TOP2A
Domain
The N-terminus has several structural domains; the ATPase domain (about residues 1-265), the transducer domain (about 266-428) and the toprim domain (455-572) (PubMed:25202966). Comparing different structures shows ATP hydrolysis induces domain shifts in the N-terminus that are probably part of the mechanism of DNA cleavage and rejoining (PubMed:25202966).
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 (PubMed:17567603, PubMed:18790802, PubMed:22013166, PubMed:22323612). May play a role in regulating the period length of BMAL1 transcriptional oscillation (By similarity).
Post-translational modifications
Phosphorylation has no effect on catalytic activity. However, phosphorylation at Ser-1106 by CSNK1D/CK1 promotes DNA cleavable complex formation.
(Microbial infection) Deubiquitinated by Epstein-Barr virus BPLF1; leading to stabilized SUMOylated TOP2A trapped in cleavage complexes, which halts the DNA damage response to TOP2A-induced double-strand DNA breaks.
SUMOylated.
Sequence Similarities
Belongs to the type II topoisomerase family.
Tissue Specificity
Expressed in the tonsil, spleen, lymph node, thymus, skin, pancreas, testis, colon, kidney, liver, brain and lung (PubMed:9155056). Also found in high-grade lymphomas, squamous cell lung tumors and seminomas (PubMed:9155056).
Cellular localization
- Cytoplasm
- Nucleus
- Nucleoplasm
- Nucleus
- Nucleus
- Nucleolus
Alternative names
TOP2, TOP2A, DNA topoisomerase 2-alpha