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Q9NUW8

- TYDP1_HUMAN

UniProt

Q9NUW8 - TYDP1_HUMAN

Protein

Tyrosyl-DNA phosphodiesterase 1

Gene

TDP1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 2 (24 Oct 2003)
      Previous versions | rss
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    Functioni

    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.5 Publications

    Kineticsi

    kcat is 7 sec(-1) with single-stranded 5'-tyrosyl DNA as substrate.

    1. KM=0.08 µM for 14-mer single-stranded oligo with a 3'-phosphotyrosine1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei263 – 2631Nucleophile
    Binding sitei265 – 2651Substrate
    Active sitei493 – 4931Proton donor
    Binding sitei495 – 4951Substrate
    Sitei518 – 5181Interaction with DNA

    GO - Molecular functioni

    1. 3'-tyrosyl-DNA phosphodiesterase activity Source: UniProtKB
    2. double-stranded DNA binding Source: UniProtKB
    3. exonuclease activity Source: UniProtKB-KW
    4. phosphoric diester hydrolase activity Source: InterPro
    5. protein binding Source: UniProtKB
    6. single-stranded DNA binding Source: UniProtKB

    GO - Biological processi

    1. cell death Source: UniProtKB-KW
    2. DNA repair Source: InterPro
    3. double-strand break repair Source: UniProtKB
    4. single strand break repair Source: UniProtKB

    Keywords - Molecular functioni

    Exonuclease, Hydrolase, Nuclease

    Keywords - Biological processi

    DNA damage, DNA repair

    Enzyme and pathway databases

    ReactomeiREACT_1201. Processing of DNA ends prior to end rejoining.
    SABIO-RKQ9NUW8.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosyl-DNA phosphodiesterase 1 (EC:3.1.4.-)
    Short name:
    Tyr-DNA phosphodiesterase 1
    Gene namesi
    Name:TDP1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:18884. TDP1.

    Subcellular locationi

    Nucleus 1 Publication. Cytoplasm 1 Publication

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nucleus Source: InterPro

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    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.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti493 – 4931H → R in SCAN1; reduces enzyme activity and leads to the accumulation of covalent complexes between TDP1 and DNA. 1 Publication
    VAR_017144

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi263 – 2631H → A: Loss of activity. 2 Publications
    Mutagenesisi265 – 2651K → A: Abolishes hydrolysis of the covalent intermediate between the active site nucleophile and DNA. 2 Publications
    Mutagenesisi265 – 2651K → S: Reduces the activity to nearly undetectable levels. 2 Publications
    Mutagenesisi283 – 2831N → A: No effect. 1 Publication
    Mutagenesisi294 – 2941Q → A: Slightly reduced hydrolysis of the covalent intermediate between the active site nucleophile and DNA. 1 Publication
    Mutagenesisi493 – 4931H → A: 3000-fold reduction in activity; abolishes hydrolysis of the covalent intermediate between the active site nucleophile and DNA. 2 Publications
    Mutagenesisi493 – 4931H → N: 15000-fold reduction in activity. 2 Publications
    Mutagenesisi495 – 4951K → A: Abolishes hydrolysis of the covalent intermediate between the active site nucleophile and DNA. 2 Publications
    Mutagenesisi495 – 4951K → S: 125-fold reduction in activity. 2 Publications
    Mutagenesisi516 – 5161N → A: Reduced hydrolysis of the covalent intermediate between the active site nucleophile and DNA. 1 Publication
    Mutagenesisi538 – 5381E → A: Abolishes hydrolysis of the covalent intermediate between the active site nucleophile and DNA. 1 Publication

    Keywords - Diseasei

    Disease mutation, Neurodegeneration

    Organism-specific databases

    MIMi607250. phenotype.
    Orphaneti94124. Spinocerebellar ataxia type 1 with axonal neuropathy.
    PharmGKBiPA421.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 608608Tyrosyl-DNA phosphodiesterase 1PRO_0000212486Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei61 – 611Phosphoserine2 Publications
    Modified residuei147 – 1471Phosphothreonine2 Publications
    Modified residuei148 – 1481Phosphoserine2 Publications

    Post-translational modificationi

    Phosphorylated on serine and/or threonine residues, but not on tyrosine residues.3 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ9NUW8.
    PaxDbiQ9NUW8.
    PRIDEiQ9NUW8.

