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FLASH GENE
Symbol KLK3 contributors: mct - updated : 16-04-2020
HGNC name kallikrein-related peptidase 3
HGNC id 6364
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a peptidase S1 domain
    • HOMOLOGY
    intraspecies homolog to KLK2
    Homologene
    FAMILY
  • peptidase s1 family
  • kallikrein subfamily
    • CATEGORY enzyme , antigen
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus
    basic FUNCTION
  • serine protease hydrolyzing the high molecular mass seminal vesicle protein
  • androgen-mediated expression by binding of the GAGATA binding factor and AR to GAGATA and AREs, respectively, of enhancer core
  • serine protease functioning in the liquefaction of seminal coagulum
  • direct transcriptional target
  • inhibit angiogenesis
  • activates TRPM8 current by inducing the accumulation of functional channels in the plasma membrane and reduces cell migration
  • by increasing TRPM8 activity by the bradykin/protein kinase C pathway, KLK3 is implicated in the inhibition of prostate cell carcinoma motility
  • exerts chymotrypsin-like proteolytic activity
  • KLK2 is a key serine protease in semen liquefaction and prostate cancer together with KLK3/prostate-specific antigen
  • chief executor of the fragmentation of semenogelins, dissolution of semen coagulum, thereby releasing sperm for active motility
  • KLK3, KLK4, KLK11, and KLK2, belong to the prostatic group of the KLKs, whose major physiological function is semen liquefaction during the fertilization process
  • significant association between the polycystic ovary syndrome and KLK3
    • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component part of KLK proteolytic cascade with KLK11 and KLK1, activated by KLK14
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • hydrolyzes semenogelin-1 (SEMG1) thus leading to the liquefaction of the seminal coagulum
  • physiological and natural TRPM8 agonist in the prostate
  • degrades semenogelins I and II much more efficiently than other previously identified protein substrates, e.g., fibronectin, galectin3 and IGFBP3
  • KLK2 most likely activates and complements chymotryptic KLK3 (prostate-specific antigen) in cleaving seminal clotting proteins, resulting in sperm liquefaction
  • overexpression of CRISP3 in prostate tumor may maintain higher KLK3 expression and lower ANXA1 expression
  • crucial role of ESR1 for the mammalian female in regulating semen coagulation and liquefaction with KLK3
  • KLK3 activated VEGFC specifically and efficiently through cleavage at a novel N-terminal site
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    lower in malignant than in normal prostatic epithelium and it is further reduced in poorly differentiated tumors
    constitutional germinal mutation     loss of function
    could lead to false-negative KLK3 findings used for screening, diagnosis, or monitoring of Prostate carcinoma
    Susceptibility
  • to prostate cancer (minor role) (PCa)
  • to infertility
    • Variant & Polymorphism SNP , other
  • two A-alleles have increased risk for prostate cancer onset under the age of 67
  • SNP increasing the risk of prostate cancer
  • rs17632542, introduces a non-synonymous amino acid change in the KLK3 protein with a predicted benign or neutral functional impact, and could influence the diagnosis of nonaggressive prostate cancer
  • five SNPs, rs266881, rs174776, rs266875, rs35192866 and rs1810020 correlated with an increased risk of infertility
    • Candidate gene
  • early marker for the presence of prostate cancer, prostate-specific antigen, being the current serum biomarker for prostate cancer
  • biomarker potential for chromophobe renal cell carcinoma
  • polymorphism T>C of rs1058205 was associated with decreased risk of PCa
    • Marker
  • only independent predictor of extensive lymph node invasion (LNI) in prostate cancer and could be an important preoperative factor for stratifying high-risk patients
  • OPSAD (the ratio of KLK3 to the outer gland volume of prostate) may be used as a new indicator for the diagnosis and prognosis of prostate cancer, and it can reduce the use of unnecessary puncture biopsy of the prostate
  • KLK3 is a marker of Testosterone concentrations and it may represent a new tool in confirming hypogonadism
    • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    potential target for tumor imaging and treatment in prostate cancer cells
    ANIMAL & CELL MODELS