Literature summary for 3.4.21.B27 extracted from

Ginefra, P.; Filippi, B.G.H.; Donovan, P.; Bessonnard, S.; Constam, D.B.
Compartment-specific biosensors reveal a complementary subcellular distribution of bioactive furin and PC7 (2018), Cell Rep., 22, 2176-2189 .

Search for more literature for 3.4.21.B27

Application

Application	Comment	Organism
additional information	compartment-specific biosensors can be used to gain insight into the regulation of proprotein convertase (PC) trafficking and to map the tropism of PC-specific inhibitors	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
the distribution of proprotein convertase (PC) activities at the tissue level are monitored by introduction of biosensor CLIP (cell-linked indicator of proteolysis). CLIP v.3 is suitable for ratiometric imaging without interference by FRET, whereas CLIP v.4 can be used as a FRET-based biosensor to quantify PC activities in specific intracellular vesicles, enzyme and CLIP expression in HEK-293T cells. Fusion to the cytosolic tail of PC7 directs CLIP v.4 to compartments that harbor furin activity, but not full-length proprotein convertase 7 (PC7). Overexpressed PC7 cleaves trans-Golgi network/endosomal CLIP v.4 variants	Homo sapiens

Cloned (Comment)

Organism

the distribution of proprotein convertase (PC) activities at the tissue level are monitored by introduction of biosensor CLIP (cell-linked indicator of proteolysis). CLIP v.3 is suitable for ratiometric imaging without interference by FRET, whereas CLIP v.4 can be used as a FRET-based biosensor to quantify PC activities in specific intracellular vesicles, enzyme and CLIP expression in HEK-293T cells. Fusion to the cytosolic tail of PC7 directs CLIP v.4 to compartments that harbor furin activity, but not full-length proprotein convertase 7 (PC7). Overexpressed PC7 cleaves trans-Golgi network/endosomal CLIP v.4 variants

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
additional information	proprotein convertase PC7 can rescue proActivin-A cleavage in furin-depleted B16-F1 melanoma cells	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
additional information	no or poor inhibition by decanoyl-RVKR-chloromethylketone	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cell surface	only overexpressed PC7 activity reaches the cell surface, endosomes, and the trans-Golgi network	Mus musculus	9986	-
endosome	only overexpressed PC7 activity reaches the cell surface, endosomes, and the trans-Golgi network	Mus musculus	5768	-
additional information	complementary subcellular distribution of bioactive furin and proprotein convertase PC7. Furin activity in endosomes is 10fold less inhibited by decanoyl-RVKR-chloromethylketone and enriched over 3fold in endosomes compared to the trans-Golgi network. Development of targeted compartment-specific biosensors. Endogenous PC7, which resists the inhibitor, is active in distinct vesicles. Overexpressed PC7 cleaves trans-Golgi network/endosomal CLIP v.4 variants	Homo sapiens	-	-
plasma membrane	-	Homo sapiens	5886	-
trans-Golgi network	-	Homo sapiens	5802	-
trans-Golgi network	only overexpressed PC7 activity reaches the cell surface, endosomes, and the trans-Golgi network. A PLC motif in the cytosolic tail of the enzyme is dispensable for endosomal activity, but it is specifically required for trans-Golgi network recycling	Mus musculus	5802	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Ca2+	required	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q16549	-	-
Mus musculus	Q61139	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
proteolytic modification	after autocleavage, proprotein convertases (PCs) exit the endoplasmatic reticulum. They remain bound to their inhibitory cleaved prosegments in latent form until arrival at the cell surface or, in the case of furin, in acidic endosomes, probably to avoid precocious activation or degradation of their substrates. Activated furin can then recycle from endosomes to the trans-Golgi network by binding to specific adaptors in the cytosol	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
B16-F1 cell	-	Homo sapiens	-
B16-F1 cell	-	Mus musculus	-
melanoma cell	-	Homo sapiens	-
melanoma cell	-	Mus musculus	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
Notch 1 + H2O	PC7 complements furin (EC 3.4.21.75) in cleaving Notch1 independently of PLC motif-mediated trans-Golgi network access	Homo sapiens	?	-	?
proactivin A + H2O	-	Homo sapiens	activin A + ?	-	?

Subunits

Subunits	Comment	Organism
More	a PLC motif in the cytosolic tail of PC7 is dispensable for endosomal activity, but it is specifically required for trans-Golgi network recycling and to rescue proActivin-A cleavage in Furin-depleted B16-F1 melanoma cells	Homo sapiens

Synonyms

Synonyms	Comment	Organism
furin	-	Homo sapiens
PC7	-	Mus musculus
PCSK7	-	Homo sapiens
Proprotein convertase	-	Homo sapiens

General Information

General Information	Comment	Organism
evolution	four of nine conserved proprotein convertases (PCs), including furin, Pace4, PC5A/B, and PC7, cleave substrates after the minimal dibasic recognition motif (K/R)-(X)n-(K/R)Y, where n is 0, 2, 4, or 6 and X can be any amino acid. In 152 PC sequences examined across species, the catalytic sites are 95% identical	Homo sapiens
malfunction	the PLC motif in the cytosolic tail of proprotein convertase 7 (PC7) is dispensable for endosomal activity, but is specifically required for trans-Golgi network (TGN) recycling and to rescue proactivin-A cleavage in furin-depleted B16-F1 melanoma cells. In sharp contrast, PC7 complements furin in cleaving Notch1 independently of PLC-mediated TGN access	Homo sapiens
metabolism	all proprotein convertase (PC) activity detected in the trans-Golgi network/endosomal system of B16-F1 cells is mediated by furin, but not by endogenous PC7. Enzyme PC7 can rescue proActivin-A cleavage in furin-depleted B16-F1 melanoma cells	Homo sapiens
additional information	a PLC motif in the cytosolic tail of PC7 is dispensable for endosomal activity, but it is specifically required for trans-Golgi network recycling and to rescue proActivin-A cleavage in furin-depleted B16-F1 melanoma cells	Homo sapiens
physiological function	CRISPR editing reveals that both furin and PC7 are functional in B16-F1 cells and able to substitute for each other during Notch1 and ADAM10 precursor processing	Homo sapiens