======= TRIP12 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: TRIP12
  * **<color #00a2e8>Official Name</color>**: thyroid hormone receptor interactor 12
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=9320|9320]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q14669|Q14669]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=TRIP12&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20TRIP12|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/604506|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is an E3 ubiquitin-protein ligase involved in the degradation of the p19ARF/ARF isoform of CDKN2A, a tumor suppressor. The encoded protein also plays a role in the DNA damage response by regulating the stability of USP7, which regulates tumor suppressor p53. [provided by RefSeq, Jan 2017]. 
  * **<color #00a2e8>UniProt Summary</color>**:  E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair. Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardeless of the presence of lysine residues in target proteins. In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress. In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation. Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A. Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation. Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins. Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes. {ECO:0000269|PubMed:18627766, ECO:0000269|PubMed:19028681, ECO:0000269|PubMed:20208519, ECO:0000269|PubMed:20829358, ECO:0000269|PubMed:22884692}.

<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'>
|HECT|
|WWE|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|negative regulation of histone ubiquitination|
|negative regulation of histone H2A K63-linked ubiquitination|
|regulation of histone H2A K63-linked ubiquitination|
|negative regulation of protein K63-linked ubiquitination|
|negative regulation of protein polyubiquitination|
|regulation of histone ubiquitination|
|regulation of protein K63-linked ubiquitination|
|regulation of protein polyubiquitination|
|thyroid hormone receptor binding|
|negative regulation of double-strand break repair|
|negative regulation of DNA repair|
|negative regulation of histone modification|
|negative regulation of chromatin organization|
|negative regulation of protein ubiquitination|
|regulation of double-strand break repair|
|negative regulation of response to DNA damage stimulus|
|negative regulation of protein modification by small protein conjugation or removal|
|negative regulation of DNA metabolic process|
|regulation of DNA repair|
|regulation of embryonic development|
|negative regulation of chromosome organization|
|regulation of histone modification|
|regulation of chromatin organization|
|regulation of protein ubiquitination|
|regulation of response to DNA damage stimulus|
|regulation of protein modification by small protein conjugation or removal|
|ubiquitin-protein transferase activity|
|protein polyubiquitination|
|regulation of chromosome organization|
|regulation of DNA metabolic process|
|negative regulation of organelle organization|
|nuclear speck|
|DNA repair|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|modification-dependent macromolecule catabolic process|
|proteolysis involved in cellular protein catabolic process|
|negative regulation of protein modification process|
|cellular protein catabolic process|
|protein catabolic process|
|protein ubiquitination|
|negative regulation of cellular component organization|
|regulation of cellular response to stress|
|DNA metabolic process|
|protein modification by small protein conjugation|
|cellular response to DNA damage stimulus|
|cellular macromolecule catabolic process|
|protein modification by small protein conjugation or removal|
|negative regulation of cellular protein metabolic process|
|macromolecule catabolic process|
|organonitrogen compound catabolic process|
|negative regulation of protein metabolic process|
|proteolysis|
|regulation of organelle organization|
|negative regulation of nucleobase-containing compound metabolic process|
|regulation of response to stress|
|negative regulation of response to stimulus|
|cellular response to stress|
|organic substance catabolic process|
|cellular catabolic process|
|regulation of protein modification process|
</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:exp392|PT-1 25μM R07 exp392]]|-2.57|
