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Overview

Uniprot ID	Q9NUW8
Protein Name	Tyrosyl-DNA phosphodiesterase 1
Gene Name	TDP1
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
53	YTCSEAQKAAHKRKI
75	TDSVLPPKRQKSGSQ

Function

DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 3'-phosphodiester bond, giving rise to DNA with a free 3' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase I active site tyrosine residue. Hydrolyzes 3'-phosphoglycolates on protruding 3' ends on DNA double-strand breaks due to DNA damage by radiation and free radicals. Acts on blunt-ended double-strand DNA breaks and on single-stranded DNA. Has low 3'exonuclease activity and can remove a single nucleoside from the 3'end of DNA and RNA molecules with 3'hydroxyl groups. Has no exonuclease activity towards DNA or RNA with a 3'phosphate

Protein Sequence

10 MSQEGDYGRW 20 TISSSDESEE 30 EKPKPDKPST 40 SSLLCARQGA 50 ANEPRYTCSE 60 AQKAAHKRKI 70 SPVKFSNTDS 80 VLPPKRQKSG 90 SQEDLGWCLS 100 SSDDELQPEM 110 PQKQAEKVVI 120 KKEKDISAPN 130 DGTAQRTENH 140 GAPACHRLKE 150 EEDEYETSGE 160 GQDIWDMLDK 170 GNPFQFYLTR 180 VSGVKPKYNS 190 GALHIKDILS 200 PLFGTLVSSA 210 QFNYCFDVDW 220 LVKQYPPEFR 230 KKPILLVHGD 240 KREAKAHLHA 250 QAKPYENISL 260 CQAKLDIAFG 270 THHTKMMLLL 280 YEEGLRVVIH 290 TSNLIHADWH 300 QKTQGIWLSP 310 LYPRIADGTH 320 KSGESPTHFK 330 ADLISYLMAY 340 NAPSLKEWID 350 VIHKHDLSET 360 NVYLIGSTPG 370 RFQGSQKDNW 380 GHFRLKKLLK 390 DHASSMPNAE 400 SWPVVGQFSS 410 VGSLGADESK 420 WLCSEFKESM 430 LTLGKESKTP 440 GKSSVPLYLI 450 YPSVENVRTS 460 LEGYPAGGSL 470 PYSIQTAEKQ 480 NWLHSYFHKW 490 SAETSGRSNA 500 MPHIKTYMRP 510 SPDFSKIAWF 520 LVTSANLSKA 530 AWGALEKNGT 540 QLMIRSYELG 550 VLFLPSAFGL 560 DSFKVKQKFF 570 AGSQEPMATF 580 PVPYDLPPEL 590 YGSKDRPWIW 600 NIPYVKAPDT HGNMWVPS

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0090734	site of DNA damage
Molecular Function	GO:0017005	3'-tyrosyl-DNA phosphodiesterase activity
Molecular Function	GO:0003690	double-stranded DNA binding
Molecular Function	GO:0004527	exonuclease activity
Molecular Function	GO:0003697	single-stranded DNA binding
Biological Process	GO:0006281	DNA repair
Biological Process	GO:0006302	double-strand break repair
Biological Process	GO:0006282	regulation of DNA repair
Biological Process	GO:0000012	single strand break repair

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] 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.