Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol SKI contributors: mct/shn - updated : 02/02/2013
HGNC name v-ski sarcoma viral oncogene homolog (avian)
HGNC id 10896
Corresponding disease
DEL1P36 chromosome 1p subtelomeric deletion syndrome
SGS2 Shprintzen-Goldberg syndrome 2 of marfanoid habitus craniosynostosis
Location 1p36.33      Physical location : 2.160.133 - 2.241.651
Synonym name
  • v-ski avian sarcoma viral oncogene homolog
  • proto-oncogene c-Ski
  • ski oncogene
  • ski oncoprotein
    • Synonym symbol(s) SK, SKV, C-ski
    DNA
    TYPE functioning gene
    STRUCTURE 81.52 kb     7 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map pter - D1S243 - SKI - D1S468 - D1S2845 - cen
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 5707 - 728 - 2009 19341714
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Skin/Tegumentskin   highly
    Urinarybladder   highly
     kidney   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text gastrula, autonomous neural axis formation
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal region (most likely from AA 261 to 491) appeared to be responsible for its ability to bind to SIAH2 and stabilize HDAC3 and RARA
  • conserved CLPQ motif
  • R-SMAD binding domain
  • C-terminal SKI (491–728) protein could not bind to SIAH2 and had no effect on the self-degradation of SIAH2, but this region – including the coiled-coil domain – appears to be required for SKI localization to the centrosomes and for SKI interaction with Aurora A
    • secondary structure
  • C-terminal region, with a alpha-helix coiled-coil domain (AA536–710) that has been shown to be important for either homo-dimerization or dimerization
    • HOMOLOGY
    interspecies homolog to avian sarcoma viral (v-ski) oncogene
    ortholog to Ski, Mus musculus
    ortholog to Ski, Rattus norvegicus
    Homologene
    FAMILY
  • SKI family
    • CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,centromere
    text
  • localized at the centrosomes and mitotic spindle during mitosis
    • basic FUNCTION
  • involved in terminal differentiation of skeletal muscle cells
  • may play a role in terminal differentiation of skeletal muscle cells but not in the determination of cells to the myogenic lineage
  • role in the morphogenesis of craniofacial structures and the central nervous system
  • participate in dorsal-ventral specification of both neuroectoderm and mesoderm
  • inhibits both TGF-beta-induced transcriptional activation and repression
  • a crucial signal in Schwann cell development and myelination
  • act as a transcriptional corepressor by multiple direct and indirect interactions with several distinct repression complexes
  • having a repressive effect on RA signaling pathway which might also apply to the other signaling pathways inhibited by the SKI protein
  • acts as a transcriptional co-repressor by multiple direct and indirect interactions with several distinct repression complexes
  • inhibits SIAH2-mediated proteasomal degradation of HDAC3
  • increases the levels of HDAC3 (and/or RARA indirectly) by interacting with SIAH2 and inhibiting SIAH2 ubiquitin ligase activity
  • negative regulator of the transforming growth factor-beta and other signalling pathways
  • in the maintenance of the neural stem cell pool and the specification of callosal neurons
  • required for transcriptional repression of Ctip2 in callosal neurons
  • a central role for Ski-Satb2 interactions in regulating transcriptional mechanisms of callosal neuron specification
  • ability of SKI to enhance UBE2I activity is essential for its transforming function
  • can enhance MDM2-mediated TP53 ubiquitination and thus proteasomal degradation, which likely results in a decreased TP53 level
  • may predominantly be required in the very proximal aorta at early stages of development for the proper regulation of TGFB signaling within the arterial media
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    TGF-beta signaling pathway
    a component
    INTERACTION
    DNA
  • TGGC/ANNNNNT/GCCAA of the nuclear factor I (NFI) and TCCCNNGGGA of the binding site of Olf-1/EBF
    • RNA
    small molecule
    protein
  • Ski Interacting Protein, SKIP
  • SnoN
  • retinoblastoma protein, Rb
  • promyelocytic leukemia, PML
  • MeCP2
  • Smad2/3
  • c-Jun
  • Smad3
  • Gli3
  • homeodomain-interacting protein kinase 2, HIPK2
  • Smad1, Smad2, Smad3, Smad4 and Smad5
  • DNA-binding domain of c-Myb
  • GATA1
  • PU.1
  • Arkadia
  • SKI is necessary for muscle terminal differentiation and it exerts this role, at least in part, through its association with SIX1 and EYA3 to regulate the MYOG transcription
  • histone deacetylase 3, HDAC3 and protein arginine methyltransferase 5, PRMT5
  • PRDM16 (MID:19049980
  • RARalpha
  • SMAD4
  • retinoic acid receptor ALPHA, RARA
  • SPI1
  • SIAH2
  • TGF-beta type I receptor
  • TP53
  • can increase MDM2 sumoylation to enhance TP53 degradation
  • can enhance UBE2I-mediated cellular sumoylation, possibly through direct interaction with UBE2I
    • cell & other
    REGULATION
    activated by AURKA that is able to phosphorylate SKI
    Phosphorylated by Akt/PKB kinase
    Other regulated during the cell cycle by ubiquitylation and subsequent proteasomal degradation
    ASSOCIATED DISORDERS
    corresponding disease(s) DEL1P36 , SGS2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    in facial clefting (and/or neural tube defect)
    tumoral     --over  
    in a variety of human cancers, including melanoma, leukemia, colorectal, pancreatic, esophageal, and gastric cancers
    Susceptibility to orofacial defect
    Variant & Polymorphism SNP (257C>G)associated with a decreased risk for orofacial defects
    Candidate gene for facial clefting in 1p36 deletion
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • defects in neurulation, craniofacial, patterning, and skeletal muscle development in ski -/- mice
  • ski-deficient heterozygous mice display susceptibility to tumorigenesis
  • Ski-deficient callosal neurons lose their identity and ectopically express the transcription factor Ctip2
  • Ski-/- mice display a lethal phenotype with associated midline facial cleft, a depressed nasal bridge, eye anomalies, skeletal muscle defects, and digital anomalies