Tchem TDP2 Tyrosyl-DNA phosphodiesterase 2

Protein Summary

Description

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. (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. This gene encodes a member of a superfamily of divalent cation-dependent phosphodiesterases. The encoded protein associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor associated factors (TRAFs), and inhibits nuclear factor-kappa-B activation. This protein has sequence and structural similarities with APE1 endonuclease, which is involved in both DNA repair and the activation of transcription factors. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• O95551
• B4DKL8
• B4DQ95
• Q2TBE2
• Q5JYM0
• Q7Z6U5
• Q9NUK5
• Q9NYY9
• Tyr-DNA phosphodiesterase 2

Gene Name

• TDP2

Ensembl ID

• ENST00000378198
• ENSP00000367440
• ENSG00000111802

Symbol

• EAP2
• TTRAP
• EAP2
• AD022
• EAPII
• TTRAP
• hTDP2
• dJ30M3.3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
kinase perturbation	0.91
molecular function	0.9
histone modification site profile	0.87
virus perturbation	0.79
transcription factor binding site profile	0.77

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 126.36   (req: < 5)

Gene RIFs: 39   (req: <= 3)

Antibodies: 276   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 126.36   (req: >= 5)

Gene RIFs: 39   (req: > 3)

Antibodies: 276   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 10

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 74

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0