InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Tdp2

Summary

InnateDB Protein

IDBP-139099.6

Last Modified

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

Gene Symbol

Tdp2

Protein Name

tyrosyl-DNA phosphodiesterase 2

Synonyms

D13Ertd656e; Ttrap;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000035660

InnateDB Gene

IDBG-139097 (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 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:22740648}.

Subcellular Localization

Nucleus {ECO:0000250}. Nucleus, PML body {ECO:0000250}. Nucleus, nucleolus {ECO:0000250}. Note=Localizes to nucleolar cavities following stress; localization to nucleolus is dependent on PML protein. {ECO:0000250}.

Disease Associations

Tissue Specificity

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

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 1 experimentally validated interaction(s) in this database.
They are also associated with 31 interaction(s) predicted by orthology.

Experimentally validated
Total	1 [view]
Protein-Protein	1 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	31 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0003697	single-stranded DNA binding
GO:0004519	endonuclease activity
GO:0005515	protein binding
GO:0008081	phosphoric diester hydrolase activity
GO:0030145	manganese ion binding
GO:0036317	tyrosyl-RNA phosphodiesterase activity
GO:0070260	5'-tyrosyl-DNA phosphodiesterase activity