    PTM databases

    PhosphoSiteiQ9NUW8.

    Expressioni

    Tissue specificityi

    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.2 Publications

    Gene expression databases

    ArrayExpressiQ9NUW8.
    BgeeiQ9NUW8.
    CleanExiHS_TDP1.
    GenevestigatoriQ9NUW8.

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Protein-protein interaction databases

    BioGridi120890. 5 interactions.
    IntActiQ9NUW8. 4 interactions.
    MINTiMINT-3074488.
    STRINGi9606.ENSP00000337353.

    Structurei

    Secondary structure

    1
    608
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni149 – 1513
    Helixi154 – 1563
    Beta strandi166 – 1694
    Helixi176 – 1794
    Helixi185 – 1884
    Helixi191 – 1933
    Beta strandi196 – 2027
    Beta strandi204 – 2063
    Helixi208 – 2147
    Helixi217 – 2193
    Beta strandi224 – 2285
    Helixi232 – 24211
    Beta strandi248 – 2525
    Beta strandi266 – 2738
    Beta strandi275 – 2806
    Helixi286 – 2894
    Beta strandi291 – 2933
    Beta strandi295 – 2984
    Helixi319 – 32810
    Helixi333 – 3353
    Helixi336 – 3438
    Beta strandi352 – 3576
    Beta strandi359 – 3635
    Helixi364 – 3696
    Helixi371 – 38212
    Helixi389 – 3913
    Beta strandi394 – 3974
    Turni408 – 4158
    Helixi416 – 4205
    Beta strandi437 – 4404
    Helixi444 – 4485
    Beta strandi450 – 4523
    Helixi454 – 4596
    Helixi464 – 4674
    Helixi471 – 4766
    Helixi483 – 4853
    Beta strandi495 – 5006
    Beta strandi504 – 51411
    Helixi519 – 5224
    Beta strandi524 – 5263
    Turni527 – 5304
    Beta strandi531 – 5344
    Beta strandi536 – 5438
    Helixi545 – 5484
    Beta strandi553 – 5553

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1JY1X-ray1.69A149-608[»]
    1MU7X-ray2.00A/B149-608[»]
    1MU9X-ray2.05A/B149-608[»]
    1NOPX-ray2.30A/B149-608[»]
    1QZQX-ray2.40A/B149-608[»]
    1RFFX-ray1.70A/B149-608[»]
    1RFIX-ray2.20A/B149-608[»]
    1RG1X-ray2.10A/B149-608[»]
    1RG2X-ray2.10A/B149-608[»]
    1RGTX-ray2.00A/B149-608[»]
    1RGUX-ray2.22A/B149-608[»]
    1RH0X-ray2.30A/B149-608[»]
    ProteinModelPortaliQ9NUW8.
    SMRiQ9NUW8. Positions 161-608.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9NUW8.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni400 – 4034Interaction with DNA

    Sequence similaritiesi

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG274417.
    HOGENOMiHOG000067775.
    HOVERGENiHBG061242.
    InParanoidiQ9NUW8.
    KOiK10862.
    OMAiNISLCQA.
    PhylomeDBiQ9NUW8.
    TreeFamiTF105989.

