MMP2

Matrix Metalloproteinase-2 (MMP2) is an enzyme that degrades components of the extracellular matrix and thus plays a pivotal role in cell migration during physiological and pathological processes. MMP2 expression is dependent on extracellular matrix metalloproteinase inducer (EMMPRIN), Her2/neu, growth factors, cytokines, and hormones. Pro-MMP-2 activation needs MT1-MMP and TIMP-2 contribution. MMP2 is changed in distribution and increased in amount in the ventral cochlear nucleus after unilateral cochlear ablation. A low level of MMP2 is linked to favorable prognosis in patients with a hormone receptor-negative tumor, usually associated with high risk.

MMP2 Related Areas

Enzyme>>Protease & Regulator>>Metalloprotease & Regulator>>Matrix Metalloproteinase>>MMP-2/MMP2

Cancer>>Angiogenesis>>Matrix Metalloproteinase>>MMP-2/MMP2

Cancer>>Cancer Biomarkers>>MMP-2/MMP2

MMP2 Alternative Names

MMP-2, MMP2, MMP-II, CLG4, CLG4A, MONA, TBE-1 [Homo sapiens]

MMP-2, Mmp2, Clg4a, GelA [Mus musculus]

Summaries for MMP2

Entrez Gene summary for MMP2:

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. MMP2 encodes an enzyme which degrades type IV collagen, the major structural component of basement membranes. The enzyme plays a role in endometrial menstrual breakdown, regulation of vascularization and the inflammatory response. Mutations in MMP2 have been associated with Winchester syndrome and Nodulosis-Arthropathy-Osteolysis (NAO) syndrome. Two transcript variants encoding different isoforms have been found for MMP2.

OMIM - description for MMP2:

Type IV collagenase, 72-kD, is officially designated matrix metalloproteinase-2 (MMP2). It is also known as gelatinase, 72-kD (Nagase et al., 1992). Type IV collagenase is a metalloproteinase that specifically cleaves type IV collagen, the major structural component of basement membranes (120090, 120130). The metastatic potential of tumor cells has been found to correlate with the activity of this enzyme.

Wikipedia summary for MMP2:

72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the MMP2 gene.

Human MMP2 Protein General Information

 

• Protein names: Matrix metalloproteinase-2, Short name=MMP2
• Sequence length: 660 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: Phosphorylation on multiple sites modulates enzymatic activity. Phosphorylated by PKC in vitro. Ref.20 The propeptide is processed by MMP14 (MT-MMP1) and MMP16 (MT-MMP3). Autocatalytic cleavage in the C-terminal produces the anti-angiogenic peptide, PEX. This processing appears to be facilitated by binding integrinv/beta3.
• Cofactor: Binds 4 calcium ions per subunit. Binds 2 zinc ions per subunit.
• Subunit structure: Interacts (via the C-terminal hemopexin-like domains-containing region) with the integrin alpha-V/beta-3; the interaction promotes vascular invasion in angiogenic vessels and melamoma cells. Interacts (via the C-terminal PEX domain) with TIMP2 (via the C-terminal); the interaction inhibits the degradation activity. Interacts with GSK3B.
• Subcellular location: Secreted › extracellular space › extracellular matrix. Membrane. Nucleus. Note: Colocalizes with integrin alphaV/beta3 at the membrane surface in angiogenic blood vessels and melanomas. Found in mitochondria, along microfibrils, and in nuclei of cardiomyocytes.
• Tissue specificity: MMP2 is produced by normal skin fibroblasts. PEX is expressed in a number of tumors including gliomas, breast and prostate.
• Involvement in disease: Defects in MMP2 are the cause of Torg-Winchester syndrome (TWS) [MIM:259600]; also known as multicentric osteolysis nodulosis and arthropathy (MONA). TWS is an autosomal recessive osteolysis syndrome. It is severe with generalized osteolysis and osteopenia. Subcutaneous nodules are usually absent. Torg-Winchester syndrome has been associated with a number of additional features including coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy. However, these features are not always present and have occasionally been observed in other osteolysis syndromes.
• Catalytic activity: Cleavage of gelatin type I and collagen types IV, V, VII, X. Cleaves the collagen-like sequence Pro-Gln-Gly-|-Ile-Ala-Gly-Gln.
• Enzyme regulation: Inhibited by histatin-3 1/24 (histatin-5).
• Induction: Aspirin appears to inhibit expression.

General information above from UniProt

Function for MMP2 Protein

UniProtKB:

Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, MMP2 can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also MMP2 cleaves KISS at a Gly-|-Leu bond. MMP2 appears to have a role in myocardial cell death pathways. MMP2 contributes to myocardial oxidative stress by regulating the activity of GSK3beta. MMP2 cleaves GSK3beta in vitro. PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.

Genatlas:

• regulator in matrix remodeling, MMP2 is involved in atherogenesis, tumor invasion and metastasis
• collagenase IVA, gelatinase A, MMP2 plays a significant role in tumour invasion and angiogenesis
• MMP2 digests type I, II, III collagens
• MMP2 is important for osteogenesis
• MMP2 plays 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
• MMP2 plays a direct role in early skeletal development and bone cell growth and proliferation
• MMP2 participates in adult axonal regeneration induced by OECs (olfactory ensheathing cells )
• MMP2 plays a crucial role in forming and maintaining the osteocytic canalicular network
• MMP2 is highly involved in early embryo implantation
• MMP2 plays an essential role in angiogenesis, inflammation, and fibrosis

Homology for human MMP2

• homolog to rattus Mmp2 (95.76 pc)
• homolog to murine Mmp2 (95.91 pc)

Phenotype Information for MMP2

• Gene/Locus: MMP2, CLG4A, MONA
• Phenotype: Torg-Winchester syndrome

Phenotype Information for MMP2 from OMIM (Online Mendelian Inheritance in Man)

Drugs for MMP2

Target	Drug Name	Disease	Drug Status
MMP2	BMS	Non-small Cell Lung Cancer, Hormone-refractory Prostate Cancer, Kaposi's Sarcoma	Discontinued in Phase III
MMP2	Prinomastat	Brain Cancer	Discontinued in Phase III
MMP2	Prinomastat	Lung Cancer, Prostate Cancer	Trial halted
MMP2	Marimastat	Pancreatic Cancer, Lung Cancer	Discontinued in Phase III
MMP2	Neovastat	Cancer/psoriasis/opthalmologic	Discontinued in Phase III
MMP2	Neovastat	Non-small Cell Lung Cancer (NSCLC), Renal Cell Carcinoma	Suspended in Phase III
MMP2	BB-3644	Cancer/Tumors	Discontinued in Phase I
MMP2	Tanomastat	Pancreatic Cancer, Lung Cancer, Ovarian Cancer, Osteoarthritis	Discontinued in Phase III
MMP2	PG-116800	Acute and chronic heart failure	Suspended in Phase II

Drugs for MMP2 from TTD (Therapeutic Targets Database)