MMP-9

MMP-9, also known as 92-kDa gelatinase B/type IV collagenase, is secreted from neutrophils, macrophages, and a number of transformed cells, and is the most complex family member in terms of domain structure and regulation of its activity. It plays an important role in tissue remodelling in normal and pathological inflammatory processes. MMP-9 is a major secretion product of macrophages and a component of cytoplasmic granules of neutrophils, and is particularly important in the pathogenesis of inflammatory, infectious, and neoplastic diseases in many organs including the lung. This enzyme is also secreted by lymphocytes and stromal cells upon stimulation by inflammatory cytokines, or upon delivery of bi-directional activation signals following integrin-mediated cell-cell or cell-extracellular matrix (ECM) contacts.

MMP-9 Related Areas

Enzyme>>Protease & Regulator>>Metalloprotease & Regulator>>Matrix Metalloproteinase>>MMP-9/MMP-9

Cancer>>Angiogenesis>>Matrix Metalloproteinase>>MMP-9/MMP-9

Cancer>>Cancer Biomarkers>>MMP-9/MMP-9

MMP-9 Alternative Names

MMP-9, MMP-9, CLG4B, GELB, MANDP2 [Homo sapiens]

MMP-9, MMP-9, pro-MMP-9, B/MMP-9, Clg4b, RP23-61O3.10, AW743869 [Mus musculus]

Summaries for MMP-9

Entrez Gene summary for MMP9:

Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The enzyme encoded by this mmp9 gene degrades type IV and V collagens. Studies in rhesus monkeys suggest that the enzyme is involved in IL-8-induced mobilization of hematopoietic progenitor cells from bone marrow, and murine studies suggest a role in tumor-associated tissue remodeling.

OMIM - description for MMP-9:

The 72- and 92-kD type IV collagenases are members of a group of secreted zinc metalloproteases which, in mammals, degrade the collagens of the extracellular matrix. Other members of this group include interstitial collagenase (MMP1; 120353) and stromelysin (MMP3; 185250). The 72-kD type IV collagenase (MMP2, or CLG4A; 120360) is secreted from normal skin fibroblasts, whereas the 92-kD collagenase (CLG4B) is produced by normal alveolar macrophages and granulocytes. The 92-kD type IV collagenase is also known as 92-kD gelatinase, type V collagenase, or matrix metalloproteinase-9 (MMP9); see the glossary of matrix metalloproteinases provided by Nagase et al.

Wikipedia summary for MMP-9:

Matrix metallopeptidase 9 (MMP-9), also known as 92 kDa type IV collagenase, 92 kDa gelatinase or gelatinase B (GELB), is an enzyme that in humans is encoded by the MMP9 gene.

Human MMP-9 Protein General Information

 

• Protein names: Matrix metalloproteinase-9, Short name=MMP-9
• Sequence length: 707 AA.
• Domain: The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
• Sequence similarities: Belongs to the peptidase M10A family. Contains 3 fibronectin type-II domains. Contains 4 hemopexin-like domains.
• Post-translational modification: Processing of the precursor yields different active forms of 64, 67 and 82 kDa. Sequentially processing by MMP3 yields the 82 kDa matrix metalloproteinase-9. N- and O-glycosylated.
• Cofactor: Binds 2 zinc ions per subunit. Binds 3 calcium ions per subunit.
• Subunit structure: Exists as monomer or homodimer; disulfide-linked. Exists also as heterodimer with a 25 kDa protein. Macrophages and transformed cell lines produce only the monomeric form. Interacts with ECM1.
• Subcellular location: Secreted › extracellular space › extracellular matrix
• Tissue specificity: Produced by normal alveolar macrophages and granulocytes.
• Involvement in disease: Defects in MMP-9 may be a cause of susceptibility to intervertebral disc disease (IDD) [MIM:603932]; also known as lumbar disk herniation (LDH). IDD is one of the most common musculo-skeletal disorders and the predominant cause of low-back pain and unilateral leg pain.
• Catalytic activity: Cleavage of gelatin types I and V and collagen types IV and V.
• Enzyme regulation: Inhibited by histatin-3 1/24 (histatin-5). Inhibited by ECM1.
• Induction: Activated by 4-aminophenylmercuric acetate and phorbol ester. Up-regulated by ARHGEF4, SPATA13 and APC via the JNK signaling pathway in colorectal tumor cells.

General information above from UniProt

Function for MMP-9 Protein

UniProtKB:

MMP-9 may play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. MMP-9 could play a role in bone osteoclastic resorption. MMP-9 cleaves KiSS1 at a Gly-|-Leu bond. MMP-9 cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. MMP-9 dgrades fibronectin but not laminin or Pz-peptide.

Genatlas:

• MMP-9 regulats the matrix remodeling
• MMP-9 plays a significant role in tumour invasion and angiogenesis
• MMP-9 is highly involved in early embryo implantation
• MMP-9 codes for an enzyme engaged in the regulation of neuronal plasticity and can also contribute to neuronal cell death in pathological conditions
• MMP9 and MMP12 promote intimal thickening by independent cleavage of N-cadherin, which elevates vascular smooth muscle cell proliferation via beta-catenin signalling
• MMP-9 is associated with neovascularization
• MMP-9 can generate angiostatin fragments by hydrolyzing plasminogen
• MMP-9 is also involved in the migratory process (acute and chronic inflammation of tumoral metastatic process and in injury processus of myofibers)
• MMP-9 plays a control role of keratinocyte growth
• MMP-9 is involved in enhanced collagen affinity, reduced IL-2 response
• pro/antiinflammatory roles
• MMP-9 may act not only as a solubilizer of bone matrix but also as a regulator of initiation of bone resorption and coupling to bone formation
• MMP-9 with MMP13 play a role in endochondral ossification
• MMP-9 is involved in a wide range of normal and pathologic conditions, including inflammation, tissue repair, tumor invasion, and metastasis
• MMP-9 initiates cross-talk between CD44 and EGFR, which in turn activates downstream effectors for cell migration

Phenotype Information for MMP-9

• Gene/Locus: MMP9, CLG4B, MANDP2
• Phenotype: Metaphyseal anadysplasia 2

Phenotype Information for MMP-9 from OMIM (Online Mendelian Inheritance in Man)

Drugs for MMP-9

Target	Drug Name	Disease	Drug Status
MMP-9	Neovastat	Cancer/psoriasis/opthalmologic	Discontinued in Phase III
MMP-9	Neovastat	Non-small Cell Lung Cancer (NSCLC), Renal Cell Carcinoma	Suspended in Phase III
MMP-9	PG-116800	Acute and chronic heart failure	Suspended in Phase II

Drugs for MMP-9 from TTD (Therapeutic Targets Database)