Macrophage metalloelastase

Function

May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.

Classification

Family (Pfam)

PF00045 Hemopexin, PF00413 Peptidase_M10, PF01471 PG_binding_1

InterPro

Hemopexin-like_dom, Hemopexin-like_dom_sf, Hemopexin-like_repeat, Hemopexin_CS, M10A_MMP, MetalloPept_cat_dom_sf, Pept_M10_metallopeptidase, Pept_M10A, Pept_M10A_Zn_BS, Peptidase_Metallo, Peptidoglycan-bd-like, PGBD-like_sf

Functional cluster

Venom Serine Proteases & Phospholipase A2

Experimental structures · PDB · 86

• 1JIZ X-ray 2.60A
• 1JK3 X-ray 1.09A
• 1OS2 X-ray 2.15A
• 1OS9 X-ray 1.85A
• 1RMZ X-ray 1.34A
• 1ROS X-ray 2.00A
• 1UTT X-ray 2.20A
• 1UTZ X-ray 2.50A
• 1Y93 X-ray 1.03A
• 1YCM NMR
• 1Z3J NMR
• 2HU6 X-ray 1.32A
• … and 74 more

A predicted model is available from AlphaFold.

Gene Ontology · 30

• GO:0005737 cytoplasm
• GO:0031012 extracellular matrix
• GO:0005576 extracellular region
• GO:0005615 extracellular space
• GO:0005634 nucleus
• GO:0005509 calcium ion binding
• GO:0005518 collagen binding
• GO:0001046 core promoter sequence-specific DNA binding
• GO:0004175 endopeptidase activity
• GO:0004222 metalloendopeptidase activity
• GO:0043565 sequence-specific DNA binding
• GO:0004252 serine-type endopeptidase activity
• GO:0008270 zinc ion binding
• GO:0098586 cellular response to virus
• GO:0030574 collagen catabolic process
• GO:0060309 elastin catabolic process
• GO:0022617 extracellular matrix disassembly
• GO:0030198 extracellular matrix organization
• GO:1904905 negative regulation of endothelial cell-matrix adhesion
• GO:0000122 negative regulation of transcription by RNA polymerase II
• GO:0060339 negative regulation of type I interferon-mediated signaling pathway
• GO:0060054 positive regulation of epithelial cell proliferation involved in wound healing
• GO:0032727 positive regulation of interferon-alpha production
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0060340 positive regulation of type I interferon-mediated signaling pathway
• GO:0006606 protein import into nucleus
• GO:0006508 proteolysis
• GO:0050691 regulation of defense response to virus by host
• GO:1904645 response to amyloid-beta
• GO:0035313 wound healing, spreading of epidermal cells

Drugs targeting this protein · 3

• MARIMASTAT inhibitor
• AZD-1236 inhibitor
• CTS-1027 inhibitor

Related proteins · sequence + function similarity

• Macrophage metalloelastase 0.97
• Macrophage metalloelastase 0.95
• Macrophage metalloelastase 0.94
• Matrix metalloproteinase-20 0.94
• Stromelysin-2 0.93
• Matrix metalloproteinase-27 0.93
• Interstitial collagenase 0.93
• Matrix metalloproteinase-27 0.93
• Matrix metalloproteinase-20 0.93
• Stromelysin-1 0.93
• Stromelysin-2 0.92
• Collagenase 3 0.92

Literature · 6 cited papers

• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
• Crystal structure of human macrophage elastase (MMP-12) in complex with a hydroxamic acid inhibitor. J. Mol. Biol. · 2001
• Substrate specificity determinants of human macrophage elastase (MMP-12) based on the 1.1 A crystal structure. J. Mol. Biol. · 2001
• Hydrolysis of a broad spectrum of extracellular matrix proteins by human macrophage elastase. J. Biol. Chem. · 1997
• Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages. J. Biol. Chem. · 1993