Matrix metallopeptidase 12

Enzyme involved in breakdown of extracellular matrix, encoded for by the MMP12 gene in humans
macrophage elastase
Identifiers
EC no.3.4.24.65
CAS no.146888-86-0
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins
MMP12
Available structures
PDBOrtholog 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
AliasesMMP12, HME, ME, MME, MMP-12, Matrix metallopeptidase 12
External IDsOMIM: 601046 MGI: 97005 HomoloGene: 20547 GeneCards: MMP12
Gene location (Human)
Chromosome 11 (human)
Chr.Chromosome 11 (human)[1]
Chromosome 11 (human)
Genomic location for MMP12
Genomic location for MMP12
Band11q22.2Start102,862,736 bp[1]
End102,874,982 bp[1]
Gene location (Mouse)
Chromosome 9 (mouse)
Chr.Chromosome 9 (mouse)[2]
Chromosome 9 (mouse)
Genomic location for MMP12
Genomic location for MMP12
Band9 A1|9 2.46 cMStart7,344,381 bp[2]
End7,369,499 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • periodontal fiber

  • appendix

  • amniotic fluid

  • rectum

  • palpebral conjunctiva

  • gums

  • lymph node

  • stromal cell of endometrium

  • thymus

  • duodenum
Top expressed in
  • secondary oocyte

  • calvaria

  • adrenal gland

  • blastocyst

  • white adipose tissue

  • spleen

  • lip

  • thymus

  • skin of abdomen

  • yolk sac
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
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

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]

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. ^ a b c GRCh38: Ensembl release 89: ENSG00000262406 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b "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. doi:10.1016/S0021-9258(20)80459-1. 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

  • 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)
  • v
  • t
  • e
  • 1jiz: Crystal Structure Analysis of human Macrophage Elastase MMP-12
    1jiz: Crystal Structure Analysis of human Macrophage Elastase MMP-12
  • 1jk3: Crystal structure of human MMP-12 (Macrophage Elastase) at true atomic resolution
    1jk3: Crystal structure of human MMP-12 (Macrophage Elastase) at true atomic resolution
  • 1os2: Ternary enzyme-product-inhibitor complexes of human MMP12
    1os2: Ternary enzyme-product-inhibitor complexes of human MMP12
  • 1os9: Binary enzyme-product complexes of human MMP12
    1os9: Binary enzyme-product complexes of human MMP12
  • 1rmz: Crystal structure of the catalytic domain of human MMP12 complexed with the inhibitor NNGH at 1.3 A resolution
    1rmz: Crystal structure of the catalytic domain of human MMP12 complexed with the inhibitor NNGH at 1.3 A resolution
  • 1ros: Crystal structure of MMP-12 complexed to 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl-4-(4-ethoxy[1,1-biphenyl]-4-yl)-4-oxobutanoic acid
    1ros: Crystal structure of MMP-12 complexed to 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl-4-(4-ethoxy[1,1-biphenyl]-4-yl)-4-oxobutanoic acid
  • 1utt: CRYSTAL STRUCTURE OF MMP-12 COMPLEXED TO 2-(1,3-DIOXO-1,3-DIHYDRO-2H-ISOINDOL-2-YL)ETHYL-4-(4-ETHOXY[1,1-BIPHENYL]-4-YL)-4-OXOBUTANOIC ACID
    1utt: CRYSTAL STRUCTURE OF MMP-12 COMPLEXED TO 2-(1,3-DIOXO-1,3-DIHYDRO-2H-ISOINDOL-2-YL)ETHYL-4-(4-ETHOXY[1,1-BIPHENYL]-4-YL)-4-OXOBUTANOIC ACID
  • 1utz: CRYSTAL STRUCTURE OF MMP-12 COMPLEXED TO (2R)-3-({[4-[(PYRI DIN-4-YL)PHENYL]-THIEN-2-YL}CARBOXAMIDO)(PHENYL)PROPANOIC ACID
    1utz: CRYSTAL STRUCTURE OF MMP-12 COMPLEXED TO (2R)-3-({[4-[(PYRI DIN-4-YL)PHENYL]-THIEN-2-YL}CARBOXAMIDO)(PHENYL)PROPANOIC ACID
  • 1y93: Crystal structure of the catalytic domain of human MMP12 complexed with acetohydroxamic acid at atomic resolution
    1y93: Crystal structure of the catalytic domain of human MMP12 complexed with acetohydroxamic acid at atomic resolution
  • 1ycm: Solution Structure of matrix metalloproteinase 12 (MMP12) in the presence of N-Isobutyl-N-[4-methoxyphenylsulfonyl]glycyl hydroxamic acid (NNGH)
    1ycm: Solution Structure of matrix metalloproteinase 12 (MMP12) in the presence of N-Isobutyl-N-[4-methoxyphenylsulfonyl]glycyl hydroxamic acid (NNGH)
  • 1z3j: Solution Structure of MMP12 in the presence of N-isobutyl-N-4-methoxyphenylsulfonyl]glycyl hydroxamic acid (NNGH)
    1z3j: Solution Structure of MMP12 in the presence of N-isobutyl-N-4-methoxyphenylsulfonyl]glycyl hydroxamic acid (NNGH)
  • 2hu6: Crystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitor
    2hu6: Crystal structure of human MMP-12 in complex with acetohydroxamic acid and a bicyclic inhibitor
  • 2oxu: Uninhibited form of human MMP-12
    2oxu: Uninhibited form of human MMP-12
  • 2oxw: Human MMP-12 complexed with the peptide IAG
    2oxw: Human MMP-12 complexed with the peptide IAG
  • 2oxz: Human MMP-12 in complex with two peptides PQG and IAG
    2oxz: Human MMP-12 in complex with two peptides PQG and IAG
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