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FLASH GENE
Symbol HPN contributors: mct - updated : 28-09-2016
HGNC name hepsin (transmembrane protease, serine 1)
HGNC id 5155
Location 19q13.11      Physical location : 35.531.409 - 35.557.475
Synonym symbol(s) HEPS, TMPRSS1
EC.number 3.4.21.106
DNA
TYPE functioning gene
STRUCTURE 26.07 kb     14 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
13 - 2389 - 417 - Kirchhofer
HPN - V1
14 - 1809 - 417 - Kirchhofer
HPN - V2
12 splicing 1116 75 - kidney, brain lung Li
  • not contain exons 4 and 5, which together encode the transmembrane domain
  • non-transmembrane isoform
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   predominantly Homo sapiens
    Lymphoid/Immunetonsils   highly
    Urinarykidney   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • catalytic subunit (C-terminal half) at the cell surface and its N terminus facing the cytosol
  • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • type II membrane-associated proteins
  • normally expressed at the cell surface
  • basic FUNCTION
  • cell membrane associated serine protease, involved in processes such as blood coagulation, fibrinolysis, and complement activation
  • having potential roles in development, cell growth, and cell-surface initiation of blood coagulation
  • activating factor VII
  • is required for normal auditory function
  • may play important and specific roles in hearing
  • promotes prostate cancer progression and metastasis and thus represents a potential therapeutic target
  • type II transmembrane trypsin-like serine protease, mediating epithelial integrity and basement membrane (BM) defects
  • HPN and TMPRSS2 colocalize on the cell surface with the secreted serine proteases KLK4 and KLK14, only in membrane protrusions, suggesting that reciprocal proteolytic interactions occur in defined cellular structures that are important during cancer dissemination for cell migration, invasion and survival
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    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
  • activates prostasin (PRSS8) and cleaves the extracellular domain of the epidermal growth factor receptor (EGFR)
  • SPINT2 is a tumor suppressor gene that inhibits proteases implicated in cancer progression, like HGFAC, HPN and ST14
  • HPN and TMPRSS2 indirectly modulate KLK4 activity by cleaving the KLK4-activating protease MMP3
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in prostate cancer with poor prognosis
    tumoral     --over  
    in ovarian cancer
    tumoral     --over  
    is one of the most consistently overexpressed genes in patients with prostate cancer
    tumoral     --over  
    in breast cancer tissues, which is associated with tumor growth and progression
    tumoral     --over  
    could be an important indication for high risk of endometrial cancer
    Susceptibility to prostate cancer
    Variant & Polymorphism SNP
  • three SNPs (rs45512696, rs2305745, rs2305747) were significantly associated with the risk of prostate cancer
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    inhibition of hepsin expression might be of therapeutic significance
    ANIMAL & CELL MODELS
  • deletion of hepsin (hepsin(-/-)) in mice resulted in enlarged hepatocytes and narrowed liver sinusoids
  • hearing impairment present in Hpn-null mice is characterized by a combination of various structural, cellular, and molecular abnormalities that are likely to affect different cochlear processes