Information on EC 3.4.21.94 - proprotein convertase 2

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The expected taxonomic range for this enzyme is: Bilateria

EC NUMBER
COMMENTARY hide
3.4.21.94
-
RECOMMENDED NAME
GeneOntology No.
proprotein convertase 2
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
release of protein hormones and neuropeptides from their precursors, generally by hydrolysis of -Lys-Arg-/- bonds
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
130960-94-0
-
130960-95-1
-
388092-42-0
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain N2, variety Bristol
-
-
Manually annotated by BRENDA team
strain N2, variety Bristol
-
-
Manually annotated by BRENDA team
collected from Heron Island Reef, Great Barrier Reef, Australia, gene PC2 encodes a PC2-like enzyme
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
medaka
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
PC2 activity is reduced in ischemic brains, brain ischemia attenuates PC2 and PC2-mediated neuropeptide processing. This attenuation may play a role in the pathology of ischemic brain injury. Intracerebroventricular administration of synthetic PC2 substrate dynorphin-A(1-8) significantly reduces the extent of ischemic brain injury, overview
metabolism
prohormone convertase 2 belongs to a family of enzymes involved in the proteolytic maturation of neuropeptide precursors into mature peptides that act as neurotransmitters, neuromodulators or neurohormones
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-aminobenzoyl-LPSDEEGESYKEVPEMEKRYGGFMQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-Gly-Arg-Pro-Glu-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-Val-Pro-Arg-Met-Glu-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Gln-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
show the reaction diagram
-
-
-
?
Ac-Arg-Phe-Ala-Arg-4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
-
-
?
Ac-Arg-Pro-Lys-Arg-4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
-
-
?
Ac-Lys-Ser-Lys-Arg-4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
-
-
?
Ac-Orn-Ser-Lys-Arg-4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
-
-
?
Boc-Gly-Arg-Arg-4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
-
-
?
Boc-Gly-Lys-Arg-4-methylcoumarin 7-amide + H2O
Boc-Gly-Lys-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
Boc-Val-Pro-Arg-4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
-
-
?
CBZ-Arg-Ser-Lys-Arg-4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
-
-
?
Cbz-Arg-Ser-Lys-Arg-aminomethylcoumarin + H2O
?
show the reaction diagram
-
-
-
?
cholecystokinin 8-containing peptide + H2O
?
show the reaction diagram
-
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
-
-
?
dynorphin A 1-17 + H2O
?
show the reaction diagram
-
-
-
?
dynorphin AB 1-32 + H2O
?
show the reaction diagram
-
-
-
?
dynorphin-A(1-8) + H2O
?
show the reaction diagram
-
-
-
-
?
glicentin1-69 + H2O
glucagon + glicentin-related polypeptide + GLP-1
show the reaction diagram
-
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
-
?
L-pGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin + H2O
L-pGlu-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
leumorphin + H2O
?
show the reaction diagram
-
-
-
?
peptide B-derived peptides + H2O
?
show the reaction diagram
-
cleavage site specificity of wild-type and mutant PC2, overview
-
-
?
pGlu-Arg-Thr-Lys-Arg-4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
pro-cholecystokinin + H2O
N-terminal propeptide + C-terminal cholecystokinin 8 Gly Arg Arg peptide + remaining CCK peptide
show the reaction diagram
-
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
show the reaction diagram
-
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
show the reaction diagram
-
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
-
-
?
pro-neurotensin/neuromedin N + H2O
neurotensin + neuromedin N
show the reaction diagram
Pro-opiomelanocortin + H2O
Opiomelanocortin + ?
show the reaction diagram
-
from mouse and pig
-
-
-
prodynorphin + H2O
dynorphin + ?
show the reaction diagram
prodynorphin + H2O
dynorphin A 1-17 + dynorphin B 1-13 + alpha-neo-endorphin + C-peptide + dynorphin A 1-8 + ?
show the reaction diagram
-
-
-
?
Proenkephalin + H2O
Enkephalin + ?
show the reaction diagram
-
human
-
-
-
proenkephalin + H2O
opioid-active enkephalin + ?
show the reaction diagram
proenkphalin-derived peptide + H2O
?
show the reaction diagram
-
the preferred cleavage site sequence of PC2 is YGGFLKR-/-FAESL
-
-
?
Proglucagon + H2O
?
show the reaction diagram
proglucagon + H2O
glucagon
show the reaction diagram
-
-
-
-
?
