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FLASH GENE
Symbol KLK6 contributors: mct/pgu - updated : 16-04-2020
HGNC name kallikrein-related peptidase 6
HGNC id 6367
DNA
TYPE functioning gene
SPECIAL FEATURE component of a cluster
text tightly clustered multigene family on chromosome 19q13.4
STRUCTURE 10.97 kb     7 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked   status confirmed
Map cen - D19S412 - D19S596 - D19S907 - KLK1 - KLK3 - KLK2 - KLK4 - KLK5 - KLK6 - KLK12 - KLK13 - KLK14 - KLK6 - KLK7 - KLK8 - KLK9 - KLK10 - KLK11 - D19S571- D19S927 - D19S418 - qter
regionally located clustered with kallikrein gene family
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
6 - 1527 - 244 - 2011 22047144
multiple transcriptional start sites exist for variant B
5 - 1495 - 137 - 2011 22047144
7 - 1527 - 244 - 2011 22047144
has a distinct C-terminus when it is compared to isoform A
5 - 1567 - 137 - 2011 22047144
6 - 1272 - 137 - 2011 22047144
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbrainhindbraincerebellum   Homo sapiens
 spinal cord    
Reproductivefemale systembreastmammary gland   Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Nervouscentral    Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Nervousoligodendrocyte Homo sapiens
cell lineage
cell lines primary mammary carcinoma lines, prostate, ovarian
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • trypsin domain
  • a peptidase S1 domain
  • HOMOLOGY
    interspecies homolog to murine Klk29
    Homologene
    FAMILY
  • peptidase S1 family
  • Kallikrein subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,microsome
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • might play a role in tissue remodeling and/or tumor invasion and metastasis
  • involved in desquamation cascade of the skin
  • as other KLKs may participate in desquamation through cleavage of desmoglein 1 and regulation by LEKTI
  • may play a crucial role in promoting cancer-cell invasion in bladder tumor
  • trypsin-like serine peptidase, having oncogenic role of KLK6 in colorectal cancer
  • exhibit trypsin-like specificity, with a strong preference for Arg at the P1 position of substrates
  • oncogenic role of KLK6 in colorectal cancer
  • regulatory activities for KLK6 in the development and progression of central nervous system (CNS) inflammation and demyelination
  • is positioned to serve as a molecular trigger of select physiological processes involved in the development of astrogliosis and this is likely to occur at least in part by activation of the G-protein-coupled receptor, F2R
  • plays a functional role in oligodendrocyte development and the expression of myelin proteins
  • KLK6 can influence astrocyte plasticity through receptor-dependent mechanisms
  • KLK6 is an important molecular link in the development of skin inflammation and in tumor-promoting inflammatory processes
  • important role for KLK6 in human gastric cancer progression
  • KLK6 is implicated in skin inflammation
  • critical function of the KLK6 enzyme in colon cancer progression and its contribution to the signaling network in colon cancer
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • KLK6-signaling axis in CNS neurons that is mediated by F2R and F2RL1 and is positioned to contribute to neurodegeneration
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • activity of KLK6 on peptides containing clusters of basic amino acids
  • kinin B1 receptor agonist induces secretion of KLK1, KLK6, KLK10, KLK13 and KLK14 into the medium nof neutrophils
  • KLK6-F2R-mediated inflammation in the skin alone is sufficient to drive inflammatory joint disease
  • cell & other
    REGULATION
    Other regulated by steroid hormones
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in cerebrospinal fluid and plasma in Alzheimer diseases
    tumoral     --over  
    in gastric cancer
    tumoral     --low  
    in breast and ovarian cancer, metastatic
    tumoral     --over  
    significantly increased in invasive cancers relative to normal ovaries
    tumoral     --over  
    in papillary renal cell carcinoma
    tumoral     --over  
    of KLK6 and KLK13 in ovarian cancer compared to normal ovarian tissues
    constitutional     --over  
    in multiple inflammatory and autoimmune conditions
    constitutional     --over  
    in demyelinating disease (pMID: 28254587)
    constitutional     --low  
    in Aneurysmal subarachnoid hemorrhage (aSAH), with the lowest levels in patients who died
    Susceptibility to aggressive PCa (prostate cancer)
    Variant & Polymorphism SNP
  • SNP in the KLK 6 region strongly associated with aggressive PCa
  • Candidate gene
  • potential biomarkers that can significantly predict prognosis in terms of recurrence-free survival and overall survival in ovarian cancer
  • high concentration of KLK6 is an indicator of tumor proliferation and an independent predictive factor in non-small cell lung cancer
  • Marker
  • potential biomarkers in ovarian cancer
  • potential ability of KLK6 as a prognostic marker for gastric cancer
  • elevations in glioblastoma KLK6 protein have utility as prognostic markers of patient survival
  • KLK6 and KLK10 may be useful markers in gastroesophageal junction tumors
  • detection of low KLK6 expression in primary tumors represents a promising tool to stratify head and neck squamous cell carcinoma (HNSCC) patients with high risk for treatment failure
  • potential biomarker in colon adenocarcinoma
  • KLK6 is a potential biomarker of Tau pathology in Alzheimer disease
  • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveovary
    potential therapeutic targets for treatment of ovarian cancer (PMID: 19707197)
    dermatologyskin 
    potential target for the treatment of skin disorders in which KLK activity is elevated
    cancerreproductiveovary
    may be therapeutic targets for treatment of ovarian cancer
    cancerdigestiveoesophagus
    potential therapeutic targets in gastroesophageal junction tumors
    dermatologyskin 
    may represent a novel druggable target for Netherton syndrome and other inflammatory conditions e.g. atopic dermatitis
    cancerbrain 
    could be used as target for therapeutic intervention in intracranial tumors
    ANIMAL & CELL MODELS