Q9JJX7 · TYDP2_MOUSE

  • Protein
    Tyrosyl-DNA phosphodiesterase 2
  • Gene
    Tdp2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Miscellaneous

Can partially complement the absence of Tdp1 due to its weak 3'-tyrosyl DNA phosphodiesterase activity.

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Mn2+ (UniProtKB | Rhea| CHEBI:29035 )

Note: Binds 1 magnesium or manganese ion per subunit.

Features

Showing features for binding site, site, active site.

TypeIDPosition(s)Description
Binding site132Mg2+ (UniProtKB | ChEBI)
Binding site162Mg2+ (UniProtKB | ChEBI)
Site188Interaction with 5' end of substrate DNA
Active site272Proton donor/acceptor
Site307Interaction with 5' end of substrate DNA
Site325Interaction with 5' end of substrate DNA
Site359Interaction with 5' end of substrate DNA

GO annotations

AspectTerm
Cellular Componentaggresome
Cellular Componentcytoplasm
Cellular Componentnucleolus
Cellular ComponentPML body
Molecular Function5'-tyrosyl-DNA phosphodiesterase activity
Molecular Functionendonuclease activity
Molecular Functionmagnesium ion binding
Molecular Functionmanganese ion binding
Molecular Functionphosphoric diester hydrolase activity
Molecular Functionsingle-stranded DNA binding
Molecular Functiontyrosyl-RNA phosphodiesterase activity
Biological Processdouble-strand break repair
Biological Processneuron development

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Tyrosyl-DNA phosphodiesterase 2
  • EC number
  • Short names
    Tyr-DNA phosphodiesterase 2
  • Alternative names
    • 5'-tyrosyl-DNA phosphodiesterase (5'-Tyr-DNA phosphodiesterase)
    • TRAF and TNF receptor-associated protein

Gene names

    • Name
      Tdp2
    • Synonyms
      Ttrap

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q9JJX7
  • Secondary accessions
    • A2RTH9

Proteomes

Organism-specific databases

Subcellular Location

Nucleus
Nucleus, PML body
Nucleus, nucleolus
Cytoplasm
Note: Localizes to nucleolar cavities following stress; localization to nucleolus is dependent on PML protein.

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis358Loss of magnesium binding.

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.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for modified residue, chain, cross-link.

TypeIDPosition(s)Description
Modified residue1N-acetylmethionine
ChainPRO_00000656791-370Tyrosyl-DNA phosphodiesterase 2
Cross-link34Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Modified residue99Phosphothreonine; by ACVR1B

Post-translational modification

Ubiquitinated by TRAF6.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Widely expressed (PubMed:10764746).
Expressed in whole brain, cerebellum, quiescent cortical astrocytes and cerebellar granule neurons (PubMed:24658003).

Gene expression databases

Interaction

Subunit

Interacts with TRAF2, TRAF3, TRAF5, TRAF6, TNFRSF8/CD30, TNFRSF5/CD40, TNFRSF1B/TNF-R75, ETS1, ETS2, FLI1, SMAD3 and ACVR1B/ALK4.

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region1-32Disordered
Region130-134Interaction with 5' end of substrate DNA
Region236-241Interaction with 5' end of substrate DNA
Region274-276Interaction with 5' end of substrate DNA
Region315-321Interaction with 5' end of substrate DNA

Sequence similarities

Belongs to the CCR4/nocturin family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    370
  • Mass (Da)
    41,034
  • Last updated
    2000-10-01 v1
  • Checksum
    A773A8889DF5BE83
MASGSSSDAAEPAGPAGRAASAPEAAQAEEDRVKRRRLQCLGFALVGGCDPTMVPSVLRENDWQTQKALSAYFELPENDQGWPRQPPTSFKSEAYVDLTNEDANDTTILEASPSGTPLEDSSTISFITWNIDGLDGCNLPERARGVCSCLALYSPDVVFLQEVIPPYCAYLKKRAASYTIITGNEEGYFTAILLKKGRVKFKSQEIIPFPNTKMMRNLLCVNVSLGGNEFCLMTSHLESTREHSAERIRQLKTVLGKMQEAPDSTTVIFAGDTNLRDQEVIKCGGLPDNVFDAWEFLGKPKHCQYTWDTKANNNLRIPAAYKHRFDRIFFRAEEGHLIPQSLDLVGLEKLDCGRFPSDHWGLLCTLNVVL

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A286YDM0A0A286YDM0_MOUSETdp294

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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