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FLASH GENE
Symbol MMP2 contributors: mct - updated : 05-02-2014
HGNC name matrix metallopeptidase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase)
HGNC id 7166
Corresponding disease
NAO multicentric osteolysis, nodulosis and arthropathy (vanishing bone)
WINCH1 Winchester syndrome 1
Location 16q12.2      Physical location : 55.513.080 - 55.540.584
Synonym name
  • matrix metalloproteinase 2 (gelatinase A, 72kD gelatinase, 72kD type IV collagenase)
  • neutrophil gelatinase
  • gelatinase A
  • collagenase type IV-A
  • Synonym symbol(s) MM02, MONA, TBE-1, CLG4, MMPII, CLG4A
    EC.number 3.4.24.24
    DNA
    TYPE functioning gene
    STRUCTURE 27.51 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   enhancer
    text structure
  • promoter variants
  • a crucial role for the enhancer element RE-1 in injury-induced MMP2 transcription of the skin (Jansen 2007)
  • AP-1 and RE-1 bindign sites in the promoter play a critical role in MMP2 transcriptional regulation in muscle atrophy (Liu 2010)
  • MAPPING cloned Y linked N status confirmed
    Map cen - D16S175 , D16S178 , D16S187 , MMP2 - D16S179 , CETP CETP , MT1@ - qter
    Physical map
    LOC388278 16 LOC388278 IRX3 19q12.2 iroquois homeobox protein 3 LOC388279 16 hypothetical gene supported by AF275804 IRX5 16q11.2-q13 iroquois homeobox protein 5 LOC388280 LOC388281 16 LOC388281 MMP2 16q13-q21 matrix metalloproteinase 2 (gelatinase A, 72kDa gelatinase, 72kDa type IV collagenase) FLJ20481 16q13 hypothetical protein FLJ20481 CAPNS2 16q13 hypothetical protein FLJ20481 SLC6A2 16q12.2 solute carrier family 6 (neurotransmitter transporter, noradrenalin), member 2 LOC390732 16 similar to carboxylesterase 3 CESR 16q13 carboxylesterase-related protein CES1 16q13-q22.1 carboxylesterase 1 (monocyte/macrophage serine esterase 1) FLJ31547 16q13 hypothetical protein FLJ31547 GNAO1 16q12.1 guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O AMFR 16q21 autocrine motility factor receptor CPSF5 16q13 cleavage and polyadenylation specific factor 5, 25 kDa FLJ10826 16q13 hypothetical protein FLJ10826 BBS2 16q21 Bardet-Biedl syndrome 2 MT4 16q13 metallothionein IV MT3 16q13 metallothionein 3 (growth inhibitory factor (neurotrophic))
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 3549 71 660 - 2012 2250927
  • isoform a
  • 13 - 3402 68 610 full length 68 kDa isoform was found only in the extracellular space 2012 2250927
  • isoform b
  • - - - 65 - - 2012 2250927
  • N-terminal truncated intracellular isoform of MMP2 induced by oxidative stress
  • not secreted and is present in cytosolic and mitochondrial fractions
  • induced mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NFKB, NFAT and IRF transcriptional pathways
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   highly
    Digestivemouthtongue  highly
     salivary gland   highly
    Endocrinepancreas   highly
    Nervousbrainlimbic systemhippocampus highly Homo sapiensFetal
    Reproductivefemale systemuterus  highly
     male systemtestis  moderately Rattus norvegicusFetal
    Respiratorylung   highly
    Urinarykidney   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectivebone   
    Epithelialbarrier/liningendometrium  
    Epithelialsecretoryglandularendocrine 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivegerm cell Rattus norvegicusFetal
    Urinarymesangial cell
    cell lineage
    cell lines tumor endothelial cells
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta, umbilical cord
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a cysteine residue, essential for latency
  • an activation locus
  • a catalytic domain with the zinc binding site (the cysteine switch)
  • a unique CBD (collagen-binding domain) containing three fibronectin type II-like modules
  • a hinge region
  • four hemopexin-like (PEX) domains with integrin binding activity
  • conjugated HemoP , MetalloP
    HOMOLOGY
    interspecies homolog to rattus Mmp2 (95.76 pc)
    homolog to murine Mmp2 (95.91 pc)
    Homologene
    FAMILY
  • peptidase M10A family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,nucleus
    text
  • extracellular matrix
  • found in mitochondria, along microfibrils and in nuclei of cardiomyocytes
  • basic FUNCTION
  • regulator in matrix remodeling, involved in atherogenesis, tumor invasion and metastasis
  • collagenase IVA, gelatinase A, playing a significant role in tumour invasion and angiogenesis
  • digests type I, II, III collagens
  • important for osteogenesis
  • a role in neurite outgrowth, cell migration, mesenchymal cell differentiation with inflammatory phenotype, enhanced collagen affinity, increased bioavailability of IGF1 and cell and TGF beta, epithelial cell migration, anti-inflammatory
  • plays a direct role in early skeletal development and bone cell growth and proliferation
  • participate in adult axonal regeneration induced by OECs (olfactory ensheathing cells)
