Information on EC 3.4.21.94 -

Information on EC 3.4.21.94 - proprotein convertase 2:

Please wait a moment until all data are loaded. This message will disappear when all data are loaded.

EC NUMBER	COMMENTARY
3.4.21.94	-

RECOMMENDED NAME	GeneOntology No.
proprotein convertase 2	GO:0004286

REACTION	REACTION DIAGRAM	COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	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		the catalytic triad is formed by the conserved residues Asp169, His210, and Ser386	Oryzias latipes	-	668720
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	Homo sapiens	-	669843

REACTION TYPE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
hydrolysis of peptide bond	-	-	-	-

PATHWAY	KEGG Link	MetaCyc Link
No entries in this field

SYSTEMATIC NAME	IUBMB Comments
No entries in this field

SYNONYMS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
Neuroendocrine convertase 2	-	-	-	-
PC2	-	-	-	-
PC2	Homo sapiens	-	-	653858, 668083, 669843, 682808, 688466, 717906
PC2	Mus musculus	-	-	653858, 668377, 668422, 669378, 669436, 670480, 677957, 686302, 686303, 688466, 688525, 689212, 700298, 709603, 717856
PC2	Rattus norvegicus	-	-	653858, 669626, 683932, 688466, 689214, 700473, 709250, 710101
PC2	Oryzias latipes	-	-	668720
PC2	Haliotis asinina	B2ZSS9	-	708778
PC2-like enzyme	Haliotis asinina	B2ZSS9	-	708778
PCSK2	Homo sapiens	-	-	689018
pro-protein convertase-2	Rattus norvegicus	-	-	710101
pro-protein convertase-2/carboxypeptidase-E	Rattus norvegicus	-	-	710101
Prohormone convertase	Mus musculus	-	-	669378
prohormone convertase 12	Mus musculus	-	-	669436
prohormone convertase 2	Mus musculus	-	-	653858, 668377, 670480, 677957, 686302, 686303, 717856
prohormone convertase 2	Rattus norvegicus	-	-	653858, 669626, 683932
prohormone convertase 2	Homo sapiens	-	-	653858, 682808, 717906
prohormone convertase 2	Haliotis asinina	B2ZSS9	-	708778
prohormone convertase-2	Mus musculus	-	-	688525, 709603
proneuropeptide convertase 2	Mus musculus	-	-	689212
proprotein convertase 2	Rattus norvegicus	-	-	689214, 709250
proprotein convertase subtilisin/kexin-type 2	Homo sapiens	-	-	689018
EGL-3/KPC2	Caenorhabditis elegans	-	-	688526
additional information	Mus musculus	-	the enzyme belongs to the proprotein protease family of mammalian calcium-dependent serine proteases	669378

CAS REGISTRY NUMBER	COMMENTARY
130960-94-0	-
130960-95-1	-
388092-42-0	-

ORGANISM	COMMENTARY	LITERATURE	SEQUENCE CODE	SEQUENCE DB	SOURCE
Caenorhabditis elegans	strain N2, variety Bristol	688526	-	-
Caenorhabditis elegans N2	strain N2, variety Bristol	688526	-	-
Haliotis asinina	collected from Heron Island Reef, Great Barrier Reef, Australia, gene PC2 encodes a PC2-like enzyme	708778	B2ZSS9	UniProt
Homo sapiens	-	29417, 29874, 29877, 668083, 669843, 682808, 688466, 689018, 717906	-	-
Homo sapiens	human	653858	-	-
Mammalia	-	29875	-	-
Mus musculus	-	668377, 668422, 669378, 669436, 670480, 677957, 686302, 688466, 688525, 700298, 717856	-	-
Mus musculus	CD-1 genetic background	689212	-	-
Mus musculus	CD-1 mice and C57B/6 mice	686303	-	-
Mus musculus	littermate mice	709603	-	-
Mus musculus	mouse	651892, 651913	-	-
Mus musculus	mouse, AtT-20 cells	651994, 653858	-	-
Mus musculus	mouse, strain CD-1	651008	-	-
Oryzias latipes	medaka	668720	-	-
Rattus norvegicus	-	688466, 689214, 700473, 709250, 710101	-	-
Rattus norvegicus	adult male Sprague-Dawley rats	683932	-	-
Rattus norvegicus	male sprague-dawley rats	669626	-	-
Rattus norvegicus	rat, Sprague-Dawley	651913, 653858	-	-

