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FLASH GENE
Symbol KNG1 contributors: mct/npt/shn - updated : 28-11-2017
HGNC name kininogen 1
HGNC id 6383
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • four homologous repeats,D1,D2,D3 cysteine proteinase inhibitor-like and D4 releasing bradykinin or lys-bradykinin
  • a D5 surface binding D5(H), that may modulate likely cell adhesion and invasion together with ACTN4, and inhibits collagen-mediated cancer cell adhesion and invasion in association with ACTN4
  • a D6 binding site for kallikrein or factor XI (F11)
    • conjugated GlycoP
    isoforms Precursor coding for high molecular (HD,110kDa) and low molecular weight (LW,65kDa) kininogene
    HOMOLOGY
    interspecies ortholog to kng1, Mus musculus
    ortholog to kng1, Rattus norvegicus
    Homologene
    FAMILY
  • cystatin superfamily
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
    text secreted protein
    basic FUNCTION
  • contact activation pathway
  • cysteine proteinase inhibitor
  • inhibiting endothelial cell proliferation and angiogenesis through domain D5
  • may be involved in smooth muscle contraction, natriuresis, diuresis, inflammatory response, positive regulation of apoptosis
  • antimicrobial activity of the heparin-binding and cell-binding domain 5 of high molecular weight kininogen
  • playing an essential role in prevention of metastasis of cancer cells
  • inhibits ERK-dependent T cell proliferation, and these observations may have a possible role in immunosenescence (Acuna-Castillo 2005)
  • acts as an important signal directing the invasion of glioma cells toward blood vessels (
  • multiple functions, including the regulation of coagulation
    • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS coagulation/hemostasis , inflammation
    text hemostasis
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • ion Zn2+ binding
    • protein
  • interacting with urokinase plasminogen activator receptor
  • neutrophil-derived PRTN3 can proteolyze KNG1 and liberate PRTN3-kinin, thereby initiating kallikrein-independent activation of the kinin pathway
    • cell & other
    REGULATION
    Other up-regulated by agonists of the farnesoid X receptor
    ASSOCIATED DISORDERS
    corresponding disease(s) KNG
    Susceptibility to shortening of the activated partial thromboplastin time (aPTT)
    Variant & Polymorphism SNP rs710446 increasing the risk of aPTT (Houlihan 2010)
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Kng1(-/-) mice are viable, but lacked plasma High-molecular-weight kininogen and low-molecular-weight kininogen , as well as DeltamHK-D5, displayed a significantly prolonged time to carotid artery occlusion following Rose Bengal administration and laser-induced arterial injury (