ID TYDP2_BOVIN Reviewed; 364 AA.
AC A7YWI9;
DT 15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 1.
DT 24-JAN-2024, entry version 89.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Basal ganglia;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC134603; AAI34604.1; -; mRNA.
DR RefSeq; NP_001098811.1; NM_001105341.1.
DR AlphaFoldDB; A7YWI9; -.
DR SMR; A7YWI9; -.
DR STRING; 9913.ENSBTAP00000000472; -.
DR PaxDb; 9913-ENSBTAP00000000472; -.
DR Ensembl; ENSBTAT00000000472.6; ENSBTAP00000000472.5; ENSBTAG00000000365.6.
DR GeneID; 507579; -.
DR KEGG; bta:507579; -.
DR CTD; 51567; -.
DR VEuPathDB; HostDB:ENSBTAG00000000365; -.
DR VGNC; VGNC:35714; TDP2.
DR eggNOG; KOG2756; Eukaryota.
DR GeneTree; ENSGT00390000014242; -.
DR HOGENOM; CLU_047318_0_0_1; -.
DR InParanoid; A7YWI9; -.
DR OMA; AENDWDM; -.
DR OrthoDB; 276861at2759; -.
DR TreeFam; TF314813; -.
DR Reactome; R-BTA-5693571; Nonhomologous End-Joining (NHEJ).
DR Proteomes; UP000009136; Chromosome 23.
DR Bgee; ENSBTAG00000000365; Expressed in duodenum and 104 other cell types or tissues.
DR GO; GO:0016235; C:aggresome; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
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; IEA:Ensembl.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0048666; P:neuron development; ISS:UniProtKB.
DR CDD; cd09080; TDP2; 1.
DR CDD; cd14344; UBA_TYDP2; 1.
DR Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 1.
DR Gene3D; 3.60.10.10; Endonuclease/exonuclease/phosphatase; 1.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR009060; UBA-like_sf.
DR PANTHER; PTHR15822; TRAF AND TNF RECEPTOR-ASSOCIATED PROTEIN; 1.
DR PANTHER; PTHR15822:SF4; TYROSYL-DNA PHOSPHODIESTERASE 2; 1.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR Pfam; PF14555; UBA_4; 1.
DR SUPFAM; SSF56219; DNase I-like; 1.
DR SUPFAM; SSF46934; UBA-like; 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..364
FT /note="Tyrosyl-DNA phosphodiesterase 2"
FT /id="PRO_0000390449"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 68..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 122..126
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT REGION 228..233
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT REGION 266..268
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT COMPBIAS 86..108
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 264
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:O95551"
FT BINDING 124
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT BINDING 154
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT SITE 180
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT SITE 299
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT SITE 317
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT SITE 353
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 88
FT /note="Phosphothreonine; by ACVR1B"
FT /evidence="ECO:0000250|UniProtKB:O95551"
FT MOD_RES 92
FT /note="Phosphothreonine; by ACVR1B"
FT /evidence="ECO:0000250|UniProtKB:O95551"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95551"
FT CROSSLNK 23
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O95551"
SQ 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
//
