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FLASH GENE
Symbol MMP12 contributors: mct - updated : 30-11-2015
HGNC name matrix metalloproteinase 12 (macrophage elastase)
HGNC id 7158
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
10 - 1877 - 470 - 2001 11704502
EXPRESSION
Type widely
constitutive of
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveesophagus   highly
Reproductivefemale systemplacenta  highly
 female systembreastmammary gland highly
Respiratorylung    
 respiratory tractlarynx  highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoietic    
cells
SystemCellPubmedSpeciesStageRna symbol
Lymphoid/Immunemacrophage
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo, pregnancy
Text placenta,cells ,chondrocytes of hypertrophic cartilage (spinal column,ribs )
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