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FLASH GENE
Symbol INSIG1 contributors: mct - updated : 08-09-2013
HGNC name insulin induced gene 1
HGNC id 6083
Location 7q36.3      Physical location : 155.089.485 - 155.101.942
Synonym name INSIG-1 membrane protein
Synonym symbol(s) CL6, ISI1
DNA
TYPE functioning gene
STRUCTURE 12.46 kb     6 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
GALNT11 7q34-q36 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 11 (GalNAc-T11) LOC392153 7 similar to TSH receptor suppressor element-binding protein-1; TSEP-1 LOC389600 7 LOC389600 MLL3 7q36 myeloid/lymphoid or mixed-lineage leukemia 3 LOC220832 7q36.2 similar to Fatty acid-binding protein, epidermal (E-FABP) (Psoriasis-associated fatty acid-binding protein homolog) (PA-FABP) LOC155100 7q36.2 similar to T-complex protein 1 XRCC2 7q36.1 X-ray repair complementing defective repair in Chinese hamster cells 2 LOC392154 7 similar to ATP synthase B chain, mitochondrial precursor ARP3BETA 7q346 similar to ATP synthase B chain, mitochondrial precursor LOC392155 7 similar to SMT3 suppressor of mif two 3 homolog 2 LOC346547 7q36.2 similar to envelope protein LOC392156 7 similar to ppg3 DPP6 7q dipeptidylpeptidase 6 PAXIP1L 7q36.3 PAX transcription activation domain interacting protein 1 like HTR5A 7q36.1 5-hydroxytryptamine (serotonin) receptor 5A LOC389601 7 LOC389601 INSIG1 7q36 insulin induced gene 1 EN2 7q36.2 engrailed homolog 2 LOC392157 7 similar to RIKEN cDNA 9630008K15 gene MGC20460 7q36.3 hypothetical protein MGC20460 SHH 7q36 sonic hedgehog homolog (Drosophila) LOC389602 7 hypothetical gene supported by AK124321 LOC346305 7q36.3 similar to hypothetical protein Tb927.2.4050 LOC285890 7q36.3 hypothetical LOC285890 C7orf13 7q36 chromosome 7 open reading frame 13 RNF32 7q36 ring finger protein 32 C7orf2 7q36 chromosome 7 open reading frame 2 C7orf3 7q36 chromosome 7 open reading frame 3 HLXB9 7q36 homeo box HB9 LOC392158 7 similar to S-adenosylmethionine decarboxylase KIAA0010 7q36.3 ubiquitin-protein isopeptide ligase (E3) DNAJB6 7q36.3 DnaJ (Hsp40) homolog, subfamily B, member 6 LOC392159 7 similar to polycystic kidney disease 1-like 3 LOC389603 7 hypothetical gene supported by AK098637 PTPRN2 7q36 protein tyrosine phosphatase, receptor type, N polypeptide 2
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
6 - 3020 - 277 - 1997 9268630
6 - 2635 - 178 - 1997 9268630
4 - 2728 - 164 - 1997 9268630
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver   highly
Lymphoid/Immunelymph node    
Reproductivefemale systembreastmammary gland  
Skin/Tegumentskin    
cell lineage
cell lines
fluid/secretion
at STAGE
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)
  • cell & other
  • unsaturated fatty acids stabilize INSIG1 without affecting its ubiquitination
  • REGULATION
    induced by insulin
    ASSOCIATED DISORDERS
    corresponding disease(s)
    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