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)
1_MELGS 6_ CLEGG 11_ REAAE 16_ EEGEP 21_ EVKKR 26_ RLLCV 31_ EFASV 36_ ASCDA 41_ AVAQC 46_ FLAEN 51_ DWEME 56_ RALNS 61_ YFEPP 66_ VEESA 71_ LERRP 76_ ETISE 81_ PKTYV 86_ DLTNE 91_ ETTDS 96_ TTSKI 101_ SPSED 106_ TQQEN 111_ GSMFS 116_ LITWN 121_ IDGLD 126_ LNNLS 131_ ERARG 136_ VCSYL 141_ ALYSP 146_ DVIFL 151_ QEVIP 156_ PYYSY 161_ LKKRS 166_ SNYEI 171_ ITGHE 176_ EGYFT 181_ AIMLK 186_ KSRVK 191_ LKSQE 196_ IIPFP 201_ STKMM 206_ RNLLC 211_ VHVNV 216_ SGNEL 221_ CLMTS 226_ HLEST 231_ RGHAA 236_ ERMNQ 241_ LKMVL 246_ KKMQE 251_ APESA 256_ TVIFA 261_ GDTNL 266_ RDREV 271_ TRCGG 276_ LPNNI 281_ VDVWE 286_ FLGKP 291_ KHCQY 296_ TWDTQ 301_ MNSNL 306_ GITAA 311_ CKLRF 316_ DRIFF 321_ RAAAE 326_ EGHII 331_ PRSLD 336_ LLGLE 341_ KLDCG 346_ RFPSD 351_ HWGLL 356_CNLDI
1: 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:27060144, PubMed:27099339). 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. Also has 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
2: (Microbial infection) Used by picornaviruses to remove the small polypeptide, VPg (virus Protein genome-linked, the primer for viral RNA synthesis), from the genomic RNA of the virus. Acts as a 5'-tyrosyl RNA phosphodiesterase and cleaves the covalent VPg-Tyr-RNA bond. This cleavage would play a role in viral replication and occur in viral replication vesicles, but would not act on viral mRNA