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Information on EC 3.4.21.93 - Proprotein convertase 1 and Organism(s) Mus musculus and UniProt Accession P63239
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3.4.21.93 Proprotein convertase 1Specify your search results
Word Map
- 3.4.21.93
- obesity
- proinsulin
- proglucagon
-
subtilisin-like
- endoproteases
- medicine
-
tmem18
-
proneuropeptides
- drug development
- analysis
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
release of protein hormones, neuropeptides and renin from their precursors, generally by hydrolysis of -Lys-Arg-/- bonds
Synonyms
pcsk1, pc1/pc3, prohormone convertase 3, proprotein convertase 1, proprotein convertase pc1/3, mpc1/3, propeptide convertase, neuroendocrine convertase 1, furin homolog, proprotein convertase pc1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Furin homolog
-
-
-
-
Neuroendocrine convertase 1
-
-
-
-
PC1
PC1/3
-
-
PC3
-
-
-
-
Prohormone convertase 3
-
-
-
-
Propeptide processing protease
-
-
-
-
PC1
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
99676-46-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
pGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin + H2O
pGlu-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
?
cholecystokinin 8-containing peptide + H2O
?
-
a synthetic peptide substrate containing the CCK 8 Gly Arg Arg peptide sequence, i.e. DYMGWMDF, and the cleavage site of pro-cholecystokinin for its liberation, overview
-
-
?
glucose-dependent insulinotropic polypeptide precursor + H2O
glucose-dependent insulinotropic polypeptide + propeptide of glucose-dependent insulinotropic polypeptide
pGlu-Arg-Thr-Lys-Arg-4-methylcoumarin 7-amide + H2O
pGlu-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
pGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin + H2O
pGlu-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
pro-cholecystokinin + H2O
N-terminal propeptide + C-terminal cholecystokinin 8 Gly Arg Arg peptide + remaining CCK peptide
-
the substrate is only cleaved in vivo since defolding proteins ar required, in vitro the cleavage site is inaccessible for the enzyme
peptide product analysis
-
?
pro-cholecystokinin + H2O
N-terminal propeptide + cholecystokinin 58
-
the substrate is only cleaved at the CKK 8 peptide in vivo since defolding proteins ar required, in vitro the cleavage site is inaccessible for the enzyme
peptide product analysis
-
?
pro-growth hormone-releasing hormone + H2O
growth hormone-releasing hormone + GHRH-RP + pro-peptide of growth hormone-releasing hormone
pro-growth hormone-releasing hormone + H2O
growth hormone-releasing hormone + pro-peptide of growth hormone-releasing hormone
pro-islet amyloid polypeptide + H2O
islet amyloid polypeptide + pro-peptides of islet amyloid polypeptide
-
precursor of IAPP or amylin, the major component of islet amyloid, cleavage at the C- and N-terminus
-
-
?
Pro-opiomelanocortin + H2O
?
-
the enzyme together with prohormone convertase 2 represents the major secretory granule processing activity responsible for processing neuroendocrine precursors
-
-
?
prodynorphin + H2O
dynorphin + ?
-
hydrolyzes peptide bonds with Tyr at position P2
-
-
?
progastrin + H2O
gastrin-34 + gastrin-17
-
PC1/3 initiates cleavage at the N-terminal di-arginine site (Arg36-Arg37) at an early stage in the processing. The endoproteolytic maturation of progastrin in normal G-cells appears to require an interplay, primarily between PC1/3 and PC2. Processing may begin with PC1/3, which is solely responsible for the cleavage of Arg36-Arg37. Subsequently, PC1/3 cleaves the crucial Arg73-Arg74. Later, in secretory granules, PC2 performs the partial cleavage of Lys53-Lys54 to ensure the production of gastrin-17
-
-
?
proglucagon1-158 + H2O
oxyntomodulin + glicentin-related polypeptide + IP2/GLP-2
-
glicentin lacks the signal sequence of proglucagon, residues -20-1, recombinant hamster substrate and murine enzyme co-expressed in rat GH4C1 cells, low activity, cleavage at the proglucagon interdomain site Lys70-Arg71-/-, and at Lys31-Arg32-/-
mature glucagon consists of residues 33-61, glicentin-related polypeptide comprises the C-terminal residues 1-32, GLP-1 is the N-terminal glucagon-like peptide comprising residues 62-69, IP2/GLP-2 comprises residues 72-158
-
?
