Literature summary for 3.4.21.B27 extracted from

Guillemot, J.; Canuel, M.; Essalmani, R.; Prat, A.; Seidah, N.G.
Implication of the proprotein convertases in iron homeostasis: proprotein convertase 7 sheds human transferrin receptor 1 and furin activates hepcidin (2013), Hepatology, 57, 2514-2524.

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Cloned(Commentary)

Cloned (Comment)	Organism
recombinant enzyme expression of wild-type enzyme mutant enzymes in HuH-7 cells, also expression of the wild-type enzyme in Hep-G2 cells, HEK-293 cells, K-562 cells, CHO cells, and COS-1 cells, functional co-expression with the human transferrin receptor 1 substrate	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
C699A	site-directed mutagenesis, the mutant activity with substrate transferrin receptor 1 is unaltered compared to the wild-type enzyme	Homo sapiens
C704A	site-directed mutagenesis, the mutant activity with substrate transferrin receptor 1 is unaltered compared to the wild-type enzyme	Homo sapiens
D188G	site-directed mutagenesis, the autocatalytic processing of the PC7 zymogen is severely impaired leading to accumulation of the inactive pro-enzyme	Homo sapiens
additional information	generation of a frameshift fsL506P enzyme mutant. Construction of an enzyme PC7 chimera, in which the transmembrane domain and the cytosolic tail are replaced by that of the convertase furin, the mutant loses its ability to cleave the transferrin receptor. Identification of the KTECER100;LA cleavage site by site-directed mutagenesis	Homo sapiens
R316C	site-directed mutagenesis, the autocatalytic processing of the PC7 zymogen is severely impaired leading to accumulation of the inactive pro-enzyme	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism	Structure
decanoyl-RVKR-chloromethylketone	-	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
endosome	-	Homo sapiens	5768	-
membrane	a transmembrane protein	Homo sapiens	16020	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
human transferrin receptor 1 + H2O	Homo sapiens	cleavage at an atypical site KTECER-/-LA, in which the P1 Arg100 and P6 Lys95 are critical,.cleavage at Arg100	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q16549	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
lipoprotein	the enzyme has palmitoylated cysteines, Cys699 and Cys704 within its C-terminus, these posttranslational modifications are not required for transferrin receptor 1 shedding	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
hepatocyte	primary	Homo sapiens	-
hepatoma cell	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
human transferrin receptor 1 + H2O	cleavage at an atypical site KTECER-/-LA, in which the P1 Arg100 and P6 Lys95 are critical,.cleavage at Arg100	Homo sapiens	?	-	?
human transferrin receptor 1 + H2O	cleavage at an atypical site KTECER-/-LA, in which the P1 Arg100 and P6 Lys95 are critical, cleavage at Arg100. Identification of the KTECER100;LA cleavage site by site-directed mutagenesis using substrate mutants, overview	Homo sapiens	?	-	?
additional information	no activity with hepcidin	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
PC7	-	Homo sapiens
proprotein convertase 7	-	Homo sapiens

Expression

Organism	Comment	Expression
Homo sapiens	depletion of iron in the medium of hepatoma cell lines incubated with the iron chelator desferrioxamine results in the enzyme downregulation	down

General Information

General Information	Comment	Organism
malfunction	an enzyme PC7 chimera, in which the transmembrane domain and the cytosolic tail are replaced by that of the convertase furin, loses its ability to cleave the transferrin receptor	Homo sapiens
metabolism	when iron is limiting, human transferrin receptor TfR1 levels increase at least in part by way of the down-regulation of PC7 enzyme expression	Homo sapiens
physiological function	the enzyme is involved in the regulation of systemic iron homeostasis via shedding of human transferrin receptor 1, TfR1, as its unique mechanism. Shedding of hTfR1 by the enzyme requires endocytosis into acidic clathrin-coated vesicles, enzyme transmembrane domain and cytosolic tail are critical for hTfR1 shedding in the endosomes	Homo sapiens

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Release 2023.1 (January 2023)