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Information on EC 3.4.21.94 - proprotein convertase 2
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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 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
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
EGL-3/KPC2
Neuroendocrine convertase 2
-
-
-
-
PC2
PCSK2
prohormone convertase 2
additional information
-
the enzyme belongs to the proprotein protease family of mammalian calcium-dependent serine proteases
PC2
-
-
-
-
PC2
-
-
prohormone convertase 2
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
release of protein hormones and neuropeptides from their precursors, generally by hydrolysis of -Lys-Arg-/- bonds
release of protein hormones and neuropeptides from their precursors, generally by hydrolysis of -Lys-Arg-/- bonds
-
-
-
-
release of protein hormones and neuropeptides from their precursors, generally by hydrolysis of -Lys-Arg-/- bonds
active site and substrate binding structure, enzyme-substrate interactions at prime and non-prime subsites
-
release of protein hormones and neuropeptides from their precursors, generally by hydrolysis of -Lys-Arg-/- bonds
the catalytic triad is formed by the conserved residues Asp169, His210, and Ser386
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
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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
-
?
L-pGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin + H2O
L-pGlu-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
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
-
-
?
Proinsulin + H2O
Insulin + ?
-
selective cleavage only at the C peptide-A chain junction
-
-
?
prothyrotropin-releasing hormone + H2O
thyrotropin-releasing hormone + pro-peptide of thyrotropin-releasing hormone
somatostatin + H2O
?
-
PC2 may function as sorting element for somatostatin for its maturation and processing to appropiate targets
-
-
?
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
-
?
Proglucagon + H2O
?
-
key endoprotease responsible for proglucagon processing in cells with the alpha-cell phenotype
-
-
?
prothyrotropin-releasing hormone + H2O
thyrotropin-releasing hormone + pro-peptide of thyrotropin-releasing hormone
-
processing and activation of the inactive prohormone is required for regulation of energy balance via leptin, enzyme regulation, overview
-
-
?
prothyrotropin-releasing hormone + H2O
thyrotropin-releasing hormone + pro-peptide of thyrotropin-releasing hormone
-
processing of the prohormone
-
-
?
additional information
?
-
-
EGL-3/KPC2 is required for processing of FMRFamide-like peptide precursors and neuropeptide-like protein precursors
-
-
?
additional information
?
-
-
EGL-3/KPC2 is required for processing of FMRFamide-like peptide precursors and neuropeptide-like protein precursors
-
-
?
additional information
?
-
-
cleavage specificity, cleaves precursors both at specific single and pairs of basic residues, not: prorenin, prosomatostatin
-
-
?
additional information
?
-
-
processing of precursors that are routed toward secretory granules
-
-
?
additional information
?
-
-
proprotein convertases play a major role in liver metastasis
-
-
?
additional information
?
-
-
PC2 may be important in insulin and glucagon cells for processing of hormone and other protein precursors
-
-
?
additional information
?
-
-
present on secretory pathway of neuroendocrine cells
-
-
?
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
-
-
?
additional information
?
-
enzyme binds hyperglycemic hormone that plays an important role in glucose metabolism and likely converts pro-CHH1 into a mature neuroendocrine hormone
-
-
?
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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
-
-
?
prothyrotropin-releasing hormone + H2O
thyrotropin-releasing hormone + pro-peptide of thyrotropin-releasing hormone
-
processing and activation of the inactive prohormone is required for regulation of energy balance via leptin, enzyme regulation, overview
-
-
?
proenkephalin + H2O
opioid-active enkephalin + ?
-
cleaves prohormones and proneuropeptides from inactive large precursors to generate activre peptide for extracellular release
-
?
Proglucagon + H2O
?
-
key endoprotease responsible for proglucagon processing in cells with the alpha-cell phenotype
-
-
?
additional information
?
-
-
processing of precursors that are routed toward secretory granules
-
-
?
additional information
?
-
-
proprotein convertases play a major role in liver metastasis
-
-
?
additional information
?
-
-
present on secretory pathway of neuroendocrine cells
-
-
?
additional information
?