GENERAL INFORMATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
malfunction	Rattus norvegicus	-	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	709250
metabolism	Haliotis asinina	B2ZSS9	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	708778
physiological function	Rattus norvegicus	-	PC2 mediates neuropeptide processing in the brain	709250
physiological function	Mus musculus	-	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	709603
physiological function	Rattus norvegicus	-	PC2 is required for the neuropeptide pro-protein processing system	710101
physiological function	Mus musculus	-	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	717856
physiological function	Homo sapiens	-	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	717906

SUBSTRATE	PRODUCT	REACTION DIAGRAM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY/ Substrate	LITERATURE/ Substrate	COMMENTARY/ Product	LITERATURE/ Product	Reversibility r=reversible ir=irreversible ?=not specified
2-aminobenzoyl-LPSDEEGESYKEVPEMEKRYGGFMQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O	?		Mus musculus	-	-	651892	-	651892	?
2-aminobenzoyl-Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-Gly-Arg-Pro-Glu-N-(2,4-dinitrophenyl)ethylenediamine + H2O	?		Mus musculus	-	-	651892	-	651892	?
2-aminobenzoyl-Val-Pro-Arg-Met-Glu-Lys-Arg-Tyr-Gly-Gly-Phe-Met-Gln-N-(2,4-dinitrophenyl)ethylenediamine + H2O	?		Mus musculus	-	-	651892	-	651892	?
Ac-Arg-Phe-Ala-Arg-4-methylcoumarin 7-amide + H2O	?		Mus musculus	-	-	651892	-	651892	?
Ac-Arg-Pro-Lys-Arg-4-methylcoumarin 7-amide + H2O	?		Mus musculus	-	-	651892	-	651892	?
Ac-Lys-Ser-Lys-Arg-4-methylcoumarin 7-amide + H2O	?		Mus musculus	-	-	651892	-	651892	?
Ac-Orn-Ser-Lys-Arg-4-methylcoumarin 7-amide + H2O	?		Mus musculus	-	-	651892	-	651892	?
Boc-Gly-Arg-Arg-4-methylcoumarin 7-amide + H2O	?		Mus musculus	-	-	651892	-	651892	?
Boc-Gly-Lys-Arg-4-methylcoumarin 7-amide + H2O	?		Mus musculus	-	-	651892	-	651892	?
Boc-Val-Pro-Arg-4-methylcoumarin 7-amide + H2O	?		Mus musculus	-	-	651892	-	651892	?
CBZ-Arg-Ser-Lys-Arg-4-methylcoumarin 7-amide + H2O	?		Mus musculus	-	-	651892	-	651892	?
Cbz-Arg-Ser-Lys-Arg-aminomethylcoumarin + H2O	?		Mus musculus	-	-	651913	-	651913	?
cholecystokinin 8-containing peptide + H2O	?		Mus musculus	-	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	670480	-	-	?
dynorphin A 1-17 + H2O	?		Mus musculus	-	-	651913	-	651913	?
dynorphin AB 1-32 + H2O	?		Mus musculus	-	-	651913	-	651913	?
dynorphin-A(1-8) + H2O	?		Rattus norvegicus	-	-	709250	-	-	?
glicentin1-69 + H2O	glucagon + glicentin-related polypeptide + GLP-1		Mus musculus	-	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	668422	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		Rattus norvegicus	-	-	709250	-	-	?
peptide B-derived peptides + H2O	?		Mus musculus	-	cleavage site specificity of wild-type and mutant PC2, overview	669378	-	-	?
pGlu-Arg-Thr-Lys-Arg-4-methylcoumarin 7-amide + H2O	?		Mus musculus	-	-	651008	-	651008	?
pGlu-Arg-Thr-Lys-Arg-4-methylcoumarin 7-amide + H2O	?		Mus musculus	-	-	651892	-	651892	?
pGlu-Arg-Thr-Lys-Arg-4-methylcoumarin 7-amide + H2O	?		Mus musculus	-	-	653858	-	653858	?
pro-cholecystokinin + H2O	N-terminal propeptide + C-terminal cholecystokinin 8 Gly Arg Arg peptide + remaining CCK peptide		Mus musculus	-	the substrate is only cleaved in vivo since defolding proteins are required, in vitro the cleavage site is inaccessible for the enzyme	670480	peptide product analysis	-	?
pro-cholecystokinin + H2O	N-terminal propeptide + cholecystokinin 58		Mus musculus	-	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	670480	peptide product analysis	-	?
pro-islet amyloid polypeptide + H2O	islet amyloid polypeptide processing intermediate + N-terminal pro-peptide		Mus musculus	-	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	668377	-	-	?
pro-neurotensin/neuromedin N + H2O	neurotensin + neuromedin N		Mus musculus, Homo sapiens, Rattus norvegicus	-	-	688466	-	-	?
