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FLASH GENE
Symbol KLK1 contributors: mct - updated : 16-04-2020
HGNC name kallikrein 1
HGNC id 6357
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