Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol INSIG1 contributors: mct - updated : 03-02-2017
HGNC name insulin induced gene 1
HGNC id 6083
PROTEIN
PHYSICAL PROPERTIES Hydrophilic
STRUCTURE
motifs/domains
  • two leucine-rich repeats domains (LRR)
  • six transmembrane segments separated by five short luminal and cytosolic loops that range from approximately 5 to 16 amino acids
  • HOMOLOGY
    interspecies homolog to C.elegans y56a3a.29
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    basic FUNCTION
  • facilitating the sterol-dependent ER retention of SCAP, there by playing a central role in cholesterol biosunthesis
  • playing a role in regulating cholesterol concentration
  • blocks proteolytic activation of sterol regulatory element-binding proteins (SREBFs), transcription factors that activate genes regulating cholesterol and fatty acid metabolism and possibly genes involved in glucose homeostasis
  • regulating the proteolytic processing of membrane-bound sterol regulatory element-binding proteins (SREBPs), transcription factors activating the synthesis of cholesterol and fatty acids
  • inhibited the lipid accumulation and free fatty acid (FFA) synthesis in a time-dependent manner
  • cellular cholesterol levels are controlled by endoplasmic reticulum (ER) sterol sensing proteins, which include SCAP and INSIG1
  • essential role of INSIG1, INSIG2 proteins in the sterol homeostasis of enterocytes
  • AMFR and INSIG1, an E3 ubiquitin ligase complex, then catalyzed the K27-linked polyubiquitination of CISD2
  • essential role of the ER proteins AMFR and INSIG1 in innate immunity, revealing an important missing link in the CISD2 signaling pathway
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism lipid/lipoprotein
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding SCAP, promoted by sterols, retaining the SCAP/SREBP complex in the ER and preventing it from moving to the Golgi for proteolytic processing
  • binding the sterol sensing domain of HMGCR and accelerating its degradation
  • binding to the ER enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, facilitating its ubiquitination and proteasomal degradation
  • interacting with SREBF1 (INSIG1 degradation is necessary for SREBF complex release from ER and its subsequent proteolytic activation in Golgi)
  • may play a critical role in protecting beta cells against glucolipotoxicity by regulating the expression of SREBP-1c
  • suppressed the high glucose induced SREBP-1c mRNA and protein expression
  • sterol-induced ubiquitination and proteasomal degradation of reductase is dictated by the complex interplay of at least four proteins: INSIG1, INSIG2, AMFR, and RNF139
  • AMFR and RNF139 are implicated in the sterol-regulated degradation of HMG-CoA reductase and INSIG1 through ER-associated degradation (ERAD)
  • gluconeogenic enzyme PCK1 phosphorylates INSIG1/INSIG2 for lipogenesis
  • cell & other
  • unsaturated fatty acids stabilize INSIG1 without affecting its ubiquitination
  • REGULATION
    induced by insulin
    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 coronary heart disease
    Variant & Polymorphism SNP
  • rs9769826 of the INSIG1 gene was associated with coronary heart disease
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS