Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

DNA topoisomerase 2-alpha

Gene

TOP2A

Organism
Homo sapiens (Human)
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).By similarity3 Publications

Catalytic activityi

ATP-dependent breakage, passage and rejoining of double-stranded DNA.PROSITE-ProRule annotation2 Publications

Cofactori

Mg2+4 Publications, Mn2+4 Publications, Ca2+4 PublicationsNote: 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+.4 Publications

Enzyme regulationi

Specifically inhibited by the intercalating agent amsacrine.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei91ATP2 Publications1
Binding sitei120ATP2 Publications1
Metal bindingi461Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi541Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi541Magnesium 21 Publication1
Metal bindingi543Magnesium 21 Publication1
Sitei804Transition state stabilizerBy similarity1
Active sitei805O-(5'-phospho-DNA)-tyrosine intermediateBy similarity1
Sitei856Important for DNA bending; intercalates between base pairs of target DNABy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi148 – 150ATP2 Publications3
Nucleotide bindingi161 – 168ATP2 Publications8
Nucleotide bindingi376 – 378ATP1 Publication1 Publication3

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • chromatin binding Source: UniProtKB
  • DNA binding Source: UniProtKB
  • DNA binding, bending Source: UniProtKB
  • DNA-dependent ATPase activity Source: UniProtKB
  • DNA topoisomerase type II (ATP-hydrolyzing) activity Source: UniProtKB
  • drug binding Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • histone deacetylase binding Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • poly(A) RNA binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • protein kinase C binding Source: UniProtKB
  • ubiquitin binding Source: UniProtKB

GO - Biological processi

  • apoptotic chromosome condensation Source: UniProtKB
  • cellular response to DNA damage stimulus Source: UniProtKB
  • chromosome segregation Source: UniProtKB
  • DNA ligation Source: UniProtKB
  • DNA topological change Source: UniProtKB
  • DNA unwinding involved in DNA replication Source: GO_Central
  • embryonic cleavage Source: Ensembl
  • hematopoietic progenitor cell differentiation Source: Ensembl
  • mitotic DNA integrity checkpoint Source: GO_Central
  • mitotic recombination Source: GO_Central
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of single stranded viral RNA replication via double stranded DNA intermediate Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • positive regulation of viral genome replication Source: UniProtKB
  • protein sumoylation Source: Reactome
  • regulation of circadian rhythm Source: UniProtKB
  • resolution of meiotic recombination intermediates Source: GO_Central
  • rhythmic process Source: UniProtKB-KW
  • sister chromatid segregation Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Isomerase, Topoisomerase

Keywords - Biological processi

Biological rhythms

Keywords - Ligandi

ATP-binding, DNA-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS05560-MONOMER.
BRENDAi5.99.1.3. 2681.
ReactomeiR-HSA-1538133. G0 and Early G1.
R-HSA-4615885. SUMOylation of DNA replication proteins.
SignaLinkiP11388.
SIGNORiP11388.

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:TOP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:11989. TOP2A.

Subcellular locationi

GO - Cellular componenti

  • condensed chromosome Source: Ensembl
  • cytoplasm Source: UniProtKB-SubCell
  • DNA topoisomerase complex (ATP-hydrolyzing) Source: UniProtKB
  • nucleolus Source: UniProtKB
  • nucleoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
  • protein complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi342 – 344KKK → AAA: Reduced enzyme activity; abolishes stimulation of ATPase activity upon DNA binding. 1 Publication3
Mutagenesisi342 – 344KKK → EEE: Strongly reduced enzyme activity; abolishes stimulation of ATPase activity upon DNA binding. 1 Publication3
Mutagenesisi461E → A or C: Impairs bending of target DNA. Strongly reduced DNA cleavage. 2 Publications1
Mutagenesisi541D → A or C: Impairs bending of target DNA. Strongly reduced DNA cleavage. 2 Publications1
Mutagenesisi543D → A or C: Impairs bending of target DNA. Strongly reduced DNA cleavage. 2 Publications1
Mutagenesisi545D → A or C: Strongly reduced DNA cleavage. 1 Publication1
Mutagenesisi1469S → A: Abolishes binding to the antibody MPM2. 1 Publication1

Organism-specific databases

DisGeNETi7153.
MalaCardsiTOP2A.
OpenTargetsiENSG00000131747.
Orphaneti635. Neuroblastoma.
PharmGKBiPA354.

Chemistry databases

ChEMBLiCHEMBL1806.
DrugBankiDB00276. Amsacrine.
DB00537. Ciprofloxacin.
DB00970. Dactinomycin.
DB00694. Daunorubicin.
DB00380. Dexrazoxane.
DB00997. Doxorubicin.
DB00467. Enoxacin.
DB00445. Epirubicin.
DB00773. Etoposide.
DB09047. Finafloxacin.
DB04576. Fleroxacin.
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.
GuidetoPHARMACOLOGYi2637.

Polymorphism and mutation databases

BioMutaiTOP2A.
DMDMi13959709.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001453631 – 1531DNA topoisomerase 2-alphaAdd BLAST1531

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1 Publication1
Modified residuei4PhosphoserineCombined sources1
Modified residuei282PhosphothreonineCombined sources1
Cross-linki639Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki662Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki676Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki1075Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei1106Phosphoserine; by CK1Combined sources2 Publications1
Cross-linki1196Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei1205PhosphothreonineCombined sources1
Modified residuei1213PhosphoserineCombined sources1
Cross-linki1228Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki1240Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Cross-linki1240Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei1244PhosphothreonineCombined sources1
Modified residuei1247PhosphoserineCombined sources1
Modified residuei1295PhosphoserineCombined sources1
Modified residuei1297PhosphoserineCombined sources1
Modified residuei1299PhosphoserineCombined sources1
Modified residuei1302PhosphoserineCombined sources1
Modified residuei1327PhosphothreonineBy similarity1
Modified residuei1332PhosphoserineCombined sources1
Modified residuei1337PhosphoserineCombined sources1
Modified residuei1343Phosphothreonine; by PLK3Combined sources1 Publication1
Modified residuei1351PhosphoserineCombined sources1
Modified residuei1354PhosphoserineCombined sources1
Modified residuei1374PhosphoserineCombined sources1
Modified residuei1377PhosphoserineCombined sources1
Cross-linki1385Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei1387PhosphoserineCombined sources1
Modified residuei1391PhosphoserineCombined sources1
Modified residuei1392PhosphoserineCombined sources1
Modified residuei1393PhosphoserineCombined sources1
Modified residuei1422N6-acetyllysineBy similarity1
Modified residuei1442N6-acetyllysine; alternateBy similarity1
Cross-linki1442Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei1449PhosphoserineCombined sources1
Modified residuei1469Phosphoserine; by CK2Combined sources1 Publication1
Modified residuei1470PhosphothreonineCombined sources1
Modified residuei1471PhosphoserineCombined sources1
Modified residuei1474PhosphoserineCombined sources1
Modified residuei1476PhosphoserineCombined sources1
Cross-linki1492Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei1495PhosphoserineCombined sources1
Modified residuei1504PhosphoserineCombined sources1
Modified residuei1525PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation has no effect on catalytic activity. However, phosphorylation at Ser-1106 by CSNK1D/CK1 promotes DNA cleavable complex formation.4 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP11388.
MaxQBiP11388.
PaxDbiP11388.
PeptideAtlasiP11388.
PRIDEiP11388.

2D gel databases

UCD-2DPAGEP11388.

PTM databases

iPTMnetiP11388.
PhosphoSitePlusiP11388.
SwissPalmiP11388.

Expressioni

Gene expression databases

BgeeiENSG00000131747.
CleanExiHS_TOP2A.
ExpressionAtlasiP11388. baseline and differential.
GenevisibleiP11388. HS.

Organism-specific databases

HPAiCAB002448.
HPA006458.
HPA026773.

Interactioni

Subunit structurei

Homodimer. Interacts with COPS5. Interacts with RECQL5; this stimulates DNA decatenation. Interacts with SETMAR; stimulates the topoisomerase activity (PubMed:18790802, PubMed:20457750).5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei489Interaction with DNAPROSITE-ProRule annotation1
Sitei492Interaction with DNA1 Publication1
Sitei661Interaction with DNA1 Publication1
Sitei662Interaction with DNA1 Publication1
Sitei723Interaction with DNA1 Publication1
Sitei757Interaction with DNA1 Publication1
Sitei763Interaction with DNA1 Publication1
Sitei931Interaction with DNA1 Publication1

Binary interactionsi

WithEntry#Exp.IntActNotes
CTNNB1P352225EBI-539628,EBI-491549
PRKCDQ0565510EBI-539628,EBI-704279

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • histone deacetylase binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • protein kinase C binding Source: UniProtKB
  • ubiquitin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113006. 98 interactors.
DIPiDIP-33887N.
IntActiP11388. 37 interactors.
MINTiMINT-98770.
STRINGi9606.ENSP00000411532.

Chemistry databases

BindingDBiP11388.

Structurei

Secondary structure

11531
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi30 – 33Combined sources4
Beta strandi34 – 36Combined sources3
Helixi39 – 45Combined sources7
Helixi48 – 51Combined sources4
Beta strandi57 – 65Combined sources9
Turni66 – 68Combined sources3
Beta strandi69 – 77Combined sources9
Helixi79 – 98Combined sources20
Beta strandi104 – 110Combined sources7
Turni111 – 114Combined sources4
Beta strandi115 – 123Combined sources9
Beta strandi128 – 130Combined sources3
Turni131 – 134Combined sources4
Helixi137 – 143Combined sources7
Beta strandi144 – 149Combined sources6
Helixi153 – 155Combined sources3
Helixi166 – 172Combined sources7
Beta strandi174 – 183Combined sources10
Turni184 – 187Combined sources4
Beta strandi188 – 195Combined sources8
Turni196 – 199Combined sources4
Beta strandi205 – 208Combined sources4
Beta strandi214 – 221Combined sources8
Helixi223 – 226Combined sources4
Helixi233 – 249Combined sources17
Beta strandi250 – 252Combined sources3
Beta strandi254 – 257Combined sources4
Helixi267 – 275Combined sources9
Beta strandi281 – 285Combined sources5
Beta strandi289 – 294Combined sources6
Beta strandi297 – 303Combined sources7
Beta strandi305 – 307Combined sources3
Beta strandi309 – 314Combined sources6
Helixi324 – 341Combined sources18
Beta strandi346 – 348Combined sources3
Helixi353 – 357Combined sources5
Beta strandi360 – 366Combined sources7
Beta strandi373 – 375Combined sources3
Helixi385 – 387Combined sources3
Beta strandi388 – 390Combined sources3
Helixi396 – 402Combined sources7
Helixi407 – 410Combined sources4
Helixi411 – 415Combined sources5
Beta strandi419 – 421Combined sources3
Beta strandi423 – 425Combined sources3
Turni445 – 448Combined sources4
Helixi452 – 454Combined sources3
Beta strandi456 – 462Combined sources7
Helixi463 – 476Combined sources14
Beta strandi478 – 486Combined sources9
Helixi498 – 503Combined sources6
Helixi505 – 514Combined sources10
Beta strandi518 – 520Combined sources3
Helixi525 – 530Combined sources6
Beta strandi534 – 539Combined sources6
Helixi544 – 560Combined sources17
Helixi562 – 566Combined sources5
Beta strandi570 – 573Combined sources4
Beta strandi577 – 581Combined sources5
Beta strandi586 – 590Combined sources5
Helixi592 – 601Combined sources10
Beta strandi607 – 612Combined sources6
Helixi616 – 618Combined sources3
Helixi621 – 629Combined sources9
Helixi631 – 634Combined sources4
Beta strandi635 – 639Combined sources5
Helixi644 – 653Combined sources10
Helixi658 – 678Combined sources21
Beta strandi685 – 688Combined sources4
Beta strandi691 – 694Combined sources4
Helixi695 – 701Combined sources7
Helixi703 – 714Combined sources12
Turni718 – 720Combined sources3
Helixi724 – 735Combined sources12
Helixi744 – 754Combined sources11
Helixi762 – 772Combined sources11
Turni793 – 799Combined sources7
Turni803 – 805Combined sources3
Helixi812 – 817Combined sources6
Helixi822 – 824Combined sources3
Helixi831 – 833Combined sources3
Turni848 – 850Combined sources3
Beta strandi853 – 856Combined sources4
Beta strandi861 – 864Combined sources4
Helixi869 – 881Combined sources13
Beta strandi897 – 903Combined sources7
Beta strandi906 – 910Combined sources5
Beta strandi921 – 923Combined sources3
Helixi932 – 938Combined sources7
Helixi940 – 944Combined sources5
Beta strandi948 – 950Combined sources3
Beta strandi955 – 959Combined sources5
Beta strandi968 – 971Combined sources4
Helixi974 – 983Combined sources10
Helixi985 – 988Combined sources4
Beta strandi992 – 996Combined sources5
Beta strandi1000 – 1003Combined sources4
Beta strandi1009 – 1011Combined sources3
Helixi1015 – 1059Combined sources45
Helixi1070 – 1080Combined sources11
Helixi1086 – 1091Combined sources6
Helixi1126 – 1129Combined sources4
Helixi1138 – 1160Combined sources23
Helixi1163 – 1189Combined sources27

