SKP2 Gene

HGNC Family	F-boxes (FBX)
Name	S-phase kinase-associated protein 2, E3 ubiquitin protein ligase
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSKP2 is a key F‐box protein that forms part of the SCF (Skp1–Cullin–F‐box) E3 ubiquitin ligase complex. Early structural studies have revealed that SKP2, in complex with Skp1 and Cul1, provides the substrate–recognition module necessary for targeting a variety of cell cycle regulators for ubiquitin‐dependent degradation. In particular, SKP2 directs the turnover of inhibitors of cyclin–dependent kinases—such as p27Kip1, p57Kip2, and the pocket protein p130—which in turn facilitates the G1–S phase transition and proper DNA recombination processes, as exemplified by RAG-2 degradation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nUpstream, SKP2 expression and activity are tightly regulated by various signaling pathways and post‐translational modifications. Cell shape and RhoA signaling can promote SKP2 expression, while oncogenic transcription factors—such as MYC—directly induce SKP2 transcription. Furthermore, SKP2 abundance and activity are controlled by modifications including neddylation, phosphorylation and acetylation. For instance, Akt-dependent phosphorylation events help prevent its degradation via APC/C(Cdh1), whereas acetylation by p300 enhances its stability and promotes cytoplasmic localization linked to increased cell migration. In addition, tumor suppressors such as FOXP3 and signaling effectors including IKKα counteract SKP2 expression, and p53 pathways are antagonized by SKP2 to suppress apoptosis. Collectively, these regulatory inputs—from cell shape cues to kinase cascades and transcriptional repressors—finely tune SKP2’s function during cell cycle progression and determine its oncogenic potential."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDownstream, SKP2 exerts potent oncogenic functions by targeting multiple substrates that modulate proliferation, survival, and DNA repair. Beyond degrading cell cycle inhibitors, SKP2 can regulate signaling pathways by facilitating ubiquitination of key proteins such as Akt and FOXO transcription factors. It also modulates autophagy by catalyzing K48-linked ubiquitination of Beclin1, and influences the DNA damage response through K63-linked ubiquitination of NBS1, thereby promoting ATM activation. Additional studies have implicated SKP2 in controlling the activity of oncoproteins like YAP and in the polyubiquitination of LKB1, mechanisms that further link its activity to tumor progression and metabolic stress responses. Overall, deregulation of SKP2—often observed in diverse human cancers—correlates with enhanced tumor aggressiveness and poor clinical outcome, positioning SKP2 as an attractive target for therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ning Zheng, Brenda A Schulman, Langzhou Song, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Simvastatin-induced cell cycle arrest through inhibition of STAT3/SKP2 axis and activation of AMPK to promote p27 and p21 accumulation in hepatocellular carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2016.472"}], "href": "https://doi.org/10.1038/cddis.2016.472"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28230855"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28230855"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Fan Yao, Zhicheng Zhou, Jongchan Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SKP2- and OTUD1-regulated non-proteolytic ubiquitination of YAP promotes YAP nuclear localization and activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-04620-y"}], "href": "https://doi.org/10.1038/s41467-018-04620-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29891922"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29891922"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Yun-Cheol Chae, Ji-Young Kim, Jin Woo Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FOXO1 degradation via G9a-mediated methylation promotes cell proliferation in colon cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gky1230"}], "href": "https://doi.org/10.1093/nar/gky1230"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30535125"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30535125"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Zhen Cai, Asad Moten, Danni Peng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Skp2 Pathway: A Critical Target for Cancer Therapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Semin Cancer Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.semcancer.2020.01.013"}], "href": "https://doi.org/10.1016/j.semcancer.2020.01.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32014608"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32014608"}]}]}]}
Synonyms	FLB1, FBL1, FBXL1
Proteins	SKP2_HUMAN
NCBI Gene ID	6502
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SKP2 has 10,581 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 113 datasets.

Click the + buttons to view associations for SKP2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SKP2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SKP2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of SKP2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of SKP2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of SKP2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SKP2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving SKP2 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of SKP2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SKP2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SKP2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SKP2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of SKP2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with SKP2 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SKP2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with SKP2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SKP2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SKP2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of SKP2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of SKP2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SKP2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SKP2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing SKP2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SKP2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	CORUM Protein Complexes	protein complexs containing SKP2 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of SKP2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SKP2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SKP2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SKP2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SKP2 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate SKP2 protein from the curated DEPOD Substrates of Phosphatases dataset.
	DGIdb Drug Targets 2026	interacting drugs for SKP2 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SKP2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SKP2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SKP2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SKP2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SKP2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SKP2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SKP2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing SKP2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SKP2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with SKP2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.