Proinsulin + H2O
?
-
the enzyme together with prohormone convertase 2 represents the major secretory granule processing activity responsible for processing neuroendocrine precursors
-
-
?
proopiomelanocortin + H2O
?
-
is cleaved by prohormone convertase 1/3 to produce peptides that regulate the body's response to energy availability
-
-
?
glucose-dependent insulinotropic polypeptide precursor + H2O
glucose-dependent insulinotropic polypeptide + propeptide of glucose-dependent insulinotropic polypeptide
-
PC1/3 is essential for pro-GIP processing
GIP
-
?
glucose-dependent insulinotropic polypeptide precursor + H2O
glucose-dependent insulinotropic polypeptide + propeptide of glucose-dependent insulinotropic polypeptide
-
i.e. pro-GIP, incretin hormone
GIP
-
?
pro-growth hormone-releasing hormone + H2O
growth hormone-releasing hormone + GHRH-RP + pro-peptide of growth hormone-releasing hormone
-
posttranslational processing mechanism, PC1 is the primary enzyme involved in the processing, overview
-
-
?
pro-growth hormone-releasing hormone + H2O
growth hormone-releasing hormone + GHRH-RP + pro-peptide of growth hormone-releasing hormone
-
proGHRH, processing
products are the pro-peptide of 1.7 kDa, the mature GHRH of 5.2 kDa, and GHRH-RP of 3.6 kDa
-
?
pro-growth hormone-releasing hormone + H2O
growth hormone-releasing hormone + pro-peptide of growth hormone-releasing hormone
-
PC1/3 and furin, EC 3.4.21.75, are major processing enzymes, processing overview
-
-
?
pro-growth hormone-releasing hormone + H2O
growth hormone-releasing hormone + pro-peptide of growth hormone-releasing hormone
-
pro-GHRH, processing, cleavage of C-terminal -RXRXXR-/-, cleavage site specificity determination by substrate mutational analysis, activity with pro-GHRH mutants R8A, R11A, and Q10R, overview
-
-
?
Pro-opiomelanocortin + H2O
Adrenocorticotropic hormone + beta-lipotropin + beta endorphin
-
-
-
-
?
Pro-opiomelanocortin + H2O
Adrenocorticotropic hormone + beta-lipotropin + beta endorphin
-
-
small amounts of beta-endorphin
?
Proinsulin + H2O
Insulin + ?
-
cleaves at both C peptide junctions to release rat insulin I but generates a larger proportion of intermediate cleaved at the B chain-C peptide junction, indicating a preference for this site
-
-
?
additional information
?
-
-
unlike prohormone convertase 2, does not hydrolyze proluteinizing-hormone-releasing-hormone
-
-
?
additional information
?
-
-
cleaves precursors both at specific single and pairs of basic residues
-
-
?
additional information
?
-
-
cleaves polypeptide hormones and many proteins at specific sites
-
?
additional information
?
-
-
implicated in processing of proproteins in the secretory pathway, synthesized as a zymogen, cleaves his own profragment in the endoplasmic reticulum
-
?
additional information
?
-
-
the enzyme is involved in the regulated secretory pathway in neuroendocrine cells
-
-
?
additional information
?
-
-
the enzyme is involved in the regulated secretory pathway in neuroendocrine cells, the enzyme activity is regulated by the PC1-propeptide and by proSAAS CT peptide
-
-
?
additional information
?
-
-
cleavage site specificity, activity with mutant proglucagon and truncation variants, analysis of importance of substrate domain structure, molecular modeling, overview
-
-
?
additional information
?
-
-
PC1/3 CT peptide is not cleaved by enzymatically active PC1/3
-
-
?
additional information
?
