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FLASH GENE
Symbol SKP1 contributors: mct - updated : 28-06-2015
HGNC name S-phase kinase-associated protein 1
HGNC id 10899
Location 5q31.1      Physical location : 133.492.083 - 133.512.724
Synonym name
  • CDK2 cyclin A associated protein p19A
  • organ of Corti protein 2
  • S-phase kinase-associated protein 1A (p19A)
  • transcription elongation factor B (SIII), polypeptide 1-like
  • RNA polymerase II elongation factor-like protein OCP2
  • Synonym symbol(s) OCP2, EMC19, MGC34403, OCP-II, TCEB1L, SKP1A, p19A, p19skp1, SIII
    EC.number 3.1.1.3
    DNA
    TYPE functioning gene
    STRUCTURE 20.64 kb     6 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 2714 18 160 - 2006 16682006
    6 - 2028 18.5 163 - 2006 16682006
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivepharynx   predominantly
     salivary gland   highly
    Hearing/EquilibriumearinnercochleaCortihighly Homo sapiens
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Connectivebone   
    cell lineage
    cell lines overexpression of SKP1A, SKP1B, SKP2 (A19.cyclin A. CDK2) in transformed cells
    fluid/secretion
    at STAGE
    physiological period fetal
    Text cochlea
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal 125 amino acids, structure similar to BTB/POZ domain fold
  • a two-helix C terminal extension
  • HOMOLOGY
    intraspecies homolog to highly to TCEB1L
    Homologene
    FAMILY
  • SPK1 family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • involved in the ubiquitin-proteasome degradation system and in the regulation of cell cycle
  • FBXO2 and SKP1 are subunits of an SCF E3 ubiquitin ligase
  • may be having a role in dopaminergic neuronal function, besides its E3 ligase activity
  • may play a crucial role at the interface between the cell cycle, differentiation, and death
  • plays a fundamental role in Dopaminergic neuron viability in the context of cell cycle arrest and differentiation
  • increases MIS12 complexes at kinetochores and restores timely chromosome alignment but forms less-robust microtubule-binding sites
  • SKP1 assists in correct folding of exogenously expressed F-box proteins
  • plays an important role in stabilizing the conformation of the F-box proteins, which increases their expression levels and substrate-binding
  • CELLULAR PROCESS cell cycle, checkpoint
    protein, degradation
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    text control at the G1/S and at the G2/M phase transitions
    PATHWAY
    metabolism
    signaling
    a component
  • complexing with CUL1, CDC34, SKP1A/B, SKP2in the SCF ubiquitin ligase complex (SKP1/CDC53-CUL1)/F-box protein, SCF complex
  • complexing with OCP1
  • part of (CUL7) E3 ubiquitin ligase complex containing the FBXW8-substrate-targeting subunit, SKP1, and the RBX1 RING finger protein
  • SKP1-CUL1-F-box protein (SCF) complex is one of the most well characterized types of ubiquitin ligase (E3), with the E3 activity of the complex being regulated in part at the level of complex formation
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • SKP2 with a core ubiquitin ligase (SCF)
  • CDK2/cyclin A (CCNA)
  • FBXL16
  • interacts with CENPE at the midbody and participates in cytokinesis (CENPE degradation is essential for faithful mitotic exit and the proteolysis of CENPE is mediated by SCF (SCF complex Skp1/Cul1/F-box protein/Roc1) via a direct SKP1 link
  • interaction with Elongin C (are structural elements responsible for selective interaction with their cognate Cullin/Rbx1 modules)
  • cochlear FBXO2 binds SKP1, the common binding partner for F-box proteins, and is an unusually abundant inner ear protein
  • SKP1 binding prevented FBXO7 from contacting XPO1
  • competitive binding mechanism between SKP1 and exportin 1 (XPO1) controls the localization of a subset of F-box proteins
  • can directly interact with FBXO7, a gene defective in PARK15-linked Parkinson disease
  • DRG2 was a substrate of a SKP1-CUL1-F-box E3 ligase complex and inhibition the function of Cullin1 prevented the degradation of DRG2 during apoptosis
  • regulates BRCA1 protein stability
  • SF3B3 overexpression reduces the binding of adaptor protein SKP1 and substrate receptor SKP2 to CUL1, whereas it has no effect on CAND1 binding to CUL1
  • SUGT1 interacts with SKP1, a small protein that heterodimerizes with proteins containing the F-box motif
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    with SKP2 (p45), cyclin A/CDK2 in transformed cells
    constitutional     --low  
    in the substantia nigra pars compacta (SNpc) of post-mortem parkinsonian brains
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativeParkinson/dementia Parkinsonism
    strategies aimed at increasing the activity or content of SKP1 may represent a novel therapeutic approach that has the potential to treat Parkinson disease
    ANIMAL & CELL MODELS
    early embryonic lethality and dysregulation of cyclin E(CCNE) in CUL-/-mice