Proglucagon + H2O
Glucagon + ?
show the reaction diagram
-
dibasic cleavage sites
-
-
proglucagon1-158 + H2O
glucagon + glicentin-related polypeptide + GLP-1 + IP2/GLP-2
show the reaction diagram
-
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
show the reaction diagram
-
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
-
-
?
Proinsulin + H2O
Insulin + ?
show the reaction diagram
-
selective cleavage only at the C peptide-A chain junction
-
-
-
proPC2 + H2O
mature PC2
show the reaction diagram
-
-
-
-
?
prothyrotropin-releasing hormone + H2O
thyrotropin-releasing hormone + pro-peptide of thyrotropin-releasing hormone
show the reaction diagram
pyr-Glu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
somatostatin + H2O
?
show the reaction diagram
-
PC2 may function as sorting element for somatostatin for its maturation and processing to appropiate targets
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
pro-cholecystokinin + H2O
N-terminal propeptide + C-terminal cholecystokinin 8 Gly Arg Arg peptide + remaining CCK peptide
show the reaction diagram
-
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
show the reaction diagram
-
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
-
-
?
proenkephalin + H2O
opioid-active enkephalin + ?
show the reaction diagram
Proglucagon + H2O
?
show the reaction diagram
prothyrotropin-releasing hormone + H2O
thyrotropin-releasing hormone + pro-peptide of thyrotropin-releasing hormone
show the reaction diagram
-
processing and activation of the inactive prohormone is required for regulation of energy balance via leptin, enzyme regulation, overview
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
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
-
-
7B2 C-terminal peptide
-
-
-
7B2 CT peptide
-
potent specific inhibition of PC2
-
CT peptide
-
a PC2-specific inhibitor
-
cystatin-related epidiymal spermatogenic protein
-
competitive inhibitor
-
decanoyl-Arg-Val-Lys-Arg-chloromethylketone
-
-
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
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
protein 7B2
-
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
-
additional information
-
leptin stimulates the PC1 expression via STAT3 acting on the PC2 promoter
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.27
Ac-Arg-Phe-Ala-Arg-4-methylcoumarin 7-amide
-
pH 5.0, 37C
0.26
Ac-Arg-Pro-Lys-Arg-4-methylcoumarin 7-amide
-
pH 5.0, 37C
0.14
Ac-Lys-Ser-Lys-Arg-4-methylcoumarin 7-amide
-
pH 5.0, 37C
0.33
Ac-Orn-Ser-Lys-Arg-4-methylcoumarin 7-amide
-
pH 5.0, 37C
0.51
Boc-Gly-Arg-Arg-4-methylcoumarin 7-amide
-
pH 5.0, 37C
0.44
Boc-Gly-Lys-Arg-4-methylcoumarin 7-amide
-
pH 5.0, 37C
1.3
Boc-Val-Pro-Arg-4-methylcoumarin 7-amide
-
pH 5.0, 37C
0.11
CBZ-Arg-Ser-Lys-Arg-4-methylcoumarin 7-amide
-
pH 5.0, 37C
0.079
dynorphin A 1-17
-
pH 5.0, 37C
-
0.1
dynorphin AB 1-32
-
pH 5.0, 37C
-
0.077
leumorphin
-
pH 5.0, 37C
0.032
pGlu-Arg-Thr-Lys-Arg-methylcoumarin amide
-
pH 5.0, 37C
additional information
additional information
-
kinetics of wild-type and mutant enzymes
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.6
Ac-Arg-Phe-Ala-Arg-4-methylcoumarin 7-amide
Mus musculus
-
pH 5.0, 37C
99
Ac-Arg-Pro-Lys-Arg-4-methylcoumarin 7-amide
Mus musculus
-
pH 5.0, 37C
43.8
Ac-Lys-Ser-Lys-Arg-4-methylcoumarin 7-amide
Mus musculus
-
pH 5.0, 37C
39.6
Ac-Orn-Ser-Lys-Arg-4-methylcoumarin 7-amide
Mus musculus
-
pH 5.0, 37C
1.8
Boc-Gly-Arg-Arg-4-methylcoumarin 7-amide
Mus musculus
-
pH 5.0, 37C
1.2
Boc-Gly-Lys-Arg-4-methylcoumarin 7-amide
Mus musculus
-
pH 5.0, 37C
34.2
CBZ-Arg-Ser-Lys-Arg-4-methylcoumarin 7-amide
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
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
-
-
0.000025
cystatin-related epidiymal spermatogenic protein
-
pH 5.0, 25C
-
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 hide
LITERATURE
0.015
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
pH optima of mutant enzymes, overview
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4 - 6
-
-
4.5 - 6
-
pH profiles of wild-type and mutant enzymes, overview
5 - 8
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.3
calculated
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
human anterior pituitary adenomas are analysed
Manually annotated by BRENDA team
-
pancreatic alpha-cell line
Manually annotated by BRENDA team
-
pituitary gland cell line, low expression level
Manually annotated by BRENDA team
-
PC2 is absent in undifferentiated bone marrow stromal stem cells, its expression is initiated upon the induction of differentiation. PC2 is expressed at a relatively lower level as compared to enzymes functioning in the constitutive pathway
Manually annotated by BRENDA team
-
insulin cells and glucagon cells express PC2, few somatostatin cells contain PC2, is absent from pancreatic polypeptide cells. Colocalization of PC2 with PC1/3, furin and 7B2