-
-
prohormone convertase 1/3 mRNA levels in the arcuate nucleus respond normally to signals of energy availability in wild-type mice but not in N2KO mice
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
glucose-dependent insulinotropic polypeptide precursor + H2O
glucose-dependent insulinotropic polypeptide + propeptide of glucose-dependent insulinotropic polypeptide
-
PC1/3 is essential for pro-GIP processing
GIP
-
?
pro-cholecystokinin + H2O
N-terminal propeptide + C-terminal cholecystokinin 8 Gly Arg Arg peptide + remaining CCK peptide
-
the substrate is only cleaved in vivo since defolding proteins ar required, in vitro the cleavage site is inaccessible for the enzyme
peptide product analysis
-
?
pro-growth hormone-releasing hormone + H2O
growth hormone-releasing hormone + GHRH-RP + pro-peptide of growth hormone-releasing hormone
-
posttranslational processing mechanism, PC1 is the primary enzyme involved in the processing, overview
-
-
?
pro-growth hormone-releasing hormone + H2O
growth hormone-releasing hormone + pro-peptide of growth hormone-releasing hormone
-
PC1/3 and furin, EC 3.4.21.75, are major processing enzymes, processing overview
-
-
?
pro-islet amyloid polypeptide + H2O
islet amyloid polypeptide + pro-peptides of islet amyloid polypeptide
-
precursor of IAPP or amylin, the major component of islet amyloid, cleavage at the C- and N-terminus
-
-
?
Pro-opiomelanocortin + H2O
?
-
the enzyme together with prohormone convertase 2 represents the major secretory granule processing activity responsible for processing neuroendocrine precursors
-
-
?
Proinsulin + H2O
?
-
the enzyme together with prohormone convertase 2 represents the major secretory granule processing activity responsible for processing neuroendocrine precursors
-
-
?
additional information
?
-
-
cleaves polypeptide hormones and many proteins at specific sites
-
?
additional information
?
-
-
implicated in processing of proproteins in the secretory pathway, synthesized as a zymogen, cleaves his own profragment in the endoplasmic reticulum
-
?
additional information
?
-
-
the enzyme is involved in the regulated secretory pathway in neuroendocrine cells
-
-
?
additional information
?
-
-
the enzyme is involved in the regulated secretory pathway in neuroendocrine cells, the enzyme activity is regulated by the PC1-propeptide and by proSAAS CT peptide
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
PC1/3 propeptide
inhibits the mature enzyme competitively, inhibition mechanism, interaction with the enzyme at the 50RRSRR54, 61KR62 and 65DDD67 sequences, molecular modeling, overview
-
PC1/3 CT peptide
-
decreases PC1/3 activity at high concentrations (micromol range)
-
proSAAS CT peptide
-
endogenous inhibitor, inhibits the C-terminal PC1 processing
-
additional information
-
in wild-type mice prohormone convertase 1/3 mRNA levels show a 75% reduction with food deprivation and exceed ad libitum-fed levels after leptin treatment. Hypothalamic prohormone convertase 1/3 mRNA levels in N2KO mice show no significant variation between the deprived condition and ad libitum feeding. Leptin-treated N2KO mice have significantly lower prohormone convertase 1/3 mRNA levels than leptin-treated wild-type mice
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
leptin
-
leptin stimulation of the prohormone convertase 1/3 promoter is regulated by Nhlh2 and STAT3 in vitro. Nhlh2 binds to both E-box motifs on the prohormone convertase 1/3 promoter. The Nhlh2 and STAT3 transcription factors heterodimerize and interact on the prohormone convertase 1/3 promoter. Leptin-treated N2KO mice have significantly higher prohormone convertase 1/3 mRNA levels than ad libitum-fed N2KO mice
-
PC1/3 CT peptide
-
increases PC1/3 activity at low concentrations (nanomol range). Interaction with the active site of PC1/3 does not result in the formation of a stable complex. Activation of PC1/3 by 5 nanomol CT-peptide is the same in the presence or absence of propeptide
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0024
proPC1/3 55-83 SALHITKRLSDDDRVTWAEQQYEKERSKR
-
pH 7.0, 25°C, mixed inhibition
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
different purified recombinant PC1 constructs, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
at pH 7.8 increase of enzymatic activity up to 50-60%, irrespective of the amount of PC1/3 CT peptide used up to 0.005 mM
