Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

TOP2A (P11388) - Overview - Molecular Target Synopsis

Protein


TOP2A, DNA topoisomerase 2-alpha
Enzyme Classification 5.6.2.3
UniProt P11388

Also Known as TOP2A_HUMAN, TOP2A, TOP2

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). Homodimer. Interacts with COPS5. Interacts with RECQL5; this stimulates DNA decatenation. Interacts with SETMAR; stimulates the topoisomerase activity (PubMed:18790802, PubMed:20457750). Interacts with DHX9; this interaction occurs in a E2 enzyme UBE2I- and RNA-dependent manner, negatively regulates DHX9-mediated double-stranded DNA and RNA duplex helicase activity and stimulates TOP2A-mediated supercoiled DNA relaxation activity (PubMed:12711669). Interacts with HNRNPU (via C-terminus); this interaction protects the topoisomerase TOP2A from degradation and positively regulates the relaxation of supercoiled DNA in a RNA-dependent manner (By similarity). Interacts with MCM3AP isoform GANP (PubMed:23652018).

5NNE
8 RESIDUE FRAGMENT OF
GKA(ALY)GK(ALY)TQMYADDITIONAL C-TERMINAL TYR ADDED FOR UV DETECTION
IN THE STRUCTURE OF
CRYSTAL STRUCTURE OF THE FIRST BROMODOMAIN OF HUMAN BRD4 IN COMPLEX WITH A DIACETYLATED TOP2A PEPTIDE (K1201AC/K1204AC)
RCSB/PDB
Inspect Structure
See all 3D Structures for TOP2A

Isoforms / Transcripts (Protein Coding)


Drugs


TOP2A is targeted by Approved Drugs Daunorubicin, Teniposide, Pixantrone, Dactinomycin, Etoposide Phosphate, Etoposide, Valrubicin, Mitoxantrone, Doxorubicin, Idarubicin. (see details)
Daunorubicin
Teniposide
Pixantrone
Dactinomycin
Etoposide Phosphate
Etoposide
Valrubicin
Mitoxantrone
Doxorubicin
Idarubicin

Sub-cellular localization


UniProt: TOP2A is active in the following subcellular-locations: cytoplasm, nucleoplasm, nucleus.
GO terms: TOP2A is active in the following subcellular-locations: condensed chromosome, cytoplasm, DNA topoisomerase complex (ATP-hydrolyzing), nucleolus, nucleoplasm, nucleus, protein-containing complex, ribonucleoprotein complex, viral integration complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project TOP2A has gain in 5 cell-lines, loss in 4 cell-lines and no signal in 996 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: OVCAR_5, A549, CCRF_CEM

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: WSU-FSCCL, NCI-H209, DMS 79

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: A549, MCF-7, HeLa-S3

(see details)

3D Structures


For TOP2A there are:
6 structures (14 chains) solved
4 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


TOP2A has been screened with 3176 compounds (5557 bioactivities), 33 compounds have bioactivities that show binding affinity of <= 500nM (34 bioactivities). (see details)