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Aliases for TDP2 Gene

Aliases for TDP2 Gene

  • Tyrosyl-DNA Phosphodiesterase 2 2 3 5
  • TRAF And TNF Receptor-Associated Protein 3 4
  • 5-Tyrosyl-DNA Phosphodiesterase 3 4
  • Tyrosyl-RNA Phosphodiesterase 3 4
  • Tyr-DNA Phosphodiesterase 2 3 4
  • 5-Tyr-DNA Phosphodiesterase 3 4
  • ETS1-Associated Protein II 3 4
  • ETS1-Associated Protein 2 3 4
  • VPg Unlinkase 3 4
  • TTRAP 3 4
  • EAPII 3 4
  • HTDP2 3 4
  • EAP2 3 4
  • TRAF And TNF Receptor Associated Protein 2
  • EC 3.1.4.- 4
  • DJ30M3.3 3
  • AD022 3

External Ids for TDP2 Gene

Previous HGNC Symbols for TDP2 Gene

  • TTRAP

Summaries for TDP2 Gene

Entrez Gene Summary for TDP2 Gene

  • This gene encodes a member of a superfamily of divalent cation-dependent phosphodiesterases. The encoded protein associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor associated factors (TRAFs), and inhibits nuclear factor-kappa-B activation. This protein has sequence and structural similarities with APE1 endonuclease, which is involved in both DNA repair and the activation of transcription factors. [provided by RefSeq, Jul 2008]

GeneCards Summary for TDP2 Gene

TDP2 (Tyrosyl-DNA Phosphodiesterase 2) is a Protein Coding gene. Diseases associated with TDP2 include Autosomal Recessive Cerebellar Ataxia-Epilepsy-Intellectual Disability Syndrome Due To Tud Deficiency and Paralytic Poliomyelitis. Among its related pathways are DNA Double Strand Break Response and DNA Double-Strand Break Repair. GO annotations related to this gene include transcription corepressor activity and single-stranded DNA binding.

UniProtKB/Swiss-Prot for TDP2 Gene

  • 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.

  • (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.

Gene Wiki entry for TDP2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TDP2 Gene

Genomics for TDP2 Gene

Regulatory Elements for TDP2 Gene

Enhancers for TDP2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH06F024716 0.5 ENCODE 21.5 -52.9 -52887 5.8 MLX CREB3L1 ZFP64 FEZF1 DMAP1 YY1 SLC30A9 ZNF416 ZNF143 SP3 C6orf62 TDP2 ENSG00000223623 ENSG00000230372 LOC101928663 SPTLC1P2 ACOT13 ENSG00000272402 KIAA0319
GH06F024657 1 FANTOM5 Ensembl ENCODE 19.9 +3.3 3280 11.6 MLX CREB3L1 ZFP64 FEZF1 DMAP1 YY1 SLC30A9 ZNF143 ZNF263 SP3 C6orf62 NUP50P2 TDP2 KIAA0319 ACOT13
GH06F024683 0.5 ENCODE 14.4 -17.3 -17258 1.9 NFIL3 ARID1B JUND SMARCA4 TAL1 IKZF1 DPF2 MIXL1 TDP2 KIAA0319 GMNN ENSG00000272345 ACOT13
GH06F024685 0.8 FANTOM5 12.6 -19.0 -19029 0.2 ZNF707 TDP2 KIAA0319 DCDC2 ENSG00000272345 ACOT13
GH06F024645 0.4 ENCODE 11.9 +20.8 20845 1.9 HDGF ZNF133 ARID4B SIN3A FEZF1 ZNF2 ZNF48 GLIS2 FOS SP3 ACOT13 KIAA0319 TDP2 C6orf62 KRT8P43
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around TDP2 on UCSC Golden Path with GeneCards custom track

Promoters for TDP2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00001494104 333 3401 MLX CREB3L1 ZFP64 FEZF1 DMAP1 YY1 SLC30A9 ZNF143 ZNF263 SP3

Genomic Location for TDP2 Gene

Chromosome:
6
Start:
24,649,977 bp from pter
End:
24,667,033 bp from pter
Size:
17,057 bases
Orientation:
Minus strand

Genomic View for TDP2 Gene

Genes around TDP2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TDP2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TDP2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TDP2 Gene

Proteins for TDP2 Gene

  • Protein details for TDP2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95551-TYDP2_HUMAN
    Recommended name:
    Tyrosyl-DNA phosphodiesterase 2
    Protein Accession:
    O95551
    Secondary Accessions:
    • B4DKL8
    • B4DQ95
    • Q2TBE2
    • Q5JYM0
    • Q7Z6U5
    • Q9NUK5
    • Q9NYY9

    Protein attributes for TDP2 Gene

    Size:
    362 amino acids
    Molecular mass:
    40930 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
    Quaternary structure:
    • Interacts with TRAF2, TRAF3, TRAF5, TRAF6, TNFRSF8/CD30, TNFRSF5/CD40, TNFRSF1B/TNF-R75, ETS1, ETS2, FLI1, SMAD3 and ACVR1B/ALK4.
    SequenceCaution:
    • Sequence=BAG59230.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=CAD92510.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for TDP2 Gene

    Alternative splice isoforms for TDP2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TDP2 Gene

Post-translational modifications for TDP2 Gene

  • Ubiquitinated by TRAF6.
  • Ubiquitination at Lys 23, Lys 82, Lys 192, Lys 203, Lys 242, Lys 247, and Lys 341
  • Modification sites at PhosphoSitePlus

Other Protein References for TDP2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for TDP2 Gene

Domains & Families for TDP2 Gene

Protein Domains for TDP2 Gene

Suggested Antigen Peptide Sequences for TDP2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

O95551

UniProtKB/Swiss-Prot:

TYDP2_HUMAN :
  • Belongs to the CCR4/nocturin family.
Family:
  • Belongs to the CCR4/nocturin family.
genes like me logo Genes that share domains with TDP2: view

No data available for Gene Families for TDP2 Gene

Function for TDP2 Gene

Molecular function for TDP2 Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=8 uM for single-stranded 5-tyrosyl DNA {ECO:0000269 PubMed:22822062}; Note=kcat is 3 sec(-1) with single-stranded 5-tyrosyl DNA as substrate.;
UniProtKB/Swiss-Prot Function:
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.
UniProtKB/Swiss-Prot Function:
(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.

Enzyme Numbers (IUBMB) for TDP2 Gene

Gene Ontology (GO) - Molecular Function for TDP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding TAS 19794497
GO:0003697 single-stranded DNA binding IDA 22822062
GO:0003714 transcription corepressor activity TAS 10764746
GO:0004518 nuclease activity IEA --
GO:0005515 protein binding IPI 18039968
genes like me logo Genes that share ontologies with TDP2: view
genes like me logo Genes that share phenotypes with TDP2: view

Animal Models for TDP2 Gene

MGI Knock Outs for TDP2:

Animal Model Products

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for TDP2 Gene

Localization for TDP2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TDP2 Gene

Nucleus. Nucleus, PML body. Nucleus, nucleolus. Cytoplasm. Note=Localizes to nucleolar cavities following stress; localization to nucleolus is dependent on PML protein.
Cytoplasm. Note=(Microbial infection) In case of infection by picornavirus, relocalizes to cytoplasmic sites distinct from those containing viral proteins associated with RNA replication or encapsidation. {ECO:0000269 PubMed:22908287}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for TDP2 Gene COMPARTMENTS Subcellular localization image for TDP2 gene
Compartment Confidence
nucleus 5
extracellular 4
cytosol 2

Gene Ontology (GO) - Cellular Components for TDP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IDA 22908287
GO:0005730 nucleolus IEA --
GO:0005737 cytoplasm IEA,IDA 22908287
GO:0016605 PML body IEA,IDA 19794497
GO:0045171 intercellular bridge IDA --
genes like me logo Genes that share ontologies with TDP2: view

Pathways & Interactions for TDP2 Gene

genes like me logo Genes that share pathways with TDP2: view

Pathways by source for TDP2 Gene

1 BioSystems pathway for TDP2 Gene

Gene Ontology (GO) - Biological Process for TDP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006281 DNA repair IEA --
GO:0006302 double-strand break repair IMP 21030584
GO:0006974 cellular response to DNA damage stimulus IEA --
GO:0007166 cell surface receptor signaling pathway TAS 10764746
GO:0048666 neuron development IMP 24658003
genes like me logo Genes that share ontologies with TDP2: view

No data available for SIGNOR curated interactions for TDP2 Gene

Transcripts for TDP2 Gene

Unigene Clusters for TDP2 Gene

Tyrosyl-DNA phosphodiesterase 2:
Representative Sequences:

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for TDP2 Gene

ExUns: 1a · 1b ^ 2a · 2b · 2c · 2d · 2e ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7a · 7b · 7c · 7d
SP1: - - - -
SP2: - - -
SP3: -
SP4:
SP5: -

Relevant External Links for TDP2 Gene

GeneLoc Exon Structure for
TDP2
ECgene alternative splicing isoforms for
TDP2

Expression for TDP2 Gene

mRNA expression in normal human tissues for TDP2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TDP2 Gene

This gene is overexpressed in Whole Blood (x4.3).

Protein differential expression in normal tissues from HIPED for TDP2 Gene

This gene is overexpressed in Cervix (15.7), CD4 Tcells (11.9), and Breast (10.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for TDP2 Gene



Protein tissue co-expression partners for TDP2 Gene

NURSA nuclear receptor signaling pathways regulating expression of TDP2 Gene:

TDP2

SOURCE GeneReport for Unigene cluster for TDP2 Gene:

Hs.403010

mRNA Expression by UniProt/SwissProt for TDP2 Gene:

O95551-TYDP2_HUMAN
Tissue specificity: 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).
genes like me logo Genes that share expression patterns with TDP2: view

Primer Products

Orthologs for TDP2 Gene

This gene was present in the common ancestor of animals.

Orthologs for TDP2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TDP2 34 35
  • 99.36 (n)
cow
(Bos Taurus)
Mammalia TDP2 34 35
  • 89.35 (n)
dog
(Canis familiaris)
Mammalia TDP2 34 35
  • 87.07 (n)
rat
(Rattus norvegicus)
Mammalia Tdp2 34
  • 79.59 (n)
mouse
(Mus musculus)
Mammalia Tdp2 34 16 35
  • 79.39 (n)
oppossum
(Monodelphis domestica)
Mammalia TDP2 35
  • 60 (a)
OneToOne
chicken
(Gallus gallus)
Aves TDP2 34 35
  • 67.94 (n)
lizard
(Anolis carolinensis)
Reptilia TDP2 35
  • 61 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia tdp2 34
  • 64.22 (n)
Str.3755 34
African clawed frog
(Xenopus laevis)
Amphibia Xl.8025 34
zebrafish
(Danio rerio)
Actinopterygii tdp2b 34 35
  • 59.54 (n)
TDP2 (2 of 2) 35
  • 30 (a)
OneToMany
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.7216 34
worm
(Caenorhabditis elegans)
Secernentea CELE_Y63D3A.4 34
  • 44.74 (n)
Y63D3A.4 35
  • 29 (a)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea CSA.2731 35
  • 34 (a)
OneToOne
Species where no ortholog for TDP2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for TDP2 Gene

ENSEMBL:
Gene Tree for TDP2 (if available)
TreeFam:
Gene Tree for TDP2 (if available)

Paralogs for TDP2 Gene

No data available for Paralogs for TDP2 Gene

Variants for TDP2 Gene

Sequence variations from dbSNP and Humsavar for TDP2 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type
rs372245668 Pathogenic 24,658,560(+) ACTTA(C/T)AAAGC splice-donor-variant
rs758350133 Uncertain significance 24,651,017(+) TGCCC(A/C)AAAAC reference, missense
rs10085192 -- 24,651,974(+) agaac(C/T)tttta intron-variant
rs1047782 -- 24,650,503(-) GTACC(A/C)CATTG utr-variant-3-prime
rs10597437 -- 24,657,626(+) CACAC(-/TATTAA)TATTA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for TDP2 Gene

Variant ID Type Subtype PubMed ID
nsv601164 CNV gain 21841781
nsv601165 CNV loss 21841781

Variation tolerance for TDP2 Gene

Residual Variation Intolerance Score: 31.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.97; 87.31% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TDP2 Gene

Human Gene Mutation Database (HGMD)
TDP2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TDP2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TDP2 Gene

Disorders for TDP2 Gene

MalaCards: The human disease database

(3) MalaCards diseases for TDP2 Gene - From: ClinVar, Orphanet, and DISEASES

- elite association - COSMIC cancer census association via MalaCards
Search TDP2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TYDP2_HUMAN
  • Spinocerebellar ataxia, autosomal recessive, 23 (SCAR23) [MIM:616949]: A 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. {ECO:0000269 PubMed:24658003}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for TDP2

Genetic Association Database (GAD)
TDP2
Human Genome Epidemiology (HuGE) Navigator
TDP2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TDP2
genes like me logo Genes that share disorders with TDP2: view

No data available for Genatlas for TDP2 Gene

Publications for TDP2 Gene

  1. TTRAP, a novel protein that associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor-associated factors (TRAFs), and that inhibits nuclear factor-kappa B activation. (PMID: 10764746) Pype S. … Remacle J.E. (J. Biol. Chem. 2000) 3 4 22 64
  2. TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function. (PMID: 24658003) GA^mez-Herreros F. … Caldecott K.W. (Nat. Genet. 2014) 3 4 64
  3. The PML nuclear bodies-associated protein TTRAP regulates ribosome biogenesis in nucleolar cavities upon proteasome inhibition. (PMID: 21921940) Vilotti S. … Gustincich S. (Cell Death Differ. 2012) 3 4 64
  4. Characterization of magnesium requirement of human 5'-tyrosyl DNA phosphodiesterase mediated reaction. (PMID: 22405347) Adhikari S. … Uren A. (BMC Res. Notes 2012) 3 4 64
  5. Biochemical characterization of human Tyrosyl DNA Phosphodiesterase 2 (TDP2/TTRAP): a Mg2+/Mn2+-dependent phosphodiesterase specific for the repair of topoisomerase cleavage complexes. (PMID: 22822062) Gao R. … Pommier Y. (J. Biol. Chem. 2012) 3 4 64

Products for TDP2 Gene

Sources for TDP2 Gene

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