Top2a

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity	IBA GO_REF:0000033	ACCEPT	Summary: Core molecular function. Top2a is an ATP-dependent type IIA DNA topoisomerase that cleaves both strands of a DNA duplex, passes a second duplex through the transient break, and religates the DNA, thereby relaxing supercoils and decatenating sister chromatids. Strongly supported by phylogeny and by direct mouse biochemistry. Reason: Core topoisomerase function of TOP2A Supporting Evidence: file:mouse/Top2a/Top2a-deep-research-falcon.md Top2a/TOP2A is an ATP-dependent type IIA DNA topoisomerase that resolves topological stress by creating a transient, enzyme-linked double-strand break in one DNA duplex (the “gate” segment) and transporting a second duplex (the “transport” segment) through the break before re-ligating the DNA.
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: Top2a carries out its catalytic function on chromatin in the nucleus. Mouse-cell evidence shows Top2a is chromatin-associated and enriched at heterochromatin. Reason: Core topoisomerase function of TOP2A Supporting Evidence: file:mouse/Top2a/Top2a-deep-research-falcon.md In mouse NIH3T3 fibroblasts, Top2α is chromatin-associated and described as enriched at heterochromatin.
GO:0000819 sister chromatid segregation	IBA GO_REF:0000033	ACCEPT	Summary: Decatenation of replicated sister chromatids by Top2a is required for their individualization and faithful segregation; this is the principal biological process the enzyme serves. Reason: Core topoisomerase function of TOP2A Supporting Evidence: file:mouse/Top2a/Top2a-deep-research-falcon.md TOP2A decatenation is required to enable sister chromatid individualization and faithful segregation, and catalytic inhibition can activate a decatenation checkpoint/G2 arrest phenotype in cell-based contexts
GO:0000712 resolution of meiotic recombination intermediates	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Top2a is expressed and active during meiosis in mouse (e.g. male meiosis), where decatenation activity can resolve recombination-derived DNA interlinks. This is a context-specific, non-core process relative to the enzyme's central mitotic/replicative decatenation role. Reason: Context-specific meiotic role, not the core molecular function
GO:0030263 apoptotic chromosome condensation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Top2a contributes to chromosome condensation; involvement in the chromatin condensation that accompanies apoptosis is a downstream, context-dependent process rather than the enzyme's core function. Reason: Context-dependent process, not the core molecular function
GO:0000166 nucleotide binding	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Generic parent of the specific ATP binding required to power the N-gate ATPase. Kept as non-core; the specific GO:0005524 (ATP binding) is the informative term. Reason: Generic parent of ATP binding; specific GO:0005524 is preferred
GO:0003677 DNA binding	IEA GO_REF:0000120	ACCEPT	Summary: Top2a binds double-stranded DNA as its catalytic substrate, forming the DNA-gate where cleavage and religation occur. Reason: Core topoisomerase function of TOP2A Supporting Evidence: file:mouse/Top2a/Top2a-deep-research-falcon.md Functionally, TOP2A’s substrate is double-stranded DNA in topologically constrained forms encountered in vivo: supercoiled DNA produced by replication/transcription and catenated sister chromatids produced by DNA replication.
GO:0003916 DNA topoisomerase activity	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Generic parent of the specific type II topoisomerase activity (GO:0003918), which is the informative core function term. Kept as non-core because the specific child term carries the informative function. Reason: Generic topoisomerase parent; specific GO:0003918 is the informative core MF
GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity	IEA GO_REF:0000120	ACCEPT	Summary: Core molecular function: ATP-dependent type II (double-strand cut) topoisomerase activity. Directly demonstrated for mouse Top2a by yeast top2-complementation and biochemical assays. Reason: Core topoisomerase function of TOP2A Supporting Evidence: file:mouse/Top2a/Top2a-deep-research-falcon.md The literature summarized here consistently describes TOP2A/Top2α as an ATP-dependent homodimeric type II topoisomerase that cleaves and religates double-stranded DNA during strand passage
GO:0005524 ATP binding	IEA GO_REF:0000120	ACCEPT	Summary: ATP binding at the N-terminal ATPase (N-gate) domain powers dimer closure and the strand-passage cycle; integral to the catalytic mechanism. Reason: Core topoisomerase function of TOP2A Supporting Evidence: file:mouse/Top2a/Top2a-deep-research-falcon.md an ATPase/N-gate (ATP binding/hydrolysis controls dimer closure)
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: Top2a executes its catalytic function on chromatin within the nucleus; it is nuclear/chromatin-associated and enriched at heterochromatin in mouse cells. Reason: Core topoisomerase function of TOP2A
