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Information on EC 3.4.21.94 - proprotein convertase 2 and Organism(s) Rattus norvegicus and UniProt Accession P28841
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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: Rattus norvegicus
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
PC2
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
130960-94-0
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130960-95-1
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388092-42-0
-
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
L-pGlu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin + H2O
L-pGlu-Arg-Thr-Lys-Arg + 7-amino-4-methylcoumarin
-
-
-
-
?
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
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-
?
prothyrotropin-releasing hormone + H2O
thyrotropin-releasing hormone + pro-peptide of thyrotropin-releasing hormone
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processing and activation of the inactive prohormone is required for regulation of energy balance via leptin, enzyme regulation, overview
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-
?
prothyrotropin-releasing hormone + H2O
thyrotropin-releasing hormone + pro-peptide of thyrotropin-releasing hormone
-
processing of the prohormone
-
-
?
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
prothyrotropin-releasing hormone + H2O
thyrotropin-releasing hormone + pro-peptide of thyrotropin-releasing hormone
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processing and activation of the inactive prohormone is required for regulation of energy balance via leptin, enzyme regulation, overview
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
starvation reduces the serum levels of leptin which decreases PC1 expression, the effect can be reversed by administration of exogenous leptin
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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
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additional information
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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
additional information
-
leptin stimulates the PC1 expression via STAT3 acting on the PC2 promoter
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pH OPTIMUM
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 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
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
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high PC2 protein content at early ischeic reperfusion hour, which decreases with reperfusion time
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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
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PC2 is confined to neurons of the deeper layer. Interneurons display stronger PC2 expression than projection neurons
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
additional information
-
present in rMTC 6-23 cells. PC12 cells lack PC2 expression
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
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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
physiological function
physiological function
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PC2 is required for the neuropeptide pro-protein processing system
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_RAT
637
0
70753
Swiss-Prot
Secretory Pathway (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
64000
-
x * 75000, pro-PC2 form, SDS-PAGE, x * 64000, mature PC2 form, SDS-PAGE
68000
-
x * 75000, proPC2, Western blot analysis. x * 68000, mature PC2, Western blot analysis
75000
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
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
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
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
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the pro-protein convertase-2, PC2, needs to activated from a pro-PC2 form to the active PC2 form
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
proPC2 levels in ischemic RCG-5 cells gradually increase with ischemia and cell death after oxygen and glucose deprivation, while PC2 activity decreasesoverview
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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
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
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
-
PC2 may be a potential target for the maturation of somatostatin
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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
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
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
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
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
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
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
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
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
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