USP7 [The Human Chemical-Genetic Interaction Map Project]

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======= USP7 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: USP7
  * **<color #00a2e8>Official Name</color>**: ubiquitin specific peptidase 7
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=7874|7874]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q93009|Q93009]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=USP7&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20USP7|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/602519|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene belongs to the peptidase C19 family, which includes ubiquitinyl hydrolases. This protein deubiquitinates target proteins such as p53 (a tumor suppressor protein) and WASH (essential for endosomal protein recycling), and regulates their activities by counteracting the opposing ubiquitin ligase activity of proteins such as HDM2 and TRIM27, involved in the respective process. Mutations in this gene have been implicated in a neurodevelopmental disorder. [provided by RefSeq, Mar 2016]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Hydrolase that deubiquitinates target proteins such as FOXO4, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX (PubMed:11923872, PubMed:15053880, PubMed:16964248, PubMed:18716620, PubMed:25283148, PubMed:26678539). Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal degradation (PubMed:15053880, PubMed:16845383, PubMed:18566590, PubMed:20153724). Deubiquitinates p53/TP53, preventing degradation of p53/TP53, and enhances p53/TP53-dependent transcription regulation, cell growth repression and apoptosis (PubMed:25283148). Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presence of excess MDM2, and also induces p53/TP53-dependent cell growth repression and apoptosis (PubMed:11923872). Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced transcriptional activity (PubMed:16964248). In association with DAXX, is involved in the deubiquitination and translocation of PTEN from the nucleus to the cytoplasm, both processes that are counteracted by PML (PubMed:18716620). Deubiquitinates KMT2E/MLL5 preventing KMT2E/MLL5 proteasomal-mediated degradation (PubMed:26678539). Involved in cell proliferation during early embryonic development. Involved in transcription-coupled nucleotide excision repair (TC- NER) in response to UV damage: recruited to DNA damage sites following interaction with KIAA1530/UVSSA and promotes deubiquitination of ERCC6, preventing UV-induced degradation of ERCC6 (PubMed:22466611, PubMed:22466612). Involved in maintenance of DNA methylation via its interaction with UHRF1 and DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1, preventing their degradation and promoting DNA methylation by DNMT1 (PubMed:21745816, PubMed:22411829). Acts as a chromatin regulator via its association with the Polycomb group (PcG) multiprotein PRC1-like complex; may act by deubiquitinating components of the PRC1-like complex (PubMed:20601937). Able to mediate deubiquitination of histone H2B; it is however unsure whether this activity takes place in vivo (PubMed:20601937). Exhibits a preference towards 'Lys-48'-linked ubiquitin chains (PubMed:22689415). Increases regulatory T-cells (Treg) suppressive capacity by deubiquitinating and stabilizing the transcription factor FOXP3 which is crucial for Treg cell function (PubMed:23973222). {ECO:0000269|PubMed:11923872, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:16845383, ECO:0000269|PubMed:16964248, ECO:0000269|PubMed:18566590, ECO:0000269|PubMed:18716620, ECO:0000269|PubMed:20153724, ECO:0000269|PubMed:20601937, ECO:0000269|PubMed:21745816, ECO:0000269|PubMed:22411829, ECO:0000269|PubMed:22466611, ECO:0000269|PubMed:22466612, ECO:0000269|PubMed:22689415, ECO:0000269|PubMed:23973222, ECO:0000269|PubMed:25283148, ECO:0000269|PubMed:26678539}.

<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'>
|USP7|
|UCH|
|MATH|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|positive regulation of DNA demethylation|
|histone H2B conserved C-terminal lysine deubiquitination|
|ubiquitinyl hydrolase activity|
|maintenance of DNA methylation|
|regulation of DNA demethylation|
|monoubiquitinated protein deubiquitination|
|Lys48-specific deubiquitinase activity|
|histone deubiquitination|
|regulation of telomere capping|
|protein K48-linked deubiquitination|
|negative regulation of proteasomal ubiquitin-dependent protein catabolic process|
|negative regulation of ubiquitin-dependent protein catabolic process|
|thiol-dependent ubiquitinyl hydrolase activity|
|negative regulation of proteasomal protein catabolic process|
|p53 binding|
|negative regulation of proteolysis involved in cellular protein catabolic process|
|transcription-coupled nucleotide-excision repair|
|regulation of telomere maintenance|
|negative regulation of NF-kappaB transcription factor activity|
|negative regulation of cellular protein catabolic process|
|cysteine-type endopeptidase activity|
|PML body|
|thiol-dependent ubiquitin-specific protease activity|
|nucleotide-excision repair|
|regulation of circadian rhythm|
|regulation of proteasomal ubiquitin-dependent protein catabolic process|
|chromosome|
|negative regulation of protein catabolic process|
|regulation of ubiquitin-dependent protein catabolic process|
|negative regulation of DNA-binding transcription factor activity|
|protein stabilization|
|regulation of proteasomal protein catabolic process|
|protein C-terminus binding|
|positive regulation of DNA metabolic process|
|regulation of proteolysis involved in cellular protein catabolic process|
|regulation of cellular protein catabolic process|
|negative regulation of cellular catabolic process|
|rhythmic process|
|protein deubiquitination|
|nuclear body|
|regulation of protein stability|
|ubiquitin protein ligase binding|
|protein modification by small protein removal|
|negative regulation of catabolic process|
|transcription factor binding|
|regulation of chromosome organization|
|negative regulation of proteolysis|
|regulation of DNA metabolic process|
|histone modification|
|covalent chromatin modification|
|regulation of protein catabolic process|
|regulation of DNA-binding transcription factor activity|
|DNA repair|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|modification-dependent macromolecule catabolic process|
|proteolysis involved in cellular protein catabolic process|
|protein-containing complex|
|cellular protein catabolic process|
|protein catabolic process|
|protein ubiquitination|
|chromatin organization|
|viral process|
|regulation of proteolysis|
|DNA metabolic process|
|protein modification by small protein conjugation|
|cellular response to DNA damage stimulus|
|symbiotic process|
|interspecies interaction between organisms|
|regulation of cellular catabolic process|
|cellular macromolecule catabolic process|
|protein modification by small protein conjugation or removal|
|regulation of catabolic process|
|negative regulation of cellular protein metabolic process|
|macromolecule catabolic process|
|organonitrogen compound catabolic process|
|chromosome organization|
|negative regulation of protein metabolic process|
|negative regulation of molecular function|
|proteolysis|
|regulation of organelle organization|
|cellular response to stress|
|organic substance catabolic process|
|cellular catabolic process|
|positive regulation of nucleobase-containing compound metabolic 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:exp512|Olaparib 4μM R08 exp512]]|-2.54|
|[[:results:exp124|GSK343 3μM R03 exp124]]|-2.23|
|[[:results:exp330|5-Azacytidine 2μM R07 exp330]]|-2.1|
|[[:results:exp343|Centrinone 0.5μM R07 exp343]]|-2.08|
|[[:results:exp502|Milciclib 2μM R08 exp502]]|-1.95|
|[[:results:exp59|UMK57 1μM R01 exp59]]|-1.82|
|[[:results:exp190|Vincristine 0.0005μM R04 exp190]]|-1.78|
|[[:results:exp147|Resveratrol 16μM R03 exp147]]|-1.77|
|[[:results:exp311|2-Methoxyestradiol 0.55 to 0.75μM  on day4 R07 exp311]]|-1.75|
|[[:results:exp155|UNC1999 2μM R03 exp155]]|-1.71|
|[[:results:exp287|HMS-I2 5μM R06 exp287]]|-1.7|
|[[:results:exp333|All-trans-Retinoic-Acid 8μM R07 exp333]]|1.84|
|[[:results:exp365|I-BRD9 4μM R07 exp365]]|2.16|
</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: 147/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|4/28|
|blood|4/28|
|bone|3/25|
|breast|6/33|
|central nervous system|7/56|
|cervix|0/4|
|colorectal|4/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|1/15|
|kidney|11/21|
|liver|6/20|
|lung|13/75|
|lymphocyte|5/14|
|ovary|3/26|
|pancreas|3/24|
|peripheral nervous system|3/16|
|plasma cell|3/15|
|prostate|1/1|
|skin|9/24|
|soft tissue|1/7|
|thyroid|0/2|
|upper aerodigestive|3/22|
|urinary tract|3/29|
|uterus|1/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 1708
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 8.49 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='USP7 Expression in NALM6 Cells: 8.49'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>