Q9JJX7 · TYDP2_MOUSE
- ProteinTyrosyl-DNA phosphodiesterase 2
- GeneTdp2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids370 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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. 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 (PubMed:23104055, PubMed:24808172, PubMed:27060144, PubMed:27099339).
Thereby, protects the transcription of many genes involved in neurological development and maintenance from the abortive activity of TOP2 (PubMed:22740648).
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. 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).
Thereby, protects the transcription of many genes involved in neurological development and maintenance from the abortive activity of TOP2 (PubMed:22740648).
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. 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).
Miscellaneous
Can partially complement the absence of Tdp1 due to its weak 3'-tyrosyl DNA phosphodiesterase activity.
Cofactor
Mn2+ (UniProtKB | Rhea| CHEBI:29035 )
Note: Binds 1 magnesium or manganese ion per subunit.
Features
Showing features for binding site, site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 132 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 162 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Site | 188 | Interaction with 5' end of substrate DNA | ||||
Sequence: Y | ||||||
Active site | 272 | Proton donor/acceptor | ||||
Sequence: D | ||||||
Site | 307 | Interaction with 5' end of substrate DNA | ||||
Sequence: W | ||||||
Site | 325 | Interaction with 5' end of substrate DNA | ||||
Sequence: F | ||||||
Site | 359 | Interaction with 5' end of substrate DNA | ||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | aggresome | |
Cellular Component | cytoplasm | |
Cellular Component | nucleolus | |
Cellular Component | PML body | |
Molecular Function | 5'-tyrosyl-DNA phosphodiesterase activity | |
Molecular Function | endonuclease activity | |
Molecular Function | magnesium ion binding | |
Molecular Function | manganese ion binding | |
Molecular Function | phosphoric diester hydrolase activity | |
Molecular Function | single-stranded DNA binding | |
Molecular Function | tyrosyl-RNA phosphodiesterase activity | |
Biological Process | double-strand break repair | |
Biological Process | neuron development |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTyrosyl-DNA phosphodiesterase 2
- EC number
- Short namesTyr-DNA phosphodiesterase 2
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9JJX7
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localizes to nucleolar cavities following stress; localization to nucleolus is dependent on PML protein.
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 358 | Loss of magnesium binding. | ||||
Sequence: D → N |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 20 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for modified residue, chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Modified residue | 1 | N-acetylmethionine | ||||
Sequence: M | ||||||
Chain | PRO_0000065679 | 1-370 | Tyrosyl-DNA phosphodiesterase 2 | |||
Sequence: MASGSSSDAAEPAGPAGRAASAPEAAQAEEDRVKRRRLQCLGFALVGGCDPTMVPSVLRENDWQTQKALSAYFELPENDQGWPRQPPTSFKSEAYVDLTNEDANDTTILEASPSGTPLEDSSTISFITWNIDGLDGCNLPERARGVCSCLALYSPDVVFLQEVIPPYCAYLKKRAASYTIITGNEEGYFTAILLKKGRVKFKSQEIIPFPNTKMMRNLLCVNVSLGGNEFCLMTSHLESTREHSAERIRQLKTVLGKMQEAPDSTTVIFAGDTNLRDQEVIKCGGLPDNVFDAWEFLGKPKHCQYTWDTKANNNLRIPAAYKHRFDRIFFRAEEGHLIPQSLDLVGLEKLDCGRFPSDHWGLLCTLNVVL | ||||||
Cross-link | 34 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 99 | Phosphothreonine; by ACVR1B | ||||
Sequence: T |
Post-translational modification
Ubiquitinated by TRAF6.
Keywords
- PTM
Proteomic databases
PTM databases
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-32 | Disordered | ||||
Sequence: MASGSSSDAAEPAGPAGRAASAPEAAQAEEDR | ||||||
Region | 130-134 | Interaction with 5' end of substrate DNA | ||||
Sequence: NIDGL | ||||||
Region | 236-241 | Interaction with 5' end of substrate DNA | ||||
Sequence: HLESTR | ||||||
Region | 274-276 | Interaction with 5' end of substrate DNA | ||||
Sequence: NLR | ||||||
Region | 315-321 | Interaction with 5' end of substrate DNA | ||||
Sequence: LRIPAAY |
Sequence similarities
Belongs to the CCR4/nocturin family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length370
- Mass (Da)41,034
- Last updated2000-10-01 v1
- ChecksumA773A8889DF5BE83
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A286YDM0 | A0A286YDM0_MOUSE | Tdp2 | 94 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ251328 EMBL· GenBank· DDBJ | CAB92971.1 EMBL· GenBank· DDBJ | mRNA | ||
AL589699 EMBL· GenBank· DDBJ | CAI26084.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH466561 EMBL· GenBank· DDBJ | EDL32475.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC132511 EMBL· GenBank· DDBJ | AAI32512.1 EMBL· GenBank· DDBJ | mRNA | ||
BC132513 EMBL· GenBank· DDBJ | AAI32514.1 EMBL· GenBank· DDBJ | mRNA |