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P11388 (TOP2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 178. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·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:TOP2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1531 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.31 Ref.33

Catalytic activity

ATP-dependent breakage, passage and rejoining of double-stranded DNA. Ref.23 Ref.24

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+ Probable. Ref.23 Ref.24 Ref.33 Ref.35

Enzyme regulation

Specifically inhibited by the intercalating agent amsacrine.

Subunit structure

Homodimer. Interacts with COPS5. Interacts with RECQL5; this stimulates DNA decatenation. Ref.14 Ref.31 Ref.35

Subcellular location

Cytoplasm. Nucleusnucleoplasm. Note: Generally located in the nucleoplasm. Ref.31

Post-translational modification

Phosphorylation has no effect on catalytic activity. However, phosphorylation at Ser-1106 by CSNK1D/CK1 promotes DNA cleavable complex formation.

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 componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
DNA-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionIsomerase
Topoisomerase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA ligation

Inferred from direct assay PubMed 15491148. Source: UniProtKB

DNA repair

Non-traceable author statement PubMed 15504738. Source: UniProtKB

DNA topological change

Inferred from direct assay Ref.33. Source: UniProtKB

DNA-dependent DNA replication

Inferred from Biological aspect of Ancestor. Source: RefGenome

apoptotic chromosome condensation

Inferred from direct assay PubMed 10959840. Source: UniProtKB

embryonic cleavage

Inferred from electronic annotation. Source: Ensembl

mitotic cell cycle

Traceable author statement. Source: Reactome

mitotic recombination

Inferred from Biological aspect of Ancestor. Source: RefGenome

phosphatidylinositol-mediated signaling

Non-traceable author statement PubMed 15504738. Source: UniProtKB

positive regulation of apoptotic process

Inferred from direct assay PubMed 16611985. Source: UniProtKB

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

Inferred from mutant phenotype PubMed 16712776. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

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 direct assay PubMed 10473615. Source: UniProtKB

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleolus

Inferred from direct assay PubMed 17567603. Source: UniProtKB

nucleoplasm

Inferred from direct assay PubMed 9049244. Source: UniProtKB

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 direct assay Ref.33. Source: UniProtKB

DNA topoisomerase type II (ATP-hydrolyzing) activity

Inferred from direct assay PubMed 16611985. Source: UniProtKB

chromatin binding

Inferred from direct assay PubMed 9049244. Source: UniProtKB

drug binding

Inferred from direct assay PubMed 16914642. Source: UniProtKB

magnesium ion binding

Inferred from direct assay Ref.33. Source: UniProtKB

ubiquitin binding

Inferred from mutant phenotype PubMed 15965487. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CTNNB1P352225EBI-539628,EBI-491549

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P11388-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P11388-2)

The sequence of this isoform differs from the canonical sequence as follows:
     401-401: A → AHLYSRFLIDPFFPNMIPNMIFSFSKA
Isoform 3 (identifier: P11388-3)

The sequence of this isoform differs from the canonical sequence as follows:
     321-321: K → KSSKYWSSRKSKQHILLNFFVLFKFINDAFFGICPFK
Isoform 4 (identifier: P11388-4)

The sequence of this isoform differs from the canonical sequence as follows:
     355-355: Q → QRELCNGAIL...SQSSGITDVK

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 15311531DNA topoisomerase 2-alpha
PRO_0000145363

Regions

Domain455 – 572118Toprim
Nucleotide binding148 – 1503ATP
Nucleotide binding161 – 1688ATP
Nucleotide binding376 – 3783ATP
Region342 – 3443Interaction with DNA Probable
Region990 – 99910Interaction with DNA
Motif1018 – 102811Nuclear export signal

Sites

Active site8051O-(5'-phospho-DNA)-tyrosine intermediate By similarity
Metal binding4611Magnesium 1; catalytic By similarity
Metal binding5411Magnesium 1; catalytic By similarity
Metal binding5411Magnesium 2
Metal binding5431Magnesium 2
Binding site911ATP
Binding site1201ATP
Site4891Interaction with DNA By similarity
Site4921Interaction with DNA
Site6611Interaction with DNA
Site6621Interaction with DNA
Site7231Interaction with DNA
Site7571Interaction with DNA
Site7631Interaction with DNA
Site8041Transition state stabilizer By similarity
Site8561Important for DNA bending; intercalates between base pairs of target DNA By similarity
Site9311Interaction with DNA

Amino acid modifications

Modified residue11N-acetylmethionine Ref.10 Ref.27 Ref.29 Ref.32
Modified residue41Phosphoserine Ref.15 Ref.20 Ref.27 Ref.29
Modified residue2821Phosphothreonine Ref.27
Modified residue11061Phosphoserine; by CK1 Ref.11 Ref.15 Ref.21 Ref.25 Ref.27 Ref.29
Modified residue12051Phosphothreonine Ref.27
Modified residue12131Phosphoserine Ref.15 Ref.16 Ref.20 Ref.21 Ref.27 Ref.29
Modified residue12471Phosphoserine Ref.15 Ref.17 Ref.20 Ref.26 Ref.27 Ref.29
Modified residue12951Phosphoserine Ref.29
Modified residue12971Phosphoserine Ref.29
Modified residue12991Phosphoserine Ref.29
Modified residue13021Phosphoserine Ref.29
Modified residue13321Phosphoserine Ref.15 Ref.20 Ref.21 Ref.27 Ref.29
Modified residue13371Phosphoserine Ref.15 Ref.20 Ref.21 Ref.27 Ref.29
Modified residue13431Phosphothreonine; by PLK3 Ref.15 Ref.18 Ref.21 Ref.27 Ref.29
Modified residue13511Phosphoserine Ref.15 Ref.21 Ref.27 Ref.29
Modified residue13541Phosphoserine Ref.15 Ref.27 Ref.29
Modified residue13741Phosphoserine Ref.15 Ref.16 Ref.26 Ref.27 Ref.29
Modified residue13771Phosphoserine Ref.15 Ref.16 Ref.20 Ref.27 Ref.29
Modified residue13871Phosphoserine Ref.26
Modified residue13921Phosphoserine Ref.21
Modified residue13931Phosphoserine Ref.21 Ref.26
Modified residue14221N6-acetyllysine By similarity
Modified residue14421N6-acetyllysine By similarity
Modified residue14491Phosphoserine Ref.21
Modified residue14691Phosphoserine; by CK2 Ref.12 Ref.21 Ref.29
Modified residue14701Phosphothreonine Ref.21 Ref.29
Modified residue14711Phosphoserine Ref.21 Ref.27 Ref.29
Modified residue14741Phosphoserine Ref.21 Ref.27 Ref.29
Modified residue14761Phosphoserine Ref.29
Modified residue14951Phosphoserine Ref.27
Modified residue15041Phosphoserine Ref.19 Ref.26 Ref.27
Modified residue15251Phosphoserine Ref.15 Ref.16 Ref.21 Ref.26 Ref.27 Ref.29

Natural variations

Alternative sequence3211K → KSSKYWSSRKSKQHILLNFF VLFKFINDAFFGICPFK in isoform 3.
VSP_006529
Alternative sequence3551Q → QRELCNGAILAHCNLRLMGS SDSPASASRVAGIAGGCHHT QLIFVFLVETGFHHVGQAGL ERLTSGDPPASASQSSGITD VK in isoform 4.
VSP_006530
Alternative sequence4011A → AHLYSRFLIDPFFPNMIPNM IFSFSKA in isoform 2.
VSP_006531
Natural variant4501R → Q in teniposide (VM-26) resistant cells. Ref.37
VAR_007532
Natural variant4871R → K in amsacrine resistant cells. Ref.36
VAR_007533
Natural variant13241T → K.
Corresponds to variant rs28969502 [ dbSNP | Ensembl ].
VAR_029245
Natural variant13861G → D.
Corresponds to variant rs34300454 [ dbSNP | Ensembl ].
VAR_052594
Natural variant15151A → S.
Corresponds to variant rs11540720 [ dbSNP | Ensembl ].
VAR_052595

