TYDP2_RAT
ID TYDP2_RAT Reviewed; 366 AA.
AC Q3T1H5;
DT 15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Tyrosyl-DNA phosphodiesterase 2;
DE Short=Tyr-DNA phosphodiesterase 2;
DE EC=3.1.4.- {ECO:0000250|UniProtKB:Q9JJX7};
DE AltName: Full=5'-tyrosyl-DNA phosphodiesterase;
DE Short=5'-Tyr-DNA phosphodiesterase;
DE AltName: Full=TRAF and TNF receptor-associated protein;
GN Name=Tdp2; Synonyms=Ttrap;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: DNA repair enzyme that can remove a variety of covalent
CC adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving
CC rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead-
CC end complexes between DNA and the topoisomerase 2 (TOP2) active site
CC tyrosine residue. The 5'-tyrosyl DNA phosphodiesterase activity can
CC enable the repair of TOP2-induced DNA double-strand breaks/DSBs without
CC the need for nuclease activity, creating a 'clean' DSB with 5'-
CC phosphate termini that are ready for ligation. Thereby, protects the
CC transcription of many genes involved in neurological development and
CC maintenance from the abortive activity of TOP2. Hydrolyzes 5'-
CC phosphoglycolates on protruding 5' ends on DSBs due to DNA damage by
CC radiation and free radicals. Has preference for single-stranded DNA or
CC duplex DNA with a 4 base pair overhang as substrate. Has also 3'-
CC tyrosyl DNA phosphodiesterase activity, but less efficiently and much
CC slower than TDP1. Constitutes the major if not only 5'-tyrosyl-DNA
CC phosphodiesterase in cells. Also acts as an adapter by participating in
CC the specific activation of MAP3K7/TAK1 in response to TGF-beta:
CC associates with components of the TGF-beta receptor-TRAF6-TAK1
CC signaling module and promotes their ubiquitination dependent complex
CC formation. Involved in non-canonical TGF-beta induced signaling routes.
CC May also act as a negative regulator of ETS1 and may inhibit NF-kappa-B
CC activation. Acts as a regulator of ribosome biogenesis following
CC stress. {ECO:0000250|UniProtKB:O95551}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9JJX7};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q9JJX7};
CC Note=Binds 1 magnesium or manganese ion per subunit.
CC {ECO:0000250|UniProtKB:Q9JJX7};
CC -!- SUBUNIT: Interacts with TRAF2, TRAF3, TRAF5, TRAF6, TNFRSF8/CD30,
CC TNFRSF5/CD40, TNFRSF1B/TNF-R75, ETS1, ETS2, FLI1, SMAD3 and
CC ACVR1B/ALK4. {ECO:0000250|UniProtKB:O95551}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O95551}. Nucleus,
CC PML body {ECO:0000250|UniProtKB:O95551}. Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:O95551}. Cytoplasm
CC {ECO:0000250|UniProtKB:O95551}. Note=Localizes to nucleolar cavities
CC following stress; localization to nucleolus is dependent on PML
CC protein. {ECO:0000250|UniProtKB:O95551}.
CC -!- PTM: Ubiquitinated by TRAF6. {ECO:0000250|UniProtKB:O95551}.
CC -!- SIMILARITY: Belongs to the CCR4/nocturin family. {ECO:0000305}.
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DR EMBL; BC101920; AAI01921.1; -; mRNA.
DR RefSeq; NP_001030119.1; NM_001034947.1.
DR AlphaFoldDB; Q3T1H5; -.
DR SMR; Q3T1H5; -.
DR STRING; 10116.ENSRNOP00000056326; -.
DR PhosphoSitePlus; Q3T1H5; -.
DR PaxDb; Q3T1H5; -.
DR PRIDE; Q3T1H5; -.
DR GeneID; 498749; -.
DR KEGG; rno:498749; -.
DR UCSC; RGD:1560342; rat.
DR CTD; 51567; -.
DR RGD; 1560342; Tdp2.
DR eggNOG; KOG2756; Eukaryota.
DR InParanoid; Q3T1H5; -.
DR OrthoDB; 1612152at2759; -.
DR PhylomeDB; Q3T1H5; -.
DR Reactome; R-RNO-5693571; Nonhomologous End-Joining (NHEJ).
DR PRO; PR:Q3T1H5; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0016605; C:PML body; ISS:UniProtKB.
DR GO; GO:0070260; F:5'-tyrosyl-DNA phosphodiesterase activity; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
DR GO; GO:0004518; F:nuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0036317; F:tyrosyl-RNA phosphodiesterase activity; ISO:RGD.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0048666; P:neuron development; ISS:UniProtKB.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cytoplasm; DNA damage; DNA repair; Hydrolase; Isopeptide bond;
KW Magnesium; Metal-binding; Nuclease; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..366
FT /note="Tyrosyl-DNA phosphodiesterase 2"
FT /id="PRO_0000390450"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 126..130
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT REGION 232..237
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT REGION 270..272
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT ACT_SITE 268
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:O95551"
FT BINDING 128
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT BINDING 158
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT SITE 184
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT SITE 303
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT SITE 321
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT SITE 355
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:O95551"
FT MOD_RES 95
FT /note="Phosphothreonine; by ACVR1B"
FT /evidence="ECO:0000250|UniProtKB:O95551"
FT CROSSLNK 30
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O95551"
SQ SEQUENCE 366 AA; 40793 MW; D64F045D2FF80E9A CRC64;
MASGSSSDAA ESAEPAAAPA AAETEEDQVK RRRLQSLGFA LVTSCDTTVA STFLSENNWQ
TKKALSAFFE QPENDLARPH QPPTSSKSED YVDLTNEDAN DTTILETSPS GTPLEDSSTI
SFITWNIDGL DGCNLPERAR GVCSCLALYS PDVVFLQEVI PSYCAYLRKR ARTYNIITGN
EEGYFTAILL KKGRVKFKGQ EIIPFPNTKM MRNLLCVNVS LGGNEFCLMT SHLESTRKHS
AERINQLKTV FQKMQEATDS TTVIFAGDTN LRDQEVIKCG GLPDNVFDAW EFLGKPKHCR
YTWDTKANDN LRIPAACKHR FDRIFFRAEE GHLIPQSLDL IGLERLDCGR FPSDHWGLLC
TLNVVL
