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FLASH GENE
Symbol KLK3 contributors: mct - updated : 17-02-2010
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
  • MAPPING cloned Y linked N status confirmed
    Map see KLK1
    Physical map
    LOC284361 19q13.33-q13.41 hypothetical protein LOC284361 SBBI54 19q13.41 hypothetical transmembrane protein SBBI54 LOC284363 19q13.41 similar to RIKEN cDNA 0610012D14 DKFZp761A179 SYT3 19q13.4 synaptotagmin III LOC342918 19q13.41 hypothetical LOC342918 SHANK1 19q13.3 SH3 and multiple ankyrin repeat domains 1 SCGF 19q13.3 stem cell growth factor; lymphocyte secreted C-type lectin GPR32P 19q13.3 G protein-coupled receptor 32, pseudogene GPR32 19q13.3 G protein-coupled receptor 32 ACPT 19q13.4 acid phosphatase, testicular MGC13170 19q13.41 multidrug resistance-related protein MGC45922 19q13.41 hypothetical gene MGC45922 KLK1 19q13.4 kallikrein 1, renal/pancreas/salivary KLK15 19q13.4 kallikrein 1, renal/pancreas/salivary KLK3 19q13.3 kallikrein 3, (prostate specific antigen) KLK2 19q13.4 kallikrein 2, prostatic KLK4 19q13.3-q13.4 kallikrein 4 (prostase, enamel matrix, prostate) LOC390956 19 similar to peptidyl-Pro cis trans isomerase KLK5 19q13.3-q13.4 kallikrein 5 KLK6 19q13.3 kallikrein 6 (neurosin, zyme) KLK7 19q13.41 kallikrein 7 (chymotryptic, stratum corneum) KLK8 19q13.3 kallikrein 8 (neuropsin/ovasin) KLK9 19q13.3-q13.4 kallikrein 9 KLK10 19q13.3 kallikrein 10 KLK11 19q13.3-q13.4 kallikrein 11 KLK12 19q13.3-q13.4 kallikrein 12 KLK13 19q13.2-q13.4 kallikrein 13 KLK14 19q13.3-q13.4 kallikrein 14 LOC90353 19q13.41 LOC90353 SIGLEC9 19q13.4 sialic acid binding Ig-like lectin 9 SIGLEC7 19q13.3 sialic acid binding Ig-like lectin 7
    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
    Homologene
    FAMILY
  • peptidase s1 family
  • kallikrein subfamily
  • CATEGORY enzyme , antigen
    SUBCELLULAR LOCALIZATION extracellular
    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
  • 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
  • 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
    Susceptibility to prostate cancer (minor role)
    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
  • Candidate gene early marker for the presence of prostate cancer, prostate-specific antigen, being the current serum biomarker for prostate cancer
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    potential target for tumor imaging and treatment in prostate cancer cells
    ANIMAL & CELL MODELS