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FLASH GENE
Symbol KLK8 contributors: mct - updated : 16-04-2020
HGNC name kallikrein-related peptidase 8
HGNC id 6369
DNA
TYPE functioning gene
SPECIAL FEATURE component of a cluster
text tightly clustered multigene family on chromosome 19q13.4
STRUCTURE 5.70 kb     6 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
regionally located clustered with kallikrein gene family
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
6 - 1013 - 260 brain 2007 17487847
neuropsin type 1
6 initiation site 1148 - 305 hippocampus, fetal brain, placenta; abundantly expressed in embryonic stem cells and in embryo brain samples, suggesting a potential role in embryogenesis 2007 17487847
  • neuropsin type 2
  • insert of 45 AA at the N terminus of leader sequence
  • important role in the normal function of the cognition
  • only in the humans
  • 4 - 590 - 119 - 2007 17487847
    3 - 456 - 32 - 2007 17487847
    5 - 863 - 139 - 2007 17487847
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Homo sapiens
    Digestiveesophagus     Homo sapiens
     salivary gland     Homo sapiens
    Lymphoid/Immunetonsils     Homo sapiens
    Nervousbraindiencephalonamygdala highly Homo sapiens
     brainlimbic systemhippocampus   Homo sapiens
    Reproductivefemale systembreast  highly Homo sapiens
    Skin/Tegumentskin appendagesskin glandsweat gland highly Homo sapiens
    Urinarykidney     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningepidermisstratum corneum  Homo sapiens
    Muscularstriatumcardiacmyocardium  Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skin/Tegumentkeratinocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion breast milk, amniotic fluid, seminal fluid and serum
    at STAGE
    physiological period fetal, pregnancy
    Text placenta, brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    Homologene
    FAMILY
  • peptidase S1 family
  • kallikrein subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic,granule
    basic FUNCTION
  • having a trypsin-like activity
  • involved in the pathogenesis of inflammatory skin diseases
  • involved in desquamation cascade of the skin
  • involved in proliferation of keratinocytes and desquamation possibly through other kallikreins
  • may play a crucial role in promoting cancer-cell invasion in bladder tumor
  • might be involved in desquamation through the degradation of adhesive molecules that connect layers of the epidermis and in tissue development and rearrangement
  • keratinocyte-specific protease, having an active role for in upper epidermis
  • active serine protease in stratum corneum and sweat, with potential regulators and targets that augment its involvement in a skin barrier proteolytic cascade
  • key regulator of the FKBP5 gene and protein expression
  • is involved in synaptic tagging and cross-tagging during long-term potentiation (LTP) at apical dendritic inputs via ITGB1 and calcium/calmodulin-dependent protein kinase II signalling
  • is believed to be involved in the maintenance of skin homeostasis and pathogenesis of inflammatory skin diseases
  • may promote cardiomyocyte hypertrophy through EGF signaling- and PARs-dependent but a kinin receptor-independent pathway
  • sex-specific difference in Alzheimer disease (AD) may be meditated by estrogen-induced KLK8 overproduction long before AD pathology emerges
  • emerges as a regulator of regulators in memory
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS development
    text both types necessary for brain development type 2, also important in brain plasticity
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • cleaves the extracellular portion of EPHB2 and facilitates the dynamic interaction of EPHB2 with the NR1 subunit of the NMDA receptor
  • KLK8 is likely involved in the proliferation and migration of keratinocytes through the upregulation and activation of KLK6 in the early stages of wound healing, and possibly in keratinocyte differentiation associated with the upregulation and activation of F2RL1 in the late stages of wound healing
  • KLK5 and KLK8 remove the N-terminal eight AAs from the proform thereby converting CCL14 to its active state
  • cell & other
    REGULATION
    induced by estradiol but not testosterone (estradiol induces KLK8 synthesis in neuronal and microglial cells)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in skin diseases, such as psoriasis vulgaris, lichen planus, and atopic dermatitis
    tumoral     --over  
    confers a favorable clinical outcome in non-small cell lung cancer by suppressing tumor cell invasiveness
    tumoral     --over  
    in oral squamous cell carcinoma and may be implicated in malignant progression
    tumoral     --over  
    in most salivary gland tumors
    constitutional     --over  
    in skin inflammation increased expression in the stratum spinosum
    constitutional     --over  
    higher levels of KLK8 in female brain may increase the risk for Alzheimer disease
    tumoral     --over  
    was correlated with the progression of Colorectal cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • KLK8-T4 alternative splice variant, alone or in combination, may be a new independent marker of unfavorable prognosis in lung cancer
  • can serve as a novel independent biomarker of unfavorable prognosis for Breast cancer patients
  • potential independent prognostic indicator for Colorectal cancer
  • potential biomarker in colon adenocarcinoma
  • potential clinical utility of blood and CSF KLK8 as a biomarker for incipient Alzheimer disease
  • Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerativealzheimer
    therapeutic potential of KLK8 inhibition by counteracting plasticity deficits in AD-affected brain
    ANIMAL & CELL MODELS
  • on stress, neuropsin-deficient mice do not show EphB2 cleavage and its dissociation from NR1 resulting in a static EphB2–NR1 interaction, attenuated induction of the Fkbp5 gene and low anxiety