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FLASH GENE
Symbol MMP13 contributors: mct/npt/pgu - updated : 27-03-2016
HGNC name matrix metalloproteinase 13 (collagenase 3)
HGNC id 7159
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)
  • a hinge region
  • a hemopexin-like C terminal domain
    • conjugated HemoP , MetalloP
    HOMOLOGY
    interspecies homolog to murine Mmp13
    intraspecies homolog to MMP8
    Homologene
    FAMILY
  • matrix metalloproteinase family of neutral endopeptidase
  • peptidase M10A family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • regulator of matrix remodeling
  • collagenase III, cleaving preferentially the type II collagen
  • playing a critical role in bone metabolism and homeostasis, and in tumor invasion and metastasis
  • involved in the degradation of extracellular matrix, prerequisite for invasive and metastatic behavior of solid tumors
  • involved in the degradation of cartilage
  • osteoclast activation
  • playing a critical role in development of growth plate cartilge and in endochondral ossification
  • anti-inflammatory activity
  • play a critical role in cartilage destruction and have an important rolen in cartilage formation
  • with MMP9 play a role in endochondral ossification
  • mediates cell cycle progression in melanocytes and melanoma cells
  • might be directly involved in the loop promoting pre-osteoclast differentiation and activity
  • has a pivotal, rate-limiting function in cartilage remodeling and degradation due to its specificity for cleaving type II collagen
  • osteocyte perilacunar remodeling of mid-cortical bone matrix requires MMP13 and is essential for the maintenance of bone quality
  • important role in wound healing by coordinating cellular activities important in the growth and maturation of granulation tissue, including myofibroblast function, inflammation, angiogenesis, and proteolysis
  • MMP13 may directly and indirectly promote tumor angiogenesis
  • promoted the secretion of VEGF from fibroblasts and endothelial cells
    • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS inflammation
    text antiinflammatory
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • binding TIMPs in a 1:1 stoechiometry
  • interacting with RUNX2 (phosphorylation of RUNX2 sites necessary for PKA stimulated MMP13 promoter activation and this event may be critical for bone remodeling)
  • HDAC4 is a basal repressor of MMP13 transcription, and PTH regulates HDAC4 to control MMP13 promoter activity
  • IL6 increased the migration and expression of MMP13 in chondrosarcoma cells
  • NOV increased the migration and expression of matrix metalloproteinase MMP13 in chondrosarcoma cells
  • CEBPB and RUNX2 cooperatively enhanced promoter activity of MMP13 through specific binding to a CEBP-binding motif and an osteoblast-specific cis-acting element 2 motif as a protein complex
  • WNT5A-ROR2 signaling might be required for expression of MMP13 gene during the development of the cartilaginous tissue
  • novel role for ELF3 as a procatabolic factor that may contribute to cartilage remodeling and degradation by regulating MMP13 gene transcription
  • possible involvement of S100A12 in the development of osteoarthritis (OA) by up-regulating MMP13 and VEGFA via MAPK14 and NFKB1 pathways
  • MMP13 is an important target of Osterix (SP7)
  • physical and functional interaction between SP7 and RUNX2 were necessary for the induction of MMP13 during endochondral ossification
  • direct regulatory role for SP7 in MMP13 gene expression in osteoblasts
  • promotes invasiveness and metastasis in Ewing sarcomas through PGF and MMP13
  • IL6 mediates suppression of ACAN and induction of MMP13 expression by NOTCH1 in chondrocytes
  • inhibition of MMP13 expression through GDF5 stimulation is mediated by DKK1
  • MMP13 proteolyzes FBLN1 and CALU protects FBLN1 from cleavage by MMP13
  • IL32 stimulation promotes the invasion and motility of osteosarcoma cells, possibly via the activation of AKT1 and the upregulation of MMP13 expression
    • cell & other
    REGULATION
    activated by proteinases and plasmin, and others MMPs (MMP14)
    MAF (can significantly enhance MMP13 promoter activity via the AP-1 site)
    induced by FOXO3
    inhibited by IL1 and RUNX2 in chondrocytic cells
    TFPI2
    repressed by ANKRD1 (in association with factors such as nucleolin, represses likely MMP13 transcription) )
    ASSOCIATED DISORDERS
    corresponding disease(s) SEMD2 , MAND2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast carcinoma, squamous cell carcinomas of head and neck and vulvar squamous cell carcinoma
    constitutional     --over  
    overexpressed in rheumatoid arthritis and inabdominal aortic aneurysm
    tumoral     --over  
    in renal cell carcinoma bone metastasis and is induced by TGF-beta1
    Susceptibility
  • to coronary artery disease
    • Variant & Polymorphism other
  • MMP13 intron polymorphism rs640198 is associated with the severity of coronary artery disease
    • Candidate gene for SEMD2
    Marker
  • could be a potential prognostic marker for colorectal cancer patients
    • Therapy target
    ANIMAL & CELL MODELS