Pro-opiomelanocortin + H2O	Opiomelanocortin + ?		Homo sapiens	-	from mouse and pig	29874	-	-	-
prodynorphin + H2O	dynorphin + ?		Homo sapiens	-	rat, cleavage at a single Arg residue, at a bond in which P2 is Thr	29874	-	-	-
prodynorphin + H2O	dynorphin A 1-17 + dynorphin B 1-13 + alpha-neo-endorphin + C-peptide + dynorphin A 1-8 + ?		Mus musculus	-	-	651913	-	651913	?
Proenkephalin + H2O	Enkephalin + ?		Homo sapiens	-	human	29874	-	-	-
proenkephalin + H2O	opioid-active enkephalin + ?		Mus musculus	-	-	651892	-	651892	?
proenkephalin + H2O	opioid-active enkephalin + ?		Mus musculus	-	-	651994	-	651994	?
proenkephalin + H2O	opioid-active enkephalin + ?		Mus musculus	-	cleaves prohormones and proneuropeptides from inactive large precursors to generate activre peptide for extracellular release	651892	-	651892	?
proenkphalin-derived peptide + H2O	?		Mus musculus	-	the preferred cleavage site sequence of PC2 is YGGFLKR-/-FAESL	669378	-	-	?
Proglucagon + H2O	Glucagon + ?		Mammalia	-	dibasic cleavage sites	29875	-	29875	-
Proglucagon + H2O	?		Mus musculus	-	-	717856	-	-	?
Proglucagon + H2O	?		Mammalia	-	key endoprotease responsible for proglucagon processing in cells with the alpha-cell phenotype	29875	-	-	-
proglucagon + H2O	glucagon		Mus musculus	-	-	686303	-	-	?
proglucagon1-158 + H2O	glucagon + glicentin-related polypeptide + GLP-1 + IP2/GLP-2		Mus musculus	-	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	668422	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		Mus musculus	-	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	686302	-	-	?
Proinsulin + H2O	Insulin + ?		Homo sapiens	-	selective cleavage only at the C peptide-A chain junction	29417	-	-	-
proPC2 + H2O	mature PC2		Mus musculus	-	-	677957	-	-	?
prothyrotropin-releasing hormone + H2O	thyrotropin-releasing hormone + pro-peptide of thyrotropin-releasing hormone		Rattus norvegicus	-	processing and activation of the inactive prohormone is required for regulation of energy balance via leptin, enzyme regulation, overview, processing of the prohormone	669626	-	-	?
pyr-Glu-Arg-Thr-Lys-Arg-7-amido-4-methylcoumarin + H2O	?		Mus musculus	-	-	700298	-	-	?
somatostatin + H2O	?		Rattus norvegicus	-	PC2 may function as sorting element for somatostatin for its maturation and processing to appropiate targets	683932	-	-	?
leumorphin + H2O	?		Mus musculus	-	-	651913	-	651913	?
additional information	?	-	Homo sapiens	-	cleavage specificity, cleaves precursors both at specific single and pairs of basic residues, not: prorenin, prosomatostatin	29874	-	-	-
additional information	?	-	Mus musculus	-	prefers Arg at positions P4 and P5 in peptide B IQ substrates, Boc-Val-Leu-Lys-4-methylcoumarin 7-amide is no substrate	651892	-	651892	?
additional information	?	-	Mammalia	-	present on secretory pathway of neuroendocrine cells	29875	-	-	-
additional information	?	-	Homo sapiens	-	processing of precursors that are routed toward secretory granules	29874	-	-	-
additional information	?	-	Mus musculus	-	glucose-dependent insulinotropic polypeptide precursor is no substrate of PC2	669436	-	-	-
additional information	?	-	Homo sapiens	-	proprotein convertases play a major role in liver metastasis	668083	-	-	-
additional information	?	-	Mus musculus	-	cleavage site specificity, activity with mutant proglucagon and truncation variants, analysis of importance of substrate domain structure, molecular modeling, overview	668422	-	-	-
additional information	?	-	Caenorhabditis elegans	-	EGL-3/KPC2 is required for processing of FMRFamide-like peptide precursors and neuropeptide-like protein precursors	688526	-	-	-
additional information	?	-	Homo sapiens	-	PC2 may be important in insulin and glucagon cells for processing of hormone and other protein precursors	682808	-	-	-
additional information	?	-	Mus musculus	-	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	688525	-	-	-