-
-
glucose-dependent insulinotropic polypeptide precursor is no substrate of PC2
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
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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
-
additional information
-
starvation reduces the serum levels of leptin which decreases PC1 expression, the effect can be reversed by administration of exogenous leptin
-
additional information
-
stable expression of antisense PC2 mRNA in rMTC 6-23 cells results in a drastic decrease in PC2 protein synthesis by more than 90%, accompanied by a marked reduction in pro-neurotensin/neuromedin N cleavage by more than 80% at sites 2, 3, and 4
-
additional information
-
oxygen and glucose deprivation inhibit the PC2 activity, the pro-PC2 maturation, and thus the neuropeptide pro-protein processing system
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
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
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenoma
TFF3-Based Candidate Gene Discrimination of Benign and Malignant Thyroid Tumors in a Region with Borderline Iodine Deficiency.
Brain Injuries
Defective neuropeptide processing and ischemic brain injury: a study on proprotein convertase 2 and its substrate neuropeptide in ischemic brains.
Brain Ischemia
Defective neuropeptide processing and ischemic brain injury: a study on proprotein convertase 2 and its substrate neuropeptide in ischemic brains.
Carcinogenesis
Islets of Langerhans from prohormone convertase-2 knockout mice show ?-cell hyperplasia and tumorigenesis with elevated ?-cell neogenesis.
Carcinoid Tumor
PCSK2 expression in neuroendocrine tumors points to a midgut, pulmonary, or pheochromocytoma-paraganglioma origin.
Carcinoma
TFF3-Based Candidate Gene Discrimination of Benign and Malignant Thyroid Tumors in a Region with Borderline Iodine Deficiency.
Carcinoma, Papillary
Gene profiling identifies genes specific for well-differentiated epithelial thyroid tumors.
Carcinoma, Papillary
TFF3-Based Candidate Gene Discrimination of Benign and Malignant Thyroid Tumors in a Region with Borderline Iodine Deficiency.
Diabetes Mellitus
Association of type 2 diabetes susceptibility genes (TCF7L2, SLC30A8, PCSK1 and PCSK2) and proinsulin conversion in a Chinese population.
Diabetes Mellitus, Type 2
Association of the prohormone convertase 2 gene (PCSK2) on chromosome 20 with NIDDM in Japanese subjects.
Diabetes Mellitus, Type 2
Association of the proprotein convertase subtilisin/kexin-type 2 (PCSK2) gene with type 2 diabetes in an African American population.
Diabetes Mellitus, Type 2
Association of type 2 diabetes susceptibility genes (TCF7L2, SLC30A8, PCSK1 and PCSK2) and proinsulin conversion in a Chinese population.
Diabetes Mellitus, Type 2
Effect of a common variant of the PCSK2 gene on reduced insulin secretion.
Diabetes Mellitus, Type 2
Enteroendocrine K and L cells in healthy and type 2 diabetic individuals.
Diabetes Mellitus, Type 2
Functional analysis of PCSK2 coding variants: A founder effect in the Old Order Amish population.
Diabetes Mellitus, Type 2
Genetic polymorphisms of PCSK2 are associated with glucose homeostasis and progression to type 2 diabetes in a Chinese population.
Hyperglycemia
Cellular responses of novel human pancreatic ?-cell line, 1.1B4 to hyperglycemia.
Myocardial Infarction
Association of genetic variants in SEMA3F, CLEC16A, LAMA3, and PCSK2 with myocardial infarction in Japanese individuals.
Neoplasm Metastasis
PCSK2 expression in neuroendocrine tumors points to a midgut, pulmonary, or pheochromocytoma-paraganglioma origin.
Neoplasms
Alterations in gene expression of proprotein convertases in human lung cancer have a limited number of scenarios.
Neoplasms
Does the 3-gene diagnostic assay accurately distinguish benign from malignant thyroid neoplasms?
Neoplasms
Gene profiling identifies genes specific for well-differentiated epithelial thyroid tumors.
Neoplasms
PCSK2 expression in neuroendocrine tumors points to a midgut, pulmonary, or pheochromocytoma-paraganglioma origin.
