Matrix metallopeptidase 12 explained

macrophage elastase
Ec Number:	3.4.24.65
Cas Number:	146888-86-0
Go Code:	0004234

Matrix metalloproteinase-12 (MMP-12) also known as macrophage metalloelastase (MME) or macrophage elastase (ME) is an enzyme that in humans is encoded by the MMP12 gene.^{[1] [2]}

Function

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. The prodomain is cleaved by extracellular proteinases when the enzyme is activated. The active enzyme is constituted by two domains, the catalytic domain responsible for its enzymatic activity and the hemopexin-like domain that in some MMPs plays a role in substrate recognition and can contribute to increasing catalytic efficiency. It is thought that the protein encoded by this gene is cleaved at both ends to yield the active enzyme, but this processing has not been fully described. The enzyme degrades soluble and insoluble elastin. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3.^[3]

Clinical significance

MMP12 may play a role in aneurysm formation^[4] and studies in mice and humans suggest a role in the development of emphysema.^[5]

Further reading

• Nagase H, Woessner JF . Matrix metalloproteinases . J. Biol. Chem. . 274 . 31 . 21491–4 . 1999 . 10419448 . 10.1074/jbc.274.31.21491 . free .
• Pendás AM, Santamaría I, Alvarez MV . Fine physical mapping of the human matrix metalloproteinase genes clustered on chromosome 11q22.3 . Genomics . 37 . 2 . 266–8 . 1997 . 8921407 . 10.1006/geno.1996.0557 .
• Gronski TJ, Martin RL, Kobayashi DK . Hydrolysis of a broad spectrum of extracellular matrix proteins by human macrophage elastase . J. Biol. Chem. . 272 . 18 . 12189–94 . 1997 . 9115292 . 10.1074/jbc.272.18.12189 . free .
• Edelstein C, Shapiro SD, Klezovitch O, Scanu AM . Macrophage metalloelastase, MMP-12, cleaves human apolipoprotein(a) in the linker region between kringles IV-4 and IV-5. Potential relevance to lipoprotein(a) biology . J. Biol. Chem. . 274 . 15 . 10019–23 . 1999 . 10187779 . 10.1074/jbc.274.15.10019 . free .
• Dias Neto E, Correa RG, Verjovski-Almeida S . Shotgun sequencing of the human transcriptome with ORF expressed sequence tags . Proc. Natl. Acad. Sci. U.S.A. . 97 . 7 . 3491–6 . 2000 . 10737800 . 10.1073/pnas.97.7.3491 . 16267 . 2000PNAS...97.3491D . free .
• Wert SE, Yoshida M, LeVine AM . Increased metalloproteinase activity, oxidant production and emphysema in surfactant protein D gene-inactivated mice . Proc. Natl. Acad. Sci. U.S.A. . 97 . 11 . 5972–7 . 2000 . 10801980 . 10.1073/pnas.100448997 . 18543 . 2000PNAS...97.5972W . free .
• Belaaouaj AA, Li A, Wun TC . Matrix metalloproteinases cleave tissue factor pathway inhibitor. Effects on coagulation . J. Biol. Chem. . 275 . 35 . 27123–8 . 2000 . 10859319 . 10.1074/jbc.M004218200 . free .
• Hiller O, Lichte A, Oberpichler A, etal . Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII . J. Biol. Chem. . 275 . 42 . 33008–13 . 2000 . 10930399 . 10.1074/jbc.M001836200 . free .
• Terp GE, Christensen IT, Jørgensen FS . Structural differences of matrix metalloproteinases. Homology modeling and energy minimization of enzyme-substrate complexes . J. Biomol. Struct. Dyn. . 17 . 6 . 933–46 . 2000 . 10949161 . 10.1080/07391102.2000.10506582. 1270176 .
• Agapova OA, Ricard CS, Salvador-Silva M, Hernandez MR . Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human optic nerve head astrocytes . Glia . 33 . 3 . 205–16 . 2001 . 11241738 . 10.1002/1098-1136(200103)33:3<205::AID-GLIA1019>3.0.CO;2-D . 25298272 .
• Lang R, Kocourek A, Braun M, etal . Substrate specificity determinants of human macrophage elastase (MMP-12) based on the 1.1 A crystal structure . J. Mol. Biol. . 312 . 4 . 731–42 . 2001 . 11575928 . 10.1006/jmbi.2001.4954 .
• Nar H, Werle K, Bauer MM, etal . Crystal structure of human macrophage elastase (MMP-12) in complex with a hydroxamic acid inhibitor . J. Mol. Biol. . 312 . 4 . 743–51 . 2001 . 11575929 . 10.1006/jmbi.2001.4953 .
• Joos L, He JQ, Shepherdson MB, etal . The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function . Hum. Mol. Genet. . 11 . 5 . 569–76 . 2002 . 11875051 . 10.1093/hmg/11.5.569 . free .
• Andolfo A, English WR, Resnati M, etal . Metalloproteases cleave the urokinase-type plasminogen activator receptor in the D1-D2 linker region and expose epitopes not present in the intact soluble receptor . Thromb. Haemost. . 88 . 2 . 298–306 . 2003 . 12195704 . 10.1055/s-0037-1613202. 374311 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Vos CM, van Haastert ES, de Groot CJ, etal . Matrix metalloproteinase-12 is expressed in phagocytotic macrophages in active multiple sclerosis lesions . J. Neuroimmunol. . 138 . 1–2 . 106–14 . 2003 . 12742660 . 10.1016/S0165-5728(03)00036-5 . 41777075 .
• Anghelina M, Schmeisser A, Krishnan P, etal . Migration of monocytes/macrophages in vitro and in vivo is accompanied by MMP12-dependent tunnel formation and by neovascularization . Cold Spring Harb. Symp. Quant. Biol. . 67 . 209–15 . 2003 . 12858542 . 10.1101/sqb.2002.67.209 .

External links

• The MEROPS online database for peptidases and their inhibitors: M10.009
• PDBe-KB provides an overview of all the structure information available in the PDB for Human Macrophage metalloelastase (MMP12)

Notes and References

1. Shapiro SD, Kobayashi DK, Ley TJ . Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages . J. Biol. Chem. . 268 . 32 . 23824–9 . November 1993 . 10.1016/S0021-9258(20)80459-1 . 8226919 . free .
2. Belaaouaj A, Shipley JM, Kobayashi DK, Zimonjic DB, Popescu N, Silverman GA, Shapiro SD . Human macrophage metalloelastase. Genomic organization, chromosomal location, gene linkage, and tissue-specific expression . J. Biol. Chem. . 270 . 24 . 14568–75 . June 1995 . 7782320 . 10.1074/jbc.270.24.14568. free .
3. Web site: Entrez Gene: MMP12 matrix metallopeptidase 12 (macrophage elastase).
4. Curci JA, Liao S, Huffman MD, Shapiro SD, Thompson RW . Expression and localization of macrophage elastase (matrix metalloproteinase-12) in abdominal aortic aneurysms . J. Clin. Invest. . 102 . 11 . 1900–10 . December 1998 . 9835614 . 509141 . 10.1172/JCI2182 .
5. Woodruff PG, Koth LL, Yang YH, Rodriguez MW, Favoreto S, Dolganov GM, Paquet AC, Erle DJ . A Distinctive Alveolar Macrophage Activation State Induced by Cigarette Smoking . Am. J. Respir. Crit. Care Med. . 172 . 11 . 1383–92 . December 2005 . 16166618 . 2718436 . 10.1164/rccm.200505-686OC .