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FLASH GENE
Symbol KLK4 contributors: mct/npt/pgu - updated : 16-04-2020
HGNC name kallikrein-related peptidase 4
HGNC id 6365
Corresponding disease
AIPH1 amelogenesis imperfecta, pigmented, hypomaturation type
Location 19q13.33      Physical location : 51.409.607 - 51.413.994
Synonym name
  • prostase serine-like antigen (PSA)
  • enamel matrix serine proteinase 1
  • kallikrein 4 (prostase, enamel matrix, prostate)
  • prostase
  • androgen-regulated message 1
  • Synonym symbol(s) PRSAR, KLK-L1, PRSS17, EMSP1, PSTS, ARM1, EMSP, MGC116827, MGC116828
    EC.number 3.4.21.-
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    text tightly clustered multigene family on chromosome 19q13.4
    STRUCTURE 4.39 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    regionally located clustered with kallikrein gene family
    RNA
    TRANSCRIPTS type messenger
    text alternate splice variants for this gene have been described, but their biological validity has not been determined (PMID: 16322328)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 1347 - 254 - 1999 10438493
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal gland   moderately
    Nervousbrain    
    Reproductivefemale systemuterus   
     male systemprostate  specific
     male systemtestis   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelial    
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveodontoblast
    cell lineage
    cell lines neoplastic prostate epithelial cells
    fluid/secretion
    at STAGE
    Text secreted into the enamel matrix of developing teeth
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a 26 aa signal peptide sequence (2.6 kda)
  • a propeptide (27-30 aa)
  • an aspartate (201) predicting a trypsin-like cleavage and 29 "invariant" aminoacids
  • a peptidase S1 domain
  • conjugated GlycoP
    isoforms Precursor a 224 aa mature peptide (24 kda)
    HOMOLOGY
    interspecies homolog to rattus Klk4 (71pc)
    homolog to murine Klk4 (69.3pc)
    intraspecies homolog to prostate specific antigen,PSA
    Homologene
    FAMILY
  • kallikrein family
  • PRS protease subfamily S, serine, PRSS domain
  • peptidase S1 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleolus
    text
  • enamel matrix
  • secreted protein
  • basic FUNCTION
  • acting as a serine-type endopeptidase
  • involved in the degradation of enamel proteins playing a critical role in enamel mineralisation
  • may play an important functional role in prostate cancer progression in addition to its biomarker potential
  • may play a role in tissue remodeling and cancer metastasis
  • exhibit trypsin-like specificity, with a strong preference for Arg at the P1 position of substrates
  • believed to play an essential role in enamel biomineralization, because defects in KLK4 cause hypomaturation amelogenesis imperfecta
  • essential for the removal of enamel proteins and the proper maturation of enamel crystals
  • principle functions of MMP20 and KLK4 in dental enamel formation are to facilitate the orderly replacement of organic matrix with mineral, generating an enamel layer that is harder, less porous, and unstained by retained enamel proteins
  • 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
  • KLK3, KLK4, KLK11, and KLK2, belong to the prostatic group of the KLKs, whose major physiological function is semen liquefaction during the fertilization process
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • HPN and TMPRSS2 indirectly modulate KLK4 activity by cleaving the KLK4-activating protease MMP3
  • cell & other
    REGULATION
    activated by CTSC (CTSC may activate KLK4 during enamel formation)
    Other in some tissues its expression is hormonally regulated
    ASSOCIATED DISORDERS
    corresponding disease(s) AIPH1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in prostate cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene KLK4 gene expression may be used as a new potential biomarker in breast cancer
    Marker
    Therapy target
    ANIMAL & CELL MODELS