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FLASH GENE
Symbol PRSS8 contributors: mct/npt - updated : 01-09-2016
HGNC name protease, serine, 8
HGNC id 9491
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a peptidase S1 domain
    • mono polymer heteromer , dimer
    HOMOLOGY
    intraspecies homolog to acrosin,strongly
    homolog to plasma kallikrein
    homolog to hepsin
    Homologene
    FAMILY
  • peptidase S1 family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    text
  • membrane-bound
  • secreted after cleavage of its C-terminus
  • majority of prostasin is located on the apical plasma membrane albeit a minor fraction of prostasin is present on the basolateral plasma membrane
    • basic FUNCTION
  • active protease serine in its membrane bound form
  • activates the epithelial sodium channel (SCNN1A) and suppresses invasion of prostate and breast cancer cells
  • critical role for prostasin in regulating epithelial monolayer function
  • glycosylphosphatidylinositol-anchored membrane serine protease believed to be critical for the regulation of epithelial sodium channel (SCNN1A) activity
  • extracellular serine protease implicated in the modulation of fluid and electrolyte regulation via proteolysis of the epithelial sodium channel
  • involved in the extracellular proteolytic modulation of the epidermal growth factor receptor (EGFR) and is an invasion suppressor
  • may regulate trophoblast cell proliferation via modulating the EGFR-MAPK signaling pathway
  • requirement of PRSS8 for conversion of the ST14 zymogen to active ST14, whereas PRSS8 zymogen activation was ST14-independent
  • membrane-anchored serine proteases, PRSS8 and ST14, constitute a single proteolytic signaling cascade that is active at multiple stages of development
  • is required for the activation of ST14 during development and placental differentiation
  • 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
  • crucial role in placental development and function
  • serves as a critical co-factor for matriptase activation
  • potential regulator of epithelial sodium channel (ENaC) function
  • is part of a cell surface proteolytic cascade that is essential for epithelial barrier formation and homeostasis
  • essential functions of prostasin are executed by a non-enzymatic activity of this unique membrane-anchored serine protease
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • ST14/PRSS8 proteolytic cascade is essential for epidermal tight junction formation and terminal epidermal differentiation
    • a component
  • heterodimer of two chains, light and heavy, held by a disulfide bond
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with SPINT1 (HAI-1B, potential physiological regulator of prostasin function)
  • cell-specific GPLD1- or peptidase-dependent pathways for PRSS8 secretion may control PRSS8 functions in a tissue-specific manner
  • displays a near-ubiquitous co-localization with its candidate activator matriptase (ST14) in a variety of normal epithelial tissues
  • ST14 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
  • HPN activates prostasin and cleaves the extracellular domain of the epidermal growth factor receptor
  • membrane-bound serine protease involved in the regulation of several different effectors, such as the epithelial sodium channel SCNN1A, the protease-activated receptor PAR2, the tight junction proteins, and the profilaggrin polypeptide
  • PRSS8 activity eliminates SPINT1 and SPINT2 deficiency-associated developmental defects by preventing ST14 activation
  • can proteolytically activate ST14 and is critical for the generation of active ST14 during placental development
  • 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
  • is a regulator of SCNN1A in colon
  • inhibitory interaction between PRSS8 and nexin-1, opening the search for specific PRSS8 antagonists that are independent of its catalytic activity
  • MSMB is a key upstream factor in mediating PRSS8 signaling that regulates PRSS8 expression and action in ovarian cancer cells
    • cell & other
    REGULATION
    Other regulated by dihydrotestosterone in prostate cells via SREBF1 stimulation and SNAI2 repression of prostasin promoter
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in hormone-refractory prostate cancers
    tumoral     --low  
    in bladder transitional cell carcinomas is associated with epithelial-mesenchymal transition (EMT), and may have functional implications in tumor invasion and resistance to chemotherapy
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Prss8(-/-) mice lack barrier formation and display fatal postnatal dehydration
  • liver-specific PRSS8 knockout (LKO) mice develop insulin resistance associated with the increase in hepatic Tlr4
  • Prss8-deficient newborns presented abnormal epidermis, and died soon after birth due to impaired skin function
  • hypomorphic mutations in Prss8, restored placentation and normal development of Spint1-deficient embryos and prevented early embryonic lethality, mid-gestation lethality due to placental labyrinth failure, and neural tube defects in Spint2-deficient embryos