NATURAL SUBSTRATES	NATURAL PRODUCTS	REACTION DIAGRAM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY SUBSTRATE	LITERATURE (Substrate)	COMMENTARY PRODUCT	LITERATURE (Product)
pro-cholecystokinin + H2O	N-terminal propeptide + C-terminal cholecystokinin 8 Gly Arg Arg peptide + remaining CCK peptide		Mus musculus	-	the substrate is only cleaved in vivo since defolding proteins are required, in vitro the cleavage site is inaccessible for the enzyme	670480	peptide product analysis	-
pro-islet amyloid polypeptide + H2O	islet amyloid polypeptide processing intermediate + N-terminal pro-peptide		Mus musculus	-	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	668377	-	-
proenkephalin + H2O	opioid-active enkephalin + ?		Mus musculus	-	-	651994	-	651994
proenkephalin + H2O	opioid-active enkephalin + ?		Mus musculus	-	cleaves prohormones and proneuropeptides from inactive large precursors to generate activre peptide for extracellular release	651892	-	651892
Proglucagon + H2O	?		Mus musculus	-	-	717856	-	-
Proglucagon + H2O	?		Mammalia	-	key endoprotease responsible for proglucagon processing in cells with the alpha-cell phenotype	29875	-	-
prothyrotropin-releasing hormone + H2O	thyrotropin-releasing hormone + pro-peptide of thyrotropin-releasing hormone		Rattus norvegicus	-	processing and activation of the inactive prohormone is required for regulation of energy balance via leptin, enzyme regulation, overview	669626	-	-
additional information	?	-	Mammalia	-	present on secretory pathway of neuroendocrine cells	29875	-	-
additional information	?	-	Homo sapiens	-	processing of precursors that are routed toward secretory granules	29874	-	-
additional information	?	-	Mus musculus	-	glucose-dependent insulinotropic polypeptide precursor is no substrate of PC2	669436	-	-
additional information	?	-	Homo sapiens	-	proprotein convertases play a major role in liver metastasis	668083	-	-

COFACTOR	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
No entries in this field

METALS and IONS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
Ca2+	Homo sapiens	-	optimum concentration 2.5 mM	653858
Ca2+	Mus musculus	-	dependent on	669378
Ca2+	Rattus norvegicus	-	-	709250

INHIBITORS	ORGANISM	UNIPROT ACCESSION NO.	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	Mus musculus	-	-	700298	2D-image
(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	Mus musculus	-	-	700298	2D-image
(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	Mus musculus	-	-	700298	2D-image
(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	Mus musculus	-	-	700298	2D-image
7B2 C-terminal peptide	Mus musculus	-	-	651994	-
7B2 CT peptide	Mus musculus	-	potent specific inhibition of PC2	669378	-
CT peptide	Rattus norvegicus	-	a PC2-specific inhibitor	709250	-
cystatin-related epidiymal spermatogenic protein	Mus musculus	-	competitive inhibitor	651008	-
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	Mus musculus	-	-	700298	2D-image
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	Mus musculus	-	-	700298	2D-image
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	Mus musculus	-	-	700298	2D-image
decanoyl-Arg-Val-Lys-Arg-chloromethylketone	Mus musculus	-	-	677957	2D-image
additional information	Rattus norvegicus	-	starvation reduces the serum levels of leptin which decreases PC1 expression, the effect can be reversed by administration of exogenous leptin	669626	-
additional information	Rattus norvegicus	-	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	688466	-
additional information	Mus musculus	-	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	700298	-
additional information	Rattus norvegicus	-	oxygen and glucose deprivation inhibit the PC2 activity, the pro-PC2 maturation, and thus the neuropeptide pro-protein processing system	710101	-

ACTIVATING COMPOUND	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
protein 7B2	Mus musculus	-	pro-PC2 requires interaction with this neuroendocrine-specific protein for its maturation and activation	651994	-
small neuroendocrine protein 7B2	Mus musculus	-	7B2 overexpression decreases the secretion and increases the activity of PC2 within alpha-TC6 cells	717856	-
additional information	Rattus norvegicus	-	leptin stimulates the PC1 expression via STAT3 acting on the PC2 promoter	669626	-

