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Overview

Uniprot IDQ13472
Protein NameDNA topoisomerase 3-alpha
Gene NameTOP3A
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
979 SDMGSTAKKPRKCSL

Function

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. As an essential component of the RMI complex it is involved in chromosome separation and the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Has DNA decatenation activity (PubMed:30057030). It is required for mtDNA decatenation and segregation after completion of replication, in a process that does not require BLM, RMI1 and RMI2 (PubMed:29290614)

Protein Sequence

10 MIFPVARYAL 20 RWLRRPEDRA 30 FSRAAMEMAL 40 RGVRKVLCVA 50 EKNDAAKGIA 60 DLLSNGRMRR 70 REGLSKFNKI 80 YEFDYHLYGQ 90 NVTMVMTSVS 100 GHLLAHDFQM 110 QFRKWQSCNP 120 LVLFEAEIEK 130 YCPENFVDIK 140 KTLERETRQC 150 QALVIWTDCD 160 REGENIGFEI 170 IHVCKAVKPN 180 LQVLRARFSE 190 ITPHAVRTAC 200 ENLTEPDQRV 210 SDAVDVRQEL 220 DLRIGAAFTR 230 FQTLRLQRIF 240 PEVLAEQLIS 250 YGSCQFPTLG 260 FVVERFKAIQ 270 AFVPEIFHRI 280 KVTHDHKDGI 290 VEFNWKRHRL 300 FNHTACLVLY 310 QLCVEDPMAT 320 VVEVRSKPKS 330 KWRPQALDTV 340 ELEKLASRKL 350 RINAKETMRI 360 AEKLYTQGYI 370 SYPRTETNIF 380 PRDLNLTVLV 390 EQQTPDPRWG 400 AFAQSILERG 410 GPTPRNGNKS 420 DQAHPPIHPT 430 KYTNNLQGDE 440 QRLYEFIVRH 450 FLACCSQDAQ 460 GQETTVEIDI 470 AQERFVAHGL 480 MILARNYLDV 490 YPYDHWSDKI 500 LPVYEQGSHF 510 QPSTVEMVDG 520 ETSPPKLLTE 530 ADLIALMEKH 540 GIGTDATHAE 550 HIETIKARMY 560 VGLTPDKRFL 570 PGHLGMGLVE 580 GYDSMGYEMS 590 KPDLRAELEA 600 DLKLICDGKK 610 DKFVVLRQQV 620 QKYKQVFIEA 630 VAKAKKLDEA 640 LAQYFGNGTE 650 LAQQEDIYPA 660 MPEPIRKCPQ 670 CNKDMVLKTK 680 KNGGFYLSCM 690 GFPECRSAVW 700 LPDSVLEASR 710 DSSVCPVCQP 720 HPVYRLKLKF 730 KRGSLPPTMP 740 LEFVCCIGGC 750 DDTLREILDL 760 RFSGGPPRAS 770 QPSGRLQANQ 780 SLNRMDNSQH 790 PQPADSRQTG 800 SSKALAQTLP 810 PPTAAGESNS 820 VTCNCGQEAV 830 LLTVRKEGPN 840 RGRQFFKCNG 850 GSCNFFLWAD 860 SPNPGAGGPP 870 ALAYRPLGAS 880 LGCPPGPGIH 890 LGGFGNPGDG 900 SGSGTSCLCS 910 QPSVTRTVQK 920 DGPNKGRQFH 930 TCAKPREQQC 940 GFFQWVDENT 950 APGTSGAPSW 960 TGDRGRTLES 970 EARSKRPRAS 980 SSDMGSTAKK 990 PRKCSLCHQP 1000 GHTRPFCPQN R

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005759 mitochondrial matrix
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0016605 PML body
Cellular Component GO:0031422 RecQ family helicase-topoisomerase III complex
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0003917 DNA topoisomerase type I (single strand cut, ATP-independent) activity
Molecular Function GO:0003697 single-stranded DNA binding
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0051304 chromosome separation
Biological Process GO:0006310 DNA recombination
Biological Process GO:0006281 DNA repair
Biological Process GO:0006265 DNA topological change
Biological Process GO:0000724 double-strand break repair via homologous recombination
Biological Process GO:0051321 meiotic cell cycle
Biological Process GO:0032042 mitochondrial DNA metabolic process
Biological Process GO:0071139 resolution of DNA recombination intermediates

Reference

[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.