USP15 [The Human Chemical-Genetic Interaction Map Project]

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======= USP15 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: USP15
  * **<color #00a2e8>Official Name</color>**: ubiquitin specific peptidase 15
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=9958|9958]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9Y4E8|Q9Y4E8]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=USP15&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20USP15|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/604731|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling, NF-kappa-B and RNF41/NRDP1-PRKN pathways (PubMed:21947082, PubMed:22344298, PubMed:24852371, PubMed:16005295, PubMed:17318178, PubMed:19826004, PubMed:19576224). Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF- beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates as well as 'Lys- 48'-linked polyubiquitin chains, protecting them against proteasomal degradation. May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B (PubMed:24526689). Acts as an inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes cleavage of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains attached by parkin on target proteins such as MFN2, thereby reducing parkin's ability to drive mitophagy (PubMed:24852371). Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF- kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP (PubMed:16005295, PubMed:17318178, PubMed:19826004, PubMed:19576224). Involved in endosome organization by mediating deubiquitination of SQSTM1: ubiquitinated SQSTM1 forms a molecular bridge that restrains cognate vesicles in the perinuclear region and its deubiquitination releases target vesicles for fast transport into the cell periphery (PubMed:27368102). {ECO:0000269|PubMed:16005295, ECO:0000269|PubMed:17318178, ECO:0000269|PubMed:19576224, ECO:0000269|PubMed:19826004, ECO:0000269|PubMed:21947082, ECO:0000269|PubMed:22344298, ECO:0000269|PubMed:24526689, ECO:0000269|PubMed:24852371, ECO:0000269|PubMed:27368102}.

<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'>
|UCH|
|DUSP|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|ubiquitin modification-dependent histone binding|
|histone H2B conserved C-terminal lysine deubiquitination|
|monoubiquitinated protein deubiquitination|
|pathway-restricted SMAD protein phosphorylation|
|histone deubiquitination|
|transforming growth factor beta receptor binding|
|SMAD binding|
|thiol-dependent ubiquitinyl hydrolase activity|
|BMP signaling pathway|
|cysteine-type endopeptidase activity|
|transforming growth factor beta receptor signaling pathway|
|response to BMP|
|cellular response to BMP stimulus|
|thiol-dependent ubiquitin-specific protease activity|
|cellular response to transforming growth factor beta stimulus|
|response to transforming growth factor beta|
|transmembrane receptor protein serine/threonine kinase signaling pathway|
|protein deubiquitination|
|protein modification by small protein removal|
|histone modification|
|covalent chromatin modification|
|cellular response to growth factor stimulus|
|ubiquitin-dependent protein catabolic process|
|response to growth factor|
|modification-dependent protein catabolic process|
|modification-dependent macromolecule catabolic process|
|proteolysis involved in cellular protein catabolic process|
|cellular protein catabolic process|
|protein catabolic process|
|chromatin organization|
|enzyme linked receptor protein signaling pathway|
|cellular macromolecule catabolic process|
|protein phosphorylation|
|protein modification by small protein conjugation or removal|
|macromolecule catabolic process|
|organonitrogen compound catabolic process|
|chromosome organization|
|identical protein binding|
|cellular response to endogenous stimulus|
|mitochondrion|
|proteolysis|
|phosphorylation|
|response to endogenous stimulus|
|organic substance catabolic process|
|cellular catabolic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' 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:exp31|Rifampicin 1μM R00 exp31]]|1.75|
|[[:results:exp289|Hydroxyurea 15μM R06 exp289]]|1.8|
|[[:results:exp503|Mitomycin-C 0.06μM R08 exp503]]|1.84|
|[[:results:exp539|42°C R08 exp539]]|2.08|
|[[:results:exp147|Resveratrol 16μM R03 exp147]]|2.12|
|[[:results:exp290|LLY-283 2.6μM R06 exp290]]|2.19|
|[[:results:exp36|TRAIL 50ng/ml R00 exp36]]|2.58|
|[[:results:exp35|TRAIL 5ng/ml R00 exp35]]|2.6|
|[[:results:exp19|Etoposide 1μM R00 exp19]]|2.74|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 8548
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.79 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='USP15 Expression in NALM6 Cells: 6.79'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>