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
alpha-cells in the islet of Langerhans express both prohormone convertase 2 and 1/3, which results in the processing of the proglucagon precursor into glucagon-like peptide 1, thereby leading to local production of this beta-cell growth factor. alpha-Cells in the adult basically only express PC2, but significant activation of PC1/3 is also observed in mouse models of insulin resistance such as pregnant, obese, diabetic and prediabetic NOD mice
additional information
-
alphaTCdeltaPC2 cells express abundant PC1/3, whereas alphaTC-1 cells express little or no PC1/3
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
additional information
-
lacks a hydrophobic transmembrane anchor, but has a potential C-terminal amphipathic helical segment similar to the putative membrane anchor of carboxypeptidase H
-
additional information
-
the enzyme is localized in the regulated secretory pathway of neuroendocrine cells
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
-
conditional Pick1-knockout mice lacking protein interacting with C-kinase 1, show elevated proinsulin levels in the circulation and in the pancreatic islets, accompanied by a reduction in the proinsulin processing enzyme prohormone convertase 1/3. The deletion of Pick1 triggers the specific elimination of chromogranin B in pancreatic beta cells
physiological function
-
proprotein convertase PC1/3 regulates the endosomal toll-like receptor TLR9. Under CpG oligodesoxynucleotide challenge, PC1/3 traffics rapidly to colocalize with TLR9 in CpG oligodesoxynucleotide-containing endosomes with acidic pH. In PC1/3 knockdown macrophages, compartmentalization of TLR9 is altered and TLR9 clustered in multivesicular bodies. This clustering of TLR9 in multivesicular bodies dampens the anti-inflammatory STAT3 signalling pathway while it promotes the pro-inflammatory NF-kappaB pathway
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). NEC1_MOUSE
753
0
84174
Swiss-Prot
Secretory Pathway (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
66000
71000
85000
87000
66000
-
Western blotting, intramolecular autocatalytically cleaved 85 kDa isoform
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
proteolytic modification
glycoprotein
-
the catalytic domain of PC1 contains two N-glycosylation sites, the C-terminal domain contains one N-glycosylation site
proteolytic modification
-
PC1 zymogen is activated by proteolytic cleavage of the signal and the propeptide and is processed at the C-terminal domain, which is regulated by the separate PC1 propeptide and the SAAS CT propeptide, overview
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D65A
site-directed mutagenesis of the propeptide residue, leads to reduced inhibition of mature PC1 by the separated propeptide mutant compared to the wild-type propeptide
D66A
site-directed mutagenesis of the propeptide residue, leads to reduced inhibition of mature PC1 by the separated propeptide mutant compared to the wild-type propeptide
D67A
site-directed mutagenesis of the propeptide residue, leads to increased inhibition of mature PC1 by the separated propeptide mutant compared to the wild-type propeptide
K61A
site-directed mutagenesis of the propeptide residue, leads to reduced inhibition of mature PC1 by the separated propeptide mutant compared to the wild-type propeptide
R50A
site-directed mutagenesis of the propeptide residue, leads to increased inhibition of mature PC1 by the separated propeptide mutant compared to the wild-type propeptide
R51A
site-directed mutagenesis of the propeptide residue, leads to increased inhibition of mature PC1 by the separated propeptide mutant compared to the wild-type propeptide
R53A
site-directed mutagenesis of the propeptide residue, leads to reduced inhibition of mature PC1 by the separated propeptide mutant compared to the wild-type propeptide
R54A
site-directed mutagenesis of the propeptide residue, leads to increased inhibition of mature PC1 by the separated propeptide mutant compared to the wild-type propeptide
R62A
site-directed mutagenesis of the propeptide residue, leads to reduced inhibition of mature PC1 by the separated propeptide mutant compared to the wild-type propeptide
S52A
site-directed mutagenesis of the propeptide residue, unaltered inhibition of mature PC1 by the separated propeptide mutant compared to the wild-type propeptide
