Protein: Tyrosyl-DNA phosphodiesterase 2 (Tyr-DNA phosphodiesterase 2) (hTDP2) (EC 3.1.4.-) (5'-tyrosyl-DNA phosphodiesterase) (5'-Tyr-DNA phosphodiesterase) (ETS1-associated protein 2) (ETS1-associated protein II) (EAPII) (TRAF and TNF receptor-associated protein) (Tyrosyl-RNA phosphodiesterase) (VPg unlinkase) (O95551)
Organism: Homo sapiens (Human)
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. 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.
Subcellular location: Nucleus {ECO:0000269|PubMed:12743594}. Nucleus, PML body {ECO:0000269|PubMed:19794497, ECO:0000269|PubMed:21921940}. Nucleus, nucleolus {ECO:0000269|PubMed:21921940}. Cytoplasm. Note=Localizes to nucleolar cavities following stress; localization to nucleolus is dependent on PML protein. {ECO:0000269|PubMed:21921940}.; SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22908287}. Note=(Microbial infection) In case of infection by picornavirus, relocalizes to cytoplasmic sites distinct from those containing viral proteins associated with RNA replication or encapsidation. {ECO:0000269|PubMed:22908287}.
Interaction partners:
- Acyl-coenzyme A thioesterase 13
- Dyslexia-associated protein KIAA0319
- Tyrosyl-DNA phosphodiesterase 1
- Ubiquitin-ribosomal protein eS31 fusion protein
- Polyubiquitin-C
- Polyubiquitin-B
- Ubiquitin-ribosomal protein eL40 fusion protein
- DNA topoisomerase 2-alpha
- Doublecortin domain-containing protein 2
- Tumor necrosis factor receptor superfamily member 5
Sequence:
MELGSCLEGGREAAEEEGEPEVKKRRLLCVEFASVASCDAAVAQCFLAENDWEMERALNSYFEPPVEESALERRPETISEPKTYVDLTNEETTDSTTSKISPSEDTQQENGSMFSLITWNIDGLDLNNLSERARGVCSYLALYSPDVIFLQEVIPPYYSYLKKRSSNYEIITGHEEGYFTAIMLKKSRVKLKSQEIIPFPSTKMMRNLLCVHVNVSGNELCLMTSHLESTRGHAAERMNQLKMVLKKMQEAPESATVIFAGDTNLRDREVTRCGGLPNNIVDVWEFLGKPKHCQYTWDTQMNSNLGITAACKLRFDRIFFRAAAEEGHIIPRSLDLLGLEKLDCGRFPSDHWGLLCNLDIIL