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FLASH GENE
Symbol KRT8 contributors: mct/ - updated : 28-08-2018
HGNC name keratin 8
HGNC id 6446
Location 12q13.13      Physical location : 53.290.970 - 53.298.868
Synonym name
  • keratin, type II cytoskeletal 8
  • cytokeratin-8
  • cardiac autoantigen 2, 120kD
  • Synonym symbol(s) K8, KO, CK8, CYK8, K2C8, CARD2
    DNA
    TYPE functioning gene
    STRUCTURE 52.68 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 1802 53.7 483 - 2017 28045574
    9 - 1901 - 483 - 2017 28045574
    9 - 1807 - 511 - 2017 28045574
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestine   highly Homo sapiens
    Nervousbrain   moderately
    Reproductivefemale systemplacenta  highly
     female systembreastmammary gland highly
    Urinarykidney   moderately
    Visualeyeanterior segmentconjunctiva   Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialabsorptive excretorydigestive epithelium (mucosa)  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveenterocyte Homo sapiens
    Visualepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • conserved central rod domain, made of four helical domains (1A,1B,2A,2B) interrupted by non alpha helical linkers (L1,2,3)
  • the homology domains H1 and H2, variable region (V1,V2), end sequences (E1,E2)
  • mono polymer heteromer , tetramer
    HOMOLOGY
    interspecies ortholog to murine Krt2-8
    homolog to rattus Rn.11083
    homolog to Xenopus Xl.2622
    homolog to Zebrafish krt8
    homolog to C.elegans F38B2.1
    Homologene
    FAMILY
  • intermediate filament family
  • type II keratin family
  • CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,intermed filament
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • plays a role in maintaining cellular structural integrity and also functions in signal transduction and cellular differentiation
  • 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
  • KRT8/KRT18 intermediate filaments constitute key promoters of the thymic epithelium integrity
  • Keratins 8/18 (KRT8/KRT18) are phosphoglycoproteins and form the major intermediate filament network of simple epithelia
  • have a dual role in retinal pigment epithelium (RPE) pathophysiology
  • 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
  • plays a direct role in the growth of Anaplastic thyroid carcinoma (ATC)
  • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    text cytoskeleton organization and biogenesis
    PATHWAY
    metabolism
    signaling
    a component
  • heterotetramerizing with KRT18 (two type I and two type II keratins)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • EXOC4 regulates KRT8 phosphorylation and cell migration by controlling the ERK and MAPK14 signalling pathways
  • 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
  • KRT8 interacts with the nucleotide-binding domain 1 (NBD1) of CFTR with phenylalanine 508 deletion (delatF508)
  • KRT8 regulates NOTCH1 signalling activity and differentiation in the epithelium of the large intestine
  • binds to ANXA2, a protein known to mediate apoptosis as well as the redox pathway
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in gastric cancer
    constitutional germinal mutation      
    in cryptogenic liver disease
    tumoral     --over  
    in metastatic cells
    constitutional   deletion    
    resulted in lower fasting glucose levels, increased glucose tolerance and insulin sensitivity, reduced glucose-stimulated insulin secretion and decreased pancreatic insulin content
    constitutional     --low  
    in intervertebral disc degeneration
    constitutional       loss of function
    confers resistance to colonocyte apoptosis in a microflora-dependent manner
    Susceptibility
  • to chronic pancreatitis
  • to hepatitis with cirrhosis
  • to inflammatory bowel disease
  • to pancreatic cancer
  • Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurosensorialvisual 
    pharmacological manipulation of KRT8 upregulation through autophagy with combined inhibition of the MAPK1/3 pathway may be attractive therapeutic strategies for the treatment of age-related macular degeneration (AMD)
    respiratoryCF (mucoviscidosis) 
    interruption of the interaction with CFTR may constitute a new therapeutic target for CF patients bearing the delta F508 mutation
    ANIMAL & CELL MODELS
  • K8-knockout (K8-/-) mice display a keratin dose-dependent hyperproliferation of colonic crypts and a colitis-phenotype
  • key role for the intermediate filament protein keratin 8 (Krt8), in the osteoblast dysfunctions in F508del-Cftr mice, providing a therapeutic strategy targeting the Krt8-F508del-CFTR interaction to correct the abnormal bone formation and bone loss in cystic fibrosis