Neuroendocrine Tumors
PCSK2 expression in neuroendocrine tumors points to a midgut, pulmonary, or pheochromocytoma-paraganglioma origin.
Paraganglioma
PCSK2 expression in neuroendocrine tumors points to a midgut, pulmonary, or pheochromocytoma-paraganglioma origin.
Pheochromocytoma
PCSK2 expression in neuroendocrine tumors points to a midgut, pulmonary, or pheochromocytoma-paraganglioma origin.
proprotein convertase 2 deficiency
Genetic deficiency for proprotein convertase subtilisin/kexin type 2 in mice is associated with decreased adiposity and protection from dietary fat-induced body weight gain.
Thyroid Nodule
TFF3-Based Candidate Gene Discrimination of Benign and Malignant Thyroid Tumors in a Region with Borderline Iodine Deficiency.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
kinetics of wild-type and mutant enzymes
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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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
-
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
collected from Heron Island Reef, Great Barrier Reef, Australia, gene PC2 encodes a PC2-like enzyme
UniProt
brenda
-
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
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
brenda
-
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
brenda
expression of the PC2-like enzyme in the adult ganglia of the vetigastropod
brenda
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
brenda
-
metastase originating from colorectal cancer, 2fold reduced expression compared to healthy liver
brenda
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
brenda
additional information
-
colocalization with somatostatin, carboxypeptidase-E and PC1 in pyramidal and non-pyramidal neurons. PC2 exhibits 30% colocalization with somatostatin and 44% with carboxypeptidase-E
brenda
-
high PC2 protein content at early ischeic reperfusion hour, which decreases with reperfusion time
brenda
PC2 protein in the hypothalamus is colocalized with free fatty acid receptor GPR40/FFA1
brenda
-
the effects of short-term (24 h) and long-term (7-day) morphine treatment on the expression of hypothalamic PC1/3 and PC2 and levels of phosphorylated cyclic-AMP-response element binding protein are studied. While short-term morphine exposure down-regulates, long-term morphine exposure up-regulates cyclic-AMP-response element binding protein, PC1/3 and PC2 protein levels in the rat hypothalamus as determined by Western blot analysis
brenda
-
PC2 is confined to neurons of the deeper layer. Interneurons display stronger PC2 expression than projection neurons
brenda
additional information
-
alpha TC1 cells express PC2, alpha TCdeltaPC2 cells do not express bioactive PC2
brenda
additional information
gene is expressed in all larval developmental stages and in neuroendrocrine cells in the adult optic lobe
brenda
additional information
-
in the striatum, PC2 is uniformly expressed. In addition to neurons, some nerve fibers in striatum are also PC2 positive. PC2 exhibits 19% colocalization with somatostatin and 44% with carboxypeptidase-E in the striatum
brenda
additional information
-
present in rMTC 6-23 cells. PC12 cells lack PC2 expression
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
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
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
-
PC2 is required for the neuropeptide pro-protein processing system
physiological function
-
PC2 expression and Akt phosphorylation are related at the molecular level, resulting in a change in cell cycle and an increase in pituitary adenoma size
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
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
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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_BOVIN
638
0
70247
Swiss-Prot
Secretory Pathway (Reliability: 3)
NEC2_CAEEL
652
0
72046
Swiss-Prot
Secretory Pathway (Reliability: 1)
NEC2_HUMAN
638
0
70565
Swiss-Prot
Secretory Pathway (Reliability: 2)
NEC2_MOUSE
637
0
70785
Swiss-Prot
Secretory Pathway (Reliability: 2)
NEC2_PIG
638
0
70452
Swiss-Prot
Secretory Pathway (Reliability: 2)
NEC2_PONAB
638
0
70566
Swiss-Prot
Secretory Pathway (Reliability: 2)
NEC2_RAT
637
0
70753
Swiss-Prot
Secretory Pathway (Reliability: 2)
Q963F2_HETGL
671
1
74163
TrEMBL
Secretory Pathway (Reliability: 1)
B2ZRZ7_DERVA
654
0
72036
TrEMBL
Secretory Pathway (Reliability: 2)
A0A7R8D220_LEPSM
738
0
82360
TrEMBL
Mitochondrion (Reliability: 5)
B7Q266_IXOSC
430
0
46915
TrEMBL
other Location (Reliability: 2)
A0A812BXB2_SEPPH
875
14
100642
TrEMBL
Secretory Pathway (Reliability: 5)
E0VP88_PEDHC
574
0
63522
TrEMBL
other Location (Reliability: 5)
A0A8B6CXZ0_MYTGA
342
0
37737
TrEMBL
Secretory Pathway (Reliability: 2)
A0A8B6DLX1_MYTGA
