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FLASH GENE
Symbol DSC3 contributors: mct - updated : 11-04-2020
HGNC name desmocollin 3
HGNC id 3037
Corresponding disease
HTSV hypotrichosis and skin vesicles
Location 18q12.1      Physical location : 28.570.052 - 28.622.781
Synonym name
  • desmosomal glycoprotein 3
  • desmocollin 4
  • cadherin family member 3
    • Synonym symbol(s) CDHF3, DSC, DSC1, DSC2, DSC4, HT-CP
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    text clustered with DSC1, DSC2 and desmogleins DSG1, DSG2, DSG3
    STRUCTURE 52.73 kb     16 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence
    MAPPING cloned Y linked N status confirmed
    Map see TTR
    regionally located clustered with DSC1, DSC2 and desmogleins DSG1, DSG2, DSG3
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 - 6935 100 896 - 1995 7665906
    17 - 6978 - 839 - 1995 7665906
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Skin/Tegumentskin    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningepidermisstratum basale 
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a number of domains, including a signal sequence (AAs 1–27)
  • a propeptide (28–135 AAs)
  • an extracellular domain (136–690 AAs), divided into five cadherin domains
  • a transmembrane domain (691–711 AAs)
  • a C-terminal cytoplasmic domain (712–896 AAs)
    • conjugated GlycoP
    HOMOLOGY
    intraspecies homolog to desmoglein DGII/DGIII
    Homologene
    FAMILY
  • cadherin superfamily of calcium dependent cell-adhesion molecule
    • CATEGORY adhesion
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane,junction,desmosome
        intracellular
    intracellular,cytoplasm
    basic FUNCTION
  • required for cell adhesion and desmosome formation
  • play a critical role in the maintenance of tissue integrity in epithelia and cardiac muscle
  • playing a role in normal function of desmosomes, maintenance of structural integrity of the interfollicular epidermis, and anchorage of the telogen hair shaft
  • DSC3-mediated binding is also crucial for cohesion of human epidermis
  • DSC3 homo- and heterophilic binding is required for maintenance of keratinocyte cohesion and interference with DSC3 binding may contribute to skin blistering in pemphigus
  • is a desmosomal cadherin that is required for maintaining cell adhesion in the epidermis as demonstrated by the intra-epidermal blistering observed in DSC3 null skin
  • DSC3 likely can contribute to the progression of tumors both by cell adhesion-dependent (skin surface) and likely by cell adhesion-independent (invading tumor cells) mechanisms
  • acts as a novel tumor suppressor gene through inhibition of epidermal growth factor receptor/extracellular signal-regulated kinase signaling in lung cancer cells
  • can mediate FSH-induced ovarian cancer cell proliferation by activating the EGFR/AKT1 signaling pathway
  • transmembrane adhesion protein of desmosomes and involved in carcinogenesis in various cancer types
  • DSC3 suppresses Colorectal cell growth through inhibition of AKT1 pathway and regulation of CDH1
    • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of desmosome
    • INTERACTION
    DNA
    RNA
    small molecule
    protein displayed heterophilic interaction with DSG1 but not with DSG3
  • LEF1 acts as a switch activating DSC2 and repressing DSC3 in the presence of JUP
  • LEF1 can act as a switch between DSC2 and DSC3 expression and the presence of LEF1 in keratinocytes can suppress the DSC3 gene
  • in ovarian cancer DSC3 and EGFR regulate each other and the activation of the AKT1 pathway, and AKT1 mediates FSH-dependent DSC3 expression
  • 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
    • cell & other
    REGULATION
    activated by C/EBPbeta but not C/EBPalpha (differentially regulated by C/EBP (CCAAT/enhancer-binding protein) family members)
    ASSOCIATED DISORDERS
    corresponding disease(s) HTSV
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    is a common event in primary breast tumor specimens, and gene silencing in breast tumors is frequently linked to aberrant cytosine methylation and concomitant changes in chromatin structure
    tumoral     --other  
    de novo expression in colorectal cancer
    constitutional germinal mutation      
    in microphthalmia
    tumoral     --low  
    in colorectal cancer (CRC)
    tumoral     --low  
    DNA methylation contributes to down-regulation of DSC3 in prostate cancer, and loss of DSC3 predicts poor clinical outcome
    constitutional     --other  
    IgG autoantibodies against DSC3, induce loss of keratinocyte adhesion and thus may contribute to blister formation in pemphigus
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • in primary lung tumors, DSC3 was a potential diagnostic marker for lung squamous cell carcinoma, and DSC3 DNA hypermethylation was correlated with poor clinical outcome
    • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivecolon
    may serve as a novel therapeutic target for CRC
    ANIMAL & CELL MODELS