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FLASH GENE

Symbol

TOP2A

contributors: mct/npt - updated : 29-04-2018

HGNC name	topoisomerase (DNA) II alpha 170kDa
HGNC id	11989

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	17q21.2      Physical location : 38.544.773 - 38.574.202
Synonym name	DNA topoisomerase II, alpha isozyme
Synonym symbol(s)	TOP2, TP2A
EC.number	5.99.1.3

DNA

TYPE	functioning gene
STRUCTURE	29.37 kb     35 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001067 35 - 5698 NP_001058 170 1531 - 2009 19223331

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune lymph node       highly Reproductive male system testis     highly Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	GRDD (glucose-regulated destruction domain), mapped to the N-terminal 70-170 amino acid sequence
	three functional domains associated with energy transduction, DNA-breakage reunion activity
	a C terminal nuclear localization signal (NLS), that appears to play significant roles in modulating the DNA cleavage/ligation reaction of the enzyme and its response to anticancer agents, and that determine its isoform-specific functions in proliferating cells

mono polymer

homomer , dimer

HOMOLOGY

Homologene

FAMILY

type II topoisomerase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus,nucleoplasm

basic FUNCTION	catalyzing the ATP dependent breakage passage and rejoining of double strand of DNA
	relaxing both positively and negatively supercoiled DNA
	target of several drugs widely used in the treatment of cancers
	playing a vital role in the removal of topological complexities left on DNA during S phase
	removes supercoils and catenanes generated during DNA metabolic processes such as transcription and replication
	TOP2A is essential for cell proliferation, whereas TOP2B is required only for aspects of nerve growth and brain development
	involvement of TOP2A in the formation of radiation-induced chromatid breaks
	acts in the same pathway of telomere protection as TERF2 and DCLRE1B
	ENDOG and TOP2A may actively participate in apoptotic chromatin degradation
	adopts a global conformation in which the second of its two inter-protomer contact points, one at the C-terminus, has separated
	TOP1, TOP2A are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication
	ZNF148 and TOP2A regulate each other through Competing endogenous RNA (ceRNA) regulatory mechanism in colorectal cancer (CRC), which has biological effects on cell proliferation.

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	interaction between its glucose-regulated destruction domain (GRDD) and MPN domain of CSN5
	SETMAR physically interacts and co-localizes with TOP2A (Topo IIalpha), the key chromosome decatenating enzyme
	SETMAR interacts with TOP2A and enhances its decatenation activity
	functional relationship between BLM, ERCC6L and TOP2A in the centromere decatenation process
	TDP2 is not only specific but also efficient in recognizing and processing trapped TOP2A cleavage complexes even in the form of a longer peptide
	TDP2 having preferential action at abortive TOP2A and possibly TOP3A cleavage complexes
	bends its DNA substrate using a bipartite, nucleolytic center formed at an N-terminal dimerization interface of the cleavage core
	KIF4A and condensin work in parallel to promote mitotic chromosome morphology, acting in apparent opposition to TOP2A
	both KIF4A and TOP2A depend on SMC2 for their localization on the chromatid axis and that SMC2 exhibits a reciprocal dependency on KIF4A for localization on the chromatid axes
	TOP2A, TOP1 are involved in initiating aphidicolin-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication
	active role of TDP1 in the repair of TOP2A-induced DNA damage
	PTEN is physically associated with a decatenation enzyme TOP2A and PTEN influences its stability through OTUD3 deubiquitinase
	MAPK6, an atypical MAPK, phosphorylates TDP2 at S60 and regulates TDP2 phosphodiesterase activity, thereby cooperatively protecting lung cancer cells against TOP2A inhibitors-induced DNA damage and growth inhibition
	SMC5/SMC6 complex physically interacts with TOP2A, and the SMC5/6 complex functions in resolving TOP2A-mediated DSB-repair intermediates generated during replication
	AIRE promote DNA breaks via its interaction with topoisomerase 2 (TOP2A)
	CTDNEP1 post-translationally modulates the activities of key regulators for chromosome segregation and mitotic checkpoint regulators including topoisomerase TOP2A and checkpoint kinase CHEK1

cell & other

REGULATION

activated by

HMGB1, HMGB2 (could significantly up-regulate TOP2A gene promoter only in cells lacking functional retinoblastoma protein pRb) (Stros 2009)

inhibited by

Rb during cell cycle

Other	markely upregulated in proliferating cells
	phosphorylated by aurora B kinase AURKB

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     or amplified simultaneously with ERBB2 in breast cancers tumoral     --over   in gastric cancer

Susceptibility

Variant & Polymorphism	including a variant associated with drug resistance

Candidate gene
Marker	its expression is a valuable prognostic indicator for colorectal cancer (useful in treatment selection for early colorectal cancer and malignant colorectal polyps resected under endoscopy)
	independent prognostic biomarker of disease free survival in postoperative non-small cell lung cancer patients who received adjuvant chemotherapy (
	TOP2A/CEP17 ratio may be a useful predictor of the effects of anthracycline-based neoadjuvant chemotherapy in breast cancer
Therapy target

ANIMAL & CELL MODELS