USP28 [The Human Chemical-Genetic Interaction Map Project]

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======= USP28 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: USP28
  * **<color #00a2e8>Official Name</color>**: ubiquitin specific peptidase 28
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=57646|57646]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q96RU2|Q96RU2]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=USP28&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20USP28|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/610748|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is a deubiquitinase involved in the DNA damage pathway and DNA damage-induced apoptosis. Overexpression of this gene is seen in several cancers. [provided by RefSeq, Oct 2016]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus. Deubiquitinates ZNF304, hence preventing ZNF304 degradation by the proteasome and leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) in a subset of colorectal cancers (CRC) cells (PubMed:24623306). {ECO:0000269|PubMed:16901786, ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:17873522, ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:24623306}.

<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|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator|
|intrinsic apoptotic signaling pathway by p53 class mediator|
|thiol-dependent ubiquitinyl hydrolase activity|
|intrinsic apoptotic signaling pathway in response to DNA damage|
|cellular response to UV|
|cysteine-type endopeptidase activity|
|thiol-dependent ubiquitin-specific protease activity|
|cellular response to light stimulus|
|signal transduction by p53 class mediator|
|DNA damage checkpoint|
|response to UV|
|DNA integrity checkpoint|
|response to ionizing radiation|
|intrinsic apoptotic signaling pathway|
|cellular response to radiation|
|cell cycle checkpoint|
|Ras protein signal transduction|
|protein deubiquitination|
|nuclear body|
|apoptotic signaling pathway|
|regulation of protein stability|
|protein modification by small protein removal|
|response to light stimulus|
|cellular response to environmental stimulus|
|cellular response to abiotic stimulus|
|small GTPase mediated signal transduction|
|response to radiation|
|DNA repair|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|modification-dependent macromolecule catabolic process|
|cell population proliferation|
|negative regulation of cell cycle|
|proteolysis involved in cellular protein catabolic process|
|protein-containing complex|
|cellular protein catabolic process|
|protein catabolic process|
|DNA metabolic process|
|cellular response to DNA damage stimulus|
|cellular macromolecule catabolic process|
|apoptotic process|
|protein modification by small protein conjugation or removal|
|macromolecule catabolic process|
|programmed cell death|
|organonitrogen compound catabolic process|
|cell death|
|response to abiotic stimulus|
|regulation of cell cycle|
|proteolysis|
|intracellular signal transduction|
|cellular response to stress|
|organic substance catabolic process|
|cellular catabolic 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:exp407|Thapsigargin 0.005μM R07 exp407]]|-1.93|
|[[:results:exp473|Cincreasin 100μM R08 exp473]]|-1.72|
|[[:results:exp468|CB-5083 0.4μM R08 exp468]]|1.8|
|[[:results:exp59|UMK57 1μM R01 exp59]]|1.9|
|[[:results:exp60|Vinblastine 0.002μM R01 exp60]]|1.96|
|[[:results:exp217|Mdivi-1 15μM R05 exp217]]|2.1|
|[[:results:exp106|UM131593 0.2μM R03 exp106]]|2.27|
|[[:results:exp460|BML-284 0.09μM R08 exp460]]|3.31|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:a:atat1|ATAT1]]|0.405|
</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>**: 17755
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 4.93 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='USP28 Expression in NALM6 Cells: 4.93'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>