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FLASH GENE
Symbol ITGB4 contributors: mct - updated : 05-11-2013
HGNC name integrin, beta 4
HGNC id 6158
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularvesselartery  highly Homo sapiens
Digestiveintestinelarge intestinecolon highly
Nervousbrain     Homo sapiens
Reproductivefemale systemovary  highly
 female systembreastmammary gland highly
 female systemuteruscervix moderately
 female systemplacenta  moderately
 male systemprostate  moderately
Respiratorylung   moderately
 respiratory tractlarynx  highly
Urinarybladder   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connective    
Epithelialbarrier liningretinal pigment epithelium (RPE) lowly
Nervous   highly Homo sapiens
skin tegumentdermis   
cells
SystemCellPubmedSpeciesStageRna symbol
Cardiovascularendothelial cell Homo sapiens
Skin/Tegumentkeratinocyte
cell lineage
cell lines Schwannomas
fluid/secretion
at STAGE
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 BÍta 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