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FLASH GENE
Symbol KLK12 contributors: mct - updated : 22-04-2020
HGNC name kallikrein 12
HGNC id 6360
DNA
TYPE functioning gene
SPECIAL FEATURE component of a cluster
text tightly clustered multigene family on chromosome 19q13.4
STRUCTURE 6.69 kb     5 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
regionally located clustered with kallikrein gene family
RNA
TRANSCRIPTS type messenger
text
  • five coding exons and one 5prime-untranslated exon with at least four alternatively spliced forms known to date (PMID: 21628462)
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 splicing 1182 26.7 248 - 2000 10766816
    5 - 814 12 111 salivary gland, stomach, uterus, trachea, prostate, thymus, lung, colon, breast, brain, thyroid gland and others 2000 10766816
  • exon 4 missing
  • globular protein
  • 7 splicing 1053 27.1 254 .salivary gland, stomach, uterus, trachea, prostate, thymus, lung, colon, breast, brain, thyroid gland and others 2000 10766816
    5 - 1071 - 138 - 2018 29874189
    6 - 942 - 144 - 2018 29874189
    6 - 1171 - 248 - 2018 29874189
    5 - 911 - 138 - 2018 29874189
    - splicing - - - . higher expression in non-cancerous than in cancerous samples . upregulated in the breast malignant compared to the benign tumors, and patients with positive KLK12sv1/2 levels presented a significantly longer disease-free survival 2018 29807016
    - splicing - - - . higher expression in non-cancerous than in cancerous samples . downregulated in the malignant breast compared to the benign tumors, and patients with positive KLK12sv3 levels presented a significantly longer disease-free survival 2018 29807016
    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