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Literature summary for 3.4.21.109 extracted from

  • Miller, G.S.; List, K.
    The matriptase-prostasin proteolytic cascade in epithelial development and pathology (2013), Cell Tissue Res., 351, 245-253.
    View publication on PubMed
Search for more literature for 3.4.21.109

Inhibitors

Inhibitors Comment Organism Structure
hepatocyte growth factor activator inhibitor-1 HAI-1, an extremely effective inhibitor of matriptase in vitro, that has a high affinity for matriptase binding and is typically co-expressed with matriptase in vivo. Matriptase activation appears to require physical interaction with its related inhibitor, HAI-1, which may serve to protect against aberrant matriptase proteolysis. Deletion or mutation of the LDLA domain of HAI-1 results in both a reduction in surface matriptase expression and abolishment of matriptase activity Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
membrane a type II transmembrane serine protease Mus musculus 16020
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
proform hepatocyte growth factor + H2O Mus musculus
-
 mature hepatocyte growth factor + ?
-
 ?
proform prostasin + H2O Mus musculus
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 mature prostasin + ?
-
 ?

Organism

Organism UniProt Comment Textmining
Mus musculus
-
-
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Posttranslational Modification

Posttranslational Modification Comment Organism
proteolytic modification matriptase zymogen is capable of auto-activation and proteolytic auotprocesses into an active protease. In order to become catalytically active, matriptase must undergo two sequential proteolytic processing events that occur near the termini of the stem region. The first cleavage occurs after Gly149 within a conserved GSVIA motif in the SEA domain and may occur spontaneously during intracellular transport as the result of conformation-induced hydrolysis. The second cleavage occurs after Arg614 within the highly conserved RVVGG activation motif and requires both the initial SEA domain cleavage event and the catalytic amino acids of the matriptase serine protease domain. Matriptase activation appears to require physical interaction with its related inhibitor, HAI-1, which may serve to protect against aberrant matriptase proteolysis Mus musculus

Source Tissue

Source Tissue Comment Organism Textmining
epidermis
-
 Mus musculus
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epithelium in polarized epithelium, matriptase and prostasin co-localize briefly at the basolateral plasma membrane prior to HAI-1-mediated matriptase endocytosis Mus musculus
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additional information in nearly all murine epithelial tissues, matriptase is coexpressed with the membrane serine protease prostasin Mus musculus
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
proform acid-sensing ion channel 1 + H2O
-
 Mus musculus mature acid-sensing ion channel 1 + ?
-
 ?
proform G-protein-coupled protease activated receptor-2 + H2O
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 Mus musculus mature G-protein-coupled protease activated receptor-2 + ?
-
 ?
proform hepatocyte growth factor + H2O
-
 Mus musculus mature hepatocyte growth factor + ?
-
 ?
proform platelet-derived growth factor-D + H2O
-
 Mus musculus mature platelet-derived growth factor-D + ?
-
 ?
proform prostasin + H2O
-
 Mus musculus mature prostasin + ?
-
 ?
proform urokinase-type plasminogen activator + H2O
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 Mus musculus mature urokinase-type plasminogen activator + ?
-
 ?

General Information

General Information Comment Organism
malfunction matriptase and prostasin null mice have identical phenotypes, mice deficient for matriptase phenocopy mice deficient for epidermal prostasin and show impaired corneocyte differentiation, imparied lipid matrix formation, loss of profilaggrin processing and loss of tight junction formation and function. Matriptase-deficient mice present with a variety of epidermal defects, including a generalized disruption of the stratum corneum architecture, loss of vesicular bodies that generate intercorneocyte lipids and hypoplasia and dysgenesis of hair follicles. Together, these defects lead to a compromised epidermal barrier and result in fatal dehydration during the neonatal period. Targeted postnatal ablation of matriptase in mice perturbs the function of multiple adult tissues, indicating an ongoing requirement for matriptase proteolysis in the maintenance of diverse types of epithelia. Matriptase-deficient Caco-2 monolayers as well as matriptase hypomorphic mice are shown to express abnormally high levels of the tight junction protein claudin-2, which is associated with the formation of ion channels that decrease the cohesion between adjacent epithelial cells. Matriptase pathophysiology, overview Mus musculus
additional information spatial and temporal co-expression of matriptase and prostasin Mus musculus
physiological function matriptase is a potential oncogene, its expression correlates with the severity of tumors in the breast and prostate and de novo matriptase expression has been found in both ovarian and cervical carcinomas. The ratio of matriptase/HAI-1 mRNA is increased in ovarian and colorectal cancer, indicating that deregulated matriptase proteolysis may contribute to tumor formation or metastasis. In the epidermis, the glycosylphosphatidylinositol anchored membrane serine protease prostasin is activated by matriptase to initiate a proteolytic cascade that is required for the development of the stratum corneum barrier function. Matriptase in epidermal barrier and epidermal development, detailed overview. Proteolytic activity of the matriptase-prostasin cascade is regulated in the epidermis via inhibition by the Kunitz-type serine protease inhibitor hepatocyte growth factor activator inhibitor-1 Mus musculus