Q9NUW8 (TYDP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	608 AA.
Sequence status	Complete.
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. Acts on blunt-ended double-strand DNA breaks and on single-stranded DNA. Has low 3'exonuclease activity and can 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. Ref.7 Ref.8 Ref.9 Ref.10 Ref.15
Subunit structure	Monomer. Ref.17
Subcellular location	Nucleus. Cytoplasm Ref.21.
Tissue specificity	Ubiquitously expressed. Similar expression throughout the central nervous system (whole brain, amygdala, caudate nucleus, cerebellum, cerebral cortex, frontal lobe, hippocampus, medulla oblongata, occipital lobe, putamen, substantia nigra, temporal lobe, thalamus, nucleus accumbens and spinal cord) and increased expression in testis and thymus. Ref.20 Ref.23
Post-translational modification	Phosphorylated on serine and/or threonine residues, but not on tyrosine residues. Ref.21
Involvement in disease	Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy (SCAN1) [MIM:607250]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAN1 is an autosomal recessive cerebellar ataxia (ARCA) associated with peripheral axonal motor and sensory neuropathy, distal muscular atrophy, pes cavus and steppage gait as seen in Charcot-Marie-Tooth neuropathy. All affected individuals have normal intelligence. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.20 Ref.21 Ref.22 Ref.23
Sequence similarities	Belongs to the tyrosyl-DNA phosphodiesterase family.
Biophysicochemical properties	Kinetic parameters: kcat is 7 sec(-1) with single-stranded 5'-tyrosyl DNA as substrate. KM=0.08 µM for 14-mer single-stranded oligo with a 3'-phosphotyrosine Ref.15

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Neurodegeneration
Domain	Repeat
Molecular function	Exonuclease Hydrolase Nuclease
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW double-strand break repair Inferred from direct assay Ref.7. Source: UniProtKB nucleic acid phosphodiester bond hydrolysis Inferred from electronic annotation. Source: GOC single strand break repair Inferred from direct assay Ref.9. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay Ref.23. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	3'-tyrosyl-DNA phosphodiesterase activity Inferred from direct assay PubMed 17118488PubMed 17576665Ref.23Ref.15. Source: UniProtKB double-stranded DNA binding Inferred from direct assay Ref.9. Source: UniProtKB exonuclease activity Inferred from electronic annotation. Source: UniProtKB-KW single-stranded DNA binding Inferred from direct assay Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 608

608

Tyrosyl-DNA phosphodiesterase 1

PRO_0000212486

Regions

Region

400 – 403

4

Interaction with DNA

Sites

Active site

263

1

Nucleophile

Active site

493

1

Proton donor

Binding site

265

1

Substrate

Binding site

495

1

Substrate

Site

518

1

Interaction with DNA

Amino acid modifications

Modified residue

61

1

Phosphoserine Ref.12

Modified residue

147

1

Phosphothreonine Ref.13

Modified residue

148

1

Phosphoserine Ref.13

Natural variations

Natural variant

95

1

E → D. Ref.2
Corresponds to variant rs35114462 [ dbSNP | Ensembl ].

VAR_025817

Natural variant

101

1

P → L. Ref.2
Corresponds to variant rs35455108 [ dbSNP | Ensembl ].

VAR_025818

Natural variant

134

1

A → T. Ref.2
Corresponds to variant rs28365054 [ dbSNP | Ensembl ].

VAR_025819

Natural variant

187

1

D → G. Ref.2
Corresponds to variant rs35271143 [ dbSNP | Ensembl ].

VAR_025820

Natural variant

304

1

R → Q. Ref.2
Corresponds to variant rs34452707 [ dbSNP | Ensembl ].

VAR_025821

Natural variant

493

1

H → R in SCAN1; reduces enzyme activity and leads to the accumulation of covalent complexes between TDP1 and DNA. Ref.10 Ref.20 Ref.21 Ref.22 Ref.23

VAR_017144

Natural variant

566

1

P → L in autosomal recessive or sporadic spinocerebellar ataxia affected Japanese individuals. Ref.20

VAR_017145

Natural variant

569

1

T → A. Ref.2
Corresponds to variant rs35973343 [ dbSNP | Ensembl ].

