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matrix metalloproteinase-1; matrixin-1; interstitial collagenase; fibroblast collagenase (MMP1, CLG)

Function: - cleaves collagens of types 1, 2, & 3 at one site in the helical domain - also cleaves collagens of types 7 & 10 - in case of HIV infection, interacts & cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity - can be activated without removal of the activation peptide - undergoes autolytic cleavage to two major forms (22 kD & 27 kD (a minor form (25 kD) is the glycosylated form of the 22 kD form) - the 27 kD form has no activity while the 22/25 kD form can act as activator for collagenase - cleavage of the triple helix of collagen at about 3/4 of the length of the molecule from the N-terminus, at 775-Gly-|-Ile-776 in the alpha-1(I) chain - cleaves synthetic substrates & alpha-macroglobulins at bonds where P1' is a hydrophobic residue Cofactor: - binds 4 Ca+2 per subunit - binds 2 Zn+2 per subunit Structure: - two distinct domains in this protein a) catalytic N-terminal b) C-terminal, involved in substrate specificity & in binding TIMP (tissue inhibitor of metalloproteinases) - conserved cysteine present in the cysteine-switch motif binds the catalytic Zn+2, thus inhibiting the enzyme; dissociation of the cysteine from the Zn+2 upon the activation-peptide release activates the enzyme - belongs to the peptidase M10A family - contains 4 hemopexin-like domains Compartment: secreted

General

matrixin or matrix metalloproteinase

Properties

SIZE: entity length = 469 aa MW = 54 kD COMPARTMENT: extracellular matrix MOTIF: signal sequence {1-19} Cysteine switch {90-97} MOTIF: Zn+2-binding site SITE: 92-92 Metalloprotease {98-276} MOTIF: N-glycosylation site {N120} Ca+2-binding site SITE: 124-124 Ca+2-binding site SITE: 158-158 Zn+2-binding site SITE: 168-168 Zn+2-binding site SITE: 170-170 Ca+2-binding site SITE: 175-175 Ca+2-binding site SITE: 176-176 Ca+2-binding site SITE: 178-178 Ca+2-binding site SITE: 180-180 Zn+2-binding site SITE: 183-183 Ca+2-binding site SITE: 190-190 Ca+2-binding site SITE: 192-192 Ca+2-binding site SITE: 194-194 Zn+2-binding site SITE: 196-196 Ca+2-binding site SITE: 198-198 Ca+2-binding site SITE: 199-199 Ca+2-binding site SITE: 201-201 Zn+2-binding site SITE: 218-218 glutamate residue {E219} Zn+2-binding site SITE: 222-222 Zn+2-binding site SITE: 228-228 peptide motif {269-270} cysteine residue {C278} MODIFICATION: cysteine residue {C466} Hemopexin-like 1 {284-326} MOTIF: Ca+2-binding site SITE: 285-285 Hemopexin-like 2 {328-372} MOTIF: Ca+2-binding site SITE: 329-329 Hemopexin-like 3 {377-424} MOTIF: Ca+2-binding site SITE: 378-378 Hemopexin-like 4 {426-466} MOTIF: Ca+2-binding site SITE: 427-427 cysteine residue {C466} MODIFICATION: cysteine residue {C278}

Database Correlations

OMIM 120353 UniProt P03956 PFAM correlations Entrez Gene 4312 Kegg hsa:4312 ENZYME 3.4.24.7

References

  1. UniProt :accession P03956
  2. Wikipedia; Note: collagenase entry http://en.wikipedia.org/wiki/collagenase