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FLASH GENE
Symbol IGFBP2 contributors: mct - updated : 03-02-2016
HGNC name insulin-like growth factor binding protein 2, 36kDa
HGNC id 5471
Location 2q35      Physical location : 217.498.126 - 217.529.156
Synonym name IGF-binding protein 2
Synonym symbol(s) IBP2, IGBP2, IGF-BP53, BP2
DNA
TYPE functioning gene
STRUCTURE 31.03 kb     5 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Physical map
ABCA12 2q34 ATP-binding cassette, sub-family A (ABC1), member 12 ATIC 2q35 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase FN1 2q35 fibronectin 1 LOC151575 2q35 similar to MLRQ subunit of the NADH: ubiquinone oxidoreductase complex FLJ10116 2q35 hypothetical protein FLJ10116 PECR 2q35 hypothetical protein FLJ10116 LOC92691 2q35 hypothetical protein BC008604 XRCC5 2q35 X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining; Ku autoantigen, 80kDa) KIAA1399 2q35 KIAA1399 protein SMARCAL1 2q34-q36 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a-like 1 RPL37A 2q35 ribosomal protein L37a LOC130700 2q35 proteasome (prosome, macropain) subunit, beta type, 3 pseudogene IGFBP2 2q33-q34 insulin-like growth factor binding protein 2, 36kDa IGFBP5 2q33-q34 insulin-like growth factor binding protein 5 LOC391483 2 similar to ribosomal protein L31 TNP1 2q34-q36 transition protein 1 (during histone to protamine replacement) LOC151363 2q35 hypothetical LOC151363 TNS 2q35-q36 tensin FLJ46536 2q35 FLJ46536 protein IL8RB 2q35 interleukin 8 receptor, beta IL8RA 2q35 interleukin 8 receptor, alpha ARPC2 13q12-q13 actin related protein 2/3 complex, subunit 2, 34kDa GPBAR1 2q36.1 G protein-coupled bile acid receptor 1 AAMP 2q36.1 angio-associated, migratory cell protein MR-1 2q35 myofibrillogenesis regulator 1 PP1201 2p24.3-p24.1 PP1201 protein MGC50811 2q35 hypothetical gene supported by BC052750
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
5 - 1439 - 328 - 2006 17020769
- - 1024 - 181 - 2006 17020769
- - 1343 - 159 - 2006 17020769
- - 1082 - 159 - 2006 17020769
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver    
Lymphoid/Immunespleen    
Nervousbrain    
Reproductivefemale systemovary  highly
 female systemuterus   
 male systemprostate  highly
Visualeye    
cell lineage
cell lines
fluid/secretion spinal fluid
at STAGE
physiological period growth/childhood, pregnancy
Text neural tissues, placenta
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
  • 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
    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