GO:0005654 nucleoplasm	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Nucleoplasmic localization consistent with chromatin-associated activity; a valid sub-nuclear localization, secondary to the core MF. Reason: Valid annotation but not the core molecular function
GO:0005730 nucleolus	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Nucleolar localization is reported (CTD lysine-rich/polyphosphoinositide regions act as nucleolar localization signals), and mouse preimplantation embryos show nucleolar Top2 staining. Falcon notes that confidence for mouse-specific nucleolar localization is lower than for bulk chromatin/heterochromatin association. Kept as a valid, secondary localization. Reason: Secondary, context-dependent localization (lower confidence in mouse) Supporting Evidence: file:mouse/Top2a/Top2a-deep-research-falcon.md confidence for mouse-specific nucleolar localization is lower
GO:0005737 cytoplasm	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Top2a is predominantly nuclear/chromatin-associated; cytoplasmic signal is minor/context-dependent and not where the catalytic function is executed. Reason: Minor, context-dependent localization; function is nuclear
GO:0006259 DNA metabolic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: High-level parent process; the informative children are DNA topological change and chromosome segregation. Kept as non-core. Reason: High-level parent of the specific topological-change process
GO:0006265 DNA topological change	IEA GO_REF:0000120	ACCEPT	Summary: Core biological-process counterpart of the topoisomerase activity: Top2a changes DNA topology by relaxing supercoils and unlinking catenated duplexes. Reason: Core topoisomerase function of TOP2A Supporting Evidence: file:mouse/Top2a/Top2a-deep-research-falcon.md This activity changes DNA topology and enables both relaxation of supercoils and decatenation (unlinking) of interlinked DNA duplexes
GO:0016853 isomerase activity	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Top-level EC-class parent (EC 5; the enzyme is EC 5.6.2.2). The informative term is the specific type II topoisomerase activity (GO:0003918). Kept as non-core. Reason: High-level isomerase parent; specific GO:0003918 is preferred
GO:0046872 metal ion binding	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: Generic metal-binding parent. The catalytically relevant metal is Mg2+ coordinated by the TOPRIM domain (captured by the specific GO:0000287 magnesium ion binding). This generic term is uninformative. Reason: Generic term; specific GO:0000287 magnesium ion binding is informative
GO:0048511 rhythmic process	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Reflects reports that Top2 activity influences circadian period (e.g. Top2 inhibition by shikonin shortens the period). This is a peripheral, context-dependent role, not the enzyme's core function. Reason: Peripheral circadian role; not the core function
GO:0005515 protein binding	IPI PMID:23698369 BAF complexes facilitate decatenation of DNA by topoisomeras...	MARK AS OVER ANNOTATED	Summary: Uninformative parent term ("protein binding"). The specific interaction (BAF/SWI-SNF chromatin remodellers facilitating Top2α decatenation) is better captured by a process annotation; per curation guidelines this generic MF term is over-annotated. Reason: Uninformative protein binding term; specific interaction is better captured elsewhere Supporting Evidence: PMID:23698369 BAF complexes facilitate decatenation of DNA by topoisomerase IIα.
GO:0000228 nuclear chromosome	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Top2a localizes to nuclear chromosomes/chromatin where it acts; becomes tightly chromosome-associated in mitosis. Valid localization, more specific than nucleus but secondary for this review. Reason: Valid chromosomal localization; secondary to core MF
GO:0000287 magnesium ion binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Catalytically meaningful: the TOPRIM domain coordinates Mg2+ required for the DNA cleavage/religation chemistry of the type II topoisomerase reaction. The specific magnesium term is preferred over generic metal ion binding. Reason: Catalytically relevant Mg2+ cofactor binding (TOPRIM) Supporting Evidence: file:mouse/Top2a/Top2a-deep-research-falcon.md DNA binding induces conformational rearrangements that assemble the cleavage–religation center, including TOPRIM-mediated metal coordination
GO:0003682 chromatin binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Top2a is chromatin-associated and enriched at heterochromatin in mouse cells; catalytic inhibition (ICRF-193) increases chromatin association and retention. Valid but secondary to the catalytic MF. Reason: Valid chromatin association; secondary to core MF Supporting Evidence: file:mouse/Top2a/Top2a-deep-research-falcon.md catalytic inhibition with ICRF-193 (a catalytic Top2 inhibitor) increases Top2α chromatin association and retention
GO:0005080 protein kinase C binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Reported protein kinase C binding; a regulatory interaction that is peripheral to the catalytic function. Kept as non-core. Reason: Valid annotation, context-dependent
