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TDP2 tyrosyl-DNA phosphodiesterase 2 [ Homo sapiens (human) ]

Gene ID: 51567, updated on 4-Jul-2021

Summary

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Official Symbol
TDP2provided by HGNC
Official Full Name
tyrosyl-DNA phosphodiesterase 2provided by HGNC
Primary source
HGNC:HGNC:17768
See related
Ensembl:ENSG00000111802 MIM:605764
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
EAP2; AD022; EAPII; TTRAP; hTDP2; dJ30M3.3
Summary
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]
Expression
Broad expression in small intestine (RPKM 97.5), colon (RPKM 87.6) and 24 other tissues See more
Orthologs
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Genomic context

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See TDP2 in Genome Data Viewer
Location:
6p22.3
Exon count:
7
Annotation release Status Assembly Chr Location
109.20210514 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (24649979..24666899, complement)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (24650207..24667127, complement)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene glycosylphosphatidylinositol specific phospholipase D1 Neighboring gene aldehyde dehydrogenase 5 family member A1 Neighboring gene KIAA0319 Neighboring gene keratin 8 pseudogene 43 Neighboring gene Sharpr-MPRA regulatory region 5933 Neighboring gene acyl-CoA thioesterase 13 Neighboring gene chromosome 6 open reading frame 62 Neighboring gene adaptor related protein complex 3 subunit sigma 1 pseudogene Neighboring gene long intergenic non-protein coding RNA 2828

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Characterization of a novel loss-of-function variant in TDP2 in two adult patients with spinocerebellar ataxia autosomal recessive 23 (SCAR23). Errichiello E, et al. J Hum Genet, 2020 Dec. PMID 32651480
  2. Tyrosyl-DNA phosphodiesterase 2 (TDP2) repairs topoisomerase 1 DNA-protein crosslinks and 3'-blocking lesions in the absence of tyrosyl-DNA phosphodiesterase 1 (TDP1). Tsuda M, et al. DNA Repair (Amst), 2020 Jul - Aug. PMID 32460231
  3. Ubiquitin stimulated reversal of topoisomerase 2 DNA-protein crosslinks by TDP2. Schellenberg MJ, et al. Nucleic Acids Res, 2020 Jun 19. PMID 32356875, Free PMC Article
  4. TDP2 suppresses genomic instability induced by androgens in the epithelial cells of prostate glands. Al Mahmud MR, et al. Genes Cells, 2020 Jul. PMID 32277721, Free PMC Article
  5. Effects of TDP2/VPg Unlinkase Activity on Picornavirus Infections Downstream of Virus Translation. Holmes AC, et al. Viruses, 2020 Jan 31. PMID 32023921, Free PMC Article

See all (70) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Characterization of a novel loss-of-function variant in TDP2 in two adult patients with spinocerebellar ataxia autosomal recessive 23 (SCAR23).
    Title: Characterization of a novel loss-of-function variant in TDP2 in two adult patients with spinocerebellar ataxia autosomal recessive 23 (SCAR23).
  2. Untangling trapped topoisomerases with tyrosyl-DNA phosphodiesterases.
    Title: Untangling trapped topoisomerases with tyrosyl-DNA phosphodiesterases.
  3. Tyrosyl-DNA phosphodiesterase 2 (TDP2) repairs topoisomerase 1 DNA-protein crosslinks and 3'-blocking lesions in the absence of tyrosyl-DNA phosphodiesterase 1 (TDP1).
    Title: Tyrosyl-DNA phosphodiesterase 2 (TDP2) repairs topoisomerase 1 DNA-protein crosslinks and 3'-blocking lesions in the absence of tyrosyl-DNA phosphodiesterase 1 (TDP1).
  4. Effects of TDP2/VPg Unlinkase Activity on Picornavirus Infections Downstream of Virus Translation.
    Title: Effects of TDP2/VPg Unlinkase Activity on Picornavirus Infections Downstream of Virus Translation.
  5. TDP2 suppresses genomic instability induced by androgens in the epithelial cells of prostate glands.
    Title: TDP2 suppresses genomic instability induced by androgens in the epithelial cells of prostate glands.
  6. Ubiquitin stimulated reversal of topoisomerase 2 DNA-protein crosslinks by TDP2.
    Title: Ubiquitin stimulated reversal of topoisomerase 2 DNA-protein crosslinks by TDP2.
  7. This article reviews TDP1 and TDP2 in the context of mitochondrial DNA repair. [review]
    Title: Mammalian Tyrosyl-DNA Phosphodiesterases in the Context of Mitochondrial DNA Repair.
  8. Data suggest that tyrosyl-DNA Phosphodiesterases 1 (TDP1) and 2 (TDP2) are promising therapeutic targets and their inhibitors are expected to significantly synergize the effects of current anti-tumor therapies [Review].
    Title: Tyrosyl-DNA phosphodiesterases: rescuing the genome from the risks of relaxation.
  9. lack of TDP2 in the mitochondria reduces the mitochondria transcription levels in two different human cell lines. In addition to identifying a novel TDP2(S) isoform, our report demonstrates the presence and importance of both TDP2 isoforms in the mitochondria.
    Title: Mitochondrial tyrosyl-DNA phosphodiesterase 2 and its TDP2<sup>S</sup> short isoform.
  10. Data indicate that tyrosyl-DNA phosphodiesterase 2 (TDP2) alone does not remove DNA topoisomerase II (TOP2)-DNA complexes from genomic DNA in vitro and that depletion of TDP2 in cells does not slow the removal of TOP2-DNA complexes.
    Title: Effect of TDP2 on the Level of TOP2-DNA Complexes and SUMOylated TOP2-DNA Complexes.
Submit: New GeneRIF Correction See all GeneRIFs (35)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Spinocerebellar ataxia, autosomal recessive 23
MedGen: C4310780 OMIM: 616949 GeneReviews: Not available
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
integrase gag-pol TTRAP and HIV-1 IN interact in vivo and in vitro. The interaction involves the first 180 amino acids of TTRAP PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC9099, MGC111021

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 5'-tyrosyl-DNA phosphodiesterase activity IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables 5'-tyrosyl-DNA phosphodiesterase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables 5'-tyrosyl-DNA phosphodiesterase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables magnesium ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables magnesium ion binding TAS
Traceable Author Statement
more info
 PubMed 
enables manganese ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables nuclease activity IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables single-stranded DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables single-stranded DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables transcription corepressor activity TAS
Traceable Author Statement
more info
 PubMed 
enables tyrosyl-RNA phosphodiesterase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in cell surface receptor signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
involved_in double-strand break repair IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in double-strand break repair IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in double-strand break repair IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of transcription, DNA-templated IEA
Inferred from Electronic Annotation
more info
  
involved_in neuron development IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in nucleic acid phosphodiester bond hydrolysis IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
is_active_in PML body IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
located_in PML body IDA
Inferred from Direct Assay
more info
 PubMed 
located_in aggresome IDA
Inferred from Direct Assay
more info
  
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nuclear body IDA
Inferred from Direct Assay
more info
  
located_in nucleolus IEA
Inferred from Electronic Annotation
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
tyrosyl-DNA phosphodiesterase 2
Names
5'-Tyr-DNA phosphodiesterase
5'-tyrosyl-DNA phosphodiesterase
ETS1-associated protein 2
ETS1-associated protein II
TRAF and TNF receptor-associated protein
VPg unlinkase
epididymis secretory sperm binding protein
tyr-DNA phosphodiesterase 2
tyrosyl-RNA phosphodiesterase
NP_057698.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_052787.1 RefSeqGene

    Range
    4989..21909
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_016614.3 → NP_057698.2  tyrosyl-DNA phosphodiesterase 2

    See identical proteins and their annotated locations for NP_057698.2

    Status: REVIEWED

    Source sequence(s)
    AL031775
    Consensus CDS
    CCDS4557.1
    UniProtKB/Swiss-Prot
    O95551
    Related
    ENSP00000367440.4, ENST00000378198.9
    Conserved Domains (2) summary
    cd09080
    Location:114 → 358
    TDP2; Phosphodiesterase domain of human TDP2, a 5'-tyrosyl DNA phosphodiesterase, and related domains
    cd14344
    Location:27 → 63
    UBA_TYDP2; UBA-like domain found in tyrosyl-DNA phosphodiesterase 2 (TDP2) and similar proteins

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p13 Primary Assembly

    Range
    24649979..24666899 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O95551.1 GenPept UniProtKB/Swiss-Prot:O95551

Gene LinkOut

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