189
0
19869
TrEMBL
Secretory Pathway (Reliability: 2)
A0JP87_XENTR
639
1
70587
TrEMBL
Secretory Pathway (Reliability: 1)
A0A8B6CUY1_MYTGA
364
0
40173
TrEMBL
other Location (Reliability: 1)
A0A6J7ZZQ3_MYTCO
323
0
36068
TrEMBL
other Location (Reliability: 5)
A0A6J8C7C0_MYTCO
652
0
72580
TrEMBL
Secretory Pathway (Reliability: 1)
D3VLC5_XENNA
Xenorhabdus nematophila (strain ATCC 19061 / DSM 3370 / CCUG 14189 / LMG 1036 / NCIMB 9965 / AN6)
1751
0
182733
TrEMBL
-
A0A073CAZ9_PLAAG
660
0
70958
TrEMBL
-
Q6GLS0_XENLA
639
0
70523
TrEMBL
Secretory Pathway (Reliability: 1)
C1LEI4_SCHJA
552
1
61003
TrEMBL
Secretory Pathway (Reliability: 3)
A0A8B6DKM9_MYTGA
162
0
16893
TrEMBL
other Location (Reliability: 2)
A0A8B6CHT3_MYTGA
615
1
67207
TrEMBL
other Location (Reliability: 2)
A0A8M1NSS0_DANRE
646
1
71779
TrEMBL
Secretory Pathway (Reliability: 2)
B0SQU9_LEPBP
Leptospira biflexa serovar Patoc (strain Patoc 1 / ATCC 23582 / Paris)
563
0
59888
TrEMBL
-
A1IHD0_CIOIN
660
0
72590
TrEMBL
Secretory Pathway (Reliability: 4)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
64000
68000
-
x * 75000, proPC2, Western blot analysis. x * 68000, mature PC2, Western blot analysis
75000
64000
-
x * 75000, pro-PC2 form, SDS-PAGE, x * 64000, mature PC2 form, SDS-PAGE
75000
-
x * 75000, proPC2, Western blot analysis. x * 68000, mature PC2, Western blot analysis
75000
-
x * 75000, pro-PC2 form, SDS-PAGE, x * 64000, mature PC2 form, SDS-PAGE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
?
-
x * 75000, proPC2, Western blot analysis. x * 68000, mature PC2, Western blot analysis
?
-
x * 75000, pro-PC2 form, SDS-PAGE, x * 64000, mature PC2 form, SDS-PAGE
additional information
-
amino acid sequence alignment of soluble ectodomain and active site cleft, domain structures, enzyme structure modeling based on the crystal structures of furin and kexin, overview
additional information
-
the preproenzyme consists of a signal peptide, a propeptide for autocatalytic activation, a Kex2-like catalytic domain, and a P-domain
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
proteolytic modification
-
enzyme activation by autocatalytic cleavage of the propeptide from the preproenzyme
proteolytic modification
-
the pro-protein convertase-2, PC2, needs to activated from a pro-PC2 form to the active PC2 form
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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
-
EGL-3/KPC2 mutants, malprocessing of both FMRFamide-like peptide precursors and neuropeptide-like protein precursors
additional information
-
EGL-3/KPC2 mutants, malprocessing of both FMRFamide-like peptide precursors and neuropeptide-like protein precursors
-
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
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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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
-
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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
-
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
-
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 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
-
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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
-
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
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
molecular biology
-
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
-
PC2 may be a potential target for the maturation of somatostatin
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
-
PCSK2 is a strong functional candidate for type 2 diabetes. Association with type 2 diabetes among four single nucleotide polymorphisms in an African American population. None of the single nucleotide polymorphisms are associated with age at type 2 diabetes diagnosis. A variant in the PCKS2 gene (rs2021785) appears to play a role in susceptibility to type 2 diabetes-end stage renal disease in this African American population
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
medicine
in a rat model of transient focal cerebral ischemia by performing 100 min of middle cerebral artery occlusion, proprotein convertase 2 activity gradually decreases in the ischemic cortex with increasing duration of reperfusion. In an in vitro model of experimental oxygen-glucose deprivation using cultured rat cortical neuron, the number of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling-positive neurons significantly increases and proprotein convertase 2 activity also decreases gradually with increasing duration of oxygen-glucose deprivation
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
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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
brenda
Seidah, N.G.; Chretien, M.
