Literature summary for 3.4.21.75 extracted from

Ortutay, Z.; Oksanen, A.; Aittomaeki, S.; Ortutay, C.; Pesu, M.
Proprotein convertase furin regulates T cell receptor-induced transactivation (2015), J. Leukoc. Biol., 98, 73-83 .

Search for more literature for 3.4.21.75

Cloned(Commentary)

Cloned (Comment)	Organism
gene FURIN, quantitative RT-PCR expression analysis	Homo sapiens
gene FURIN, quantitative RT-PCR expression analysis	Mus musculus

Protein Variants

Protein Variants	Comment	Organism
D46A	a loss-of-function furin mutant	Homo sapiens
additional information	retroviral deletion of furin from HEK 293E cells	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
pro-Notch1 + H2O	Homo sapiens	-	Notch1 + propeptide	-	?
pro-Notch1 + H2O	Mus musculus	-	Notch1 + propeptide	-	?
proform tissue growth factor 1beta + H2O	Homo sapiens	-	tissue growth factor beta1 + propeptide	-	?
proform tissue growth factor 1beta + H2O	Mus musculus	-	tissue growth factor beta1 + propeptide	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P09958	-	-
Mus musculus	P23188	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
culture condition:CD4+ cell	-	Mus musculus	-
HEK-293E cell	-	Homo sapiens	-
JURKAT cell	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
pro-Notch1 + H2O	-	Homo sapiens	Notch1 + propeptide	-	?
pro-Notch1 + H2O	-	Mus musculus	Notch1 + propeptide	-	?
proform tissue growth factor 1beta + H2O	-	Homo sapiens	tissue growth factor beta1 + propeptide	-	?
proform tissue growth factor 1beta + H2O	-	Mus musculus	tissue growth factor beta1 + propeptide	-	?

Synonyms

Synonyms	Comment	Organism
furin	-	Homo sapiens
furin	-	Mus musculus
Proprotein convertase	-	Homo sapiens
Proprotein convertase	-	Mus musculus

Expression

Organism	Comment	Expression
Homo sapiens	furin expression is upregulated by the Th1 hallmark cytokine interleukin-12. T cell activation via T cell receptor induces furin expression	up
Mus musculus	furin expression is upregulated by the Th1 hallmark cytokine interleukin-12. T-cell activation via T-cell receptor induces FURIN expression	up

General Information

General Information	Comment	Organism
malfunction	interleukin-2 is increased initially in furin-deficient mouse CD4+ T cells, but the T-cell receptor-induced interleukin-2 mRNA expression is not sustained in the absence of furin. Conditional deletion of FURIN in CD4+ T-cells leads to hyperactive T-cells and the overproduction of Th1 and Th2 cytokines and systemic autoimmunity as a result of the loss of Treg-mediated immunologic tolerance	Mus musculus
malfunction	the inhibition of furin in human Jurkat T cell lines also results in a decrease in interleukin-2 production, whereas the overexpression of wild-type furin is associated with elevated interleukin-2 levels	Homo sapiens
metabolism	furin promotes the activation of T cell receptor-induced transcription factors	Homo sapiens
metabolism	furin-dependent transactivators in different mouse CD4+ T-cell subsets, overview	Mus musculus
physiological function	proprotein convertase substilisin/kexin-type (PCSK) enzymes regulate proprotein maturation by catalyzing the proteolytic cleavage of their substrates. The prototype PCSK furin is induced upon T cell receptor (TCR) activation, and its expression in T cells is critical for the maintenance of peripheral immune tolerance. Proprotein convertase furin regulates T cell receptor-induced transactivation. TGF-beta1 and NOTCH1 are synthesized initially as inactive precursors and are proteolytically activated during T cell activation. In Jurkat cells, furin is dispensable for immediate T cell receptor (TCR) signaling steps, such as ERK, ZAP70, or LAT phosphorylation. Furin regulates the expression of interleukin-2 in human Jurkat T cell lines, specific TGF-beta1-independent role for furin in interleukin-2 regulation. Furin activates specifically and nonredundantly the anti-inflammatory cytokine pro-TGF-beta1 and thus, directly modulates the activity of CD4+ and CD8+ T cells. Importantly, Furin regulates its own activity by autocleavage, and its mRNA and protein levels are modulated dynamically during alterations in T cell physiology. Furin does not affect TCR-induced immediate phosphorylation events in Jurkat T cells	Homo sapiens
physiological function	proprotein convertase substilisin/kexin-type (PCSK) enzymes regulate proprotein maturation by catalyzing the proteolytic cleavage of their substrates. The prototype PCSK furin is induced upon T-cell receptor (TCR) activation, and its expression in T cells is critical for the maintenance of peripheral immune tolerance. Proprotein convertase furin regulates T cell receptor-induced transactivation. TGF-beta1 and NOTCH1 are synthesized initially as inactive precursors and are proteolytically activated during T-cell activation. In Jurkat cells, furin is dispensable for immediate T-cell receptor (TCR) signaling steps, such as ERK, ZAP70, or LAT phosphorylation. Furin regulates the expression of interleukin-2 in human Jurkat T-cell lines, specific TGF-beta1-independent role for furin in interleukin-2 regulation. Furin activates specifically and nonredundantly the anti-inflammatory cytokine pro-TGF-beta1 and thus, directly modulates the activity of CD4+ and CD8+ T-cells. Importantly, Furin regulates its own activity by autocleavage, and its mRNA and protein levels are modulated dynamically during alterations in T-cell physiology	Mus musculus

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Release 2023.1 (January 2023)