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Information on EC 3.4.21.94 - proprotein convertase 2 and Organism(s) Mus musculus and UniProt Accession P21661
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EC Tree
3.4.21.94 proprotein convertase 2Specify your search results
Word Map
- 3.4.21.94
-
neuropeptides
-
proopiomelanocortin
- medicine
-
secretogranin
-
prodynorphin
-
peptidomic
-
convertase-1
- molecular biology
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 and neuropeptides from their precursors, generally by hydrolysis of -Lys-Arg-/- bonds
Synonyms
pcsk2, proprotein convertase 2, prohormone convertase-2, pc2-like enzyme, pro-protein convertase-2, proprotein convertase subtilisin/kexin-type 2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Neuroendocrine convertase 2
-
-
-
-
PC2
prohormone convertase 2
-
-
additional information
-
the enzyme belongs to the proprotein protease family of mammalian calcium-dependent serine proteases
PC2
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
130960-94-0
-
130960-95-1
-
388092-42-0
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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
2-aminobenzoyl-LPSDEEGESYKEVPEMEKRYGGFMQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
2-aminobenzoyl-LPSDEEGESYKEVPEMEKR + YGGFMQ-N-(2,4-dinitrophenyl)ethylenediamine
-
-
-
?
2-aminobenzoyl-Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-Gly-Arg-Pro-Glu-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-Val-Pro-Arg-Met-Glu-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Gln-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
?
Ac-Arg-Phe-Ala-Arg-4-methylcoumarin 7-amide + H2O
Ac-Arg-Phe-Ala-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Ac-Arg-Pro-Lys-Arg-4-methylcoumarin 7-amide + H2O
Ac-Arg-Pro-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Ac-Lys-Ser-Lys-Arg-4-methylcoumarin 7-amide + H2O
Ac-Lys-Ser-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Ac-Orn-Ser-Lys-Arg-4-methylcoumarin 7-amide + H2O
Ac-Orn-Ser-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Boc-Gly-Arg-Arg-4-methylcoumarin 7-amide + H2O
Boc-Gly-Arg-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Boc-Gly-Lys-Arg-4-methylcoumarin 7-amide + H2O
Boc-Gly-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Boc-Val-Pro-Arg-4-methylcoumarin 7-amide + H2O
Boc-Val-Pro-Arg + 7-amino-4-methylcoumarin
-
-
-
?
CBZ-Arg-Ser-Lys-Arg-4-methylcoumarin 7-amide + H2O
CBZ-Arg-Ser-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
-
-
?
glicentin1-69 + H2O
glucagon + glicentin-related polypeptide + GLP-1
-
glicentin lacks the signal sequence of proglucagon, residues -20-1, recombinant hamster substrate and murine enzyme co-expressed in rat GH4C1 cells, cleavage at the proglucagon interdomain site Lys70-Arg71-/-, at Lys31-Arg32-/-, and at -/-Lys62-Arg63
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
-
?
peptide B-derived peptides + H2O
?
-
cleavage site specificity of wild-type and mutant PC2, overview
-
-
?
pGlu-Arg-Thr-Lys-Arg-4-methylcoumarin 7-amide + 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 are 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 are required, in vitro the cleavage site is inaccessible for the enzyme
peptide product analysis
-
?
pro-islet amyloid polypeptide + H2O
islet amyloid polypeptide processing intermediate + N-terminal pro-peptide
-
precursor of IAPP or amylin, the major component of islet amyloid, cleavage at the N-terminus, but not the C-terminus, which would also be required for activation, the complete activation is catalyzed by PC1, EC 3.4.21.93
-
-
?
prodynorphin + H2O
dynorphin A 1-17 + dynorphin B 1-13 + alpha-neo-endorphin + C-peptide + dynorphin A 1-8 + ?
-
-
-
?
proenkphalin-derived peptide + H2O
?
-
the preferred cleavage site sequence of PC2 is YGGFLKR-/-FAESL
-
-
?
proglucagon1-158 + H2O
glucagon + glicentin-related polypeptide + GLP-1 + IP2/GLP-2
-
recombinant hamster substrate and murine enzyme co-expressed in rat GH4C1 cells, cleavage at the proglucagon interdomain site Lys70-Arg71-/-, at Lys31-Arg32-/-, and at -/-Lys62-Arg63
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
-
?
proIAPP + H2O
mature IAPP
-
enhanced NH(2)-terminal processing of proIAPP by adenoviral expression of PC2, reducing (pro)IAPP-induced cell death in GH3 cells. Overexpression of PC2 in INS-1 beta-cells also enhances NH(2)-terminal processing of proIAPP
-
-
?
pGlu-Arg-Thr-Lys-Arg-4-methylcoumarin 7-amide + H2O
pGlu-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
?
pGlu-Arg-Thr-Lys-Arg-4-methylcoumarin 7-amide + H2O
pGlu-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
?
pGlu-Arg-Thr-Lys-Arg-4-methylcoumarin 7-amide + H2O
pGlu-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
?
proenkephalin + H2O
opioid-active enkephalin + ?
-
cleaves prohormones and proneuropeptides from inactive large precursors to generate activre peptide for extracellular release
-
?
additional information
?
-
-
prefers Arg at positions P4 and P5 in peptide B IQ substrates, Boc-Val-Leu-Lys-4-methylcoumarin 7-amide is no substrate
-
?
additional information
?
-
-
glucose-dependent insulinotropic polypeptide precursor is no substrate of PC2
-
-
?
additional information
?
-
-
cleavage site specificity, activity with mutant proglucagon and truncation variants, analysis of importance of substrate domain structure, molecular modeling, overview
-
-
?
additional information
?
-
-
sequences with a Trp, Tyr and/or Pro in the P1' or P2' position, or a basic residue in the P3 position, are preferentially cleaved by PC2
-
-
?
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
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 are required, in vitro the cleavage site is inaccessible for the enzyme
peptide product analysis
-
?
pro-islet amyloid polypeptide + H2O
islet amyloid polypeptide processing intermediate + N-terminal pro-peptide
-
precursor of IAPP or amylin, the major component of islet amyloid, cleavage at the N-terminus, but not the C-terminus, which would also be required for activation, the complete activation is catalyzed by PC1, EC 3.4.21.93
-
-
?
additional information
?
-
-
glucose-dependent insulinotropic polypeptide precursor is no substrate of PC2
-
-
?
proenkephalin + H2O
opioid-active enkephalin + ?
-
cleaves prohormones and proneuropeptides from inactive large precursors to generate activre peptide for extracellular release
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2R)-1-[2-[3,5-bis(trifluoromethyl)phenyl]ethyl]-4-[(1R)-2-cyclohexyl-1-[[(2S)-2-[[(2R)-2-(cyclohexylmethyl)piperazin-1-yl]methyl]pyrrolidin-1-yl]methyl]ethyl]-2-(cyclohexylmethyl)piperazine
-
-
(2R)-4-((R)-1-cyclohexyl-3-((S)-2-(((R)-2-(cyclohexylmethyl)piperazin-1-yl)methyl)pyrrolidin-1-yl)propan-2-yl)-2-(cyclohexylmethyl)-1-(2-(4-isobutylphenyl)propyl)piperazine
-
-
(2R)-4-((R)-1-cyclohexyl-3-((S)-2-(((S)-2-(cyclohexylmethyl)piperazin-1-yl)methyl)pyrrolidin-1-yl)propan-2-yl)-2-(cyclohexylmethyl)-1-(2-(4-isobutylphenyl)propyl)piperazine
-
-
(R)-1-((4-tert-butylcyclohexyl)methyl)-4-((R)-1-cyclohexyl-3-((S)-2-(((S)-2-(cyclohexylmethyl)piperazin-1-yl)methyl)pyrrolidin-1-yl)propan-2-yl)-2-(cyclohexylmethyl)piperazine
-
-
N-((R)-1-((2R,5R)-2,5-bis(4-hydroxybenzyl)-2,3,5,6-tetrahydro-1H-imidazo[1,2-a]imidazol-1-yl)-3-(4-hydroxyphenyl)propan-2-yl)-3-(3,4,5-trimethoxyphenyl)propanamide
