Matrix metallopeptidase 12

macrophage elastase
Identifiers
EC no.	3.4.24.65
CAS no.	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
Search PMC articles PubMed articles NCBI proteins

MMP12
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1JIZ, 1JK3, 1OS2, 1OS9, 1RMZ, 1ROS, 1UTT, 1UTZ, 1Y93, 1YCM, 1Z3J, 2HU6, 2JXY, 2K2G, 2K9C, 2KRJ, 2MLR, 2MLS, 2OXU, 2OXW, 2OXZ, 2POJ, 2W0D, 2WO8, 2WO9, 2WOA, 2Z2D, 3BA0, 3EHX, 3EHY, 3F15, 3F16, 3F17, 3F18, 3F19, 3F1A, 3LIK, 3LIL, 3LIR, 3LJG, 3LK8, 3LKA, 3N2U, 3N2V, 3NX7, 3RTS, 3RTT, 3TS4, 3TSK, 3UVC, 4EFS, 4GQL, 4GR0, 4GR3, 4GR8, 4GUY, 4H30, 4H49, 4H76, 4H84, 4I03, 4IJO, 2N8R, 5I4O, 5I0L, 5I2Z, 5I3M, 5I43
Identifiers
Aliases	MMP12, HME, ME, MME, MMP-12, Matrix metallopeptidase 12
External IDs	OMIM: 601046; MGI: 97005; HomoloGene: 20547; GeneCards: MMP12; OMA:MMP12 - orthologs
Gene location (Human) Chr. Chromosome 11 (human) Band 11q22.2 Start 102,862,736 bp End 102,874,982 bp
Gene location (Mouse) Chr. Chromosome 9 (mouse) Band 9 A1|9 2.46 cM Start 7,344,381 bp End 7,369,499 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in periodontal fiber mucosa of ileum mucosa of sigmoid colon decidua cartilage tissue appendix amniotic fluid rectum testicle epithelium of nasopharynx Top expressed in zygote secondary oocyte lactiferous gland embryo calvaria embryo blastocyst primary oocyte right kidney adrenal gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptidase activity endopeptidase activity hydrolase activity metallopeptidase activity metal ion binding serine-type endopeptidase activity metalloendopeptidase activity calcium ion binding collagen binding zinc ion binding sequence-specific DNA binding Cellular component extracellular matrix extracellular region extracellular space nucleus cytoplasm Biological process collagen catabolic process wound healing, spreading of epidermal cells extracellular matrix disassembly positive regulation of epithelial cell proliferation involved in wound healing wound healing negative regulation of transcription by RNA polymerase II proteolysis protein import into nucleus positive regulation of gene expression positive regulation of transcription by RNA polymerase II regulation of defense response to virus by host negative regulation of type I interferon-mediated signaling pathway positive regulation of type I interferon-mediated signaling pathway cellular response to virus response to hypoxia elastin catabolic process negative regulation of endothelial cell-matrix adhesion via fibronectin extracellular matrix organization response to amyloid-beta Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4321 17381 Ensembl ENSG00000262406 ENSMUSG00000049723 UniProt P39900 P34960 RefSeq (mRNA) NM_002426 NM_008605 NM_001320076 NM_001320077 RefSeq (protein) NP_002417 NP_001307005 NP_001307006 NP_032631 Location (UCSC) Chr 11: 102.86 – 102.87 Mb Chr 9: 7.34 – 7.37 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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.

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.

Clinical significance

MMP12 may play a role in aneurysm formation and studies in mice and humans suggest a role in the development of emphysema.

Further reading

• Nagase H, Woessner JF (1999). "Matrix metalloproteinases". J. Biol. Chem. 274 (31): 21491–4. doi:10.1074/jbc.274.31.21491. PMID 10419448.
• Pendás AM, Santamaría I, Alvarez MV (1997). "Fine physical mapping of the human matrix metalloproteinase genes clustered on chromosome 11q22.3". Genomics. 37 (2): 266–8. doi:10.1006/geno.1996.0557. PMID 8921407.
• Gronski TJ, Martin RL, Kobayashi DK (1997). "Hydrolysis of a broad spectrum of extracellular matrix proteins by human macrophage elastase". J. Biol. Chem. 272 (18): 12189–94. doi:10.1074/jbc.272.18.12189. PMID 9115292.
• Edelstein C, Shapiro SD, Klezovitch O, Scanu AM (1999). "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. doi:10.1074/jbc.274.15.10019. PMID 10187779.
• Dias Neto E, Correa RG, Verjovski-Almeida S (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. Bibcode:2000PNAS...97.3491D. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800.
• Wert SE, Yoshida M, LeVine AM (2000). "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. Bibcode:2000PNAS...97.5972W. doi:10.1073/pnas.100448997. PMC 18543. PMID 10801980.
• Belaaouaj AA, Li A, Wun TC (2000). "Matrix metalloproteinases cleave tissue factor pathway inhibitor. Effects on coagulation". J. Biol. Chem. 275 (35): 27123–8. doi:10.1074/jbc.M004218200. PMID 10859319.
• Hiller O, Lichte A, Oberpichler A, et al. (2000). "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. doi:10.1074/jbc.M001836200. PMID 10930399.
• Terp GE, Christensen IT, Jørgensen FS (2000). "Structural differences of matrix metalloproteinases. Homology modeling and energy minimization of enzyme-substrate complexes". J. Biomol. Struct. Dyn. 17 (6): 933–46. doi:10.1080/07391102.2000.10506582. PMID 10949161. S2CID 1270176.
• Agapova OA, Ricard CS, Salvador-Silva M, Hernandez MR (2001). "Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human optic nerve head astrocytes". Glia. 33 (3): 205–16. doi:10.1002/1098-1136(200103)33:3<205::AID-GLIA1019>3.0.CO;2-D. PMID 11241738. S2CID 25298272.
• Lang R, Kocourek A, Braun M, et al. (2001). "Substrate specificity determinants of human macrophage elastase (MMP-12) based on the 1.1 A crystal structure". J. Mol. Biol. 312 (4): 731–42. doi:10.1006/jmbi.2001.4954. PMID 11575928.
• Nar H, Werle K, Bauer MM, et al. (2001). "Crystal structure of human macrophage elastase (MMP-12) in complex with a hydroxamic acid inhibitor". J. Mol. Biol. 312 (4): 743–51. doi:10.1006/jmbi.2001.4953. PMID 11575929.
• Joos L, He JQ, Shepherdson MB, et al. (2002). "The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function". Hum. Mol. Genet. 11 (5): 569–76. doi:10.1093/hmg/11.5.569. PMID 11875051.
• Andolfo A, English WR, Resnati M, et al. (2003). "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. doi:10.1055/s-0037-1613202. PMID 12195704. S2CID 374311.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Vos CM, van Haastert ES, de Groot CJ, et al. (2003). "Matrix metalloproteinase-12 is expressed in phagocytotic macrophages in active multiple sclerosis lesions". J. Neuroimmunol. 138 (1–2): 106–14. doi:10.1016/S0165-5728(03)00036-5. PMID 12742660. S2CID 41777075.
• Anghelina M, Schmeisser A, Krishnan P, et al. (2003). "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. 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)