Experimental info

Mutagenesis342 – 3443KKK → AAA: Reduced enzyme activity; abolishes stimulation of ATPase activity upon DNA binding. Ref.30
Mutagenesis342 – 3443KKK → EEE: Strongly reduced enzyme activity; abolishes stimulation of ATPase activity upon DNA binding. Ref.30
Mutagenesis4611E → A or C: Impairs bending of target DNA. Strongly reduced DNA cleavage. Ref.24 Ref.33
Mutagenesis5411D → A or C: Impairs bending of target DNA. Strongly reduced DNA cleavage. Ref.24 Ref.33
Mutagenesis5431D → A or C: Impairs bending of target DNA. Strongly reduced DNA cleavage. Ref.24 Ref.33
Mutagenesis5451D → A or C: Strongly reduced DNA cleavage. Ref.24
Mutagenesis14691S → A: Abolishes binding to the antibody MPM2. Ref.12
Sequence conflict1521D → H in CAA09762. Ref.4
Sequence conflict1801E → Q in CAA09762. Ref.4
Sequence conflict3271D → H in CAA09762. Ref.4
Sequence conflict10221F → L in CAA09762. Ref.4
Sequence conflict12741T → S in CAA09762. Ref.4
Sequence conflict12951S → P in AAA61209. Ref.1

Secondary structure

............................................................................................................................................................................................ 1531
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 4, 2001. Version 3.
Checksum: 3DF40BC9E84789DC

FASTA1,531174,385
        10         20         30         40         50         60 
MEVSPLQPVN ENMQVNKIKK NEDAKKRLSV ERIYQKKTQL EHILLRPDTY IGSVELVTQQ 

        70         80         90        100        110        120 
MWVYDEDVGI NYREVTFVPG LYKIFDEILV NAADNKQRDP KMSCIRVTID PENNLISIWN 

       130        140        150        160        170        180 
NGKGIPVVEH KVEKMYVPAL IFGQLLTSSN YDDDEKKVTG GRNGYGAKLC NIFSTKFTVE 

       190        200        210        220        230        240 
TASREYKKMF KQTWMDNMGR AGEMELKPFN GEDYTCITFQ PDLSKFKMQS LDKDIVALMV 

       250        260        270        280        290        300 
RRAYDIAGST KDVKVFLNGN KLPVKGFRSY VDMYLKDKLD ETGNSLKVIH EQVNHRWEVC 

       310        320        330        340        350        360 
LTMSEKGFQQ ISFVNSIATS KGGRHVDYVA DQIVTKLVDV VKKKNKGGVA VKAHQVKNHM 

       370        380        390        400        410        420 
WIFVNALIEN PTFDSQTKEN MTLQPKSFGS TCQLSEKFIK AAIGCGIVES ILNWVKFKAQ 

       430        440        450        460        470        480 
VQLNKKCSAV KHNRIKGIPK LDDANDAGGR NSTECTLILT EGDSAKTLAV SGLGVVGRDK 

       490        500        510        520        530        540 
YGVFPLRGKI LNVREASHKQ IMENAEINNI IKIVGLQYKK NYEDEDSLKT LRYGKIMIMT 

       550        560        570        580        590        600 
DQDQDGSHIK GLLINFIHHN WPSLLRHRFL EEFITPIVKV SKNKQEMAFY SLPEFEEWKS 

       610        620        630        640        650        660 
STPNHKKWKV KYYKGLGTST SKEAKEYFAD MKRHRIQFKY SGPEDDAAIS LAFSKKQIDD 

       670        680        690        700        710        720 
RKEWLTNFME DRRQRKLLGL PEDYLYGQTT TYLTYNDFIN KELILFSNSD NERSIPSMVD 

       730        740        750        760        770        780 
GLKPGQRKVL FTCFKRNDKR EVKVAQLAGS VAEMSSYHHG EMSLMMTIIN LAQNFVGSNN 

       790        800        810        820        830        840 
LNLLQPIGQF GTRLHGGKDS ASPRYIFTML SSLARLLFPP KDDHTLKFLY DDNQRVEPEW 

       850        860        870        880        890        900 
YIPIIPMVLI NGAEGIGTGW SCKIPNFDVR EIVNNIRRLM DGEEPLPMLP SYKNFKGTIE 

       910        920        930        940        950        960 
ELAPNQYVIS GEVAILNSTT IEISELPVRT WTQTYKEQVL EPMLNGTEKT PPLITDYREY 

       970        980        990       1000       1010       1020 
HTDTTVKFVV KMTEEKLAEA ERVGLHKVFK LQTSLTCNSM VLFDHVGCLK KYDTVLDILR 

      1030       1040       1050       1060       1070       1080 
DFFELRLKYY GLRKEWLLGM LGAESAKLNN QARFILEKID GKIIIENKPK KELIKVLIQR 

      1090       1100       1110       1120       1130       1140 
GYDSDPVKAW KEAQQKVPDE EENEESDNEK ETEKSDSVTD SGPTFNYLLD MPLWYLTKEK 

      1150       1160       1170       1180       1190       1200 
KDELCRLRNE KEQELDTLKR KSPSDLWKED LATFIEELEA VEAKEKQDEQ VGLPGKGGKA 

      1210       1220       1230       1240       1250       1260 
KGKKTQMAEV LPSPRGQRVI PRITIEMKAE AEKKNKKKIK NENTEGSPQE DGVELEGLKQ 

      1270       1280       1290       1300       1310       1320 
RLEKKQKREP GTKTKKQTTL AFKPIKKGKK RNPWSDSESD RSSDESNFDV PPRETEPRRA 

      1330       1340       1350       1360       1370       1380 
ATKTKFTMDL DSDEDFSDFD EKTDDEDFVP SDASPPKTKT SPKLSNKELK PQKSVVSDLE 

      1390       1400       1410       1420       1430       1440 
ADDVKGSVPL SSSPPATHFP DETEITNPVP KKNVTVKKTA AKSQSSTSTT GAKKRAAPKG 

      1450       1460       1470       1480       1490       1500 
TKRDPALNSG VSQKPDPAKT KNRRKRKPST SDDSDSNFEK IVSKAVTSKK SKGESDDFHM 

      1510       1520       1530 
DFDSAVAPRA KSVRAKKPIK YLEESDEDDL F 

« Hide

Isoform 2 [UniParc].

Checksum: 4DE312DFAEC443EA
Show »

FASTA1,557177,501
Isoform 3 [UniParc].

Checksum: E5322E9ED4DD7BF5
Show »

FASTA1,567178,712
Isoform 4 [UniParc].

Checksum: AB857EA93238BD4A
Show »