S52A/R53A
site-directed mutagenesis of the propeptide residues, leads to increased inhibition of mature PC1 by the separated propeptide mutant compared to the wild-type propeptide
N222D
-
leads to obesity, abnormal proinsulin processing, reduced fecundity, impaired autocatalysis and multiple endocrinological defects in mice homozygous for the mutation. Increased energy intake, a more efficient metabolism and reduced alpha-MSH signaling contribute to the obesity. Heterozygous littermates exhibit an intermediate phenotype for both sexes, thus this mutation results in a semi-dominant phenotype
additional information
additional information
single amino acid substitution in the PC1/3 propeptide can induce significant modifications of its inhibitory profile toward its cognate enzyme
additional information
-
construction of PC1 prosegment, amino acids 1-110, fused to the C-terminal PC1 tail, amino acids 619-753, termed proCT construct
additional information
-
generation of chimeric PC1-propeptide/SAAS CT peptide constructs, effects on C-terminal PC1 processing are limited to the construct containing the PC1 propeptide alone when expressed in AtT20 cells, while both the PC1 propeptide and the SAAS CT propeptide are inhibitory on C-terminal PC1 zymogen processing when expressed in HEK293 cells, overview
additional information
-
PC1/3 null mutant mice show C-terminally impaired but not completely blocked proIAPP processing, overview
additional information
-
concentration of progastrin in the antrum of PC1/3-null mice is elevated 3fold. Progastrin molecule is only partly cleaved at the dibasic Arg36-Arg37 site and even less at the Lys53-Lys54 site in the PC1/3-null mice
additional information
-
PC1/3DELTA significantly decreases prohormone convertase 1/3 promoter activity by more than 60%. A 50% reduction when both E-boxes are mutated, even though the STAT3 sites remain intact (PC1/3DELTAE12). Mutation of both STAT3 sites (PC1/3DELTAS12) does not affect basal prohormone convertase 1/3 promoter activity, but leptin stimulation is lost. Mutating the E-box furthest from the start site (E-box 1, PC1/3DELTAE1) only has a significant effect on prohormone convertase 1/3 promoter activity under leptin stimulation, whereas mutating the E-box closest to the start site (E-box 2, PC1/3DELTAE2) has a more pronounced effect on luciferase expression with a loss of approximately 50% prohormone convertase 1/3 promoter activity levels in both leptin-stimulated and unstimulated cells
additional information
-
design of prohormone convertase-2-specific mutations into the catalytic domain of PC1/3 in order to investigate the molecular contributions of these sequences to PC1/3-specific properties. The exchange of residues RQG314 with the SY sequence present in the same location within PC2 shifts the pH optimum of PC1/3 upward into the neutral range, other mutations in the catalytic domain had no effect. None of the full-length PC1/3 mutants examined exhibits increased specific activity, but the 66-kDa form of the RQG314SY mutant is 2 to 4 times more active than the 66-kDa form of wild-type PC1/3. Mutation of GIVTDA243248 to QPFMTDI, a molecular determinant of 7B2 binding, results in increased zymogen expression but no propeptide cleavage or secretion, suggesting that this mutant is trapped in the endoplasmic reticulum. None of the mutations examined confers PC2-specific properties. No mutant exhibits altered calcium requirements
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme from insect cells and larvae, about 48fold from larvae by PEG precipitation, concanavalin A affinity and hydroxyapatite chromatography, and gel filtration
-
recombinant PC1/3 purified. PC1/3 CT peptide purified by His-affinity chromatography and RP-HPLC
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
co-expression of PC1/3 and rat pro-islet amyloid polypeptide, proIAPP, in GH3 cells lacking the enzyme, leads to cleavage of recombinant proIAPP
-
expressed in GH4 cells, entire C-terminal tail of PC1 overexpressed in AtT-20 cells
-
expression in Spodoptera frugiperda Sf9 cells and Trichoplusioa ni larvae using the baculovirus Autographa californica transfection system, method optimization, modification of the enzyme by C-terminal truncation and exchange of the PC1/3 signal peptide for the glycoprotein gp67 signal peptide, overview