-
-
N-((R)-1-((2R,5R)-2,5-bis(4-hydroxybenzyl)-2,3,5,6-tetrahydro-1H-imidazo[1,2-a]imidazol-1-yl)-3-(4-methoxyphenyl)propan-2-yl)-3,4-dimethoxybenzamide
-
-
N-((R)-1-((2R,5R)-2,5-bis(4-hydroxybenzyl)-2,3,5,6-tetrahydro-1H-imidazo[1,2-a]imidazol-1-yl)-3-(4-methoxyphenyl)propan-2-yl)-3-(3,4-dimethoxyphenyl)propanamide
-
-
additional information
-
after screening 38 small-molecule positional scanning libraries against PC2, two promising chemical scaffolds are identified: bicyclic guanidines, and pyrrolidine bis-piperazines. A set of individual compounds is designed from each library and tested against PC2. Pyrrolidine bis-piperazines are irreversible, time-dependent inhibitors of PC2, exhibiting noncompetitive inhibition kinetics
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
protein 7B2
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pro-PC2 requires interaction with this neuroendocrine-specific protein for its maturation and activation
-
small neuroendocrine protein 7B2
-
7B2 overexpression decreases the secretion and increases the activity of PC2 within alpha-TC6 cells
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
kinetics of wild-type and mutant enzymes
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00054
(2R)-1-[2-[3,5-bis(trifluoromethyl)phenyl]ethyl]-4-[(1R)-2-cyclohexyl-1-[[(2S)-2-[[(2R)-2-(cyclohexylmethyl)piperazin-1-yl]methyl]pyrrolidin-1-yl]methyl]ethyl]-2-(cyclohexylmethyl)piperazine
-
-
0.00056
(2R)-4-((R)-1-cyclohexyl-3-((S)-2-(((R)-2-(cyclohexylmethyl)piperazin-1-yl)methyl)pyrrolidin-1-yl)propan-2-yl)-2-(cyclohexylmethyl)-1-(2-(4-isobutylphenyl)propyl)piperazine
-
-
0.00066
(2R)-4-((R)-1-cyclohexyl-3-((S)-2-(((S)-2-(cyclohexylmethyl)piperazin-1-yl)methyl)pyrrolidin-1-yl)propan-2-yl)-2-(cyclohexylmethyl)-1-(2-(4-isobutylphenyl)propyl)piperazine
-
-
0.00059
(R)-1-((4-tert-butylcyclohexyl)methyl)-4-((R)-1-cyclohexyl-3-((S)-2-(((S)-2-(cyclohexylmethyl)piperazin-1-yl)methyl)pyrrolidin-1-yl)propan-2-yl)-2-(cyclohexylmethyl)piperazine
-
-
0.0036
N-((R)-1-((2R,5R)-2,5-bis(4-hydroxybenzyl)-2,3,5,6-tetrahydro-1H-imidazo[1,2-a]imidazol-1-yl)-3-(4-hydroxyphenyl)propan-2-yl)-3-(3,4,5-trimethoxyphenyl)propanamide
-
-
0.01
N-((R)-1-((2R,5R)-2,5-bis(4-hydroxybenzyl)-2,3,5,6-tetrahydro-1H-imidazo[1,2-a]imidazol-1-yl)-3-(4-methoxyphenyl)propan-2-yl)-3,4-dimethoxybenzamide
-
-
0.0033
N-((R)-1-((2R,5R)-2,5-bis(4-hydroxybenzyl)-2,3,5,6-tetrahydro-1H-imidazo[1,2-a]imidazol-1-yl)-3-(4-methoxyphenyl)propan-2-yl)-3-(3,4-dimethoxyphenyl)propanamide
-
-
additional information
additional information
-
inhibition kinetics of wild-type and mutant enzymes
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
PC2 protein in the hypothalamus is colocalized with free fatty acid receptor GPR40/FFA1
additional information
-
alpha TC1 cells express PC2, alpha TCdeltaPC2 cells do not express bioactive PC2
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
in wolframin knockout mice, the activity of PC2 in hippocampus is significantly increased, while the protein levels of proPC2 and PC2 and of chaperone secretogranin are unchanged. The processing of proSAAS and proenkephalin is altered in the hippocampus of wolframin knockout mice
physiological function
physiological function
-
PC2 functions in the generation of neuropeptides from their precursors, of neuropeptides/secretory pathway proteins, quantitative peptidomics, overview. Role of PC2 in the processing of peptides in a variety of brain regions
physiological function
-