KM VALUE [mM]	KM VALUE [mM] Maximum	SUBSTRATE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
0.27	-	Ac-Arg-Phe-Ala-Arg-4-methylcoumarin 7-amide	Mus musculus	-	pH 5.0, 37�C	651892	2D-image
0.26	-	Ac-Arg-Pro-Lys-Arg-4-methylcoumarin 7-amide	Mus musculus	-	pH 5.0, 37�C	651892	2D-image
0.14	-	Ac-Lys-Ser-Lys-Arg-4-methylcoumarin 7-amide	Mus musculus	-	pH 5.0, 37�C	651892	2D-image
0.33	-	Ac-Orn-Ser-Lys-Arg-4-methylcoumarin 7-amide	Mus musculus	-	pH 5.0, 37�C	651892	2D-image
0.51	-	Boc-Gly-Arg-Arg-4-methylcoumarin 7-amide	Mus musculus	-	pH 5.0, 37�C	651892	2D-image
0.44	-	Boc-Gly-Lys-Arg-4-methylcoumarin 7-amide	Mus musculus	-	pH 5.0, 37�C	651892	2D-image
1.3	-	Boc-Val-Pro-Arg-4-methylcoumarin 7-amide	Mus musculus	-	pH 5.0, 37�C	651892	2D-image
0.11	-	CBZ-Arg-Ser-Lys-Arg-4-methylcoumarin 7-amide	Mus musculus	-	pH 5.0, 37�C	651892	2D-image
0.079	-	dynorphin A 1-17	Mus musculus	-	pH 5.0, 37�C	651913	-
0.1	-	dynorphin AB 1-32	Mus musculus	-	pH 5.0, 37�C	651913	-
0.032	-	pGlu-Arg-Thr-Lys-Arg-methylcoumarin amide	Mus musculus	-	pH 5.0, 37�C	651913	2D-image
0.077	-	leumorphin	Mus musculus	-	pH 5.0, 37�C	651913	2D-image
additional information	-	additional information	Mus musculus	-	kinetics of wild-type and mutant enzymes	669378	-

TURNOVER NUMBER [1/s]	TURNOVER NUMBER MAXIMUM[1/s]	SUBSTRATE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
0.6	-	Ac-Arg-Phe-Ala-Arg-4-methylcoumarin 7-amide	Mus musculus	-	pH 5.0, 37�C	651892	2D-image
99	-	Ac-Arg-Pro-Lys-Arg-4-methylcoumarin 7-amide	Mus musculus	-	pH 5.0, 37�C	651892	2D-image
43.8	-	Ac-Lys-Ser-Lys-Arg-4-methylcoumarin 7-amide	Mus musculus	-	pH 5.0, 37�C	651892	2D-image
39.6	-	Ac-Orn-Ser-Lys-Arg-4-methylcoumarin 7-amide	Mus musculus	-	pH 5.0, 37�C	651892	2D-image
1.8	-	Boc-Gly-Arg-Arg-4-methylcoumarin 7-amide	Mus musculus	-	pH 5.0, 37�C	651892	2D-image
1.2	-	Boc-Gly-Lys-Arg-4-methylcoumarin 7-amide	Mus musculus	-	pH 5.0, 37�C	651892	2D-image
34.2	-	CBZ-Arg-Ser-Lys-Arg-4-methylcoumarin 7-amide	Mus musculus	-	pH 5.0, 37�C	651892	2D-image
34.2	-	pGlu-Arg-Thr-Lys-Arg-4-methylcoumarin 7-amide	Mus musculus	-	pH 5.0, 37�C	651892	2D-image

kcat/KM VALUE [1/mMs^-1]	kcat/KM VALUE [1/mMs^-1] Maximum	SUBSTRATE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
No entries in this field

Ki VALUE [mM]	Ki VALUE [mM] Maximum	INHIBITOR	ORGANISM	UNIPROT ACCESSION NO.	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	Mus musculus	-	-	700298	2D-image
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	Mus musculus	-	-	700298	2D-image
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	Mus musculus	-	-	700298	2D-image
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	Mus musculus	-	-	700298	2D-image
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	Mus musculus	-	-	700298	2D-image
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	Mus musculus	-	-	700298	2D-image
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	Mus musculus	-	-	700298	2D-image
2.5e-05	-	cystatin-related epidiymal spermatogenic protein	Mus musculus	-	pH 5.0, 25�C	651008	-
additional information	-	additional information	Mus musculus	-	inhibition kinetics of wild-type and mutant enzymes	669378	-

IC50 VALUE [mM]	IC50 VALUE [mM] Maximum	INHIBITOR	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
No entries in this field

SPECIFIC ACTIVITY [µmol/min/mg]	SPECIFIC ACTIVITY MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
0.015	-	Mus musculus	-	-	651913

pH OPTIMUM	pH MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
5	-	Mus musculus	-	-	651994
5	-	Mus musculus	-	wild-type enzyme	669378
5	-	Mus musculus	-	assay at	700298
5	-	Rattus norvegicus	-	assay at	709250
5.5	-	Homo sapiens	-	-	29417, 653858
additional information	-	Mus musculus	-	pH optima of mutant enzymes, overview	669378

pH RANGE	pH RANGE MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
4	6	Mus musculus	-	-	651994
4.5	6	Mus musculus	-	pH profiles of wild-type and mutant enzymes, overview	669378
5	8	Homo sapiens	-	-	653858

