Matrix metalloproteinase-9

Function

Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption (By similarity). Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves NINJ1 to generate the Secreted ninjurin-1 form. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.

Classification

Family (Pfam)

PF00040 fn2, PF00045 Hemopexin, PF00413 Peptidase_M10

InterPro

FN_type2_dom, FN_type2_sf, Hemopexin-like_dom, Hemopexin-like_dom_sf, Hemopexin-like_repeat, Hemopexin_CS, Kringle-like, M10A_MMP, MetalloPept_cat_dom_sf, Pept_M10_metallopeptidase, Pept_M10A, Pept_M10A_Zn_BS, Peptidase_Metallo, PGBD-like_sf

Functional cluster

Venom Serine Proteases & Phospholipase A2

Experimental structures · PDB · 29

• 1GKC X-ray 2.30A
• 1GKD X-ray 2.10A
• 1ITV X-ray 1.95A
• 1L6J X-ray 2.50A
• 2OVX X-ray 2.00A
• 2OVZ X-ray 2.00A
• 2OW0 X-ray 2.00A
• 2OW1 X-ray 2.20A
• 2OW2 X-ray 2.90A
• 4H1Q X-ray 1.59A
• 4H2E X-ray 2.90A
• 4H3X X-ray 1.76A
• … and 17 more

A predicted model is available from AlphaFold.

Gene Ontology · 36

• GO:0070062 extracellular exosome
• GO:0031012 extracellular matrix
• GO:0005576 extracellular region
• GO:0005615 extracellular space
• GO:1904813 ficolin-1-rich granule lumen
• GO:1904724 tertiary granule lumen
• GO:0005518 collagen binding
• GO:0004175 endopeptidase activity
• GO:0042802 identical protein binding
• GO:0004222 metalloendopeptidase activity
• GO:0008237 metallopeptidase activity
• GO:0008233 peptidase activity
• GO:0004252 serine-type endopeptidase activity
• GO:0008270 zinc ion binding
• GO:0016477 cell migration
• GO:0071222 cellular response to lipopolysaccharide
• GO:0071492 cellular response to UV-A
• GO:0030574 collagen catabolic process
• GO:0035987 endodermal cell differentiation
• GO:0048013 ephrin receptor signaling pathway
• GO:0022617 extracellular matrix disassembly
• GO:0030198 extracellular matrix organization
• GO:0030225 macrophage differentiation
• GO:0043066 negative regulation of apoptotic process
• GO:1904063 negative regulation of cation transmembrane transport
• GO:2000697 negative regulation of epithelial cell differentiation involved in kidney development
• GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
• GO:0043388 positive regulation of DNA binding
• GO:0045742 positive regulation of epidermal growth factor receptor signaling pathway
• GO:0051549 positive regulation of keratinocyte migration
• GO:0001934 positive regulation of protein phosphorylation
• GO:0090200 positive regulation of release of cytochrome c from mitochondria
• GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation
• GO:0006508 proteolysis
• GO:0150077 regulation of neuroinflammatory response
• GO:1904645 response to amyloid-beta

Disease associations

• intervertebral disk degenerative disorder MONDO:0011385
• metaphyseal anadysplasia 2 MONDO:0013113

Drugs targeting this protein · 4

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

Related proteins · sequence + function similarity

• Matrix metalloproteinase-9 0.98
• Matrix metalloproteinase-9 0.97
• Matrix metalloproteinase-9 0.97
• Matrix metalloproteinase-9 0.96
• Matrix metalloproteinase-9 0.94
• 72 kDa type IV collagenase 0.87
• 72 kDa type IV collagenase 0.87
• 72 kDa type IV collagenase 0.87
• 72 kDa type IV collagenase 0.86
• 72 kDa type IV collagenase 0.85
• 72 kDa type IV collagenase 0.83
• Matrix metalloproteinase-19 0.82

Co-cited proteins · studied together in the literature

• Staphylococcal superantigen-like 5 2 shared papers
• Neutrophil gelatinase-associated lipocalin 2 shared papers
• Thrombospondin-2 1 shared papers
• Stromelysin-1 1 shared papers
• Extracellular matrix protein 1 1 shared papers
• Collagenase 3 1 shared papers
• Gingipain R2 1 shared papers
• Cell surface glycolipoprotein MPB83 1 shared papers
• Metalloproteinase inhibitor 1 1 shared papers
• 72 kDa type IV collagenase 2 shared papers
• Matrix metalloproteinase-9 2 shared papers
• Metastasis-suppressor KiSS-1 1 shared papers

Literature · 32 cited papers

• Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells. Cell Commun. Signal. · 2021
• Anti-inflammatory actions of soluble ninjurin-1 ameliorate atherosclerosis. Circulation · 2020
• Role of sialic acid-containing glycans of matrix metalloproteinase-9 (MMP-9) in the interaction between MMP-9 and staphylococcal superantigen-like protein 5. Microbiol. Immunol. · 2018
• Non-acylated Mycobacterium bovis glycoprotein MPB83 binds to TLR1/2 and stimulates production of matrix metalloproteinase 9. Biochem. Biophys. Res. Commun. · 2010
• Staphylococcal superantigen-like protein 5 inhibits matrix metalloproteinase 9 from human neutrophils. Infect. Immun. · 2010
• The adenomatous polyposis coli-associated exchange factors Asef and Asef2 are required for adenoma formation in Apc(Min/+)mice. EMBO Rep. · 2009
• Mutations in MMP9 and MMP13 determine the mode of inheritance and the clinical spectrum of metaphyseal anadysplasia. Am. J. Hum. Genet. · 2009
• A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation. Am. J. Hum. Genet. · 2008
• Extracellular matrix protein 1 inhibits the activity of matrix metalloproteinase 9 through high-affinity protein/protein interactions. Exp. Dermatol. · 2006
• 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
• Cleavage of metastasis suppressor gene product KiSS-1 protein/metastin by matrix metalloproteinases. Oncogene · 2003
• … and 20 more in the literature graph