|[[:results:exp429|Rapamycin 0.001μM R08 exp429]]|-2.57|
|[[:results:exp30|Rapamycin 10μM R00 exp30]]|-2.56|
|[[:results:exp169|BH1 1μM R04 exp169]]|-2.51|
|[[:results:exp307|Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307]]|-2.5|
|[[:results:exp222|Betulinic acid 10 to 15μM on day4 R05 exp222]]|-2.49|
|[[:results:exp75|MK-1775 0.32μM R02 exp75]]|-2.49|
|[[:results:exp228|Demecolcine 0.03μM R05 exp228]]|-2.39|
|[[:results:exp410|THZ531 0.11 to 0.125μM on day4 R07 exp410]]|-2.36|
|[[:results:exp29|Rapamycin 1μM R00 exp29]]|-2.35|
|[[:results:exp535|Trimetrexate 0.03μM R08 exp535]]|-2.34|
|[[:results:exp275|Citral 75μM R06 exp275]]|-2.23|
|[[:results:exp131|L-74142 5μM R03 exp131]]|-2.2|
|[[:results:exp365|I-BRD9 4μM R07 exp365]]|-2.09|
|[[:results:exp21|MLN-4924 0.2μM R00 exp21]]|-2.09|
|[[:results:exp216|Erlotinib 10μM R05 exp216]]|-2.07|
|[[:results:exp490|Hydroxychloroquine 30μM R08 exp490]]|-2.04|
|[[:results:exp318|ABT-702 5μM R07 exp318]]|-2|
|[[:results:exp270|Campthothecin 0.001μM R06 exp270]]|-1.99|
|[[:results:exp329|Hydroxyurea 100μM R07 exp329]]|-1.99|
|[[:results:exp102|Nifuroxazide 5μM R03 exp102]]|-1.98|
|[[:results:exp438|NN-Diethyl-meta-toluamide 500μM R08 exp438]]|-1.93|
|[[:results:exp288|HMS-I2 10μM R06 exp288]]|-1.92|
|[[:results:exp434|Vemurafenib 6.6μM R08 exp434]]|-1.89|
|[[:results:exp319|ABT-702 5μM plus Dimethyloxaloylglycine 11μM R07 exp319]]|-1.88|
|[[:results:exp191|Hypoxia 5%O2 R04 exp191]]|-1.87|
|[[:results:exp480|ETC-159 50μM R08 exp480]]|-1.86|
|[[:results:exp308|Rapamycin 2μM plus FK-506 5μM R07 exp308]]|-1.84|
|[[:results:exp471|Cholesterol 0.003 to 0.006 to 0.1μM on day2 then day6 R08 exp471]]|-1.82|
|[[:results:exp47|Lapatinib 5μM R01 exp47]]|-1.81|
|[[:results:exp340|BN82002 4μM R07 exp340]]|-1.8|
|[[:results:exp317|Geldanamycin 0.015 to 0.05μM on day4 R07 exp317]]|-1.79|
|[[:results:exp516|Pyrazinamide 100μM R08 exp516]]|-1.76|
|[[:results:exp463|Caffeine 2600μM R08 exp463]]|-1.75|
|[[:results:exp215|Colchicine 0.009μM R05 exp215]]|-1.73|
|[[:results:exp177|Apcin 25μM plus proTAME 2μM R04 exp177]]|1.77|
|[[:results:exp514|Phorbol-12-myristate-13-acetate 0.57μM R08 exp514]]|1.78|
|[[:results:exp22|MLN-4924 2μM R00 exp22]]|1.84|
|[[:results:exp106|UM131593 0.2μM R03 exp106]]|1.93|
|[[:results:exp499|LY2090314 0.003μM R08 exp499]]|1.97|
|[[:results:exp435|JQ1 0.8μM R08 exp435]]|2.13|
|[[:results:exp503|Mitomycin-C 0.06μM R08 exp503]]|2.25|
|[[:results:exp96|BI-2536 0.02μM R03 exp96]]|2.28|
|[[:results:exp451|Atovaquone 15μM R08 exp451]]|2.34|
|[[:results:exp478|Doxorubicin 0.02μM R08 exp478]]|2.35|
|[[:results:exp531|THZ1 0.06μM R08 exp531]]|2.46|
|[[:results:exp532|TIC10 10μM R08 exp532]]|2.48|
|[[:results:exp67|BVD-523 15μM R02 exp67]]|2.56|
|[[:results:exp500|LY2090314 0.003μM R08 exp500 no dilution day6]]|2.89|
|[[:results:exp294|Nutlin-3A 1.6μM R06 exp294]]|4.44|
|[[:results:exp468|CB-5083 0.4μM R08 exp468]]|4.8|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:m:med23|MED23]]|0.493|
|[[:human genes:c:cbx3|CBX3]]|0.492|
|[[:human genes:o:otud5|OTUD5]]|0.469|
|[[:human genes:n:nsd1|NSD1]]|0.467|
|[[:human genes:r:rptor|RPTOR]]|0.463|
|[[:human genes:t:tti2|TTI2]]|0.459|
|[[:human genes:b:bap1|BAP1]]|0.457|
|[[:human genes:p:pdcd5|PDCD5]]|0.452|
|[[:human genes:i:id3|ID3]]|0.452|
|[[:human genes:f:fbxo11|FBXO11]]|0.449|
|[[:human genes:a:atf7ip|ATF7IP]]|0.445|
|[[:human genes:t:trim28|TRIM28]]|0.437|
|[[:human genes:a:arl14ep|ARL14EP]]|0.435|
|[[:human genes:u:ubr5|UBR5]]|0.434|
|[[:human genes:r:rbmx2|RBMX2]]|0.434|
|[[:human genes:m:mtor|MTOR]]|0.432|
|[[:human genes:h:hars|HARS]]|0.42|
|[[:human genes:c:csnk2b|CSNK2B]]|0.415|
|[[:human genes:t:telo2|TELO2]]|0.414|
|[[:human genes:a:asb7|ASB7]]|0.409|
|[[:human genes:d:dohh|DOHH]]|0.409|
|[[:human genes:t:tle4|TLE4]]|0.408|
|[[:human genes:c:cbfb|CBFB]]|0.407|
|[[:human genes:w:wdr24|WDR24]]|0.407|
|[[:human genes:d:dr1|DR1]]|0.404|
|[[:human genes:t:tsen54|TSEN54]]|0.402|
|[[:human genes:z:znf445|ZNF445]]|0.401|
|[[:human genes:c:ccdc101|CCDC101]]|0.4|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 1/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|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>**: 4669
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.96 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='TRIP12 Expression in NALM6 Cells: 7.96'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>