InnateDB: Systems Biology of the Innate Immune Response

Bos taurus Protein: TDP2

Summary

InnateDB Protein

IDBP-687419.2

Last Modified

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

Gene Symbol

TDP2

Protein Name

Tyrosyl-DNA phosphodiesterase 2

Synonyms

TTRAP;

Species

Bos taurus

Ensembl Protein

ENSBTAP00000000472

InnateDB Gene

IDBG-635578 (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 (By similarity). {ECO:0000250}.

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

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 0 experimentally validated interaction(s) in this database.
They are also associated with 29 interaction(s) predicted by orthology.

Predicted by orthology
Total	29 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0003697	single-stranded DNA binding
GO:0004518	nuclease activity
GO:0005515	protein binding
GO:0016787	hydrolase activity
GO:0030145	manganese ion binding
GO:0036317	tyrosyl-RNA phosphodiesterase activity
GO:0046872	metal ion binding
GO:0070260	5'-tyrosyl-DNA phosphodiesterase activity

Biological Process

GO:0006281	DNA repair
GO:0006302	double-strand break repair
GO:0006974	cellular response to DNA damage stimulus
GO:0090305	nucleic acid phosphodiester bond hydrolysis

Cellular Component

GO:0005634	nucleus
GO:0005730	nucleolus
GO:0005737	cytoplasm
GO:0016605	PML body
GO:0045171	intercellular bridge

Protein Structure and Domains

PDB ID

InterPro

IPR005135 Endonuclease/exonuclease/phosphatase
IPR009060 UBA-like

PFAM

PF03372
PF14529

PRINTS

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

A7YWI9

PhosphoSite

PhosphoSite-

TrEMBL

UniProt Splice Variant

Entrez Gene

507579

UniGene

Bt.68977

RefSeq

NP_001098811

HUGO

OMIM

CCDS

HPRD

IMGT

EMBL

BC134603

GenPept

AAI34604