DNA topoisomerase 2-alpha

Details

Name
DNA topoisomerase 2-alpha
Synonyms
  • 5.99.1.3
  • DNA topoisomerase II, alpha isozyme
  • TOP2
Gene Name
TOP2A
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001480|DNA topoisomerase 2-alpha
MEVSPLQPVNENMQVNKIKKNEDAKKRLSVERIYQKKTQLEHILLRPDTYIGSVELVTQQ
MWVYDEDVGINYREVTFVPGLYKIFDEILVNAADNKQRDPKMSCIRVTIDPENNLISIWN
NGKGIPVVEHKVEKMYVPALIFGQLLTSSNYDDDEKKVTGGRNGYGAKLCNIFSTKFTVE
TASREYKKMFKQTWMDNMGRAGEMELKPFNGEDYTCITFQPDLSKFKMQSLDKDIVALMV
RRAYDIAGSTKDVKVFLNGNKLPVKGFRSYVDMYLKDKLDETGNSLKVIHEQVNHRWEVC
LTMSEKGFQQISFVNSIATSKGGRHVDYVADQIVTKLVDVVKKKNKGGVAVKAHQVKNHM
WIFVNALIENPTFDSQTKENMTLQPKSFGSTCQLSEKFIKAAIGCGIVESILNWVKFKAQ
VQLNKKCSAVKHNRIKGIPKLDDANDAGGRNSTECTLILTEGDSAKTLAVSGLGVVGRDK
YGVFPLRGKILNVREASHKQIMENAEINNIIKIVGLQYKKNYEDEDSLKTLRYGKIMIMT
DQDQDGSHIKGLLINFIHHNWPSLLRHRFLEEFITPIVKVSKNKQEMAFYSLPEFEEWKS
STPNHKKWKVKYYKGLGTSTSKEAKEYFADMKRHRIQFKYSGPEDDAAISLAFSKKQIDD
RKEWLTNFMEDRRQRKLLGLPEDYLYGQTTTYLTYNDFINKELILFSNSDNERSIPSMVD
GLKPGQRKVLFTCFKRNDKREVKVAQLAGSVAEMSSYHHGEMSLMMTIINLAQNFVGSNN
LNLLQPIGQFGTRLHGGKDSASPRYIFTMLSSLARLLFPPKDDHTLKFLYDDNQRVEPEW
YIPIIPMVLINGAEGIGTGWSCKIPNFDVREIVNNIRRLMDGEEPLPMLPSYKNFKGTIE
ELAPNQYVISGEVAILNSTTIEISELPVRTWTQTYKEQVLEPMLNGTEKTPPLITDYREY
HTDTTVKFVVKMTEEKLAEAERVGLHKVFKLQTSLTCNSMVLFDHVGCLKKYDTVLDILR
DFFELRLKYYGLRKEWLLGMLGAESAKLNNQARFILEKIDGKIIIENKPKKELIKVLIQR
GYDSDPVKAWKEAQQKVPDEEENEESDNEKETEKSDSVTDSGPTFNYLLDMPLWYLTKEK
KDELCRLRNEKEQELDTLKRKSPSDLWKEDLATFIEELEAVEAKEKQDEQVGLPGKGGKA
KGKKTQMAEVLPSPRGQRVIPRITIEMKAEAEKKNKKKIKNENTEGSPQEDGVELEGLKQ
RLEKKQKREPGTKTKKQTTLAFKPIKKGKKRNPWSDSESDRSSDESNFDVPPRETEPRRA
ATKTKFTMDLDSDEDFSDFDEKTDDEDFVPSDASPPKTKTSPKLSNKELKPQKSVVSDLE
ADDVKGSVPLSSSPPATHFPDETEITNPVPKKNVTVKKTAAKSQSSTSTTGAKKRAAPKG
TKRDPALNSGVSQKPDPAKTKNRRKRKPSTSDDSDSNFEKIVSKAVTSKKSKGESDDFHM
DFDSAVAPRAKSVRAKKPIKYLEESDEDDLF
Number of residues
1531
Molecular Weight
174383.88
Theoretical pI
9.17
GO Classification
Functions
ATP binding / chromatin binding / DNA binding / DNA binding, bending / DNA topoisomerase type II (ATP-hydrolyzing) activity / DNA-dependent ATPase activity / drug binding / enzyme binding / histone deacetylase binding / magnesium ion binding / poly(A) RNA binding / protein C-terminus binding / protein heterodimerization activity / protein homodimerization activity / protein kinase C binding / ubiquitin binding
Processes
apoptotic chromosome condensation / cellular response to DNA damage stimulus / chromosome segregation / DNA ligation / DNA topological change / DNA unwinding involved in DNA replication / embryonic cleavage / hematopoietic progenitor cell differentiation / mitotic cell cycle / mitotic DNA integrity checkpoint / mitotic recombination / positive regulation of apoptotic process / positive regulation of single stranded viral RNA replication via double stranded DNA intermediate / positive regulation of transcription from RNA polymerase II promoter / positive regulation of viral genome replication / regulation of circadian rhythm / resolution of meiotic recombination intermediates / rhythmic process / sister chromatid segregation
Components
condensed chromosome / cytoplasm / DNA topoisomerase complex (ATP-hydrolyzing) / nucleolus / nucleoplasm / nucleus / protein complex
General Function
Ubiquitin binding
Specific 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. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0019005|DNA topoisomerase 2-alpha (TOP2A)
ATGGAAGTGTCACCATTGCAGCCTGTAAATGAAAATATGCAAGTCAACAAAATAAAGAAA
AATGAAGATGCTAAGAAAAGACTGTCTGTTGAAAGAATCTATCAAAAGAAAACACAATTG
GAACATATTTTGCTCCGCCCAGACACCTACATTGGTTCTGTGGAATTAGTGACCCAGCAA
ATGTGGGTTTACGATGAAGATGTTGGCATTAACTATAGGGAAGTCACTTTTGTTCCTGGT
TTGTACAAAATCTTTGATGAGATTCTAGTTAATGCTGCGGACAACAAACAAAGGGACCCA
AAAATGTCTTGTATTAGAGTCACAATTGATCCGGAAAACAATTTAATTAGTATATGGAAT
AATGGAAAAGGTATTCCTGTTGTTGAACACAAAGTTGAAAAGATGTATGTCCCAGCTCTC
ATATTTGGACAGCTCCTAACTTCTAGTAACTATGATGATGATGAAAAGAAAGTGACAGGT
GGTCGAAATGGCTATGGAGCCAAATTGTGTAACATATTCAGTACCAAATTTACTGTGGAA
ACAGCCAGTAGAGAATACAAGAAAATGTTCAAACAGACATGGATGGATAATATGGGAAGA
GCTGGTGAGATGGAACTCAAGCCCTTCAATGGAGAAGATTATACATGTATCACCTTTCAG
CCTGATTTGTCTAAGTTTAAAATGCAAAGCCTGGACAAAGATATTGTTGCACTAATGGTC
AGAAGAGCATATGATATTGCTGGATCCACCAAAGATGTCAAAGTCTTTCTTAATGGAAAT
AAACTGCCAGTAAAAGGATTTCGTAGTTATGTGGACATGTATTTGAAGGACAAGTTGGAT
GAAACTGGTAACTCCTTGAAAGTAATACATGAACAAGTAAACCACAGGTGGGAAGTGTGT
TTAACTATGAGTGAAAAAGGCTTTCAGCAAATTAGCTTTGTCAACAGCATTGCTACATCC
AAGGGTGGCAGACATGTTGATTATGTAGCTGATCAGATTGTGACTAAACTTGTTGATGTT
GTGAAGAAGAAGAACAAGGGTGGTGTTGCAGTAAAAGCACATCAGGTGAAAAATCACATG
TGGATTTTTGTAAATGCCTTAATTGAAAACCCAACCTTTGACTCTCAGACAAAAGAAAAC
ATGACTTTACAACCCAAGAGCTTTGGATCAACATGCCAATTGAGTGAAAAATTTATCAAA
GCTGCCATTGGCTGTGGTATTGTAGAAAGCATACTAAACTGGGTGAAGTTTAAGGCCCAA
GTCCAGTTAAACAAGAAGTGTTCAGCTGTAAAACATAATAGAATCAAGGGAATTCCCAAA
CTCGATGATGCCAATGATGCAGGGGGCCGAAACTCCACTGAGTGTACGCTTATCCTGACT
GAGGGAGATTCAGCCAAAACTTTGGCTGTTTCAGGCCTTGGTGTGGTTGGGAGAGACAAA
TATGGGGTTTTCCCTCTTAGAGGAAAAATACTCAATGTTCGAGAAGCTTCTCATAAGCAG
ATCATGGAAAATGCTGAGATTAACAATATCATCAAGATTGTGGGTCTTCAGTACAAGAAA
AACTATGAAGATGAAGATTCATTGAAGACGCTTCGTTATGGGAAGATAATGATTATGACA
GATCAGGACCAAGATGGTTCCCACATCAAAGGCTTGCTGATTAATTTTATCCATCACAAC
TGGCCCTCTCTTCTGCGACATCGTTTTCTGGAGGAATTTATCACTCCCATTGTAAAGGTA
TCTAAAAACAAGCAAGAAATGGCATTTTACAGCCTTCCTGAATTTGAAGAGTGGAAGAGT
TCTACTCCAAATCATAAAAAATGGAAAGTCAAATATTACAAAGGTTTGGGCACCAGCACA
TCAAAGGAAGCTAAAGAATACTTTGCAGATATGAAAAGACATCGTATCCAGTTCAAATAT
TCTGGTCCTGAAGATGATGCTGCTATCAGCCTGGCCTTTAGCAAAAAACAGATAGATGAT
CGAAAGGAATGGTTAACTAATTTCATGGAGGATAGAAGACAACGAAAGTTACTTGGGCTT
CCTGAGGATTACTTGTATGGACAAACTACCACATATCTGACATATAATGACTTCATCAAC
AAGGAACTTATCTTGTTCTCAAATTCTGATAACGAGAGATCTATCCCTTCTATGGTGGAT
GGTTTGAAACCAGGTCAGAGAAAGGTTTTGTTTACTTGCTTCAAACGGAATGACAAGCGA
GAAGTAAAGGTTGCCCAATTAGCTGGATCAGTGGCTGAAATGTCTTCTTATCATCATGGT
GAGATGTCACTAATGATGACCATTATCAATTTGGCTCAGAATTTTGTGGGTAGCAATAAT
CTAAACCTCTTGCAGCCCATTGGTCAGTTTGGTACCAGGCTACATGGTGGCAAGGATTCT
GCTAGTCCACGATACATCTTTACAATGCTCAGCTCTTTGGCTCGATTGTTATTTCCACCA
AAAGATGATCACACGTTGAAGTTTTTATATGATGACAACCAGCGTGTTGAGCCTGAATGG
TACATTCCTATTATTCCCATGGTGCTGATAAATGGTGCTGAAGGAATCGGTACTGGGTGG
TCCTGCAAAATCCCCAACTTTGATGTGCGTGAAATTGTAAATAACATCAGGCGTTTGATG
GATGGAGAAGAACCTTTGCCAATGCTTCCAAGTTACAAGAACTTCAAGGGTACTATTGAA
GAACTGGCTCCAAATCAATATGTGATTAGTGGTGAAGTAGCTATTCTTAATTCTACAACC
ATTGAAATCTCAGAGCTTCCCGTCAGAACATGGACCCAGACATACAAAGAACAAGTTCTA
GAACCCATGTTGAATGGCACCGAGAAGACACCTCCTCTCATAACAGACTATAGGGAATAC
CATACAGATACCACTGTGAAATTTGTTGTGAAGATGACTGAAGAAAAACTGGCAGAGGCA
GAGAGAGTTGGACTACACAAAGTCTTCAAACTCCAAACTAGTCTCACATGCAACTCTATG
GTGCTTTTTGACCACGTAGGCTGTTTAAAGAAATATGACACGGTGTTGGATATTCTAAGA
GACTTTTTTGAACTCAGACTTAAATATTATGGATTAAGAAAAGAATGGCTCCTAGGAATG
CTTGGTGCTGAATCTGCTAAACTGAATAATCAGGCTCGCTTTATCTTAGAGAAAATAGAT
GGCAAAATAATCATTGAAAATAAGCCTAAGAAAGAATTAATTAAAGTTCTGATTCAGAGG
GGATATGATTCGGATCCTGTGAAGGCCTGGAAAGAAGCCCAGCAAAAGGTTCCAGATGAA
GAAGAAAATGAAGAGAGTGACAACGAAAAGGAAACTGAAAAGAGTGACTCCGTAACAGAT
TCTGGACCAACCTTCAACTATCTTCTTGATATGCCCCTTTGGTATTTAACCAAGGAAAAG
AAAGATGAACTCTGCAGGCTAAGAAATGAAAAAGAACAAGAGCTGGACACATTAAAAAGA
AAGAGTCCATCAGATTTGTGGAAAGAAGACTTGGCTACATTTATTGAAGAATTGGAGGCT
GTTGAAGCCAAGGAAAAACAAGATGAACAAGTCGGACTTCCTGGGAAAGGGGGGAAGGCC
AAGGGGAAAAAAACACAAATGGCTGAAGTTTTGCCTTCTCCGCGTGGTCAAAGAGTCATT
CCACGAATAACCATAGAAATGAAAGCAGAGGCAGAAAAGAAAAATAAAAAGAAAATTAAG
AATGAAAATACTGAAGGAAGCCCTCAAGAAGATGGTGTGGAACTAGAAGGCCTAAAACAA
AGATTAGAAAAGAAACAGAAAAGAGAACCAGGTACAAAGACAAAGAAACAAACTACATTG
GCATTTAAGCCAATCAAAAAAGGAAAGAAGAGAAATCCCTGGTCTGATTCAGAATCAGAT
AGGAGCAGTGACGAAAGTAATTTTGATGTCCCTCCACGAGAAACAGAGCCACGGAGAGCA
GCAACAAAAACAAAATTCACAATGGATTTGGATTCAGATGAAGATTTCTCAGATTTTGAT
GAAAAAACTGATGATGAAGATTTTGTCCCATCAGATGCTAGTCCACCTAAGACCAAAACT
TCCCCAAAACTTAGTAACAAAGAACTGAAACCACAGAAAAGTGTCGTGTCAGACCTTGAA
GCTGATGATGTTAAGGGCAGTGTACCACTGTCTTCAAGCCCTCCTGCTACACATTTCCCA
GATGAAACTGAAATTACAAACCCAGTTCCTAAAAAGAATGTGACAGTGAAGAAGACAGCA
GCAAAAAGTCAGTCTTCCACCTCCACTACCGGTGCCAAAAAAAGGGCTGCCCCAAAAGGA
ACTAAAAGGGATCCAGCTTTGAATTCTGGTGTCTCTCAAAAGCCTGATCCTGCCAAAACC
AAGAATCGCCGCAAAAGGAAGCCATCCACTTCTGATGATTCTGACTCTAATTTTGAGAAA
ATTGTTTCGAAAGCAGTCACAAGCAAGAAATCCAAGGGGGAGAGTGATGACTTCCATATG
GACTTTGACTCAGCTGTGGCTCCTCGGGCAAAATCTGTACGGGCAAAGAAACCTATAAAG
TACCTGGAAGAGTCAGATGAAGATGATCTGTTTTAA
Chromosome Location
17
Locus
17q21-q22
External Identifiers
ResourceLink
UniProtKB IDP11388
UniProtKB Entry NameTOP2A_HUMAN
GenBank Protein ID292830
GenBank Gene IDJ04088
GenAtlas IDTOP2A
HGNC IDHGNC:11989
General References
  1. Tsai-Pflugfelder M, Liu LF, Liu AA, Tewey KM, Whang-Peng J, Knutsen T, Huebner K, Croce CM, Wang JC: Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7177-81. [PubMed:2845399]
  2. Wasserman RA, Austin CA, Fisher LM, Wang JC: Use of yeast in the study of anticancer drugs targeting DNA topoisomerases: expression of a functional recombinant human DNA topoisomerase II alpha in yeast. Cancer Res. 1993 Aug 1;53(15):3591-6. [PubMed:8393377]
  3. Lang AJ, Mirski SE, Cummings HJ, Yu Q, Gerlach JH, Cole SP: Structural organization of the human TOP2A and TOP2B genes. Gene. 1998 Oct 23;221(2):255-66. [PubMed:9795238]
  4. Sng JH, Heaton VJ, Bell M, Maini P, Austin CA, Fisher LM: Molecular cloning and characterization of the human topoisomerase IIalpha and IIbeta genes: evidence for isoform evolution through gene duplication. Biochim Biophys Acta. 1999 Mar 19;1444(3):395-406. [PubMed:10095062]
  5. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. [PubMed:16625196]
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  7. Escargueil AE, Plisov SY, Filhol O, Cochet C, Larsen AK: Mitotic phosphorylation of DNA topoisomerase II alpha by protein kinase CK2 creates the MPM-2 phosphoepitope on Ser-1469. J Biol Chem. 2000 Nov 3;275(44):34710-8. [PubMed:10942766]
  8. Mirski SE, Bielawski JC, Cole SP: Identification of functional nuclear export sequences in human topoisomerase IIalpha and beta. Biochem Biophys Res Commun. 2003 Jul 11;306(4):905-11. [PubMed:12821127]
  9. Yun J, Tomida A, Andoh T, Tsuruo T: Interaction between glucose-regulated destruction domain of DNA topoisomerase IIalpha and MPN domain of Jab1/CSN5. J Biol Chem. 2004 Jul 23;279(30):31296-303. Epub 2004 May 4. [PubMed:15126503]
  10. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983]
  11. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. [PubMed:16964243]
  12. Yu LR, Zhu Z, Chan KC, Issaq HJ, Dimitrov DS, Veenstra TD: 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. J Proteome Res. 2007 Nov;6(11):4150-62. Epub 2007 Oct 9. [PubMed:17924679]
  13. Iida M, Matsuda M, Komatani H: Plk3 phosphorylates topoisomerase IIalpha at Thr(1342), a site that is not recognized by Plk1. Biochem J. 2008 Apr 1;411(1):27-32. [PubMed:18062778]
  14. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. [PubMed:18220336]
  15. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [PubMed:18691976]
  16. Williamson EA, Rasila KK, Corwin LK, Wray J, Beck BD, Severns V, Mobarak C, Lee SH, Nickoloff JA, Hromas R: The SET and transposase domain protein Metnase enhances chromosome decatenation: regulation by automethylation. Nucleic Acids Res. 2008 Oct;36(18):5822-31. doi: 10.1093/nar/gkn560. Epub 2008 Sep 12. [PubMed:18790802]
  17. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648]
  18. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330]
  19. Deweese JE, Burch AM, Burgin AB, Osheroff N: Use of divalent metal ions in the dna cleavage reaction of human type II topoisomerases. Biochemistry. 2009 Mar 10;48(9):1862-9. doi: 10.1021/bi8023256. [PubMed:19222228]
  20. Deweese JE, Guengerich FP, Burgin AB, Osheroff N: Metal ion interactions in the DNA cleavage/ligation active site of human topoisomerase IIalpha. Biochemistry. 2009 Sep 29;48(38):8940-7. doi: 10.1021/bi900875c. [PubMed:19697956]
  21. Grozav AG, Chikamori K, Kozuki T, Grabowski DR, Bukowski RM, Willard B, Kinter M, Andersen AH, Ganapathi R, Ganapathi MK: Casein kinase I delta/epsilon phosphorylates topoisomerase IIalpha at serine-1106 and modulates DNA cleavage activity. Nucleic Acids Res. 2009 Feb;37(2):382-92. doi: 10.1093/nar/gkn934. Epub 2008 Nov 29. [PubMed:19043076]
  22. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332]
  23. De Haro LP, Wray J, Williamson EA, Durant ST, Corwin L, Gentry AC, Osheroff N, Lee SH, Hromas R, Nickoloff JA: Metnase promotes restart and repair of stalled and collapsed replication forks. Nucleic Acids Res. 2010 Sep;38(17):5681-91. doi: 10.1093/nar/gkq339. Epub 2010 May 10. [PubMed:20457750]
  24. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [PubMed:20068231]
  25. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  26. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [PubMed:21406692]
  27. Schmidt BH, Osheroff N, Berger JM: Structure of a topoisomerase II-DNA-nucleotide complex reveals a new control mechanism for ATPase activity. Nat Struct Mol Biol. 2012 Nov;19(11):1147-54. doi: 10.1038/nsmb.2388. Epub 2012 Sep 30. [PubMed:23022727]
  28. Ramamoorthy M, Tadokoro T, Rybanska I, Ghosh AK, Wersto R, May A, Kulikowicz T, Sykora P, Croteau DL, Bohr VA: RECQL5 cooperates with Topoisomerase II alpha in DNA decatenation and cell cycle progression. Nucleic Acids Res. 2012 Feb;40(4):1621-35. doi: 10.1093/nar/gkr844. Epub 2011 Oct 19. [PubMed:22013166]
  29. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [PubMed:22814378]
  30. Lee S, Jung SR, Heo K, Byl JA, Deweese JE, Osheroff N, Hohng S: DNA cleavage and opening reactions of human topoisomerase IIalpha are regulated via Mg2+-mediated dynamic bending of gate-DNA. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2925-30. doi: 10.1073/pnas.1115704109. Epub 2012 Feb 9. [PubMed:22323612]
  31. Hendriks IA, D'Souza RC, Yang B, Verlaan-de Vries M, Mann M, Vertegaal AC: Uncovering global SUMOylation signaling networks in a site-specific manner. Nat Struct Mol Biol. 2014 Oct;21(10):927-36. doi: 10.1038/nsmb.2890. Epub 2014 Sep 14. [PubMed:25218447]
  32. Wei H, Ruthenburg AJ, Bechis SK, Verdine GL: Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA topoisomerase. J Biol Chem. 2005 Nov 4;280(44):37041-7. Epub 2005 Aug 12. [PubMed:16100112]
  33. Wendorff TJ, Schmidt BH, Heslop P, Austin CA, Berger JM: The structure of DNA-bound human topoisomerase II alpha: conformational mechanisms for coordinating inter-subunit interactions with DNA cleavage. J Mol Biol. 2012 Dec 7;424(3-4):109-24. doi: 10.1016/j.jmb.2012.07.014. Epub 2012 Jul 25. [PubMed:22841979]
  34. Hinds M, Deisseroth K, Mayes J, Altschuler E, Jansen R, Ledley FD, Zwelling LA: Identification of a point mutation in the topoisomerase II gene from a human leukemia cell line containing an amsacrine-resistant form of topoisomerase II. Cancer Res. 1991 Sep 1;51(17):4729-31. [PubMed:1651812]
  35. Bugg BY, Danks MK, Beck WT, Suttle DP: Expression of a mutant DNA topoisomerase II in CCRF-CEM human leukemic cells selected for resistance to teniposide. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7654-8. [PubMed:1652758]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00276Amsacrineapproved, investigationalyesinhibitorDetails
DB00380Dexrazoxaneapproved, withdrawnyesinhibitorDetails
DB00385ValrubicinapprovedyesinhibitorDetails
DB00444TeniposideapprovedyesinhibitorDetails
DB00773EtoposideapprovedyesinhibitorDetails
DB00997Doxorubicinapproved, investigationalyesinhibitorDetails
DB01177IdarubicinapprovedyesinhibitorDetails
DB01204Mitoxantroneapproved, investigationalyesinhibitorDetails
DB00445EpirubicinapprovedunknowninhibitorDetails
DB01179PodofiloxapprovedyesinhibitorDetails
DB01645GenisteininvestigationalunknownDetails
DB00537Ciprofloxacinapproved, investigationalunknowninhibitorDetails
DB00467Enoxacinapproved, investigationalnoinhibitorDetails
DB04576FleroxacinexperimentalyesinhibitorDetails
DB01137Levofloxacinapproved, investigationalyesinhibitorDetails
DB00978Lomefloxacinapproved, investigationalunknowninhibitorDetails
DB00218Moxifloxacinapproved, investigationalunknowninhibitorDetails
DB01059NorfloxacinapprovedunknowninhibitorDetails
DB00487PefloxacinapprovedunknowninhibitorDetails
DB01208Sparfloxacinapproved, investigational, withdrawnyesinhibitorDetails
DB00685Trovafloxacinapproved, investigational, withdrawnunknowninhibitorDetails
DB01165OfloxacinapprovedunknowninhibitorDetails
DB05129ElsamitrucininvestigationalunknownDetails
DB04975BanoxantroneinvestigationalunknownDetails
DB04978SP1049CinvestigationalunknownDetails
DB04967LucanthoneinvestigationalyesinhibitorDetails
DB05022AmonafideinvestigationalunknownDetails
DB06042ZEN-012investigationalunknownDetails
DB05920RTA 744investigationalunknownDetails
DB0570613-deoxydoxorubicininvestigationalunknownDetails
DB06263AmrubicininvestigationalunknownDetails
DB06362BecatecarininvestigationalunknownDetails
DB06420AnnamycininvestigationalunknownDetails
DB06421DeclopramideinvestigationalunknownDetails
DB00694DaunorubicinapprovedyesinhibitorDetails
DB09047Finafloxacinapproved, investigationalyesinhibitorDetails
DB06013AldoxorubicininvestigationalyesinhibitorDetails
DB00970Dactinomycinapproved, investigationalunknowninhibitorDetails