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FLASH GENE
Symbol KRT18 contributors: mct/ - updated : 28-08-2018
HGNC name keratin 18
HGNC id 6430
Corresponding disease
CCRH chronic hepatitis, cryptogenic cirrhosis
Location 12q13.13      Physical location : 53.342.654 - 53.346.684
Synonym name
  • tissue-polypeptide specific antigen identified by monoclonal antibody M3, 13 kD, (fragment of KRT18)
  • cell proliferation-inducing gene 46 protein
  • cytokeratin-18
  • keratin, type I cytoskeletal 18
  • Synonym symbol(s) K1CR, K18, CYK18, PIG46
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    STRUCTURE 4.03 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    motif repetitive sequence   ALU
    text structure
  • including a 3' locus control region KRT18-LCR
  • an EGR1 binding site was situated in the promoter of KRT18
  • MAPPING cloned Y linked Y status confirmed
    Physical map
    KRT6A 12q13 keratin 6A KRT6C 12q12-q13 keratin 6C KRT5 12q13.2-q13.3 keratin 5 (epidermolysis bullosa simplex, Dowling-Meara/Kobner/Weber-Cockayne types) KRT6IRS 12q13.13 keratin 5 (epidermolysis bullosa simplex, Dowling-Meara/Kobner/Weber-Cockayne types) K6IRS4 12q13.13 keratin 5 (epidermolysis bullosa simplex, Dowling-Meara/Kobner/Weber-Cockayne types) K6IRS2 12q13.13 keratin 5 (epidermolysis bullosa simplex, Dowling-Meara/Kobner/Weber-Cockayne types) K6IRS3 12q13.3 keratin 5 (epidermolysis bullosa simplex, Dowling-Meara/Kobner/Weber-Cockayne types) KRT2A 12q13.1-q13.2 keratin 2A (epidermal ichthyosis bullosa of Siemens) KRT1 12q13 keratin 1 (epidermolytic hyperkeratosis) LOC387860 12 similar to keratin 1b LOC341409 12q13.13 similar to DEAD (Asp-Glu-Ala-Asp) box polypeptide 23 LOC387861 12 similar to K+ channel tetramerization protein HUMCYT2A 12q13.13 cytokeratin 2 KRT3 12q13 keratin 3 KRT4 12q13 keratin 4 KRT6L 12q13.13 keratin 6L K5B 12q13.13 keratin 5b KRT8 12q13 keratin 8 KRT18 12q13 keratin 18 EIF4B 12q13.13 eukaryotic translation initiation factor 4B PRO1843 12q13.13 hypothetical protein PRO1843 TENC1 12q12 tensin like C1 domain-containing phosphatase FLJ14800 12q13.13 hypothetical protein FLJ14800 IGFBP6 12q13 insulin-like growth factor binding protein 6 SOAT2 12q13.13 sterol O-acyltransferase 2 LOC387862 12 hypothetical gene supported by AK130082; NM_001416 CSAD 12q13.11-q14.3 cysteine sulfinic acid decarboxylase LOC390316 12 similar to oriLyt TD-element binding protein 7 ITGB7 12q13.2 integrin, beta 7 MGC11308 12q13.13 hypothetical protein MGC11308 ESPL1 8 extra spindle poles like 1 (S. cerevisiae) PFDN5 12q13.1 prefoldin 5 C12orf10 12q13 chromosome 12 open reading frame 10 AAAS 12q13 achalasia, adrenocortical insufficiency, alacrimia (Allgrove, triple-A) SP7 12q12 Sp7 transcription factor
    RNA
    TRANSCRIPTS type messenger
    text two transcripts encode the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 1485 48 430 - 2012 23045527
    8 - 1439 48 430 - 2012 23045527
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines only breast adenocarcinoma cell line, cutaneous squamous cell carcinoma
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text early, simple epithelia
    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