SKP2

Gene Information

Official Symbol: SKP2
Official Name: S-phase kinase associated protein 2
Aliases and Previous Symbols: N/A
Entrez ID: 6502
UniProt: Q13309
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: 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].
UniProt Summary: 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}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
Quinacrine 2.5μM R03 exp146	-2.05
Genistein 15μM R07 exp360	-1.98
Lead acetate 2000μM R08 exp497	-1.97
Tubastatin-A 2.5μM R07 exp417	-1.75
BI-2536 0.0042μM R03 exp95	1.96
Nocodazole 0.02μM R00 exp23	2.04
42°C R08 exp539	2.11
MK-1775 0.32μM R02 exp75	4.63

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

Essentiality in NALM6

Essentiality Rank: 1633
Expression level (log2 read counts): 6.83

Expression Distribution

F-box-like
F-box

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