Pro-protein convertases of subtilisin/kexin family
Methods Enzymol.
244
175-188
1994
Homo sapiens
brenda
Rouille, Y.; Westermark, G.; Martin, S.K.; Steiner, D.F.
Proglucagon is processed to glucagon by prohormone convertase PC2 in alpha TC1-6 cells
Proc. Natl. Acad. Sci. USA
91
3242-3246
1994
Mammalia
brenda
Smeekens, S.P.; Steiner, D.F.
Identification of a human insulinoma cDNA encoding a novel mammalian protein structurally related to the yeast dibasic processing protease Kex2
J. Biol. Chem.
265
2997-3000
1990
Homo sapiens
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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
brenda
Tzimas, G.N.; Chevet, E.; Jenna, S.; Nguyen, D.T.; Khatib, A.M.; Marcus, V.; Zhang, Y.; Chretien, M.; Seidah, N.; Metrakos, P.
Abnormal expression and processing of the proprotein convertases PC1 and PC2 in human colorectal liver metastases
BMC Cancer
5
149
2005
Homo sapiens
brenda
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
brenda
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
brenda
Ogiwara, K.; Shinohara, M.; Takahashi, T.
Expression of proprotein convertase 2 mRNA in the ovarian follicles of the medaka, Oryzias latipes
Gene
337
79-89
2004
Oryzias latipes
brenda
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
brenda
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
brenda
Sanchez, V.C.; Goldstein, J.; Stuart, R.C.; Hovanesian, V.; Huo, L.; Munzberg, H.; Friedman, T.C.; Bjorbaek, C.; Nillni, E.A.
Regulation of hypothalamic prohormone convertases 1 and 2 and effects on processing of prothyrotropin-releasing hormone
J. Clin. Invest.
114
357-369
2004
Rattus norvegicus
brenda
Henrich, S.; Lindberg, I.; Bode, W.; Than, M.E.
Proprotein convertase models based on the crystal structures of furin and kexin: explanation of their specificity
J. Mol. Biol.
345
211-227
2004
Homo sapiens
brenda
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
brenda
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
brenda
Portela-Gomes, G.M.; Grimelius, L.; Stridsberg, M.
Prohormone convertases 1/3, 2, furin and protein 7B2 (Secretogranin V) in endocrine cells of the human pancreas
Regul. Pept.
146
117-124
2008
Homo sapiens
brenda
Billova, S.; Galanopoulou, A.S.; Seidah, N.G.; Qiu, X.; Kumar, U.
Immunohistochemical expression and colocalization of somatostatin, carboxypeptidase-E and prohormone convertases 1 and 2 in rat brain
Neuroscience
147
403-418
2007
Rattus norvegicus
brenda
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
brenda
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
brenda
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
brenda
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
brenda
Husson, S.J.; Clynen, E.; Baggerman, G.; Janssen, T.; Schoofs, L.
Defective processing of neuropeptide precursors in Caenorhabditis elegans lacking proprotein convertase 2 (KPC-2/EGL-3): mutant analysis by mass spectrometry
J. Neurochem.
98
1999-2012
2006
Caenorhabditis elegans, Caenorhabditis elegans N2
brenda
Leak, T.S.; Keene, K.L.; Langefeld, C.D.; Gallagher, C.J.; Mychaleckyj, J.C.; Freedman, B.I.; Bowden, D.W.; Rich, S.S.; Sale, M.M.
