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Q01320 (TOP2A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
DNA topoisomerase 2-alpha

EC=5.99.1.3
Alternative name(s):
DNA topoisomerase II, alpha isozyme
Gene names
Name:Top2a
Synonyms:Top-2, Top2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1528 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.1

Catalytic activity

ATP-dependent breakage, passage and rejoining of double-stranded DNA. Ref.1

Cofactor

Magnesium. Binds two Mg2+ per subunit. The magnesium ions form salt bridges with both the protein and the DNA. Can also accept other divalent metal cations, such as Mn2+ and Ca2+ By similarity.

Subunit structure

Homodimer. Interacts with COPS5. Interacts with RECQL5; this stimulates DNA decatenation By similarity.

Subcellular location

Nucleus.

Post-translational modification

Phosphorylation has no effect on catalytic activity. However, phosphorylation at Ser-1105 by CSNK1D/CK1 promotes DNA cleavable complex formation By similarity.

Miscellaneous

Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.

Sequence similarities

Belongs to the type II topoisomerase family.

Contains 1 Toprim domain.

Ontologies

Keywords
   Cellular componentNucleus
   LigandATP-binding
DNA-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionIsomerase
Topoisomerase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP catabolic process

Inferred from direct assay Ref.1PubMed 7842491PubMed 9094096. Source: GOC

DNA ligation

Inferred from electronic annotation. Source: Ensembl

DNA topological change

Inferred from direct assay Ref.1PubMed 9224616. Source: MGI

DNA-dependent DNA replication

Inferred from Biological aspect of Ancestor. Source: RefGenome

apoptotic chromosome condensation

Inferred from electronic annotation. Source: Ensembl

cellular response to DNA damage stimulus

Inferred from electronic annotation. Source: Ensembl

chromosome condensation

Inferred from mutant phenotype PubMed 11835580. Source: MGI

chromosome segregation

Inferred from direct assay PubMed 7842491. Source: MGI

embryonic cleavage

Inferred from mutant phenotype PubMed 11835580. Source: MGI

mitotic DNA integrity checkpoint

Inferred from Biological aspect of Ancestor. Source: RefGenome

mitotic recombination

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of single stranded viral RNA replication via double stranded DNA intermediate

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 1683482. Source: MGI

resolution of meiotic recombination intermediates

Inferred from Biological aspect of Ancestor. Source: RefGenome

sister chromatid segregation

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentDNA topoisomerase complex (ATP-hydrolyzing)

Inferred from electronic annotation. Source: Ensembl

centriole

Inferred from electronic annotation. Source: Ensembl

condensed chromosome

Inferred from direct assay PubMed 11835579. Source: MGI

nucleolus

Inferred from direct assay PubMed 11835579. Source: MGI

nucleoplasm

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 9094096PubMed 9224616. Source: MGI

synaptonemal complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA binding, bending

Inferred from sequence or structural similarity. Source: UniProtKB

DNA topoisomerase type II (ATP-hydrolyzing) activity

Inferred from direct assay Ref.1PubMed 7842491PubMed 9094096. Source: MGI

chromatin binding

Inferred from electronic annotation. Source: Ensembl

drug binding

Inferred from electronic annotation. Source: Ensembl

magnesium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 15281528DNA topoisomerase 2-alpha
PRO_0000145364

Regions

Domain454 – 571118Toprim
Nucleotide binding147 – 1493ATP By similarity
Nucleotide binding160 – 1678ATP By similarity
Nucleotide binding375 – 3773ATP By similarity
Region341 – 3433Interaction with DNA By similarity
Region989 – 99810Interaction with DNA By similarity

Sites

Active site8041O-(5'-phospho-DNA)-tyrosine intermediate By similarity
Metal binding4601Magnesium 1; catalytic By similarity
Metal binding5401Magnesium 1; catalytic By similarity
Metal binding5401Magnesium 2 By similarity
Metal binding5421Magnesium 2 By similarity
Binding site901ATP By similarity
Binding site1191ATP By similarity
Site4881Interaction with DNA By similarity
Site4911Interaction with DNA By similarity
Site6601Interaction with DNA By similarity
Site6611Interaction with DNA By similarity
Site7221Interaction with DNA By similarity
Site7561Interaction with DNA By similarity
Site7621Interaction with DNA By similarity
Site8031Transition state stabilizer By similarity
Site8551Important for DNA bending; intercalates between base pairs of target DNA By similarity
Site9301Interaction with DNA By similarity

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue41Phosphoserine By similarity
Modified residue2811Phosphothreonine By similarity
Modified residue11051Phosphoserine; by CK1 By similarity
Modified residue12111Phosphoserine By similarity
Modified residue12911Phosphoserine By similarity
Modified residue12931Phosphoserine By similarity
Modified residue12951Phosphoserine By similarity
Modified residue12981Phosphoserine By similarity
Modified residue13281Phosphoserine By similarity
Modified residue13331Phosphoserine By similarity
Modified residue13701Phosphoserine By similarity
Modified residue13731Phosphoserine By similarity
Modified residue13841Phosphoserine By similarity
Modified residue14181N6-acetyllysine Ref.4
Modified residue14381N6-acetyllysine Ref.4
Modified residue14651Phosphoserine By similarity
Modified residue14671Phosphoserine By similarity
Modified residue14701Phosphoserine By similarity
Modified residue14721Phosphoserine By similarity
Modified residue15211Phosphoserine By similarity