-
expression of chimeric PC1-propeptide/SAAS CT peptide constructs in AtT20 cells and in HEK293 cells
-
expression of PC1 in GH3 cells, co-expression with proGHRH or preproGHRH, GH3 cells lack endogenous PC1 but contain PC2, EC 3.4.21.94, another prohormone processing enzyme
-
into pGL3 basic vector to yield wild-type prohormone convertase 1/3 promoter construct, expressed in N29/2 cell line
-
PC1/3 produced using the baculovirus expression system in Sf9 insect cells or through intracoelemic injection in insect larvae. PC1/3 CT-peptide from positions 592-726 cloned into a pet24b+ bacterial expression vector. The resulting C-terminally His-tagged protein expressed in Escherichia coli strain BL21 (DE3)
-
recombinant enzyme expressed in Sf9 cells, mPC1 cDNA inserted intoAutographa californica nuclear polyhedrosis virus, infection of Sf9 cells, mPC1 insert excised from recombinant vaccinia virus vector containg full-length cDNA
-
transient enzyme expression in enzyme-deficient rat GH4C1 cells, co-expression with wild-type and mutant proglucagon, glicentin, and/or glicentin-related polypeptide-glucagon, and oxyntomodulin from hamster, overview
-
transient expression of proCT construct in HEK293, FD11, CHO-K1, and AtT20 cells, the proCT construct is processed in the secretory pathway
-
transplantation of encapsulated PC2-expressing alpha TC-1 cells with PC1/3-expressing alpha TCdeltaPC2 cells in normal mice and low-dose streptozotocin-treated mice
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
UVB irradiation to the eye and stress loading increase the expression of prohormone convertase 1/3 and prohormone convertase 2 in the pituitary gland. The increase in expression of pituitary prohormone convertase 2 is greater in animals subjected to UVB eye irradiation than to stress, whereas no difference is seen between the two groups for the increase in PC1/3
analysis
-
highly specific and potent PC1 inhibitors proSAAS-(235-246) and proSAAS-(235-244) may be useful in development of an effective affinity procedure for the purification of PC1
medicine
additional information
-
PC1/3, through its various domains, is capable of controlling its enzymatic activity in all regions of the cell that it encounters
medicine
-
Pc1 N222D homozygous mice are obese and mimic humans with mutations in PC1. This mutation will be a valuable resource in understanding the role of prohormone processing in energy homeostasis
medicine
-
transplantation of PC1/3-expressing alpha-cells prevents streptozotocin-induced hyperglycemia by preserving beta-cell area and islet morphology, possibly via stimulating beta-cell replication. Expression of PC1/3 rather than PC2 in alpha-cells induces glucagon-like peptide 1 and glucagon-like peptide 2 production and converts the alpha-cell from a hyperglycemia-promoting cell to one that lowers blood glucose levels. Alteration of proglucagon processing in the alpha-cell may be therapeutically useful in the context of type 1 diabetes
medicine
-
significant activation of PC1/3 in the alpha-cells of pancreatic islet is observed in mouse models of insulin resistance such as pregnant, obese, diabetic and prediabetic NOD mice. Data suggest a role of alpha-cells for beta-cell proliferation and further for the endocrine cell network within an islet
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Steiner, D.F.; Smeekens, S.P.; Ohagi, S.; Chan, S.J.
The new enzymology of precursor processing endoproteases
J. Biol. Chem.
267
23435-23438
1992
Homo sapiens, Mus musculus
Smeekens, S.P.; Avruch, A.S.; LaMendola, J.; Chan, S.J.; Steiner, D.F.
Identification of a cDNA encoding a second putative prohormone convertase related to PC2 in AtT20 cells and islets of Langerhans
Proc. Natl. Acad. Sci. USA
88
340-344
1991
Mus musculus
Seidah, N.G.; Chretien, M.
Pro-protein convertases of subtilisin/kexin family
Methods Enzymol.
244
175-188
1994
Homo sapiens, Mus musculus
Basak, A.; Lazure, C.
Synthetic peptides derived from the prosegments of proprotein convertase 1/3 and furin are potent inhibitors of both enzymes
Biochem. J.
373
231-239
2003
Mus musculus
Jutras, I.; Seidah, N.G.; Reudelhuber, T.L.; Brechler, V.
Two activation states of the prohormone convertase PC1 in the secretory pathway
J. Biol. Chem.
272
15184-15188
1997
Mus musculus
Boudreault, A.; Gauthier, D.; Lazure, C.
