Description: Homo sapiens tyrosyl-DNA phosphodiesterase 2 (TDP2), mRNA. RefSeq Summary (NM_016614): 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]. Transcript (Including UTRs) Position: hg19 chr6:24,650,205-24,667,115 Size: 16,911 Total Exon Count: 7 Strand: - Coding Region Position: hg19 chr6:24,651,016-24,667,090 Size: 16,075 Coding Exon Count: 7
ID:TYDP2_HUMAN DESCRIPTION: RecName: Full=Tyrosyl-DNA phosphodiesterase 2; Short=Tyr-DNA phosphodiesterase 2; Short=hTDP2; EC=3.1.4.-; AltName: Full=5'-tyrosyl-DNA phosphodiesterase; Short=5'-Tyr-DNA phosphodiesterase; AltName: Full=ETS1-associated protein 2; AltName: Full=ETS1-associated protein II; Short=EAPII; AltName: Full=TRAF and TNF receptor-associated protein; AltName: Full=Tyrosyl-RNA phosphodiesterase; AltName: Full=VPg unlinkase; 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 to 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. COFACTOR: Magnesium. Can use other divalent cations as cofactor in vitro, such as manganese. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=8 uM for single-stranded 5'-tyrosyl DNA; Note=kcat is 3 sec(-1) with single-stranded 5'-tyrosyl DNA as substrate; SUBUNIT: Interacts with TRAF2, TRAF3, TRAF5, TRAF6, TNFRSF8/CD30, TNFRSF5/CD40, TNFRSF1B/TNF-R75, ETS1, ETS2, FLI1, SMAD3 and ACVR1B/ALK4. SUBCELLULAR LOCATION: 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. TISSUE SPECIFICITY: Widely expressed. PTM: Ubiquitinated by TRAF6. SIMILARITY: Belongs to the CCR4/nocturin family. SEQUENCE CAUTION: Sequence=BAG59230.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=CAD92510.1; Type=Erroneous gene model prediction; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/ttrap/";
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Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): TDP2 CDC HuGE Published Literature: TDP2 Positive Disease Associations: Hypertrophy, Left Ventricular Related Studies:
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O95551
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
