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: -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

Miscellaneous

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

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

Activity 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

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Isomerase, Topoisomerase
Biological processBiological rhythms
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi5.99.1.3 2681
ReactomeiR-HSA-1362277 Transcription of E2F targets under negative control by DREAM complex
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

EuPathDBiHostDB:ENSG00000131747.14
HGNCiHGNC:11989 TOP2A
MIMi126430 gene
neXtProtiNX_P11388

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
DrugBankiDB05022 Amonafide
DB06263 Amrubicin
DB00276 Amsacrine
DB04975 Banoxantrone
DB00537 Ciprofloxacin
DB00970 Dactinomycin
DB00694 Daunorubicin
DB00380 Dexrazoxane
DB00997 Doxorubicin
DB05129 Elsamitrucin
DB00467 Enoxacin
DB00445 Epirubicin
DB00773 Etoposide
DB09047 Finafloxacin
DB04576 Fleroxacin
DB01645 Genistein
DB01177 Idarubicin
DB01137 Levofloxacin
DB00978 Lomefloxacin
DB04967 Lucanthone
DB01204 Mitoxantrone
DB00218 Moxifloxacin
DB01059 Norfloxacin
DB01165 Ofloxacin
DB00487 Pefloxacin
DB01179 Podofilox
DB05920 RTA 744
DB04978 SP1049C
DB01208 Sparfloxacin
DB00444 Teniposide
DB00685 Trovafloxacin
DB00385 Valrubicin
DB06042 ZEN-012
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
Cross-linki17Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki156Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki157Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki261Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei282PhosphothreonineCombined sources1
Cross-linki352Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki386Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki397Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki416Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki418Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki425Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki440Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki466Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki480Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki529Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki584Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki599Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki614Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki622Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki625Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki632Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki639Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki655Glycyl 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-linki1114Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki1196Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki1204Glycyl 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); alternateCombined sources
Cross-linki1240Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei1244PhosphothreonineCombined sources1
Modified residuei1247PhosphoserineCombined sources1
Cross-linki1259Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki1276Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki1283Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki1286Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
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
Cross-linki1363Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki1367Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki1373Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
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-acetyllysine; alternateBy similarity1
Cross-linki1422Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei1442N6-acetyllysine; alternateBy similarity1
Cross-linki1442Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei1449PhosphoserineCombined sources1
Cross-linki1454Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki1459Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei1469Phosphoserine; by CK2Combined sources1 Publication1
Modified residuei1470PhosphothreonineCombined sources1
Modified residuei1471PhosphoserineCombined sources1
Modified residuei1474PhosphoserineCombined sources1
Modified residuei1476PhosphoserineCombined sources1
Cross-linki1484Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
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
ProteomicsDBi52767
52768 [P11388-2]
52769 [P11388-3]
52770 [P11388-4]

2D gel databases

UCD-2DPAGEiP11388

PTM databases

CarbonylDBiP11388
iPTMnetiP11388
PhosphoSitePlusiP11388
SwissPalmiP11388

Expressioni

Gene expression databases

BgeeiENSG00000131747 Expressed in 158 organ(s), highest expression level in heart
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). Interacts with DHX9; this interaction occurs in a E2 enzyme UBE2I- and RNA-dependent manner, negatively regulates DHX9-mediated double-stranded DNA and RNA duplex helicase activity and stimulates TOP2A-mediated supercoiled DNA relaxation activity (PubMed:12711669). Interacts with HNRNPU (via C-terminus); this interaction protects the topoisomerase TOP2A from degradation and positively regulates the relaxation of supercoiled DNA in a RNA-dependent manner (By similarity).By similarity6 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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113006, 128 interactors
CORUMiP11388
DIPiDIP-33887N
IntActiP11388, 53 interactors
MINTiP11388
STRINGi9606.ENSP00000411532

Chemistry databases

BindingDBiP11388

Structurei

Secondary structure

11531
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Phylogenomic databases

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

Family and domain databases

CDDicd00075 HATPase_c, 1 hit
cd00187 TOP4c, 1 hit
cd03365 TOPRIM_TopoIIA, 1 hit
Gene3Di3.30.230.10, 1 hit
3.30.565.10, 1 hit
3.40.50.670, 1 hit
3.90.199.10, 1 hit
InterProiView protein in InterPro
IPR012542 DTHCT
IPR003594 HATPase_C
IPR036890 HATPase_C_sf
IPR020568 Ribosomal_S5_D2-typ_fold
IPR014721 Ribosomal_S5_D2-typ_fold_subgr
IPR001241 Topo_IIA
IPR013760 Topo_IIA-like_dom_sf
IPR002205 Topo_IIA_A/C
IPR013758 Topo_IIA_A/C_ab
IPR013759 Topo_IIA_B_C
IPR013506 Topo_IIA_bsu_dom2
IPR018522 TopoIIA_CS
IPR031660 TOPRIM_C
IPR006171 TOPRIM_domain
IPR034157 TOPRIM_TopoII
PANTHERiPTHR10169 PTHR10169, 1 hit
PfamiView protein in Pfam
PF00204 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
SMARTiView protein in SMART
SM00433 TOP2c, 1 hit
SM00434 TOP4c, 1 hit
SUPFAMiSSF54211 SSF54211, 1 hit
SSF55874 SSF55874, 1 hit
SSF56719 SSF56719, 1 hit
PROSITEiView protein in PROSITE
PS00177 TOPOISOMERASE_II, 1 hit
PS50880 TOPRIM, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

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

This entry has 4 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3KTB7J3KTB7_HUMAN
DNA topoisomerase 2-alpha
TOP2A
147Annotation score:
J3QR57J3QR57_HUMAN
DNA topoisomerase 2-alpha
TOP2A
27Annotation score:

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 dbSNP:rs746765101Ensembl.1
Natural variantiVAR_007533487R → K in amsacrine resistant cells. 1 PublicationCorresponds to variant dbSNP:rs267607133EnsemblClinVar.1
Natural variantiVAR_0292451324T → K. Corresponds to variant dbSNP:rs28969502Ensembl.1
Natural variantiVAR_0525941386G → D. Corresponds to variant dbSNP:rs34300454Ensembl.1
Natural variantiVAR_0525951515A → S. Corresponds to variant dbSNP:rs11540720Ensembl.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

Similar proteinsi

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[»]
5GWKX-ray3.15A/B429-1188[»]
5NNEX-ray1.15C1198-1207[»]
ProteinModelPortaliP11388
SMRiP11388
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113006, 128 interactors
CORUMiP11388
DIPiDIP-33887N
IntActiP11388, 53 interactors
MINTiP11388
STRINGi9606.ENSP00000411532

Chemistry databases

BindingDBiP11388
ChEMBLiCHEMBL1806
DrugBankiDB05022 Amonafide
DB06263 Amrubicin
DB00276 Amsacrine
DB04975 Banoxantrone
DB00537 Ciprofloxacin
DB00970 Dactinomycin
DB00694 Daunorubicin
DB00380 Dexrazoxane
DB00997 Doxorubicin
DB05129 Elsamitrucin
DB00467 Enoxacin
DB00445 Epirubicin
DB00773 Etoposide
DB09047 Finafloxacin
DB04576 Fleroxacin
DB01645 Genistein
DB01177 Idarubicin
DB01137 Levofloxacin
DB00978 Lomefloxacin
DB04967 Lucanthone
DB01204 Mitoxantrone
DB00218 Moxifloxacin
DB01059 Norfloxacin
DB01165 Ofloxacin
DB00487 Pefloxacin
DB01179 Podofilox
DB05920 RTA 744
DB04978 SP1049C
DB01208 Sparfloxacin
DB00444 Teniposide
DB00685 Trovafloxacin
DB00385 Valrubicin
DB06042 ZEN-012
GuidetoPHARMACOLOGYi2637

PTM databases

CarbonylDBiP11388
iPTMnetiP11388
PhosphoSitePlusiP11388
SwissPalmiP11388

Polymorphism and mutation databases

BioMutaiTOP2A
DMDMi13959709

2D gel databases

UCD-2DPAGEiP11388

Proteomic databases

EPDiP11388
MaxQBiP11388
PaxDbiP11388
PeptideAtlasiP11388
PRIDEiP11388
ProteomicsDBi52767
52768 [P11388-2]
52769 [P11388-3]
52770 [P11388-4]

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
EuPathDBiHostDB:ENSG00000131747.14
GeneCardsiTOP2A
H-InvDBiHIX0013797
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
OMAiGESDDFH
OrthoDBiEOG091G00U2
PhylomeDBiP11388
TreeFamiTF105282

Enzyme and pathway databases

BRENDAi5.99.1.3 2681
ReactomeiR-HSA-1362277 Transcription of E2F targets under negative control by DREAM complex
R-HSA-4615885 SUMOylation of DNA replication proteins
SignaLinkiP11388
SIGNORiP11388

Miscellaneous databases

EvolutionaryTraceiP11388
GeneWikiiTOP2A
GenomeRNAii7153
PROiPR:P11388
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000131747 Expressed in 158 organ(s), highest expression level in heart
CleanExiHS_TOP2A
ExpressionAtlasiP11388 baseline and differential
GenevisibleiP11388 HS

Family and domain databases

CDDicd00075 HATPase_c, 1 hit
cd00187 TOP4c, 1 hit
cd03365 TOPRIM_TopoIIA, 1 hit
Gene3Di3.30.230.10, 1 hit
3.30.565.10, 1 hit
3.40.50.670, 1 hit
3.90.199.10, 1 hit
InterProiView protein in InterPro
IPR012542 DTHCT
IPR003594 HATPase_C
IPR036890 HATPase_C_sf
IPR020568 Ribosomal_S5_D2-typ_fold
IPR014721 Ribosomal_S5_D2-typ_fold_subgr
IPR001241 Topo_IIA
IPR013760 Topo_IIA-like_dom_sf
IPR002205 Topo_IIA_A/C
IPR013758 Topo_IIA_A/C_ab
IPR013759 Topo_IIA_B_C
IPR013506 Topo_IIA_bsu_dom2
IPR018522 TopoIIA_CS
IPR031660 TOPRIM_C
IPR006171 TOPRIM_domain
IPR034157 TOPRIM_TopoII
PANTHERiPTHR10169 PTHR10169, 1 hit
PfamiView protein in Pfam
PF00204 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
SMARTiView protein in SMART
SM00433 TOP2c, 1 hit
SM00434 TOP4c, 1 hit
SUPFAMiSSF54211 SSF54211, 1 hit
SSF55874 SSF55874, 1 hit
SSF56719 SSF56719, 1 hit
PROSITEiView protein in PROSITE
PS00177 TOPOISOMERASE_II, 1 hit
PS50880 TOPRIM, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTOP2A_HUMAN
AccessioniPrimary (citable) accession number: P11388
Secondary accession number(s): B2RTS1
, Q71UN1, Q71UQ5, Q9HB24, Q9HB25, Q9HB26, Q9UP44, Q9UQP9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: May 4, 2001
Last modified: November 7, 2018
This is version 228 of the entry and version 3 of the sequence. See 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

Keywords - Technical termi

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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again