Literature summary for 3.4.21.109 extracted from

List, K.; Bugge, T.H.; Szabo, R.
Matriptase: potent proteolysis on the cell surface (2006), Mol. Med., 12, 1-7.

Activating Compound

Activating Compound	Comment	Organism	Structure
additional information	activation of the matriptase zymogen requires sequential N-terminal cleavage, activation site autocleavage, and transient association with HAI-1, different activation mechanisms, matriptase translocates to the cell surface and is activated within min after exposure of breast cancer cells to sphingosine-1-phosphate, a serum-derived lipid that signals through specific G-protein-coupled receptor, this activation process was shown to require actin cytoskeleton remodeling, overview	Homo sapiens

Protein Variants	Comment	Organism
additional information	mutations in any of the residues of the catalytic triad render matriptase unable to undergo activation site cleavage, inactivating mutations in the Ca2+-binding motifs of any or all of the four LDLRA domains prevents the activation of matriptase	Homo sapiens

Inhibitors	Comment	Organism	Structure
hepatocyte growth factor activator inhibitor	HAI-1, the cognate transmembrane inhibitor of the enzyme, which is coexpressed with matriptase in epithelium	Homo sapiens
additional information	autoinhibitory role of the LDLRA modules that may prevent premature activation of matriptase in the absence of appropriate activation stimuli	Homo sapiens

Localization	Comment	Organism	GeneOntology No.	Textmining
cell surface	matriptase translocates to the cell surface and is activated within min after exposure of breast cancer cells to sphingosine-1-phosphate requiring actin cytoskeleton remodeling	Homo sapiens	9986	-
plasma membrane	lacks a classical signal peptide, and the N-terminal signal anchor, which is not removed during synthesis, functions as a single-span transmembrane domain that orients the protease in the plasma membrane as a type II integral membrane protein with a cytoplasmic N-terminus and an extracellular C-terminus	Homo sapiens	5886	-

Metals/Ions	Comment	Organism	Structure
Ca2+	required for autoactivation	Homo sapiens

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
additional information	Homo sapiens	matriptase has an essential physiological role in profilaggrin processing, corneocyte maturation, and lipid matrix formation associated with terminal differentiation of the oral epithelium and the epidermis, and is also critical for hair follicle growth, matriptase and HAI expression are frequently dysregulated in human cancer, and matriptase expression, that is unopposed by HAI-1, potently promotes carcinogenesis and metastatic dissemination in animal models, matriptase dramatically increases apoptosis of immature thymocytes in the thymus, leading to thymocyte depletion, physiological functions of matriptase, the enzyme is involved in epithelial carcinogenesis, detailed overview	?	-	?

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Posttranslational Modification	Comment	Organism
glycoprotein	matriptase contains four functional N-glycosylation sites, Asn109, 302, 485, and 772, whereas the inactivation of Asn109 and Asn485 has no effect on the activation of matriptase, glycosylation of the first CUB domain, Asn302, and the catalytic domain, Asn772, is required for zymogen activation in cultured breast cancer cells	Homo sapiens
proteolytic modification	activation of the matriptase zymogen requires sequential N-terminal cleavage, activation site autocleavage, and transient association with HAI-1, the mature single-chain proenzyme is first cleaved after Gly149 located in a conserved GSVIA motif in the N-terminal SEA domain by an unknown proteolytic activity or possibly by nonenzymatic hydrolysis of the dependent on SEA domain cleavage, matriptase next is converted into its active conformation by proteolytic cleavage after Arg614 within the highly conserved activation cleavage site R-VVGG in the serine protease domain	Homo sapiens

Source Tissue	Comment	Organism	Textmining
adrenal gland	-	Homo sapiens	-
alveolus	-	Homo sapiens	-
breast cancer cell	-	Homo sapiens	-
bronchiole	-	Homo sapiens	-
colon	-	Homo sapiens	-
duodenum	-	Homo sapiens	-
epidermis	-	Homo sapiens	-
epididymis	-	Homo sapiens	-
epithelial carcinoma cell	-	Homo sapiens	-
epithelium	expression in most human epithelia	Homo sapiens	-
esophagus	-	Homo sapiens	-
gall bladder	-	Homo sapiens	-
kidney	-	Homo sapiens	-
additional information	expression profile of matriptase in cancer tissues, overview	Homo sapiens	-
ovary	-	Homo sapiens	-
pancreas	-	Homo sapiens	-
prostate gland	-	Homo sapiens	-
rectum	-	Homo sapiens	-
seminal vesicle	-	Homo sapiens	-
small intestine	-	Homo sapiens	-
stomach	-	Homo sapiens	-
thyroid gland	-	Homo sapiens	-
trachea	-	Homo sapiens	-
urinary bladder	-	Homo sapiens	-
uterus	-	Homo sapiens	-
vagina	-	Homo sapiens	-

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	matriptase has an essential physiological role in profilaggrin processing, corneocyte maturation, and lipid matrix formation associated with terminal differentiation of the oral epithelium and the epidermis, and is also critical for hair follicle growth, matriptase and HAI expression are frequently dysregulated in human cancer, and matriptase expression, that is unopposed by HAI-1, potently promotes carcinogenesis and metastatic dissemination in animal models, matriptase dramatically increases apoptosis of immature thymocytes in the thymus, leading to thymocyte depletion, physiological functions of matriptase, the enzyme is involved in epithelial carcinogenesis, detailed overview	Homo sapiens	?	-	?
additional information	matriptase binds cytosolic proteins to regulate enzymatic activity and cellular distribution of the protease	Homo sapiens	?	-	?

Subunits	Comment	Organism
?	x * 80000-90000, domain structure, overview	Homo sapiens