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FLASH GENE
Symbol LTBP4 contributors: mct/npt - updated : 31-03-2015
HGNC name latent transforming growth factor beta binding protein 4
HGNC id 6717
DNA
TYPE functioning gene
STRUCTURE 36.93 kb     33 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
text at least four different forms (Saharinen)
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
33 - 5052 170 1587 - 2010 20175115
30 - 4979 - 1557 major form of LTBP4 in lung and intestine 2010 20175115
  • also called LTBP4S
  • majority of LTBP4S was secreted in a free form
  • 33 - 5163 - 1624 liver expressed mainly LTBP4L 2010 20175115
  • also called LTBP4L
  • N terminal extended including a RGD
  • during secretion, LTBP-4L was complexed with TGF-beta1
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Homo sapiens
     vesselsaorta   
    Digestiveintestinesmall intestine    Homo sapiens
     liver     Homo sapiens
    Lymphoid/Immunetonsils   highly
    Nervousnervecranial nerve  highly
    Reproductivefemale systemovary  highly
    Respiratorylung     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal   Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • possess heparin binding activity, especially in its N-terminal region
  • 36 EGF-like motifs (18 calcium-binding cbEGF)
  • three 8 cysteine residues motif, one of F type(two of LT type)
  • seven ANK repeats
  • three LNR (lin/notch) repeats
  • C-terminal domain associated with the matrix structures, domain supported fibroblast adhesion, a property reduced by soluble heparin (Kantola 2008)
  • mono polymer homomer
    HOMOLOGY
    Homologene
    FAMILY
  • fibrillin superfamily
  • NOTCH family
  • LTBP family
  • CATEGORY signaling growth factor
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytoskeleton,microfilament
    intracellular,nucleus
    text
  • microfibrillar
  • FBLN5 specifically colocalized with LTBP4 on microfibrils
  • basic FUNCTION
  • functioning as a receptor for membrane- bound ligands delta and serrate to regulate cell-fate determination
  • playing an essential role for proper differentiation of ectoderm
  • having functions as an adhesion molecule (Kantola 2008)
  • may contribute to Abdominal Aortic Aneurysm progression (Thompson 2009)
  • LTBP4 functions are modified by tissue-specific expression of the two N-terminally distinct variants, which in addition exhibit significant differences in cellular processing and targeting
  • unique function for LTBP4 during elastic fibrogenesis
  • orchestrates elastin deposition onto microfibrils by binding with FBLN5, which is bound to tropoelastin
  • elastogenic activity of LTBP4 is not dependent on associated TGFB1, but is attributed to LTBP4 itself
  • promoted elastic fiber assembly by facilitating tropoelastin deposition on microfibrils
  • increases elastic fibers by promoting elastin deposition on microfibrils could be an approach toward regenerative treatment for diseases caused by elastic fiber degradation
  • role in regulating FBLN5 dependent elastic fiber assembly
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • extracellular matrix constituent likely bound to TGFB1 complex
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • regulating the bioavailability of TGF-betas
  • binds directly to fibronectin (FN), which was indispensable for the matrix assembly of LTBP4 (Kantola 2008)
  • LTBP4 is necessary for linear deposition of FBLN5 to microfibrils
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) CPVS , ARCL1C
    Susceptibility
  • to Abdominal Aortic Aneurysm
  • to variation of age of ambulatory loss in Duchenne muscular dystrophy
  • Variant & Polymorphism SNP
  • significant association with the LTBP4 21011A>T genotype in Abdominal Aortic Aneurysm (Thompson 2009)
  • in Duchenne muscular dystrophy, individuals homozygous for the IAAM LTBP4 haplotype remained ambulatory significantly longer than those heterozygous or homozygous for the VTTT haplotype
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    dermatologyskin 
    potential therapeutic target for elastic fiber regeneration
    ANIMAL & CELL MODELS
  • mice deficient in Ltbp4 display a defect in lung septation and elastogenesis