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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei90 – 901ATPBy similarity
Binding sitei118 – 1181ATPBy similarity
Metal bindingi459 – 4591Magnesium 1; catalyticPROSITE-ProRule annotation
Metal bindingi539 – 5391Magnesium 1; catalyticPROSITE-ProRule annotation
Metal bindingi539 – 5391Magnesium 2PROSITE-ProRule annotation
Metal bindingi541 – 5411Magnesium 2PROSITE-ProRule annotation
Sitei802 – 8021Transition state stabilizerBy similarity
Active sitei803 – 8031O-(5'-phospho-DNA)-tyrosine intermediateBy similarity
Sitei854 – 8541Important for DNA bending; intercalates between base pairs of target DNABy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi146 – 1483ATPBy similarity
Nucleotide bindingi159 – 1668ATPBy similarity
Nucleotide bindingi374 – 3763ATPBy similarity

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
  • regulation of circadian rhythm Source: UniProtKB
  • response to drug Source: RGD
  • response to parathyroid hormone Source: RGD
  • rhythmic process Source: UniProtKB-KW
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

ChEMBLiCHEMBL3400.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 15261526DNA topoisomerase 2-alphaPRO_0000145366Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei4 – 41PhosphoserineCombined sources
Modified residuei280 – 2801PhosphothreonineBy similarity
Cross-linki637 – 637Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki660 – 660Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki674 – 674Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki1073 – 1073Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki1193 – 1193Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1210 – 12101PhosphoserineCombined sources
Cross-linki1237 – 1237Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1244 – 12441PhosphothreonineBy similarity
Modified residuei1291 – 12911PhosphoserineBy similarity
Modified residuei1293 – 12931PhosphoserineBy similarity
Modified residuei1295 – 12951PhosphoserineBy similarity
Modified residuei1298 – 12981PhosphoserineBy similarity
Modified residuei1323 – 13231PhosphothreonineBy similarity
Modified residuei1328 – 13281PhosphoserineCombined sources
Modified residuei1333 – 13331PhosphoserineCombined sources
Modified residuei1350 – 13501PhosphothreonineCombined sources
Modified residuei1370 – 13701PhosphoserineBy similarity
Modified residuei1373 – 13731PhosphoserineBy similarity
Cross-linki1381 – 1381Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1383 – 13831PhosphoserineCombined sources
Modified residuei1387 – 13871PhosphoserineCombined sources
Modified residuei1418 – 14181N6-acetyllysineBy similarity
Modified residuei1438 – 14381N6-acetyllysine; alternateBy similarity
Cross-linki1438 – 1438Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei1465 – 14651PhosphoserineBy similarity
Modified residuei1467 – 14671PhosphoserineBy similarity
Modified residuei1470 – 14701PhosphoserineBy similarity
Modified residuei1472 – 14721PhosphoserineBy similarity
Cross-linki1488 – 1488Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1521 – 15211PhosphoserineBy similarity

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.

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)LengthDescriptionGraphical viewFeature identifierActions
Sitei487 – 4871Interaction with DNAPROSITE-ProRule annotation
Sitei490 – 4901Interaction with DNAPROSITE-ProRule annotation
Sitei659 – 6591Interaction with DNAPROSITE-ProRule annotation
Sitei660 – 6601Interaction with DNAPROSITE-ProRule annotation
Sitei721 – 7211Interaction with DNAPROSITE-ProRule annotation
Sitei755 – 7551Interaction with DNAPROSITE-ProRule annotation
Sitei761 – 7611Interaction with DNAPROSITE-ProRule annotation
Sitei929 – 9291Interaction with DNAPROSITE-ProRule annotation

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000040257.

Structurei

3D structure databases

ProteinModelPortaliP41516.
SMRiP41516. Positions 28-403.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini453 – 570118ToprimPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni340 – 3423Interaction with DNABy similarity
Regioni988 – 99710Interaction with DNABy similarity

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.
SMRiP41516. Positions 28-403.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000040257.

Chemistry

ChEMBLiCHEMBL3400.

PTM databases

iPTMnetiP41516.

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

NextBioi672745.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Nucleotide sequence analysis of the cDNA for rat DNA topoisomerase II."
    Park S.H., Yoon J.H., Kwon Y.D., Park S.D.
    Biochem. Biophys. Res. Commun. 193:787-793(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Testis.
  2. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4; SER-1210; SER-1328; SER-1333; THR-1350; SER-1383 AND SER-1387, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

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: May 11, 2016
This is version 148 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.