GO:0005814 centriole	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Centriole localization is a context-dependent/minor pool; not where the core decatenation function is executed. Reason: Valid annotation, context-dependent
GO:0006325 chromatin organization	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Top2a contributes to chromatin organization (e.g. heterochromatin/repeat integrity), a process supporting genome stability but secondary to the catalytic MF. Reason: Valid annotation, context-dependent
GO:0006974 DNA damage response	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Top2 catalytic activity is required for the integrity of heterochromatin and repetitive DNA; trapped cleavage complexes generate protein-linked DNA breaks. This is a downstream/context role rather than the core function. Reason: Context-dependent role in genome-integrity/damage responses
GO:0007059 chromosome segregation	IEA GO_REF:0000107	ACCEPT	Summary: Decatenation of sister chromatids by Top2a is essential for chromosome segregation; inhibition/depletion causes chromosome bridges and segregation failure. A core biological process for this enzyme. Reason: Core topoisomerase function of TOP2A Supporting Evidence: file:mouse/Top2a/Top2a-deep-research-falcon.md TOP2A is a major mitotic chromosome-associated factor with key roles in chromosome structure and segregation
GO:0008094 ATP-dependent activity, acting on DNA	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Generic parent capturing the ATP-driven action on DNA. The specific type II topoisomerase activity (GO:0003918) is the informative MF. Reason: Generic parent of the specific topoisomerase MF
GO:0008301 DNA binding, bending	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: DNA bending accompanies type II topoisomerase strand passage; captured here as a mechanistic sub-feature, secondary to the core catalytic MF. Reason: Valid annotation, context-dependent
GO:0009330 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Top2a functions as a homodimeric type II topoisomerase complex; this complex term is consistent with the homodimerization activity but secondary to the catalytic MF. Reason: Valid annotation, context-dependent
GO:0030263 apoptotic chromosome condensation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Top2a contributes to chromosome condensation; the chromatin condensation accompanying apoptosis is a downstream, context-dependent process rather than the enzyme's core decatenation function. Reason: Context-dependent process, not the core molecular function
GO:0032991 protein-containing complex	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Generic protein-containing-complex parent; uninformative as a standalone term. The relevant complex is the homodimeric type II topoisomerase (GO:0009330). Reason: Valid annotation, context-dependent
GO:0042803 protein homodimerization activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Top2a is an obligate homodimer; homodimerization assembles the two-gate enzyme. A structural prerequisite for catalysis, recorded as non-core MF. Reason: Valid annotation, context-dependent
GO:0043065 positive regulation of apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Top2a-associated DNA damage (e.g. from trapped cleavage complexes) can promote apoptosis; a downstream/context-dependent effect, non-core. Reason: Valid annotation, context-dependent
GO:0043130 ubiquitin binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Reported ubiquitin binding; a regulatory/turnover-related interaction peripheral to the catalytic function. Non-core. Reason: Valid annotation, context-dependent
GO:0045870 positive regulation of single stranded viral RNA replication via double stranded DNA intermediate	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Reflects a viral-replication context annotation transferred by orthology; peripheral and not the core mammalian function. Reason: Valid annotation, context-dependent
GO:0046982 protein heterodimerization activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Heterodimerization (e.g. with Top2b) is reported; peripheral to the obligate homodimeric catalytic mechanism. Non-core. Reason: Valid annotation, context-dependent
GO:1990904 ribonucleoprotein complex	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Generic ribonucleoprotein-complex parent transferred by orthology. Top2a is not a ribonucleoprotein; its functional assembly is the protein homodimer. This term is inapplicable and represents an over-annotation. Reason: Top2a is not a ribonucleoprotein complex; term is inapplicable and over-annotated
GO:0009330 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: Top2a functions as a homodimeric type II topoisomerase complex; this complex term is consistent with the homodimerization activity but secondary to the catalytic MF. Reason: Valid annotation, context-dependent
GO:0000228 nuclear chromosome	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Top2a localizes to nuclear chromosomes/chromatin where it acts and becomes tightly chromosome-associated during mitosis. Valid localization, secondary to the core MF. Reason: Valid annotation, context-dependent
