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Protein

DNA topoisomerase 2-alpha

Gene

Top2a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (PubMed:24321095).2 Publications

Catalytic activityi

ATP-dependent breakage, passage and rejoining of double-stranded DNA.PROSITE-ProRule annotation1 Publication

Cofactori

Mg2+PROSITE-ProRule annotation, Mn2+PROSITE-ProRule annotation, Ca2+PROSITE-ProRule annotationNote: 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+ or Ca2+.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei90ATPBy similarity1
Binding sitei119ATPBy similarity1
Metal bindingi460Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi540Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi540Magnesium 2PROSITE-ProRule annotation1
Metal bindingi542Magnesium 2PROSITE-ProRule annotation1
Sitei803Transition state stabilizerBy similarity1
Active sitei804O-(5'-phospho-DNA)-tyrosine intermediateBy similarity1
Sitei855Important for DNA bending; intercalates between base pairs of target DNABy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi147 – 149ATPBy similarity3
Nucleotide bindingi160 – 167ATPBy similarity8
Nucleotide bindingi375 – 377ATPBy similarity3

GO - Molecular functioni

GO - Biological processi

  • apoptotic chromosome condensation Source: MGI
  • cellular response to DNA damage stimulus Source: MGI
  • chromosome condensation Source: MGI
  • chromosome segregation Source: MGI
  • DNA ligation Source: MGI
  • DNA topological change Source: MGI
  • DNA unwinding involved in DNA replication Source: GO_Central
  • embryonic cleavage Source: MGI
  • hematopoietic progenitor cell differentiation Source: MGI
  • mitotic DNA integrity checkpoint Source: GO_Central
  • mitotic recombination Source: GO_Central
  • positive regulation of apoptotic process Source: MGI
  • positive regulation of single stranded viral RNA replication via double stranded DNA intermediate Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of viral genome replication Source: MGI
  • protein sumoylation Source: Reactome
  • regulation of circadian rhythm Source: UniProtKB
  • resolution of meiotic recombination intermediates Source: GO_Central
  • rhythmic process Source: UniProtKB-KW
  • sister chromatid segregation Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Isomerase, Topoisomerase

Keywords - Biological processi

Biological rhythms

Keywords - Ligandi

ATP-binding, DNA-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-1538133. G0 and Early G1.
R-MMU-4615885. SUMOylation of DNA replication proteins.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA topoisomerase 2-alpha (EC:5.99.1.3)
Alternative name(s):
DNA topoisomerase II, alpha isozyme
Gene namesi
Name:Top2a
Synonyms:Top-2, Top2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:98790. Top2a.

Subcellular locationi

GO - Cellular componenti

  • centriole Source: Ensembl
  • condensed chromosome Source: MGI
  • DNA topoisomerase complex (ATP-hydrolyzing) Source: MGI
  • nuclear chromosome Source: Ensembl
  • nucleolus Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: MGI
  • protein complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3586.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001453641 – 1528DNA topoisomerase 2-alphaAdd BLAST1528

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei4PhosphoserineBy similarity1
Modified residuei281PhosphothreonineBy similarity1
Cross-linki638Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki661Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki675Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki1074Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1105Phosphoserine; by CK1By similarity1
Cross-linki1193Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1211PhosphoserineCombined sources1
Cross-linki1226Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki1238Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Cross-linki1238Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1245PhosphothreonineCombined sources1
Modified residuei1291PhosphoserineBy similarity1
Modified residuei1293PhosphoserineBy similarity1
Modified residuei1295PhosphoserineBy similarity1
Modified residuei1298PhosphoserineBy similarity1
Modified residuei1323PhosphothreonineCombined sources1
Modified residuei1328PhosphoserineCombined sources1
Modified residuei1333PhosphoserineCombined sources1
Modified residuei1350PhosphothreonineCombined sources1
Modified residuei1370PhosphoserineBy similarity1
Modified residuei1373PhosphoserineCombined sources1
Cross-linki1382Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1384PhosphoserineBy similarity1
Modified residuei1388PhosphoserineCombined sources1
Modified residuei1418N6-acetyllysineCombined sources1
Modified residuei1438N6-acetyllysine; alternateCombined sources1
Cross-linki1438Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei1465PhosphoserineBy similarity1
Modified residuei1467PhosphoserineBy similarity1
Modified residuei1470PhosphoserineBy similarity1
Modified residuei1472PhosphoserineBy similarity1
Cross-linki1488Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1521PhosphoserineCombined sources1

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ01320.
MaxQBiQ01320.
PaxDbiQ01320.
PeptideAtlasiQ01320.
PRIDEiQ01320.

