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Protein

DNA topoisomerase 2-alpha

Gene

Top2a

Organism
Rattus norvegicus (Rat)
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.By similarity

Catalytic activityi

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

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 sitei118ATPBy similarity1
Metal bindingi459Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi539Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi539Magnesium 2PROSITE-ProRule annotation1
Metal bindingi541Magnesium 2PROSITE-ProRule annotation1
Sitei802Transition state stabilizerBy similarity1
Active sitei803O-(5'-phospho-DNA)-tyrosine intermediateBy similarity1
Sitei854Important for DNA bending; intercalates between base pairs of target DNABy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi146 – 148ATPBy similarity3
Nucleotide bindingi159 – 166ATPBy similarity8
Nucleotide bindingi374 – 376ATPBy similarity3

GO - Molecular functioni

  • ATP binding Source: RGD
  • chromatin binding Source: RGD
  • DNA binding Source: RGD
  • DNA binding, bending Source: UniProtKB
  • DNA topoisomerase activity Source: RGD
  • DNA topoisomerase type II (ATP-hydrolyzing) activity Source: RGD
  • magnesium ion binding Source: UniProtKB
  • sequence-specific DNA binding Source: RGD
  • structure-specific DNA binding Source: RGD

GO - Biological processi

  • aging Source: RGD
  • brain development Source: RGD
  • cerebellar granule cell differentiation Source: RGD
  • cerebellar Purkinje cell differentiation Source: RGD
  • DNA topological change Source: RGD
  • DNA unwinding involved in DNA replication Source: GO_Central
  • mitotic DNA integrity checkpoint Source: GO_Central
  • mitotic recombination Source: GO_Central
  • regulation of circadian rhythm Source: UniProtKB
  • resolution of meiotic recombination intermediates Source: GO_Central
  • response to drug Source: RGD
  • response to parathyroid hormone Source: RGD
  • 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

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi62048. Top2a.

Subcellular locationi

GO - Cellular componenti

  • DNA topoisomerase complex (ATP-hydrolyzing) Source: RGD
  • nucleolus Source: RGD
  • nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3400.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001453661 – 1526DNA topoisomerase 2-alphaAdd BLAST1526

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei4PhosphoserineCombined sources1
Modified residuei280PhosphothreonineBy similarity1
Cross-linki637Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki660Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki674Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki1073Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki1193Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1210PhosphoserineCombined sources1
Cross-linki1237Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Cross-linki1237Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1244PhosphothreonineBy similarity1
Modified residuei1291PhosphoserineBy similarity1
Modified residuei1293PhosphoserineBy similarity1
Modified residuei1295PhosphoserineBy similarity1
Modified residuei1298PhosphoserineBy similarity1
Modified residuei1323PhosphothreonineBy similarity1
Modified residuei1328PhosphoserineCombined sources1
Modified residuei1333PhosphoserineCombined sources1
Modified residuei1350PhosphothreonineCombined sources1
Modified residuei1370PhosphoserineBy similarity1
Modified residuei1373PhosphoserineBy similarity1
Cross-linki1381Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1383PhosphoserineCombined sources1
Modified residuei1387PhosphoserineCombined sources1
Modified residuei1418N6-acetyllysineBy similarity1
Modified residuei1438N6-acetyllysine; alternateBy similarity1
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 residuei1521PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation has no effect on catalytic activity.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP41516.
PRIDEiP41516.

PTM databases

iPTMnetiP41516.
PhosphoSitePlusiP41516.

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
Sitei487Interaction with DNAPROSITE-ProRule annotation1
Sitei490Interaction with DNAPROSITE-ProRule annotation1
Sitei659Interaction with DNAPROSITE-ProRule annotation1
Sitei660Interaction with DNAPROSITE-ProRule annotation1
Sitei721Interaction with DNAPROSITE-ProRule annotation1
Sitei755Interaction with DNAPROSITE-ProRule annotation1
Sitei761Interaction with DNAPROSITE-ProRule annotation1
Sitei929Interaction with DNAPROSITE-ProRule annotation1

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000040257.

Structurei

3D structure databases

ProteinModelPortaliP41516.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini453 – 570ToprimPROSITE-ProRule annotationAdd BLAST118

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni340 – 342Interaction with DNABy similarity3
Regioni988 – 997Interaction 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.
HOGENOMiHOG000216693.
HOVERGENiHBG052998.
InParanoidiP41516.
KOiK03164.
PhylomeDBiP41516.

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.

