UniProt Accession

 TOP2A_HUMAN; P11388; B2RTS1; Q71UN1; Q71UQ5; Q9HB24; Q9HB25; Q9HB26; Q9UP44; Q9UQP9 

Genbank Protein ID

 J04088; AF071747; AF071738; AF071739; AF071740; AF071741; AF071742; AF071743; AF071744; AF071745; AF071746; AJ011741; AJ011742; AJ011743; AJ011744; AJ011745; AJ011746; AJ011747; AJ011748; AJ011749; AJ011750; AJ011751; AJ011752; AJ011753; AJ011754; AJ011755; AJ011756; AJ011757; AJ011758; AC080112; AF285157; AF285158; CH471152; BC140791; AF285159; AF069522; AF064590 

Genbank Nucleotide ID

 AAA61209.1; AAC77388.1; AAC77388.1; AAC77388.1; AAC77388.1; AAC77388.1; AAC77388.1; AAC77388.1; AAC77388.1; AAC77388.1; AAC77388.1; CAA09762.1; CAA09762.1; CAA09762.1; CAA09762.1; CAA09762.1; CAA09762.1; CAA09762.1; CAA09762.1; CAA09762.1; CAA09762.1; CAA09762.1; CAA09762.1; CAA09762.1; CAA09762.1; CAA09762.1; CAA09762.1; CAA09762.1; CAA09762.1; AAG13403.1; AAG13404.1; EAW60663.1; AAI40792.1; AAG13405.1; AAC23518.1; AAC16736.1 

Protein Name

 DNA topoisomerase 2-alpha 

Protein Synonyms/Alias

 DNA topoisomerase II, alpha isozyme 

Gene Name

 TOP2A 

Gene Synonyms/Alias

 TOP2 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
17	NENMQVNKIKKNEDA	ubiquitination	[1, 2]
19	NMQVNKIKKNEDAKK	ubiquitination	[2]
20	MQVNKIKKNEDAKKR	ubiquitination	[2]
156	SNYDDDEKKVTGGRN	ubiquitination	[2]
191	REYKKMFKQTWMDNM	ubiquitination	[1, 2]
225	TFQPDLSKFKMQSLD	ubiquitination	[3]
227	QPDLSKFKMQSLDKD	ubiquitination	[2, 3]
233	FKMQSLDKDIVALMV	ubiquitination	[2, 4]
251	YDIAGSTKDVKVFLN	ubiquitination	[2, 5]
254	AGSTKDVKVFLNGNK	acetylation	[5]
261	KVFLNGNKLPVKGFR	ubiquitination	[2, 4]
265	NGNKLPVKGFRSYVD	ubiquitination	[2]
276	SYVDMYLKDKLDETG	ubiquitination	[2]
278	VDMYLKDKLDETGNS	acetylation	[6]
278	VDMYLKDKLDETGNS	ubiquitination	[2, 7]
287	DETGNSLKVIHEQVN	ubiquitination	[4, 8]
321	VNSIATSKGGRHVDY	ubiquitination	[2, 4, 5]
336	VADQIVTKLVDVVKK	ubiquitination	[2]
343	KLVDVVKKKNKGGVA	ubiquitination	[2]
386	ENMTLQPKSFGSTCQ	ubiquitination	[2, 4, 5, 8]
397	STCQLSEKFIKAAIG	ubiquitination	[2, 5]
418	ILNWVKFKAQVQLNK	ubiquitination	[2, 4]
440	NRIKGIPKLDDANDA	ubiquitination	[2]
466	LTEGDSAKTLAVSGL	ubiquitination	[2, 5, 8, 9]
480	LGVVGRDKYGVFPLR	ubiquitination	[2, 4, 5]
499	NVREASHKQIMENAE	ubiquitination	[4]
520	IVGLQYKKNYEDEDS	ubiquitination	[2, 4, 5, 7]
529	YEDEDSLKTLRYGKI	acetylation	[10]
529	YEDEDSLKTLRYGKI	ubiquitination	[2, 3, 4, 5, 7, 8]
579	EFITPIVKVSKNKQE	ubiquitination	[2, 3, 5, 7, 8]
582	TPIVKVSKNKQEMAF	ubiquitination	[2]
584	IVKVSKNKQEMAFYS	ubiquitination	[2, 7, 8]
614	KWKVKYYKGLGTSTS	ubiquitination	[2, 4, 5, 8]
622	GLGTSTSKEAKEYFA	ubiquitination	[2, 5, 7]
625	TSTSKEAKEYFADMK	ubiquitination	[2, 5]
632	KEYFADMKRHRIQFK	ubiquitination	[1, 2, 3, 5]
639	KRHRIQFKYSGPEDD	ubiquitination	[2, 3, 7, 8]
655	AISLAFSKKQIDDRK	ubiquitination	[1, 2, 3, 4, 7, 8, 9]
656	ISLAFSKKQIDDRKE	ubiquitination	[2, 5]
662	KKQIDDRKEWLTNFM	sumoylation	[11]
676	MEDRRQRKLLGLPED	ubiquitination	[3, 7]
723	PSMVDGLKPGQRKVL	ubiquitination	[2, 4, 5]
821	ARLLFPPKDDHTLKF	ubiquitination	[4]
827	PKDDHTLKFLYDDNQ	ubiquitination	[4]
893	LPMLPSYKNFKGTIE	ubiquitination	[7]
896	LPSYKNFKGTIEELA	ubiquitination	[2]
936	RTWTQTYKEQVLEPM	ubiquitination	[2, 7, 8]
949	PMLNGTEKTPPLITD	ubiquitination	[2, 7, 8]
971	TTVKFVVKMTEEKLA	acetylation	[12]
976	VVKMTEEKLAEAERV	ubiquitination	[2, 5]
1011	DHVGCLKKYDTVLDI	ubiquitination	[4]
1028	DFFELRLKYYGLRKE	ubiquitination	[4]
1058	QARFILEKIDGKIII	ubiquitination	[2, 5]
1062	ILEKIDGKIIIENKP	ubiquitination	[2, 5, 7]
1068	GKIIIENKPKKELIK	ubiquitination	[2, 5]
1071	IIENKPKKELIKVLI	ubiquitination	[2]
1075	KPKKELIKVLIQRGY	ubiquitination	[2, 4, 5]
1088	GYDSDPVKAWKEAQQ	ubiquitination	[2, 5]
1151	LCRLRNEKEQELDTL	ubiquitination	[5]
1159	EQELDTLKRKSPSDL	ubiquitination	[2, 5, 7, 8]
1186	EAVEAKEKQDEQVGL	ubiquitination	[2]
1196	EQVGLPGKGGKAKGK	ubiquitination	[1, 3, 5, 7]
1199	GLPGKGGKAKGKKTQ	ubiquitination	[2]
1203	KGGKAKGKKTQMAEV	ubiquitination	[2]
1204	GGKAKGKKTQMAEVL	ubiquitination	[7]
1228	PRITIEMKAEAEKKN	sumoylation	[13]
1228	PRITIEMKAEAEKKN	ubiquitination	[2]
1240	KKNKKKIKNENTEGS	sumoylation	[13]
1259	GVELEGLKQRLEKKQ	ubiquitination	[3, 7, 8]
1283	KQTTLAFKPIKKGKK	acetylation	[10]
1286	TLAFKPIKKGKKRNP	ubiquitination	[8]
1367	TSPKLSNKELKPQKS	acetylation	[5]
1367	TSPKLSNKELKPQKS	ubiquitination	[2]
1454	LNSGVSQKPDPAKTK	acetylation	[5, 10]
1454	LNSGVSQKPDPAKTK	ubiquitination	[2]
1492	AVTSKKSKGESDDFH	ubiquitination	[2]

Reference

 [1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [6] Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome.
 Morselli E, Mariño G, Bennetzen MV, Eisenberg T, Megalou E, Schroeder S, Cabrera S, Bénit P, Rustin P, Criollo A, Kepp O, Galluzzi L, Shen S, Malik SA, Maiuri MC, Horio Y, López-Otín C, Andersen JS, Tavernarakis N, Madeo F, Kroemer G.
 J Cell Biol. 2011 Feb 21;192(4):615-29. [PMID: 21339330]
 [7] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [8] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [9] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [10] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [11] PIASy-dependent SUMOylation regulates DNA topoisomerase IIalpha activity.
 Ryu H, Furuta M, Kirkpatrick D, Gygi SP, Azuma Y.
 J Cell Biol. 2010 Nov 15;191(4):783-94. [PMID: 21079245]
 [12] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [13] Site-specific identification of SUMO-2 targets in cells reveals an inverted SUMOylation motif and a hydrophobic cluster SUMOylation motif.
 Matic I, Schimmel J, Hendriks IA, van Santen MA, van de Rijke F, van Dam H, Gnad F, Mann M, Vertegaal AC.
 Mol Cell. 2010 Aug 27;39(4):641-52. [PMID: 20797634] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 455 572 Toprim.
 NP_BIND 148 150 ATP.
 NP_BIND 161 168 ATP.
 NP_BIND 376 378 ATP.
 REGION 342 344 Interaction with DNA (Probable).
 REGION 990 999 Interaction with DNA.
 MOTIF 1018 1028 Nuclear export signal.
 ACT_SITE 805 805 O-(5'-phospho-DNA)-tyrosine intermediate
 METAL 461 461 Magnesium 1; catalytic (By similarity).
 METAL 541 541 Magnesium 1; catalytic (By similarity).
 METAL 541 541 Magnesium 2.
 METAL 543 543 Magnesium 2.
 BINDING 91 91 ATP.
 BINDING 120 120 ATP.
 MOD_RES 1 1 N-acetylmethionine.
 MOD_RES 4 4 Phosphoserine.
 MOD_RES 29 29 Phosphoserine (By similarity).
 MOD_RES 282 282 Phosphothreonine.
 MOD_RES 1106 1106 Phosphoserine; by CK1.
 MOD_RES 1205 1205 Phosphothreonine.
 MOD_RES 1213 1213 Phosphoserine.
 MOD_RES 1247 1247 Phosphoserine.
 MOD_RES 1295 1295 Phosphoserine.
 MOD_RES 1297 1297 Phosphoserine.
 MOD_RES 1299 1299 Phosphoserine.
 MOD_RES 1302 1302 Phosphoserine.
 MOD_RES 1332 1332 Phosphoserine.
 MOD_RES 1337 1337 Phosphoserine.
 MOD_RES 1343 1343 Phosphothreonine; by PLK3.
 MOD_RES 1351 1351 Phosphoserine.
 MOD_RES 1354 1354 Phosphoserine.
 MOD_RES 1374 1374 Phosphoserine.
 MOD_RES 1377 1377 Phosphoserine.
 MOD_RES 1387 1387 Phosphoserine.
 MOD_RES 1392 1392 Phosphoserine.
 MOD_RES 1393 1393 Phosphoserine.
 MOD_RES 1449 1449 Phosphoserine.
 MOD_RES 1469 1469 Phosphoserine; by CK2.
 MOD_RES 1470 1470 Phosphothreonine.
 MOD_RES 1471 1471 Phosphoserine.
 MOD_RES 1474 1474 Phosphoserine.
 MOD_RES 1476 1476 Phosphoserine.
 MOD_RES 1495 1495 Phosphoserine.
 MOD_RES 1504 1504 Phosphoserine.
 MOD_RES 1525 1525 Phosphoserine.  

Keyword

 3D-structure; Acetylation; Alternative splicing; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; DNA-binding; Isomerase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Topoisomerase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1531 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
 GO:0009330; C:DNA topoisomerase complex (ATP-hydrolyzing); IDA:UniProtKB.
 GO:0005730; C:nucleolus; IDA:UniProtKB.
 GO:0005654; C:nucleoplasm; IDA:UniProtKB.
 GO:0000795; C:synaptonemal complex; IBA:RefGenome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0003682; F:chromatin binding; IDA:UniProtKB.
 GO:0008301; F:DNA binding, bending; IDA:UniProtKB.
 GO:0003918; F:DNA topoisomerase type II (ATP-hydrolyzing) activity; IDA:UniProtKB.
 GO:0008144; F:drug binding; IDA:UniProtKB.
 GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
 GO:0043130; F:ubiquitin binding; IMP:UniProtKB.
 GO:0030263; P:apoptotic chromosome condensation; IDA:UniProtKB.
 GO:0006266; P:DNA ligation; IDA:UniProtKB.
 GO:0006281; P:DNA repair; NAS:UniProtKB.
 GO:0006265; P:DNA topological change; IDA:UniProtKB.
 GO:0006261; P:DNA-dependent DNA replication; IBA:RefGenome.
 GO:0040016; P:embryonic cleavage; IEA:Compara.
 GO:0000278; P:mitotic cell cycle; TAS:Reactome.
 GO:0006312; P:mitotic recombination; IBA:RefGenome.
 GO:0048015; P:phosphatidylinositol-mediated signaling; NAS:UniProtKB.
 GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
 GO:0045870; P:positive regulation of retroviral genome replication; IMP:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0000712; P:resolution of meiotic recombination intermediates; IBA:RefGenome.
 GO:0000819; P:sister chromatid segregation; IBA:RefGenome. 

Interpro

 IPR024946; Arg_repress_C-like.
 IPR012542; DTHCT.
 IPR003594; HATPase_ATP-bd.
 IPR020568; Ribosomal_S5_D2-typ_fold.
 IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
 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. 

Pfam

 PF00204; DNA_gyraseB
 PF00521; DNA_topoisoIV
 PF08070; DTHCT
 PF02518; HATPase_c
 PF01751; Toprim 

SMART

 SM00387; HATPase_c
 SM00433; TOP2c
 SM00434; TOP4c 

PROSITE

 PS00177; TOPOISOMERASE_II
 PS50880; TOPRIM 

PRINTS

 PR00418; TPI2FAMILY.