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FLASH GENE
Symbol TMPRSS2 contributors: mct/pgu - updated : 02-04-2020
HGNC name transmembrane protease, serine 2
HGNC id 11876
Location 21q22.3      Physical location : 42.836.478 - 42.880.085
Synonym name
  • epitheliasin
  • serine protease 10
    • Synonym symbol(s) PRSS10, TMS2, PP9284, FLJ41954
    EC.number 3.4.21.-
    DNA
    TYPE functioning gene
    STRUCTURE 43.85 kb     14 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    cytosine-phosphate-guanine/HTF
    Binding site   enhancer   HRE
    text structure
  • initiator-like element and potential regulatory element including SREBP, SP1, ERE
  • androgen-responsive promoter elements
  • an enhancer at 13 kb upstream of the TMPRSS2 transcription start site is crucial for the androgen regulation of the TMPRSS2 gene, and the GATA-2 binding sites are involved in the enhancer activity
    • MAPPING cloned Y linked N status provisional
    Map cen - ERG - MX1 - TMPRSS2 - D21S56 - qter
    Authors PMID: 9325052
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 3450 53.7 492 - 2015 2637904
    14 - 3250 57.6 529 in lung-derived cell lines and tissues 2015 2637904
  • TMPRSS2 isoform 1 colocalizes with HA and cleaves and activates hemagglutinin (HA)
  • having extended N-terminal cytoplasmic domain (isoform 1)
  • activates the SARS-CoV spike protein for cathepsin L-independent entry into target cells
  • is expressed in viral target cells and might contribute to viral activation in the host
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
     intestinelarge intestinecolon highly
     stomach   lowly
    Nervousbrain   highly
    Reproductivemale systemprostate  highly
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductiveepithelial cell
    cell lineage
    cell lines cells of epithelial prostate carcinoid
    fluid/secretion
    at STAGE
    physiological period fetal
    Text lung, kidney
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a serine protease domain of the S1 family
  • a scavenger receptor cysteine rich (SRCR) domain
  • an LDL receptor class A (LDLRA) domain
  • a predicted transmembrane domain
    • HOMOLOGY
    intraspecies homolog to enteropeptidase gene
    Homologene
    FAMILY
  • serine protease, peptidase family
  • peptidase S1 family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm
    text type II transmembrane-bound serine protease
    basic FUNCTION
  • may contribute to prostate tumour metastasis via the activation of F2RL1
  • important role for TMPRSS2 and possibly TMPRSS4 in influenza virus replication and highlight the former protease as a potential therapeutic target
  • TMPRSS2 and TMPRSS11D are expressed by important influenza and SARS-coronavirus target cells and could thus support viral spread in the human host
  • TMPRSS2 and TMPRSS11D can cleave and activate the spike protein (S) of the severe acute respiratory syndrome coronavirus (SARS-CoV) for membrane fusion
  • plays a major role in in vivo replication of emerging H7N9 and seasonal influenza viruses
  • cleaves and activates the influenza virus and coronavirus surface protein
  • activate the SARS- and MERS-CoV S proteins for cathepsin B/L-independent host cell entry, presumably by cleaving the S proteins at or close to the cell surface
  • activates HCV infection at the postbinding and entry stage
  • 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
  • is a novel membrane-anchored mediator in cancer pain
  • SARS-2-S employs TMPRSS2 for S protein priming in human lung cells
  • may also play an important role in SARS-CoV-2 cell entry
  • TMPRSS2 is also likely to be a key protease for SARS-CoV-2 replication
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TMPRSS2 and potentially related proteases promote SARS-CoV entry by two separate mechanisms: ACE2 cleavage, which might promote viral uptake, and SARS-S cleavage, which activates the S protein for membrane fusion
  • TMPRSS2 was found to compete with the metalloprotease ADAM17 for ACE2 processing, but only cleavage by TMPRSS2 resulted in augmented SARS-S-driven entry
  • role for inflammation-induced oxidative stress in the formation of DNA breaks leading to recurrent TMPRSS2-ERG gene fusions
  • in contrast with HPN, TMPRSS2 degrades KLK14, and TMPRSS2 cleavage is mediated by KLK14
    • cell & other
    REGULATION
    activated by androgens
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in prostate carcinoma, with down-regulation of KLK11 gene in advanced and more aggressive tumors may open the feasibility of being used as biomarkers distinguishing the tumor aggressiveness
    tumoral fusion      
    with ERG, ETV1 and ETV4 in prostate cancer
    tumoral somatic mutation translocation    
    Loss of PTEN and concomitant activation of AKTcould act in partnership with the TMPRSS2-ERG fusion protein to promote progression to prostate cancer
    tumoral fusion      
    TMPRSS2-ERG gene fusions were observed in 44p 100 of prostate cancer, and over 90p100 of these fusions occurred in ERG exons 3 or 4
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • development of the TMPRSS2-ERG fusion gene is a noninvasive tumor marker for therapy assessment, risk stratification, and relapse detection to improve personalized therapy strategies for patients with prostate cancer
  • urinary TMPRSS2:ERG might become a valuable test not only for diagnosing PCa but also for distinguishing the aggressive tumors from the indolent ones
    • Therapy target
    SystemTypeDisorderPubmed
    immunologyinfectious 
    TMPRSS2-related therapeutic agents may be a promising countermeasure against the current and new outbreaks of CoVs
    ANIMAL & CELL MODELS
  • Tmprss2 plays a crucial role in viral spread within the airway of murine models infected by SARS-CoV and MERS-CoV and in the resulting immunopathology