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LWZmodel-A431-1200[»]
1ZXMX-ray1.87A/B29-428[»]
1ZXNX-ray2.51A/B/C/D29-428[»]
4FM9X-ray2.90A431-1193[»]
4R1FX-ray2.51A/B/C/D29-428[»]
ProteinModelPortaliP11388.
SMRiP11388.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP11388.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini455 – 572ToprimPROSITE-ProRule annotationAdd BLAST118

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni342 – 344Interaction with DNA1 Publication3
Regioni990 – 999Interaction with DNA1 Publication10

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1018 – 1028Nuclear export signalAdd BLAST11

Domaini

The N-terminus has several structural domains; the ATPase domain (about residues 1-265), the transducer domain (about 266-428) and the toprim domain (455-572) (PubMed:25202966). Comparing different structures shows ATP hydrolysis induces domain shifts in the N-terminus that are probably part of the mechanism of DNA cleavage and rejoining (PubMed:25202966).By similarity1 Publication

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.
GeneTreeiENSGT00390000016222.
HOVERGENiHBG052998.
InParanoidiP11388.
KOiK03164.
OMAiVKFIVKM.
OrthoDBiEOG091G00U2.
PhylomeDBiP11388.
TreeFamiTF105282.

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]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P11388-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MEVSPLQPVN ENMQVNKIKK NEDAKKRLSV ERIYQKKTQL EHILLRPDTY
60 70 80 90 100
IGSVELVTQQ MWVYDEDVGI NYREVTFVPG LYKIFDEILV NAADNKQRDP
110 120 130 140 150
KMSCIRVTID PENNLISIWN NGKGIPVVEH KVEKMYVPAL IFGQLLTSSN
160 170 180 190 200
YDDDEKKVTG GRNGYGAKLC NIFSTKFTVE TASREYKKMF KQTWMDNMGR
210 220 230 240 250
AGEMELKPFN GEDYTCITFQ PDLSKFKMQS LDKDIVALMV RRAYDIAGST
260 270 280 290 300
KDVKVFLNGN KLPVKGFRSY VDMYLKDKLD ETGNSLKVIH EQVNHRWEVC
310 320 330 340 350
LTMSEKGFQQ ISFVNSIATS KGGRHVDYVA DQIVTKLVDV VKKKNKGGVA
360 370 380 390 400
VKAHQVKNHM WIFVNALIEN PTFDSQTKEN MTLQPKSFGS TCQLSEKFIK
410 420 430 440 450
AAIGCGIVES ILNWVKFKAQ VQLNKKCSAV KHNRIKGIPK LDDANDAGGR
460 470 480 490 500
NSTECTLILT EGDSAKTLAV SGLGVVGRDK YGVFPLRGKI LNVREASHKQ
510 520 530 540 550
IMENAEINNI IKIVGLQYKK NYEDEDSLKT LRYGKIMIMT DQDQDGSHIK
560 570 580 590 600
GLLINFIHHN WPSLLRHRFL EEFITPIVKV SKNKQEMAFY SLPEFEEWKS
610 620 630 640 650
STPNHKKWKV KYYKGLGTST SKEAKEYFAD MKRHRIQFKY SGPEDDAAIS
660 670 680 690 700
LAFSKKQIDD RKEWLTNFME DRRQRKLLGL PEDYLYGQTT TYLTYNDFIN
710 720 730 740 750
KELILFSNSD NERSIPSMVD GLKPGQRKVL FTCFKRNDKR EVKVAQLAGS
760 770 780 790 800
VAEMSSYHHG EMSLMMTIIN LAQNFVGSNN LNLLQPIGQF GTRLHGGKDS
810 820 830 840 850
ASPRYIFTML SSLARLLFPP KDDHTLKFLY DDNQRVEPEW YIPIIPMVLI
860 870 880 890 900
NGAEGIGTGW SCKIPNFDVR EIVNNIRRLM DGEEPLPMLP SYKNFKGTIE
910 920 930 940 950
ELAPNQYVIS GEVAILNSTT IEISELPVRT WTQTYKEQVL EPMLNGTEKT
960 970 980 990 1000
PPLITDYREY HTDTTVKFVV KMTEEKLAEA ERVGLHKVFK LQTSLTCNSM
1010 1020 1030 1040 1050
VLFDHVGCLK KYDTVLDILR DFFELRLKYY GLRKEWLLGM LGAESAKLNN
1060 1070 1080 1090 1100
QARFILEKID GKIIIENKPK KELIKVLIQR GYDSDPVKAW KEAQQKVPDE
1110 1120 1130 1140 1150
EENEESDNEK ETEKSDSVTD SGPTFNYLLD MPLWYLTKEK KDELCRLRNE
1160 1170 1180 1190 1200
KEQELDTLKR KSPSDLWKED LATFIEELEA VEAKEKQDEQ VGLPGKGGKA
1210 1220 1230 1240 1250
KGKKTQMAEV LPSPRGQRVI PRITIEMKAE AEKKNKKKIK NENTEGSPQE
1260 1270 1280 1290 1300
DGVELEGLKQ RLEKKQKREP GTKTKKQTTL AFKPIKKGKK RNPWSDSESD
1310 1320 1330 1340 1350
RSSDESNFDV PPRETEPRRA ATKTKFTMDL DSDEDFSDFD EKTDDEDFVP
1360 1370 1380 1390 1400
SDASPPKTKT SPKLSNKELK PQKSVVSDLE ADDVKGSVPL SSSPPATHFP
1410 1420 1430 1440 1450
DETEITNPVP KKNVTVKKTA AKSQSSTSTT GAKKRAAPKG TKRDPALNSG
1460 1470 1480 1490 1500
VSQKPDPAKT KNRRKRKPST SDDSDSNFEK IVSKAVTSKK SKGESDDFHM
1510 1520 1530
DFDSAVAPRA KSVRAKKPIK YLEESDEDDL F
Length:1,531
Mass (Da):174,385
Last modified:May 4, 2001 - v3
Checksum:i3DF40BC9E84789DC
GO
Isoform 2 (identifier: P11388-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     401-401: A → AHLYSRFLIDPFFPNMIPNMIFSFSKA

Show »
Length:1,557
Mass (Da):177,501
Checksum:i4DE312DFAEC443EA
GO
Isoform 3 (identifier: P11388-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     321-321: K → KSSKYWSSRKSKQHILLNFFVLFKFINDAFFGICPFK

Show »
Length:1,567
Mass (Da):178,712
Checksum:iE5322E9ED4DD7BF5
GO
Isoform 4 (identifier: P11388-4) [UniParc]FASTAAdd to basket

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

Show »
Length:1,612
Mass (Da):182,681
Checksum:iAB857EA93238BD4A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti152D → H in CAA09762 (PubMed:10095062).Curated1
Sequence conflicti180E → Q in CAA09762 (PubMed:10095062).Curated1
Sequence conflicti327D → H in CAA09762 (PubMed:10095062).Curated1
Sequence conflicti1022F → L in CAA09762 (PubMed:10095062).Curated1
Sequence conflicti1274T → S in CAA09762 (PubMed:10095062).Curated1
Sequence conflicti1295S → P in AAA61209 (PubMed:2845399).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_007532450R → Q in teniposide (VM-26) resistant cells. 1 PublicationCorresponds to variant rs746765101dbSNPEnsembl.1
Natural variantiVAR_007533487R → K in amsacrine resistant cells. 1 PublicationCorresponds to variant rs267607133dbSNPEnsembl.1
Natural variantiVAR_0292451324T → K.Corresponds to variant rs28969502dbSNPEnsembl.1
Natural variantiVAR_0525941386G → D.Corresponds to variant rs34300454dbSNPEnsembl.1
Natural variantiVAR_0525951515A → S.Corresponds to variant rs11540720dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_006529321K → KSSKYWSSRKSKQHILLNFF VLFKFINDAFFGICPFK in isoform 3. 1 Publication1
Alternative sequenceiVSP_006530355Q → QRELCNGAILAHCNLRLMGS SDSPASASRVAGIAGGCHHT QLIFVFLVETGFHHVGQAGL ERLTSGDPPASASQSSGITD VK in isoform 4. 1 Publication1
Alternative sequenceiVSP_006531401A → AHLYSRFLIDPFFPNMIPNM IFSFSKA in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04088 mRNA. Translation: AAA61209.1.
AF071747
, AF071738, AF071739, AF071740, AF071741, AF071742, AF071743, AF071744, AF071745, AF071746 Genomic DNA. Translation: AAC77388.1.
AJ011741
, 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.
CCDSiCCDS45672.1. [P11388-1]
PIRiA40493.
RefSeqiNP_001058.2. NM_001067.3. [P11388-1]
UniGeneiHs.156346.