FASTA1,612182,681

References

« Hide 'large scale' references
[1]"Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22."
Tsai-Pflugfelder M., Liu L.F., Liu A.A., Tewey K.M., Whang-Peng J., Knutsen T., Huebner K., Croce C.M., Wang J.C.
Proc. Natl. Acad. Sci. U.S.A. 85:7177-7181(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Use of yeast in the study of anticancer drugs targeting DNA topoisomerases: expression of a functional recombinant human DNA topoisomerase II alpha in yeast."
Wasserman R.A., Austin C.A., Fisher L.M., Wang J.C.
Cancer Res. 53:3591-3596(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION TO 109-114.
[3]"Structural organization of the human TOP2A and TOP2B genes."
Lang A.J., Mirski S.E., Cummings H.J., Yu Q., Gerlach J.H., Cole S.P.
Gene 221:255-266(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[4]"Molecular cloning and characterization of the human topoisomerase IIalpha and IIbeta genes: evidence for isoform evolution through gene duplication."
Sng J.H., Heaton V.J., Bell M., Mani P., Austin C.A., Fisher L.M.
Biochim. Biophys. Acta 1444:395-406(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[5]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[8]"Two differentially spliced forms of topoisomerase II alpha and beta mRNAs are conserved between birds and humans."
Petruti-Mot A.S., Earnshaw W.C.
Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-500 (ISOFORMS 2; 3 AND 4).
[9]Neri S., Govoni M., Perrotta L., Pozzi S., Pession A.
Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21 AND 48-72.
[10]Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 1-17; 74-96; 124-131; 169-184; 243-251; 277-287; 325-336; 387-397; 467-478; 481-487; 500-519; 569-579; 702-713; 805-815; 828-835; 864-877; 937-958; 1021-1026 AND 1185-1196, ACETYLATION AT MET-1, MASS SPECTROMETRY.
Tissue: Ovarian carcinoma.
[11]Bienvenut W.V., Waridel P., Quadroni M.
Submitted (MAR-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 135-157; 228-241; 307-321; 325-336; 387-397; 401-416; 467-478; 536-550; 569-579; 640-655; 702-713; 805-815; 1011-1020; 1097-1114; 1169-1184; 1239-1259 AND 1374-1411, PHOSPHORYLATION AT SER-1106, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[12]"Mitotic phosphorylation of DNA topoisomerase II alpha by protein kinase CK2 creates the MPM-2 phosphoepitope on Ser-1469."
Escargueil A.E., Plisov S.Y., Filhol O., Cochet C., Larsen A.K.
J. Biol. Chem. 275:34710-34718(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-1469, MUTAGENESIS OF SER-1469.
[13]"Identification of functional nuclear export sequences in human topoisomerase IIalpha and beta."
Mirski S.E., Bielawski J.C., Cole S.P.
Biochem. Biophys. Res. Commun. 306:905-911(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEAR EXPORT SIGNAL.
[14]"Interaction between glucose-regulated destruction domain of DNA topoisomerase IIalpha and MPN domain of Jab1/CSN5."
Yun J., Tomida A., Andoh T., Tsuruo T.
J. Biol. Chem. 279:31296-31303(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH COPS5.
[15]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4; SER-1106; SER-1213; SER-1247; SER-1332; SER-1337; THR-1343; SER-1351; SER-1354; SER-1374; SER-1377 AND SER-1525, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1213; SER-1374; SER-1377 AND SER-1525, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[17]"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra."
Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.
J. Proteome Res. 6:4150-4162(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1247, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[18]"Plk3 phosphorylates topoisomerase IIalpha at Thr(1342), a site that is not recognized by Plk1."
Iida M., Matsuda M., Komatani H.
Biochem. J. 411:27-32(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-1343.
[19]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1504, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[20]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4; SER-1213; SER-1247; SER-1332; SER-1337 AND SER-1377, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[21]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1106; SER-1213; SER-1332; SER-1337; THR-1343; SER-1351; SER-1392; SER-1393; SER-1449; SER-1469; THR-1470; SER-1471; SER-1474 AND SER-1525, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"Use of divalent metal ions in the DNA cleavage reaction of human type II topoisomerases."
Deweese J.E., Burch A.M., Burgin A.B., Osheroff N.
Biochemistry 48:1862-1869(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, COFACTOR.
[24]"Metal ion interactions in the DNA cleavage/ligation active site of human topoisomerase IIalpha."
Deweese J.E., Guengerich F.P., Burgin A.B., Osheroff N.
Biochemistry 48:8940-8947(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF GLU-461; ASP-541; ASP-543 AND ASP-545, PUTATIVE METAL-BINDING SITES, CATALYTIC ACTIVITY, COFACTOR.
[25]"Casein kinase I delta/epsilon phosphorylates topoisomerase IIalpha at serine-1106 and modulates DNA cleavage activity."
Grozav A.G., Chikamori K., Kozuki T., Grabowski D.R., Bukowski R.M., Willard B., Kinter M., Andersen A.H., Ganapathi R., Ganapathi M.K.
Nucleic Acids Res. 37:382-392(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-1106 BY CSNK1D/CK1.
[26]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1247; SER-1374; SER-1387; SER-1393; SER-1504 AND SER-1525, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[27]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4; THR-282; SER-1106; THR-1205; SER-1213; SER-1247; SER-1332; SER-1337; THR-1343; SER-1351; SER-1354; SER-1374; SER-1377; SER-1471; SER-1474; SER-1495; SER-1504 AND SER-1525, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[28]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[29]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4; SER-1106; SER-1213; SER-1247; SER-1295; SER-1297; SER-1299; SER-1302; SER-1332; SER-1337; THR-1343; SER-1351; SER-1354; SER-1374; SER-1377; SER-1469; THR-1470; SER-1471; SER-1474; SER-1476 AND SER-1525, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[30]"Structure of a topoisomerase II-DNA-nucleotide complex reveals a new control mechanism for ATPase activity."
Schmidt B.H., Osheroff N., Berger J.M.
Nat. Struct. Mol. Biol. 19:1147-1154(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF 342-LYS--LYS-344.
[31]"RECQL5 cooperates with Topoisomerase II alpha in DNA decatenation and cell cycle progression."
Ramamoorthy M., Tadokoro T., Rybanska I., Ghosh A.K., Wersto R., May A., Kulikowicz T., Sykora P., Croteau D.L., Bohr V.A.
Nucleic Acids Res. 40:1621-1635(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RECQL5.
[32]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[33]"DNA cleavage and opening reactions of human topoisomerase IIalpha are regulated via Mg2+-mediated dynamic bending of gate-DNA."
Lee S., Jung S.R., Heo K., Byl J.A., Deweese J.E., Osheroff N., Hohng S.
Proc. Natl. Acad. Sci. U.S.A. 109:2925-2930(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF GLU-461; ASP-541 AND ASP-543, COFACTOR.
[34]"Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA topoisomerase."
Wei H., Ruthenburg A.J., Bechis S.K., Verdine G.L.
J. Biol. Chem. 280:37041-37047(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 29-428 IN COMPLEX WITH ADP, X-RAY CRYSTALLOGRAPHY (1.87 ANGSTROMS) OF 29-428 IN COMPLEX WITH AMPPNP.
[35]"The structure of DNA-bound human topoisomerase II alpha: conformational mechanisms for coordinating inter-subunit interactions with DNA cleavage."
Wendorff T.J., Schmidt B.H., Heslop P., Austin C.A., Berger J.M.
J. Mol. Biol. 424:109-124(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 431-1193 IN COMPLEX WITH DNA AND MAGNESIUM ION, SUBUNIT, COFACTOR.
[36]"Identification of a point mutation in the topoisomerase II gene from a human leukemia cell line containing an amsacrine-resistant form of topoisomerase II."
Hinds M., Deisseroth K., Mayes J., Altschuler E., Jansen R., Ledley F.D., Zwelling L.A.
Cancer Res. 51:4729-4731(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AMSACRINE-RESISTANT LYS-487.
[37]"Expression of a mutant DNA topoisomerase II in CCRF-CEM human leukemic cells selected for resistance to teniposide."
Bugg B.Y., Danks M.K., Beck W.T., Suttle D.P.
Proc. Natl. Acad. Sci. U.S.A. 88:7654-7658(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TENIPOSIDE-RESISTANT GLN-450.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J04088 mRNA. Translation: AAA61209.1.
AF071747 expand/collapse EMBL AC list , AF071738, AF071739, AF071740, AF071741, AF071742, AF071743, AF071744, AF071745, AF071746 Genomic DNA. Translation: AAC77388.1.
AJ011741 expand/collapse EMBL AC list , AJ011742, AJ011743, AJ011744, AJ011745, AJ011746, AJ011747, AJ011748, AJ011749, AJ011750, AJ011751, AJ011752, AJ011753, AJ011754, AJ011755, AJ011756, AJ011757, AJ011758 Genomic DNA. Translation: CAA09762.1.
AC080112 Genomic DNA. No translation available.
AF285157 mRNA. Translation: AAG13403.1.
AF285158 mRNA. Translation: AAG13404.1.
CH471152 Genomic DNA. Translation: EAW60663.1.
BC140791 mRNA. Translation: AAI40792.1.
AF285159 mRNA. Translation: AAG13405.1.
AF069522 Genomic DNA. Translation: AAC23518.1.
AF064590 Genomic DNA. Translation: AAC16736.1.
PIRA40493.
RefSeqNP_001058.2. NM_001067.3.
UniGeneHs.156346.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LWZmodel-A431-1200[»]
1ZXMX-ray1.87A/B29-428[»]
1ZXNX-ray2.51A/B/C/D29-428[»]
4FM9X-ray2.90A431-1193[»]
ProteinModelPortalP11388.
SMRP11388. Positions 29-1190.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113006. 56 interactions.
DIPDIP-33887N.
IntActP11388. 17 interactions.
MINTMINT-98770.

Chemistry

BindingDBP11388.
ChEMBLCHEMBL1806.
DrugBankDB00276. Amsacrine.
DB00537. Ciprofloxacin.
DB00380. Dexrazoxane.
DB00997. Doxorubicin.
DB00467. Enoxacin.
DB00445. Epirubicin.
DB00773. Etoposide.
DB04576. Fleroxacin.
DB01044. Gatifloxacin.
DB01177. Idarubicin.
DB01137. Levofloxacin.
DB00978. Lomefloxacin.
DB04967. Lucanthone.
DB01204. Mitoxantrone.
DB00218. Moxifloxacin.
DB01059. Norfloxacin.
DB01165. Ofloxacin.
DB00487. Pefloxacin.
DB01179. Podofilox.
DB01208. Sparfloxacin.
DB00444. Teniposide.
DB00685. Trovafloxacin.
DB00385. Valrubicin.
GuidetoPHARMACOLOGY2637.

PTM databases

PhosphoSiteP11388.

Polymorphism databases

DMDM13959709.

2D gel databases

UCD-2DPAGEP11388.

Proteomic databases

PaxDbP11388.
PRIDEP11388.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000423485; ENSP00000411532; ENSG00000131747. [P11388-1]
GeneID7153.
KEGGhsa:7153.
UCSCuc002huq.3. human. [P11388-1]

Organism-specific databases

CTD7153.
GeneCardsGC17M038544.
H-InvDBHIX0013797.
HGNCHGNC:11989. TOP2A.
HPACAB002448.
HPA006458.
HPA026773.
MIM126430. gene.
neXtProtNX_P11388.
Orphanet635. Neuroblastoma.
PharmGKBPA354.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0187.
HOVERGENHBG052998.
KOK03164.
OMAENMTLQV.
OrthoDBEOG73JKTM.
TreeFamTF105282.

Enzyme and pathway databases

BRENDA5.99.1.3. 2681.
ReactomeREACT_115566. Cell Cycle.
SignaLinkP11388.

Gene expression databases

ArrayExpressP11388.
BgeeP11388.
CleanExHS_TOP2A.
GenevestigatorP11388.

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

EvolutionaryTraceP11388.
GeneWikiTOP2A.
GenomeRNAi7153.
NextBio27992.
PROP11388.
SOURCESearch...

Entry information

Entry nameTOP2A_HUMAN
AccessionPrimary (citable) accession number: P11388
Secondary accession number(s): B2RTS1 expand/collapse secondary AC list , Q71UN1, Q71UQ5, Q9HB24, Q9HB25, Q9HB26, Q9UP44, Q9UQP9
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: May 4, 2001
Last modified: March 19, 2014
This is version 178 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM