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FLASH GENE
Symbol ITGB4 contributors: mct - updated : 05-11-2013
HGNC name integrin, beta 4
HGNC id 6158
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a 27 AAs signal peptide (2.7 kDa)
  • a globular domain
  • a stalk region with four EGF-like repeat domains each with eight cysteine residues
  • a single transmembrane (1TM) segment
  • a cytoplasmic tail, highly homolog to the EGF-calcium binding motif
  • a very large cytoplasmic domain, with three serine residues that play a critical role in the regulation of hemidesmosomes disassembly
  • mono polymer heteromer , dimer
    isoforms Precursor a 1795 amino acids mature peptide (199.4 kDa)
    HOMOLOGY
    interspecies homolog to rattus Itgb4 (87.80 pc)
    homolog to murine Itgb4 (88.78 pc)
    Homologene
    FAMILY
  • integrin Bêta chain family
  • CATEGORY adhesion , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • cell surface adhesion receptor 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
  • promotes epidermal growth and wound healing through a previously unrecognized effect on nuclear translocation of NF-kappaB and mitogen-activated protein kinases
  • important role of ITGB4 phosphorylation on residues Ser-1356 and Ser-1364 in the formation and/or stability of hemidesmosomes
  • promotes carcinoma invasion through its ability to promote directed migration and polarization of carcinoma cells
  • receptor for laminins that promotes carcinoma invasion through its ability to regulate key signaling pathways and cytoskeletal dynamics
  • play an important role in matrix remodeling and invasion
  • is a master regulator of transcription and translation of other integrin subunits and underscore its pivotal role in wound healing and cancer
  • hemidesmosome component, that attach epithelia to basal lamina and disassemble during migration and carcinoma invasion
  • endothelial ITGB4 is predominantly expressed in arterioles, where it promotes vascular remodeling in the hypoxic brain
  • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • dimerizing with ITGA6, laminin receptor, also constituent of hemi-desmosomes, beta 4 receptor of laminins
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ITGA6, laminin receptor
  • interacting with ARRDC3 (binds ITGB4 after ubiquitination, and seems likely to have a role in targeting ITGB4 for degradation)
  • ITGB4 associates with MMP9 and its ectodomain is a target for cleavage by MMP9
  • SPARC is an effector of ITGB4-mediated invasion
  • ITGB4 has the ability to regulate the expression of specific miRNAs and that such miRNAs can influence ITGB4-mediated migration and invasion
  • calcium/calcineurin pathway promotes hemidesmosome stability through inhibition of ITGB4 phosphorylation
  • ITGB4 and SRC activation is important early signaling events to lead MTOR activation and cap-dependent translation of VEGFA
  • important role for S1PR2 and S1PR3 in S1P/HGF-mediated EC barrier responses that are associated with their complex formation with ITGB4
  • cell & other
    REGULATION
    Other calcineurin, a serine-threonine protein phosphatase, regulates ITGB4 phosphorylation
    ASSOCIATED DISORDERS
    corresponding disease(s) EBJPAB , EBJ2D
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    altered in agressive behavior of cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    ARRCD3-ITGB4 pathway is a new therapeutic target in breast cancer
    cardiovascularaquired 
    might be a potential target for therapy in cardiovascular diseases
    ANIMAL & CELL MODELS