Genome annotation databases

EnsembliENST00000423485; ENSP00000411532; ENSG00000131747. [P11388-1]
GeneIDi7153.
KEGGihsa:7153.
UCSCiuc002huq.4. human. [P11388-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04088 mRNA. Translation: AAA61209.1.
AF071747
, AF071738, AF071739, AF071740, AF071741, AF071742, AF071743, AF071744, AF071745, AF071746 Genomic DNA. Translation: AAC77388.1.
AJ011741
, 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.
CCDSiCCDS45672.1. [P11388-1]
PIRiA40493.
RefSeqiNP_001058.2. NM_001067.3. [P11388-1]
UniGeneiHs.156346.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LWZmodel-A431-1200[»]
1ZXMX-ray1.87A/B29-428[»]
1ZXNX-ray2.51A/B/C/D29-428[»]
4FM9X-ray2.90A431-1193[»]
4R1FX-ray2.51A/B/C/D29-428[»]
ProteinModelPortaliP11388.
SMRiP11388.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113006. 98 interactors.
DIPiDIP-33887N.
IntActiP11388. 37 interactors.
MINTiMINT-98770.
STRINGi9606.ENSP00000411532.

Chemistry databases

BindingDBiP11388.
ChEMBLiCHEMBL1806.
DrugBankiDB00276. Amsacrine.
DB00537. Ciprofloxacin.
DB00970. Dactinomycin.
DB00694. Daunorubicin.
DB00380. Dexrazoxane.
DB00997. Doxorubicin.
DB00467. Enoxacin.
DB00445. Epirubicin.
DB00773. Etoposide.
DB09047. Finafloxacin.
DB04576. Fleroxacin.
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.
GuidetoPHARMACOLOGYi2637.

PTM databases

iPTMnetiP11388.
PhosphoSitePlusiP11388.
SwissPalmiP11388.

Polymorphism and mutation databases

BioMutaiTOP2A.
DMDMi13959709.

2D gel databases

UCD-2DPAGEP11388.

Proteomic databases

EPDiP11388.
MaxQBiP11388.
PaxDbiP11388.
PeptideAtlasiP11388.
PRIDEiP11388.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000423485; ENSP00000411532; ENSG00000131747. [P11388-1]
GeneIDi7153.
KEGGihsa:7153.
UCSCiuc002huq.4. human. [P11388-1]

Organism-specific databases

CTDi7153.
DisGeNETi7153.
GeneCardsiTOP2A.
H-InvDBHIX0013797.
HGNCiHGNC:11989. TOP2A.
HPAiCAB002448.
HPA006458.
HPA026773.
MalaCardsiTOP2A.
MIMi126430. gene.
neXtProtiNX_P11388.
OpenTargetsiENSG00000131747.
Orphaneti635. Neuroblastoma.
PharmGKBiPA354.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0355. Eukaryota.
COG0187. LUCA.
COG0188. LUCA.
GeneTreeiENSGT00390000016222.
HOVERGENiHBG052998.
InParanoidiP11388.
KOiK03164.
OMAiVKFIVKM.
OrthoDBiEOG091G00U2.
PhylomeDBiP11388.
TreeFamiTF105282.

Enzyme and pathway databases

BioCyciZFISH:HS05560-MONOMER.
BRENDAi5.99.1.3. 2681.
ReactomeiR-HSA-1538133. G0 and Early G1.
R-HSA-4615885. SUMOylation of DNA replication proteins.
SignaLinkiP11388.
SIGNORiP11388.

Miscellaneous databases

EvolutionaryTraceiP11388.
GeneWikiiTOP2A.
GenomeRNAii7153.
PROiP11388.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000131747.
CleanExiHS_TOP2A.
ExpressionAtlasiP11388. baseline and differential.
GenevisibleiP11388. HS.

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...

Entry informationi

Entry nameiTOP2A_HUMAN
AccessioniPrimary (citable) accession number: P11388
Secondary accession number(s): B2RTS1
, Q71UN1, Q71UQ5, Q9HB24, Q9HB25, Q9HB26, Q9UP44, Q9UQP9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: May 4, 2001
Last modified: November 2, 2016
This is version 208 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.