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50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SKP1
S-phase kinase associated protein 1
Chromosome 5 · 5q31.1
NCBI Gene: 6500Ensembl: ENSG00000113558.20HGNC: HGNC:10899UniProt: P63208
616PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub Gene
RESEARCH IMPACT
Highly StudiedTrending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
proteasome-mediated ubiquitin-dependent protein catabolic processPcG protein complexcullin family protein bindingmolecular function activator activitycancerHIV infectionneurodegenerative diseaseneuroinflammatory disorder
✦AI Summary

SKP1 (S-phase kinase associated protein 1) functions as an essential adapter component of SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complexes, which mediate targeted protein degradation through the ubiquitin-proteasome pathway 1. The protein serves as a crucial link between F-box proteins and CUL1, enabling the formation of diverse SCF complexes with distinct substrate specificities 2. SKP1-containing complexes target numerous proteins for ubiquitination, including cell cycle regulators, transcription factors, and signaling molecules 3. Beyond canonical SCF complexes, SKP1 participates in E3-E3 super-assemblies with RBR-type ligases like ARIH1, expanding the range of substrates that can be effectively ubiquitinated 3. The protein also plays specialized roles in meiosis, where SKP1 localizes to chromosome 5 and orchestrates the prophase I to metaphase I transition by maintaining chromosome 5 and enabling metaphase competence acquisition 4. Additionally, SKP1 mediates non-canonical ubiquitination pathways, including sugar-mediated ubiquitination that regulates transcription factor activation 5. Loss of SKP1 has been implicated in cancer progression, particularly in breast cancer where 5q deletions affect SKP1 expression and contribute to oncogenic signaling 6.

Sources cited
1
SKP1 is an essential component of SCF ubiquitin ligase complexes that catalyze protein ubiquitination
PMID: 11438690
2
SKP1 serves as an adapter linking F-box proteins to CUL1 in SCF complex assembly
PMID: 37028429
3
SKP1 participates in E3-E3 super-assemblies with RBR-type ligases for substrate ubiquitination
PMID: 33536622
4
SKP1 plays essential roles in meiotic chromosome dynamics and metaphase I transition
PMID: 32232159
5
SKP1 mediates non-canonical sugar-mediated ubiquitination pathways
PMID: 39116872
6
SKP1 loss in breast cancer 5q deletions contributes to oncogenic signaling
PMID: 27251275
Disease Associationsⓘ20
cancerOpen Targets
0.52Moderate
HIV infectionOpen Targets
0.50Moderate
neurodegenerative diseaseOpen Targets
0.44Moderate
neuroinflammatory disorderOpen Targets
0.26Weak
keratoconus 1Open Targets
0.11Weak
cervical squamous intraepithelial neoplasiaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
urinary bladder carcinomaOpen Targets
0.07Suggestive
hepatocellular carcinomaOpen Targets
0.06Suggestive
Parkinson diseaseOpen Targets
0.06Suggestive
colorectal cancerOpen Targets
0.05Suggestive
systemic lupus erythematosusOpen Targets
0.04Suggestive
lung cancerOpen Targets
0.04Suggestive
Abruptio PlacentaeOpen Targets
0.03Suggestive
breast benign neoplasmOpen Targets
0.03Suggestive
rheumatoid arthritisOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.03Suggestive
cystOpen Targets
0.02Suggestive
glioblastomaOpen Targets
0.02Suggestive
Huntington diseaseOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CCNE1Protein interaction100%CDK2Protein interaction100%CDKN1AProtein interaction100%CDKN1BProtein interaction100%CDKN1CProtein interaction100%CKS1BProtein interaction100%
Tissue Expression6 tissues
Brain
100%
Heart
50%
Bone Marrow
41%
Ovary
40%
Lung
31%
Liver
29%
Gene Interaction Network
Click a node to explore
SKP1CCNE1CDK2CDKN1ACDKN1BCDKN1CCKS1B
PROTEIN STRUCTURE
Preparing viewer…
PDB1FS1 · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.32Highly Constrained
pLIⓘ
0.98Intolerant
Observed/Expected LoF0.00 [0.00–0.32]
RankingsWhere SKP1 stands among ~20K protein-coding genes
  • #379of 20,598
    Most Researched616 · top 5%
  • #1,319of 17,882
    Most Constrained (LOEUF)0.32 · top 10%
Genes detectedSKP1
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Proteogenomics connects somatic mutations to signalling in breast cancer.
PMID: 27251275
Nature · 2016
1.00
2
Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation.
PMID: 11438690
Proc Natl Acad Sci U S A · 2001
0.90
3
Novel Skp1 inhibitor has potent preclinical efficacy against castration-resistant prostate cancer.
PMID: 40253488
Br J Cancer · 2025
0.88
4
Hypoxic and Acidic Tumor Microenvironment-Driven AVL9 Promotes Chemoresistance of Pancreatic Ductal Adenocarcinoma via the AVL9-IκBα-SKP1 Complex.
PMID: 39566663
Gastroenterology · 2025
0.84
5
The characteristics and roles of β-TrCP1/2 in carcinogenesis.
PMID: 33021036
FEBS J · 2021
0.82