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Entry version 169 (29 Sep 2021)
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 (PubMed:27099339, PubMed:27060144).

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.

9 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+5 Publications, Mn2+3 PublicationsNote: Binds 1 magnesium or manganese ion per subunit.5 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 <a href="http://www.uniprot.org/help/function_section">Function</a> 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 bindingi122MagnesiumCombined sources1 Publication1
Metal bindingi152MagnesiumCombined sources1 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> 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 sitei262Proton donor/acceptor1 Publication1

<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, Host-virus interaction
LigandMagnesium, Metal-binding

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

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PathwayCommonsi
O95551

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-5693571, Nonhomologous End-Joining (NHEJ)

SIGNOR Signaling Network Open Resource

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SIGNORi
O95551

<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.-5 Publications)
Short name:
Tyr-DNA phosphodiesterase 21 Publication
Short name:
hTDP2
Alternative name(s):
5'-tyrosyl-DNA phosphodiesterase1 Publication
Short name:
5'-Tyr-DNA phosphodiesterase
ETS1-associated protein 2
ETS1-associated protein II
Short name:
EAPII1 Publication
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:TDP21 Publication
Synonyms:EAP21 Publication, TTRAP2 Publications
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

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HGNCi
HGNC:17768, TDP2

Online Mendelian Inheritance in Man (OMIM)

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MIMi
605764, gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_O95551

Eukaryotic Pathogen, Vector and Host Database Resources

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VEuPathDBi
HostDB:ENSG00000111802

<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

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 variants 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.
Related information in OMIM

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
Mutagenesisi178Y → F or W: Strongly decreased phosphodiesterase activity. 1 Publication1
Mutagenesisi206R → A or K: Loss of phosphodiesterase activity. 1 Publication1
Mutagenesisi262D → A: Loss of phosphodiesterase activity. 2 Publications1
Mutagenesisi262D → H, L or M: Loss of phosphodiesterase activity. 1 Publication1
Mutagenesisi305L → A, F or W: Decreased phosphodiesterase activity. 1 Publication1
Mutagenesisi316D → N: Strongly decreased phosphodiesterase activity. 1 Publication1
Mutagenesisi350D → N: Strongly decreased phosphodiesterase activity. 1 Publication1
Mutagenesisi351H → A: Loss of phosphodiesterase activity. 1 Publication1
Mutagenesisi351H → Q: Loss of phosphodiesterase activity. 1 Publication1

Keywords - Diseasei

Mental retardation, Neurodegeneration, Spinocerebellar ataxia

Organism-specific databases

DisGeNET

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DisGeNETi
51567

MalaCards human disease database

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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

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PharmGKBi
PA165618310

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

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Pharosi
O95551, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL2169736

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

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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 or proteolytic cleavage.<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

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EPDi
O95551

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
O95551

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
O95551

MaxQB - The MaxQuant DataBase

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MaxQBi
O95551

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

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PaxDbi
O95551

PeptideAtlas

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PeptideAtlasi
O95551

PRoteomics IDEntifications database

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PRIDEi
O95551

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
50937 [O95551-1]
50938 [O95551-2]
50939 [O95551-3]

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

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GlyGeni
O95551, 1 site, 1 O-linked glycan (1 site)

iPTMnet integrated resource for PTMs in systems biology context

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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 colonic mucosa and 248 other tissues

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
O95551, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
O95551, HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
ENSG00000111802, Tissue enhanced (blood, intestine)

<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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei178Interaction with 5' end of substrate DNABy similarity1
Sitei297Interaction with 5' end of substrate DNABy similarity1
Sitei315Interaction with 5' end of substrate DNABy similarity1
Sitei351Interaction with 5' end of substrate DNABy similarity1

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

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BioGRIDi
119615, 58 interactors

Protein interaction database and analysis system

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IntActi
O95551, 45 interactors

STRING: functional protein association networks

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STRINGi
9606.ENSP00000367440

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
O95551

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

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RNActi
O95551, protein

<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

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

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SMRi
O95551

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
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

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1 – 20DisorderedSequence analysisAdd BLAST20
Regioni87 – 109DisorderedSequence analysisAdd BLAST23
Regioni120 – 124Interaction with 5' end of substrate DNABy similarity5
Regioni226 – 231Interaction with 5' end of substrate DNABy similarity6
Regioni264 – 266Interaction with 5' end of substrate DNABy similarity3

<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

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eggNOGi
KOG2756, Eukaryota

Ensembl GeneTree

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GeneTreei
ENSGT00390000014242

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
CLU_047318_0_0_1

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
O95551

Identification of Orthologs from Complete Genome Data

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OMAi
YTIIPGN

Database of Orthologous Groups

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OrthoDBi
1612152at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
O95551

TreeFam database of animal gene trees

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TreeFami
TF314813

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
3.60.10.10, 1 hit

Integrated resource of protein families, domains and functional sites

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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>. The information is filed in different subsections. The current subsections and their content are listed below:<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 <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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

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.

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. Truncated N-terminus.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 → V Slightly decreased phosphodiesterase activity. 1 PublicationCorresponds to variant dbSNP:rs77273535EnsemblClinVar.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

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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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

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CCDSi
CCDS4557.1 [O95551-1]

NCBI Reference Sequences

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

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENST00000378198; ENSP00000367440; ENSG00000111802 [O95551-1]

Database of genes from NCBI RefSeq genomes

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GeneIDi
51567

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:51567

UCSC genome browser

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UCSCi
uc003nej.4, human [O95551-1]

Keywords - Coding sequence diversityi

Alternative splicing

<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:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5INOX-ray3.21A/B108-362[»]
5J3PX-ray3.10A/B113-362[»]
5J3SX-ray3.40A113-362[»]
6Q00X-ray0.85B25-66[»]
6Q01X-ray0.85C/D25-66[»]
SMRiO95551
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi119615, 58 interactors
IntActiO95551, 45 interactors
STRINGi9606.ENSP00000367440

Chemistry databases

BindingDBiO95551
ChEMBLiCHEMBL2169736

PTM databases

GlyGeniO95551, 1 site, 1 O-linked glycan (1 site)
iPTMnetiO95551
PhosphoSitePlusiO95551

Genetic variation databases

BioMutaiTDP2

Proteomic databases

EPDiO95551
jPOSTiO95551
MassIVEiO95551
MaxQBiO95551
PaxDbiO95551
PeptideAtlasiO95551
PRIDEiO95551
ProteomicsDBi50937 [O95551-1]
50938 [O95551-2]
50939 [O95551-3]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

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Antibodypediai
10651, 302 antibodies

The CPTC Antibody Portal

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CPTCi
O95551, 3 antibodies

The DNASU plasmid repository

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DNASUi
51567

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

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GeneCardsi
TDP2
HGNCiHGNC:17768, TDP2
HPAiENSG00000111802, Tissue enhanced (blood, intestine)
MalaCardsiTDP2
MIMi605764, gene
616949, phenotype
neXtProtiNX_O95551
OpenTargetsiENSG00000111802
Orphaneti404493, Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to TUD deficiency
PharmGKBiPA165618310
VEuPathDBiHostDB:ENSG00000111802

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG2756, Eukaryota
GeneTreeiENSGT00390000014242
HOGENOMiCLU_047318_0_0_1
InParanoidiO95551
OMAiYTIIPGN
OrthoDBi1612152at2759
PhylomeDBiO95551
TreeFamiTF314813

Enzyme and pathway databases

PathwayCommonsiO95551
ReactomeiR-HSA-5693571, Nonhomologous End-Joining (NHEJ)
SIGNORiO95551

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

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BioGRID-ORCSi
51567, 97 hits in 1021 CRISPR screens

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

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GeneWikii
TTRAP

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

More...
GenomeRNAii
51567
PharosiO95551, Tchem

Protein Ontology

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PROi
PR:O95551
RNActiO95551, protein

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000111802, Expressed in colonic mucosa and 248 other tissues
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

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
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: September 29, 2021
This is version 169 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, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  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
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