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

Summary

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: mouse all

Genomic context

Location:: 6p22.3

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
109.20200815	current	GRCh38.p13 (GCF_000001405.39)	6	NC_000006.12 (24649979..24666899, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (24650205..24667115, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Ubiquitin stimulated reversal of topoisomerase 2 DNA-protein crosslinks by TDP2.
Title: Ubiquitin stimulated reversal of topoisomerase 2 DNA-protein crosslinks by TDP2.
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.
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.
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.
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.
TDP2 re-localizes from the nucleus to the cytoplasm of EMCV infected cells.
Title: VPg unlinkase/TDP2 in cardiovirus infected cells: Re-localization and proteolytic cleavage.
These findings uncover a ZNF451-TDP2-catalyzed and SUMO2-modulated pathway for direct resolution of TOP2 cleavage complex.
Title: ZATT (ZNF451)-mediated resolution of topoisomerase 2 DNA-protein cross-links.
TDP2 suppresses chromosome rearrangements induced by TOP2 and reduces TOP2-induced chromosome translocations that arise during gene transcription.
Title: TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription.
Both the genome instability and cell death of MRE11-null and MRE11-mutated H129N cells are significantly reversed by overexpression of Tdp2, an enzyme that eliminates covalent Top2 conjugates; thus, the essential role of Mre11 nuclease activity is likely to remove the DNA lesions.
Title: Mre11 Is Essential for the Removal of Lethal Topoisomerase 2 Covalent Cleavage Complexes.
Study revealed a post-translational regulation of TDP2 activity and discovered a new role of ERK3 in increasing cancer cells' DNA damage response and chemoresistance to Top2 inhibitors.
Title: ERK3 regulates TDP2-mediated DNA damage response and chemoresistance in lung cancer cells.

Submit: New GeneRIF Correction See all GeneRIFs (30)

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	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G19612 (e-PCR)
- UniSTS:357

A001T03 (e-PCR)
- UniSTS:358

RH36217 (e-PCR)
- UniSTS:56728

RH93934 (e-PCR)
- UniSTS:92916

Homology

Homologs of the TDP2 gene: The TDP2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, C.elegans, and frog.
Orthologs from Annotation Pipeline: 329 organisms have orthologs with human gene TDP2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
5'-tyrosyl-DNA phosphodiesterase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
5'-tyrosyl-DNA phosphodiesterase activity	IDA Inferred from Direct Assay more info	PubMed
5'-tyrosyl-DNA phosphodiesterase activity	IMP Inferred from Mutant Phenotype more info	PubMed
magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
magnesium ion binding	TAS Traceable Author Statement more info	PubMed
manganese ion binding	IDA Inferred from Direct Assay more info	PubMed
nuclease activity	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
single-stranded DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
single-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
transcription corepressor activity	TAS Traceable Author Statement more info	PubMed
tyrosyl-RNA phosphodiesterase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
cell surface receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
double-strand break repair	IBA Inferred from Biological aspect of Ancestor more info	PubMed
double-strand break repair	IDA Inferred from Direct Assay more info	PubMed
double-strand break repair	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of nucleic acid-templated transcription	IEA Inferred from Electronic Annotation more info
neuron development	IMP Inferred from Mutant Phenotype more info	PubMed
nucleic acid phosphodiester bond hydrolysis	IEA Inferred from Electronic Annotation more info
viral process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
PML body	IBA Inferred from Biological aspect of Ancestor more info	PubMed
PML body	IDA Inferred from Direct Assay more info	PubMed
aggresome	IDA Inferred from Direct Assay more info
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
nuclear body	IDA Inferred from Direct Assay more info
nucleolus	IEA Inferred from Electronic Annotation more info
nucleoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleoplasm	IDA Inferred from Direct Assay more info
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

EC 3.1.4.-

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

NG_052787.1 RefSeqGene

Range

4989..21909

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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