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FLASH GENE
Symbol MMP12 contributors: mct - updated : 30-11-2015
HGNC name matrix metalloproteinase 12 (macrophage elastase)
HGNC id 7158
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a cysteine residue essential for latency and involved in autocatalytic activation
  • a catalytic domain with the zinc-binding site (the cysteine switch)that alone binds and degrades collagens I and III
  • a hinge region
  • a hemopexin-like C terminal domain
    • conjugated HemoP , MetalloP
    HOMOLOGY
    Homologene
    FAMILY
  • MMP family
  • peptidase M10A family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • regulator in matrix remodeling
  • playing a role in extracellular matrix remodeling during fetal bone development and in chondrocytes malignant transformation
  • macrophage metalloelastase, essential for macrophage migration
  • MMP9 and MMP12 promote intimal thickening by independent cleavage of N-cadherin, which elevates vascular smooth muscle cell proliferation via beta-catenin signalling
  • remodeling of elastotic areas in sun damaged skin
  • generation of angiostatin-like fragment
  • macrophage-secreting proteinase
  • its overexpression in myeloid lineage cells plays a key role in modulating myelopoiesis, immune suppression, and lung tumorigenesis
    • CELLULAR PROCESS nucleotide, repair
    cell migration & motility
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • zinc Zn2+
  • calcium Ca2+
    • protein
  • binding TIMPs in a 1:1 stoechiometry
  • is a PGRN proteolytic enzyme, and SLPI an inhibitor of MMP12-induced PGRN proteolysis
  • MMP12 regulates adipose tissue expansion, insulin sensitivity, and expression of NOS2
    • cell & other
    REGULATION
    activated by proteinases
    inhibited by TFPI2
    Other regulated by the Ca2+ (may be involved in controlling the activity of MMP12)
    regulation by a PPAR alpha agonist in human monocyte-derived macrophages
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in ulcerative colitis and Crohn's disease and in colorectal carcinoma with better prognosis
    constitutional     --over  
    with ADAMDEC1, in bronchoalveolar lavage samples from patients with sarcoidosis, correlating with disease severity
    tumoral     --over  
    correlated with poor prognosis of hepatocellular carcinoma
    constitutional     --over  
    in atherosclerotic lesions
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • MMP12 mRNA may be a valuable prognostic marker for both overall survival and tumour recurrence of hepatocellular carcinoma patients after liver resection
    • Therapy target
    SystemTypeDisorderPubmed
    allergyasthm 
    In allergen-sensitized sheep pharmacologic inhibition of MMP12 downregulates both early and late airway responses in response to allergic stimuli
    ANIMAL & CELL MODELS