Experimental info

Sequence conflict1841E → A in BAA02076. Ref.1
Sequence conflict2601S → M in BAA02076. Ref.1
Sequence conflict6401S → P in BAA02076. Ref.1
Sequence conflict8411I → N in BAA02076. Ref.1
Sequence conflict844 – 8452IP → NT in BAA02076. Ref.1
Sequence conflict13161A → R in BAA02076. Ref.1
Sequence conflict13161A → R in AAC52135. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q01320 [UniParc].

Last modified December 14, 2011. Version 2.
Checksum: 63CBF8F649D103C7

FASTA1,528172,790
        10         20         30         40         50         60 
MELSPLQPVN ENMLMNKKKN EDGKKRLSIE RIYQKKTQLE HILLRPDTYI GSVELVTQQM 

        70         80         90        100        110        120 
WVYDEDVGIN YREVTFVPGL YKIFDEILVN AADNKQRDPK MSCIRVTIDP ENNVISIWNN 

       130        140        150        160        170        180 
GKGIPVVEHK VEKIYVPALI FGQLLTSSNY DDDEKKVTGG RNGYGAKLCN IFSTKFTVET 

       190        200        210        220        230        240 
ASREYKKMFK QTWMDNMGRA GDMELKPFSG EDYTCITFQP DLSKFKMQSL DKDIVALMVR 

       250        260        270        280        290        300 
RAYDIAGSTK DVKVFLNGNS LPVKGFRSYV DLYLKDKVDE TGNSLKVIHE QVNPRWEVCL 

       310        320        330        340        350        360 
TMSERGFQQI SFVNSIATSK GGRHVDYVAD QIVSKLVDVV KKKNKGGVAV KAHQVKNHMW 

       370        380        390        400        410        420 
IFVNALIENP TFDSQTKENM TLQAKSFGST CQLSEKFIKA AIGCGIVESI LNWVKFKAQI 

       430        440        450        460        470        480 
QLNKKCSAVK HTKIKGIPKL DDANDAGSRN STECTLILTE GDSAKTLAVS GLGVVGRDKY 

       490        500        510        520        530        540 
GVFPLRGKIL NVREASHKQI MENAEINNII KIVGLQYKKN YEDEDSLKTL RYGKIMIMTD 

       550        560        570        580        590        600 
QDQDGSHIKG LLINFIHHNW PSLLRHRFLE EFITPIVKVS KNKQEIAFYS LPEFEEWKSS 

       610        620        630        640        650        660 
TPNHKKWKVK YYKGLGTSTS KEAKEYFADM KRHRIQFKYS GPEDDAAISL AFSKKQVDDR 

       670        680        690        700        710        720 
KEWLTNFMED RRQRKLLGLP EDYLYGQSTS YLTYNDFINK ELILFSNSDN ERSIPSMVDG 

       730        740        750        760        770        780 
LKPGQRKVLF TCFKRNDKRE VKVAQLAGSV AEMSSYHHGE MSLMMTIINL AQNFVGSNNL 

       790        800        810        820        830        840 
NLLQPIGQFG TRLHGGKDSA SPRYIFTMLS PLARLLFPPK DDHTLRFLYD DNQRVEPEWY 

       850        860        870        880        890        900 
IPIIPMVLIN GAEGIGTGWS CKIPNFDVRE VVNNIRRLLD GEEPLPMLPS YKNFKGTIEE 

       910        920        930        940        950        960 
LASNQYVING EVAILDSTTI EISELPIRTW TQTYKEQVLE PMLNGTEKTP SLITDYREYH 

       970        980        990       1000       1010       1020 
TDTTVKFVIK MTEEKLAEAE RVGLHKVFKL QSSLTCNSMV LFDHVGCLKK YDTVLDILRD 

      1030       1040       1050       1060       1070       1080 
FFELRLKYYG LRKEWLLGML GAESSKLNNQ ARFILEKIDG KIVIENKPKK ELIKVLIQRG 

      1090       1100       1110       1120       1130       1140 
YDSDPVKAWK EAQQKVPDEE ENEESDTETS TSDSAAEAGP TFNYLLDMPL WYLTKEKKDE 

      1150       1160       1170       1180       1190       1200 
LCKQRNEKEQ ELNTLKQKSP SDLWKEDLAV FIEELEVVEA KEKQDEQVGL PGKAGKAKGK 

      1210       1220       1230       1240       1250       1260 
KAQMCADVLP SPRGKRVIPQ VTVEMKAEAE KKIRKKIKSE NVEGTPAEDG AEPGSLRQRI 

      1270       1280       1290       1300       1310       1320 
EKKQKKEPGA KKQTTLPFKP VKKGRKKNPW SDSESDVSSN ESNVDVPPRQ KEQRSAAAKA 

