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Literature summary for 3.4.24.80 extracted from
- Coordinate action of membrane-type matrix metalloproteinase -1 (MT1-MMP) and MMP-2 enhances pericellular proteolysis and invasion (2010), Cancer Sci., 101, 843-847.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| claudin | recruits MT-MMP and MMP-2 at a tight junction to achieve elevated focal concentrations, and consequently enhances activation of pro-MMP-2 | Mus musculus | |
| claudin | recruits MT-MMP and MMP-2 at a tight junction to achieve elevated focal concentrations, and consequently enhances activation of pro-MMP-2 | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | a MT1-MMP-deficient mouse produces only a faint level of active MMP-2. MT1-MMP-null mice have severe defects in skeletal development and angiogenesis and die within several weeks after birth, phenotype, overview | Mus musculus |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| additional information | MT1-MMP is inhibited by endogenous inhibitors TIMP-2, -3, and -4, but not by TIMP-1. MT1-MMP on cell surface rapidly turns over by auto-degradation or clathrin-dependent internalization. MT1-MMP inactivated by TIMP-2 avoids auto-degradation, and accumulates on the cell surface, overview | Homo sapiens | |
| additional information | MT1-MMP on cell surface rapidly turns over by auto-degradation or clathrin-dependent internalization. MT1-MMP inactivated by TIMP-2 avoids auto-degradation, and accumulates on the cell surface, overview | Mus musculus | |
| tissue inhibitor of MMP-2 | MMP-2 activation involves tissue inhibitor of MMP-2, i.e. TIMP-2, as a bridging molecule between MT1-MMP and pro-MMP-2. Thus, net activity of MT1-MMP and MMP-2 is regulated in a complex manner depending on TIMP-2 concentration. MT1-MMP auto-degradation is suppressed in the presence of TIMP-2, and MT1-MMP/TIMP-2 complex accumulates on cell surface. MT1-MMP cannot cleave other direct substrates at the TIMP-2 level that induces efficient pro-MMP-2 processing | Homo sapiens | |
| tissue inhibitor of MMP-2 | MMP-2 activation involves tissue inhibitor of MMP-2, i.e. TIMP-2, as a bridging molecule between MT1-MMP and pro-MMP-2. Thus, net activity of MT1-MMP and MMP-2 is regulated in a complex manner depending on TIMP-2 concentration. MT1-MMP auto-degradation is suppressed in the presence of TIMP-2, and MT1-MMP/TIMP-2 complex accumulates on cell surface. MT1-MMP cannot cleave other direct substrates at the TIMP-2 level that induces efficient pro-MMP-2 processing | Mus musculus | |
| tissue inhibitor of MMP-3 | i.e. TIMP-3 | Homo sapiens | |
| tissue inhibitor of MMP-4 | i.e. TIMP-4 | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cell surface | MT1-MMP on cell surface rapidly turns over by auto-degradation or clathrin-dependent internalization. MT1-MMP inactivated by TIMP-2 avoids auto-degradation, and accumulates on the cell surface, overview | Mus musculus | 9986 | - |
| cell surface | MT1-MMP on cell surface rapidly turns over by auto-degradation or clathrin-dependent internalization. MT1-MMP inactivated by TIMP-2 avoids auto-degradation, and accumulates on the cell surface, overview | Homo sapiens | 9986 | - |
| extracellular | - |
Mus musculus | - |
- |
| extracellular | - |
Homo sapiens | - |
- |
| plasma membrane | - |
Mus musculus | 5886 | - |
| plasma membrane | - |
Homo sapiens | 5886 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | Mus musculus | MT1-MMP on cell surface rapidly turns over by auto-degradation or clathrin-dependent internalization. MT1-MMP inactivated by TIMP-2 avoids auto-degradation, and accumulates on the cell surface, overview. Tetraspanins are attracting attention as binding proteins of MT1-MMP, which regulate subcellular localization and compartmentalization of MT1-MMP and consequent MT1-MMP activities | ? | - |
? |  |
| additional information | Homo sapiens | MT1-MMP on cell surface rapidly turns over by auto-degradation or clathrin-dependent internalization. MT1-MMP inactivated by TIMP-2 avoids auto-degradation, and accumulates on the cell surface, overview. Tetraspanins are attracting attention as binding proteins of MT1-MMP, which regulate subcellular localization and compartmentalization of MT1-MMP and consequent MT1-MMP activities | ? | - |
? | |
| pro-MMP-2 + H2O | Mus musculus | the TIMP-2-dependent pathway of MMP-2 activation involves tissue inhibitor of MMP (TIMP)-2 as a bridging molecule between MT1-MMP and pro-MMP-2. Thus, net activity of MT1-MMP and MMP-2 is regulated in a complex manner depending on TIMP-2 concentration. For the TIMP-2-independent pathway, claudin recruits MT-MMP and MMP-2 at a tight junction to achieve elevated focal concentrations, and consequently enhances activation of pro-MMP-2. Pro-MMP-2 associates with TIMP-2-deficient cells through the hemopexin domain, and is processed by MT2-MMP | MMP-2 + MMP-2 propeptide | - |
? | |
| pro-MMP-2 + H2O | Homo sapiens | the TIMP-2-dependent pathway of MMP-2 activation involves tissue inhibitor of MMP-2 as a bridging molecule between MT1-MMP and pro-MMP-2. Thus, net activity of MT1-MMP and MMP-2 is regulated in a complex manner depending on TIMP-2 concentration. For the TIMP-2-independent pathway, claudin recruits MT-MMP and MMP-2 at a tight junction to achieve elevated focal concentrations, and consequently enhances activation of pro-MMP-2. Pro-MMP-2 associates with TIMP-2-deficient cells through the hemopexin domain, and is processed by MT2-MMP | MMP-2 + MMP-2 propeptide | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Mus musculus | - |
- |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| carcinoma cell | - |
Mus musculus | - |
| carcinoma cell | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | MT1-MMP on cell surface rapidly turns over by auto-degradation or clathrin-dependent internalization. MT1-MMP inactivated by TIMP-2 avoids auto-degradation, and accumulates on the cell surface, overview. Tetraspanins are attracting attention as binding proteins of MT1-MMP, which regulate subcellular localization and compartmentalization of MT1-MMP and consequent MT1-MMP activities | Mus musculus | ? | - |
? | |
| additional information | MT1-MMP on cell surface rapidly turns over by auto-degradation or clathrin-dependent internalization. MT1-MMP inactivated by TIMP-2 avoids auto-degradation, and accumulates on the cell surface, overview. Tetraspanins are attracting attention as binding proteins of MT1-MMP, which regulate subcellular localization and compartmentalization of MT1-MMP and consequent MT1-MMP activities | Homo sapiens | ? | - |
? | |
| pro-MMP-2 + H2O | the TIMP-2-dependent pathway of MMP-2 activation involves tissue inhibitor of MMP (TIMP)-2 as a bridging molecule between MT1-MMP and pro-MMP-2. Thus, net activity of MT1-MMP and MMP-2 is regulated in a complex manner depending on TIMP-2 concentration. For the TIMP-2-independent pathway, claudin recruits MT-MMP and MMP-2 at a tight junction to achieve elevated focal concentrations, and consequently enhances activation of pro-MMP-2. Pro-MMP-2 associates with TIMP-2-deficient cells through the hemopexin domain, and is processed by MT2-MMP | Mus musculus | MMP-2 + MMP-2 propeptide | - |
? | |
| pro-MMP-2 + H2O | the TIMP-2-dependent pathway of MMP-2 activation involves tissue inhibitor of MMP-2 as a bridging molecule between MT1-MMP and pro-MMP-2. Thus, net activity of MT1-MMP and MMP-2 is regulated in a complex manner depending on TIMP-2 concentration. For the TIMP-2-independent pathway, claudin recruits MT-MMP and MMP-2 at a tight junction to achieve elevated focal concentrations, and consequently enhances activation of pro-MMP-2. Pro-MMP-2 associates with TIMP-2-deficient cells through the hemopexin domain, and is processed by MT2-MMP | Homo sapiens | MMP-2 + MMP-2 propeptide | - |
? | |
| pro-MMP-2 + H2O | pro-MMP-2 is cleaved by an adjacent TIMP-2-free MT1-MMP between Asn37 and Leu38, generating an activated intermediate form that is further processed to the fully activated form by an intermolecular auto-cleavage when an intermediate form is present at a sufficiently high concentration at the cell surface, mechanism, overview. MT1-MMP cannot cleave other direct substrates at the TIMP-2 level that induces efficient pro-MMP-2 processing | Mus musculus | MMP-2 + MMP-2 propeptide | - |
? | |
| pro-MMP-2 + H2O | pro-MMP-2 is cleaved by an adjacent TIMP-2-free MT1-MMP between Asn37 and Leu38, generating an activated intermediate form that is further processed to the fully activated form by an intermolecular auto-cleavage when an intermediate form is present at a sufficiently high concentration at the cell surface, mechanism, overview. MT1-MMP cannot cleave other direct substrates at the TIMP-2 level that induces efficient pro-MMP-2 processing | Homo sapiens | MMP-2 + MMP-2 propeptide | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| membrane-type matrix metalloproteinase-1 | - |
Mus musculus |
| membrane-type matrix metalloproteinase-1 | - |
Homo sapiens |
| MT1-MMP | - |
Mus musculus |
| MT1-MMP | - |
Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| physiological function | an essential role for MT1-MMP in the process of angiogenesis and bone growth. Tetraspanins are attracting attention as binding proteins of MT1-MMP, which regulate subcellular localization and compartmentalization of MT1-MMP and consequent MT1-MMP activities. MT1-MMP plays an essential role in angiogenesis, CD151 may contribute to endothelial homeostasis through the regulation of MT1-MMP. CD9, CD81, and TSPAN12 also associate with cell surface molecules including integrins. Tetraspanin-regulated cell surface localization of MT1-MMP increases the local concentration for focal proteolysis within the pericellular environment and leads to efficient extracellular matrix degradation and MMP-2 activation | Mus musculus |
| physiological function | tetraspanins are attracting attention as binding proteins of MT1-MMP, which regulate subcellular localization and compartmentalization of MT1-MMP and consequent MT1-MMP activities. MT1-MMP plays an essential role in angiogenesis, CD151 may contribute to endothelial homeostasis through the regulation of MT1-MMP. CD9, CD81, and TSPAN12 also associate with cell surface molecules including integrins. Tetraspanin-regulated cell surface localization of MT1-MMP increases the local concentration for focal proteolysis within the pericellular environment and leads to efficient extracellular matrix degradation and MMP-2 activation | Homo sapiens |
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