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FLASH GENE
Symbol INSIG2 contributors: mct - updated : 30-12-207
HGNC name insulin induced gene 2
HGNC id 20452
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • six transmembrane helices
    • HOMOLOGY
    interspecies homolog to murine Insig2 (96.9pc)
    homolog to rattus Insig2 (96.4pc)
    intraspecies homolog to INSIG1
    Homologene
    FAMILY
  • INSIG family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    basic FUNCTION
  • negative regulator of cholesterol synthesis
  • involved in adipocyte metabolism and body weight regulation
  • in the presence of sterols, INSIG2 regulates lipid synthesis by blocking the proteolytic activation of SREBPs by SCAP and causing SREBPs to be retained in the ER (Yabe 2002)
  • essential role of INSIG1, INSIG2 proteins in the sterol homeostasis of enterocytes
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism lipid/lipoprotein
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with SCAP (to block export of sterol regulatory element-binding proteins)
  • sterol-induced ubiquitination and proteasomal degradation of reductase is dictated by the complex interplay of at least four proteins: INSIG1, INSIG2, AMFR, and RNF139
  • gluconeogenic enzyme PCK1 phosphorylates INSIG1/INSIG2 for lipogenesis
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    . cholesterol metabolic aberrations, induced through disruption of either DHCR7 or INSIG1 and INSIG2 , result in osteoblast differentiation abnormalities
    Susceptibility
  • to severe obesity
  • to metabolic syndrome
    • Variant & Polymorphism SNP
  • significantly associated with obesity
  • common INSIG2 variant rs9308762 was associated with poorer metabolic control and a greater sensitivity of trigylcerides to a modern dietary pattern
    • Candidate gene putative positive prognostic biomarker for colon cancer prognosis
    Marker
    Therapy target
    ANIMAL & CELL MODELS