PTM databases

iPTMnetiQ01320.
PhosphoSitePlusiQ01320.

Expressioni

Gene expression databases

BgeeiENSMUSG00000020914.
CleanExiMM_TOP2A.
GenevisibleiQ01320. MM.

Interactioni

Subunit structurei

Homodimer. Interacts with COPS5. Interacts with RECQL5; this stimulates DNA decatenation. Interacts with SETMAR; stimulates the topoisomerase activity.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei488Interaction with DNAPROSITE-ProRule annotation1
Sitei491Interaction with DNAPROSITE-ProRule annotation1
Sitei660Interaction with DNAPROSITE-ProRule annotation1
Sitei661Interaction with DNAPROSITE-ProRule annotation1
Sitei722Interaction with DNAPROSITE-ProRule annotation1
Sitei756Interaction with DNAPROSITE-ProRule annotation1
Sitei762Interaction with DNAPROSITE-ProRule annotation1
Sitei930Interaction with DNAPROSITE-ProRule annotation1

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204276. 11 interactors.
DIPiDIP-40621N.
IntActiQ01320. 12 interactors.
MINTiMINT-1712967.
STRINGi10090.ENSMUSP00000068896.

Structurei

3D structure databases

ProteinModelPortaliQ01320.
SMRiQ01320.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini454 – 571ToprimPROSITE-ProRule annotationAdd BLAST118

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni341 – 343Interaction with DNABy similarity3
Regioni989 – 998Interaction with DNABy similarity10

Sequence similaritiesi

Belongs to the type II topoisomerase family.Curated
Contains 1 Toprim domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0355. Eukaryota.
COG0187. LUCA.
COG0188. LUCA.
GeneTreeiENSGT00390000016222.
HOGENOMiHOG000216693.
HOVERGENiHBG052998.
InParanoidiQ01320.
KOiK03164.
OMAiVKFIVKM.
OrthoDBiEOG091G00U2.
TreeFamiTF105282.

