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Protein

Tyrosyl-DNA phosphodiesterase 2

Gene

Tdp2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript 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 (By similarity).By similarity

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 bindingi126 – 1261MagnesiumBy similarity
Metal bindingi158 – 1581MagnesiumBy similarity
Metal bindingi268 – 2681MagnesiumBy similarity
Metal bindingi270 – 2701MagnesiumBy similarity
Metal bindingi354 – 3541MagnesiumBy similarity
Active sitei355 – 3551Proton acceptorBy similarity
Metal bindingi355 – 3551MagnesiumBy 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

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1560342. 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 – 366366Tyrosyl-DNA phosphodiesterase 2PRO_0000390450Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei95 – 951Phosphothreonine; by ACVR1BBy similarity

Post-translational modificationi

Ubiquitinated by TRAF6.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ3T1H5.

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

STRINGi10116.ENSRNOP00000056326.

Structurei

3D structure databases

ProteinModelPortaliQ3T1H5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the CCR4/nocturin family.Curated

Phylogenomic databases

eggNOGiKOG2756. Eukaryota.
ENOG410XP85. LUCA.
HOVERGENiHBG079625.
InParanoidiQ3T1H5.
KOiK19619.
PhylomeDBiQ3T1H5.

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.

Q3T1H5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASGSSSDAA ESAEPAAAPA AAETEEDQVK RRRLQSLGFA LVTSCDTTVA
60 70 80 90 100
STFLSENNWQ TKKALSAFFE QPENDLARPH QPPTSSKSED YVDLTNEDAN
110 120 130 140 150
DTTILETSPS GTPLEDSSTI SFITWNIDGL DGCNLPERAR GVCSCLALYS
160 170 180 190 200
PDVVFLQEVI PSYCAYLRKR ARTYNIITGN EEGYFTAILL KKGRVKFKGQ
210 220 230 240 250
EIIPFPNTKM MRNLLCVNVS LGGNEFCLMT SHLESTRKHS AERINQLKTV
260 270 280 290 300
FQKMQEATDS TTVIFAGDTN LRDQEVIKCG GLPDNVFDAW EFLGKPKHCR
310 320 330 340 350
YTWDTKANDN LRIPAACKHR FDRIFFRAEE GHLIPQSLDL IGLERLDCGR
360
FPSDHWGLLC TLNVVL
Length:366
Mass (Da):40,793
Last modified:October 11, 2005 - v1
Checksum:iD64F045D2FF80E9A
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC101920 mRNA. Translation: AAI01921.1.
RefSeqiNP_001030119.1. NM_001034947.1.
UniGeneiRn.115091.

Genome annotation databases

GeneIDi498749.
KEGGirno:498749.
UCSCiRGD:1560342. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC101920 mRNA. Translation: AAI01921.1.
RefSeqiNP_001030119.1. NM_001034947.1.
UniGeneiRn.115091.

3D structure databases

ProteinModelPortaliQ3T1H5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000056326.

Proteomic databases

PaxDbiQ3T1H5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi498749.
KEGGirno:498749.
UCSCiRGD:1560342. rat.

Organism-specific databases

CTDi51567.
RGDi1560342. Tdp2.

Phylogenomic databases

eggNOGiKOG2756. Eukaryota.
ENOG410XP85. LUCA.
HOVERGENiHBG079625.
InParanoidiQ3T1H5.
KOiK19619.
PhylomeDBiQ3T1H5.

Miscellaneous databases

PROiQ3T1H5.

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

  1. "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: Prostate.

Entry informationi

Entry nameiTYDP2_RAT
AccessioniPrimary (citable) accession number: Q3T1H5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 2009
Last sequence update: October 11, 2005
Last modified: June 8, 2016
This is version 64 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.