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FLASH GENE
Symbol IGF1R contributors: mct/npt/pgu - updated : 02-07-2019
HGNC name insulin-like growth factor 1 receptor
HGNC id 5465
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a receptor-L domain
  • two fibronectin type 3-like domains
  • a tyrosine kinase catalytic domain
  • a furin-like cysteine-rich region
  • a 30-residue signal peptide
  • intracellular domain directly binds to the NT2 domain of PTK2 and the PTK2-NT2 domain co-localizes with IGF1R in pancreatic cancer cells
    • mono polymer heteromer , tetramer
    HOMOLOGY
    interspecies homolog to murine Igf1r
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • insulin receptor subfamily
    • CATEGORY signaling , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    text type 1 membrane protein
    basic FUNCTION
  • insulin-like growth factor 1, receptor with high affinity
  • receptor tyrosine kinase, class II, with potent mitogenic, antiapoptotic and transforming activities required for oncogenic transformation
  • activates PI3K
  • positive regulation of cell proliferation
  • inhibits MAP3K5 (complexed with, in perinuclear structures) and then supresses stimulation of JNK/p38 pathway and induction of programmed cell death
  • binds its ligand and then initiates metabolic cascades resulting in stimulation of protein synthesis, glucose intake, glycogen synthesis or lipid storage
  • its activation prevents high glucose-induced mitochondrial dysfunction, cytochrome-c release and apoptosis
    • CELLULAR PROCESS cell cycle
    cell life, proliferation/growth
    cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP binding
    • protein
  • IGF1 binding
  • linked to RAS/RAF/MAPK and PI3K/PKB/AKT signal transduction cascade
  • associates with SNAP29
  • binding to PIK3R3
  • MAP3K5 binding
  • interaction with PTK2 (role in phosphorylation, signaling and stability of the IGF1R)
  • interaction with PTK2 plays an important role in cancer cell survival, providing survival signals in human pancreatic cancer cells
  • CAMP may act as a partial agonist for IGF1R, with subsequent intra-cellular signaling activation driven by the binding of ARRB1 to the IGF1R
  • PDZK1 expression was indirectly regulated by ESR1 stimulation, requiring insulinlike growth factor 1 receptor (IGF1R) expression and function
  • UBQLN1 interacts with IGF1R and ESYT2 through the STI domains and stabilizes these proteins through its UBA domain
  • IGF1R is the functional receptor for DIPK2A
  • CD36 functioned through ubiquitination-dependent binding to IRS1 and inhibiting its interaction with CUL7, a key component of the multisubunit cullin-RING E3 ubiquitin ligase complex
  • IRS1 modulates how long ligand-activated IGFIR remains at the cell surface before undergoing endocytosis in cell
    • cell & other
    REGULATION
    activated by the chimeric PAX3/FKHR oncoprotein,IGF1,IGF2
    inhibited by TNF and IFNG (inhibition of promoter activity)
    p53, BRCA1, suppressing the activity of the promoter
    ASSOCIATED DISORDERS
    corresponding disease(s) DEL15QD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast and prostate cancer where it functions as an anti-apoptotic agent by enhancing cell survival
    constitutional germinal mutation      
    associated with an insensitivity to IGF1 due to IGF1R haploinsufficiency
    constitutional germinal mutation      
    in intrauterine and postnatal growth retardation
    Susceptibility
  • to breast cancer with poor survival
  • to spontaneous preterm birth
    • Variant & Polymorphism SNP , other
  • polymorphisms in the IGF1R and IGFBP3 genes may be associated with altered survival among subgroups of breast cancer patients defined by menopausal status
  • association of a 6-SNP IGF1R haplotype with spontaneous preterm birth in the fetuses
    • Candidate gene for low birth weight, insuline resistance and type II diabetes
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerendocrineadrenal
    target for future therapeutic approaches in adrenal neoplasia
    ANIMAL & CELL MODELS