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Overview

Uniprot IDP11387
Protein NameDNA topoisomerase 1
Gene NameTOP1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
101 VRASGDAKIKKEKEN
137 KEDIKPLKRPRDEDD
150 DDADYKPKKIKTEDT
151 DADYKPKKIKTEDTK
164 TKKEKKRKLEEEEDG
172 LEEEEDGKLKKPKNK
184 KNKDKDKKVPEPDNK
202 PKKEEEQKWKWWEEE
299 NIITNLSKCDFTQMS
540 DSIRYYNKVPVEKRV
642 APPKTFEKSMMNLQT

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-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the BMAL1 promoter

Protein Sequence

10 MSGDHLHNDS 20 QIEADFRLND 30 SHKHKDKHKD 40 REHRHKEHKK 50 EKDREKSKHS 60 NSEHKDSEKK 70 HKEKEKTKHK 80 DGSSEKHKDK 90 HKDRDKEKRK 100 EEKVRASGDA 110 KIKKEKENGF 120 SSPPQIKDEP 130 EDDGYFVPPK 140 EDIKPLKRPR 150 DEDDADYKPK 160 KIKTEDTKKE 170 KKRKLEEEED 180 GKLKKPKNKD 190 KDKKVPEPDN 200 KKKKPKKEEE 210 QKWKWWEEER 220 YPEGIKWKFL 230 EHKGPVFAPP 240 YEPLPENVKF 250 YYDGKVMKLS 260 PKAEEVATFF 270 AKMLDHEYTT 280 KEIFRKNFFK 290 DWRKEMTNEE 300 KNIITNLSKC 310 DFTQMSQYFK 320 AQTEARKQMS 330 KEEKLKIKEE 340 NEKLLKEYGF 350 CIMDNHKERI 360 ANFKIEPPGL 370 FRGRGNHPKM 380 GMLKRRIMPE 390 DIIINCSKDA 400 KVPSPPPGHK 410 WKEVRHDNKV 420 TWLVSWTENI 430 QGSIKYIMLN 440 PSSRIKGEKD 450 WQKYETARRL 460 KKCVDKIRNQ 470 YREDWKSKEM 480 KVRQRAVALY 490 FIDKLALRAG 500 NEKEEGETAD 510 TVGCCSLRVE 520 HINLHPELDG 530 QEYVVEFDFL 540 GKDSIRYYNK 550 VPVEKRVFKN 560 LQLFMENKQP 570 EDDLFDRLNT 580 GILNKHLQDL 590 MEGLTAKVFR 600 TYNASITLQQ 610 QLKELTAPDE 620 NIPAKILSYN 630 RANRAVAILC 640 NHQRAPPKTF 650 EKSMMNLQTK 660 IDAKKEQLAD 670 ARRDLKSAKA 680 DAKVMKDAKT 690 KKVVESKKKA 700 VQRLEEQLMK 710 LEVQATDREE 720 NKQIALGTSK 730 LNYLDPRITV 740 AWCKKWGVPI 750 EKIYNKTQRE 760 KFAWAIDMAD EDYEF

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005694 chromosome
Cellular Component GO:0001651 dense fibrillar component
Cellular Component GO:0001650 fibrillar center
Cellular Component GO:0005730 nucleolus
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0000932 P-body
Cellular Component GO:0043204 perikaryon
Cellular Component GO:0032993 protein-DNA complex
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0003682 chromatin binding
Molecular Function GO:0031490 chromatin DNA binding
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0008301 DNA binding, bending
Molecular Function GO:0003917 DNA topoisomerase type I (single strand cut, ATP-independent) activity
Molecular Function GO:0003690 double-stranded DNA binding
Molecular Function GO:0140693 molecular condensate scaffold activity
Molecular Function GO:0019904 protein domain specific binding
Molecular Function GO:0004674 protein serine/threonine kinase activity
Molecular Function GO:0044877 protein-containing complex binding
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
Molecular Function GO:0003697 single-stranded DNA binding
Molecular Function GO:0097100 supercoiled DNA binding
Biological Process GO:0031100 animal organ regeneration
Biological Process GO:0071373 cellular response to luteinizing hormone stimulus
Biological Process GO:0006338 chromatin remodeling
Biological Process GO:0007059 chromosome segregation
Biological Process GO:0032922 circadian regulation of gene expression
Biological Process GO:0007623 circadian rhythm
Biological Process GO:0006260 DNA replication
Biological Process GO:0006265 DNA topological change
Biological Process GO:0012501 programmed cell death
Biological Process GO:0051591 response to cAMP
Biological Process GO:0010332 response to gamma radiation
Biological Process GO:0009266 response to temperature stimulus
Biological Process GO:0009410 response to xenobiotic stimulus
Biological Process GO:0009303 rRNA transcription

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[3] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[4] 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.

[5] Bao Q, Wan N, He Z, Cao J, Yuan W et al.. Subcellular Proteomic Mapping of Lysine Lactylation.. J Am Soc Mass Spectrom 35(12):3221-3232. 2024 Dec 4. PMID: 39569522.

[6] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[7] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.