Family and domain databases

Gene3Di1.10.268.10. 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.
InterProiIPR024946. Arg_repress_C-like.
IPR012542. DTHCT.
IPR003594. HATPase_C.
IPR020568. Ribosomal_S5_D2-typ_fold.
IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
IPR028466. Top2a.
IPR001241. Topo_IIA.
IPR013760. Topo_IIA-like_dom.
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.
IPR018522. TopoIIA_CS.
IPR031660. TOPRIM_C.
IPR006171. Toprim_domain.
[Graphical view]
PANTHERiPTHR10169:SF46. PTHR10169:SF46. 1 hit.
PfamiPF00204. DNA_gyraseB. 1 hit.
PF00521. DNA_topoisoIV. 1 hit.
PF08070. DTHCT. 1 hit.
PF02518. HATPase_c. 1 hit.
PF01751. Toprim. 1 hit.
PF16898. TOPRIM_C. 1 hit.
[Graphical view]
PRINTSiPR00418. TPI2FAMILY.
SMARTiSM00433. TOP2c. 1 hit.
SM00434. TOP4c. 1 hit.
[Graphical view]
SUPFAMiSSF54211. SSF54211. 1 hit.
SSF55874. SSF55874. 1 hit.
SSF56719. SSF56719. 1 hit.
PROSITEiPS00177. TOPOISOMERASE_II. 1 hit.
PS50880. TOPRIM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q01320-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELSPLQPVN ENMLMNKKKN EDGKKRLSIE RIYQKKTQLE HILLRPDTYI
60 70 80 90 100
GSVELVTQQM WVYDEDVGIN YREVTFVPGL YKIFDEILVN AADNKQRDPK
110 120 130 140 150
MSCIRVTIDP ENNVISIWNN GKGIPVVEHK VEKIYVPALI FGQLLTSSNY
160 170 180 190 200
DDDEKKVTGG RNGYGAKLCN IFSTKFTVET ASREYKKMFK QTWMDNMGRA
210 220 230 240 250
GDMELKPFSG EDYTCITFQP DLSKFKMQSL DKDIVALMVR RAYDIAGSTK
260 270 280 290 300
DVKVFLNGNS LPVKGFRSYV DLYLKDKVDE TGNSLKVIHE QVNPRWEVCL
310 320 330 340 350
TMSERGFQQI SFVNSIATSK GGRHVDYVAD QIVSKLVDVV KKKNKGGVAV
360 370 380 390 400
KAHQVKNHMW IFVNALIENP TFDSQTKENM TLQAKSFGST CQLSEKFIKA
410 420 430 440 450
AIGCGIVESI LNWVKFKAQI QLNKKCSAVK HTKIKGIPKL DDANDAGSRN
460 470 480 490 500
STECTLILTE GDSAKTLAVS GLGVVGRDKY GVFPLRGKIL NVREASHKQI
510 520 530 540 550
MENAEINNII KIVGLQYKKN YEDEDSLKTL RYGKIMIMTD QDQDGSHIKG
560 570 580 590 600
LLINFIHHNW PSLLRHRFLE EFITPIVKVS KNKQEIAFYS LPEFEEWKSS
610 620 630 640 650
TPNHKKWKVK YYKGLGTSTS KEAKEYFADM KRHRIQFKYS GPEDDAAISL
660 670 680 690 700
AFSKKQVDDR KEWLTNFMED RRQRKLLGLP EDYLYGQSTS YLTYNDFINK
710 720 730 740 750
ELILFSNSDN ERSIPSMVDG LKPGQRKVLF TCFKRNDKRE VKVAQLAGSV
760 770 780 790 800
AEMSSYHHGE MSLMMTIINL AQNFVGSNNL NLLQPIGQFG TRLHGGKDSA
810 820 830 840 850
SPRYIFTMLS PLARLLFPPK DDHTLRFLYD DNQRVEPEWY IPIIPMVLIN
860 870 880 890 900
GAEGIGTGWS CKIPNFDVRE VVNNIRRLLD GEEPLPMLPS YKNFKGTIEE
910 920 930 940 950
LASNQYVING EVAILDSTTI EISELPIRTW TQTYKEQVLE PMLNGTEKTP
960 970 980 990 1000
SLITDYREYH TDTTVKFVIK MTEEKLAEAE RVGLHKVFKL QSSLTCNSMV
1010 1020 1030 1040 1050
LFDHVGCLKK YDTVLDILRD FFELRLKYYG LRKEWLLGML GAESSKLNNQ
1060 1070 1080 1090 1100
ARFILEKIDG KIVIENKPKK ELIKVLIQRG YDSDPVKAWK EAQQKVPDEE
1110 1120 1130 1140 1150
ENEESDTETS TSDSAAEAGP TFNYLLDMPL WYLTKEKKDE LCKQRNEKEQ
1160 1170 1180 1190 1200
ELNTLKQKSP SDLWKEDLAV FIEELEVVEA KEKQDEQVGL PGKAGKAKGK
1210 1220 1230 1240 1250
KAQMCADVLP SPRGKRVIPQ VTVEMKAEAE KKIRKKIKSE NVEGTPAEDG
1260 1270 1280 1290 1300
AEPGSLRQRI EKKQKKEPGA KKQTTLPFKP VKKGRKKNPW SDSESDVSSN
1310 1320 1330 1340 1350
ESNVDVPPRQ KEQRSAAAKA KFTVDLDSDE DFSGLDEKDE DEDFLPLDAT
1360 1370 1380 1390 1400
PPKAKIPPKN TKKALKTQGS SMSVVDLESD VKDSVPASPG VPAADFPAET
1410 1420 1430 1440 1450
EQSKPSKKTV GVKKTATKSQ SSVSTAGTKK RAAPKGTKSD SALSARVSEK
1460 1470 1480 1490 1500
PAPAKAKNSR KRKPSSSDSS DSDFERAISK GATSKKAKGE EQDFPVDLED
1510 1520
TIAPRAKSDR ARKPIKYLEE SDDDDDLF
Length:1,528
Mass (Da):172,790
Last modified:December 14, 2011 - v2
Checksum:i63CBF8F649D103C7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti184E → A in BAA02076 (PubMed:1331984).Curated1
Sequence conflicti260S → M in BAA02076 (PubMed:1331984).Curated1
Sequence conflicti640S → P in BAA02076 (PubMed:1331984).Curated1
Sequence conflicti841I → N in BAA02076 (PubMed:1331984).Curated1
Sequence conflicti844 – 845IP → NT in BAA02076 (PubMed:1331984).Curated2
Sequence conflicti1316A → R in BAA02076 (PubMed:1331984).Curated1
Sequence conflicti1316A → R in AAC52135 (PubMed:8261398).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D12513 mRNA. Translation: BAA02076.1.
AL591067 Genomic DNA. No translation available.
U01915 mRNA. Translation: AAC52135.1.
CCDSiCCDS25370.1.
PIRiJS0703.
RefSeqiNP_035753.2. NM_011623.2.
XP_006533216.1. XM_006533153.2.
UniGeneiMm.4237.