Association of the proprotein convertase subtilisin/kexin-type 2 (PCSK2) gene with type 2 diabetes in an African American population
Mol. Genet. Metab.
92
145-150
2007
Homo sapiens
brenda
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
brenda
Marandi, M.; Mowla, S.J.; Tavallaei, M.; Yaghoobi, M.M.; Jafarnejad, S.M.
Proprotein convertases 1 and 2 (PC1 and PC2) are expressed in neurally differentiated rat bone marrow stromal stem cells (BMSCs)
Neurosci. Lett.
420
198-203
2007
Rattus norvegicus
brenda
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
brenda
Espinosa, V.P.; Liu, Y.; Ferrini, M.; Anghel, A.; Nie, Y.; Tripathi, P.V.; Porche, R.; Jansen, E.; Stuart, R.C.; Nillni, E.A.; Lutfy, K.; Friedman, T.C.
Differential regulation of prohormone convertase 1/3, prohormone convertase 2 and phosphorylated cyclic-AMP-response element binding protein by short-term and long-term morphine treatment: implications for understanding the "switch" to opiate addiction
Neuroscience
156
788-799
2008
Rattus norvegicus
brenda
Cummins, S.F.; York, P.S.; Hanna, P.H.; Degnan, B.M.; Croll, R.P.
Expression of prohormone convertase 2 and the generation of neuropeptides in the developing nervous system of the gastropod Haliotis
Int. J. Dev. Biol.
53
1081-1088
2009
Haliotis asinina (B2ZSS9), Haliotis asinina
brenda
Zhan, S.; Zhao, H.; J White, A.; Minami, M.; Pignataro, G.; Yang, T.; Zhu, X.; Lan, J.; Xiong, Z.; Steiner, D.F.; Simon, R.P.; Zhou, A.
Defective neuropeptide processing and ischemic brain injury: a study on proprotein convertase 2 and its substrate neuropeptide in ischemic brains
J. Cereb. Blood Flow Metab.
29
698-706
2009
Rattus norvegicus
brenda
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
brenda
Tang, S.S.; Zhang, J.H.; Liu, H.X.; Zhou, D.; Qi, R.
Pro-protein convertase-2/carboxypeptidase-E mediated neuropeptide processing of RGC-5 cell after in vitro ischemia
Neurosci. Bull.
25
7-14
2009
Rattus norvegicus
brenda
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
brenda
Iino, K.; Oki, Y.; Yamashita, M.; Matsushita, F.; Hayashi, C.; Yogo, K.; Nishizawa, S.; Yamada, S.; Maekawa, M.; Sasano, H.; Nakamura, H.
Possible relevance between prohormone convertase 2 expression and tumor growth in human adrenocorticotropin-producing pituitary adenoma
J. Clin. Endocrinol. Metab.
95
4003-4011
2010
Homo sapiens
brenda
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)
brenda
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
brenda
Tangprasittipap, A.; Chouwdee, S.; Phiwsaiya, K.; Laiphrom, S.; Senapin, S.; Flegel, T.W.; Sritunyalucksana, K.
Structure and expression of a shrimp prohormone convertase 2
Gen. Comp. Endocrinol.
178
185-193
2012
Penaeus monodon (I6M2I5)
brenda
Zhan, S.; Zhou, A.; Piper, C.; Yang, T.
Dynamic changes in proprotein convertase 2 activity in cortical neurons after ischemia/reperfusion and oxygen-glucose deprivation
Neural Regen. Res.
8
83-89
2013
Rattus norvegicus (P28841)
brenda
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)
brenda
Tein, K.; Kasvandik, S.; Koks, S.; Vasar, E.; Terasmaa, A.
Prohormone convertase 2 activity is increased in the hippocampus of Wfs1 knockout mice
Front. Mol. Neurosci.
8
45
2015
Mus musculus (P21661)
brenda
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