proglucagon cleavage has a greater dependence on PC2 activity than other precursors (e.g. proopiomelanocortin) and 7B2-dependent routing of PC2 to secretory granules is cell line-specific
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). NEC2_MOUSE
637
0
70785
Swiss-Prot
Secretory Pathway (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A322T/S323N
-
site-directed mutagenesis, the mutant shows unaltered activity, but slightly decreased sensitivity for inhibitor 7B2 CT peptide compared to the wild-type enzyme
D278E
-
site-directed mutagenesis of the S4/S5 subsite residue, the mutant shows altered substrate preferences, increased activity and reduced sensitivity to inhibitor 7B2 CT peptide compared to the wild-type enzyme
L341W
-
site-directed mutagenesis of the residue from the far edge of subsite S2', the mutant shows increased activity, and slightly decreased sensitivity for inhibitor 7B2 CT peptide compared to the wild-type enzyme
N356S
-
site-directed mutagenesis of the distant prime site residue, the mutant shows altered substrate preferences compared to the wild-type enzyme
R281G/E282R
-
site-directed mutagenesis of the S6 edge residue R281, the mutant shows largely altered substrate preferences and reduced activity compared to the wild-type enzyme
S380T
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
S383A
-
active site mutant, seems to be folded correctly. Is efficiently secreted as the intact zymogen in CHO-K1 cells. Its propeptide can productively insert into the mutated binding pocket without causing misfolding. In AtT-20 cells, mutant S383A is cleaved at the secondary cleavage site within the propeptide. The mutant can not be cleaved by active PC2, so that other proprotein convertases, but not PC2, may be responsible for secondary site processing. This cleavage event is pH-dependent and is inhibited by the proprotein convertase inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethylketone
T271E
-
site-directed mutagenesis of the residue separating the subsites S3 and S5, the mutant shows increased activity compared to the wild-type enzyme
T271N
-
site-directed mutagenesis of the residue separating the subsites S3 and S5, the mutant shows unaltered activity, but slightly decreased sensitivity for inhibitor 7B2 CT peptide compared to the wild-type enzyme
additional information
additional information
-
PC2-deficient cells do not show alterations in glucose-dependent insulinotropic polypeptide precursor processing activity
additional information
-
approximately one third of peptides found in wild-type mice are not detectable in PC2 knock-out mice, and another third are present at levels ranging from 25 to 75% of wild-type levels
additional information
-
in PC2-null mice, basal responses and responses after a cold swim are similar to wild-type mice. After a short forced swim in warm water, PC2-null mice are significantly less responsive to the stimuli than wild-type mice, an indication of increased opioid-mediated stress-induced analgesia. Enhanced analgesia in PC2-null mice may be caused by an accumulation of opioid precursor processing intermediates with potent analgesic effects, or by loss of anti-opioid peptides
additional information
-
islets from mice lacking PC2 and with beta-cell expression of human proIAPP develop amyloid associated with beta-cell death during 2-week culture. Rescue of PC2 expression by ex vivo transduction with Ad-PC2 restores NH(2)-terminal processing to mature IAPP and decreases both the extent of amyloid formation and the number of TUNEL-positive cells, and enhances cell survival
additional information
-
PC2-/- mice, brain levels of neuromedin N are reduced by more than 50% with a compensatory increase in the levels of large neuromedin N. Processing at site 2 is impaired. 20% reduction in neurotensin levels
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant PC2 wild-type and mutant S383A purified on anion-exchange column and by gel filtration
-
recombinant wild-type and mutant PC2 from CHO-K1 cells by adsorption chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
co-expression of PC2 and rat pro-islet amyloid polypeptide, proIAPP, in GH3 cells lacking the enzyme, does not lead to complete cleavage of recombinant proIAPP, but to cleavage of the C-terminal site of proIAPP
-
gene PC2, genotyping of wild-type and haplotype and holotype PC2-deficient mice
-
GH3 cells or INS-1 beta-cells cotransduced with proIAPP and PC2 by adenoviral expression
-
overexpressed in Chinese hamster ovary cells supertransfected with rat cDNA 7B2
-
pcDNA3 plasmid encoding either PC2 wild-type or mutant S383A expressed in CHO-K1/7B2 cells or AtT-20/7B2 cells
-
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
-
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
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
intracerebroventricular injection of docosahexaenoic acid or GW9508, a free fatty acid receptor GPR40/FFA1 agonsit, significantly increases PC2 protein expression in the hypothalamus. This increase in PC2 expression is inhibited by pretreatment with GW1100, a GPR40/FFA1 antagonist. application of complete Freund's adjuvant also increases expression
mutant transcriptional factor paired box Pax6 R266Stop protein is stable and regulates the activity of prohormone convertase 2 promoter. The wild-type PAX6 protein imparts a transcriptional effect, and the mutant PAX6 can also regulate the downstream molecules
-
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
medicine
medicine
-
defects in processing, sorting, and/or secretion of (pro)IAPP associated with beta-cell dysfunction in type 2 diabetes and insulinomas may result in production and secretion of elevated levels of proIAPP and its NH(2)-terminally unprocessed form, leading to intracellular and/or fibril formation and beta-cell apoptosis. Restoration of intact IAPP processing may be a potential therapeutic approach to prevent or slow (pro)IAPP-induced beta-cell apoptosis and maintain beta-cell mass in type 2 diabetes
medicine
-
transplantation of PC2-expressing alpha-cells increases plasma glucagon levels and causes mild fasting hyperglycemia, impairs glucose tolerance, and alpha-cell hypoplasia. PC2-expressing alpha-cells neither prevent streptozotocin-induced hyperglycemia nor increased beta-cell proliferation in the context of type 1 diabetes
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Cornwall, G.A.; Cameron, A.; Lindberg, I.; Hardy, D.M.; Cormier, N.; Hsia, N.
The cystatin-related epididymal spermatogenic protein inhibits the serine protease prohormone convertase 2
Endocrinology
144
901-908
2003
Mus musculus
Johanning, K.; Juliano, M.A.; Juliano, L.; Lazure, C.; Lamango, N.S.; Steiner, D.F.; Lindberg, I.
Specificity of prohormone convertase 2 on proenkephalin and proenkephalin-related substrates
J. Biol. Chem.
273
22672-22680
1998
Mus musculus
Day, R.; Lazure, C.; Basak, A.; Boudreault, A.; Limperis, P.; Dong, W.; Lindberg, I.
Prodynorphin processing by proprotein convertase 2. Cleavage at single basic residues and enhanced processing in the presence of carboxypeptidase activity
J. Biol. Chem.
273
829-836
1998
Mus musculus, Rattus norvegicus
Apletalina, E.V.; Muller, L.; Lindberg, I.