    Family and domain databases

    Gene3Di3.30.870.20. 1 hit.
    InterProiIPR010347. Tdp1.
    IPR027415. TDP_C.
    [Graphical view]
    PANTHERiPTHR12415. PTHR12415. 1 hit.
    PfamiPF06087. Tyr-DNA_phospho. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9NUW8-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSQEGDYGRW TISSSDESEE EKPKPDKPST SSLLCARQGA ANEPRYTCSE    50
    AQKAAHKRKI SPVKFSNTDS VLPPKRQKSG SQEDLGWCLS SSDDELQPEM 100
    PQKQAEKVVI KKEKDISAPN DGTAQRTENH GAPACHRLKE EEDEYETSGE 150
    GQDIWDMLDK GNPFQFYLTR VSGVKPKYNS GALHIKDILS PLFGTLVSSA 200
    QFNYCFDVDW LVKQYPPEFR KKPILLVHGD KREAKAHLHA QAKPYENISL 250
    CQAKLDIAFG THHTKMMLLL YEEGLRVVIH TSNLIHADWH QKTQGIWLSP 300
    LYPRIADGTH KSGESPTHFK ADLISYLMAY NAPSLKEWID VIHKHDLSET 350
    NVYLIGSTPG RFQGSQKDNW GHFRLKKLLK DHASSMPNAE SWPVVGQFSS 400
    VGSLGADESK WLCSEFKESM LTLGKESKTP GKSSVPLYLI YPSVENVRTS 450
    LEGYPAGGSL PYSIQTAEKQ NWLHSYFHKW SAETSGRSNA MPHIKTYMRP 500
    SPDFSKIAWF LVTSANLSKA AWGALEKNGT QLMIRSYELG VLFLPSAFGL 550
    DSFKVKQKFF AGSQEPMATF PVPYDLPPEL YGSKDRPWIW NIPYVKAPDT 600
    HGNMWVPS 608
    Length:608
    Mass (Da):68,420
    Last modified:October 24, 2003 - v2
    Checksum:iF30202BD8329E5CE
    GO
    Isoform 2 (identifier: Q9NUW8-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-25: MSQEGDYGRWTISSSDESEEEKPKP → MVISERLRLTSMPRPSLTRTSLSAR
         26-264: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:369
    Mass (Da):41,630
    Checksum:i8674BAEED98FA149
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti389 – 3891A → P in BAA91997. (PubMed:14702039)Curated
    Sequence conflicti511 – 5111L → R in AAF65624. (PubMed:10521354)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti95 – 951E → D.1 Publication
    Corresponds to variant rs35114462 [ dbSNP | Ensembl ].
    VAR_025817
    Natural varianti101 – 1011P → L.1 Publication
    Corresponds to variant rs35455108 [ dbSNP | Ensembl ].
    VAR_025818
    Natural varianti134 – 1341A → T.1 Publication
    Corresponds to variant rs28365054 [ dbSNP | Ensembl ].
    VAR_025819
    Natural varianti187 – 1871D → G.1 Publication
    Corresponds to variant rs35271143 [ dbSNP | Ensembl ].
    VAR_025820
    Natural varianti304 – 3041R → Q.1 Publication
    Corresponds to variant rs34452707 [ dbSNP | Ensembl ].
    VAR_025821
    Natural varianti493 – 4931H → R in SCAN1; reduces enzyme activity and leads to the accumulation of covalent complexes between TDP1 and DNA. 1 Publication
    VAR_017144
    Natural varianti566 – 5661P → L in autosomal recessive or sporadic spinocerebellar ataxia affected Japanese individuals. 1 Publication
    VAR_017145
    Natural varianti569 – 5691T → A.1 Publication
    Corresponds to variant rs35973343 [ dbSNP | Ensembl ].
    VAR_025822

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 2525MSQEG…EKPKP → MVISERLRLTSMPRPSLTRT SLSAR in isoform 2. 1 PublicationVSP_055765Add
    BLAST
    Alternative sequencei26 – 264239Missing in isoform 2. 1 PublicationVSP_055766Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    BX161451 mRNA. Translation: CAD61915.1.
    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.
    CCDSiCCDS9888.1.
    RefSeqiNP_001008744.1. NM_001008744.1.
    NP_060789.2. NM_018319.3.
    XP_005267904.1. XM_005267847.1.
    XP_005267905.1. XM_005267848.1.
    XP_006720260.1. XM_006720197.1.
    XP_006720261.1. XM_006720198.1.
    UniGeneiHs.209945.

    Genome annotation databases

    EnsembliENST00000335725; ENSP00000337353; ENSG00000042088. [Q9NUW8-1]
    ENST00000393454; ENSP00000377099; ENSG00000042088. [Q9NUW8-1]
    GeneIDi55775.
    KEGGihsa:55775.
    UCSCiuc001xxy.3. human.

    Polymorphism databases

    DMDMi37999797.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    BX161451 mRNA. Translation: CAD61915.1 .
    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 .
    CCDSi CCDS9888.1.
    RefSeqi NP_001008744.1. NM_001008744.1.
    NP_060789.2. NM_018319.3.
    XP_005267904.1. XM_005267847.1.
    XP_005267905.1. XM_005267848.1.
    XP_006720260.1. XM_006720197.1.
    XP_006720261.1. XM_006720198.1.
    UniGenei Hs.209945.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 149-608 [» ]
    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 [» ]
    ProteinModelPortali Q9NUW8.
    SMRi Q9NUW8. Positions 161-608.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 120890. 5 interactions.
    IntActi Q9NUW8. 4 interactions.
    MINTi MINT-3074488.
    STRINGi 9606.ENSP00000337353.

    Chemistry

    BindingDBi Q9NUW8.
    ChEMBLi CHEMBL1075138.

    PTM databases

    PhosphoSitei Q9NUW8.

    Polymorphism databases

    DMDMi 37999797.

    Proteomic databases

    MaxQBi Q9NUW8.
    PaxDbi Q9NUW8.
    PRIDEi Q9NUW8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000335725 ; ENSP00000337353 ; ENSG00000042088 . [Q9NUW8-1 ]
    ENST00000393454 ; ENSP00000377099 ; ENSG00000042088 . [Q9NUW8-1 ]
    GeneIDi 55775.
    KEGGi hsa:55775.
    UCSCi uc001xxy.3. human.

    Organism-specific databases

    CTDi 55775.
    GeneCardsi GC14P090422.
    GeneReviewsi TDP1.
    HGNCi HGNC:18884. TDP1.
    MIMi 607198. gene.
    607250. phenotype.
    neXtProti NX_Q9NUW8.
    Orphaneti 94124. Spinocerebellar ataxia type 1 with axonal neuropathy.
    PharmGKBi PA421.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG274417.
    HOGENOMi HOG000067775.
    HOVERGENi HBG061242.
    InParanoidi Q9NUW8.
    KOi K10862.
    OMAi NISLCQA.
    PhylomeDBi Q9NUW8.
    TreeFami TF105989.

    Enzyme and pathway databases

    Reactomei REACT_1201. Processing of DNA ends prior to end rejoining.
    SABIO-RK Q9NUW8.

    Miscellaneous databases

    EvolutionaryTracei Q9NUW8.
    GeneWikii TDP1.
    GenomeRNAii 55775.
    NextBioi 60841.
    PROi Q9NUW8.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9NUW8.
    Bgeei Q9NUW8.
    CleanExi HS_TDP1.
    Genevestigatori Q9NUW8.

    Family and domain databases

    Gene3Di 3.30.870.20. 1 hit.
    InterProi IPR010347. Tdp1.
    IPR027415. TDP_C.
    [Graphical view ]
    PANTHERi PTHR12415. PTHR12415. 1 hit.
    Pfami PF06087. Tyr-DNA_phospho. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Full-length cDNA libraries and normalization."
      Li W.B., Gruber C., Jessee J., Polayes D.
      Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Placenta.
    2. "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] (ISOFORM 1).
      Tissue: Placenta.
    3. 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.
    4. "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].
    5. "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] (ISOFORM 1).
      Tissue: Pancreas.
    6. "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 (ISOFORM 1).
    7. "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.
    8. "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.
    9. "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.
    10. "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.
    11. "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.
    12. "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.
    13. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-61, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    14. "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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    15. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    16. "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.
    17. "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.
    18. "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.
    19. "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.
    20. "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.
    21. "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.
    22. "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.
    23. "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.
    24. Cited for: CHARACTERIZATION OF VARIANT SCAN1 ARG-493, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiTYDP1_HUMAN
    AccessioniPrimary (citable) accession number: Q9NUW8
    Secondary accession number(s): Q2HXX4
    , Q86TV8, Q96BK7, Q9NZM7, Q9NZM8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 24, 2003
    Last sequence update: October 24, 2003
    Last modified: October 1, 2014
    This is version 122 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny 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.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 14
      Human chromosome 14: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3