, ECO:0000269\|PubMed:22013166, ECO:0000269\|PubMed:22323612}.
Interaction	P35222:CTNNB1; NbExp=5; IntAct=EBI-539628, EBI-491549;
Miscellaneous	Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.
Ptm	Phosphorylation has no effect on catalytic activity. However, phosphorylation at Ser-1106 by CSNK1D/CK1 promotes DNA cleavable complex formation. {ECO:0000269\|PubMed:10942766, ECO:0000269\|PubMed:16964243, ECO:0000269\|PubMed:17081983, ECO:0000269\|PubMed:17924679, ECO:0000269\|PubMed:18062778, ECO:0000269\|PubMed:18220336, ECO:0000269\|PubMed:18669648, ECO:0000269\|PubMed:18691976, ECO:0000269\|PubMed:19043076, ECO:0000269\|PubMed:19690332, ECO:0000269\|PubMed:20068231, ECO:0000269\|PubMed:21406692, ECO:0000269\|Ref.11}.
Similarity	Belongs to the type II topoisomerase family. {ECO:0000305}.
Similarity	Contains 1 Toprim domain. {ECO:0000255\|PROSITE- ProRule:PRU00995}.
Subcellular Location	Cytoplasm {ECO:0000269\|PubMed:22013166}. Nucleus, nucleoplasm {ECO:0000269\|PubMed:22013166}. Note=Generally located in the nucleoplasm.
Subunit	Homodimer. Interacts with COPS5. Interacts with RECQL5; this stimulates DNA decatenation. Interacts with SETMAR; stimulates the topoisomerase activity (PubMed:18790802, PubMed:20457750). {ECO:0000269\|PubMed:15126503, ECO:0000269\|PubMed:16100112, ECO:0000269\|PubMed:20457750, ECO:0000269\|PubMed:22013166, ECO:0000269\|PubMed:22841979}.