P41516-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MELSPLQPVN ENMLLNKKKN EDGKKRLSVE RIYQKKTQLE HILLRPDTYI
60 70 80 90 100
GSVELVTQQM WVYDEDVGIN YREVTFVPGL YKIFDEILVN AADNKQRDPK
110 120 130 140 150
MSCIRVTMMR NNLISIWNNG KGIPVVEHKV EKMYVPALIF GQLLTSSNYD
160 170 180 190 200
DDEKKVTGGR NGYGAKLCNI FSTKFTVETA SREYKKMFKQ TWMDNMGRAG
210 220 230 240 250
DMELKPFSGE DYTCITFQPD LSKFKMQSLD KDIVALMVRR AYDIAGSTKD
260 270 280 290 300
VKVFLNGNRL PVKGFRSYVD MYLKDKVDET GNALKVVHEQ VNPRWEVCLT
310 320 330 340 350
MSEKGFQQIS FVNSIATSKG GRHVDYVADQ IVSKLVDVVK KKNKGGVAVK
360 370 380 390 400
ADQVKNHMWI FGNAVIENPT FDSQTKENMT LQAKSFGSTC QLSEKFIKAA
410 420 430 440 450
IGCGIVESIL NWVKFKAQIQ LNKKCSAVKH NRIKGIPKLD DANDAGSRNS
460 470 480 490 500
AECTLILTEG DSAKTLAVSG LGVVGRDKYG VFPLRGKILN VREASHKQIM
510 520 530 540 550
ENAEINNIIK IVGLQYKKNY EDEDSLKTLR YGKIMIMTDQ DQDGSHIKGL
560 570 580 590 600
LINFIHHNWP SLLRHRFLEE FITPIVKVSK NKQEIAFYSL PEFEEWKSTN
610 620 630 640 650
PNHKKWKVKY YKGLGTSTSK EAKEYFANMK RHRIQFKYSG PEDDAAISLA
660 670 680 690 700
FSKKQVDDRK EWLTNFMEDR RQRKLLGLPE DYLYGQTTMY LTYNDFINKE
710 720 730 740 750
LILFSNSDNE RSIPSMVDGL KPGQRKVLFT CFKRNDKREV KVAQLAGSVA
760 770 780 790 800
EMSSYHHGEM SLMMTIINLA QNFVGSNNLN LLQPIGQFGT RLHGGKDSAS
810 820 830 840 850
PRYIFTMLSP LARLLFPSKD DHTLRFLYDD NQRVEPEWYI PIIPMVLING
860 870 880 890 900
AEGIGTGWSC KIPNFDVREV VNNIRRLLDG EEPLPMLPSY KNYKGTIEEL
910 920 930 940 950
ASNQYVINGE VAILNSTTIE ITELPIRTWT QTYKEQVLEP MLNGTEKTPP
960 970 980 990 1000
LITDYREYHT DTTVKFVIKM TEEKLAEAER VGLHKVFKLQ TSLTCNSMVL
1010 1020 1030 1040 1050
FDHVGCLKKY DTVLDILRDF FELRLKYYGL RKEWLLGMLG AESSKLNNQA
1060 1070 1080 1090 1100
RFILEKIDGK IVIENKPKKE LIKVLIQRGY DSDPVKAWKE AQQKVPEEEE
1110 1120 1130 1140 1150
NEENEESESE STSPAAESGP TFNYLLDMPL WYLTKEKKDE LCKQRDEKEQ
1160 1170 1180 1190 1200
ELNTLKKKTP SDLWKEDLAA FVEELEVVEA KEKQDEQVGL PGKGVKAKGK
1210 1220 1230 1240 1250
KAQISEVLPS PVGKRVIPQV TMEMRAEAEK KIRRKIKSEN VEGTPAEDGA
1260 1270 1280 1290 1300
EPGLRQRLEK RQKREPGTRA KKQTTLPFKP IKKAQKQNPW SDSESDMSSN
1310 1320 1330 1340 1350
ESNFDVPPRE KEPRIAATKA KFTADLDSDD DFSGLDEKDE DEDFFPLDDT
1360 1370 1380 1390 1400
PPKTKMPPKN TKKALKPQKS STSVDLESDG KDSVPASPGA SAADVPAETE
1410 1420 1430 1440 1450
PSKPSSKQTV GVKRTITKGQ SLTSTAGTKK RAVPKETKSD SALNAHVSKK
1460 1470 1480 1490 1500
PAPAKAKNSR KRMPSSSDSS DSEFEKAISK GATSKKLKGE ERDFHVDLDD
1510 1520
TVAPRAKSGR ARKPIKYLEE SDDDLF
Length:1,526
Mass (Da):173,221
Last modified:November 1, 1995 - v1
Checksum:iA1961ABBDB1B050F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46372 mRNA. Translation: CAA86496.1.
Z19552 mRNA. Translation: CAA79611.1.
Z29676 Genomic DNA. No translation available.
PIRiA48536.
JN0598.
RefSeqiNP_071519.2. NM_022183.2.
UniGeneiRn.90996.

Genome annotation databases

GeneIDi360243.
KEGGirno:360243.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46372 mRNA. Translation: CAA86496.1.
Z19552 mRNA. Translation: CAA79611.1.
Z29676 Genomic DNA. No translation available.
PIRiA48536.
JN0598.
RefSeqiNP_071519.2. NM_022183.2.
UniGeneiRn.90996.

3D structure databases

ProteinModelPortaliP41516.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000040257.

Chemistry databases

ChEMBLiCHEMBL3400.

PTM databases

iPTMnetiP41516.
PhosphoSitePlusiP41516.

Proteomic databases

PaxDbiP41516.
PRIDEiP41516.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi360243.
KEGGirno:360243.

Organism-specific databases

CTDi7153.
RGDi62048. Top2a.

Phylogenomic databases

eggNOGiKOG0355. Eukaryota.
COG0187. LUCA.
COG0188. LUCA.
HOGENOMiHOG000216693.
HOVERGENiHBG052998.
InParanoidiP41516.
KOiK03164.
PhylomeDBiP41516.

Miscellaneous databases

PROiP41516.

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_RAT
AccessioniPrimary (citable) accession number: P41516
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 2, 2016
This is version 153 of the entry and version 1 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. 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.