Manually annotated by BRENDA team
expression of the PC2-like enzyme in the adult ganglia of the vetigastropod
Manually annotated by BRENDA team
expression of the PC2-like enzyme during larval development of the vetigastropod. During trochophore and early veliger larval stages, PC2 is expressed in the vicinity of the forming ganglia of the central nervous system and parts of the putative peripheral nervous system. Later in larval development, at the time the veliger becomes competent to interact with the external environment and initiate metamorphosis, PC2 expression largely restricts to cells of the major ganglia and their commissures
Manually annotated by BRENDA team
-
high expression level of PC2 in normal, unaffected liver
Manually annotated by BRENDA team
-
metastase originating from colorectal cancer, 2fold reduced expression compared to healthy liver
Manually annotated by BRENDA team
during trochophore and early veliger larval stages, PC2 is expressed in the vicinity of the forming ganglia of the central nervous system and parts of the putative peripheral nervous system
Manually annotated by BRENDA team
high gene epression
Manually annotated by BRENDA team
-
in small growing follicles
Manually annotated by BRENDA team
-
small growing ovarian follicles, oocytes
Manually annotated by BRENDA team
-
ovarian follicles
Manually annotated by BRENDA team
-
normal and alphaTC1-6
Manually annotated by BRENDA team
-
ischemic retinal ganglion cells
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
64000
-
bioactive PC2, Western blot analysis
66000
-
Western blot analysis
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
42.5
-
no significant loss of PC2 activity is observed below 42.5C
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme
-
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
-
wild-type, partially
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNA construction of PC2 mutants, expressed in CHO/21-kDA 7B2 cells
-
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
-
DNA and amino acid sequence determination and analysis, the ovarian mRNA is shorter than the mRNA from brain and kidney lacking about 300 bp just before the poly(A)+ tail
-
expression of PC2 in human 293T cells, leptin has a stimulatory effect on the PC2 promoter, which is enhanced by co-expression of STAT3, overview
-
expression of wild-type and mutant PC2 in CHO-K1 cells
-
gene PC2, DNA and amino acid sequence determination and analysis, phylogenetic analysis
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
-
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
-
recombinant PC2 is expressed in stably transfected CHO cells
-
stable transfection of PC2 in PC12 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
gene expression is negatively related with shrimp body weight
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
-
proPC2 levels in ischemic RCG-5 cells gradually increase with ischemia and cell death after oxygen and glucose deprivation, while PC2 activity decreasesoverview
-
transient upregulation of the mRNA level for PC2 in cerebral cortex at an early reperfusion h in a cerebral ischemia model in rats
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
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
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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
S206K
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site-directed mutagenesis of the S1' subsite residue, inactive mutant
S206R
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site-directed mutagenesis of the S1' subsite residue, inactive mutant
S380T
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site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme
S383A
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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
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site-directed mutagenesis of the residue separating the subsites S3 and S5, the mutant shows increased activity compared to the wild-type enzyme
T271N
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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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
molecular biology
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the regulation of the prohormone processing system by morphine may lead to alterations in the levels of multiple bioactive hormones and may be a compensatory mechanism whereby the organism tries to restore its homeostatic hormonal milieu. The down-regulation of PC1/3, PC2 and P-CREB by short-term morphine and up-regulation by long-term morphine treatment may be a signal mediating the switch from drug use to drug abuse
additional information
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PC2 may be a potential target for the maturation of somatostatin