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FLASH GENE
Symbol ITGB3 contributors: mct - updated : 27-06-2017
HGNC name integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61)
HGNC id 6156
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • six N terminal domains highly conserved between ITGBx
  • a transmembrane (1TM) segment
  • a cytoplasmic segment containing potential phosphorylation sites
  • four cys rich repeats
    • conjugated GlycoP
    mono polymer heteromer , dimer
    isoforms Precursor
    HOMOLOGY
    intraspecies paralog to ITGB1
    Homologene
    FAMILY
  • integrin beta chain family
    • CATEGORY adhesion , antigen , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,nucleus
    basic FUNCTION
  • cell surface adhesion receptor for fibronectin, fibrinogen, vitronectin, prothrombin, thrombospondin and others, mediating cell-adhesion to extra cellular matrix or to other cells, through hetero dimerization and connecting to the cytoskeleton and various signaling molecules within cells
  • collectively, ITGA2B /ITGB3 in mast cells plays an important part in fibrinogen (FB)-associated, chronic inflammation and innate immune responses
  • required for iron transportation during enamel formation
  • neurite elongation promoted by vascular endothelial cells requires ITGB3
  • inhibits LPS-induced autophagy in cardiomyocytes, and the inhibition of AKT1 signaling might be an important mechanism in this process
  • expression of ITGB3, as well as tumor-produced factors associated with bone destruction (GLI2 and PTHRP), significantly increased with matrix rigidity
  • rigid mineralized bone matrix can alter gene expression and bone destruction in an ITGB3/TGFB1-dependent manner
    • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • dimerizing with ITGA2B, ITGAV (see symbols)
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ITGA2B, ITGAV
  • may interact with SLC6A4 in mediating autism susceptibility
  • interacting with FOXC2
  • MARCKSL1 downregulation by ITGB3 is not required for increased cell spreading but instead is a secondary effect of increased cell spreading
  • HOXA10 activates ITGB3 transcription in myeloid progenitor cells and differentiating phagocytes
  • interaction between Trp110 of ITGA2B and Arg261 of ITGB3 is critical for ITGA2B/ITGB3 integrity and outside-in signaling-related functions
  • PTK2B was rapidly phosphorylated and activated in platelets adherent to fibrinogen through integrin ITGA2B/ITGB3
  • deoxyribose-1-phosphate (dRP) is a novel autocrine amplifier of platelet activity, which acts on platelet redox levels and modulates ITGA2B/ITGB3
  • constitutive interaction between ITGB3 and SRC kinase
  • SPRY4 overexpression resulted in decreased ITGB3 protein levels in a post-transcriptional manner in part by modulating its tyrosine phosphorylation by SRC
  • ITGB3 is a modulator of serotonergic systems via genetic interactions with the 5-HT transporter gene (SLC6A4)
  • serine/threonine phosphatases regulate platelet ITGA2B/ITGB3 integrin receptor outside-in signaling mechanisms and clot retraction
  • protein ubiquitination promotes megakaryopoiesis via degrading SKIL, an inhibitor of ITGB3 expression, strengths the roles of ubiquitination in cellular differentiation
  • CDK11A is an anti-metastatic gene in ESR1-positive breast cancer and that the regulation of ITGB3 by CDK11 via the repression of ESR1 signaling may constitute part of a signaling pathway underlying breast cancer invasion
  • loss of traction force on ligand-bound ITGB3 causes recruitment of DAB2/clathrin, resulting in endocytosis of integrins
    • cell & other
    REGULATION
    activated by FERMT3 (role of FERMT3 phosphorylation in ITGB3 activation, providing a basis for functional differences between FERMT3 and the two other kindlin paralogs)
    Other regulated by NFATC1
    ASSOCIATED DISORDERS
    corresponding disease(s) GT3
    related resource Glanzmann Thrombasthenia Database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in human hepatocellular carcinoma cells (Wu 2009)
    constitutional     --low  
    significantly reduced ITGB3 expression compared to controls, in recurrent pregnancy loss
    constitutional     --over  
    ITGA2B/ITGB3 is significantly higher in atopic myelitis (AM) patients than in controls as well as in females compared with males
    constitutional germinal mutation     gain of function
    activating mutations in ITGA2B and ITGB3 represent the etiology of a subset of congenital macrothrombocytopenias
    Susceptibility
  • in association with PAI1 in susceptibility to myocardial infarction in Finnish population (see PAI1)
  • to cardiovascular disease
  • to neonatal autoimmune thrombocytopenia, post transfusion
  • to autism
    • Variant & Polymorphism SNP
  • 98 C>T in susceptibility to preeclampsia
  • Leu 33 associated with lower serotonin levels and with autism
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    reconstitution of ITGB3 in hepatocellular carcinoma may be a potential therapeutic approach to inhibit aggressive growth of liver cancer
    neurologyneurodegenerativealzheimer
    ITGA2B/ITGB3 complex activation could be a putative prognostic biomarker for the rate of cognitive decline and a potential new treatment target in Alzheimer patients
    cancermetastases 
    ITGB3 inhibitors are a potential therapeutic approach for blocking tumor transition to a bone destructive phenotype
    ANIMAL & CELL MODELS