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]
96	LVNAADNKQRDPKMS	ubiquitination	[2]
101	DNKQRDPKMSCIRVT	ubiquitination	[2]
123	ISIWNNGKGIPVVEH	ubiquitination	[2]
131	GIPVVEHKVEKMYVP	ubiquitination	[2]
134	VVEHKVEKMYVPALI	ubiquitination	[2]
156	SNYDDDEKKVTGGRN	ubiquitination	[2]
157	NYDDDEKKVTGGRNG	ubiquitination	[2]
191	REYKKMFKQTWMDNM	ubiquitination	[1, 2]
227	QPDLSKFKMQSLDKD	ubiquitination	[2]
233	FKMQSLDKDIVALMV	ubiquitination	[2, 3, 4]
251	YDIAGSTKDVKVFLN	ubiquitination	[2]
261	KVFLNGNKLPVKGFR	ubiquitination	[2, 3, 4]
265	NGNKLPVKGFRSYVD	ubiquitination	[2]
276	SYVDMYLKDKLDETG	ubiquitination	[2]
278	VDMYLKDKLDETGNS	ubiquitination	[2]
287	DETGNSLKVIHEQVN	ubiquitination	[4]
321	VNSIATSKGGRHVDY	ubiquitination	[2, 3, 4]
336	VADQIVTKLVDVVKK	ubiquitination	[2]
343	KLVDVVKKKNKGGVA	ubiquitination	[2]
467	ENMTLQPKSFGSTCQ	ubiquitination	[2, 3, 4]
478	STCQLSEKFIKAAIG	ubiquitination	[2, 3]
499	ILNWVKFKAQVQLNK	ubiquitination	[2, 4]
521	NRIKGIPKLDDANDA	ubiquitination	[2]
547	LTEGDSAKTLAVSGL	ubiquitination	[2]
561	LGVVGRDKYGVFPLR	ubiquitination	[2, 3]
570	GVFPLRGKILNVREA	ubiquitination	[3, 4]
580	NVREASHKQIMENAE	ubiquitination	[3, 4]
601	IVGLQYKKNYEDEDS	ubiquitination	[2, 4]
610	YEDEDSLKTLRYGKI	ubiquitination	[2, 4]
616	LKTLRYGKIMIMTDQ	ubiquitination	[3]
660	EFITPIVKVSKNKQE	ubiquitination	[2]
663	TPIVKVSKNKQEMAF	ubiquitination	[2]
665	IVKVSKNKQEMAFYS	ubiquitination	[2]
695	KWKVKYYKGLGTSTS	ubiquitination	[2, 3, 4]
703	GLGTSTSKEAKEYFA	ubiquitination	[2]
706	TSTSKEAKEYFADMK	ubiquitination	[2]
713	KEYFADMKRHRIQFK	ubiquitination	[1, 2]
720	KRHRIQFKYSGPEDD	ubiquitination	[2]
736	AISLAFSKKQIDDRK	ubiquitination	[1, 2, 4]
737	ISLAFSKKQIDDRKE	ubiquitination	[2]
743	KKQIDDRKEWLTNFM	ubiquitination	[4]
804	PSMVDGLKPGQRKVL	ubiquitination	[2, 3, 4]
809	GLKPGQRKVLFTCFK	ubiquitination	[3]
902	ARLLFPPKDDHTLKF	ubiquitination	[4]
908	PKDDHTLKFLYDDNQ	ubiquitination	[4]
977	LPSYKNFKGTIEELA	ubiquitination	[2]
1017	RTWTQTYKEQVLEPM	ubiquitination	[2]
1030	PMLNGTEKTPPLITD	ubiquitination	[2]
1048	YHTDTTVKFVVKMTE	ubiquitination	[4]
1057	VVKMTEEKLAEAERV	ubiquitination	[2]
1092	DHVGCLKKYDTVLDI	ubiquitination	[3, 4]
1109	DFFELRLKYYGLRKE	ubiquitination	[4]
1139	QARFILEKIDGKIII	ubiquitination	[2]
1143	ILEKIDGKIIIENKP	ubiquitination	[2]
1149	GKIIIENKPKKELIK	ubiquitination	[2]
1152	IIENKPKKELIKVLI	ubiquitination	[2]
1156	KPKKELIKVLIQRGY	ubiquitination	[2, 4]
1169	GYDSDPVKAWKEAQQ	ubiquitination	[2]
1240	EQELDTLKRKSPSDL	ubiquitination	[2]
1267	EAVEAKEKQDEQVGL	ubiquitination	[2]
1277	EQVGLPGKGGKAKGK	ubiquitination	[1]
1280	GLPGKGGKAKGKKTQ	ubiquitination	[2]
1284	KGGKAKGKKTQMAEV	ubiquitination	[2]
1285	GGKAKGKKTQMAEVL	ubiquitination	[2]
1309	PRITIEMKAEAEKKN	ubiquitination	[2]
1340	GVELEGLKQRLEKKQ	ubiquitination	[3]
1448	TSPKLSNKELKPQKS	ubiquitination	[2]
1535	LNSGVSQKPDPAKTK	ubiquitination	[2]
1573	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] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [4] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 

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.