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FLASH GENE
Symbol KLK3 contributors: mct - updated : 16-04-2020
HGNC name kallikrein-related peptidase 3
HGNC id 6364
Location 19q13.33      Physical location : 51.358.170 - 51.364.020
Synonym name
  • kallikrein 3, (prostate specific antigen)
  • semininantigen
  • P-30 antigen
  • gamma-seminoprotein
  • seminin
  • semenogelase
    • Synonym symbol(s) APS, PSA, KLK2A1, hK3
    EC.number 3.4.21.77
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    text tightly clustered multigene family on chromosome 19q13.4
    STRUCTURE 5.85 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (CAAT box)
    Binding site   HRE
    text structure
  • a polymorphic androgen response element (ARE) sequence with two alleles, A and G
  • 455-bp enhancer core region located about 4 kb upstream of the TATA box
  • another regulatory element (GAGATA), located at the region designated PSA3.1, contributes to transcriptional regulation by androgens
  • androgen response elements in the promoter and enhancer of KLK2 , interacting with the androgen receptor
  • three regions upstream of the KLK3 gene, including the distal enhancer, are known to contain consensus androgen-responsive elements required for AR-mediated transcriptional activation
    • MAPPING cloned Y linked N status confirmed
    Map see KLK1
    regionally located clustered with kallikrein gene family
    RNA
    TRANSCRIPTS type messenger
    text preprostate-specific antigen (PSARP1) resulting of alternating splicing (PSA : isoform 29kDa, PSARP1 : 27kDa)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 splicing 1464 28.7 261 - 2002 11834722
    also called KLK3 I1, PSARP1
    5 splicing 1906 - 238 - 2002 11834722
    - splicing - 25 180 - 2001 11502200
    also called PSARP2
    5 - 1335 - 218 - 2002 11834722
    6 - 1341 - 220 - 2002 11834722
    2 - 555 - 69 - 2002 11834722
    - - - - - in the secretory epithelial cells of the prostate 2002 11834722
  • also called PSA-LM
  • up-regulated in response to androgenic stimulation
    		•
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivefemale systembreastmammary gland  
     male systemprostate  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Connectivebone   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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