UniProt Accession

 TYDP2_MOUSE; Q9JJX7; A2RTH9 

Genbank Protein ID

 AJ251328; AL589699; CH466561; BC132511; BC132513 

Genbank Nucleotide ID

 CAB92971.1; CAI26084.1; EDL32475.1; AAI32512.1; AAI32514.1 

Protein Name

 Tyrosyl-DNA phosphodiesterase 2 

Protein Synonyms/Alias

 Tyr-DNA phosphodiesterase 2; 5'-tyrosyl-DNA phosphodiesterase; 5'-Tyr-DNA phosphodiesterase; TRAF and TNF receptor-associated protein 

Gene Name

 Tdp2 

Gene Synonyms/Alias

 Ttrap 

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
202	KKGRVKFKSQEIIPF	ubiquitination	[1]
310	CQYTWDTKANNNLRI	ubiquitination	[1]

Reference

 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 

Functional 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. 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 to 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. 

Sequence Annotation

 ACT_SITE 359 359 Proton acceptor (By similarity).
 METAL 130 130 Magnesium (By similarity).
 METAL 162 162 Magnesium (By similarity).
 METAL 272 272 Magnesium (By similarity).
 METAL 274 274 Magnesium (By similarity).
 METAL 358 358 Magnesium (By similarity).
 METAL 359 359 Magnesium (By similarity).
 MOD_RES 1 1 N-acetylmethionine (By similarity).
 MOD_RES 99 99 Phosphothreonine; by ACVR1B (By  

Keyword

 3D-structure; Acetylation; Complete proteome; DNA damage; DNA repair; Hydrolase; Magnesium; Metal-binding; Nuclease; Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 370 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IEA:Compara.
 GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
 GO:0016605; C:PML body; ISS:UniProtKB.
 GO:0070260; F:5'-tyrosyl-DNA phosphodiesterase activity; ISS:UniProtKB.
 GO:0004519; F:endonuclease activity; ISA:MGI.
 GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
 GO:0030145; F:manganese ion binding; ISS:UniProtKB.
 GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
 GO:0036317; F:tyrosyl-RNA phosphodiesterase activity; IEA:Compara.
 GO:0006302; P:double-strand break repair; ISS:UniProtKB. 

Interpro

 IPR005135; Endo/exonuclease/phosphatase. 

Pfam

 PF03372; Exo_endo_phos 

SMART

  

PROSITE

  

PRINTS