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Protein

Tyrosyl-DNA phosphodiesterase 2

Gene

Tdp2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 (By similarity). 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. 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).By similarity1 Publication

Miscellaneous

Can partially complement the absence of Tdp1 due to its weak 3'-tyrosyl DNA phosphodiesterase activity.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)DescriptionActionsGraphical viewLength
Metal bindingi130MagnesiumBy similarity1
Metal bindingi162MagnesiumBy similarity1
Metal bindingi272MagnesiumBy similarity1
Metal bindingi274MagnesiumBy similarity1
Metal bindingi358MagnesiumBy similarity1
Active sitei359Proton acceptorBy similarity1
Metal bindingi359MagnesiumBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Nuclease
Biological processDNA damage, DNA repair
LigandMagnesium, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:1860486 Tdp2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3813588

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000656791 – 370Tyrosyl-DNA phosphodiesterase 2Add BLAST370

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Cross-linki34Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei99Phosphothreonine; by ACVR1BBy similarity1

Post-translational modificationi

Ubiquitinated by TRAF6.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9JJX7
MaxQBiQ9JJX7
PaxDbiQ9JJX7
PeptideAtlasiQ9JJX7
PRIDEiQ9JJX7

PTM databases

iPTMnetiQ9JJX7
PhosphoSitePlusiQ9JJX7

Expressioni

Tissue specificityi

Widely expressed (PubMed:10764746). Expressed in whole brain, cerebellum, quiescent cortical astrocytes and cerebellar granule neurons (PubMed:24658003).2 Publications

Gene expression databases

BgeeiENSMUSG00000035958 Expressed in 284 organ(s), highest expression level in cochlea
CleanExiMM_TTRAP
ExpressionAtlasiQ9JJX7 baseline and differential
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, 2 interactors
STRINGi10090.ENSMUSP00000035660

Chemistry databases

BindingDBiQ9JJX7

Structurei

Secondary structure

1370
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9JJX7
SMRiQ9JJX7
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
OrthoDBiEOG091G0FBI
PhylomeDBiQ9JJX7
TreeFamiTF314813

Family and domain databases

Gene3Di3.60.10.10, 1 hit
InterProiView protein in InterPro
IPR036691 Endo/exonu/phosph_ase_sf
IPR005135 Endo/exonuclease/phosphatase
PfamiView protein in Pfam
PF03372 Exo_endo_phos, 1 hit
SUPFAMiSSF56219 SSF56219, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A286YDM0A0A286YDM0_MOUSE
Tyrosyl-DNA phosphodiesterase 2
Tdp2
94Annotation score:

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

Similar proteinsi

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
PDB 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[»]
5HT2X-ray1.43A/B118-370[»]
5INKX-ray2.15A/B118-370[»]
5INLX-ray1.55A/B118-370[»]
5INMX-ray2.40A/B/C/D/E118-370[»]
5INNX-ray2.80A/B/C/D/E118-370[»]
5INPX-ray1.95A/B118-370[»]
5INQX-ray1.85A/B118-370[»]
5J3ZX-ray1.80A/B118-370[»]
5J42X-ray1.70A/B118-370[»]
5TVPX-ray2.40A/B/E/G/I/K/M/O118-370[»]
5TVQX-ray2.35A118-370[»]
ProteinModelPortaliQ9JJX7
SMRiQ9JJX7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi207835, 2 interactors
STRINGi10090.ENSMUSP00000035660

Chemistry databases

BindingDBiQ9JJX7
ChEMBLiCHEMBL3813588

PTM databases

iPTMnetiQ9JJX7
PhosphoSitePlusiQ9JJX7

Proteomic databases

EPDiQ9JJX7
MaxQBiQ9JJX7
PaxDbiQ9JJX7
PeptideAtlasiQ9JJX7
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
OrthoDBiEOG091G0FBI
PhylomeDBiQ9JJX7
TreeFamiTF314813

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiTdp2 mouse
PROiPR:Q9JJX7
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000035958 Expressed in 284 organ(s), highest expression level in cochlea
CleanExiMM_TTRAP
ExpressionAtlasiQ9JJX7 baseline and differential
GenevisibleiQ9JJX7 MM

Family and domain databases

Gene3Di3.60.10.10, 1 hit
InterProiView protein in InterPro
IPR036691 Endo/exonu/phosph_ase_sf
IPR005135 Endo/exonuclease/phosphatase
PfamiView protein in Pfam
PF03372 Exo_endo_phos, 1 hit
SUPFAMiSSF56219 SSF56219, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTYDP2_MOUSE
AccessioniPrimary (citable) accession number: Q9JJX7
Secondary accession number(s): A2RTH9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: October 1, 2000
Last modified: November 7, 2018
This is version 111 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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