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FLASH GENE
Symbol PKP1 contributors: mct - updated : 23-06-2015
HGNC name plakophilin 1 (ectodermal dysplasia/skin fragility syndrome)
HGNC id 9023
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal head domain including a potential coiled-coil forming alpha-helix segment, and head domains of PKP1 and PKP2 were sufficient to bind single-stranded DNA
  • a central domain with ten repeats of the Armadillo motif
  • a C terminal tail domain, with AAs 686-726 required for its localization to the plasma membrane
    • HOMOLOGY
    interspecies homolog to Drosophila Armadillo segment polarity gene
    ortholog to murine Pkp1
    Homologene
    FAMILY
  • beta-catenin family
  • arm-repeat (armadillo) family
  • plakophilin gene family
    • CATEGORY adhesion , structural protein
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,desmosome
        intracellular
    intracellular,cytoplasm,cytoskeleton,intermed filament
    intracellular,nucleus,nucleoplasm
    text
  • of the three Pkps, PKP1 is most readily detected in the nucleus, where it is localized to the nucleoplasm
    • basic FUNCTION
  • enhancing lateral interaction between desmoplakines molecules
  • involved in cutaneous cell-cell interaction and epidermal morphogenesis
  • playing a role in junctional plaques
  • plays an important role in desmosome stability and/or assembly
  • significant role of PKP1 in stabilization of desmosome structure and function, predominantly in the spinous layers of the epidermis (pMID: 19945625)
  • is a regulator of translation and proliferation via modulation of EIF4A1 activity and suggest that PKP1 controls cell growth in physiological and pathological conditions
  • in addition to mediating desmosome assembly, the nuclear pool of PKP1, PKP2 can influence cell survival by interactions with DNA
  • armadillo family protein critical for desmosomal adhesion and epidermal integrity
  • PKP1 expression transforms desmosome adhesion from a calcium-dependent to a calcium-independent and hyperadhesive state
    • CELLULAR PROCESS cell communication
    cell migration & motility
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component essential plaque protein of desmosomes in stratified epithelia with desmosomal location
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • desmogleins
  • desmocollins
  • direct association of PKP1 with the eukaryotic translation initiation factor 4A1 (EIF4A1), and PKP1 directly promoted EIF4A1 adenosine triphosphatase activity
  • PKP1 associates specifically with nuclear components
  • binding of PKP1/3 to FXR1 was RNA independent, and both PKP3 and FXR1 stabilized PKP2 mRNA
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) EBSPD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    PKP1 loss secondary to promoter methylation, as well as other mechanisms, may promote the progression of Barrett esophagus (BE) to esophageal adenocarcinoma (EAC) in a subset of patients via decreased desmosome assembly and increased cell motility
    constitutional     --low  
    results in an integral weakness within the desmosomal plaque, leading to desmosomal detachment and cell-cell separation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS