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

Gene ID: 51567, updated on 11-Jun-2025
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; AllianceGenome:HGNC:17768
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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See TDP2 in Genome Data Viewer
Location:
6p22.3
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (24649979..24666899, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (24520363..24537292, complement)
RS_2024_09 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 aldehyde dehydrogenase 5 family member A1 Neighboring gene uncharacterized LOC124901277 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr6:24538795-24539994 Neighboring gene NANOG hESC enhancer GRCh37_chr6:24547459-24547981 Neighboring gene KIAA0319 Neighboring gene MPRA-validated peak5735 silencer Neighboring gene keratin 8 pseudogene 43 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16993 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:24666173-24666845 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:24666846-24667517 Neighboring gene uncharacterized LOC124901279 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:24682160-24682927 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:24682928-24683696 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr6:24683697-24684463 Neighboring gene acyl-CoA thioesterase 13 Neighboring gene uncharacterized LOC124901278

Go to nucleotide: Graphics FASTA GenBank

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Related articles in PubMed

  1. A novel non-sense mutation in TDP2 causes spinocerebellar ataxia autosomal recessive 23 accompanied by bilateral upward gaze; report of a case and review of the literature. Zoghi S, et al. Eur J Med Genet, 2021 Dec. PMID 34606976
  2. The PML nuclear bodies-associated protein TTRAP regulates ribosome biogenesis in nucleolar cavities upon proteasome inhibition. Vilotti S, et al. Cell Death Differ, 2012 Mar. PMID 21921940, Free PMC Article
  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. 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
  5. 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

See all (86) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Exploring the removal of Spo11 and topoisomerases from DNA breaks in S. cerevisiae by human Tyrosyl DNA Phosphodiesterase 2.
    Title: Exploring the removal of Spo11 and topoisomerases from DNA breaks in S. cerevisiae by human Tyrosyl DNA Phosphodiesterase 2.
  2. Inactivating TDP2 missense mutation in siblings with congenital abnormalities reminiscent of fanconi anemia.
    Title: Inactivating TDP2 missense mutation in siblings with congenital abnormalities reminiscent of fanconi anemia.
  3. A novel non-sense mutation in TDP2 causes spinocerebellar ataxia autosomal recessive 23 accompanied by bilateral upward gaze; report of a case and review of the literature.
    Title: A novel non-sense mutation in TDP2 causes spinocerebellar ataxia autosomal recessive 23 accompanied by bilateral upward gaze; report of a case and review of the literature.
  4. DNA and RNA Cleavage Complexes and Repair Pathway for TOP3B RNA- and DNA-Protein Crosslinks.
    Title: DNA and RNA Cleavage Complexes and Repair Pathway for TOP3B RNA- and DNA-Protein Crosslinks.
  5. 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).
  6. Untangling trapped topoisomerases with tyrosyl-DNA phosphodiesterases.
    Title: Untangling trapped topoisomerases with tyrosyl-DNA phosphodiesterases.
  7. 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).
  8. 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.
  9. 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.
  10. Ubiquitin stimulated reversal of topoisomerase 2 DNA-protein crosslinks by TDP2.
    Title: Ubiquitin stimulated reversal of topoisomerase 2 DNA-protein crosslinks by TDP2.
Submit: New GeneRIF Correction See all GeneRIFs (39)

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: C4750914 OMIM: 616949 GeneReviews: Not available
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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Products Interactant Other Gene Complex Source Pubs Description

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
  
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 DNA binding IEA
Inferred from Electronic Annotation
more info
  
enables catalytic activity IEA
Inferred from Electronic Annotation
more info
  
enables hydrolase activity IEA
Inferred from Electronic Annotation
more info
  
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 metal ion binding IEA
Inferred from Electronic Annotation
more info
  
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
  
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-DNA phosphodiesterase activity IEA
Inferred from Electronic Annotation
more info
  
enables tyrosyl-RNA phosphodiesterase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in DNA damage response IEA
Inferred from Electronic Annotation
more info
  
involved_in DNA repair IEA
Inferred from Electronic Annotation
more info
  
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
  
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 DNA-templated transcription IEA
Inferred from Electronic Annotation
more info
  
involved_in neuron development IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
is_active_in PML body IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in PML body IDA
Inferred from Direct Assay
more info
 PubMed 
located_in PML body IEA
Inferred from Electronic Annotation
more info
  
located_in aggresome IDA
Inferred from Direct Assay
more info
  
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm IEA
Inferred from Electronic Annotation
more info
  
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 
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  
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

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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
    B4DKL8, B4DQ95, O95551, Q2TBE2, Q5JYM0, Q7Z6U5, Q9NUK5, Q9NYY9
    UniProtKB/TrEMBL
    A0A384MDM5
    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: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

    Range
    24649979..24666899 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060930.1 Alternate T2T-CHM13v2.0

    Range
    24520363..24537292 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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