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Aliases for TDP2 Gene

Aliases for TDP2 Gene

  • Tyrosyl-DNA Phosphodiesterase 2 2 3
  • TRAF And TNF Receptor Associated Protein 2 3
  • 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
  • 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 reading disorder. Among its related pathways are DNA Double-Strand Break Repair and G2/M DNA damage checkpoint. 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. Hydrolyzes 5-phosphoglycolates on protruding 5 ends on DNA double-strand breaks (DSBs) due to DNA damage by radiation and free radicals. The 5-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DSBs without the need for nuclease activity, creating a clean DSB with 5-phosphate termini that are ready for ligation. Has preference for single-stranded DNA or duplex DNA with a 4 base pair overhang as substrate. 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 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. 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. Acts as a regulator of ribosome biogenesis following stress.

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

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

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

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for TDP2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TDP2 Gene

No data available for Regulatory Elements 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; Note=Magnesium. Can use other divalent cations as cofactor in vitro, such as manganese.;
    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};

    Alternative splice isoforms for TDP2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TDP2 Gene

Proteomics data for TDP2 Gene at MOPED

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:

Antibody Products

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. Hydrolyzes 5-phosphoglycolates on protruding 5 ends on DNA double-strand breaks (DSBs) due to DNA damage by radiation and free radicals. The 5-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DSBs without the need for nuclease activity, creating a clean DSB with 5-phosphate termini that are ready for ligation. Has preference for single-stranded DNA or duplex DNA with a 4 base pair overhang as substrate. 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 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. 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. Acts as a regulator of ribosome biogenesis following stress.

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

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for TDP2

In Situ Assay Products

Flow Cytometry Products

No data available for 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. In case of infection by picornavirus, relocalizes to cytoplasmic sites distinct from those containing viral proteins associated with RNA replication or encapsidation.

Subcellular locations from

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

Gene Ontology (GO) - Cellular Components for TDP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 22908287
GO:0005654 nucleoplasm IDA --
GO:0005730 nucleolus IEA --
GO:0005737 cytoplasm IDA 22908287
GO:0016605 PML body IDA 19794497
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:0006302 double-strand break repair IMP 21030584
GO:0007166 cell surface receptor signaling pathway TAS 10764746
GO:0090305 nucleic acid phosphodiester bond hydrolysis IEA --
GO:1903507 negative regulation of nucleic acid-templated transcription TAS 10764746
genes like me logo Genes that share ontologies with TDP2: view

No data available for SIGNOR curated interactions for TDP2 Gene

Drugs & Compounds for TDP2 Gene

No Compound Related Data Available

Transcripts for TDP2 Gene

Unigene Clusters for TDP2 Gene

Tyrosyl-DNA phosphodiesterase 2:
Representative Sequences:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for TDP2

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, MOPED, and MaxQB for TDP2 Gene



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.
genes like me logo Genes that share expression patterns with TDP2: view

Protein tissue co-expression partners for TDP2 Gene

Primer Products

In Situ Assay 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
cow
(Bos Taurus)
Mammalia TDP2 35
  • 89.35 (n)
  • 86.22 (a)
TDP2 36
  • 84 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TDP2 35
  • 87.07 (n)
  • 83.62 (a)
TDP2 36
  • 81 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Tdp2 35
  • 79.39 (n)
  • 69.53 (a)
Tdp2 16
Tdp2 36
  • 64 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia TDP2 35
  • 99.36 (n)
  • 99.45 (a)
TDP2 36
  • 92 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Tdp2 35
  • 79.59 (n)
  • 68.64 (a)
oppossum
(Monodelphis domestica)
Mammalia TDP2 36
  • 60 (a)
OneToOne
chicken
(Gallus gallus)
Aves TDP2 35
  • 67.94 (n)
  • 65.19 (a)
TDP2 36
  • 60 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TDP2 36
  • 61 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.3755 35
tdp2 35
  • 64.22 (n)
  • 64.52 (a)
African clawed frog
(Xenopus laevis)
Amphibia Xl.8025 35
zebrafish
(Danio rerio)
Actinopterygii tdp2b 35
  • 59.54 (n)
  • 56.63 (a)
TDP2 (2 of 2) 36
  • 30 (a)
OneToMany
tdp2b 36
  • 49 (a)
OneToMany
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.7216 35
worm
(Caenorhabditis elegans)
Secernentea CELE_Y63D3A.4 35
  • 44.74 (n)
  • 33.55 (a)
Y63D3A.4 36
  • 29 (a)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea CSA.2731 36
  • 34 (a)
OneToOne
Species with no ortholog for TDP2:
  • 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 MAF
rs12393 -- 24,650,009(+) TTCTC(C/T)TGTGG utr-variant-3-prime
rs707887 -- 24,650,443(-) TATTT(A/G)AAATA utr-variant-3-prime
rs1047782 -- 24,650,503(-) GTACC(A/C/G)CATTG utr-variant-3-prime
rs1129643 -- 24,653,154(-) GTGCA(G/T)GTGAA splice-acceptor-variant
rs1129644 -- 24,653,148(-) GTGAA(C/T)GTGTC reference, synonymous-codon, nc-transcript-variant

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

Variant ID Type Subtype PubMed ID
nsv883481 CNV Loss 21882294

Variation tolerance for TDP2 Gene

Residual Variation Intolerance Score: 31.85% 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

HapMap Linkage Disequilibrium report
TDP2
Human Gene Mutation Database (HGMD)
TDP2

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

Disorders for TDP2 Gene

MalaCards: The human disease database

(2) MalaCards diseases for TDP2 Gene - From: Orphanet and DISEASES

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 UniProtKB/Swiss-Prot and Genatlas for TDP2 Gene

Publications for TDP2 Gene

  1. Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules. (PMID: 14609633) Lee B.H. … Arikawa J. (Virus Res. 2003) 23 67
  2. Sequence analysis identifies TTRAP, a protein that associates with CD40 and TNF receptor-associated factors, as a member of a superfamily of divalent cation-dependent phosphodiesterases. (PMID: 11478795) Rodrigues-Lima F. … Cassinat B. (Biochem. Biophys. Res. Commun. 2001) 2 67
  3. 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) 23 67
  4. The BioPlex Network: A Systematic Exploration of the Human Interactome. (PMID: 26186194) Huttlin E.L. … Gygi S.P. (Cell 2015) 67
  5. Involvement of the host DNA-repair enzyme TDP2 in formation of the covalently closed circular DNA persistence reservoir of hepatitis B viruses. (PMID: 25201958) KAPniger C. … Nassal M. (Proc. Natl. Acad. Sci. U.S.A. 2014) 67

Products for TDP2 Gene

Sources for TDP2 Gene

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