SKP2
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]
Function
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 (PubMed:11931757, PubMed:12435635, PubMed:12769844, PubMed:12840033, PubMed:15342634, PubMed:15668399, PubMed:15949444, PubMed:16103164, PubMed:16262255, PubMed:16581786, PubMed:16951159, PubMed:17908926, PubMed:17962192, PubMed:22770219, PubMed:32267835).
Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition (By similarity).
Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, FOXO1, UBP43, YTHDF2, and probably MYC, TOB1 and TAL1 (PubMed:11931757, PubMed:12435635, PubMed:12769844, PubMed:12840033, PubMed:15342634, PubMed:15668399, PubMed:15949444, PubMed:16103164, PubMed:17962192, PubMed:16581786, PubMed:16951159, PubMed:17908926, PubMed:32267835).
Degradation of TAL1 also requires STUB1 (PubMed:17962192).
Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2 (PubMed:16262255).
Promotes ubiquitination and destruction of CDH1 in a CK1-dependent manner, thereby regulating cell migration (PubMed:22770219).
Through the ubiquitin-mediated proteasomal degradation of hepatitis C virus non-structural protein 5A, has an antiviral activity towards that virus.
Biological Process
Biological Process defense response to virusManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process G1/S transition of mitotic cell cycleManual Assertion Based On ExperimentTAS:ProtInc
Biological Process G2/M transition of mitotic cell cycleManual Assertion Based On ExperimentIBA:GO_Central
Biological Process innate immune responseManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of intracellular estrogen receptor signaling pathwayIEA:Ensembl
Biological Process positive regulation of protein polyubiquitinationIEA:Ensembl
Biological Process proteasome-mediated ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process protein K48-linked ubiquitinationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of apoptotic processManual Assertion Based On ExperimentIDA:MGI
Biological Process regulation of cell cycleManual Assertion Based On ExperimentIBA:GO_Central
Biological Process SCF-dependent proteasomal ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIBA:GO_Central
PTM
Ubiquitinated by the APC/C complex, leading to its degradation by the proteasome. Deubiquitinated by USP13.
Acetylation at Lys-68 and Lys-71 increases stability through impairment of APC/C-mediated proteolysis and promotes cytoplasmic retention. Deacetylated by SIRT3.