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Protein

Tyrosyl-DNA phosphodiesterase 2

Gene

Tdp2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

Cofactori

Mg2+By similarity, Mn2+By similarityNote: Magnesium. Can use other divalent cations as cofactor in vitro, such as manganese.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi130 – 1301MagnesiumBy similarity
Metal bindingi162 – 1621MagnesiumBy similarity
Metal bindingi272 – 2721MagnesiumBy similarity
Metal bindingi274 – 2741MagnesiumBy similarity
Metal bindingi358 – 3581MagnesiumBy similarity
Active sitei359 – 3591Proton acceptorBy similarity
Metal bindingi359 – 3591MagnesiumBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Nuclease

Keywords - Biological processi

DNA damage, DNA repair

Keywords - Ligandi

Magnesium, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-5693571. Nonhomologous End-Joining (NHEJ).

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosyl-DNA phosphodiesterase 2 (EC:3.1.4.-)
Short name:
Tyr-DNA phosphodiesterase 2
Alternative name(s):
5'-tyrosyl-DNA phosphodiesterase
Short name:
5'-Tyr-DNA phosphodiesterase
TRAF and TNF receptor-associated protein
Gene namesi
Name:Tdp2
Synonyms:Ttrap
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:1860486. Tdp2.

Subcellular locationi

  • Nucleus By similarity
  • NucleusPML body By similarity
  • Nucleusnucleolus By similarity

  • Note: Localizes to nucleolar cavities following stress; localization to nucleolus is dependent on PML protein.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 370370Tyrosyl-DNA phosphodiesterase 2PRO_0000065679Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei99 – 991Phosphothreonine; by ACVR1BBy similarity

Post-translational modificationi

Ubiquitinated by TRAF6.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9JJX7.
MaxQBiQ9JJX7.
PaxDbiQ9JJX7.
PRIDEiQ9JJX7.

PTM databases

iPTMnetiQ9JJX7.
PhosphoSiteiQ9JJX7.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiQ9JJX7.
CleanExiMM_TTRAP.
GenevisibleiQ9JJX7. MM.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi207835. 1 interaction.
STRINGi10090.ENSMUSP00000035660.

Structurei

Secondary structure

1
370
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi119 – 1224Combined sources
Beta strandi123 – 1308Combined sources
Helixi139 – 15315Combined sources
Beta strandi156 – 1638Combined sources
Helixi165 – 17410Combined sources
Beta strandi178 – 1836Combined sources
Beta strandi185 – 19511Combined sources
Turni196 – 1983Combined sources
Beta strandi199 – 20810Combined sources
Beta strandi217 – 2259Combined sources
Beta strandi228 – 2347Combined sources
Helixi241 – 2433Combined sources
Helixi244 – 26017Combined sources
Beta strandi265 – 2728Combined sources
Helixi277 – 2837Combined sources
Beta strandi290 – 2923Combined sources
Helixi293 – 2964Combined sources
Helixi301 – 3033Combined sources
Beta strandi306 – 3083Combined sources
Turni309 – 3113Combined sources
Beta strandi326 – 3316Combined sources
Beta strandi333 – 3353Combined sources
Beta strandi336 – 34510Combined sources
Beta strandi361 – 3688Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4GYZX-ray2.56A/B/C/D/E/F/G/H/I118-370[»]
4GZ0X-ray2.11A/B/E/G/I/K118-370[»]
4GZ1X-ray1.50A/B118-370[»]
4GZ2X-ray1.85A/B118-369[»]
4PUQX-ray1.60A/B118-370[»]
ProteinModelPortaliQ9JJX7.
SMRiQ9JJX7. Positions 43-370.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the CCR4/nocturin family.Curated

Phylogenomic databases

eggNOGiKOG2756. Eukaryota.
ENOG410XP85. LUCA.
GeneTreeiENSGT00390000014242.
HOGENOMiHOG000236334.
HOVERGENiHBG079625.
InParanoidiQ9JJX7.
KOiK19619.
OMAiTGNEEGY.
OrthoDBiEOG7XPZ5W.
PhylomeDBiQ9JJX7.
TreeFamiTF314813.

Family and domain databases

Gene3Di3.60.10.10. 1 hit.
InterProiIPR005135. Endo/exonuclease/phosphatase.
[Graphical view]
PfamiPF03372. Exo_endo_phos. 1 hit.
[Graphical view]
SUPFAMiSSF56219. SSF56219. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9JJX7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASGSSSDAA EPAGPAGRAA SAPEAAQAEE DRVKRRRLQC LGFALVGGCD
60 70 80 90 100
PTMVPSVLRE NDWQTQKALS AYFELPENDQ GWPRQPPTSF KSEAYVDLTN
110 120 130 140 150
EDANDTTILE ASPSGTPLED SSTISFITWN IDGLDGCNLP ERARGVCSCL
160 170 180 190 200
ALYSPDVVFL QEVIPPYCAY LKKRAASYTI ITGNEEGYFT AILLKKGRVK
210 220 230 240 250
FKSQEIIPFP NTKMMRNLLC VNVSLGGNEF CLMTSHLEST REHSAERIRQ
260 270 280 290 300
LKTVLGKMQE APDSTTVIFA GDTNLRDQEV IKCGGLPDNV FDAWEFLGKP
310 320 330 340 350
KHCQYTWDTK ANNNLRIPAA YKHRFDRIFF RAEEGHLIPQ SLDLVGLEKL
360 370
DCGRFPSDHW GLLCTLNVVL
Length:370
Mass (Da):41,034
Last modified:October 1, 2000 - v1
Checksum:iA773A8889DF5BE83
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ251328 mRNA. Translation: CAB92971.1.
AL589699 Genomic DNA. Translation: CAI26084.1.
CH466561 Genomic DNA. Translation: EDL32475.1.
BC132511 mRNA. Translation: AAI32512.1.
BC132513 mRNA. Translation: AAI32514.1.
CCDSiCCDS26381.1.
RefSeqiNP_062424.1. NM_019551.2.
UniGeneiMm.427162.

Genome annotation databases

EnsembliENSMUST00000038039; ENSMUSP00000035660; ENSMUSG00000035958.
GeneIDi56196.
KEGGimmu:56196.
UCSCiuc007pwl.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ251328 mRNA. Translation: CAB92971.1.
AL589699 Genomic DNA. Translation: CAI26084.1.
CH466561 Genomic DNA. Translation: EDL32475.1.
BC132511 mRNA. Translation: AAI32512.1.
BC132513 mRNA. Translation: AAI32514.1.
CCDSiCCDS26381.1.
RefSeqiNP_062424.1. NM_019551.2.
UniGeneiMm.427162.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4GYZX-ray2.56A/B/C/D/E/F/G/H/I118-370[»]
4GZ0X-ray2.11A/B/E/G/I/K118-370[»]
4GZ1X-ray1.50A/B118-370[»]
4GZ2X-ray1.85A/B118-369[»]
4PUQX-ray1.60A/B118-370[»]
ProteinModelPortaliQ9JJX7.
SMRiQ9JJX7. Positions 43-370.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi207835. 1 interaction.
STRINGi10090.ENSMUSP00000035660.

PTM databases

iPTMnetiQ9JJX7.
PhosphoSiteiQ9JJX7.

Proteomic databases

EPDiQ9JJX7.
MaxQBiQ9JJX7.
PaxDbiQ9JJX7.
PRIDEiQ9JJX7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000038039; ENSMUSP00000035660; ENSMUSG00000035958.
GeneIDi56196.
KEGGimmu:56196.
UCSCiuc007pwl.2. mouse.

Organism-specific databases

CTDi51567.
MGIiMGI:1860486. Tdp2.

Phylogenomic databases

eggNOGiKOG2756. Eukaryota.
ENOG410XP85. LUCA.
GeneTreeiENSGT00390000014242.
HOGENOMiHOG000236334.
HOVERGENiHBG079625.
InParanoidiQ9JJX7.
KOiK19619.
OMAiTGNEEGY.
OrthoDBiEOG7XPZ5W.
PhylomeDBiQ9JJX7.
TreeFamiTF314813.

Enzyme and pathway databases

ReactomeiR-MMU-5693571. Nonhomologous End-Joining (NHEJ).

Miscellaneous databases

ChiTaRSiTdp2. mouse.
NextBioi312014.
PROiQ9JJX7.
SOURCEiSearch...

Gene expression databases

BgeeiQ9JJX7.
CleanExiMM_TTRAP.
GenevisibleiQ9JJX7. MM.

Family and domain databases

Gene3Di3.60.10.10. 1 hit.
InterProiIPR005135. Endo/exonuclease/phosphatase.
[Graphical view]
PfamiPF03372. Exo_endo_phos. 1 hit.
[Graphical view]
SUPFAMiSSF56219. SSF56219. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "TTRAP, a novel protein that associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor-associated factors (TRAFs), and that inhibits nuclear factor-kappa B activation."
    Pype S., Declercq W., Ibrahimi A., Michiels C., Van Rietschoten J.G.I., Dewulf N., de Boer M., Vandenabeele P., Huylebroeck D., Remacle J.E.
    J. Biol. Chem. 275:18586-18593(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  5. "TDP2 promotes repair of topoisomerase I-mediated DNA damage in the absence of TDP1."
    Zeng Z., Sharma A., Ju L., Murai J., Umans L., Vermeire L., Pommier Y., Takeda S., Huylebroeck D., Caldecott K.W., El-Khamisy S.F.
    Nucleic Acids Res. 40:8371-8380(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiTYDP2_MOUSE
AccessioniPrimary (citable) accession number: Q9JJX7
Secondary accession number(s): A2RTH9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: October 1, 2000
Last modified: March 16, 2016
This is version 95 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Can partially complement the absence of Tdp1 due to its weak 3'-tyrosyl DNA phosphodiesterase activity.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.