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Literature summary for 3.4.24.23 extracted from

  • Ishikawa, T.; Kimura, Y.; Hirano, H.; Higashi, S.
    Matrix metalloproteinase-7 induces homotypic tumor cell aggregation via proteolytic cleavage of the membrane-bound Kunitz-type inhibitor HAI-1 (2017), J. Biol. Chem., 292, 20769-20784 .
    View publication on PubMedView publication on EuropePMC

Protein Variants

Protein Variants Comment Organism
additional information generation of mutant MMP-7(29,33,51,55/M2)DELTAC3, a variant of MMP-7 lacking affinity for cell surface cholesterol sulfate (CS) Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
EDTA inhibits MMP-7-induced cell aggregation Homo sapiens
methyl-beta-cyclodextrin inhibits release of the HAI-1 fragment by MMP-7-catalyzed cleavage Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cell surface extracellular MMP-7 binds to cell-surface cholesterol sulfate (CS) and acts as a membrane-associated protease Homo sapiens 9986
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Metals/Ions

Metals/Ions Comment Organism Structure
additional information metal ions are required for the MMP-7-induced cell aggregation Homo sapiens
Zn2+ a zinc metalloproteinase Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
hepatocyte growth factor activator inhibitor type 1 + H2O Homo sapiens membrane-bound, biotinylated Kunitz-type inhibitor HAI-1, cell-bound MMP-7 cleaves HAI-1 mainly between Gly451 and Leu452 and thereby releases the extracellular region as soluble HAI-1 (sHAI-1, comprising amino acids 141-249). The peptide bonds corresponding to Gly375-Phe376 and Glu378-Leu379 in HAI-1 are slightly susceptible to MMP-7 cleavage ?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P09237
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-

Source Tissue

Source Tissue Comment Organism Textmining
carcinoma cell
-
Homo sapiens
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Colo-201 cell
-
Homo sapiens
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colonic cancer cell
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Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
hepatocyte growth factor activator inhibitor type 1 + H2O membrane-bound, biotinylated Kunitz-type inhibitor HAI-1, cell-bound MMP-7 cleaves HAI-1 mainly between Gly451 and Leu452 and thereby releases the extracellular region as soluble HAI-1 (sHAI-1, comprising amino acids 141-249). The peptide bonds corresponding to Gly375-Phe376 and Glu378-Leu379 in HAI-1 are slightly susceptible to MMP-7 cleavage Homo sapiens ?
-
?
hepatocyte growth factor activator inhibitor type 1 + H2O membrane-bound, biotinylated Kunitz-type inhibitor HAI-1 Homo sapiens ?
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?

Synonyms

Synonyms Comment Organism
Matrix metalloproteinase-7
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Homo sapiens
MMP-7
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Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
assay at Homo sapiens

General Information

General Information Comment Organism
metabolism MMP-7-induced cancer cell aggregation is an important mechanism in cancer metastasis, and the soluble fragment of hepatocyte growth factor activator inhibitor type 1 (sHAI-1) is an essential component of MMP-7-induced stimulation of cancer metastasis Homo sapiens
physiological function matrix metalloproteinase-7 (MMP-7) plays important roles in tumor progression and metastasis. Treatment of human colon carcinoma cells with active MMP-7 in vitro induces cell aggregation by cleaving cell-surface proteins. MMP-7 binds to colon cancer cells via cell surface-bound cholesterol sulfate and induces significant cell aggregation by cleaving cell-surface protein(s). These aggregated cells exhibit a dramatically enhanced metastatic potential. MMP-7 induces homotypic tumor cell aggregation via proteolytic cleavage of the membrane-bound Kunitz-type inhibitor HAI-1. Cell-bound MMP-7 cleaves HAI-1 mainly between Gly451 and Leu452 and thereby releases the extracellular region as soluble HAI-1 (sHAI-1). sHAI-1 can induce cancer cell aggregation. MMP-7-catalyzed generation of sHAI-1 requires cholesterol sulfate (CS). Binding of MMP-7 to CS is important for cleavage of HAI-1 localized in raft region. The MMP-7-induced cell aggregation of colon carcinoma cells consists of two steps, initial loose cell aggregation is secondly converted to tight cell aggregation. Region of HAI-1 corresponding to amino acid residues 141-249 is essential for cell aggregation-inducing activity of MMP-7 Homo sapiens