GO:0000287 magnesium ion binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Catalytically meaningful Mg2+ cofactor binding: the TOPRIM domain coordinates the magnesium ion required for DNA cleavage/religation chemistry of the type II topoisomerase reaction. Reason: Valid annotation, context-dependent
GO:0003677 DNA binding	ISO GO_REF:0000096	ACCEPT	Summary: Top2a binds double-stranded DNA as its catalytic substrate, forming the DNA-gate where cleavage and religation occur. Core to the topoisomerase mechanism. Reason: Core topoisomerase function of TOP2A
GO:0003677 DNA binding	ISO GO_REF:0000119	ACCEPT	Summary: Top2a binds double-stranded DNA as its catalytic substrate, forming the DNA-gate where cleavage and religation occur. Core to the topoisomerase mechanism. Reason: Core topoisomerase function of TOP2A
GO:0003682 chromatin binding	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: Top2a is chromatin-associated and enriched at heterochromatin in mouse cells; catalytic inhibition increases chromatin association. Valid but secondary to the catalytic MF. Reason: Valid annotation, context-dependent
GO:0003682 chromatin binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Top2a is chromatin-associated and enriched at heterochromatin in mouse cells; catalytic inhibition increases chromatin association. Valid but secondary to the catalytic MF. Reason: Valid annotation, context-dependent
GO:0003916 DNA topoisomerase activity	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: Generic topoisomerase-activity parent; the informative core function term is the specific type II (double-strand cut, ATP-hydrolyzing) activity GO:0003918. Kept as non-core because the specific child carries the informative function. Reason: Generic topoisomerase parent; specific GO:0003918 is the informative core MF
GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity	ISO GO_REF:0000096	ACCEPT	Summary: Core molecular function: ATP-dependent type II (double-strand cut) topoisomerase activity. Directly demonstrated for mouse Top2a by yeast top2-complementation and biochemical assays. Reason: Core topoisomerase function of TOP2A
GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity	ISO GO_REF:0000119	ACCEPT	Summary: Core molecular function: ATP-dependent type II (double-strand cut) topoisomerase activity. Directly demonstrated for mouse Top2a by yeast top2-complementation and biochemical assays. Reason: Core topoisomerase function of TOP2A
GO:0005080 protein kinase C binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Reported protein kinase C binding; a regulatory interaction that is peripheral to the catalytic function. Kept as non-core. Reason: Valid annotation, context-dependent
GO:0005524 ATP binding	ISO GO_REF:0000096	ACCEPT	Summary: ATP binding at the N-terminal ATPase (N-gate) domain powers dimer closure and the strand-passage cycle; integral to the catalytic mechanism. Reason: Core topoisomerase function of TOP2A
GO:0005634 nucleus	ISO GO_REF:0000119	ACCEPT	Summary: Top2a executes its catalytic function on chromatin within the nucleus; it is nuclear/chromatin-associated and enriched at heterochromatin in mouse cells. Reason: Core topoisomerase function of TOP2A
GO:0005654 nucleoplasm	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Nucleoplasmic localization consistent with chromatin-associated activity; a valid sub-nuclear localization, secondary to the core MF. Reason: Valid annotation but not the core molecular function
GO:0005730 nucleolus	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Nucleolar localization is reported (CTD lysine-rich regions act as nucleolar localization signals) and mouse embryos show nucleolar Top2 staining, though mouse-specific nucleolar confidence is lower. Secondary localization. Reason: Valid annotation, context-dependent
GO:0005737 cytoplasm	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Top2a is predominantly nuclear/chromatin-associated; cytoplasmic signal is minor and context-dependent, not where catalysis occurs. Reason: Valid annotation, context-dependent
GO:0005814 centriole	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Centriole localization is a context-dependent/minor pool; not where the core decatenation function is executed. Reason: Valid annotation, context-dependent
GO:0006265 DNA topological change	ISO GO_REF:0000096	ACCEPT	Summary: Core biological-process counterpart of the topoisomerase activity: Top2a changes DNA topology by relaxing supercoils and unlinking catenated duplexes. Reason: Core topoisomerase function of TOP2A
GO:0006265 DNA topological change	ISO GO_REF:0000119	ACCEPT	Summary: Core biological-process counterpart of the topoisomerase activity: Top2a changes DNA topology by relaxing supercoils and unlinking catenated duplexes. Reason: Core topoisomerase function of TOP2A
GO:0006325 chromatin organization	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Top2a contributes to chromatin organization (e.g. heterochromatin/repeat integrity), a process supporting genome stability but secondary to the catalytic MF. Reason: Valid annotation, context-dependent
GO:0006974 DNA damage response	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Top2 catalytic activity is required for heterochromatin/repetitive-DNA integrity; trapped cleavage complexes generate DNA breaks. A downstream/context role, not the core function. Reason: Valid annotation but not the core molecular function
GO:0007059 chromosome segregation	ISO GO_REF:0000119	ACCEPT	Summary: Decatenation of sister chromatids by Top2a is essential for chromosome segregation; inhibition/depletion causes chromosome bridges and segregation failure. Core biological process. Reason: Core topoisomerase function of TOP2A
GO:0008094 ATP-dependent activity, acting on DNA	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Generic parent describing ATP-driven action on DNA; the specific type II topoisomerase activity (GO:0003918) is the informative MF. Reason: Valid annotation, context-dependent
GO:0008301 DNA binding, bending	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: DNA bending accompanies type II topoisomerase strand passage; captured here as a mechanistic sub-feature, secondary to the core catalytic MF. Reason: Valid annotation, context-dependent
GO:0009330 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Top2a functions as a homodimeric type II topoisomerase complex; this complex term is consistent with the homodimerization activity but secondary to the catalytic MF. Reason: Valid annotation, context-dependent
GO:0030263 apoptotic chromosome condensation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Top2a contributes to chromosome condensation; the chromatin condensation accompanying apoptosis is a downstream, context-dependent process rather than the enzyme's core decatenation function. Reason: Context-dependent process, not the core molecular function
GO:0032991 protein-containing complex	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Generic protein-containing-complex parent; uninformative as a standalone term. The relevant complex is the homodimeric type II topoisomerase (GO:0009330). Reason: Valid annotation, context-dependent
GO:0042803 protein homodimerization activity	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Top2a is an obligate homodimer; homodimerization assembles the two-gate enzyme. A structural prerequisite for catalysis, recorded as non-core MF. Reason: Valid annotation, context-dependent
GO:0043065 positive regulation of apoptotic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Top2a-associated DNA damage (e.g. from trapped cleavage complexes) can promote apoptosis; a downstream/context-dependent effect, non-core. Reason: Valid annotation, context-dependent
GO:0043130 ubiquitin binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Reported ubiquitin binding; a regulatory/turnover-related interaction peripheral to the catalytic function. Non-core. Reason: Valid annotation, context-dependent
GO:0043565 sequence-specific DNA binding	ISO GO_REF:0000096	MARK AS OVER ANNOTATED	Summary: Type II topoisomerases act on duplex DNA largely without strict sequence specificity; Top2a recognizes DNA topology/geometry rather than a defined sequence motif. Sequence-specific DNA binding is therefore inapplicable and represents an over-annotation; the informative term is general DNA binding (GO:0003677). Reason: Top2a binds duplex DNA without strict sequence specificity; sequence-specific binding is inapplicable and over-annotated
GO:0045870 positive regulation of single stranded viral RNA replication via double stranded DNA intermediate	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Reflects a viral-replication context annotation transferred by orthology; peripheral and not the core mammalian function. Reason: Valid annotation, context-dependent
GO:0046982 protein heterodimerization activity	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Heterodimerization (e.g. with Top2b) is reported; peripheral to the obligate homodimeric catalytic mechanism. Non-core. Reason: Valid annotation, context-dependent
GO:1990904 ribonucleoprotein complex	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Generic ribonucleoprotein-complex parent transferred by orthology. Top2a is not a ribonucleoprotein; its functional assembly is the protein homodimer. This term is inapplicable and represents an over-annotation. Reason: Top2a is not a ribonucleoprotein complex; term is inapplicable and over-annotated
GO:0005515 protein binding	IPI PMID:31839538 GCNA Interacts with Spartan and Topoisomerase II to Regulate...	MARK AS OVER ANNOTATED	Summary: Uninformative generic protein-binding term. The specific interaction (GCNA/Spartan with Top2 to resolve topoisomerase cleavage complexes and maintain genome stability) is better captured by dedicated process/interaction annotations; per curation guidelines this generic MF term is over-annotated. Reason: Uninformative protein binding term; specific interaction is better captured elsewhere Supporting Evidence: PMID:31839538 2019 Dec 12. GCNA Interacts with Spartan and Topoisomerase II to Regulate Genome Stability.
