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Identification
HMDB Protein ID HMDBP14491
Secondary Accession Numbers None
Name Tyrosyl-DNA phosphodiesterase 2
Synonyms
  1. Tyr-DNA phosphodiesterase 2
  2. hTDP2
  3. 5'-tyrosyl-DNA phosphodiesterase
  4. ETS1-associated protein 2
  5. ETS1-associated protein II
  6. TRAF and TNF receptor-associated protein
  7. Tyrosyl-RNA phosphodiesterase
  8. VPg unlinkase
  9. 5'-Tyr-DNA phosphodiesterase
  10. EAPII
Gene Name TDP2
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. The 5'-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DNA double-strand breaks/DSBs without the need for nuclease activity, creating a 'clean' DSB with 5'-phosphate termini that are ready for ligation (PubMed:27099339, PubMed:27060144). Thereby, protects the transcription of many genes involved in neurological development and maintenance from the abortive activity of TOP2. Hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DSBs due to DNA damage by radiation and free radicals. Has preference for single-stranded DNA or duplex DNA with a 4 base pair overhang as substrate. Acts as a regulator of ribosome biogenesis following stress. Has also 3'-tyrosyl DNA phosphodiesterase activity, but less efficiently and much slower than TDP1. Constitutes the major if not only 5'-tyrosyl-DNA phosphodiesterase in cells. Also acts as an adapter by participating in the specific activation of MAP3K7/TAK1 in response to TGF-beta: associates with components of the TGF-beta receptor-TRAF6-TAK1 signaling module and promotes their ubiquitination dependent complex formation. Involved in non-canonical TGF-beta induced signaling routes. May also act as a negative regulator of ETS1 and may inhibit NF-kappa-B activation.(Microbial infection) Also acts as a 5'-tyrosyl-RNA phosphodiesterase following picornavirus infection: its activity is hijacked by picornavirus and acts by specifically cleaving the protein-RNA covalent linkage generated during the viral genomic RNA replication steps of a picornavirus infection, without impairing the integrity of viral RNA.
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
neuron development
double-strand break repair
cell surface receptor signaling pathway
viral reproduction
Cellular Component
cytoplasm
nucleolus
aggresome
nucleus
nucleoplasm
PML body
nuclear body
Molecular Function
manganese ion binding
magnesium ion binding
5'-tyrosyl-DNA phosphodiesterase activity
tyrosyl-RNA phosphodiesterase activity
nuclease activity
single-stranded DNA binding
transcription corepressor activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 362
Molecular Weight 40929.135
Theoretical pI 5.094
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID O95551
UniProtKB/Swiss-Prot Entry Name TYDP2_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  4. Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM, Huang GY, Chen Z, Chen MD, Chen JL: Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9543-8. [PubMed:10931946 ]
  5. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  6. Esguerra CV, Nelles L, Vermeire L, Ibrahimi A, Crawford AD, Derua R, Janssens E, Waelkens E, Carmeliet P, Collen D, Huylebroeck D: Ttrap is an essential modulator of Smad3-dependent Nodal signaling during zebrafish gastrulation and left-right axis determination. Development. 2007 Dec;134(24):4381-93. [PubMed:18039968 ]
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  8. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [PubMed:23186163 ]
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  15. Zeng Z, Cortes-Ledesma F, El Khamisy SF, Caldecott KW: TDP2/TTRAP is the major 5'-tyrosyl DNA phosphodiesterase activity in vertebrate cells and is critical for cellular resistance to topoisomerase II-induced DNA damage. J Biol Chem. 2011 Jan 7;286(1):403-9. doi: 10.1074/jbc.M110.181016. Epub 2010 Oct 28. [PubMed:21030584 ]
  16. Varady G, Sarkadi B, Fatyol K: TTRAP is a novel component of the non-canonical TRAF6-TAK1 TGF-beta signaling pathway. PLoS One. 2011;6(9):e25548. doi: 10.1371/journal.pone.0025548. Epub 2011 Sep 27. [PubMed:21980489 ]
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  22. Hornyak P, Askwith T, Walker S, Komulainen E, Paradowski M, Pennicott LE, Bartlett EJ, Brissett NC, Raoof A, Watson M, Jordan AM, Ogilvie DJ, Ward SE, Atack JR, Pearl LH, Caldecott KW, Oliver AW: Mode of action of DNA-competitive small molecule inhibitors of tyrosyl DNA phosphodiesterase 2. Biochem J. 2016 Jul 1;473(13):1869-79. doi: 10.1042/BCJ20160180. Epub 2016 Apr 20. [PubMed:27099339 ]
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