TEMPERATURE OPTIMUM	TEMPERATURE OPTIMUM MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
37	-	Mus musculus	-	assay at	669378, 700298
37	-	Rattus norvegicus	-	assay at	709250

TEMPERATURE RANGE	TEMPERATURE MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

pI VALUE	pI VALUE MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

SOURCE TISSUE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	SOURCE
adenoma cell	Homo sapiens	-	human anterior pituitary adenomas are analysed	717906
alpha-TC1.9 cell	Mus musculus	-	pancreatic alpha-cell line	669436
amygdala	Mus musculus	-	-	709603
AtT-20 cell	Mus musculus	-	pituitary gland cell line, low expression level	669436
B-cell	Mus musculus	-	-	668377
bone marrow stromal stem cell	Rattus norvegicus	-	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	689214
brain	Oryzias latipes	-	-	668720
brain	Rattus norvegicus	-	-	683932
brain	Homo sapiens, Mus musculus, Rattus norvegicus	-	PC2 is the most abundant PC in the brain	688466
brain	Rattus norvegicus	-	healthy and ischemic	709250
brain	Mus musculus	-	-	709603
cell culture	Rattus norvegicus	-	-	709250
cerebral cortex	Rattus norvegicus	-	colocalization with somatostatin, carboxypeptidase-E and PC1 in pyramidal and non-pyramidal neurons. PC2 exhibits 30% colocalization with somatostatin and 44% with carboxypeptidase-E	683932
cerebral cortex	Rattus norvegicus	-	high PC2 protein content at early ischeic reperfusion hour, which decreases with reperfusion time	709250
colonic cancer cell	Homo sapiens	-	primary	668083
corpus striatum	Mus musculus	-	-	709603
endocrine pancreas	Homo sapiens	-	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	682808
follicle	Oryzias latipes	-	small growing ovarian follicles, oocytes	668720
ganglion	Haliotis asinina	B2ZSS9	expression of the PC2-like enzyme in the adult ganglia of the vetigastropod	708778
hippocampus	Rattus norvegicus	-	PC2 expressed in all the regions with similar levels	683932
hippocampus	Mus musculus	-	-	709603
hypothalamus	Rattus norvegicus	-	-	669626
hypothalamus	Mus musculus	-	-	688525, 709603
hypothalamus	Rattus norvegicus	-	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	700473
insulinoma cell	Homo sapiens	-	-	29417, 29877
kidney	Oryzias latipes	-	-	668720
larva	Haliotis asinina	B2ZSS9	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	708778
liver	Homo sapiens	-	high expression level of PC2 in normal, unaffected liver	668083
nervous system	Haliotis asinina	B2ZSS9	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	708778
neuroendocrine cell	Homo sapiens, Mus musculus, Rattus norvegicus	-	-	688466
neuron	Rattus norvegicus	-	hypothalamic	669626
neuron	Rattus norvegicus	-	PC2 is confined to neurons of the deeper layer. Interneurons display stronger PC2 expression than projection neurons	683932
neuron	Homo sapiens, Mus musculus, Rattus norvegicus	-	-	688466
neuronal cell	Rattus norvegicus	-	-	709250
oocyte	Oryzias latipes	-	in small growing follicles	668720
ovary	Oryzias latipes	-	ovarian follicles	668720
pancreatic alpha cell	Mammalia	-	normal and alphaTC1-6	29875
prefrontal cortex	Mus musculus	-	-	709603
RGC-5 cell	Rattus norvegicus	-	ischemic retinal ganglion cells	710101
thalamus	Mus musculus	-	-	709603
liver cancer cell	Homo sapiens	-	metastase originating from colorectal cancer, 2fold reduced expression compared to healthy liver	668083
additional information	Homo sapiens	-	distribution in tissues	29874
additional information	Rattus norvegicus	-	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	683932
additional information	Mus musculus	-	alpha TC1 cells express PC2, alpha TCdeltaPC2 cells do not express bioactive PC2	686303
additional information	Homo sapiens	-	coloDM320 cell line lacks PC2 expression	688466
additional information	Rattus norvegicus	-	present in rMTC 6-23 cells. PC12 cells lack PC2 expression	688466
additional information	Haliotis asinina	B2ZSS9	PC2 tissue distributionm, overview	708778

LOCALIZATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	GeneOntology No.	LITERATURE	SOURCE
cytoplasm	Homo sapiens	-	-	5737	682808
cytoplasm	Rattus norvegicus	-	-	5737	683932

