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Tyrosyl-DNA phosphodiesterase 2 (Tyr-DNA phosphodiesterase 2) (EC 3.1.4.-) (5'-tyrosyl-DNA phosphodiesterase) (5'-Tyr-DNA phosphodiesterase) (TRAF and TNF receptor-associated protein)

 TYDP2_BOVIN             Reviewed;         364 AA.
A7YWI9;
15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
23-OCT-2007, sequence version 1.
16-JAN-2019, entry version 68.
RecName: Full=Tyrosyl-DNA phosphodiesterase 2;
Short=Tyr-DNA phosphodiesterase 2;
EC=3.1.4.-;
AltName: Full=5'-tyrosyl-DNA phosphodiesterase;
Short=5'-Tyr-DNA phosphodiesterase;
AltName: Full=TRAF and TNF receptor-associated protein;
Name=TDP2; Synonyms=TTRAP;
Bos taurus (Bovine).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia;
Pecora; Bovidae; Bovinae; Bos.
NCBI_TaxID=9913;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=Hereford; TISSUE=Basal ganglia;
NIH - Mammalian Gene Collection (MGC) project;
Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
-!- 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. Thereby, protects the transcription of
many genes involved in neurological development and maintenance
from the abortive activity of TOP2. 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.
{ECO:0000250|UniProtKB:O95551}.
-!- COFACTOR:
Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
Note=Magnesium. Can use other divalent cations as cofactor in
vitro, such as manganese. {ECO:0000250};
-!- SUBUNIT: Interacts with TRAF2, TRAF3, TRAF5, TRAF6, TNFRSF8/CD30,
TNFRSF5/CD40, TNFRSF1B/TNF-R75, ETS1, ETS2, FLI1, SMAD3 and
ACVR1B/ALK4. {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Nucleus, PML body
{ECO:0000250}. Nucleus, nucleolus {ECO:0000250}. Note=Localizes to
nucleolar cavities following stress; localization to nucleolus is
dependent on PML protein. {ECO:0000250}.
-!- PTM: Ubiquitinated by TRAF6. {ECO:0000250}.
-!- SIMILARITY: Belongs to the CCR4/nocturin family. {ECO:0000305}.
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EMBL; BC134603; AAI34604.1; -; mRNA.
RefSeq; NP_001098811.1; NM_001105341.1.
UniGene; Bt.13626; -.
ProteinModelPortal; A7YWI9; -.
SMR; A7YWI9; -.
STRING; 9913.ENSBTAP00000000472; -.
PaxDb; A7YWI9; -.
Ensembl; ENSBTAT00000000472; ENSBTAP00000000472; ENSBTAG00000000365.
GeneID; 507579; -.
KEGG; bta:507579; -.
CTD; 51567; -.
VGNC; VGNC:35714; TDP2.
eggNOG; KOG2756; Eukaryota.
eggNOG; ENOG410XP85; LUCA.
GeneTree; ENSGT00390000014242; -.
HOVERGEN; HBG079625; -.
InParanoid; A7YWI9; -.
KO; K19619; -.
OMA; TGNEEGY; -.
OrthoDB; 1612152at2759; -.
TreeFam; TF314813; -.
Reactome; R-BTA-5693571; Nonhomologous End-Joining (NHEJ).
Proteomes; UP000009136; Chromosome 23.
Bgee; ENSBTAG00000000365; Expressed in 10 organ(s), highest expression level in colon.
GO; GO:0016235; C:aggresome; IEA:Ensembl.
GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
GO; GO:0016605; C:PML body; ISS:UniProtKB.
GO; GO:0070260; F:5'-tyrosyl-DNA phosphodiesterase activity; ISS:UniProtKB.
GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
GO; GO:0004518; F:nuclease activity; IEA:UniProtKB-KW.
GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
GO; GO:0036317; F:tyrosyl-RNA phosphodiesterase activity; IEA:Ensembl.
GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
GO; GO:0048666; P:neuron development; ISS:UniProtKB.
Gene3D; 3.60.10.10; -; 1.
InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
InterPro; IPR005135; Endo/exonuclease/phosphatase.
