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FLASH GENE
Symbol KRT18 contributors: mct/ - updated : 28-08-2018
HGNC name keratin 18
HGNC id 6430
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • conserved central rod domain, with four helical domains (1A, 1B, 2A, 2B) interrupted by non alpha helical linkers (L1, 2, 3)
  • the homology domain H1, by variable region (V1, V2) and end sequences (E1, E2)
  • myosin tail
  • C-terminal tail of KRT18 was found to be a critical determinant for binding CFTR
    • conjugated GlycoP
    mono polymer heteromer , tetramer
    HOMOLOGY
    interspecies homolog to murine Krt18
    Homologene
    FAMILY
  • intermediate filament family
  • type I keratin family
    • CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,intermed filament
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • when phosphorylated, plays a role in filament reorganization
  • KRT8/KRT18-coexpression plays a causal role in basement membrane invasion by transformed keratinocytes
  • KRT8/KRT18 intermediate filament (IF) contribution to the cell stiffness- extracellular matrix (ECM) rigidity interplay through a modulation of RHO-dependent actin organization and dynamics in simple epithelial cells
  • KRT18 enhances the stability of mature CFTR without altering the biosynthesis or maturation of CFTR
  • KRT8/KRT18 intermediate filaments constitute key promoters of the thymic epithelium integrity
  • is dispensable for the prostate morphogenesis but contributes to adult prostate regeneration
  • Keratins 8/18 (KRT8/KRT18) are phosphoglycoproteins and form the major intermediate filament network of simple epithelia
  • may likely play an active role during the earlier stages of epithelial-mesenchymal transition (EMT)
  • KRT8/KRT18 expression could constitute a novel factor regulating primordial follicle death/survival, raising the possibility that alterations of KRT8/KRT18 expression could be involved in the accelerated depletion of the ovarian reserve leading to premature ovarian insufficiency
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism nucleic
    signaling
    a component
  • dimerizing with KRT8
  • heterotetramer of two type I and two type II keratins
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • KRT18 controls the function of CFTR, and increases the cell surface expression of CFTR by interacting with the CFTR C-terminal hydrophobic patch
  • TNF confers cardioprotection through ectopic expression of keratins KRT8 and KRT18
  • interplay between ARHGEF40 and KRT8/KRT18 filaments plays a crucial role in tensile force-induced RHOA activation and consequent actin cytoskeletal reinforcement
  • critically contributes to initiating TGFB1-induced EMT via the SMAD2/3 -mediated regulation of SNAI1, SNAI2 expression in breast epithelial cells
  • KRT8/KRT18 interact with NOTCH1 and regulate NOTCH1 signalling activity during differentiation of the colonic epithelium
    • cell & other
    REGULATION
    Other regulation of its expression by ELF5 in lung epithelial cells
    positive interplay between O-GlcNAcylation and phosphorylation at adjacent sites on KRT18 to regulate its fundamental properties
    cleaved by the action of caspases during apoptosis, and the resulting fragments are released into the blood as caspase-cleaved CK (CCCK18)
    KRT18 expression is directly regulated by EGR1, contributing to decrease malignancy of non-small-cell lung carcinoma (NSCLC)
    ASSOCIATED DISORDERS
    corresponding disease(s) CCRH
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    detectable in the vascular smooth muscle cells of atherosclerotic lesions
    tumoral     --over  
    in metastatic cells
    constitutional     --over  
    of total KRT18 serum and urine levels in CKD patients, possibly indicating that epithelial cell necrosis is prevalent in chronic kidney disease (CKD)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • KRT18 is a promising non-invasive biomarker for Nonalcoholic steatohepatitis (NASH) in children with fatty liver disease
  • KRT18 is promising plasma biomarker to identify patients with HELLP syndrome
  • high circulating caspase-cleaved KRT18 (CCCK18) is associated with injury severity and a poor clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH)
  • correlation between serum KRT18 and the progression or regression of non-alcoholic fatty liver disease
    • Therapy target
    ANIMAL & CELL MODELS