PDB	SCOP	CATH	ORGANISM
No entries in this field

MOLECULAR WEIGHT	MOLECULAR WEIGHT MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
64000	-	Mus musculus	-	bioactive PC2, Western blot analysis	651994
66000	-	Mus musculus	-	Western blot analysis	651994

SUBUNITS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
?	Rattus norvegicus	-	x * 75000, proPC2, Western blot analysis. x * 68000, mature PC2, Western blot analysis	683932
?	Rattus norvegicus	-	x * 75000, pro-PC2 form, SDS-PAGE, x * 64000, mature PC2 form, SDS-PAGE	709250
additional information	Oryzias latipes	-	the preproenzyme consists of a signal peptide, a propeptide for autocatalytic activation, a Kex2-like catalytic domain, and a P-domain	668720
additional information	Homo sapiens	-	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	669843

POSTTRANSLATIONAL MODIFICATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
proteolytic modification	Oryzias latipes	-	enzyme activation by autocatalytic cleavage of the propeptide from the preproenzyme	668720
proteolytic modification	Rattus norvegicus	-	the pro-protein convertase-2, PC2, needs to activated from a pro-PC2 form to the active PC2 form	710101

Crystallization/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

pH STABILITY	pH STABILITY MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

TEMPERATURE STABILITY	TEMPERATURE STABILITY MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
42.5	-	Mus musculus	-	no significant loss of PC2 activity is observed below 42.5�C	651913

GENERAL STABILITY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

ORGANIC SOLVENT	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

OXIDATION STABILITY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

STORAGE STABILITY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

Purification/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
recombinant enzyme	Mus musculus	-	651892, 651913
recombinant PC2 wild-type and mutant S383A purified on anion-exchange column and by gel filtration	Mus musculus	-	677957
recombinant wild-type and mutant PC2 from CHO-K1 cells by adsorption chromatography	Mus musculus	-	669378
wild-type, partially	Mus musculus	-	651994

Cloned/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
gene PC2, DNA and amino acid sequence determination and analysis, phylogenetic analysis	Haliotis asinina	B2ZSS9	708778
-	Homo sapiens	-	29417, 29874
cDNA construction of PC2 mutants, expressed in CHO/21-kDA 7B2 cells	Mus musculus	-	651994
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	Mus musculus	-	668377
expression of wild-type and mutant PC2 in CHO-K1 cells	Mus musculus	-	669378
gene PC2, genotyping of wild-type and haplotype and holotype PC2-deficient mice	Mus musculus	-	709603
GH3 cells or INS-1 beta-cells cotransduced with proIAPP and PC2 by adenoviral expression	Mus musculus	-	686302
overexpressed in Chinese hamster ovary cells supertransfected with rat cDNA	Mus musculus	-	651892
overexpressed in Chinese hamster ovary cells supertransfected with rat cDNA 7B2	Mus musculus	-	651913
pcDNA3 plasmid encoding either PC2 wild-type or mutant S383A expressed in CHO-K1/7B2 cells or AtT-20/7B2 cells	Mus musculus	-	677957
recombinant PC2 is expressed in stably transfected CHO cells	Mus musculus	-	700298
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	Mus musculus	-	668422
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	Mus musculus	-	686303
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	Oryzias latipes	-	668720
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	Rattus norvegicus	-	669626
stable transfection of PC2 in PC12 cells	Rattus norvegicus	-	688466

EXPRESSION	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
transient upregulation of the mRNA level for PC2 in cerebral cortex at an early reperfusion h in a cerebral ischemia model in rats	Rattus norvegicus	-	709250
proPC2 levels in ischemic RCG-5 cells gradually increase with ischemia and cell death after oxygen and glucose deprivation, while PC2 activity decreasesoverview	Rattus norvegicus	-	710101

ENGINEERING	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
A322T/S323N	Mus musculus	-	site-directed mutagenesis, the mutant shows unaltered activity, but slightly decreased sensitivity for inhibitor 7B2 CT peptide compared to the wild-type enzyme	669378
D278E	Mus musculus	-	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	669378
N356S	Mus musculus	-	site-directed mutagenesis of the distant prime site residue, the mutant shows altered substrate preferences compared to the wild-type enzyme	669378
R281G/E282R	Mus musculus	-	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	669378
S206K	Mus musculus	-	site-directed mutagenesis of the S1' subsite residue, inactive mutant	669378
S206R	Mus musculus	-	site-directed mutagenesis of the S1' subsite residue, inactive mutant	669378
S380T	Mus musculus	-	site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme	669378
S383A	Mus musculus	-	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	677957
T271E	Mus musculus	-	site-directed mutagenesis of the residue separating the subsites S3 and S5, the mutant shows increased activity compared to the wild-type enzyme	669378
T271N	Mus musculus	-	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	669378
additional information	Caenorhabditis elegans	-	EGL-3/KPC2 mutants, malprocessing of both FMRFamide-like peptide precursors and neuropeptide-like protein precursors	688526
L341W	Mus musculus	-	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	669378
additional information	Mus musculus	-	PC2-deficient cells do not show alterations in glucose-dependent insulinotropic polypeptide precursor processing activity	669436
additional information	Mus musculus	-	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	686302
additional information	Mus musculus	-	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	688466
additional information	Mus musculus	-	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	688525
additional information	Mus musculus	-	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	689212