Mutations in the catalytic domain of prohormone convertase 2 result in decreased binding to 7B2 and loss of inhibition with 7B2 C-terminal peptide
J. Biol. Chem.
275
14667-14677
2000
Mus musculus
Li, Q.L.; Naqvi, S.; Shen, X.; Liu, Y.J.; Lindberg, I.; Friedman, T.C.
Prohormone convertase 2 enzymatic activity and its regulation in neuro-endocrine cells and tissues
Regul. Pept.
110
197-205
2003
Homo sapiens, Mus musculus, Rattus norvegicus
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
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
Kacprzak, M.M.; Than, M.E.; Juliano, L.; Juliano, M.A.; Bode, W.; Lindberg, I.
Mutations of the PC2 substrate binding pocket alter enzyme specificity
J. Biol. Chem.
280
31850-31858
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
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
Lee, S.N.; Kacprzak, M.M.; Day, R.; Lindberg, I.
Processing and trafficking of a prohormone convertase 2 active site mutant
Biochem. Biophys. Res. Commun.
355
825-829
2007
Mus musculus
Marzban, L.; Rhodes, C.J.; Steiner, D.F.; Haataja, L.; Halban, P.A.; Verchere, C.B.
Impaired NH2-terminal processing of human proislet amyloid polypeptide by the prohormone convertase PC2 leads to amyloid formation and cell death
Diabetes
55
2192-2201
2006
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
Kitabgi, P.
Prohormone convertases differentially process pro-neurotensin/neuromedin N in tissues and cell lines
J. Mol. Med.
84
628-634
2006
Homo sapiens, Mus musculus, Rattus norvegicus
Pan, H.; Che, F.Y.; Peng, B.; Steiner, D.F.; Pintar, J.E.; Fricker, L.D.
The role of prohormone convertase-2 in hypothalamic neuropeptide processing: a quantitative neuropeptidomic study
J. Neurochem.
98
1763-1777
2006
Mus musculus
Croissandeau, G.; Wahnon, F.; Yashpal, K.; Seidah, N.G.; Coderre, T.J.; Chretien, M.; Mbikay, M.
Increased stress-induced analgesia in mice lacking the proneuropeptide convertase PC2
Neurosci. Lett.
406
71-75
2006
Mus musculus
Kowalska, D.; Liu, J.; Appel, J.R.; Ozawa, A.; Nefzi, A.; Mackin, R.B.; Houghten, R.A.; Lindberg, I.
Synthetic small-molecule prohormone convertase 2 inhibitors
Mol. Pharmacol.
75
617-625
2009
Mus musculus
Zhang, X.; Pan, H.; Peng, B.; Steiner, D.F.; Pintar, J.E.; Fricker, L.D.
Neuropeptidomic analysis establishes a major role for prohormone convertase-2 in neuropeptide biosynthesis
J. Neurochem.
112
1168-1179
2010
Mus musculus
Helwig, M.; Lee, S.N.; Hwang, J.R.; Ozawa, A.; Medrano, J.F.; Lindberg, I.
Dynamic modulation of PC2-mediated precursor processing by 7B2: preferential effect on glucagon synthesis
J. Biol. Chem.
286
42504-42513
2011
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 (P21661)
Chen, Y.; Cao, W.; Zhou, S.; Shen, L.; Wen, J.
Mutant PAX6 downregulates prohormone convertase 2 expression in mouse islets
Exp. Biol. Med. (Maywood)
238
1259-1264
2013
Mus musculus
Nakamoto, K.; Aizawa, F.; Nishinaka, T.; Tokuyama, S.
Regulation of prohormone convertase 2 protein expression via GPR40/FFA1 in the hypothalamus
Eur. J. Pharmacol.
762
459-463
2015
Mus musculus (P21661)
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