Proprotein convertase PC1/3-related peptides are potent slow tight-binding inhibitors of murine PC1/3 and Hfurin
J. Biol. Chem.
273
31574-31580
1998
Mus musculus
Viale, A.; Ortola, C.; Hervieu, G.; Furuta, M.; Barbero, P.; Steiner, D.F.; Seidah, N.G.; Nahon, J.L.
Cellular localization and role of prohormone convertases in the processing of pro-melanin concentrating hormone in mammals
J. Biol. Chem.
274
6536-6545
1999
Mus musculus, Rattus norvegicus, Rattus norvegicus Wistar
Jutras, I.; Seidah, N.G.; Reudelhuber, T.L.
A predicted alpha-helix mediates targeting of the proprotein convertase PC1 to the regulated secretory pathway
J. Biol. Chem.
275
40337-40343
2000
Mus musculus, Rattus norvegicus
Basak, A.; Koch, P.; Dupelle, M.; Fricker, L.D.; Devi, L.A.; Chretien, M.; Seidah, N.G.
Inhibitory specificity and potency of proSAAS-derived peptides toward proprotein convertase 1
J. Biol. Chem.
276
32720-32728
2001
Mus musculus
Li, Q.L.; Jansen, E.; Friedman, T.C.
Regulation of prohormone convertase 1 (PC1) by gp130-related cytokines
Mol. Cell. Endocrinol.
158
143-152
1999
Mus musculus, Rattus norvegicus
Muller, L.; Lindberg, I.
The cell biology of the prohormone convertases PC1 and PC2
Prog. Nucleic Acid Res. Mol. Biol.
63
69-108
1999
Drosophila sp. (in: flies), Mus musculus, no activity in Caenorhabditis elegans, Rattus norvegicus, no activity in Lymnaea stagnalis
Boudreault, A.; Gauthier, D.; Rondeau, N.; Savaria, D.; Seidah, N.G.; Chretien, M.; Lazure, C.
Molecular characterization, enzymatic analysis, and purification of murine proprotein convertase-1/3 (PC1/PC3) secreted from recombinant baculovirus-infected insect cells
Protein Expr. Purif.
14
353-366
1998
Mus musculus
Marzban, L.; Trigo-Gonzalez, G.; Zhu, X.; Rhodes, C.J.; Halban, P.A.; Steiner, D.F.; Verchere, C.B.
Role of beta-cell prohormone convertase (PC)1/3 in processing of pro-islet amyloid polypeptide
Diabetes
53
141-148
2004
Mus musculus
Posner, S.F.; Vaslet, C.A.; Jurofcik, M.; Lee, A.; Seidah, N.G.; Nillni, E.A.
Stepwise posttranslational processing of pro-growth hormone-releasing hormone (proGHRH) polypeptide by furin and PC1
Endocrine
23
199-213
2004
Mus musculus
Dey, A.; Norrbom, C.; Zhu, X.; Stein, J.; Zhang, C.; Ueda, K.; Steiner, D.F.
Furin and prohormone convertase 1/3 are major convertases in the processing of mouse pro-growth hormone-releasing hormone
Endocrinology
145
1961-1971
2004
Mus musculus
Dey, A.; Lipkind, G.M.; Rouille, Y.; Norrbom, C.; Stein, J.; Zhang, C.; Carroll, R.; Steiner, D.F.
Significance of prohormone convertase 2, PC2, mediated initial cleavage at the proglucagon interdomain site, Lys70-Arg71, to generate glucagon
Endocrinology
146
713-727
2005
Mus musculus
Salvas, A.; Benjannet, S.; Reudelhuber, T.L.; Chretien, M.; Seidah, N.G.
Evidence for proprotein convertase activity in the endoplasmic reticulum/early Golgi
FEBS Lett.
579
5621-5625
2005
Mus musculus
Ugleholdt, R.; Poulsen, M.L.; Holst, P.J.; Irminger, J.C.; Orskov, C.; Pedersen, J.; Rosenkilde, M.M.; Zhu, X.; Steiner, D.F.; Holst, J.J.
Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor
J. Biol. Chem.
281
11050-11057
2006
Mus musculus
Rabah, N.; Gauthier, D.; Wilkes, B.C.; Gauthier, D.J.; Lazure, C.
Single amino acid substitution in the PC1/3 propeptide can induce significant modifications of its inhibitory profile toward its cognate enzyme
J. Biol. Chem.
281
7556-7567
2006
Mus musculus (P63239)
Lee, S.N.; Prodhomme, E.; Lindberg, I.
Prohormone convertase 1 (PC1) processing and sorting: effect of PC1 propeptide and proSAAS
J. Endocrinol.
182
353-364
2004
Mus musculus
Tagen, M.B.; Beinfeld, M.C.
Recombinant prohormone convertase 1 and 2 cleave purified pro cholecystokinin (CCK) and a synthetic peptide containing CCK 8 Gly Arg Arg and the carboxyl-terminal flanking peptide
Peptides
26
2530-2535
2005
Mus musculus
Rabah, N.; Gauthier, D.J.; Gauthier, D.; Lazure, C.
Improved PC1/3 production through recombinant expression in insect cells and larvae
Protein Expr. Purif.
37
377-384
2004
Mus musculus
Rabah, N.; Gauthier, D.; Dikeakos, J.D.; Reudelhuber, T.L.; Lazure, C.
The C-terminal region of the proprotein convertase 1/3 (PC1/3) exerts a bimodal regulation of the enzyme activity in vitro
FEBS J.
274
3482-3491
2007
Mus musculus
Wideman, R.D.; Covey, S.D.; Webb, G.C.; Drucker, D.J.; Kieffer, T.J.
A switch from prohormone convertase (PC)-2 to PC1/3 expression in transplanted alpha-cells is accompanied by differential processing of proglucagon and improved glucose homeostasis in mice
Diabetes
56
2744-2752
2007
Mus musculus
Lloyd, D.J.; Bohan, S.; Gekakis, N.
Obesity, hyperphagia and increased metabolic efficiency in Pc1 mutant mice
Hum. Mol. Genet.
15
1884-1893
2006
Homo sapiens, Mus musculus, Mus musculus C57BL/6
Lou, H.; Smith, A.M.; Coates, L.C.; Cawley, N.X.; Loh, Y.P.; Birch, N.P.
The transmembrane domain of the prohormone convertase PC3: a key motif for targeting to the regulated secretory pathway
Mol. Cell. Endocrinol.
267
17-25
2007
Mus musculus, Rattus norvegicus
Rehfeld, J.F.; Zhu, X.; Norrbom, C.; Bundgaard, J.R.; Johnsen, A.H.; Nielsen, J.E.; Vikesaa, J.; Stein, J.; Dey, A.; Steiner, D.F.; Friis-Hansen, L.
Prohormone convertases 1/3 and 2 together orchestrate the site-specific cleavages of progastrin to release gastrin-34 and gastrin-17
Biochem. J.
415
35-43
2008
Mus musculus
Fox, D.L.; Good, D.J.
Nescient helix-loop-helix 2 interacts with signal transducer and activator of transcription 3 to regulate transcription of prohormone convertase 1/3
Mol. Endocrinol.
22
1438-1448
2008
Mus musculus
Ozawa, A.; Peinado, J.R.; Lindberg, I.
Modulation of prohormone convertase 1/3 properties using site-directed mutagenesis
Endocrinology
151
4437-4445
2010
Mus musculus
Kilimnik, G.; Kim, A.; Steiner, D.; Friedman, T.; Hara, M.
Intraislet production of GLP-1 by activation of prohormone convertase 1/3 in pancreatic alpha-cells in mouse models of beta-cell regeneration
Islets
2
149-155
2010
Mus musculus
Hiramoto, K.; Yamate, Y.; Kobayashi, H.; Ishii, M.; Sato, E.F.; Inoue, M.
Ultraviolet B irradiation of the mouse eye induces pigmentation of the skin more strongly than does stress loading, by increasing the levels of prohormone convertase 2 and alpha-melanocyte-stimulating hormone
Clin. Exp. Dermatol.
38
71-76
2013
Mus musculus (P63239)
Li, J.; Mao, Z.; Huang, J.; Xia, J.
PICK1 is essential for insulin production and the maintenance of glucose homeostasis
Mol. Biol. Cell
29
587-596
2018
Mus musculus
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