TYDP2_CHICK
ID TYDP2_CHICK Reviewed; 369 AA.
AC F1NW29;
DT 31-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 59.
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;
GN Name=TDP2;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Red jungle fowl;
RX PubMed=15592404; DOI=10.1038/nature03154;
RA Hillier L.W., Miller W., Birney E., Warren W., Hardison R.C., Ponting C.P.,
RA Bork P., Burt D.W., Groenen M.A.M., Delany M.E., Dodgson J.B.,
RA Chinwalla A.T., Cliften P.F., Clifton S.W., Delehaunty K.D., Fronick C.,
RA Fulton R.S., Graves T.A., Kremitzki C., Layman D., Magrini V.,
RA McPherson J.D., Miner T.L., Minx P., Nash W.E., Nhan M.N., Nelson J.O.,
RA Oddy L.G., Pohl C.S., Randall-Maher J., Smith S.M., Wallis J.W.,
RA Yang S.-P., Romanov M.N., Rondelli C.M., Paton B., Smith J., Morrice D.,
RA Daniels L., Tempest H.G., Robertson L., Masabanda J.S., Griffin D.K.,
RA Vignal A., Fillon V., Jacobbson L., Kerje S., Andersson L.,
RA Crooijmans R.P., Aerts J., van der Poel J.J., Ellegren H., Caldwell R.B.,
RA Hubbard S.J., Grafham D.V., Kierzek A.M., McLaren S.R., Overton I.M.,
RA Arakawa H., Beattie K.J., Bezzubov Y., Boardman P.E., Bonfield J.K.,
RA Croning M.D.R., Davies R.M., Francis M.D., Humphray S.J., Scott C.E.,
RA Taylor R.G., Tickle C., Brown W.R.A., Rogers J., Buerstedde J.-M.,
RA Wilson S.A., Stubbs L., Ovcharenko I., Gordon L., Lucas S., Miller M.M.,
RA Inoko H., Shiina T., Kaufman J., Salomonsen J., Skjoedt K., Wong G.K.-S.,
RA Wang J., Liu B., Wang J., Yu J., Yang H., Nefedov M., Koriabine M.,
RA Dejong P.J., Goodstadt L., Webber C., Dickens N.J., Letunic I., Suyama M.,
RA Torrents D., von Mering C., Zdobnov E.M., Makova K., Nekrutenko A.,
RA Elnitski L., Eswara P., King D.C., Yang S.-P., Tyekucheva S.,
RA Radakrishnan A., Harris R.S., Chiaromonte F., Taylor J., He J.,
RA Rijnkels M., Griffiths-Jones S., Ureta-Vidal A., Hoffman M.M., Severin J.,
RA Searle S.M.J., Law A.S., Speed D., Waddington D., Cheng Z., Tuzun E.,
RA Eichler E., Bao Z., Flicek P., Shteynberg D.D., Brent M.R., Bye J.M.,
RA Huckle E.J., Chatterji S., Dewey C., Pachter L., Kouranov A.,
RA Mourelatos Z., Hatzigeorgiou A.G., Paterson A.H., Ivarie R., Brandstrom M.,
RA Axelsson E., Backstrom N., Berlin S., Webster M.T., Pourquie O.,
RA Reymond A., Ucla C., Antonarakis S.E., Long M., Emerson J.J., Betran E.,
RA Dupanloup I., Kaessmann H., Hinrichs A.S., Bejerano G., Furey T.S.,
RA Harte R.A., Raney B., Siepel A., Kent W.J., Haussler D., Eyras E.,
RA Castelo R., Abril J.F., Castellano S., Camara F., Parra G., Guigo R.,
RA Bourque G., Tesler G., Pevzner P.A., Smit A., Fulton L.A., Mardis E.R.,
RA Wilson R.K.;
RT "Sequence and comparative analysis of the chicken genome provide unique
RT perspectives on vertebrate evolution.";
RL Nature 432:695-716(2004).
RN [2]
RP FUNCTION.
RX PubMed=22740648; DOI=10.1093/nar/gks622;
RA Zeng Z., Sharma A., Ju L., Murai J., Umans L., Vermeire L., Pommier Y.,
RA Takeda S., Huylebroeck D., Caldecott K.W., El-Khamisy S.F.;
RT "TDP2 promotes repair of topoisomerase I-mediated DNA damage in the absence
RT of TDP1.";
RL Nucleic Acids Res. 40:8371-8380(2012).
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. Hydrolyzes 5'-phosphoglycolates on protruding 5' ends
CC on DNA double-strand breaks (DSBs) due to DNA damage by radiation and
CC free radicals. The 5'-tyrosyl DNA phosphodiesterase activity can enable
CC the repair of TOP2-induced DSBs without the need for nuclease activity,
CC creating a 'clean' DSB with 5'-phosphate termini that are ready for
CC ligation (By similarity). Has also 3'-tyrosyl DNA phosphodiesterase
CC activity, but less efficiently and much slower than TDP1.
CC {ECO:0000250|UniProtKB:Q9JJX7, ECO:0000269|PubMed:22740648}.
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 -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O95551}. Nucleus,
CC PML body {ECO:0000250|UniProtKB:O95551}.
CC -!- MISCELLANEOUS: Can partially complement the absence of TDP1 due to its
CC weak 3'-tyrosyl DNA phosphodiesterase activity.
CC {ECO:0000305|PubMed:22740648}.
CC -!- SIMILARITY: Belongs to the CCR4/nocturin family. TTRAP/TDP2 subfamily.
CC {ECO:0000305}.
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DR EMBL; AADN02008334; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001263313.1; NM_001276384.1.
DR AlphaFoldDB; F1NW29; -.
DR SMR; F1NW29; -.
DR STRING; 9031.ENSGALP00000022145; -.
DR PaxDb; F1NW29; -.
DR PRIDE; F1NW29; -.
DR Ensembl; ENSGALT00000085077; ENSGALP00000064624; ENSGALG00000013637.
DR GeneID; 421007; -.
DR KEGG; gga:421007; -.
DR CTD; 51567; -.
DR VEuPathDB; HostDB:geneid_421007; -.
DR eggNOG; KOG2756; Eukaryota.
DR GeneTree; ENSGT00390000014242; -.
DR HOGENOM; CLU_047318_0_0_1; -.
DR InParanoid; F1NW29; -.
DR OMA; AENDWDM; -.
DR OrthoDB; 1612152at2759; -.
DR TreeFam; TF314813; -.
DR PRO; PR:F1NW29; -.
DR Proteomes; UP000000539; Chromosome 2.
DR Bgee; ENSGALG00000013637; Expressed in ovary and 13 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016605; C:PML body; IBA:GO_Central.
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:0006302; P:double-strand break repair; ISS:UniProtKB.
DR Gene3D; 3.60.10.10; -; 1.
DR InterPro; IPR036691; Endo/exonu/phosph_ase_sf.
DR InterPro; IPR005135; Endo/exonuclease/phosphatase.
DR InterPro; IPR009060; UBA-like_sf.
DR Pfam; PF03372; Exo_endo_phos; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR SUPFAM; SSF56219; SSF56219; 1.
PE 3: Inferred from homology;
KW Developmental protein; DNA damage; DNA repair; Hydrolase; Magnesium;
KW Metal-binding; Nuclease; Nucleus; Reference proteome.
FT CHAIN 1..369
FT /note="Tyrosyl-DNA phosphodiesterase 2"
FT /id="PRO_0000419986"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 80..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 127..131
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT REGION 233..238
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT REGION 271..273
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT COMPBIAS 1..17
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 97..117
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 269
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:O95551"
FT BINDING 129
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT BINDING 159
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT SITE 185
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT SITE 304
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT SITE 322
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
FT SITE 358
FT /note="Interaction with 5' end of substrate DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9JJX7"
SQ SEQUENCE 369 AA; 41002 MW; 81B49505F191718E CRC64;
MELEARAEPR SPRAGRGEEE EDEDEELRLA KRRKVLCSEF AAVTSSDEAV ASGFLAGSGW
HLERALDAYF EAPMNEQTTA AAAGGGSAGP GSCIDLTADD TASNTSSSGA DSKQQDDDSS
FSLITWNIDG LDLGNLQERA RGVCSYLALY SPDVVFLQEV IPPYLCILQR RAGGYTIIPG
NVDGYFTAML LKKPRVKVLK QEIIRFPTTS MMRNLLVVHV NISGNELCLM TSHLESTRDH
SKERMKQLQI VLNKMQEESQ STTVIFGGDT NLRDSEVAKL GGLPKNITDI WEFLGKPQHC
RYTWDTSSNT NLRIESKCKL RFDRLYFRPA AEGGHIIPRN MDLIGLEKLD CGRFPSDHWG
LLCRFDVIL
