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FLASH GENE
Symbol IGFBP2 contributors: mct - updated : 03-02-2017
HGNC name insulin-like growth factor binding protein 2, 36kDa
HGNC id 5471
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • invariant cysteine residues, 12 N terminal, 6 C terminal
  • a N terminal IGFBP motif
  • a central domain lacking cysteine residue, with a RGD motif
  • a thyroglobulin type-I domain
  • two heparin-binding domains (HBDs), contributing differentially to GAG binding in free IGFBP2 and the IGF2/IGFBP2 protein complex
  • C-terminal domains contribute to high-affinity IGF binding, and confer binding specificity and have overlapping but variable interactions with many other molecules, and this C-terminus, but not the RGD domain, of extrinsic IGFBP2 was essential for support of HSC activity
  • secondary structure a thyroglobulin type 1 fold consisting of an alpha-helix, a three-stranded anti-parallel beta-sheet and three flexible loops
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY signaling cytokine growth factor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle
    intracellular,cytoplasm,cytosolic,vesicle
    basic FUNCTION
  • having important functions in IGF-I actions in activated microglia/macrophages in the brain
  • major prostatic IGFBP and may be involved in regulating prostate growth
  • oncogenic factor for glioma progression in combination with platelet-derived growth factor-beta (PDGFB)
  • selective malignant factor that may contribute significantly to glioblastoma pathogenesis by enriching for glioma stem cells and mediating their survival
  • as an environmental factor, IGFBP2 supports the survival and cycling of HSCs
  • is an important regulator of osteoclastogenesis and both the heparin- and the IGF-binding domains of IGFBP2 are essential for the formation of fully differentiated and functional osteoclasts
  • NTF3 can synergize with IGFBP2 to promote hematopoietic cell expansion
  • nuclear IGFBP2 is required for the activation of VEGFA expression and consequent angiogenesis
  • is an extrinsic factor that supports the activity of hematopoietic stem cells (HSCs)
  • is a critical cell-autonomous factor that promotes the survival and migration of acute leukemia cells
  • TRIB3 and IGFBP2, both of which are known to be overexpressed in several types of cancers, are pro-survival modulators of cell viability in nutrient-deficient microenvironments
  • modulate both IGF and integrin signaling and is a mediator of cell growth, invasion and resistance in other tumor types
  • important novel role of IGFBP2 in regulation of corneal fibroblast differentiation
  • IGF1 and IGFBP2 function coordinately to stimulate AKT1 and osteoblast differentiation
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS development
    text regulation
    PATHWAY
    metabolism
    signaling
    a component
  • major IGFBP constituent of the spinal fluid
  • HMGA2-IGF2BP2 axis functions as a key regulator of satellite cell activation and therefore skeletal muscle development
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • bind insulin-like growth factors I and II (IGF-I/II)
  • IGFBP2 stimulates osteoblast differentiation and this effect is mediated through its heparin-binding domain-1 interacting with PTPRZ1
  • attenuate the biological action of IGF1
  • is the gene most substantially upregulated by TRIB3
  • CD5L binds to IGFBP2, IGFBP3 and IGFBP4, and this interaction may contribute to the mechanism of CD5L-mediated anti-apoptosis function
  • early induction of AMPK in response to IGF1/IGFBP2 followed by suppression is required for osteoblast differentiation
  • IGFBP2/IGF1 stimulated vimentin binding to PTPRZ1 and this was required for PTPRZ1 polymerization
  • IGFBP2 was shown to be positively associated with BSG expression
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in glioblastoma multiforme (GBM), and expression is inversely correlated to GBM patient survival
    tumoral     --other  
    deregulated in pancreatic beta cell tumorigenesis
    constitutional     --over  
    increase with age and it is generally assumed that IGFBP2 is a negative predictor of healthy aging
    tumoral     --over  
    in certain human AML and acute lymphoblastic leukemia (ALL) cells
    tumoral     --over  
    in clinical tissues of melanoma compared with the control group, and its expression exhibited a positive association with BSG
    Susceptibility to breast cancer
    Variant & Polymorphism
    Candidate gene
  • potentialy target for the treatment of prostate cancer
  • IGFBP2 inhibition may be an advantageous clinical approach to ablate the most malignant cancer cells in glioblastoma without off-target effects on normal cells
  • Marker
  • a high circulating level of IGFBP2 is significantly associated with poor survival, suggesting that blood IGFBP2 levels could be a prognostic biomarker for lung cancer
  • may be a useful biomarker integrating the nutritional status, as well as the biological effects of GH, IGF1, and insulin
  • Therapy target
    SystemTypeDisorderPubmed
    cancerbrain 
    marker and potential therapeutic target for CDKN2A-deleted gliomas
    neurosensorialvisualanterior chamber
    can be a therapeutic candidate for corneal antifibrotic strategy
    ANIMAL & CELL MODELS
  • Igfbp2-null mice have fewer hematopoietic stem cells than wild-type mice