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-5228515	KEEP AS NON CORE	Summary: Nucleoplasmic localization consistent with chromatin-associated activity; a valid sub-nuclear localization, secondary to the core MF. Reason: Valid annotation but not the core molecular function
GO:0005654 nucleoplasm	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Nucleoplasmic localization consistent with chromatin-associated activity; a valid sub-nuclear localization, secondary to the core MF. Reason: Valid annotation but not the core molecular function
GO:0005737 cytoplasm	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Top2a is predominantly nuclear/chromatin-associated; cytoplasmic signal is minor and context-dependent, not where catalysis occurs. Reason: Valid annotation, context-dependent
GO:0000775 chromosome, centromeric region	IDA PMID:26919979 Conditional mutation of Smc5 in mouse embryonic stem cells p...	UNDECIDED	Summary: The cited reference (PMID:26919979) characterizes the Smc5/6 complex and condensin localization in mouse embryonic stem cells; its abstract does not mention Top2a, and the previous supporting_text was only the paper title. Centromeric/pericentromeric localization of Top2a is biologically plausible, but a Top2a-specific IDA cannot be verified from this reference without an extracted quote. Marked UNDECIDED pending verification of Top2a-specific text in the paper body. Reason: Cited PMID:26919979 (Smc5/6 paper) does not mention Top2a in its abstract; Top2a-specific support not verifiable
GO:1990904 ribonucleoprotein complex	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Generic ribonucleoprotein-complex parent transferred by orthology. Top2a is not a ribonucleoprotein; its functional assembly is the protein homodimer. This term is inapplicable and represents an over-annotation. Reason: Top2a is not a ribonucleoprotein complex; term is inapplicable and over-annotated
GO:0005634 nucleus	IDA PMID:25961503 Condensin confers the longitudinal rigidity of chromosomes.	UNDECIDED	Summary: Nuclear localization of Top2a is well established and is a core feature, but the cited reference (PMID:25961503) is a study of condensin longitudinal rigidity in mouse oocytes; its abstract does not mention Top2a, and the previous supporting_text was only the paper title. This specific IDA citation cannot be verified for Top2a. Marked UNDECIDED; nuclear localization itself remains well-supported by other annotations (e.g. PMID:9094096, PMID:9224616). Reason: Cited PMID:25961503 (condensin paper) does not mention Top2a in its abstract; this IDA citation not verifiable
GO:0007143 female meiotic nuclear division	IMP PMID:25961503 Condensin confers the longitudinal rigidity of chromosomes.	UNDECIDED	Summary: The cited reference (PMID:25961503) is a study of condensin I/II in mouse oocyte meiosis I; its abstract does not mention Top2a, and the previous supporting_text was only the paper title. A Top2a-specific IMP for female meiotic nuclear division cannot be verified from this reference without an extracted quote. Marked UNDECIDED pending verification of Top2a-specific text in the paper body. Reason: Cited PMID:25961503 (condensin paper) does not mention Top2a in its abstract; Top2a-specific IMP not verifiable
GO:0051309 female meiosis chromosome separation	TAS PMID:25961503 Condensin confers the longitudinal rigidity of chromosomes.	UNDECIDED	Summary: The cited reference (PMID:25961503) is a study of condensin in mouse oocyte meiosis I; its abstract does not mention Top2a, and the previous supporting_text was only the paper title. A Top2a-specific annotation for female meiosis chromosome separation cannot be verified from this reference without an extracted quote. Marked UNDECIDED pending verification of Top2a-specific text in the paper body. Reason: Cited PMID:25961503 (condensin paper) does not mention Top2a in its abstract; Top2a-specific support not verifiable
GO:0000793 condensed chromosome	IMP PMID:21795393 Condensins I and II are essential for construction of bivale...	KEEP AS NON CORE	Summary: Top2a is associated with condensed mitotic/meiotic chromosomes and contributes to their architecture; a localization/process consistent with its role but secondary to the catalytic MF. Reason: Valid annotation but not the core molecular function Supporting Evidence: PMID:21795393 2011 Jul 27. Condensins I and II are essential for construction of bivalent chromosomes in mouse oocytes.
GO:0042752 regulation of circadian rhythm	IMP PMID:24321095 Shikonin shortens the circadian period: possible involvement...	KEEP AS NON CORE	Summary: Top2 activity influences circadian period (Top2 inhibition shortens the period); a peripheral regulatory role, not the core function. Reason: Valid annotation, context-dependent Supporting Evidence: PMID:24321095 Shikonin shortens the circadian period: possible involvement of Top2 inhibition.
