TYDP1_YEAST
ID TYDP1_YEAST Reviewed; 544 AA.
AC P38319; D6VQM0;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Tyrosyl-DNA phosphodiesterase 1;
DE Short=Tyr-DNA phosphodiesterase 1;
DE EC=3.1.4.- {ECO:0000269|PubMed:16751265};
GN Name=TDP1; OrderedLocusNames=YBR223C; ORFNames=YBR1520;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7813418; DOI=10.1002/j.1460-2075.1994.tb06923.x;
RA Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C.,
RA Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M.,
RA Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M.,
RA Cziepluch C., Demolis N., Delaveau T., Doignon F., Domdey H.,
RA Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D.,
RA Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N.,
RA Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J.,
RA Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C.,
RA Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P.,
RA Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y.,
RA Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F.,
RA Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E.,
RA Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M.,
RA Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B.,
RA Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L.,
RA Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M.,
RA Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S.,
RA Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K.,
RA Mewes H.-W., Kleine K.;
RT "Complete DNA sequence of yeast chromosome II.";
RL EMBO J. 13:5795-5809(1994).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP FUNCTION.
RX PubMed=10521354; DOI=10.1126/science.286.5439.552;
RA Pouliot J.J., Yao K.C., Robertson C.A., Nash H.A.;
RT "Yeast gene for a Tyr-DNA phosphodiesterase that repairs topoisomerase I
RT complexes.";
RL Science 286:552-555(1999).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=12206772; DOI=10.1016/s0022-2836(02)00652-6;
RA Teixeira M.T., Dujon B., Fabre E.;
RT "Genome-wide nuclear morphology screen identifies novel genes involved in
RT nuclear architecture and gene-silencing in Saccharomyces cerevisiae.";
RL J. Mol. Biol. 321:551-561(2002).
RN [5]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-182, AND ACTIVE SITE.
RX PubMed=16751265; DOI=10.1073/pnas.0603455103;
RA Nitiss K.C., Malik M., He X., White S.W., Nitiss J.L.;
RT "Tyrosyl-DNA phosphodiesterase (Tdp1) participates in the repair of Top2-
RT mediated DNA damage.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:8953-8958(2006).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), MUTAGENESIS OF HIS-432, AND ACTIVE
RP SITE.
RX PubMed=17707402; DOI=10.1016/j.jmb.2007.07.055;
RA He X., van Waardenburg R.C.A.M., Babaoglu K., Price A.C., Nitiss K.C.,
RA Nitiss J.L., Bjornsti M.-A., White S.W.;
RT "Mutation of a conserved active site residue converts tyrosyl-DNA
RT phosphodiesterase I into a DNA topoisomerase I-dependent poison.";
RL J. Mol. Biol. 372:1070-1081(2007).
CC -!- FUNCTION: DNA repair enzyme that can remove a variety of covalent
CC adducts from DNA through hydrolysis of a 3'-phosphodiester bond, giving
CC rise to DNA with a free 3' phosphate. Catalyzes the hydrolysis of dead-
CC end complexes between DNA and the topoisomerase I active site tyrosine
CC residue. Hydrolyzes 3'-phosphoglycolates on protruding 3' ends on DNA
CC double-strand breaks due to DNA damage by radiation and free radicals.
CC Cleaves also 5' phosphotyrosyl adducts resulting from dead-end
CC complexes between DNA and the active site tyrosine of topoisomerase II.
CC Contributes to DNA repair after radiation damage. Acts on blunt-ended
CC double-strand DNA breaks and on single-stranded DNA. May have low
CC 3'exonuclease activity and may be able to remove a single nucleoside
CC from the 3'end of DNA and RNA molecules with 3'hydroxyl groups. Has no
CC exonuclease activity towards DNA or RNA with a 3'phosphate (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:10521354,
CC ECO:0000269|PubMed:16751265}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12206772}.
CC -!- MISCELLANEOUS: Present with 2130 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the tyrosyl-DNA phosphodiesterase family.
CC {ECO:0000305}.
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DR EMBL; Z36092; CAA85186.1; -; Genomic_DNA.
DR EMBL; BK006936; DAA07340.1; -; Genomic_DNA.
DR PIR; S46099; S46099.
DR RefSeq; NP_009782.3; NM_001178571.3.
DR PDB; 1Q32; X-ray; 2.03 A; A/B/C/D=1-544.
DR PDB; 3SQ3; X-ray; 2.50 A; A/B/C/D=79-539.
DR PDB; 3SQ5; X-ray; 2.30 A; A/B/C/D=79-539.
DR PDB; 3SQ7; X-ray; 2.00 A; A/B/C/D=79-539.
DR PDB; 3SQ8; X-ray; 2.10 A; A/B/C/D=79-539.
DR PDBsum; 1Q32; -.
DR PDBsum; 3SQ3; -.
DR PDBsum; 3SQ5; -.
DR PDBsum; 3SQ7; -.
DR PDBsum; 3SQ8; -.
DR AlphaFoldDB; P38319; -.
DR SMR; P38319; -.
DR BioGRID; 32920; 112.
DR DIP; DIP-4945N; -.
DR IntAct; P38319; 16.
DR MINT; P38319; -.
DR STRING; 4932.YBR223C; -.
DR CarbonylDB; P38319; -.
DR MaxQB; P38319; -.
DR PaxDb; P38319; -.
DR PRIDE; P38319; -.
DR EnsemblFungi; YBR223C_mRNA; YBR223C; YBR223C.
DR GeneID; 852525; -.
DR KEGG; sce:YBR223C; -.
DR SGD; S000000427; TDP1.
DR VEuPathDB; FungiDB:YBR223C; -.
DR eggNOG; KOG2031; Eukaryota.
DR GeneTree; ENSGT00390000002211; -.
DR HOGENOM; CLU_010413_2_1_1; -.
DR InParanoid; P38319; -.
DR OMA; PSHSKFY; -.
DR BioCyc; YEAST:G3O-29158-MON; -.
DR BRENDA; 3.1.4.1; 984.
DR EvolutionaryTrace; P38319; -.
DR PRO; PR:P38319; -.
DR Proteomes; UP000002311; Chromosome II.
DR RNAct; P38319; protein.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0017005; F:3'-tyrosyl-DNA phosphodiesterase activity; IDA:SGD.
DR GO; GO:0070260; F:5'-tyrosyl-DNA phosphodiesterase activity; IDA:SGD.
DR GO; GO:0003690; F:double-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0004527; F:exonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0006281; P:DNA repair; IMP:SGD.
DR GO; GO:0006302; P:double-strand break repair; IBA:GO_Central.
DR GO; GO:0000012; P:single strand break repair; IBA:GO_Central.
DR InterPro; IPR010347; Tdp1.
DR PANTHER; PTHR12415; PTHR12415; 1.
DR Pfam; PF06087; Tyr-DNA_phospho; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA damage; DNA repair; Exonuclease; Hydrolase; Nuclease;
KW Nucleus; Reference proteome; Repeat.
FT CHAIN 1..544
FT /note="Tyrosyl-DNA phosphodiesterase 1"
FT /id="PRO_0000212490"
FT REGION 312..316
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT ACT_SITE 182
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:16751265"
FT ACT_SITE 432
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000269|PubMed:17707402"
FT BINDING 184
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT BINDING 434
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT SITE 467
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT MUTAGEN 182
FT /note="H->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:16751265"
FT MUTAGEN 432
FT /note="H->N: Strongly reduced release of the covalent
FT intermediate with DNA that is formed during the enzyme
FT reaction, leading to the accumulation of toxic adducts. No
FT effect on bleomycin sensitivity."
FT /evidence="ECO:0000269|PubMed:17707402"
FT MUTAGEN 432
FT /note="H->R: Interferes with the hydrolysis of the covalent
FT intermediate with DNA that is formed during the enzyme
FT reaction. No effect on bleomycin sensitivity."
FT /evidence="ECO:0000269|PubMed:17707402"
FT STRAND 81..85
FT /evidence="ECO:0007829|PDB:3SQ7"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 105..109
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 114..120
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 126..130
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 139..145
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 159..165
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 168..173
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 185..190
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 193..202
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 206..210
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 215..218
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 222..224
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 232..242
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 247..252
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 254..258
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:3SQ3"
FT HELIX 282..293
FT /evidence="ECO:0007829|PDB:3SQ7"
FT TURN 294..296
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 301..309
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 311..313
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 319..321
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 325..328
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 330..334
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 336..338
FT /evidence="ECO:0007829|PDB:3SQ8"
FT HELIX 356..366
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 368..373
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 378..380
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 386..392
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 398..400
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 401..409
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 414..416
FT /evidence="ECO:0007829|PDB:3SQ7"
FT TURN 419..421
FT /evidence="ECO:0007829|PDB:3SQ7"
FT TURN 424..428
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 434..441
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 454..463
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 468..471
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 474..476
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 479..488
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 489..491
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 492..495
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 498..502
FT /evidence="ECO:0007829|PDB:3SQ7"
FT HELIX 503..505
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 516..521
FT /evidence="ECO:0007829|PDB:3SQ7"
FT STRAND 523..527
FT /evidence="ECO:0007829|PDB:3SQ3"
FT TURN 530..532
FT /evidence="ECO:0007829|PDB:3SQ7"
SQ SEQUENCE 544 AA; 62333 MW; E84C6685312DEC3F CRC64;
MSRETNFNGT KRKRSDVAEK VAQRWKSVRY SAEMENMAPV NSNNDSDDCV IVSESKIIDL
TNQEQDLSER IETNDTAKGA VFKLMKSDFY EREDFMGEVE DMITLKDIFG TETLKRSILF
SFQYELDFLL RQFHQNVENI TIVGQKGTIM PIEARAMDAT LAVILKKVKL IEITMPPFAS
HHTKLIINFY DNGECKIFLP SNNFTSMETN LPQQVCWCSP LLKIGKEGLP VPFKRSLIEY
LNSYHLKDID ELITKSVEEV NFAPLSELEF VYSTPSKFQS SGLLSFYNKL EKLSAGTSAS
DTAKHYLCQT SSIGTSLSRA RDENLWTHLM IPLFTGIMSP PAKDTAGRKK AEILPTNSLI
NEYSQRKIKP YIIFPTEQEF VTSPLKWSSS GWFHFQYLQK KSYYEMLRNK FKVFYKQDPA
MVTRRRGTTP AHSKFYMHCA TNSAGPCDAS QVFKELEWCL YTSANLSQTA WGTVSRKPRN
YEAGVLYHSR RLANTRKVTC RTFTRDRRGC AGNPTHVAVP FTLPVIPYDL AEDECFCLAR
HEND
