Biology:Matrix metallopeptidase 12
| macrophage elastase | |||||||||
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| Identifiers | |||||||||
| EC number | 3.4.24.65 | ||||||||
| CAS number | 146888-86-0 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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 Generic protein structure example |
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][3]
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.[1]
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]
References
- ↑ 1.0 1.1 "Entrez Gene: MMP12 matrix metallopeptidase 12 (macrophage elastase)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4321.
- ↑ "Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages". J. Biol. Chem. 268 (32): 23824–9. November 1993. doi:10.1016/S0021-9258(20)80459-1. PMID 8226919.
- ↑ "Human macrophage metalloelastase. Genomic organization, chromosomal location, gene linkage, and tissue-specific expression". J. Biol. Chem. 270 (24): 14568–75. June 1995. doi:10.1074/jbc.270.24.14568. PMID 7782320.
- ↑ "Expression and localization of macrophage elastase (matrix metalloproteinase-12) in abdominal aortic aneurysms". J. Clin. Invest. 102 (11): 1900–10. December 1998. doi:10.1172/JCI2182. PMID 9835614.
- ↑ "A Distinctive Alveolar Macrophage Activation State Induced by Cigarette Smoking". Am. J. Respir. Crit. Care Med. 172 (11): 1383–92. December 2005. doi:10.1164/rccm.200505-686OC. PMID 16166618.
Further reading
- "Matrix metalloproteinases". J. Biol. Chem. 274 (31): 21491–4. 1999. doi:10.1074/jbc.274.31.21491. PMID 10419448.
- "Fine physical mapping of the human matrix metalloproteinase genes clustered on chromosome 11q22.3". Genomics 37 (2): 266–8. 1997. doi:10.1006/geno.1996.0557. PMID 8921407.
- "Hydrolysis of a broad spectrum of extracellular matrix proteins by human macrophage elastase". J. Biol. Chem. 272 (18): 12189–94. 1997. doi:10.1074/jbc.272.18.12189. PMID 9115292.
- "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. doi:10.1074/jbc.274.15.10019. PMID 10187779.
- "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. 2000. doi:10.1073/pnas.97.7.3491. PMID 10737800. Bibcode: 2000PNAS...97.3491D.
- "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. doi:10.1073/pnas.100448997. PMID 10801980. Bibcode: 2000PNAS...97.5972W.
- "Matrix metalloproteinases cleave tissue factor pathway inhibitor. Effects on coagulation". J. Biol. Chem. 275 (35): 27123–8. 2000. doi:10.1074/jbc.M004218200. PMID 10859319.
- "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. doi:10.1074/jbc.M001836200. PMID 10930399.
- "Structural differences of matrix metalloproteinases. Homology modeling and energy minimization of enzyme-substrate complexes". J. Biomol. Struct. Dyn. 17 (6): 933–46. 2000. doi:10.1080/07391102.2000.10506582. PMID 10949161.
- "Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human optic nerve head astrocytes". Glia 33 (3): 205–16. 2001. doi:10.1002/1098-1136(200103)33:3<205::AID-GLIA1019>3.0.CO;2-D. PMID 11241738.
- "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. doi:10.1006/jmbi.2001.4954. PMID 11575928.
- "Crystal structure of human macrophage elastase (MMP-12) in complex with a hydroxamic acid inhibitor". J. Mol. Biol. 312 (4): 743–51. 2001. doi:10.1006/jmbi.2001.4953. PMID 11575929.
- "The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function". Hum. Mol. Genet. 11 (5): 569–76. 2002. doi:10.1093/hmg/11.5.569. PMID 11875051.
- "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. doi:10.1055/s-0037-1613202. PMID 12195704.
- "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. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Matrix metalloproteinase-12 is expressed in phagocytotic macrophages in active multiple sclerosis lesions". J. Neuroimmunol. 138 (1–2): 106–14. 2003. doi:10.1016/S0165-5728(03)00036-5. PMID 12742660.
- "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. doi:10.1101/sqb.2002.67.209. PMID 12858542.
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)
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