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FLASH GENE
Symbol EPCAM contributors: mct/npt/pgu - updated : 21-06-2023
HGNC name epithelial cell adhesion molecule
HGNC id 11529
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
9 - 1731 35 314 - 2009 19584271
  • EpCAM(MF)
  • non-glycosylated, cleaved form of EPCAM in the microsomes
  • - - - - - highly expressed in cancers of the endometrium and bladder 2014 24465008
    truncated variant
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly Homo sapiens
     intestinesmall intestine  highly Mus musculusFetal
     stomach   highly
    Skin/Tegumentskin   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialabsorptive excretorydigestive epithelium (mucosa) highly Mus musculusFetal
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveepithelial cell Mus musculusFetal
    not specificepidermal dendritic cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text
  • placenta
  • highly expressed in embryonic stem cells (ESCs)
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a thyroglobulin type 1 repeat
  • two epidermal growth factor-like extracellular domains
  • one single transmembrane domain
  • and one small intercellular domain (EpICD), that alone is sufficient to induce proliferation signals
  • PDZ-domain identified in its C-terminal end
  • conjugated GlycoP
    isoforms Precursor N-terminal signal peptide is cleaved off during processing of EpCAM in both microsomes and human cells, and that 35 kDa is the normal size of non-glycosylated EPCAM
    HOMOLOGY
    intraspecies homolog to TACSTD2
    Homologene
    FAMILY
  • EPCAM family
  • CATEGORY adhesion , antigen
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane,junction,tight
        intracellular
    intracellular,cytoplasm,organelle
    intracellular,cytoplasm,cytosolic,microsome
    text
  • CLDN7 colocalized with EPCAM at cell-cell junctions, and the two proteins were found to associate with each other
  • type I integral membrane protein
  • non-glycosylated, cleaved form of EPCAM in the microsomes
  • basic FUNCTION
  • playing a central role in cell adhesion function
  • carcinoma associated antigen
  • having a direct impact on cell cycle and proliferation, and the ability to rapidly upregulate the proto-oncogene c-myc and cyclin A/E
  • having an oncogenic potential and activated by release of its intracellular domain, which can signal into the cell nucleus by engagement of elements of the wnt pathway
  • functions partly via homotypic protein interactions mediating cell-to-cell adhesion of epithelial cells
  • regulates morphogenetic movements through intracellular signaling
  • EPCAM and its associated protein, CLDN7, play a critical role in reprogramming
  • not merely a passenger gene that is up-regulated during reprogramming but a main player in a positive feedback loop among key factors that propel the reprogramming machinery
  • enhances cell cycle progression via the classical cyclin-regulated pathway
  • is an important regulator of movement of epithelial cells of distinct lineages with respect to each other
  • is a negative regulator of adhesion between epithelial cells
  • contributes to formation of intestinal barrier by recruiting claudins to cell-cell junctions
  • involved in numerous cellular processes including cell adhesion, proliferation, maintenance of stemness of embryonic cells and progenitors, migration and invasion
  • epithelial and cancer cell protein
  • regulates the composition and function of tight junctions
  • modulates adhesion and TJ function by regulating intracellular localization and degradation of selected claudins
  • EPCAM acts likely as a prosurvival factor counteracting terminal differentiation processes in normal mammary glands
  • EPCAM can act as an oncogene still depending on additional driver mutations and epithelial phenotype of tumor cells
  • EPCAM plays a key role in proliferation, differentiation and adhesion processes in stem and epithelial cells
  • important positive regulator of cell adhesion and migration, playing an essential role in embryonic morphogenesis as well as intestinal homeostasis
  • EPCAM plays multiple important roles, in cell proliferation as well as in cell adhesion and migration
  • essential for maintaining the homeostasis of the intestinal epithelium
  • forms intercellular, homophilic adhesions, modulates epithelial junctional protein complex formation, and promotes epithelial tissue homeostasis
  • overlapping functions of EPCAM and TACSTD2 as regulators of epithelial development in both intestinal and extraintestinal tissues
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • protein constituent of membrane
  • an EPCAM-CLDN7 complex, rather than EPCAM itself, can promote proliferation, apoptosis resistance, migration, and tumorigenicity
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • MMP7 is a direct SOX18 target gene as well as other potential candidates including guidance molecules, suggesting a function of this transcription factor in the regulation of vessel formation
  • MMP7 is a target gene of EPCAM signalling via EpICD nuclear translocation
  • interact directly with the TJ protein claudin -7 (CLDN7 was required for association of CLDN1 with EPCAM)
  • association between ERAP2 and EPCAM is a unique and novel finding that provides new ideas on EPCAM processing and on how antigen presentation may be regulated in cancer
  • TACSTD2 was able to compensate for the loss of EPCAM in stabilizing CLDN7 expression and cell membrane localization in tissues that co-express both proteins
  • cytosolic EPCAM cooperates with HRAS to regulate epithelial to mesenchymal transition through ZEB1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) HNPCC1 , DIAR5
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in esophageal carcinoma, with long survival
    tumoral     --over  
    in retinoblastoma
    tumoral     --over  
    in colorectal and lung carcinomas
    tumoral germinal mutation deletion    
    contributing to germline MLH1 hypermethylation, and to Lynch syndrome
    tumoral     --over  
    in gastric cancer tissues and cell lines
    tumoral     --over  
    is the unfavorable predictor for the shorter overall survival (OS) and disease-free survival (DFS) for Hepatocellular carcinoma (HCC) patients
    constitutional       loss of function
    loss of EPCAM may cause the reduction and mislocalization of proteins that compose adherens junctions partly via the downregulation of nectin 1 in the intestines
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • significant prognostic factor in pancreatic cancer patients by suppressing cell activity, and its expression was found to be related to the suppression of pancreatic cancer cell activity and the good prognosis in pancreatic cancer patients receiving the curative resection
  • marker highly expressed in carcinomas and showing a strong correlation with poor cancer prognosis
  • Therapy target
    SystemTypeDisorderPubmed
    cancereye 
    target for therapy in retinoblastoma
    cancerdigestivestomach
    potential value of EPCAM in the therapy of gastric cancer in clinic
    ANIMAL & CELL MODELS
  • EpCAM-/- embryos become nonviable because of placental insufficiency resulting from attenuated development of the labyrinthine layer, a process that involves invasion of fetal elements into the maternal decidua