InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TDP2

Summary

InnateDB Protein

IDBP-65488.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TDP2

Protein Name

tyrosyl-DNA phosphodiesterase 2

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000345345

InnateDB Gene

IDBG-65484 (TDP2)

Protein Structure

UniProt Annotation

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. Hydrolyzes 5'- phosphoglycolates on protruding 5' ends on DNA double-strand breaks (DSBs) due to DNA damage by radiation and free radicals. The 5'-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DSBs without the need for nuclease activity, creating a 'clean' DSB with 5'-phosphate termini that are ready for ligation. Has preference for single-stranded DNA or duplex DNA with a 4 base pair overhang as substrate. 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 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. 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. Acts as a regulator of ribosome biogenesis following stress. {ECO:0000269PubMed:19794497, ECO:0000269PubMed:21030584, ECO:0000269PubMed:21921940, ECO:0000269PubMed:21980489, ECO:0000269PubMed:22405347, ECO:0000269PubMed:22822062, ECO:0000269PubMed:22908287}.

Subcellular Localization

Nucleus. Nucleus, PML body. Nucleus, nucleolus. Cytoplasm. Note=Localizes to nucleolar cavities following stress; localization to nucleolus is dependent on PML protein. In case of infection by picornavirus, relocalizes to cytoplasmic sites distinct from those containing viral proteins associated with RNA replication or encapsidation.

Disease Associations

Tissue Specificity

Widely expressed. {ECO:0000269PubMed:10764746}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 39 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.