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Entry version 154 (08 May 2019)
Sequence version 1 (01 May 1999)
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Protein

Tyrosyl-DNA phosphodiesterase 2

Gene

TDP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. The 5'-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DNA double-strand breaks/DSBs without the need for nuclease activity, creating a 'clean' DSB with 5'-phosphate termini that are ready for ligation. Thereby, protects the transcription of many genes involved in neurological development and maintenance from the abortive activity of TOP2. Hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DSBs due to DNA damage by radiation and free radicals. Has preference for single-stranded DNA or duplex DNA with a 4 base pair overhang as substrate. Acts as a regulator of ribosome biogenesis following stress. Has also 3'-tyrosyl DNA phosphodiesterase activity, but less efficiently and much slower than TDP1. Constitutes the major if not only 5'-tyrosyl-DNA phosphodiesterase in cells. Also acts as an adapter by participating in the specific activation of MAP3K7/TAK1 in response to TGF-beta: associates with components of the TGF-beta receptor-TRAF6-TAK1 signaling module and promotes their ubiquitination dependent complex formation. Involved in non-canonical TGF-beta induced signaling routes. May also act as a negative regulator of ETS1 and may inhibit NF-kappa-B activation.7 Publications
(Microbial infection) Also acts as a 5'-tyrosyl-RNA phosphodiesterase following picornavirus infection: its activity is hijacked by picornavirus and acts by specifically cleaving the protein-RNA covalent linkage generated during the viral genomic RNA replication steps of a picornavirus infection, without impairing the integrity of viral RNA.1 Publication

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Mg2+3 Publications, Mn2+3 PublicationsNote: Magnesium. Can use other divalent cations as cofactor in vitro, such as manganese.3 Publications

<p>This subsection of the ‘Function’ section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

kcat is 3 sec(-1) with single-stranded 5'-tyrosyl DNA as substrate.
  1. KM=8 µM for single-stranded 5'-tyrosyl DNA1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Function’ section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi120MagnesiumCurated1
    Metal bindingi152MagnesiumBy similarity1
    Metal bindingi262MagnesiumCurated1
    Metal bindingi264MagnesiumBy similarity1
    Metal bindingi350MagnesiumBy similarity1
    <p>This subsection of the ‘Function’ section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei351Proton acceptorCurated1
    Metal bindingi351MagnesiumCurated1

    <p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

    GO - Biological processi

    <p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

    Molecular functionHydrolase, Nuclease
    Biological processDNA damage, DNA repair
    LigandMagnesium, Metal-binding

    Enzyme and pathway databases

    Reactome - a knowledgebase of biological pathways and processes

    More...
    Reactomei
    R-HSA-5693571 Nonhomologous End-Joining (NHEJ)

    <p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
    Recommended name:
    Tyrosyl-DNA phosphodiesterase 2 (EC:3.1.4.-)
    Short name:
    Tyr-DNA phosphodiesterase 2
    Short name:
    hTDP2
    Alternative name(s):
    5'-tyrosyl-DNA phosphodiesterase
    Short name:
    5'-Tyr-DNA phosphodiesterase
    ETS1-associated protein 2
    ETS1-associated protein II
    Short name:
    EAPII
    TRAF and TNF receptor-associated protein
    Tyrosyl-RNA phosphodiesterase
    VPg unlinkase
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
    Name:TDP2
    Synonyms:EAP2, TTRAP
    ORF Names:AD-022
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    <p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
    • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 6

    Organism-specific databases

    Human Gene Nomenclature Database

    More...
    HGNCi
    HGNC:17768 TDP2

    Online Mendelian Inheritance in Man (OMIM)

    More...
    MIMi
    605764 gene

    neXtProt; the human protein knowledge platform

    More...
    neXtProti
    NX_O95551

    <p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    <p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

    <p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

    Spinocerebellar ataxia, autosomal recessive, 23 (SCAR23)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR23 patients manifest epilepsy, intellectual disability, and gait ataxia.
    See also OMIM:616949

