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FLASH GENE
Symbol KLK1 contributors: mct - updated : 16-04-2020
HGNC name kallikrein 1
HGNC id 6357
Location 19q13.33      Physical location : 51.322.403 - 51.327.043
Synonym name
  • glandular kallikrein, renal
  • kallikrein 1, renal/pancreas/salivary
  • kallikrein serine protease 1
  • kidney/pancreas/salivary gland kallikrein
  • tissue kallikrein
  • Synonym symbol(s) KLKR, KLK6, hK1, TK
    EC.number 3.4.21.35
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    text tightly clustered multigene family on chromosome 19q13.4
    STRUCTURE 4.64 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   enhancer
    motif repetitive sequence   other
    text structure
  • poly- g length polymorphism
  • a GATA3 binding site in -954/-855 of the promoter
  • MAPPING cloned Y linked Y status confirmed
    Map cen - APOC2 APOC2 - CKM - ERCC1 - DM1 - D19S321 - GYS1 - D19S320 - [KLK1 - KLK3 - KLK2 ] - D19S50 - D19S22 - qter
    regionally located clustered with kallikrein gene family
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 874 28.7 262 - 1991 1783409
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Homo sapiens
     vessel     Homo sapiens
    Digestivesalivary gland   highly
    Endocrinepancreas   highly
    Lymphoid/Immunetonsils   highly
    Skin/Tegumentskin   highly
    Urinarykidneytubule  highly Homo sapiens
    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
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus
    basic FUNCTION
  • serine protease, releasing the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen
  • as other KLKs may participate in desquamation through cleavage of desmoglein 1 and regulation by LEKTI
  • critical role in arterial function
  • is also involved in the control of ionic transport in the renal tubule, an action that may not be kinin-mediated
  • kinin-forming serine protease synthesized in many organs including arteries and kidney
  • KLK9 and KLK10, once activated, are unlikely to participate in further pro-KLK activation pathways, although similar to KLK1 they may activate other bioactive peptides
  • tissue KLK1 is essential for invasive capacity of circulating proangiogenic cells
  • is a tissue enzyme responsible for kinin release in inflammatory cascade
  • plays likely an antihypertensive role in hyperaldosteronism
  • KLK1/kinin system plays a role in the effects of radiation on cardiac function and recruitment of inflammatory cells, at least in part by altering Erk1/2 signaling
  • KLK1 and TIMP1 are important in inhibiting vascular smooth muscle cell (VSMC) proliferation and improving vascular remodeling, respectively
  • initiated autophagy while maintaining normal autophagic flux
  • secretion of KLK1, the kinin-forming enzyme, may perpetuate formation of kinin in the inflammatory milieu by hydrolyzing extravasated kininogens present in tissue edema
  • KLK1 is responsible for the generation of kinins (bradykinin and kallidin), which promote local vasodilation and long-term vascularization
  • KLK1 intervenes early in the antiviral defense modulating the severity of influenza infection
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • part of KLK proteolytic cascade with KLK11 and KLK3, activated by KLK14
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • kinin B1 receptor agonist induces secretion of KLK1, KLK6, KLK10, KLK13 and KLK14 into the medium nof neutrophils
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    decreased in renal clear cell carcinoma
    constitutional     --low  
    decreased KLK1 expression in Chronic obstructive pulmonary disease (COPD) patients could contribute to the worsening of influenza
    constitutional       gain of function
    in tubular epithelial cells that may mediate pro-inflammatory pathway and F2RL3 activation during diabetic nephropathy
    constitutional     --over  
    by astrocytes in the hippocampus of patients with refractory temporal lobe epilepsy, associated with hippocampal sclerosis
    Susceptibility
  • to hypertension and/or hypertension asociated with end- stage renal disease
  • to aortic aneurysm (AA)
  • to coronary artery stenosis (CAS)
  • Variant & Polymorphism SNP
  • KLK1 rs5516 G allele is closely associated with AA
  • polymorphism of the KLK1 A1789G gene is associated with CAS
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    reproductionfertility 
    targets for the treatment of azoospermia
    ANIMAL & CELL MODELS
  • inactivating the Klk1 gene or treating WT mice with an anti-Klk1 monoclonal antibody to remove Klk1 activity accelerated the initial virus-induced apoptotic depletion of alveolar macrophages