Matrix metallopeptidase 12

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.[5][6][7]

macrophage elastase
Identifiers
EC number3.4.24.65
CAS number146888-86-0
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
MMP12
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMMP12, HME, ME, MME, MMP-12, Matrix metallopeptidase 12
External IDsOMIM: 601046 MGI: 97005 HomoloGene: 20547 GeneCards: MMP12
Gene location (Human)
Chr.Chromosome 11 (human)[1]
Band11q22.2Start102,862,736 bp[1]
End102,874,982 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
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 MbChr 9: 7.34 – 7.37 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5]

Clinical significance

MMP12 may play a role in aneurysm formation[8] and studies in mice and humans suggest a role in the development of emphysema.[9]

References

  1. GRCh38: Ensembl release 89: ENSG00000262406 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000049723 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: MMP12 matrix metallopeptidase 12 (macrophage elastase)".
  6. Shapiro SD, Kobayashi DK, Ley TJ (November 1993). "Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages". J. Biol. Chem. 268 (32): 23824–9. PMID 8226919.
  7. Belaaouaj A, Shipley JM, Kobayashi DK, Zimonjic DB, Popescu N, Silverman GA, Shapiro SD (June 1995). "Human macrophage metalloelastase. Genomic organization, chromosomal location, gene linkage, and tissue-specific expression". J. Biol. Chem. 270 (24): 14568–75. doi:10.1074/jbc.270.24.14568. PMID 7782320.
  8. Curci JA, Liao S, Huffman MD, Shapiro SD, Thompson RW (December 1998). "Expression and localization of macrophage elastase (matrix metalloproteinase-12) in abdominal aortic aneurysms". J. Clin. Invest. 102 (11): 1900–10. doi:10.1172/JCI2182. PMC 509141. PMID 9835614.
  9. Woodruff PG, Koth LL, Yang YH, Rodriguez MW, Favoreto S, Dolganov GM, Paquet AC, Erle DJ (December 2005). "A Distinctive Alveolar Macrophage Activation State Induced by Cigarette Smoking". Am. J. Respir. Crit. Care Med. 172 (11): 1383–92. doi:10.1164/rccm.200505-686OC. PMC 2718436. PMID 16166618.

Further reading

  • 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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