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FLASH GENE
Symbol ITGB4 contributors: mct - updated : 05-11-2013
HGNC name integrin, beta 4
HGNC id 6158
DNA
TYPE functioning gene
STRUCTURE 36.38 kb     40 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked   status confirmed
RNA
TRANSCRIPTS type messenger
text five alternatively spliced (mutation at branch point), expressed in tissu specific, unknown function (Chavanas)
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
40 - 5925 202.1 1822 - 2006 16713569
  • also called ITGB4C
  • a 27 amino acids signal peptide (2.7 kDa)
  • a 40 exons variant
  • containing exon 2a (longer than 2b)
  • lacking exon 35
  • encoding for the longest product
  • 39 - 5695 201.7 1805 - 2006 16713569
  • also called ITGB4B
  • a 27 amino acids signal peptide (2.7 kDa)
  • a 39 exons variant
  • containing exon 2b (shorter than 2a)
  • lacking exons 1 & 33
  • 39 - 5715 195 1752 - 2006 16713569
  • also called ITGB4A
  • a 27 amino acids signal peptide (2.7 kDa)
  • a 39 exons variant
  • containing exon 2a (longer than 2b)
  • lacking exons 33 & 35
  • - - - - 1745 - -
  • also called ITGB4D
  • - - - - 964 - -
  • also called ITGB4E
  • 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 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