GO:0002244 hematopoietic progenitor cell differentiation	IMP PMID:24029230 Haploinsufficiency of SAMD9L, an endosome fusion facilitator...	UNDECIDED	Summary: Cannot be adjudicated here: PMID:24029230 is cached abstract-only. Prior observation, not a verdict: The cited reference (PMID:24029230) is a study of SAMD9L, an endosome fusion facilitator, in mouse myeloid malignancies; the abstract makes no mention of Top2a or topoisomerase. There is no support in this paper for a Top2a role in hematopoietic progenitor cell differentiation, so this annotation was suspected to be a database/reference error, and it was questioned. Reason: PMID:24029230 is cached abstract-only, so the curator's experimental evidence cannot be inspected here; per CLAUDE.md an experimental annotation is not overruled on that basis. Recorded observation, not a verdict: Cited PMID:24029230 is a SAMD9L study with no Top2a/topoisomerase connection; annotation is unsupported
GO:0000287 magnesium ion binding	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Catalytically meaningful Mg2+ cofactor binding: the TOPRIM domain coordinates the magnesium ion required for DNA cleavage/religation chemistry of the type II topoisomerase reaction. Reason: Valid annotation, context-dependent
GO:0008301 DNA binding, bending	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: DNA bending accompanies type II topoisomerase strand passage; captured here as a mechanistic sub-feature, secondary to the core catalytic MF. Reason: Valid annotation, context-dependent
GO:0000793 condensed chromosome	IDA PMID:11835579 DNA topoisomerase II distribution in mouse preimplantation e...	KEEP AS NON CORE	Summary: Top2a is associated with condensed mitotic/meiotic chromosomes and contributes to their architecture; a localization/process consistent with its role but secondary to the catalytic MF. Reason: Valid annotation but not the core molecular function Supporting Evidence: PMID:11835579 DNA topoisomerase II distribution in mouse preimplantation embryos.
GO:0005730 nucleolus	IDA PMID:11835579 DNA topoisomerase II distribution in mouse preimplantation e...	KEEP AS NON CORE	Summary: Nucleolar localization is reported (CTD lysine-rich regions act as nucleolar localization signals) and mouse embryos show nucleolar Top2 staining, though mouse-specific nucleolar confidence is lower. Secondary localization. Reason: Valid annotation, context-dependent Supporting Evidence: PMID:11835579 DNA topoisomerase II distribution in mouse preimplantation embryos.
GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity	IDA PMID:7842491 Modulation of topoisomerase activities by tumor necrosis fac...	ACCEPT	Summary: Core molecular function: type II topoisomerase activity. This reference directly assayed topoisomerase II enzymatic activity in murine L929 cells, supporting the type II topoisomerase activity of mouse Top2a. Reason: Core topoisomerase function of TOP2A; reference directly assays topoisomerase II activity in murine cells Supporting Evidence: PMID:7842491 topoisomerase I and II activities were assayed following TNF addition to murine L929 cells. Topoisomerase I and II activities increased within 15 min of TNF addition
GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity	IDA PMID:9094096 Analysis of expression and function of topoisomerase I and I...	ACCEPT	Summary: Core molecular function: ATP-dependent type II (double-strand cut) topoisomerase activity. Directly demonstrated for mouse Top2a by yeast top2-complementation and biochemical assays. Reason: Core topoisomerase function of TOP2A Supporting Evidence: PMID:9094096 Analysis of expression and function of topoisomerase I and II during meiosis in male mice.
GO:0005634 nucleus	IDA PMID:9094096 Analysis of expression and function of topoisomerase I and I...	ACCEPT	Summary: Top2a executes its catalytic function on chromatin within the nucleus; it is nuclear/chromatin-associated and enriched at heterochromatin in mouse cells. Reason: Core topoisomerase function of TOP2A Supporting Evidence: PMID:9094096 Analysis of expression and function of topoisomerase I and II during meiosis in male mice.
GO:0007059 chromosome segregation	IDA PMID:7842491 Modulation of topoisomerase activities by tumor necrosis fac...	UNDECIDED	Summary: The cited reference (PMID:7842491) measured topoisomerase I/II enzymatic activity in murine L929 cells under TNF treatment; it supports type II topoisomerase activity (GO:0003918) but does not directly demonstrate a role in chromosome segregation, and the previous supporting_text was only the paper title. This specific IDA for chromosome segregation is not supported by this reference. Marked UNDECIDED; the chromosome segregation role of Top2a itself remains well-supported by other annotations (e.g. PMID:11835580). Reason: Cited PMID:7842491 assays topoisomerase activity, not chromosome segregation directly; IDA for this term not supported by this reference
GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity	IDA PMID:1331984 Characterization of cDNA encoding the mouse DNA topoisomeras...	ACCEPT	Summary: Core molecular function: ATP-dependent type II (double-strand cut) topoisomerase activity. Directly demonstrated for mouse Top2a by yeast top2-complementation and biochemical assays. Reason: Core topoisomerase function of TOP2A Supporting Evidence: PMID:1331984 Characterization of cDNA encoding the mouse DNA topoisomerase II that can complement the budding yeast top2 mutation.
GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity	IGI PMID:1331984 Characterization of cDNA encoding the mouse DNA topoisomeras...	ACCEPT	Summary: Core molecular function: ATP-dependent type II (double-strand cut) topoisomerase activity. Directly demonstrated for mouse Top2a by yeast top2-complementation and biochemical assays. Reason: Core topoisomerase function of TOP2A Supporting Evidence: PMID:1331984 Characterization of cDNA encoding the mouse DNA topoisomerase II that can complement the budding yeast top2 mutation.
GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity	IGI PMID:7937150 Mutant isolation of mouse DNA topoisomerase II alpha in yeas...	ACCEPT	Summary: Core molecular function: ATP-dependent type II (double-strand cut) topoisomerase activity. Directly demonstrated for mouse Top2a by yeast top2-complementation and biochemical assays. Reason: Core topoisomerase function of TOP2A Supporting Evidence: PMID:7937150 Mutant isolation of mouse DNA topoisomerase II alpha in yeast.
GO:0005634 nucleus	IDA PMID:9224616 Cellular distribution of mammalian DNA topoisomerase II is d...	ACCEPT	Summary: Top2a executes its catalytic function on chromatin within the nucleus; it is nuclear/chromatin-associated and enriched at heterochromatin in mouse cells. Reason: Core topoisomerase function of TOP2A Supporting Evidence: PMID:9224616 Cellular distribution of mammalian DNA topoisomerase II is determined by its catalytically dispensable C-terminal domain.
GO:0006265 DNA topological change	IDA PMID:1331984 Characterization of cDNA encoding the mouse DNA topoisomeras...	ACCEPT	Summary: Core biological-process counterpart of the topoisomerase activity: Top2a changes DNA topology by relaxing supercoils and unlinking catenated duplexes. Reason: Core topoisomerase function of TOP2A Supporting Evidence: PMID:1331984 Characterization of cDNA encoding the mouse DNA topoisomerase II that can complement the budding yeast top2 mutation.
GO:0006265 DNA topological change	IDA PMID:9224616 Cellular distribution of mammalian DNA topoisomerase II is d...	ACCEPT	Summary: Core biological-process counterpart of the topoisomerase activity: Top2a changes DNA topology by relaxing supercoils and unlinking catenated duplexes. Reason: Core topoisomerase function of TOP2A Supporting Evidence: PMID:9224616 Cellular distribution of mammalian DNA topoisomerase II is determined by its catalytically dispensable C-terminal domain.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:1683482 Possible role of DNA topoisomerase II on transcription of th...	KEEP AS NON CORE	Summary: Top2a has been linked to transcriptional activation (e.g. Hox-2.1 in F9 cells), consistent with topoisomerase relief of transcription-associated torsional stress. A context role, non-core. Reason: Valid annotation but not the core molecular function Supporting Evidence: PMID:1683482 Possible role of DNA topoisomerase II on transcription of the homeobox gene Hox-2.1 in F9 embryonal carcinoma cells.
GO:0007059 chromosome segregation	IMP PMID:11835580 DNA topoisomerase II is essential for preimplantation mouse ...	ACCEPT	Summary: Decatenation of sister chromatids by Top2a is essential for chromosome segregation; inhibition/depletion causes chromosome bridges and segregation failure. Core biological process. Reason: Core topoisomerase function of TOP2A Supporting Evidence: PMID:11835580 DNA topoisomerase II is essential for preimplantation mouse development.
GO:0030261 chromosome condensation	IMP PMID:11835580 DNA topoisomerase II is essential for preimplantation mouse ...	KEEP AS NON CORE	Summary: Top2a contributes to chromosome condensation, supporting mitotic/meiotic chromosome architecture. A supporting process, secondary to the catalytic MF. Reason: Valid annotation, context-dependent Supporting Evidence: PMID:11835580 DNA topoisomerase II is essential for preimplantation mouse development.
GO:0040016 embryonic cleavage	IMP PMID:11835580 DNA topoisomerase II is essential for preimplantation mouse ...	KEEP AS NON CORE	Summary: Top2a is essential for preimplantation/embryonic cleavage in mouse (knockout arrests at the 4-8 cell stage); a developmental requirement downstream of its replication/segregation function. Reason: Valid annotation, context-dependent Supporting Evidence: PMID:11835580 DNA topoisomerase II is essential for preimplantation mouse development.

Gene Description

Existing Annotations Review

Core Functions

Catalyzes ATP-dependent transient double-strand breaks in DNA to pass another DNA duplex through, resolving supercoils and decatenating sister chromatids after replication.

References

Deep Research

Falcon

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