Reviewed, UniProtKB/Swiss-Prot P38319 (TYDP1_YEAST)

Names and origin

Protein names

Recommended name:
    Tyrosyl-DNA phosphodiesterase 1
      Short name=Tyr-DNA phosphodiesterase 1
    EC=3.1.4.-

Gene names

Name:	TDP1
Ordered Locus Names:	YBR223C
ORF Names:	YBR1520

Organism

Saccharomyces cerevisiae (Baker's yeast) [Complete proteome]

Taxonomic identifier

4932 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	544 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 3'-phosphodiester bond, giving rise to DNA with a free 3' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase I active site tyrosine residue. Hydrolyzes 3'-phosphoglycolates on protruding 3' ends on DNA double-strand breaks due to DNA damage by radiation and free radicals. Cleaves also 5' phosphotyrosyl adducts resulting from dead-end complexes between DNA and the active site tyrosine of topoisomerase II. Contributes to DNA repair after radiation damage. Acts on blunt-ended double-strand DNA breaks and on single-stranded DNA. May have low 3'exonuclease activity and may be able to remove a single nucleoside from the 3'end of DNA and RNA molecules with 3'hydroxyl groups. Has no exonuclease activity towards DNA or RNA with a 3'phosphate By similarity.
Subcellular location	Nucleus. Ref.3
Miscellaneous	Present with 2130 molecules/cell in log phase SD medium. Ref.4
Sequence similarities	Belongs to the tyrosyl-DNA phosphodiesterase family.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Domain	Repeat
Molecular function	Exonuclease Hydrolase Nuclease
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	DNA repair Ref.2 Inferred from mutant phenotype. Source: SGD
Cellular component	nucleus Ref.3 Inferred from direct assay. Source: SGD
Molecular function	3'-tyrosyl-DNA phosphodiesterase activity Ref.2 Inferred from direct assay. Source: SGD 5'-tyrosyl-DNA phosphodiesterase activity Ref.5 Inferred from direct assay. Source: SGD exonuclease activity Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SMT3	Q12306	1	EBI-20997,EBI-17490
TAF2	P23255	1	EBI-20997,EBI-18862

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 544

544

Tyrosyl-DNA phosphodiesterase 1

PRO_0000212490

Regions

Region

312 – 318

7

Interaction with DNA By similarity

Sites

Active site

182

1

Nucleophile

Active site

432

1

Proton donor

Binding site

184

1

Substrate By similarity

Binding site

434

1

Substrate By similarity

Site

467

1

Interaction with DNA By similarity

Experimental info

Mutagenesis

182

1

H → A: Loss of activity. Ref.5

Mutagenesis

432

1

H → N: Strongly reduced release of the covalent intermediate with DNA that is formed during the enzyme reaction, leading to the accumulation of toxic adducts. No effect on bleomycin sensitivity. Ref.6

Mutagenesis

432

1

H → R: Interferes with the hydrolysis of the covalent intermediate with DNA that is formed during the enzyme reaction. No effect on bleomycin sensitivity. Ref.6

Secondary structure

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544

Helix Strand Turn

Details...

Beta strand

81 – 85

5

Turn

88 – 91

4

Helix

105 – 109

5

Beta strand

114 – 120

7

Helix

126 – 130

5

Beta strand

139 – 145

7

Helix

154 – 156

3

Helix

159 – 165

7

Beta strand

168 – 173

6

Beta strand

185 – 191

7

Beta strand

194 – 202

9

Helix

206 – 210

5

Beta strand

211 – 213

3

Beta strand

215 – 218

4

Beta strand

222 – 224

3

Helix

232 – 242

11

Helix

247 – 252

6

Helix

254 – 258

5

Helix

263 – 265

3

Beta strand

269 – 273

5

Helix

282 – 292

11

Beta strand

303 – 309

7

Beta strand

311 – 313

3

Beta strand

319 – 321

3

Helix

325 – 328

4

Helix

330 – 335

6

Helix

356 – 366

11

Beta strand

368 – 373

6

Helix

378 – 380

3

Helix

386 – 392

7

Helix

398 – 400

3

Helix

401 – 409

9

Beta strand

414 – 416

3

Turn

419 – 421

3

Turn

424 – 428

5

Beta strand

434 – 441

8

Beta strand

454 – 463

10

Helix

468 – 471

4

Beta strand

474 – 476

3

Beta strand

479 – 488

10

Helix

489 – 491

3

Beta strand

498 – 502

5

Helix

503 – 505

3

Beta strand

516 – 521

6

Turn

530 – 532

3

Sequences

	Sequence		Length	Mass (Da)
	P38319-1 [UniParc]. Last modified October 1, 1994. Version 1. Checksum: E84C6685312DEC3F	FASTA	544	62,333
	10 20 30 40 50 60 MSRETNFNGT KRKRSDVAEK VAQRWKSVRY SAEMENMAPV NSNNDSDDCV IVSESKIIDL 70 80 90 100 110 120 TNQEQDLSER IETNDTAKGA VFKLMKSDFY EREDFMGEVE DMITLKDIFG TETLKRSILF 130 140 150 160 170 180 SFQYELDFLL RQFHQNVENI TIVGQKGTIM PIEARAMDAT LAVILKKVKL IEITMPPFAS 190 200 210 220 230 240 HHTKLIINFY DNGECKIFLP SNNFTSMETN LPQQVCWCSP LLKIGKEGLP VPFKRSLIEY 250 260 270 280 290 300 LNSYHLKDID ELITKSVEEV NFAPLSELEF VYSTPSKFQS SGLLSFYNKL EKLSAGTSAS 310 320 330 340 350 360 DTAKHYLCQT SSIGTSLSRA RDENLWTHLM IPLFTGIMSP PAKDTAGRKK AEILPTNSLI 370 380 390 400 410 420 NEYSQRKIKP YIIFPTEQEF VTSPLKWSSS GWFHFQYLQK KSYYEMLRNK FKVFYKQDPA 430 440 450 460 470 480 MVTRRRGTTP AHSKFYMHCA TNSAGPCDAS QVFKELEWCL YTSANLSQTA WGTVSRKPRN 490 500 510 520 530 540 YEAGVLYHSR RLANTRKVTC RTFTRDRRGC AGNPTHVAVP FTLPVIPYDL AEDECFCLAR HEND

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete DNA sequence of yeast chromosome II." Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C., Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M., Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M., Cziepluch C. , Demolis N., Delaveau T., Doignon F., Domdey H., Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D., Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N., Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J., Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C., Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P., Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y., Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F., Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E., Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M., Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B., Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L., Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M., Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S., Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K., Mewes H.-W., Kleine K. EMBO J. 13:5795-5809(1994) [PubMed: 7813418] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[2]	"Yeast gene for a Tyr-DNA phosphodiesterase that repairs topoisomerase I complexes." Pouliot J.J., Yao K.C., Robertson C.A., Nash H.A. Science 286:552-555(1999) [PubMed: 10521354] [Abstract] Cited for: FUNCTION.
[3]	"Genome-wide nuclear morphology screen identifies novel genes involved in nuclear architecture and gene-silencing in Saccharomyces cerevisiae." Teixeira M.T., Dujon B., Fabre E. J. Mol. Biol. 321:551-561(2002) [PubMed: 12206772] [Abstract] Cited for: SUBCELLULAR LOCATION.
[4]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[5]	"Tyrosyl-DNA phosphodiesterase (Tdp1) participates in the repair of Top2-mediated DNA damage." Nitiss K.C., Malik M., He X., White S.W., Nitiss J.L. Proc. Natl. Acad. Sci. U.S.A. 103:8953-8958(2006) [PubMed: 16751265] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF HIS-182.
[6]	"Mutation of a conserved active site residue converts tyrosyl-DNA phosphodiesterase I into a DNA topoisomerase I-dependent poison." He X., van Waardenburg R.C.A.M., Babaoglu K., Price A.C., Nitiss K.C., Nitiss J.L., Bjornsti M.-A., White S.W. J. Mol. Biol. 372:1070-1081(2007) [PubMed: 17707402] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), MUTAGENESIS OF HIS-432.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

Z36092 Genomic DNA. Translation: CAA85186.1.

PIR

S46099.

RefSeq

NP_009782.1.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Q32	X-ray	2.03	A/B/C/D	1-544	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:4945N.

IntAct

P38319. 7 interactions.

Genome annotation databases

Ensembl

YBR223C. Saccharomyces cerevisiae. [Contig view]

GeneID

852525.

GenomeReviews

Gene locus YBR223C in contig Y13134_GR.

KEGG

sce:YBR223C.

NMPDR

fig|4932.3.peg.494.

Organism-specific databases

CYGD

YBR223c.

SGD

S000000427. TDP1.

Yeast-GFP

Search...

Phylogenomic databases

HOGENOM

P38319.

OMA

P38319. FLPSNNF.

Gene expression databases

ArrayExpress

P38319.

GermOnline

YBR223C. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR010347. Tyr-DNA_phospho.
[Graphical view]

PANTHER

PTHR12415. Tyr-DNA_phospho. 1 hit.

Pfam

PF06087. Tyr-DNA_phospho. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

971568.

Entry information

Entry name

TYDP1_YEAST

Accession

Primary (citable) accession number: P38319

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	October 1, 1994
Last modified:	June 16, 2009
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

FPAP (Fungal Proteome Annotation Project)