TYDP1_ARATH
ID TYDP1_ARATH Reviewed; 605 AA.
AC Q8H1D9; Q8VZM6; Q9LXG4;
DT 22-JUL-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Tyrosyl-DNA phosphodiesterase 1 {ECO:0000303|PubMed:22214184};
DE Short=AtTDP {ECO:0000303|PubMed:20876339};
DE Short=Tyr-DNA phosphodiesterase 1 {ECO:0000303|PubMed:22214184};
DE EC=3.1.4.- {ECO:0000305};
GN Name=TDP1 {ECO:0000303|PubMed:22214184};
GN OrderedLocusNames=At5g15170 {ECO:0000312|Araport:AT5G15170};
GN ORFNames=F8M21.60 {ECO:0000312|EMBL:CAB89327.1};
OS Arabidopsis thaliana (Mouse-ear cress).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX NCBI_TaxID=3702 {ECO:0000312|EMBL:AAN13014.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DISRUPTION PHENOTYPE, TISSUE
RP SPECIFICITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 235-HIS--TYR-244.
RX PubMed=20876339; DOI=10.1104/pp.110.165068;
RA Lee S.Y., Kim H., Hwang H.J., Jeong Y.M., Na S.H., Woo J.C., Kim S.G.;
RT "Identification of tyrosyl-DNA phosphodiesterase as a novel DNA damage
RT repair enzyme in Arabidopsis.";
RL Plant Physiol. 154:1460-1469(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=11130714; DOI=10.1038/35048507;
RA Tabata S., Kaneko T., Nakamura Y., Kotani H., Kato T., Asamizu E.,
RA Miyajima N., Sasamoto S., Kimura T., Hosouchi T., Kawashima K., Kohara M.,
RA Matsumoto M., Matsuno A., Muraki A., Nakayama S., Nakazaki N., Naruo K.,
RA Okumura S., Shinpo S., Takeuchi C., Wada T., Watanabe A., Yamada M.,
RA Yasuda M., Sato S., de la Bastide M., Huang E., Spiegel L., Gnoj L.,
RA O'Shaughnessy A., Preston R., Habermann K., Murray J., Johnson D.,
RA Rohlfing T., Nelson J., Stoneking T., Pepin K., Spieth J., Sekhon M.,
RA Armstrong J., Becker M., Belter E., Cordum H., Cordes M., Courtney L.,
RA Courtney W., Dante M., Du H., Edwards J., Fryman J., Haakensen B.,
RA Lamar E., Latreille P., Leonard S., Meyer R., Mulvaney E., Ozersky P.,
RA Riley A., Strowmatt C., Wagner-McPherson C., Wollam A., Yoakum M., Bell M.,
RA Dedhia N., Parnell L., Shah R., Rodriguez M., Hoon See L., Vil D.,
RA Baker J., Kirchoff K., Toth K., King L., Bahret A., Miller B., Marra M.A.,
RA Martienssen R., McCombie W.R., Wilson R.K., Murphy G., Bancroft I.,
RA Volckaert G., Wambutt R., Duesterhoeft A., Stiekema W., Pohl T.,
RA Entian K.-D., Terryn N., Hartley N., Bent E., Johnson S., Langham S.-A.,
RA McCullagh B., Robben J., Grymonprez B., Zimmermann W., Ramsperger U.,
RA Wedler H., Balke K., Wedler E., Peters S., van Staveren M., Dirkse W.,
RA Mooijman P., Klein Lankhorst R., Weitzenegger T., Bothe G., Rose M.,
RA Hauf J., Berneiser S., Hempel S., Feldpausch M., Lamberth S.,
RA Villarroel R., Gielen J., Ardiles W., Bents O., Lemcke K., Kolesov G.,
RA Mayer K.F.X., Rudd S., Schoof H., Schueller C., Zaccaria P., Mewes H.-W.,
RA Bevan M., Fransz P.F.;
RT "Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana.";
RL Nature 408:823-826(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=cv. Columbia;
RX PubMed=27862469; DOI=10.1111/tpj.13415;
RA Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA Town C.D.;
RT "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT genome.";
RL Plant J. 89:789-804(2017).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=cv. Columbia;
RX PubMed=14593172; DOI=10.1126/science.1088305;
RA Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M.,
RA Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G.,
RA Liu S.X., Lam B., Sakano H., Wu T., Yu G., Miranda M., Quach H.L.,
RA Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C.,
RA Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J.,
RA Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A.,
RA Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C.,
RA Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X.,
RA Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M.,
RA Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K.,
RA Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A.,
RA Ecker J.R.;
RT "Empirical analysis of transcriptional activity in the Arabidopsis
RT genome.";
RL Science 302:842-846(2003).
RN [5]
RP FUNCTION, MUTAGENESIS OF HIS-236; LYS-238; HIS-466 AND LYS-468,
RP BIOPHYSICOCHEMICAL PROPERTIES, DOMAIN, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=22214184; DOI=10.1042/bj20111308;
RA Kim H., Na S.H., Lee S.Y., Jeong Y.M., Hwang H.J., Hur J.Y., Park S.H.,
RA Woo J.C., Kim S.G.;
RT "Structure-function studies of a plant tyrosyl-DNA phosphodiesterase
RT provide novel insights into DNA repair mechanisms of Arabidopsis
RT thaliana.";
RL Biochem. J. 443:49-56(2012).
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. {ECO:0000269|PubMed:20876339, ECO:0000269|PubMed:22214184}.
CC -!- ACTIVITY REGULATION: Inhibited by vanadate analogs.
CC {ECO:0000269|PubMed:22214184}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=703 nM for 18-mer single-stranded oligo with a 3'-phosphotyrosine
CC {ECO:0000269|PubMed:22214184};
CC Vmax=7.9 umol/min/mg enzyme with 18-mer single-stranded oligo with a
CC 3'-phosphotyrosine as substrate {ECO:0000269|PubMed:22214184};
CC Note=kcat is 1077 min(-1) with 18-mer single-stranded oligo with a
CC 3'-phosphotyrosine as substrate. {ECO:0000269|PubMed:22214184};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20876339,
CC ECO:0000269|PubMed:22214184}.
CC -!- TISSUE SPECIFICITY: Ubiquitous, with a low level in roots.
CC {ECO:0000269|PubMed:20876339}.
CC -!- DOMAIN: The TDP domain (123-605) is sufficient to confer the full
CC phosphodiesterase activity. {ECO:0000269|PubMed:22214184}.
CC -!- DISRUPTION PHENOTYPE: Developmental defects, including loss of apical
CC dominance, early flowering and dwarf phenotype, when homozygous
CC (PubMed:20876339). Hypersensitivity to camptothecin and failure of DNA
CC damage repair resulting in progressive cell death (PubMed:20876339). No
CC visible phenotype when heterozygous (PubMed:20876339).
CC {ECO:0000269|PubMed:20876339}.
CC -!- SIMILARITY: Belongs to the tyrosyl-DNA phosphodiesterase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB89327.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; FJ858738; ACO60340.1; -; mRNA.
DR EMBL; AL353993; CAB89327.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CP002688; AED92124.1; -; Genomic_DNA.
DR EMBL; AY064005; AAL36361.1; -; mRNA.
DR EMBL; AY150498; AAN13014.1; -; mRNA.
DR PIR; T49952; T49952.
DR RefSeq; NP_197021.2; NM_121521.4.
DR AlphaFoldDB; Q8H1D9; -.
DR SMR; Q8H1D9; -.
DR IntAct; Q8H1D9; 1.
DR STRING; 3702.AT5G15170.1; -.
DR PaxDb; Q8H1D9; -.
DR PRIDE; Q8H1D9; -.
DR ProteomicsDB; 242601; -.
DR EnsemblPlants; AT5G15170.1; AT5G15170.1; AT5G15170.
DR GeneID; 831369; -.
DR Gramene; AT5G15170.1; AT5G15170.1; AT5G15170.
DR KEGG; ath:AT5G15170; -.
DR Araport; AT5G15170; -.
DR TAIR; locus:2150931; AT5G15170.
DR eggNOG; KOG2031; Eukaryota.
DR HOGENOM; CLU_010413_1_0_1; -.
DR InParanoid; Q8H1D9; -.
DR OMA; PLIKECW; -.
DR OrthoDB; 1295967at2759; -.
DR PhylomeDB; Q8H1D9; -.
DR BRENDA; 3.1.4.1; 399.
DR PRO; PR:Q8H1D9; -.
DR Proteomes; UP000006548; Chromosome 5.
DR ExpressionAtlas; Q8H1D9; baseline and differential.
DR Genevisible; Q8H1D9; AT.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0017005; F:3'-tyrosyl-DNA phosphodiesterase activity; IDA:UniProtKB.
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; NAS:UniProtKB.
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 CDD; cd00060; FHA; 1.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR010347; Tdp1.
DR PANTHER; PTHR12415; PTHR12415; 1.
DR Pfam; PF06087; Tyr-DNA_phospho; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
PE 1: Evidence at protein level;
KW DNA damage; DNA repair; Exonuclease; Hydrolase; Nuclease; Nucleus;
KW Reference proteome.
FT CHAIN 1..605
FT /note="Tyrosyl-DNA phosphodiesterase 1"
FT /id="PRO_0000433477"
FT REGION 379..382
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT MOTIF 81..86
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:22214184"
FT ACT_SITE 236
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:22214184"
FT ACT_SITE 466
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:22214184"
FT BINDING 238
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT BINDING 468
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT SITE 489
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q9NUW8"
FT MUTAGEN 235..244
FT /note="Missing: Reduces activity 1000-fold."
FT /evidence="ECO:0000269|PubMed:20876339"
FT MUTAGEN 236
FT /note="H->A: Total loss of activity."
FT /evidence="ECO:0000269|PubMed:22214184"
FT MUTAGEN 238
FT /note="K->A: Reduces activity 10-fold."
FT /evidence="ECO:0000269|PubMed:22214184"
FT MUTAGEN 466
FT /note="H->A: Reduces activity 100-fold."
FT /evidence="ECO:0000269|PubMed:22214184"
FT MUTAGEN 468
FT /note="K->A: Reduces activity 100-fold."
FT /evidence="ECO:0000269|PubMed:22214184"
FT CONFLICT 443
FT /note="K -> E (in Ref. 4; AAL36361)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 605 AA; 68139 MW; E6AC86CC844197B5 CRC64;
MAHSQVAYLI PLKADLKEDN SSPRITLSEG PNIIGRGNVS IVDKRLSRKH ITIIVSTSGS
ASLSVDGTNP VVIRSSGDGE RKKVKPSEEV SVCNDDLIEL IPGHHFFKLV LLNGRAAKKA
RKAEDDVEAI RRFCPPNEKL PSTFRLLSVD ALPDWANTSC VSINDVIEGD VVAAILSNYM
VDIDWLMSAC PKLANIPQVM VIHGEGDGRQ EYIQRKKPAN WILHKPRLPI SFGTHHSKAI
FLVYPRGVRV VVHTANLIHV DWNNKSQGLW MQDFPWKDDD KDPPKGCGFE GDLIDYLNVL
KWPEFTANLP GRGNVKINAA FFKKFDYSDA TVRLIASVPG YHTGFNLNKW GHMKLRTILQ
ECIFDREFRR SPLIYQFSSL GSLDEKWLAE FGNSLSSGIT EDKTPLGPGD SLIIWPTVED
VRCSLEGYAA GNAIPSPLKN VEKPFLKKYW ARWKADHSAR GRAMPHIKTF TRYNDQKIAW
FLLTSSNLSK AAWGALQKNN SQLMIRSYEL GVLFLPSPIK TQGCVFSCTE SNPSVMKAKQ
ETKDEVEKRS KLVTMTWQGD RDLPEIISLP VPYQLPPKPY SPEDVPWSWD RGYSKKDVYG
QVWPR
