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Protein

DNA topoisomerase 3-alpha

Gene

TOP3A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Has DNA decatenation activity.2 Publications

Catalytic activityi

ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.PROSITE-ProRule annotation2 Publications

Cofactori

Mg2+1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei362O-(5'-phospho-DNA)-tyrosine intermediateBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri658 – 685C4-typeSequence analysisAdd BLAST28

GO - Molecular functioni

  • DNA binding Source: ProtInc
  • DNA topoisomerase type I activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • DNA replication Source: Reactome
  • DNA synthesis involved in DNA repair Source: Reactome
  • DNA topological change Source: UniProtKB
  • meiotic cell cycle Source: ProtInc
  • regulation of signal transduction by p53 class mediator Source: Reactome
  • strand displacement Source: Reactome

Keywordsi

Molecular functionDNA-binding, Isomerase, Topoisomerase
LigandMagnesium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5685938. HDR through Single Strand Annealing (SSA).
R-HSA-5685942. HDR through Homologous Recombination (HRR).
R-HSA-5693554. Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
R-HSA-5693568. Resolution of D-loop Structures through Holliday Junction Intermediates.
R-HSA-5693579. Homologous DNA Pairing and Strand Exchange.
R-HSA-5693607. Processing of DNA double-strand break ends.
R-HSA-5693616. Presynaptic phase of homologous DNA pairing and strand exchange.
R-HSA-6804756. Regulation of TP53 Activity through Phosphorylation.
R-HSA-69473. G2/M DNA damage checkpoint.
R-HSA-912446. Meiotic recombination.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA topoisomerase 3-alpha (EC:5.99.1.2)
Alternative name(s):
DNA topoisomerase III alpha
Gene namesi
Name:TOP3A
Synonyms:TOP3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000177302.14.
HGNCiHGNC:11992. TOP3A.

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

Pathology & Biotechi

Organism-specific databases

DisGeNETi7156.
OpenTargetsiENSG00000177302.
PharmGKBiPA36673.

Polymorphism and mutation databases

BioMutaiTOP3A.
DMDMi2501242.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001451901 – 1001DNA topoisomerase 3-alphaAdd BLAST1001

Proteomic databases

EPDiQ13472.
MaxQBiQ13472.
PaxDbiQ13472.
PeptideAtlasiQ13472.
PRIDEiQ13472.

PTM databases

iPTMnetiQ13472.
PhosphoSitePlusiQ13472.

Expressioni

Tissue specificityi

High expression is found in testis, heart, skeletal muscle and pancreas.

Gene expression databases

BgeeiENSG00000177302.
CleanExiHS_TOP3A.
ExpressionAtlasiQ13472. baseline and differential.
GenevisibleiQ13472. HS.

Organism-specific databases

HPAiCAB002449.

Interactioni

Subunit structurei

Interacts (via N-terminal region) with BLM; the interaction is direct. Directly interacts with RMI1. Component of the RMI complex, containing at least TOP3A, RMI1 and RMI2. The RMI complex interacts with BLM.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RMI1Q9H9A710EBI-621345,EBI-621339

Protein-protein interaction databases

BioGridi113009. 51 interactors.
CORUMiQ13472.
DIPiDIP-33323N.
IntActiQ13472. 16 interactors.
MINTiMINT-6610291.
STRINGi9606.ENSP00000321636.

Structurei

Secondary structure

11001
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi23 – 30Combined sources8
Beta strandi35 – 42Combined sources8
Helixi43 – 54Combined sources12
Beta strandi59 – 61Combined sources3
Beta strandi70 – 77Combined sources8
Beta strandi80 – 88Combined sources9
Beta strandi95 – 98Combined sources4
Helixi100 – 103Combined sources4
Helixi105 – 107Combined sources3
Helixi110 – 114Combined sources5
Beta strandi118 – 121Combined sources4
Helixi124 – 126Combined sources3
Helixi127 – 139Combined sources13
Beta strandi141 – 147Combined sources7
Helixi151 – 165Combined sources15
Beta strandi172 – 175Combined sources4
Helixi183 – 191Combined sources9
Helixi198 – 229Combined sources32
Helixi231 – 234Combined sources4
Helixi245 – 261Combined sources17
Beta strandi266 – 276Combined sources11
Beta strandi279 – 285Combined sources7
Helixi293 – 304Combined sources12
Beta strandi309 – 321Combined sources13
Helixi329 – 338Combined sources10
Helixi344 – 356Combined sources13
Helixi376 – 381Combined sources6
Turni382 – 385Combined sources4
Turni387 – 389Combined sources3
Helixi390 – 398Combined sources9
Helixi428 – 444Combined sources17
Beta strandi449 – 460Combined sources12
Beta strandi463 – 474Combined sources12
Helixi476 – 479Combined sources4
Beta strandi503 – 511Combined sources9
Helixi520 – 530Combined sources11
Turni534 – 537Combined sources4
Helixi538 – 547Combined sources10
Beta strandi550 – 553Combined sources4
Beta strandi559 – 561Combined sources3
Helixi563 – 573Combined sources11
Helixi583 – 596Combined sources14
Helixi602 – 622Combined sources21
Helixi625 – 635Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4CGYX-ray2.85A2-753[»]
4CHTX-ray3.25A2-753[»]
ProteinModelPortaliQ13472.
SMRiQ13472.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 179ToprimPROSITE-ProRule annotationAdd BLAST145
Repeati812 – 8391Add BLAST28
Repeati896 – 9232Add BLAST28

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni812 – 9232 X 27 AA approximate repeatsAdd BLAST112

Sequence similaritiesi

Belongs to the type IA topoisomerase family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri658 – 685C4-typeSequence analysisAdd BLAST28

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1956. Eukaryota.
COG0550. LUCA.
GeneTreeiENSGT00530000063430.
HOGENOMiHOG000184377.
HOVERGENiHBG056668.
InParanoidiQ13472.
KOiK03165.
OMAiHVCKAVK.
OrthoDBiEOG091G03BD.
PhylomeDBiQ13472.
TreeFamiTF105287.

Family and domain databases

CDDicd00186. TOP1Ac. 1 hit.
cd03362. TOPRIM_TopoIA_TopoIII. 1 hit.
Gene3Di2.70.20.10. 1 hit.
4.10.60.10. 1 hit.
InterProiView protein in InterPro
IPR000380. Topo_IA.
IPR003601. Topo_IA_2.
IPR023406. Topo_IA_AS.
IPR013497. Topo_IA_cen.
IPR013825. Topo_IA_cen_sub2.
IPR023405. Topo_IA_core_domain.
IPR003602. Topo_IA_DNA-bd_dom.
IPR013498. Topo_IA_Znf.
IPR006171. TOPRIM_domain.
IPR034144. TOPRIM_TopoIII.
IPR036875. Znf_CCHC_sf.
IPR010666. Znf_GRF.
PANTHERiPTHR11390. PTHR11390. 1 hit.
PfamiView protein in Pfam
PF01131. Topoisom_bac. 1 hit.
PF01751. Toprim. 1 hit.
PF01396. zf-C4_Topoisom. 1 hit.
PF06839. zf-GRF. 2 hits.
PRINTSiPR00417. PRTPISMRASEI.
SMARTiView protein in SMART
SM00437. TOP1Ac. 1 hit.
SM00436. TOP1Bc. 1 hit.
SM00493. TOPRIM. 1 hit.
SUPFAMiSSF56712. SSF56712. 1 hit.
PROSITEiView protein in PROSITE
PS00396. TOPOISOMERASE_I_PROK. 1 hit.
PS50880. TOPRIM. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: Q13472-1) [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
MIFPVARYAL RWLRRPEDRA FSRAAMEMAL RGVRKVLCVA EKNDAAKGIA
60 70 80 90 100
DLLSNGRMRR REGLSKFNKI YEFDYHLYGQ NVTMVMTSVS GHLLAHDFQM
110 120 130 140 150
QFRKWQSCNP LVLFEAEIEK YCPENFVDIK KTLERETRQC QALVIWTDCD
160 170 180 190 200
REGENIGFEI IHVCKAVKPN LQVLRARFSE ITPHAVRTAC ENLTEPDQRV
210 220 230 240 250
SDAVDVRQEL DLRIGAAFTR FQTLRLQRIF PEVLAEQLIS YGSCQFPTLG
260 270 280 290 300
FVVERFKAIQ AFVPEIFHRI KVTHDHKDGI VEFNWKRHRL FNHTACLVLY
310 320 330 340 350
QLCVEDPMAT VVEVRSKPKS KWRPQALDTV ELEKLASRKL RINAKETMRI
360 370 380 390 400
AEKLYTQGYI SYPRTETNIF PRDLNLTVLV EQQTPDPRWG AFAQSILERG
410 420 430 440 450
GPTPRNGNKS DQAHPPIHPT KYTNNLQGDE QRLYEFIVRH FLACCSQDAQ
460 470 480 490 500
GQETTVEIDI AQERFVAHGL MILARNYLDV YPYDHWSDKI LPVYEQGSHF
510 520 530 540 550
QPSTVEMVDG ETSPPKLLTE ADLIALMEKH GIGTDATHAE HIETIKARMY
560 570 580 590 600
VGLTPDKRFL PGHLGMGLVE GYDSMGYEMS KPDLRAELEA DLKLICDGKK
610 620 630 640 650
DKFVVLRQQV QKYKQVFIEA VAKAKKLDEA LAQYFGNGTE LAQQEDIYPA
660 670 680 690 700
MPEPIRKCPQ CNKDMVLKTK KNGGFYLSCM GFPECRSAVW LPDSVLEASR
710 720 730 740 750
DSSVCPVCQP HPVYRLKLKF KRGSLPPTMP LEFVCCIGGC DDTLREILDL
760 770 780 790 800
RFSGGPPRAS QPSGRLQANQ SLNRMDNSQH PQPADSRQTG SSKALAQTLP
810 820 830 840 850
PPTAAGESNS VTCNCGQEAV LLTVRKEGPN RGRQFFKCNG GSCNFFLWAD
860 870 880 890 900
SPNPGAGGPP ALAYRPLGAS LGCPPGPGIH LGGFGNPGDG SGSGTSCLCS
910 920 930 940 950
QPSVTRTVQK DGPNKGRQFH TCAKPREQQC GFFQWVDENT APGTSGAPSW
960 970 980 990 1000
TGDRGRTLES EARSKRPRAS SSDMGSTAKK PRKCSLCHQP GHTRPFCPQN

R
Length:1,001
Mass (Da):112,372
Last modified:November 1, 1997 - v1
Checksum:i06558C749569E0C2
GO
Isoform Short (identifier: Q13472-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: Missing.

Show »
Length:976
Mass (Da):109,341
Checksum:i4AB9262B5DE7D05B
GO
Isoform 3 (identifier: Q13472-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-105: MIFPVARYAL...HDFQMQFRKW → MNLIIICMAR

Note: No experimental confirmation available.
Show »
Length:906
Mass (Da):101,208
Checksum:i60F389C5FF1A92F9
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052588459D → N. Corresponds to variant dbSNP:rs28671051Ensembl.1
Natural variantiVAR_007529596C → Y. 1
Natural variantiVAR_052589742D → N. Corresponds to variant dbSNP:rs9909732Ensembl.1
Natural variantiVAR_052590773N → D. Corresponds to variant dbSNP:rs9911283Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0541891 – 105MIFPV…QFRKW → MNLIIICMAR in isoform 3. 1 PublicationAdd BLAST105
Alternative sequenceiVSP_0065241 – 25Missing in isoform Short. 1 PublicationAdd BLAST25

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43431 mRNA. Translation: AAB03694.1.
U43431 mRNA. Translation: AAB03695.1.
HQ205026 Genomic DNA. Translation: ADP90454.1.
HQ205027 Genomic DNA. Translation: ADP90455.1.
HQ205028 Genomic DNA. Translation: ADP90456.1.
HQ205029 Genomic DNA. Translation: ADP90457.1.
HQ205030 Genomic DNA. Translation: ADP90458.1.
HQ205031 Genomic DNA. Translation: ADP90459.1.
HQ205032 Genomic DNA. Translation: ADP90460.1.
HQ205033 Genomic DNA. Translation: ADP90461.1.
HQ205034 Genomic DNA. Translation: ADP90462.1.
HQ205035 Genomic DNA. Translation: ADP90463.1.
HQ205036 Genomic DNA. Translation: ADP90464.1.
HQ205037 Genomic DNA. Translation: ADP90465.1.
HQ205038 Genomic DNA. Translation: ADP90466.1.
HQ205039 Genomic DNA. Translation: ADP90467.1.
HQ205040 Genomic DNA. Translation: ADP90468.1.
HQ205041 Genomic DNA. Translation: ADP90469.1.
HQ205042 Genomic DNA. Translation: ADP90470.1.
HQ205043 Genomic DNA. Translation: ADP90471.1.
HQ205044 Genomic DNA. Translation: ADP90472.1.
HQ205045 Genomic DNA. Translation: ADP90473.1.
HQ205046 Genomic DNA. Translation: ADP90474.1.
HQ205047 Genomic DNA. Translation: ADP90475.1.
HQ205048 Genomic DNA. Translation: ADP90476.1.
HQ205049 Genomic DNA. Translation: ADP90477.1.
HQ205050 Genomic DNA. Translation: ADP90478.1.
HQ205051 Genomic DNA. Translation: ADP90479.1.
HQ205052 Genomic DNA. Translation: ADP90480.1.
HQ205053 Genomic DNA. Translation: ADP90481.1.
HQ205054 Genomic DNA. Translation: ADP90482.1.
HQ205055 Genomic DNA. Translation: ADP90483.1.
HQ205056 Genomic DNA. Translation: ADP90484.1.
HQ205057 Genomic DNA. Translation: ADP90485.1.
HQ205058 Genomic DNA. Translation: ADP90486.1.
HQ205059 Genomic DNA. Translation: ADP90487.1.
HQ205060 Genomic DNA. Translation: ADP90488.1.
HQ205061 Genomic DNA. Translation: ADP90489.1.
HQ205062 Genomic DNA. Translation: ADP90490.1.
HQ205063 Genomic DNA. Translation: ADP90491.1.
HQ205064 Genomic DNA. Translation: ADP90492.1.
HQ205065 Genomic DNA. Translation: ADP90493.1.
AK292926 mRNA. Translation: BAF85615.1.
AK296437 mRNA. Translation: BAG59092.1.
AC127537 Genomic DNA. No translation available.
CH471196 Genomic DNA. Translation: EAW55646.1.
CH471196 Genomic DNA. Translation: EAW55648.1.
CH471196 Genomic DNA. Translation: EAW55649.1.
BC051748 mRNA. Translation: AAH51748.1.
CCDSiCCDS11194.1. [Q13472-1]
RefSeqiNP_001307688.1. NM_001320759.1. [Q13472-3]
NP_004609.1. NM_004618.4. [Q13472-1]
UniGeneiHs.592115.
Hs.713037.

Genome annotation databases

EnsembliENST00000321105; ENSP00000321636; ENSG00000177302. [Q13472-1]
ENST00000542570; ENSP00000442336; ENSG00000177302. [Q13472-1]
ENST00000580095; ENSP00000462790; ENSG00000177302. [Q13472-2]
ENST00000638894; ENSP00000492229; ENSG00000284238. [Q13472-1]
ENST00000639065; ENSP00000491260; ENSG00000284238. [Q13472-2]
ENST00000640743; ENSP00000491689; ENSG00000284238. [Q13472-1]
GeneIDi7156.
KEGGihsa:7156.
UCSCiuc002gsx.1. human. [Q13472-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTOP3A_HUMAN
AccessioniPrimary (citable) accession number: Q13472
Secondary accession number(s): A8KA61
, B4DK80, D3DXC7, Q13473
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: October 25, 2017
This is version 162 of the entry and version 1 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, 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