Genome annotation databases

EnsembliENSMUST00000068031; ENSMUSP00000068896; ENSMUSG00000020914.
GeneIDi21973.
KEGGimmu:21973.
UCSCiuc007lid.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D12513 mRNA. Translation: BAA02076.1.
AL591067 Genomic DNA. No translation available.
U01915 mRNA. Translation: AAC52135.1.
CCDSiCCDS25370.1.
PIRiJS0703.
RefSeqiNP_035753.2. NM_011623.2.
XP_006533216.1. XM_006533153.2.
UniGeneiMm.4237.

3D structure databases

ProteinModelPortaliQ01320.
SMRiQ01320.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204276. 11 interactors.
DIPiDIP-40621N.
IntActiQ01320. 12 interactors.
MINTiMINT-1712967.
STRINGi10090.ENSMUSP00000068896.

Chemistry databases

ChEMBLiCHEMBL3586.

PTM databases

iPTMnetiQ01320.
PhosphoSitePlusiQ01320.

Proteomic databases

EPDiQ01320.
MaxQBiQ01320.
PaxDbiQ01320.
PeptideAtlasiQ01320.
PRIDEiQ01320.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000068031; ENSMUSP00000068896; ENSMUSG00000020914.
GeneIDi21973.
KEGGimmu:21973.
UCSCiuc007lid.1. mouse.

Organism-specific databases

CTDi7153.
MGIiMGI:98790. Top2a.

Phylogenomic databases

eggNOGiKOG0355. Eukaryota.
COG0187. LUCA.
COG0188. LUCA.
GeneTreeiENSGT00390000016222.
HOGENOMiHOG000216693.
HOVERGENiHBG052998.
InParanoidiQ01320.
KOiK03164.
OMAiVKFIVKM.
OrthoDBiEOG091G00U2.
TreeFamiTF105282.

Enzyme and pathway databases

ReactomeiR-MMU-1538133. G0 and Early G1.
R-MMU-4615885. SUMOylation of DNA replication proteins.

Miscellaneous databases

ChiTaRSiTop2a. mouse.
PROiQ01320.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020914.
CleanExiMM_TOP2A.
GenevisibleiQ01320. MM.

Family and domain databases

Gene3Di1.10.268.10. 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.
InterProiIPR024946. Arg_repress_C-like.
IPR012542. DTHCT.
IPR003594. HATPase_C.
IPR020568. Ribosomal_S5_D2-typ_fold.
IPR014721. Ribosomal_S5_D2-typ_fold_subgr.
IPR028466. Top2a.
IPR001241. Topo_IIA.
IPR013760. Topo_IIA-like_dom.
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.
IPR018522. TopoIIA_CS.
IPR031660. TOPRIM_C.
IPR006171. Toprim_domain.
[Graphical view]
PANTHERiPTHR10169:SF46. PTHR10169:SF46. 1 hit.
PfamiPF00204. DNA_gyraseB. 1 hit.
PF00521. DNA_topoisoIV. 1 hit.
PF08070. DTHCT. 1 hit.
PF02518. HATPase_c. 1 hit.
PF01751. Toprim. 1 hit.
PF16898. TOPRIM_C. 1 hit.
[Graphical view]
PRINTSiPR00418. TPI2FAMILY.
SMARTiSM00433. TOP2c. 1 hit.
SM00434. TOP4c. 1 hit.
[Graphical view]
SUPFAMiSSF54211. SSF54211. 1 hit.
SSF55874. SSF55874. 1 hit.
SSF56719. SSF56719. 1 hit.
PROSITEiPS00177. TOPOISOMERASE_II. 1 hit.
PS50880. TOPRIM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTOP2A_MOUSE
AccessioniPrimary (citable) accession number: Q01320
Secondary accession number(s): E9PX08
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: December 14, 2011
Last modified: November 2, 2016
This is version 166 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.