InterPro; IPR009060; UBA-like_sf.
Pfam; PF03372; Exo_endo_phos; 1.
SUPFAM; SSF46934; SSF46934; 1.
SUPFAM; SSF56219; SSF56219; 1.
2: Evidence at transcript level;
Acetylation; Complete proteome; DNA damage; DNA repair; Hydrolase;
Isopeptide bond; Magnesium; Metal-binding; Nuclease; Nucleus;
Phosphoprotein; Reference proteome; Ubl conjugation.
CHAIN 1 364 Tyrosyl-DNA phosphodiesterase 2.
/FTId=PRO_0000390449.
ACT_SITE 353 353 Proton acceptor. {ECO:0000250}.
METAL 122 122 Magnesium. {ECO:0000250}.
METAL 154 154 Magnesium. {ECO:0000250}.
METAL 264 264 Magnesium. {ECO:0000250}.
METAL 266 266 Magnesium. {ECO:0000250}.
METAL 352 352 Magnesium. {ECO:0000250}.
METAL 353 353 Magnesium. {ECO:0000250}.
MOD_RES 1 1 N-acetylmethionine.
{ECO:0000250|UniProtKB:O95551}.
MOD_RES 88 88 Phosphothreonine; by ACVR1B.
{ECO:0000250|UniProtKB:O95551}.
MOD_RES 92 92 Phosphothreonine; by ACVR1B.
{ECO:0000250|UniProtKB:O95551}.
MOD_RES 95 95 Phosphoserine.
{ECO:0000250|UniProtKB:O95551}.
CROSSLNK 23 23 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in SUMO2).
{ECO:0000250|UniProtKB:O95551}.
SEQUENCE 364 AA; 40826 MW; 1BEF10BA57C1199A CRC64;
MERNSGPEAG PEAELEEGEP EVKKRKLMCV EFASVASCDA AVAQCYLAEN DWEMERALNS
YFEPAVEESA SESRPESLSE PGSCVDLTKE ETNDSISSKT STSEDKSVQQ EDGSVFSFIT
WNIDGLDMNN LLERARGVCS YLTLYSPDVI FLQEVIPPYY AYLKKKASSY KIITGREEGY
FTAIMLKKSR VKFKSQEIIP FPNTQMMRNL LCVHVSVSGN ELCLMTSHLE STRGHAKERM
NQFKMVLEKM QEAPGSATVI FAGDTNLRDQ EVTKCGGLPN NILDVWEFLG KPKHCQYTWD
TQMNSNLGIA ANCKLRFDRI FFRAAAEGGH IIPQSLDLLG LEKLDCGRFP SDHWGLLCTL
DVIL


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Related Genes :
[TDP2 EAP2 TTRAP AD-022] Tyrosyl-DNA phosphodiesterase 2 (Tyr-DNA phosphodiesterase 2) (hTDP2) (EC 3.1.4.-) (5'-tyrosyl-DNA phosphodiesterase) (5'-Tyr-DNA phosphodiesterase) (ETS1-associated protein 2) (ETS1-associated protein II) (EAPII) (TRAF and TNF receptor-associated protein) (Tyrosyl-RNA phosphodiesterase) (VPg unlinkase)
[Tdp2 Ttrap] Tyrosyl-DNA phosphodiesterase 2 (Tyr-DNA phosphodiesterase 2) (EC 3.1.4.-) (5'-tyrosyl-DNA phosphodiesterase) (5'-Tyr-DNA phosphodiesterase) (TRAF and TNF receptor-associated protein)
[TDP2 TTRAP] Tyrosyl-DNA phosphodiesterase 2 (Tyr-DNA phosphodiesterase 2) (EC 3.1.4.-) (5'-tyrosyl-DNA phosphodiesterase) (5'-Tyr-DNA phosphodiesterase) (TRAF and TNF receptor-associated protein)
[TDP1] Tyrosyl-DNA phosphodiesterase 1 (Tyr-DNA phosphodiesterase 1) (EC 3.1.4.-)
[Tdp2 Ttrap] Tyrosyl-DNA phosphodiesterase 2 (Tyr-DNA phosphodiesterase 2) (EC 3.1.4.-) (5'-tyrosyl-DNA phosphodiesterase) (5'-Tyr-DNA phosphodiesterase) (TRAF and TNF receptor-associated protein)
[TDP1 YBR223C YBR1520] Tyrosyl-DNA phosphodiesterase 1 (Tyr-DNA phosphodiesterase 1) (EC 3.1.4.-)
[Tdp1] Tyrosyl-DNA phosphodiesterase 1 (Tyr-DNA phosphodiesterase 1) (EC 3.1.4.-) (Protein expressed in male leptotene and zygotene spermatocytes 501) (MLZ-501)
[gkt Tdp1 CG8825 CG8826] Probable tyrosyl-DNA phosphodiesterase (Tyr-DNA phosphodiesterase) (EC 3.1.4.-) (Protein glaikit)
[regA pde2 DDB_G0284331] 3',5'-cyclic-nucleotide phosphodiesterase regA (PDEase regA) (EC 3.1.4.53) (Phosphodiesterase 2) (DdPDE2) (Response regulator protein A) (cAMP-specific 3',5'-cAMP phosphodiesterase 2)
[] Protein VP3 [Includes: 2',5'-phosphodiesterase (EC 3.1.4.-); mRNA guanylyltransferase (EC 2.7.7.50); mRNA (guanine-N(7)-)-methyltransferase (EC 2.1.1.56)]
[ENPP1 M6S1 NPPS PC1 PDNP1] Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (E-NPP 1) (Membrane component chromosome 6 surface marker 1) (Phosphodiesterase I/nucleotide pyrophosphatase 1) (Plasma-cell membrane glycoprotein PC-1) [Includes: Alkaline phosphodiesterase I (EC 3.1.4.1); Nucleotide pyrophosphatase (NPPase) (EC 3.6.1.9) (Nucleotide diphosphatase)]
[Enpp1 Npps Pc1 Pdnp1] Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (E-NPP 1) (Lymphocyte antigen 41) (Ly-41) (Phosphodiesterase I/nucleotide pyrophosphatase 1) (Plasma-cell membrane glycoprotein PC-1) [Includes: Alkaline phosphodiesterase I (EC 3.1.4.1); Nucleotide pyrophosphatase (NPPase) (EC 3.6.1.9) (Nucleotide diphosphatase)]
[pdeD gbpA pde5 DDB_G0274383] cGMP-dependent 3',5'-cGMP phosphodiesterase A (EC 3.1.4.35) (Cyclic GMP-binding protein A) (Phosphodiesterase 5) (DdPDE5) (Phosphodiesterase D)
[pdeE gbpB pde6 DDB_G0276027] cAMP/cGMP-dependent 3',5'-cAMP/cGMP phosphodiesterase B (EC 3.1.4.35) (EC 3.1.4.53) (Cyclic GMP-binding protein B) (Phosphodiesterase 6) (DdPDE6) (Phosphodiesterase E)
[] Genome polyprotein [Cleaved into: Capsid protein C (Capsid protein) (Core protein); Protein prM (Precursor membrane protein); Peptide pr (Peptide precursor); Small envelope protein M (Matrix protein); Envelope protein E; Non-structural protein 1 (NS1); Non-structural protein 2A (NS2A); Serine protease subunit NS2B (Flavivirin protease NS2B regulatory subunit) (Non-structural protein 2B); Serine protease NS3 (EC 3.4.21.91) (EC 3.6.1.15) (EC 3.6.4.13) (Flavivirin protease NS3 catalytic subunit) (Non-structural protein 3); Non-structural protein 4A (NS4A); Peptide 2k; Non-structural protein 4B (NS4B); RNA-directed RNA polymerase NS5 (EC 2.1.1.56) (EC 2.1.1.57) (EC 2.7.7.48) (Non-structural protein 5)]
[dtd yihZ b3887 JW3858] D-aminoacyl-tRNA deacylase (DTD) (EC 3.1.1.96) (D-tyrosyl RNA deacylase) (D-tyrosyl-tRNA(Tyr) deacylase) (Gly-tRNA(Ala) deacylase) (EC 3.1.1.-) (Gly-tRNA(Gly) deacylase)
[Traf2] TNF receptor-associated factor 2 (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRAF2) (RING-type E3 ubiquitin transferase TRAF2)
[Pde1c] Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C (Cam-PDE 1C) (3',5'-cyclic-AMP phosphodiesterase) (EC 3.1.4.-) (3',5'-cyclic-GMP phosphodiesterase) (EC 3.1.4.35)
[cpdA icc Rv0805] 3',5'-cyclic adenosine monophosphate phosphodiesterase CpdA (3',5'-cyclic AMP phosphodiesterase) (cAMP phosphodiesterase) (EC 3.1.4.53)
[PDE1C] Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C (Cam-PDE 1C) (3',5'-cyclic-AMP phosphodiesterase) (EC 3.1.4.-) (3',5'-cyclic-GMP phosphodiesterase) (EC 3.1.4.35) (Hcam3)
[PDE6C PDEA2] Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' (EC 3.1.4.35) (cGMP phosphodiesterase 6C)
[Pde1c] Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C (Cam-PDE 1C) (3',5'-cyclic-AMP phosphodiesterase) (EC 3.1.4.-) (3',5'-cyclic-GMP phosphodiesterase) (EC 3.1.4.35)
[PDE11A] Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A (EC 3.1.4.35) (EC 3.1.4.53) (cAMP and cGMP phosphodiesterase 11A)
[PDE4D DPDE3] cAMP-specific 3',5'-cyclic phosphodiesterase 4D (EC 3.1.4.53) (DPDE3) (PDE43)
[] Genome polyprotein [Cleaved into: Core protein p21 (Capsid protein C) (p21); Core protein p19; Envelope glycoprotein E1 (gp32) (gp35); Envelope glycoprotein E2 (NS1) (gp68) (gp70); p7; Protease NS2-3 (p23) (EC 3.4.22.-); Serine protease NS3 (EC 3.4.21.98) (EC 3.6.1.15) (EC 3.6.4.13) (Hepacivirin) (NS3P) (p70); Non-structural protein 4A (NS4A) (p8); Non-structural protein 4B (NS4B) (p27); Non-structural protein 5A (NS5A) (p56); RNA-directed RNA polymerase (EC 2.7.7.48) (NS5B) (p68)]
[ENPP3 PDNP3] Ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (E-NPP 3) (NPP3) (Phosphodiesterase I beta) (PD-Ibeta) (Phosphodiesterase I/nucleotide pyrophosphatase 3) (CD antigen CD203c) [Includes: Alkaline phosphodiesterase I (EC 3.1.4.1); Nucleotide pyrophosphatase (NPPase) (EC 3.6.1.9) (Nucleotide diphosphatase)]
[PDE2A] cGMP-dependent 3',5'-cyclic phosphodiesterase (EC 3.1.4.17) (Cyclic GMP-stimulated phosphodiesterase) (CGS-PDE) (cGSPDE)
[Pde2a] cGMP-dependent 3',5'-cyclic phosphodiesterase (EC 3.1.4.17) (Cyclic GMP-stimulated phosphodiesterase) (CGS-PDE) (cGSPDE)
[TRAF2 TRAP3] TNF receptor-associated factor 2 (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRAF2) (RING-type E3 ubiquitin transferase TRAF2) (Tumor necrosis factor type 2 receptor-associated protein 3)
[GDPD5 GDE2 PP6037 PP9363 UNQ1850/PRO3580] Glycerophosphodiester phosphodiesterase domain-containing protein 5 (EC 3.1.4.11) (Glycerophosphodiester phosphodiesterase 2)

Bibliography :
[29353210] VPg unlinkase/TDP2 in cardiovirus infected cells: Re-localization and proteolytic cleavage.
[26715620] Divergent Requirement for a DNA Repair Enzyme during Enterovirus Infections.
[21030584] TDP2/TTRAP is the major 5'-tyrosyl DNA phosphodiesterase activity in vertebrate cells and is critical for cellular resistance to topoisomerase II-induced DNA damage.
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