      1330       1340       1350       1360       1370       1380 
KFTVDLDSDE DFSGLDEKDE DEDFLPLDAT PPKAKIPPKN TKKALKTQGS SMSVVDLESD 

      1390       1400       1410       1420       1430       1440 
VKDSVPASPG VPAADFPAET EQSKPSKKTV GVKKTATKSQ SSVSTAGTKK RAAPKGTKSD 

      1450       1460       1470       1480       1490       1500 
SALSARVSEK PAPAKAKNSR KRKPSSSDSS DSDFERAISK GATSKKAKGE EQDFPVDLED 

      1510       1520 
TIAPRAKSDR ARKPIKYLEE SDDDDDLF 

« Hide

References

« Hide 'large scale' references
[1]"Characterization of cDNA encoding the mouse DNA topoisomerase II that can complement the budding yeast top2 mutation."
Adachi N., Miyaike M., Ikeda H., Kikuchi A.
Nucleic Acids Res. 20:5297-5303(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION.
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]"Characterization of a DNA topoisomerase IIalpha gene rearrangement in adriamycin-resistant P388 leukemia: expression of a fusion messenger RNA transcript encoding topoisomerase IIalpha and the retinoic acid receptor alpha locus."
McPherson J., Brown G.A., Goldenberg G.J.
Cancer Res. 53:5885-5889(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1254-1528.
Tissue: Lymphoma.
[4]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1418 AND LYS-1438, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D12513 mRNA. Translation: BAA02076.1.
AL591067 Genomic DNA. No translation available.
U01915 mRNA. Translation: AAC52135.1.
PIRJS0703.
RefSeqNP_035753.2. NM_011623.2.
XP_006533216.1. XM_006533153.1.
UniGeneMm.4237.

3D structure databases

ProteinModelPortalQ01320.
SMRQ01320. Positions 28-404, 433-1187.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-40621N.
IntActQ01320. 8 interactions.
MINTMINT-1712967.

Chemistry

BindingDBQ01320.
ChEMBLCHEMBL3586.
GuidetoPHARMACOLOGY2637.

PTM databases

PhosphoSiteQ01320.

Proteomic databases

PaxDbQ01320.
PRIDEQ01320.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000068031; ENSMUSP00000068896; ENSMUSG00000020914.
GeneID21973.
KEGGmmu:21973.
UCSCuc007lid.1. mouse.

Organism-specific databases

CTD7153.
MGIMGI:98790. Top2a.

Phylogenomic databases

eggNOGCOG0187.
GeneTreeENSGT00390000016222.
HOGENOMHOG000216693.
HOVERGENHBG052998.
InParanoidQ01320.
KOK03164.
OMAENMTLQV.
OrthoDBEOG73JKTM.
TreeFamTF105282.

Gene expression databases

ArrayExpressQ01320.
BgeeQ01320.
CleanExMM_TOP2A.
GenevestigatorQ01320.

Family and domain databases

Gene3D1.10.268.10. 1 hit.
3.30.1360.40. 1 hit.
3.30.230.10. 1 hit.
3.30.565.10. 1 hit.
3.40.50.670. 1 hit.
3.90.199.10. 1 hit.
InterProIPR024946. Arg_repress_C-like.
IPR012542. DTHCT.
IPR003594. HATPase_ATP-bd.
IPR020568. Ribosomal_S5_D2-typ_fold.
IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
IPR028466. Top2a.
IPR001241. Topo_IIA.
IPR002205. Topo_IIA_A/C.
IPR013758. Topo_IIA_A/C_ab.
IPR013757. Topo_IIA_A_a.
IPR013506. Topo_IIA_bsu_dom2.
IPR013759. Topo_IIA_cen_dom.
IPR013760. Topo_IIA_like_dom.
IPR018522. TopoIIA_CS.
IPR006171. Toprim_domain.
[Graphical view]
PANTHERPTHR10169:SF17. PTHR10169:SF17. 1 hit.
PfamPF00204. DNA_gyraseB. 1 hit.
PF00521. DNA_topoisoIV. 1 hit.
PF08070. DTHCT. 1 hit.
PF02518. HATPase_c. 1 hit.
PF01751. Toprim. 1 hit.
[Graphical view]
PRINTSPR00418. TPI2FAMILY.
SMARTSM00387. HATPase_c. 1 hit.
SM00433. TOP2c. 1 hit.
SM00434. TOP4c. 1 hit.
[Graphical view]
SUPFAMSSF54211. SSF54211. 1 hit.
SSF55874. SSF55874. 1 hit.
SSF56719. SSF56719. 1 hit.
PROSITEPS00177. TOPOISOMERASE_II. 1 hit.
PS50880. TOPRIM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTOP2A. mouse.
NextBio301670.
PROQ01320.
SOURCESearch...

Entry information

Entry nameTOP2A_MOUSE
AccessionPrimary (citable) accession number: Q01320
Secondary accession number(s): E9PX08
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: December 14, 2011
Last modified: April 16, 2014
This is version 139 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot