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FLASH GENE
Symbol MMP12 contributors: mct - updated : 30-11-2015
HGNC name matrix metalloproteinase 12 (macrophage elastase)
HGNC id 7158
Location 11q22.2      Physical location : 102.733.464 - 102.745.764
Synonym name
  • macrophage metallo-elastase
  • macrophage metalloelastase
    • Synonym symbol(s) HME, MME, MM12
    EC.number 3.4.24.65
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    text member of the MMP cluster
    STRUCTURE 12.25 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    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