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FLASH GENE
Symbol KLK12 contributors: mct - updated : 22-04-2020
HGNC name kallikrein 12
HGNC id 6360
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinelarge intestinecolon  
 salivary gland   highly Homo sapiens
 stomach   highly Homo sapiens
Reproductivemale systemprostate  highly Homo sapiens
Respiratorylung   highly Homo sapiens
 respiratory tracttrachea  highly Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticbone marrow  highly Homo sapiens
Connectivebone  highly Homo sapiens
Epithelialsecretoryglandularendocrine 
cell lineage
cell lines
fluid/secretion salivary gland
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
isoforms Precursor secreted as an inactive pro-enzyme, which is able to autoactivate to gain enzymatic activity
HOMOLOGY
interspecies homolog to murine neuropsin
Homologene
FAMILY kallikrein gene family
CATEGORY enzyme
SUBCELLULAR LOCALIZATION extracellular
    intracellular
intracellular,cytoplasm,cytosolic,granule
basic FUNCTION
  • involved in pathogenesis and/or progression of certain cancer types
  • possesses trypsin-like activity, cleaving peptide bonds after both arginine and lysine
  • may participate in enzymatic cascades involving other kallikreins
  • may indirectly regulate the bioavailability and activity of several growth factors through processing of their CCN binding partners
  • involvement of KLK12 in different homeostatic and disease pathways through modulation of growth factor availability and/or activity
  • play a critical role in controlling normal angiogenesis
  • KLK12-mediated proteolysis of CYR61 and WISP3 can reduce or abolish the binding of VEGFA, BMP2, and TGFB1
  • KLK12-mediated hydrolysis of CCNs may be involved in the modulation of the bioavailability and/or activity of several growth factors including VEGFA, BMP2, TGFB1, and FGF2
  • may play an important role in angiogenesis modulating proangiogenic factor bioavailability and activating the kinin receptor B2 pathway
  • proangiogenic activity of KLK12 in lung endothelial cells was not related to a kinin release
  • KLK5, KLK12 are involved in the cleavage activation of human-adapted influenza virus subtypes
  • KLK12 proangiogenic effect is mediated through several molecular mechanisms
  • plays likely a tumor-supporting role in Triple-negative breast cancer (TNBC)
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • might be responsible for the shedding of CYR61 from the cell surface
  • can target all six members of the CCN family at different proteolytic sites (WISP1, WISP2, WISP3, CYR61, CTGF, NOV)
  • interacting with CYR61 and WISP3 (fragmentation of CYR61 and WISP3 by KLK12 on cells of the tumor microenvironment, including neoplastic and endothelial cells)
  • angiogenesis is stimulated by KLK12 acting via a PDGFB-dependent paracrine pathway
  • efficiently cleaved the extracellular matrix proteins fibronectin and tenascin, both of which are involved in the regulation of endothelial cell adhesion and migration
  • cell & other
    REGULATION
    induced by steroid hormone
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in breast cancer
    tumoral     --over  
    in prostate cancer
    tumoral     --over  
    in Gastric cancer tissue
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • may have potential use as a cancer biomarker
  • KLK12 might serve as a novel diagnosis and prognosis biomarker in gastric cancer
  • Therapy target
    ANIMAL & CELL MODELS