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FLASH GENE
Symbol MMP8 contributors: mct - updated : 01-09-2021
HGNC name matrix metalloproteinase 8 (neutrophil collagenase)
HGNC id 7175
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • four hemoplexin-like domains
    • conjugated HemoP , MetalloP
    HOMOLOGY
    interspecies homolog to rattus Mmp8 (72.9pc)
    homolog to murine Mmp8 (74.5pc)
    Homologene
    FAMILY
  • peptidase M10A family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,cytosolic,granule
    text secreted, extracellular space, extra cellular matrix
    basic FUNCTION
  • regulator in matrix remodeling
  • degradation of type I, II, III collagens, preferentially the type I collagen
  • degrading fibrillar collagens imparting strength to the fetal membranes
  • abilitiy to inhibit melanoma progression (Palavalli 2009)
  • has an inhibitory effect on cancer metastasis (Decock 2007)
  • is a key player in atherogenesis
  • is an essential mediator in Systemic inflammatory response syndrome (SIRS)
  • evidence of the most relevant regulatory pathways and activities mediated by MMP8 in atherogenesis
  • role of MMP8 in macrophage differentiation and polarization
  • macrophage-derived MMP8 is a regulator in SMC differentiation from adventitia stem/progenitor cells (AdSPCs) and neointimal smooth muscle cells (SMCs) in response to injury
  • MMP8 participates in eye diseases including xerophthalmia and retinal disease
  • MMP8 can facilitate RPE cells proliferation and migration via modulating cell apoptotic activity and secretion of inflammatory factor, thus participating in Rhegmatogenous retinal detachment (RRD) pathogenesis and progression
    • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • binding two ions Zn2+ per subunit
  • binding three ions Ca2+ per subunit
    • protein
  • binding TIMPs in a 1:1 stoechiometry
  • MMP8 plays an important role in intestinal ischemia-reperfusion (I/R) injury through mechanisms involving increased inflammation and loss of claudin-3
  • FXYD5 is a novel substrate of MMP8 and reducing FXYD5 levels either with siRNA or cleavage by MMP8 increases cell adhesion leading to reduced motility
    • cell & other
    REGULATION
    activated by autocatalytic cleavage
    inhibited by TIMPs and TFPI2
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in ovarian cancer with invasive potential
    constitutional       gain of function
    in chronic obstructive pulmonary disease
    constitutional     --over  
    at the site of abdominal aortic aneurysm rupture
    tumoral somatic mutation      
    five mutations reducing MMP enzyme activity in melanoma (Palavalli 2009)
    constitutional     --over  
    intraplaque MMP8 levels are increased in asymptomatic patients with carotid plaque progression on ultrasound (Turu 2006)
    constitutional     --over  
    increased local MMP8 expression in the periodontal connective tissues of smokers with periodontal disease (Liu 2006)
    constitutional     --over  
    serum MMP-8 concentrations are elevated in prevalent or subclinical atherosclerosis and associate with the worst cardiovascular outcome in men (Tuomainen 2007)
    Susceptibility
  • to preterm premature rupture of membranes
  • bacterial vaginosis is associated with increased levels of matrix metalloproteinase-8(MMP-8) in vaginal fluid of pregnant women (Diaz-Cueto 2006)
  • to osteonecrosis of the femoral head (ONFH)
    • Variant & Polymorphism SNP , other
  • SNP associated with preterm premature rupture of membranes
  • a promoter SNP with its minor allele (T) associating with reduced susceptibility to lymph node metastasis in breast cancer (Decock 2007)
  • polymorphism +17 C/G in matrix metalloprotease MMP8 decreases lung cancer risk (González-Arriaga 2008)
  • remarkable association between rs11225394 in MMP8 gene and an increased risk of ONFH and a significant association between MMP8 rs2012390 and the decreased risk of ONFH
    • Candidate gene
    Marker
  • increase in the duration of response to the cold test was associated with an increase in MMP8 levels in teeth with pulpitis
    • Therapy target
    ANIMAL & CELL MODELS