Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol ST14 contributors: npt/mct/pgu - updated : 28-08-2015
HGNC name suppression of tumorigenicity 14 (colon carcinoma)
HGNC id 11344
Corresponding disease
ARIH ichthyosis with hypotrichosis syndrome
Location 11q24.3      Physical location : 130.029.681 - 130.080.256
Synonym name
  • epithin
  • matriptase
  • serine protease tumor-associated differentially expressed gene (TADG)-15
  • membrane-type serine protease matriptase
  • tumor-associated differentially-expressed gene 15 protein
  • prostamin
    • Synonym symbol(s) SNC19, HAI, MTSP1, MT-SP1, MTSP-1, PRSS14, TADG-15, TMPRSS14
    EC.number 3.4.21.109
    DNA
    TYPE functioning gene
    STRUCTURE 50.58 kb     19 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
    19 - 3319 94.8 855 - 1999 10373424
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly
     pharynx   highly
     stomach   highly
    Endocrinethyroid   highly
    Respiratorylung   highly
    Skin/Tegumentskin   highly Homo sapiens
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningepidermis highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
     epithelial cell
    Lymphoid/Immunemacrophage Homo sapiens
    cell lineage
    cell lines
    fluid/secretion milk
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four LDL-receptor class A domains
  • two CUB domains
  • signal anchor
  • an extracellular protease domain
    • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine St14
    homolog to Drosophila CG11824
    homolog to C.elegans C07G1.1
    Homologene
    FAMILY
  • peptidase family S1
    • CATEGORY enzyme , tumor suppressor
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    text is a modular type II transmembrane serine protease
    basic FUNCTION
  • epithelial-derived integral membrane serine protease, trypsin-like protease activity
  • cleaving and activating hepatocyte growth factor/scattering factor and urokinase plasminogen activator
  • functioning as an epithelial membrane activator for other proteases and latent growth factors
  • playing a role in cancer invasion, and metastasis
  • degrading extracellular matrix proteins
  • has pleiotropic functions in epithelial development and postnatal homeostasis, at least in part through its capacity to regulate epithelial tight junction formation in simple and stratified epithelia
  • involved in activation of growth and angiogenic factors and degradation of extracellular matrix components
  • is a type II transmembrane serine protease containing the non-catalytic domains (stem domain) and catalytic domain in the extra-cellular region
  • serine protease, which regulates processing of profilaggrin to filaggrin
  • playing a significant role in epidermal desquamation
  • implicated in pericellular proteolytic pathway that plays a critical role in the terminal differentiation of epidermal tissues
  • key role in regulating intestinal epithelial barrier competence, suggesting an intriguing link between pericellular serine protease activity and tight junction assembly in polarized epithelia
  • key mediator of TGF-beta-induced epithelial–mesenchymal transition in tumor progression
  • involved in normal epithelial development and tumor progression
  • regulates endothelial TEK functions, plays a critical role in the fine tuning of transendothelial migration for normal and cancer cells
  • may play an important role in the transendothelial migration of activated macrophages in the inflammatory microenvironment, and the mode of action is similar to the events in cancer metastasis
  • plays an important role in IFNG-enhanced transendothelial migration of macrophages
  • membrane-anchored serine proteases, PRSS8 and ST14, constitute a single proteolytic signaling cascade that is active at multiple stages of development
  • PRSS8-ST14 cell surface protease cascade activity must be suppressed by SPINT1 and SPINT2 to enable early embryonic ectoderm formation, placental morphogenesis, and neural tube closure
  • H9N2 viruses with R-S-S-R or R-S-R-R cleavage sites are activated by ST14 in addition to TMPRSS11D and TMPRSS2 and, therefore, can be activated in a wide range of tissues what may affect virus spread, tissue tropism and pathogenicity
  • imbalance between SPINT2 and ST14 expression led to ST14 activation, thereby increasing cell migration, invasion, tumorigenicity and metastasis
    • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • ST14/PRSS8 proteolytic cascade is essential for epidermal tight junction formation and terminal epidermal differentiation
    • a component
  • forming a complex with the Kunitz-type serine protease inhibitor HAI-1 in milk
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • antithrombin III has robust inhibitory properties toward ST14, TMPRSS6, HPN and TMPRSS11E, whereas plasminogen activator inhibitor-1 and alpha(2)-antiplasmin inhibited TMPRSS6, HPN and TMPRSS11E, and to a much lesser extent ST14
  • role of the stem domain in the interaction between ST14 and its physiological inhibitor, SPINT1
  • activates PRSS8 by cleaving in the N-terminal pro-peptide region of PRSS8, presumably at the Arg residue of position 44 (R44) of the full-length human PRSS8
  • interacts with TEK and degrades the TEK extracellular portion that contains the ligand-binding domain
  • ST14 activity can be rapidly inhibited by SPINT1 and other SPINT1-like protease inhibitors and "locked" in an inactive autoactivation intermediate, all of which places ST14 under very tight control
  • activation of ST14 through the cleavage of SPINT1 is one of the MMP14 multifunctions essential for invasive growth of squamous carcinoma cells
  • PRSS8 is required for the activation of ST14 during development and placental differentiation
  • SPINT1 is critically required for the cell surface localization of ST14 in trophoblasts, and, in the absence of SPINT1, physiological activation of PRSS8 and other protease(s) initiated by cell surface matriptase may be impaired
  • SPINT2 is important for regulation of ST14
  • SPINT2 is a tumor suppressor gene that inhibits proteases implicated in cancer progression, like HGFAC, hepsin and ST14
    • cell & other
    REGULATION
    activated by sphingosine 1-phosphate
    TGF-beta (transcriptionally upregulated by TGF-beta and this upregulation is essential for mediating TGF-beta-induced EMT, thereby enhancing cell migration and invasion)
    Other regulated by serum
    ASSOCIATED DISORDERS
    corresponding disease(s) ARIH
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in colorectal, breast and ovarian carcinomas
    tumoral     --over  
    in ovarian tumors and in cevical carcinoma
    Susceptibility to breast cancer
    Variant & Polymorphism other ST14 variant rs704624 and protein expression of matriptase have prognostic significance in breast cancer
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • matriptase-deficient mice exhibit ichthyotic skin with a selective shift in skin microbiota