VAR_025822

Experimental info

Mutagenesis

263

1

H → A: Loss of activity. Ref.6 Ref.8

Mutagenesis

265

1

K → A: Abolishes hydrolysis of the covalent intermediate between the active site nucleophile and DNA. Ref.6 Ref.8

Mutagenesis

265

1

K → S: Reduces the activity to nearly undetectable levels. Ref.6 Ref.8

Mutagenesis

283

1

N → A: No effect. Ref.8

Mutagenesis

294

1

Q → A: Slightly reduced hydrolysis of the covalent intermediate between the active site nucleophile and DNA. Ref.8

Mutagenesis

493

1

H → A: 3000-fold reduction in activity; abolishes hydrolysis of the covalent intermediate between the active site nucleophile and DNA. Ref.6 Ref.8

Mutagenesis

493

1

H → N: 15000-fold reduction in activity. Ref.6 Ref.8

Mutagenesis

495

1

K → A: Abolishes hydrolysis of the covalent intermediate between the active site nucleophile and DNA. Ref.6 Ref.8

Mutagenesis

495

1

K → S: 125-fold reduction in activity. Ref.6 Ref.8

Mutagenesis

516

1

N → A: Reduced hydrolysis of the covalent intermediate between the active site nucleophile and DNA. Ref.8

Mutagenesis

538

1

E → A: Abolishes hydrolysis of the covalent intermediate between the active site nucleophile and DNA. Ref.8

Sequence conflict

389

1

A → P in BAA91997. Ref.1

Sequence conflict

511

1

L → R in AAF65624. Ref.5

Secondary structure

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608

Helix Strand Turn

Details...

Turn

149 – 151

3

Helix

154 – 156

3

Beta strand

166 – 169

4

Helix

176 – 179

4

Helix

185 – 188

4

Helix

191 – 193

3

Beta strand

196 – 202

7

Beta strand

204 – 206

3

Helix

208 – 214

7

Helix

217 – 219

3

Beta strand

224 – 228

5

Helix

232 – 242

11

Beta strand

248 – 252

5

Beta strand

266 – 273

8

Beta strand

275 – 280

6

Helix

286 – 289

4

Beta strand

291 – 293

3

Beta strand

295 – 298

4

Helix

319 – 328

10

Helix

333 – 335

3

Helix

336 – 343

8

Beta strand

352 – 357

6

Beta strand

359 – 363

5

Helix

364 – 369

6

Helix

371 – 382

12

Helix

389 – 391

3

Beta strand

394 – 397

4

Turn

408 – 415

8

Helix

416 – 420

5

Beta strand

437 – 440

4

Helix

444 – 448

5

Beta strand

450 – 452

3

Helix

454 – 459

6

Helix

464 – 467

4

Helix

471 – 476

6

Helix

483 – 485

3

Beta strand

495 – 500

6

Beta strand

504 – 514

11

Helix

519 – 522

4

Beta strand

524 – 526

3

Turn

527 – 530

4

Beta strand

531 – 534

4

Beta strand

536 – 543

8

Helix

545 – 548

4

Beta strand

553 – 555

3

Sequences

	Sequence		Length	Mass (Da)
	Q9NUW8 [UniParc]. Last modified October 24, 2003. Version 2. Checksum: F30202BD8329E5CE	FASTA	608	68,420
	10 20 30 40 50 60 MSQEGDYGRW TISSSDESEE EKPKPDKPST SSLLCARQGA ANEPRYTCSE AQKAAHKRKI 70 80 90 100 110 120 SPVKFSNTDS VLPPKRQKSG SQEDLGWCLS SSDDELQPEM PQKQAEKVVI KKEKDISAPN 130 140 150 160 170 180 DGTAQRTENH GAPACHRLKE EEDEYETSGE GQDIWDMLDK GNPFQFYLTR VSGVKPKYNS 190 200 210 220 230 240 GALHIKDILS PLFGTLVSSA QFNYCFDVDW LVKQYPPEFR KKPILLVHGD KREAKAHLHA 250 260 270 280 290 300 QAKPYENISL CQAKLDIAFG THHTKMMLLL YEEGLRVVIH TSNLIHADWH QKTQGIWLSP 310 320 330 340 350 360 LYPRIADGTH KSGESPTHFK ADLISYLMAY NAPSLKEWID VIHKHDLSET NVYLIGSTPG 370 380 390 400 410 420 RFQGSQKDNW GHFRLKKLLK DHASSMPNAE SWPVVGQFSS VGSLGADESK WLCSEFKESM 430 440 450 460 470 480 LTLGKESKTP GKSSVPLYLI YPSVENVRTS LEGYPAGGSL PYSIQTAEKQ NWLHSYFHKW 490 500 510 520 530 540 SAETSGRSNA MPHIKTYMRP SPDFSKIAWF LVTSANLSKA AWGALEKNGT QLMIRSYELG 550 560 570 580 590 600 VLFLPSAFGL DSFKVKQKFF AGSQEPMATF PVPYDLPPEL YGSKDRPWIW NIPYVKAPDT HGNMWVPS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[2]	NIEHS SNPs program Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ASP-95; LEU-101; THR-134; GLY-187; GLN-304 AND ALA-569.
[3]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-608.
[6]	"The tyrosyl-DNA phosphodiesterase Tdp1 is a member of the phospholipase D superfamily." Interthal H., Pouliot J.J., Champoux J.J. Proc. Natl. Acad. Sci. U.S.A. 98:12009-12014(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SIMILARITY TO PHOSPHOLIPASE D SUPERFAMILY, MUTAGENESIS OF HIS-263; LYS-265; HIS-493 AND LYS-495.
[7]	"Conversion of phosphoglycolate to phosphate termini on 3' overhangs of DNA double strand breaks by the human tyrosyl-DNA phosphodiesterase hTdp1." Inamdar K.V., Pouliot J.J., Zhou T., Lees-Miller S.P., Rasouli-Nia A., Povirk L.F. J. Biol. Chem. 277:27162-27168(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Analysis of human tyrosyl-DNA phosphodiesterase I catalytic residues." Raymond A.C., Rideout M.C., Staker B., Hjerrild K., Burgin A.B. Jr. J. Mol. Biol. 338:895-906(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME MECHANISM, MUTAGENESIS OF HIS-263; LYS-265; ASN-283; GLN-294; HIS-493; LYS-495; ASN-516 AND GLU-538.
[9]	"Substrate specificity of tyrosyl-DNA phosphodiesterase I (Tdp1)." Raymond A.C., Staker B.L., Burgin A.B. Jr. J. Biol. Chem. 280:22029-22035(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkages." Interthal H., Chen H.J., Champoux J.J. J. Biol. Chem. 280:36518-36528(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CHARACTERIZATION OF VARIANT SCAN1 ARG-493.
[11]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-61, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-147 AND SER-148, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"Biochemical characterization of human Tyrosyl DNA Phosphodiesterase 2 (TDP2/TTRAP): a Mg2+/Mn2+-dependent phosphodiesterase specific for the repair of topoisomerase cleavage complexes." Gao R., Huang S.Y., Marchand C., Pommier Y. J. Biol. Chem. 287:30842-30852(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[16]	"Insights into substrate binding and catalytic mechanism of human tyrosyl-DNA phosphodiesterase (Tdp1) from vanadate and tungstate-inhibited structures." Davies D.R., Interthal H., Champoux J.J., Hol W.G.J. J. Mol. Biol. 324:917-932(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 149-608 IN COMPLEXES WITH SUBSTRATE; VANADATE AND TUNGSTATE.
[17]	"The crystal structure of human tyrosyl-DNA phosphodiesterase, Tdp1." Davies D.R., Interthal H., Champoux J.J., Hol W.G.J. Structure 10:237-248(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.69 ANGSTROMS) OF 149-608, SUBUNIT.
[18]	"Crystal structure of a transition state mimic for TDP1 assembled from vanadate, DNA, and a topoisomerase I-derived peptide." Davies D.R., Interthal H., Champoux J.J., Hol W.G.J. Chem. Biol. 10:139-147(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 149-608.
[19]	"Explorations of peptide and oligonucleotide binding sites of tyrosyl-DNA phosphodiesterase using vanadate complexes." Davies D.R., Interthal H., Champoux J.J., Hol W.G.J. J. Med. Chem. 47:829-837(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 149-608 IN COMPLEXES WITH SUBSTRATES.
[20]	"Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy." Takashima H., Boerkoel C.F., John J., Saifi G.M., Salih M.A.M., Armstrong D., Mao Y., Quiocho F.A., Roa B.B., Nakagawa M., Stockton D.W., Lupski J.R. Nat. Genet. 32:267-272(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SCAN1 ARG-493, VARIANT LEU-566, TISSUE SPECIFICITY.
[21]	"Deficiency in 3'-phosphoglycolate processing in human cells with a hereditary mutation in tyrosyl-DNA phosphodiesterase (TDP1)." Zhou T., Lee J.W., Tatavarthi H., Lupski J.R., Valerie K., Povirk L.F. Nucleic Acids Res. 33:289-297(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT SCAN1 ARG-493, SUBCELLULAR LOCATION, PHOSPHORYLATION.
[22]	"SCAN1 mutant Tdp1 accumulates the enzyme-DNA intermediate and causes camptothecin hypersensitivity." Interthal H., Chen H.J., Kehl-Fie T.E., Zotzmann J., Leppard J.B., Champoux J.J. EMBO J. 24:2224-2233(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT SCAN1 ARG-493.
[23]	"Spinocerebellar ataxia with axonal neuropathy: consequence of a Tdp1 recessive neomorphic mutation?" Hirano R., Interthal H., Huang C., Nakamura T., Deguchi K., Choi K., Bhattacharjee M.B., Arimura K., Umehara F., Izumo S., Northrop J.L., Salih M.A.M., Inoue K., Armstrong D.L., Champoux J.J., Takashima H., Boerkoel C.F. EMBO J. 26:4732-4743(2007) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT SCAN1 ARG-493, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK001952 mRNA. Translation: BAA91997.1.
DQ367843 Genomic DNA. Translation: ABC79301.1.
AL137128 Genomic DNA. No translation available.
BC015474 mRNA. Translation: AAH15474.1.
AF182002 mRNA. Translation: AAF65623.1.
AF182003 mRNA. Translation: AAF65624.1.

IPI

IPI00655885.

RefSeq

NP_001008744.1. NM_001008744.1.
NP_060789.2. NM_018319.3.

UniGene

Hs.209945.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JY1	X-ray	1.69	A	149-608	[»]
1MU7	X-ray	2.00	A/B	149-608	[»]
1MU9	X-ray	2.05	A/B	149-608	[»]
1NOP	X-ray	2.30	A/B	149-608	[»]
1QZQ	X-ray	2.40	A/B	147-608	[»]
1RFF	X-ray	1.70	A/B	149-608	[»]
1RFI	X-ray	2.20	A/B	149-608	[»]
1RG1	X-ray	2.10	A/B	149-608	[»]
1RG2	X-ray	2.10	A/B	149-608	[»]
1RGT	X-ray	2.00	A/B	149-608	[»]
1RGU	X-ray	2.22	A/B	149-608	[»]
1RH0	X-ray	2.30	A/B	149-608	[»]

ProteinModelPortal

Q9NUW8.

ModBase

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Protein-protein interaction databases

IntAct

Q9NUW8. 1 interaction.

MINT

MINT-3074488.

STRING

9606.ENSP00000337353.

PTM databases

PhosphoSite

Q9NUW8.

Polymorphism databases

DMDM

37999797.

Proteomic databases

PaxDb

Q9NUW8.

PRIDE

Q9NUW8.

Protocols and materials databases

StructuralBiologyKnowledgebase

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Genome annotation databases

Ensembl

ENST00000335725; ENSP00000337353; ENSG00000042088.
ENST00000393454; ENSP00000377099; ENSG00000042088.

GeneID

55775.

KEGG

hsa:55775.

UCSC

uc001xxy.3. human.

Organism-specific databases

CTD

55775.

GeneCards

GC14P090422.

HGNC

HGNC:18884. TDP1.

MIM

607198. gene.
607250. phenotype.

neXtProt

NX_Q9NUW8.

Orphanet

94124. Spinocerebellar ataxia type 1 with axonal neuropathy.

PharmGKB

PA421.

GenAtlas

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Phylogenomic databases

eggNOG

NOG274417.

HOGENOM

HOG000067775.

HOVERGEN

HBG061242.

InParanoid

Q9NUW8.

KO

K10862.

OMA

WGHLRLR.

OrthoDB

EOG4NP736.

PhylomeDB

Q9NUW8.

Enzyme and pathway databases

Reactome

REACT_216. DNA Repair.

SABIO-RK

Q9NUW8.

Gene expression databases

ArrayExpress

Q9NUW8.

Bgee

Q9NUW8.

CleanEx

HS_TDP1.

Genevestigator

Q9NUW8.

GermOnline

ENSG00000042088. Homo sapiens.

Family and domain databases

InterPro

IPR010347. Tyr-DNA_phospho.
[Graphical view]

PANTHER

PTHR12415. PTHR12415. 1 hit.

Pfam

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

ProtoNet

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Other

BindingDB

Q9NUW8.

ChEMBL

CHEMBL1075138.

EvolutionaryTrace

Q9NUW8.

GenomeRNAi

55775.

NextBio

60841.

SOURCE

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Entry information

Entry name

TYDP1_HUMAN

Accession

Primary (citable) accession number: Q9NUW8
Secondary accession number(s): Q2HXX4 , Q96BK7, Q9NZM7, Q9NZM8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 24, 2003
Last sequence update:	October 24, 2003
Last modified:	May 1, 2013
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.