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matrix metalloproteinase-9 (matrixin-9, 92 kD gelatinase, gelatinase-B, MMP9, CLG4B)

Function: 1) role in local proteolysis of the extracellular matrix & in leukocyte migration 2) monomer, disulfide-linked homodimer, & heterodimer with a 25 kD protein 3) substrates: a) collagen-4 & collagen-5 b) gelatin types 1 & 5 c) elastin d) laminin e) pro-TNF-alpha f) amyloid A4 peptide g) TGF-beta 4) inhibited by histatin-3 1/24 (histatin-5) 5) processing of the precursor yields different active forms of 64, 67 & 82 kD 6) sequentially processing by MMP3 yields the 82 kD matrix metalloproteinase-9 7) S-nitrosylation activated MMP9 in vitro & induced neuronal apoptosis [5] Cofactor: - binds 2 Zn+2 per subunit - binds 3 Ca+2 per subunit Compartment: extracellular matrix Expression: - alveolar macrophages; macrophages & transformed cell lines produce only the monomeric form - granulocytes - activated by 4-aminophenylmercuric acetate & phorbol ester Pathology: - polymorphism in promoter region of gene associated with severity of atherosclerosis in patients with coronary artery disease & possibly development of pulmonary emphysema in smokers - elevated in stroke - elevated in CSF in multiple sclerosis - elevated levels in synovial fluid of arthritis patients a) may contribute to the pathogenesis of joint destruction b) may be useful marker of disease status - elevated in asthma Laboratory: - matrix metallopeptidase 9 in serum - matrix metallopeptidase 9 in blood

General

collagenase-4 or gelatinase matrixin or matrix metalloproteinase

Properties

SIZE: entity length = 707 aa MW = 78 kD COMPARTMENT: extracellular matrix MOTIF: signal sequence {1-19} N-glycosylation site {N38} peptide motif {59-60} Cysteine switch {97-104} MOTIF: Zn+2-binding site SITE: 99-99 peptide motif {106-107} N-glycosylation site {N120} N-glycosylation site {N127} Ca+2-binding site SITE: 131-131 Ca+2-binding site SITE: 165-165 Zn+2-binding site SITE: 175-175 Zn+2-binding site SITE: 177-177 Ca+2-binding site SITE: 182-182 Ca+2-binding site SITE: 183-183 Ca+2-binding site SITE: 185-185 Ca+2-binding site SITE: 187-187 Zn+2-binding site SITE: 190-190 Ca+2-binding site SITE: 197-197 Ca+2-binding site SITE: 199-199 Ca+2-binding site SITE: 201-201 Zn+2-binding site SITE: 203-203 Ca+2-binding site SITE: 205-205 Ca+2-binding site SITE: 206-206 Ca+2-binding site SITE: 208-208 fibronectin type II domain or F2 module SITE: 225-273 FOR-BINDING-OF: collagen MOTIF: cysteine residue {*1} MODIFICATION: cysteine residue {*3} cysteine residue {*2} MODIFICATION: cysteine residue {*4} cysteine residue {*3} MODIFICATION: cysteine residue {*1} cysteine residue {*4} MODIFICATION: cysteine residue {*2} cysteine residue {C230} MODIFICATION: cysteine residue {C256} cysteine residue {C244} MODIFICATION: cysteine residue {C271} cysteine residue {C256} MODIFICATION: cysteine residue {C230} cysteine residue {C271} MODIFICATION: cysteine residue {C244} fibronectin type II domain or F2 module SITE: 283-331 FOR-BINDING-OF: collagen MOTIF: cysteine residue {*1} MODIFICATION: cysteine residue {*3} cysteine residue {*2} MODIFICATION: cysteine residue {*4} cysteine residue {*3} MODIFICATION: cysteine residue {*1} cysteine residue {*4} MODIFICATION: cysteine residue {*2} cysteine residue {C288} MODIFICATION: cysteine residue {C314} cysteine residue {C302} MODIFICATION: cysteine residue {C329} cysteine residue {C314} MODIFICATION: cysteine residue {C288} cysteine residue {C329} MODIFICATION: cysteine residue {C302} fibronectin type II domain or F2 module SITE: 342-390 FOR-BINDING-OF: collagen MOTIF: cysteine residue {*1} MODIFICATION: cysteine residue {*3} cysteine residue {*2} MODIFICATION: cysteine residue {*4} cysteine residue {*3} MODIFICATION: cysteine residue {*1} cysteine residue {*4} MODIFICATION: cysteine residue {*2} cysteine residue {C347} MODIFICATION: cysteine residue {C373} cysteine residue {C361} MODIFICATION: cysteine residue {C388} cysteine residue {C373} MODIFICATION: cysteine residue {C347} cysteine residue {C388} MODIFICATION: cysteine residue {C361} Zn+2-binding site SITE: 401-401 glutamate residue {E402} Zn+2-binding site SITE: 405-405 Zn+2-binding site SITE: 411-411 cysteine residue {C516} MODIFICATION: cysteine residue {C704} Hemopexin-like 1 {521-565} Hemopexin-like 2 {567-608} Hemopexin-like 3 {613-659} Hemopexin-like 4 {661-704} MOTIF: cysteine residue {C704} MODIFICATION: cysteine residue {C516}

Database Correlations

OMIM 120361 UniProt P14780 PFAM correlations Entrez Gene 4318 KEGG correlations ENZYME 3.4.24.35

References

  1. Selkoe DJ. Clearing the brain's amyloid cobwebs. Neuron. 2001 Oct 25;32(2):177-80. Review. PMID: 11683988
  2. UniProt :accession P14780
  3. OMIM :accession 120361
  4. Chang C, Werb Z. The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis. Trends Cell Biol. 2001 Nov;11(11):S37-43. Review. PMID: 11684441
  5. Gu Z, Kaul M, Yan B, Kridel SJ, Cui J, Strongin A, Smith JW, Liddington RC, Lipton SA. S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death. Science. 2002 Aug 16;297(5584):1186-90. PMID: 12183632
  6. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/MMP9ID41408ch20q11.html
  7. SeattleSNPs http://pga.gs.washington.edu/data/mmp9/