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi88T → A: Abolishes function, but retains ability to interact with SMAD3; when associated with A-92. 1 Publication1
    Mutagenesisi92T → A: Abolishes function, but retains ability to interact with SMAD3; when associated with A-88. 1 Publication1
    Mutagenesisi120N → A: Strongly reduced phosphodiesterase activity. 1 Publication1
    Mutagenesisi152E → A: Loss of phosphodiesterase activity. 2 Publications1
    Mutagenesisi262D → A: Loss of phosphodiesterase activity. 2 Publications1
    Mutagenesisi351H → A: Loss of phosphodiesterase activity. 1 Publication1

    Keywords - Diseasei

    Mental retardation, Neurodegeneration, Spinocerebellar ataxia

    Organism-specific databases

    DisGeNET

    More...
    DisGeNETi
    51567

    MalaCards human disease database

    More...
    MalaCardsi
    TDP2
    MIMi616949 phenotype

    Open Targets

    More...
    OpenTargetsi
    ENSG00000111802

    Orphanet; a database dedicated to information on rare diseases and orphan drugs

    More...
    Orphaneti
    404493 Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to TUD deficiency

    The Pharmacogenetics and Pharmacogenomics Knowledge Base

    More...
    PharmGKBi
    PA165618310

    Chemistry databases

    ChEMBL database of bioactive drug-like small molecules

    More...
    ChEMBLi
    CHEMBL2169736

    Polymorphism and mutation databases

    BioMuta curated single-nucleotide variation and disease association database

    More...
    BioMutai
    TDP2

    <p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000656781 – 362Tyrosyl-DNA phosphodiesterase 2Add BLAST362

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei1N-acetylmethionineCombined sources1
    <p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki23Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
    Cross-linki82Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
    Modified residuei88Phosphothreonine; by ACVR1B1 Publication1
    Modified residuei92Phosphothreonine; by ACVR1B1 Publication1
    Modified residuei95PhosphoserineCombined sources1

    <p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

    Ubiquitinated by TRAF6.1 Publication

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    Encyclopedia of Proteome Dynamics

    More...
    EPDi
    O95551

    jPOST - Japan Proteome Standard Repository/Database

    More...
    jPOSTi
    O95551

    MaxQB - The MaxQuant DataBase

    More...
    MaxQBi
    O95551

    PaxDb, a database of protein abundance averages across all three domains of life

    More...
    PaxDbi
    O95551

    PeptideAtlas

    More...
    PeptideAtlasi
    O95551

    PRoteomics IDEntifications database

    More...
    PRIDEi
    O95551

    ProteomicsDB human proteome resource

    More...
    ProteomicsDBi
    50937
    50938 [O95551-2]
    50939 [O95551-3]

    PTM databases

    iPTMnet integrated resource for PTMs in systems biology context

    More...
    iPTMneti
    O95551

    Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

    More...
    PhosphoSitePlusi
    O95551

    <p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

    <p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

    Widely expressed (PubMed:10764746). Highly expressed in various brain regions, including the frontal and occipital lobes, the hippocampus, the striatum and the cerebellum (PubMed:24658003).2 Publications

    Gene expression databases

    Bgee dataBase for Gene Expression Evolution

    More...
    Bgeei
    ENSG00000111802 Expressed in 236 organ(s), highest expression level in colonic mucosa

    ExpressionAtlas, Differential and Baseline Expression

    More...
    ExpressionAtlasi
    O95551 baseline and differential

    Genevisible search portal to normalized and curated expression data from Genevestigator

    More...
    Genevisiblei
    O95551 HS

    Organism-specific databases

    Human Protein Atlas

    More...
    HPAi
    CAB073398
    HPA074011

    <p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

    <p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

    Interacts with TRAF2, TRAF3, TRAF5, TRAF6, TNFRSF8/CD30, TNFRSF5/CD40, TNFRSF1B/TNF-R75, ETS1, ETS2, FLI1, SMAD3 and ACVR1B/ALK4.3 Publications

    Protein-protein interaction databases

    The Biological General Repository for Interaction Datasets (BioGrid)

    More...
    BioGridi
    119615, 44 interactors

    Protein interaction database and analysis system

    More...
    IntActi
    O95551, 26 interactors

    Molecular INTeraction database

    More...
    MINTi
    O95551

    STRING: functional protein association networks

    More...
    STRINGi
    9606.ENSP00000367440

    Chemistry databases

    BindingDB database of measured binding affinities

    More...
    BindingDBi
    O95551

    <p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

    Secondary structure

    1362
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    Select the link destinations:

    Protein Data Bank Europe

    More...
    PDBei

    Protein Data Bank RCSB

    More...
    RCSB PDBi

    Protein Data Bank Japan

    More...
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    5INOX-ray3.21A/B108-362[»]
    5J3PX-ray3.10A/B113-362[»]
    5J3SX-ray3.40A113-362[»]

    SWISS-MODEL Repository - a database of annotated 3D protein structure models

    More...
    SMRi
    O95551

    Database of comparative protein structure models

    More...
    ModBasei
    Search...

    MobiDB: a database of protein disorder and mobility annotations

    More...
    MobiDBi
    Search...

    <p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

    <p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

    Belongs to the CCR4/nocturin family.Curated

    Phylogenomic databases

    evolutionary genealogy of genes: Non-supervised Orthologous Groups

    More...
    eggNOGi
    KOG2756 Eukaryota
    ENOG410XP85 LUCA

    Ensembl GeneTree

    More...
    GeneTreei
    ENSGT00390000014242

    InParanoid: Eukaryotic Ortholog Groups

    More...
    InParanoidi
    O95551

    KEGG Orthology (KO)

    More...
    KOi
    K19619

    Identification of Orthologs from Complete Genome Data

    More...
    OMAi
    MFSFITW

    Database of Orthologous Groups

    More...
    OrthoDBi
    1612152at2759

    Database for complete collections of gene phylogenies

    More...
    PhylomeDBi
    O95551

    TreeFam database of animal gene trees

    More...
    TreeFami
    TF314813

    Family and domain databases

    Gene3D Structural and Functional Annotation of Protein Families

    More...
    Gene3Di
    3.60.10.10, 1 hit

    Integrated resource of protein families, domains and functional sites

    More...
    InterProi
    View protein in InterPro
    IPR036691 Endo/exonu/phosph_ase_sf
    IPR005135 Endo/exonuclease/phosphatase
    IPR009060 UBA-like_sf

    Pfam protein domain database

    More...
    Pfami
    View protein in Pfam
    PF03372 Exo_endo_phos, 1 hit

    Superfamily database of structural and functional annotation

    More...
    SUPFAMi
    SSF46934 SSF46934, 1 hit
    SSF56219 SSF56219, 1 hit

    <p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

    <p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

    This entry describes 3 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

    Isoform 1 (identifier: O95551-1) [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
            10         20         30         40         50
    MELGSCLEGG REAAEEEGEP EVKKRRLLCV EFASVASCDA AVAQCFLAEN
    60 70 80 90 100
    DWEMERALNS YFEPPVEESA LERRPETISE PKTYVDLTNE ETTDSTTSKI
    110 120 130 140 150
    SPSEDTQQEN GSMFSLITWN IDGLDLNNLS ERARGVCSYL ALYSPDVIFL
    160 170 180 190 200
    QEVIPPYYSY LKKRSSNYEI ITGHEEGYFT AIMLKKSRVK LKSQEIIPFP
    210 220 230 240 250
    STKMMRNLLC VHVNVSGNEL CLMTSHLEST RGHAAERMNQ LKMVLKKMQE
    260 270 280 290 300
    APESATVIFA GDTNLRDREV TRCGGLPNNI VDVWEFLGKP KHCQYTWDTQ
    310 320 330 340 350
    MNSNLGITAA CKLRFDRIFF RAAAEEGHII PRSLDLLGLE KLDCGRFPSD
    360
    HWGLLCNLDI IL
    Length:362
    Mass (Da):40,930
    Last modified:May 1, 1999 - v1
    <p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i37892E125DB64410
    GO
    Isoform 2 (identifier: O95551-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MRERHDTGACAEPRVGLLFRLKGRCRGGRKM

    Note: No experimental confirmation available.
    Show »
    Length:392
    Mass (Da):44,339
    Checksum:i6B822134BDD395F3
    GO
    Isoform 3 (identifier: O95551-3) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         60-137: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:284
    Mass (Da):32,176
    Checksum:i3FBF514CDDECB196
    GO

    <p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

    There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    X6R5A3X6R5A3_HUMAN
    TRAF and TNF receptor associated pr...
    TDP2 TTRAP, hCG_37519
    304Annotation score:

    Annotation score:2 out of 5

    <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

    <p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

    The sequence BAG59230 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti31E → R in AAF64144 (PubMed:10931946).Curated1
    Sequence conflicti61Y → C in BAA92119 (PubMed:14702039).Curated1
    Sequence conflicti72E → G in BAG60857 (PubMed:14702039).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_051464166S → G. Corresponds to variant dbSNP:rs35977478Ensembl.1
    Natural variantiVAR_022634249Q → E1 PublicationCorresponds to variant dbSNP:rs2294689Ensembl.1
    Natural variantiVAR_022635268R → Q1 PublicationCorresponds to variant dbSNP:rs17249952Ensembl.1
    Natural variantiVAR_076867307I → V1 PublicationCorresponds to variant dbSNP:rs77273535Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0385231M → MRERHDTGACAEPRVGLLFR LKGRCRGGRKM in isoform 2. 1 Publication1
    Alternative sequenceiVSP_03852460 – 137Missing in isoform 3. 1 PublicationAdd BLAST78

    Sequence databases

    Select the link destinations:

    EMBL nucleotide sequence database

    More...
    EMBLi

    GenBank nucleotide sequence database

    More...
    GenBanki

    DNA Data Bank of Japan; a nucleotide sequence database

    More...
    DDBJi
    Links Updated
    AJ269473 mRNA Translation: CAB92966.1
    AF201687 mRNA Translation: AAG35600.1
    AF223469 mRNA Translation: AAF64144.1
    AK002168 mRNA Translation: BAA92119.1
    AK296623 mRNA Translation: BAG59230.1 Different initiation.
    AK298699 mRNA Translation: BAG60857.1
    AY613922 Genomic DNA Translation: AAT09764.1
    AL031775 Genomic DNA No translation available.
    BC017553 mRNA Translation: AAH17553.1
    BC110375 mRNA Translation: AAI10376.1

    The Consensus CDS (CCDS) project

    More...
    CCDSi
    CCDS4557.1 [O95551-1]

    NCBI Reference Sequences

    More...
    RefSeqi
    NP_057698.2, NM_016614.2 [O95551-1]

    Genome annotation databases

    Ensembl eukaryotic genome annotation project

    More...
    Ensembli
    ENST00000378198; ENSP00000367440; ENSG00000111802 [O95551-1]

    Database of genes from NCBI RefSeq genomes

    More...
    GeneIDi
    51567

    KEGG: Kyoto Encyclopedia of Genes and Genomes

    More...
    KEGGi
    hsa:51567

    UCSC genome browser

    More...
    UCSCi
    uc003nej.4 human [O95551-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    <p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

    <p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

    <p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AJ269473 mRNA Translation: CAB92966.1
    AF201687 mRNA Translation: AAG35600.1
    AF223469 mRNA Translation: AAF64144.1
    AK002168 mRNA Translation: BAA92119.1
    AK296623 mRNA Translation: BAG59230.1 Different initiation.
    AK298699 mRNA Translation: BAG60857.1
    AY613922 Genomic DNA Translation: AAT09764.1
    AL031775 Genomic DNA No translation available.
    BC017553 mRNA Translation: AAH17553.1
    BC110375 mRNA Translation: AAI10376.1
    CCDSiCCDS4557.1 [O95551-1]
    RefSeqiNP_057698.2, NM_016614.2 [O95551-1]

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    5INOX-ray3.21A/B108-362[»]
    5J3PX-ray3.10A/B113-362[»]
    5J3SX-ray3.40A113-362[»]
    SMRiO95551
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi119615, 44 interactors
    IntActiO95551, 26 interactors
    MINTiO95551
    STRINGi9606.ENSP00000367440

    Chemistry databases

    BindingDBiO95551
    ChEMBLiCHEMBL2169736

    PTM databases

    iPTMnetiO95551
    PhosphoSitePlusiO95551

    Polymorphism and mutation databases

    BioMutaiTDP2

    Proteomic databases

    EPDiO95551
    jPOSTiO95551
    MaxQBiO95551
    PaxDbiO95551
    PeptideAtlasiO95551
    PRIDEiO95551
    ProteomicsDBi50937
    50938 [O95551-2]
    50939 [O95551-3]

    Protocols and materials databases

    The DNASU plasmid repository

    More...
    DNASUi
    51567
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000378198; ENSP00000367440; ENSG00000111802 [O95551-1]
    GeneIDi51567
    KEGGihsa:51567
    UCSCiuc003nej.4 human [O95551-1]

    Organism-specific databases

    Comparative Toxicogenomics Database

    More...
    CTDi
    51567
    DisGeNETi51567

    GeneCards: human genes, protein and diseases

    More...
    GeneCardsi
    TDP2
    HGNCiHGNC:17768 TDP2
    HPAiCAB073398
    HPA074011
    MalaCardsiTDP2
    MIMi605764 gene
    616949 phenotype
    neXtProtiNX_O95551
    OpenTargetsiENSG00000111802
    Orphaneti404493 Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to TUD deficiency
    PharmGKBiPA165618310

    GenAtlas: human gene database

    More...
    GenAtlasi
    Search...

    Phylogenomic databases

    eggNOGiKOG2756 Eukaryota
    ENOG410XP85 LUCA
    GeneTreeiENSGT00390000014242
    InParanoidiO95551
    KOiK19619
    OMAiMFSFITW
    OrthoDBi1612152at2759
    PhylomeDBiO95551
    TreeFamiTF314813

    Enzyme and pathway databases

    ReactomeiR-HSA-5693571 Nonhomologous End-Joining (NHEJ)

    Miscellaneous databases

    ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

    More...
    ChiTaRSi
    TDP2 human

    The Gene Wiki collection of pages on human genes and proteins

    More...
    GeneWikii
    TTRAP

    Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

    More...
    GenomeRNAii
    51567

    Protein Ontology

    More...
    PROi
    PR:O95551

    The Stanford Online Universal Resource for Clones and ESTs

    More...
    SOURCEi
    Search...

    Gene expression databases

    BgeeiENSG00000111802 Expressed in 236 organ(s), highest expression level in colonic mucosa
    ExpressionAtlasiO95551 baseline and differential
    GenevisibleiO95551 HS

    Family and domain databases

    Gene3Di3.60.10.10, 1 hit
    InterProiView protein in InterPro
    IPR036691 Endo/exonu/phosph_ase_sf
    IPR005135 Endo/exonuclease/phosphatase
    IPR009060 UBA-like_sf
    PfamiView protein in Pfam
    PF03372 Exo_endo_phos, 1 hit
    SUPFAMiSSF46934 SSF46934, 1 hit
    SSF56219 SSF56219, 1 hit

    ProtoNet; Automatic hierarchical classification of proteins

    More...
    ProtoNeti
    Search...

    <p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

    <p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiTYDP2_HUMAN
    <p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: O95551
    Secondary accession number(s): B4DKL8
    , B4DQ95, Q2TBE2, Q5JYM0, Q7Z6U5, Q9NUK5, Q9NYY9
    <p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 7, 2005
    Last sequence update: May 1, 1999
    Last modified: May 8, 2019
    This is version 154 of the entry and version 1 of the sequence. See complete history.
    <p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

    <p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

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