SKP2 [The Human Chemical-Genetic Interaction Map Project]

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======= SKP2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: SKP2
  * **<color #00a2e8>Official Name</color>**: S-phase kinase associated protein 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=6502|6502]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q13309|Q13309]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=SKP2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20SKP2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/601436|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class; in addition to an F-box, this protein contains 10 tandem leucine-rich repeats. This protein is an essential element of the cyclin A-CDK2 S-phase kinase. It specifically recognizes phosphorylated cyclin-dependent kinase inhibitor 1B (CDKN1B, also referred to as p27 or KIP1) predominantly in S phase and interacts with S-phase kinase-associated protein 1 (SKP1 or p19). In addition, this gene is established as a protooncogene causally involved in the pathogenesis of lymphomas. Alternative splicing of this gene generates three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2011]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Substrate recognition component of a SCF (SKP1-CUL1-F- box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, FOXO1, UBP43, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a CK1-Dependent Manner, thereby regulating cell migration. {ECO:0000269|PubMed:11931757, ECO:0000269|PubMed:12435635, ECO:0000269|PubMed:12769844, ECO:0000269|PubMed:12840033, ECO:0000269|PubMed:15342634, ECO:0000269|PubMed:15668399, ECO:0000269|PubMed:15949444, ECO:0000269|PubMed:16103164, ECO:0000269|PubMed:16262255, ECO:0000269|PubMed:16581786, ECO:0000269|PubMed:16951159, ECO:0000269|PubMed:17908926, ECO:0000269|PubMed:17962192, ECO:0000269|PubMed:22770219}.

<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'>
|F-box-like|
|F-box|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|cellular response to cell-matrix adhesion|
|positive regulation of intracellular estrogen receptor signaling pathway|
|positive regulation of protein polyubiquitination|
|positive regulation of intracellular steroid hormone receptor signaling pathway|
|regulation of protein polyubiquitination|
|regulation of intracellular estrogen receptor signaling pathway|
|protein K48-linked ubiquitination|
|SCF ubiquitin ligase complex|
|regulation of intracellular steroid hormone receptor signaling pathway|
|positive regulation of smooth muscle cell proliferation|
|SCF-dependent proteasomal ubiquitin-dependent protein catabolic process|
|positive regulation of protein ubiquitination|
|G1/S transition of mitotic cell cycle|
|cell cycle G1/S phase transition|
|G2/M transition of mitotic cell cycle|
|cell cycle G2/M phase transition|
|regulation of smooth muscle cell proliferation|
|positive regulation of protein modification by small protein conjugation or removal|
|defense response to virus|
|regulation of protein ubiquitination|
|ubiquitin protein ligase activity|
|regulation of protein modification by small protein conjugation or removal|
|cellular response to extracellular stimulus|
|mitotic cell cycle phase transition|
|cell cycle phase transition|
|response to virus|
|protein deubiquitination|
|protein modification by small protein removal|
|protein polyubiquitination|
|proteasome-mediated ubiquitin-dependent protein catabolic process|
|cellular response to external stimulus|
|proteasomal protein catabolic process|
|post-translational protein modification|
|ubiquitin-dependent protein catabolic process|
|response to extracellular stimulus|
|modification-dependent protein catabolic process|
|modification-dependent macromolecule catabolic process|
|proteolysis involved in cellular protein catabolic process|
|mitotic cell cycle process|
|cellular protein catabolic process|
|mitotic cell cycle|
|protein catabolic process|
|protein ubiquitination|
|viral process|
|innate immune response|
|protein modification by small protein conjugation|
|symbiotic process|
|interspecies interaction between organisms|
|nucleolus|
|cellular macromolecule catabolic process|
|positive regulation of cell population proliferation|
|defense response to other organism|
|protein modification by small protein conjugation or removal|
|cell cycle process|
|macromolecule catabolic process|
|organonitrogen compound catabolic process|
|identical protein binding|
|immune effector process|
|regulation of cell cycle|
|positive regulation of protein modification process|
|proteolysis|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|defense response|
|cell cycle|
|regulation of apoptotic process|
|regulation of programmed cell death|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|positive regulation of signal transduction|
|regulation of cell death|
|positive regulation of protein metabolic process|
|organic substance catabolic process|
|cellular catabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of protein modification process|
|immune response|
</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:exp146|Quinacrine 2.5μM R03 exp146]]|-2.05|
|[[:results:exp360|Genistein 15μM R07 exp360]]|-1.98|
|[[:results:exp497|Lead acetate 2000μM R08 exp497]]|-1.97|
|[[:results:exp417|Tubastatin-A 2.5μM R07 exp417]]|-1.75|
|[[:results:exp95|BI-2536 0.0042μM R03 exp95]]|1.96|
|[[:results:exp23|Nocodazole 0.02μM R00 exp23]]|2.04|
|[[:results:exp539|42°C R08 exp539]]|2.11|
|[[:results:exp75|MK-1775 0.32μM R02 exp75]]|4.63|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:c:cks1b|CKS1B]]|0.618|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 154/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|3/28|
|blood|4/28|
|bone|6/26|
|breast|10/33|
|central nervous system|17/56|
|cervix|3/4|
|colorectal|5/17|
|esophagus|1/13|
|fibroblast|1/1|
|gastric|4/16|
|kidney|3/21|
|liver|3/20|
|lung|18/75|
|lymphocyte|2/16|
|ovary|9/26|
|pancreas|2/24|
|peripheral nervous system|4/16|
|plasma cell|6/15|
|prostate|0/1|
|skin|4/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|2/22|
|urinary tract|12/29|
|uterus|2/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 1633
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.83 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='SKP2 Expression in NALM6 Cells: 6.83'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>