MMP-2 active protein
Human MMP-2
NCBI and Uniprot Product Information
NCBI Description
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. This gene 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 this gene have been associated with Winchester syndrome and Nodulosis-Arthropathy-Osteolysis (NAO) syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Uniprot Description
Function: 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, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.22 Ref.24PEX, 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. Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.22 Ref.24Isoform 2:Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways. Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.22 Ref.24
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.
Cofactor: Binds 4 calcium ions per subunit.Binds 2 zinc ions per subunit.
Enzyme regulation: Inhibited by histatin-3 1/24 (histatin-5). Ref.17
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. Ref.10 Ref.16 Ref.18 Ref.22
Subcellular location: Isoform 1: 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. Ref.11 Ref.20 Ref.24Isoform 2: Cytoplasm. Mitochondrion Ref.11 Ref.20 Ref.24.
Tissue specificity: Produced by normal skin fibroblasts. PEX is expressed in a number of tumors including gliomas, breast and prostate. Ref.16
Induction: Aspirin appears to inhibit expression. Ref.17 Ref.23
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.
Post-translational modification: Phosphorylation on multiple sites modulates enzymatic activity. Phosphorylated by PKC in vitro. Ref.21The 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.
Involvement in disease: Multicentric osteolysis, nodulosis, and arthropathy (MONA) [MIM:259600]: An autosomal recessive syndrome characterized by severe multicentric osteolysis with predominant involvement of the hands and feet. Additional features include coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.34 Ref.35 Ref.36
Sequence similarities: Belongs to the peptidase M10A family.Contains 3 fibronectin type-II domains.Contains 4 hemopexin repeats.
Research Articles on MMP-2
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Product Notes
The MMP-2 mmp2 (Catalog #AAA691550) is an Active Protein produced from E Coli and is intended for research purposes only. The product is available for immediate purchase. The Human MMP-2 reacts with Human and may cross-react with other species as described in the data sheet. The amino acid sequence is listed below: MYNFFPRKPK WDKNQITYRI IGYTPDLDPE TVDDAFARAF QVWSDV TPLR FSRIHDGEAD IMINFGRWEH GDGYPFDGKD GLLAHAFAPG T GVGGDSHFD DDELWTLGEG QVVRVKYGNA DGEYCKFPFL FNGKEYN SCT DTGRSDGFLW CSTTYNFEKD GKYGFCPHEA LFTMGGNAEG QP CKFPFRFQ GTSYDSCTTE GRTDGYRWCG TTEDYDRDKK YGFCPETA MS TVGGNSEGAP CVFPFTFLGN KYESCTSAGR SDGKMWCATT ANY DDDRKWG FCPDQGYSLF LVAAHEFGHA MGLEHSQDPG ALMAPIYTY T KNFRLSQDDI KGIQELYGAS PDIDLGTGPT PTLGPVTPEI CKQD IVFDGI AQIRGEIFFF KDRFIWRTVT PRDKPMGPLL VATFWPELPE KIDAVYEAPQ EEKAVFFAGN EYWIYSASTL ERGYPKPLTS LGLPP DVQRV DAAFNWSKNK KTYIFAGDKF WRYNEVKKKM DPGFPKLIAD AWNAIPDNLD AVVDLQGGGH SYFFKGAYYL KLENQSLKSV KFGSIK SDWL GC. It is sometimes possible for the material contained within the vial of "MMP-2, Active Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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