  • plays a crucial role in forming and maintaining the osteocytic canalicular network
  • highly involved in early embryo implantation (Gremlich 2007)
  • plays an essential role in angiogenesis, inflammation, and fibrosis (Jansen 2007)
  • functions in diverse biological processes through the degradation of extracellular and non-extracellular matrix molecules
  • MMP2 plays a critical role in TGFB2-mediated matrix contraction, which appears to be independent of MMP14
  • role of MMP2 and its genetic variants in the pathophysiology of migraine
  • important regulator of cell migration and invasion through degradation of the extracellular matrix (ECM) in many diseases, such as cancer and endometriosis
  • CELLULAR PROCESS cell life, differentiation
    protein, degradation
    cell migration & motility
    PHYSIOLOGICAL PROCESS inflammation
    text anti-inflammatory effect
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • two Zn2+ per subunit
  • four Ca2+ per subunit
  • protein
  • CSF2
  • binding TIMPs in a 1:1 stoechiometry
  • WISP1 interacting with MMP2 (increased the migration and expression of MMP2 in human chondrosarcoma cells) (
  • UTS2 and NOX4 stimulated FOXO2, FOXO3 activity and MMP2 is a target gene of FOXO3
  • novel regulatory mechanism for pro-MMP2 activation that is modulated through homodimerization of MMP2
  • TACR1 was a potential regulator of human glioma cell migration by the up-regulation of MMP2 and MMP14
  • physical association between PAK4 and MM2, suggesting the future therapeutic potential of PAK4/MMP2 dual targeting in glioma treatment
  • CAPN7 interacted with activator protein 2 (TFAP2A), an important transcription factor of MMP2
  • HDAC10 binds to the promoter regions of MMP2 and -9, deacetylates histones H3 and H4 in these regions, blocks the binding of RNA polymerase II, and consequently down-regulates MMP2 and -9 expression
  • ID4 decreased MMP2 expression by a direct inhibitory interaction with TWIST1, a basic helix-loop-helix transcription factor known to increase MMP2 expression
  • cell & other
    REGULATION
    activated by MMP14 in a process tightly regulated by the level of TIMP2 in the late luteal phase (major cause of the remodeling in corpus luteum during structural luteolysis)
    transactivated by TP53 decreased by ATF3
    prolonged hypoxia
    MMP15, MMP16, MMP24, MMP25
    proteinases
    inhibited by TIMPs, TFPI2, short hypoxia, PCOLCE, RECK and chlorotoxin
    Chitooligosaccharides (COS)
    repressed by SPI1 (PU1) in mesangial cells
    aspirin
    Other regulated by PTEN
    cleaved into PEX
    MMP2 mRNA expression and its enzymatic activity was correlated with the expression of ZNF580 (Sun 2010)
    ASSOCIATED DISORDERS
    corresponding disease(s) NAO , WINCH1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in inflammatory bowel diseases, poly and dermatomyositis
    tumoral     --over  
    in prostate tumor and in malignant mesothelioma and in thymoma with poor prognosis
    tumoral       gain of function
    in head and neck cancer (by CSF2) and in invasive glioma (inhibited by PTEN)
    tumoral     --over  
    in head and neck carcinoma with lymph node metastasis and in breast carcinoma with short survival
    constitutional       loss of function
    linked with an autosomal recessive form of multicentric osteolysis
    constitutional     --low  
    contribute to the endothelial dysfunction that is central to the pathophysiology of preeclampsia
    constitutional     --over  
    in scarred keratoconic cornea
    tumoral       gain of function
    in high expression of estrogen receptors associated with increased BCL2 levels in breast carcinoma
    constitutional     --over  
    have been detected after skin injury (jansen 2007)
    constitutional     --over  
    in women with pelvic organ prolapse (Connell 2008)
    tumoral       gain of function
    resulting from decreased ID4 expression in glioblastoma multiforme (GBM), may contribute to the morbidity and mortality of GBM patients
    constitutional       gain of function
    SPARC, MMP2 and MM9 were significantly up-regulated in intracranial aneurysms relative to the expression levels in the normal Circle of Willis arteries
    Susceptibility
  • to toxic epidermal necrolysis and to Stevens-Johnson syndrome
  • to nasopharyngeal carcinoma
  • to intrauterine growth retardation (IUGR)
  • Variant & Polymorphism other
  • polymorphisms increasing the risk of nasopharyngeal carcinoma
  • MMP2 C-1306T mutation rate was higher within the IUGR (Gremlich 2007)
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    ARP101 known as a selective matrix metalloproteinase-2 (MMP-2) inhibitor, strongly induced autophagy and autophagy-mediated cell death of cancer cells
    ANIMAL & CELL MODELS
  • a MONA-like progressive osteolysis and arthritis phenotype has been demonstrated in Mmp2-knockout mice