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FLASH GENE
Symbol DSP contributors: mct/npt - updated : 15-09-2018
HGNC name desmoplakin
HGNC id 3052
Corresponding disease
ARVD8 arrhythmogenic right ventricular dysplasia, familial, 8
DCWHK cardiomyopathy, dilated, with wooly hair and keratoderma
EBSLA epidermolysis bullosa simplex, lethal acantholytic
PPKS2 palmoplantar keratoderma (hyperkeratosis) striata
Location 6p24.3      Physical location : 7.541.869 - 7.586.946
Synonym name
  • 250/210 kDa paraneoplastic pemphigus antigen
  • desmoplakin (DPI, DPII)
    • Synonym symbol(s) KPS2, KPPS2, DPI, DPII, DP
    DNA
    TYPE functioning gene
    STRUCTURE 45.14 kb     24 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
    24 - 9730 - 2871 - 2007 17475244
    24 - 7933 - 2272 - 2007 17475244
    24 - 8473 - 2428 - 2007 17475244
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouth   highly
     pharynx   highly
    Endocrinepancreasislet of Langerhans   
    Respiratoryrespiratory tractlarynx  highly
    Skin/Tegumentskin   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/liningepidermisstratum basale 
    Epithelialsecretoryglandularendocrine 
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • globular N terminus required for localisation to desmosomal plaque, with AAs 1-34 necessary for subsequent recruitment of desmoplakin to the membrane and desmosome assembly , DPNT that binds to the cadherin/plakoglobin/plakophilin complex
  • N-terminal region contains a plakin domain common to members of the plakin family (Plakin domains contain multiple copies of spectrin repeats (SRs))
  • 12 plectin repeats
  • a central coiled-coil domain that dimerizes the molecule
  • C-terminal tail consisiting of characteristic repeat sequences and interacting with intermediate filament, and C-terminal tail (DPCTT)that is a molecular switch that modulates, via its conformational dynamics, DSP overall efficacy as a substrate for GSK3
    • HOMOLOGY
    intraspecies homolog to BPAG1
    Homologene
    FAMILY
  • plakin or cytolinker family
    • CATEGORY adhesion , structural protein
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytoskeleton,intermed filament
    intracellular,nucleus
    basic FUNCTION
  • involved in attachment of intermediate filaments to the desmosome (cell-cell junction)
  • playing an important role in the integrity and function of the myocardium
  • major obligate plaque protein which plays a fundamental role in anchoring intermediate filaments to desmosomal cadherins
  • may participate in the regulation of keratinocyte cell proliferation by, in part at least, regulating cell cycle progression
  • important cytoskeletal linker for the function of the desmosomes
  • integral part of desmosomes, where it links desmosomal cadherins to the intermediate filaments
  • is part of all desmosomes, which are abundantly expressed in both myocardial and epidermal tissue and serve as intercellular mechanical junctions
  • plays a crucial role in the stability of the interconnected components as well as gap junction connexin proteins
  • is necessary for normal motor regeneration
  • function of desmoplakin in motor nerve regeneration by linking CDH2 to intermediate filaments in regenerating motor axons
  • cytoskeletal linker protein that connects the desmosomal cadherin/plakoglobin/plakophilin complex to intermediate filaments (IFs)
    • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • intermediate filament associated protein (IFAP,type III) component of desmosomal plaque
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • N terminus with N terminal region of plakoglobin 1
  • associates with PKP2 in plaque precursors that form in the cytoplasm and translocate to nascent desmosomes
  • SOX30 acts as a master switch of desmosomal genes (DSC3, DSP, JUP), inhibits lung adenocarcinoma cell proliferation, migration and invasion by activating the transcription of desmosomal genes
  • DSP and TLN2 mRNAs associate with FXR1 in a complex
  • important novel regulatory pathway in hippocampal development, by linking transcriptional functions of BCL11B to DSP, a molecule known to act on cell adhesion
  • keratins control intercellular adhesion involving PRKCA-mediated DSP phosphorylation
  • interaction between MAPRE1 and DSP, and DSP/MAPRE1 interactions enable DSP to modify microtubule organization and dynamics near sites of cell-cell contact
  • GSK3A, and PRMT1 cooperate to orchestrate a series of posttranslational modifications on the Intermediate filament (IF) -anchoring protein desmoplakin (DSP) that play an essential role in coordinating cytoskeletal dynamics and cellular adhesion
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) PPKS2 , DCWHK , ARVD8 , EBSLA
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    can lead to loss of cell-cell adhesion via desmosomes, and disrupt the keratin intermediate filament network
    tumoral       loss of function
    in lung cancer cell lines, is inactivated by an epigenetic mechanism, increases the sensitivity to anticancer drug-induced apoptosis and has tumor-suppressive function (
    Susceptibility to idiopathic pulmonary fibrosis (IPF)
    Variant & Polymorphism other
  • IPF-associated intron 5 variant (rs2076295) is associated with increased risk of IPF
  • rare missense variants in DSP, were identified that have a statistically significant relationship with IPF
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS