DNA topoisomerase 2-alpha - Mus musculus (Mouse)

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Q01320 (TOP2A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 129. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1528 AA.
Sequence status	Complete.
Protein existence	Evidence 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 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 component	Nucleus
Ligand	ATP-binding DNA-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Isomerase Topoisomerase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA ligation Inferred from electronic annotation. Source: Compara DNA topological change Inferred from direct assay Ref.1 PubMed 9224616. Source: MGI DNA-dependent DNA replication Inferred from Biological aspect of Ancestor. Source: RefGenome apoptotic chromosome condensation Inferred from electronic annotation. Source: Compara chromosome condensation Inferred from mutant phenotype PubMed 11835580. 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: Compara positive regulation of retroviral genome replication Inferred from electronic annotation. Source: Compara 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 response to DNA damage stimulus Inferred from electronic annotation. Source: Compara sister chromatid segregation Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	DNA topoisomerase complex (ATP-hydrolyzing) Inferred from electronic annotation. Source: Compara centriole Inferred from electronic annotation. Source: Compara nucleolus Inferred from direct assay PubMed 11835579. Source: MGI nucleoplasm Inferred from electronic annotation. Source: Compara synaptonemal complex Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	ATP 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.1 PubMed 7842491 PubMed 9094096. Source: MGI chromatin binding Inferred from electronic annotation. Source: Compara drug binding Inferred from electronic annotation. Source: Compara magnesium ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1528

1528

DNA topoisomerase 2-alpha

PRO_0000145364

Regions

Domain

454 – 571

118

Toprim

Nucleotide binding

147 – 149

ATP By similarity

Nucleotide binding

160 – 167

ATP By similarity

Nucleotide binding

375 – 377

ATP By similarity

Region

341 – 343

Interaction with DNA By similarity

Region

989 – 998

Interaction with DNA By similarity

Sites

Active site

804

O-(5'-phospho-DNA)-tyrosine intermediate By similarity

Metal binding

460

Magnesium 1; catalytic By similarity

Metal binding

540

Magnesium 1; catalytic By similarity

Metal binding

540

Magnesium 2 By similarity

Metal binding

542

Magnesium 2 By similarity

Binding site

ATP By similarity

Binding site

119

ATP By similarity

Site

488

Interaction with DNA By similarity

Site

491

Interaction with DNA By similarity

Site

660

Interaction with DNA By similarity

Site

661

Interaction with DNA By similarity

Site

722

Interaction with DNA By similarity

Site

756

Interaction with DNA By similarity

Site

762

Interaction with DNA By similarity

Site

803

Transition state stabilizer By similarity

Site

855

Important for DNA bending; intercalates between base pairs of target DNA By similarity

Site

930

Interaction with DNA By similarity

Amino acid modifications

Modified residue

N-acetylmethionine By similarity

Modified residue

Phosphoserine By similarity

Modified residue

Phosphoserine Ref.6

Modified residue

281

Phosphothreonine By similarity

Modified residue

1105

Phosphoserine; by CK1 By similarity

Modified residue

1211

Phosphoserine By similarity

Modified residue

1291

Phosphoserine By similarity

Modified residue

1293

Phosphoserine By similarity

Modified residue

1295

Phosphoserine By similarity

Modified residue

1298

Phosphoserine By similarity

Modified residue

1328

Phosphoserine By similarity

Modified residue

1333

Phosphoserine Ref.5

Modified residue

1367

Phosphothreonine Ref.4

Modified residue

1370

Phosphoserine Ref.4

Modified residue

1371

Phosphoserine Ref.4

Modified residue

1373

Phosphoserine Ref.4

Modified residue

1379

Phosphoserine Ref.4

Modified residue

1384

Phosphoserine By similarity

Modified residue

1465

Phosphoserine Ref.4

Modified residue

1466

Phosphoserine Ref.4

Modified residue

1467

Phosphoserine Ref.4

Modified residue

1469

Phosphoserine Ref.4

Modified residue

1470

Phosphoserine Ref.4

Modified residue

1472

Phosphoserine Ref.4

Modified residue

1521

Phosphoserine By similarity

Experimental info

Sequence conflict

184

E → A in BAA02076. Ref.1

Sequence conflict

260

S → M in BAA02076. Ref.1

Sequence conflict

640

S → P in BAA02076. Ref.1

Sequence conflict

841

I → N in BAA02076. Ref.1

Sequence conflict

844 – 845

IP → NT in BAA02076. Ref.1

Sequence conflict

1316

A → R in BAA02076. Ref.1

Sequence conflict

1316

A → R in AAC52135. Ref.3

Sequences

Sequence

Length

Mass (Da)

Tools

Q01320 [UniParc].

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

1,528

172,790

        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' referencesShow '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. 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]	"A differential phosphoproteomic analysis of retinoic acid-treated P19 cells." Smith J.C., Duchesne M.A., Tozzi P., Ethier M., Figeys D. J. Proteome Res. 6:3174-3186(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1367; SER-1370; SER-1371; SER-1373; SER-1379; SER-1465; SER-1466; SER-1467; SER-1469; SER-1470 AND SER-1472, MASS SPECTROMETRY. Tissue: Teratocarcinoma.
[5]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1333, MASS SPECTROMETRY. Tissue: Melanoma.
[6]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28, MASS SPECTROMETRY. Tissue: Macrophage.
+	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.
IPI	IPI00122223.
PIR	JS0703.
RefSeq	NP_035753.2. NM_011623.2.
UniGene	Mm.4237.
3D structure databases
ProteinModelPortal	Q01320.
SMR	Q01320. Positions 28-404, 433-1187.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q01320. 6 interactions.
PTM databases
PhosphoSite	Q01320.
Proteomic databases
PaxDb	Q01320.
PRIDE	Q01320.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000068031; ENSMUSP00000068896; ENSMUSG00000020914.
GeneID	21973.
KEGG	mmu:21973.
UCSC	uc007lid.1. mouse.
Organism-specific databases
CTD	7153.
MGI	MGI:98790. Top2a.
Phylogenomic databases
eggNOG	COG0187.
GeneTree	ENSGT00390000016222.
HOGENOM	HOG000216693.
HOVERGEN	HBG052998.
InParanoid	Q01320.
KO	K03164.
OMA	MFKQTWM.
OrthoDB	EOG4KWJS0.
Gene expression databases
ArrayExpress	Q01320.
Bgee	Q01320.
CleanEx	MM_TOP2A.
Genevestigator	Q01320.
GermOnline	ENSMUSG00000020914. Mus musculus.
Family and domain databases
Gene3D	1.10.268.10. 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.
InterPro	IPR024946. Arg_repress_C-like. IPR012542. DTHCT. IPR003594. HATPase_ATP-bd. IPR020568. Ribosomal_S5_D2-typ_fold. IPR014721. Ribosomal_S5_D2-typ_fold_subgr. 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]
Pfam	PF00204. DNA_gyraseB. 1 hit. PF00521. DNA_topoisoIV. 1 hit. PF08070. DTHCT. 1 hit. PF02518. HATPase_c. 1 hit. PF01751. Toprim. 1 hit. [Graphical view]
PRINTS	PR00418. TPI2FAMILY.
SMART	SM00387. HATPase_c. 1 hit. SM00433. TOP2c. 1 hit. SM00434. TOP4c. 1 hit. [Graphical view]
SUPFAM	SSF55874. ATP_bd_ATPase. 1 hit. SSF54211. Ribosomal_S5_D2-typ_fold. 1 hit. SSF56719. Topo_IIA_cen. 1 hit.
PROSITE	PS00177. TOPOISOMERASE_II. 1 hit. PS50880. TOPRIM. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q01320.
ChEMBL	CHEMBL3586.
ChiTaRS	TOP2A. mouse.
NextBio	301670.
SOURCE	Search...

Entry information

Entry name

TOP2A_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 129 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents