TDP2 [The Human Chemical-Genetic Interaction Map Project]

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======= TDP2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: TDP2
  * **<color #00a2e8>Official Name</color>**: tyrosyl-DNA phosphodiesterase 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=51567|51567]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O95551|O95551]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=TDP2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20TDP2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/605764|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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. The 5'-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DNA double-strand breaks/DSBs without the need for nuclease activity, creating a 'clean' DSB with 5'-phosphate termini that are ready for ligation. Thereby, protects the transcription of many genes involved in neurological development and maintenance from the abortive activity of TOP2. Hydrolyzes 5'- phosphoglycolates on protruding 5' ends on DSBs due to DNA damage by radiation and free radicals. Has preference for single-stranded DNA or duplex DNA with a 4 base pair overhang as substrate. Acts as a regulator of ribosome biogenesis following stress. 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 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. {ECO:0000269|PubMed:19794497, ECO:0000269|PubMed:21030584, ECO:0000269|PubMed:21921940, ECO:0000269|PubMed:21980489, ECO:0000269|PubMed:22405347, ECO:0000269|PubMed:22822062, ECO:0000269|PubMed:24658003}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Exo endo phos|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|tyrosyl-RNA phosphodiesterase activity|
|5-tyrosyl-DNA phosphodiesterase activity|
|nuclease activity|
|aggresome|
|manganese ion binding|
|PML body|
|single-stranded DNA binding|
|double-strand break repair|
|magnesium ion binding|
|transcription corepressor activity|
|nuclear body|
|nucleic acid phosphodiester bond hydrolysis|
|DNA repair|
|DNA metabolic process|
|cellular response to DNA damage stimulus|
|neuron development|
|nucleolus|
|neuron differentiation|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|negative regulation of RNA metabolic process|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|negative regulation of cellular biosynthetic process|
|generation of neurons|
|negative regulation of biosynthetic process|
|neurogenesis|
|cell development|
|cellular response to stress|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp198|Etoposide 0.1μM R05 exp198]]|-3.8|
|[[:results:exp360|Genistein 15μM R07 exp360]]|-2.98|
|[[:results:exp240|Pyridostatin 4μM R05 exp240]]|-2.25|
|[[:results:exp357|Dorsomorphin 5μM R07 exp357]]|-2.03|
|[[:results:exp69|Deguelin 0.05μM R02 exp69]]|-1.73|
|[[:results:exp125|GSK461364A 0.005μM R03 exp125]]|1.87|
|[[:results:exp42|BI-6727 0.001μM R01 exp42]]|2.08|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:z:znf451|ZNF451]]|0.404|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 4/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|1/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|1/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|1/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 3494
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.65 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='TDP2 Expression in NALM6 Cells: 5.65'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>