Renatured/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

APPLICATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
medicine	Homo sapiens	-	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	689018
medicine	Mus musculus	-	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	686302
medicine	Mus musculus	-	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	686303
molecular biology	Rattus norvegicus	-	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	700473
additional information	Rattus norvegicus	-	PC2 may be a potential target for the maturation of somatostatin	683932

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.	PubMed
Brain Injuries	Defective neuropeptide processing and ischemic brain injury: a study on proprotein convertase 2 and its substrate neuropeptide in ischemic brains.	PubMed
Brain Ischemia	Defective neuropeptide processing and ischemic brain injury: a study on proprotein convertase 2 and its substrate neuropeptide in ischemic brains.	PubMed
Carcinoma	Rap2A Is Upregulated in Invasive Cells Dissected from Follicular Thyroid Cancer.	PubMed
Carcinoma	TFF3-Based Candidate Gene Discrimination of Benign and Malignant Thyroid Tumors in a Region with Borderline Iodine Deficiency.	PubMed
Carcinoma, Papillary	Gene profiling identifies genes specific for well-differentiated epithelial thyroid tumors.	PubMed
Carcinoma, Papillary	TFF3-Based Candidate Gene Discrimination of Benign and Malignant Thyroid Tumors in a Region with Borderline Iodine Deficiency.	PubMed
Diabetes Mellitus	Association of type 2 diabetes susceptibility genes (TCF7L2, SLC30A8, PCSK1 and PCSK2) and proinsulin conversion in a Chinese population.	PubMed
Diabetes Mellitus, Type 2	Association of the prohormone convertase 2 gene (PCSK2) on chromosome 20 with NIDDM in Japanese subjects.	PubMed
Diabetes Mellitus, Type 2	Association of type 2 diabetes susceptibility genes (TCF7L2, SLC30A8, PCSK1 and PCSK2) and proinsulin conversion in a Chinese population.	PubMed
Myocardial Infarction	Association of genetic variants in SEMA3F, CLEC16A, LAMA3, and PCSK2 with myocardial infarction in Japanese individuals.	PubMed
Neoplasms	Does the 3-gene diagnostic assay accurately distinguish benign from malignant thyroid neoplasms?	PubMed
Neoplasms	Gene profiling identifies genes specific for well-differentiated epithelial thyroid tumors.	PubMed
Neoplasms	Rap2A Is Upregulated in Invasive Cells Dissected from Follicular Thyroid Cancer.	PubMed
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.	PubMed
Thyroid Nodule	TFF3-Based Candidate Gene Discrimination of Benign and Malignant Thyroid Tumors in a Region with Borderline Iodine Deficiency.	PubMed

REF.	AUTHORS	TITLE	JOURNAL	VOL.	PAGES	YEAR	ORGANISM	LINK TO PUBMED	SOURCE
29417	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	PubMed
29874	Seidah, N.G.; Chretien, M.	Pro-protein convertases of subtilisin/kexin family	Methods Enzymol.	244	175-188	1994	Homo sapiens	PubMed
29875	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	PubMed
29877	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	PubMed
651008	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	PubMed
651892	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	PubMed
651913	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	PubMed
651994	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	PubMed
653858	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	PubMed
668083	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	PubMed
668377	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	PubMed
668422	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	PubMed
668720	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	PubMed
669378	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	PubMed
669436	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	PubMed
669626	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	PubMed
669843	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	-
670480	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	PubMed
677957	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	PubMed
682808	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	PubMed
683932	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	PubMed
686302	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	PubMed
686303	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	PubMed
688466	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	PubMed
688525	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	PubMed
688526	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	PubMed
689018	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	PubMed
689212	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	PubMed
689214	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	PubMed
700298	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	PubMed
700473	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	PubMed
708778	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	PubMed
709250	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	PubMed
709603	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	PubMed
710101	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	PubMed
717856	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	PubMed
717906	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	PubMed

LINKS TO OTHER DATABASES (specific for EC-Number 3.4.21.94)

NCBI: PubMed, Protein, Nucleotide, Structure, Genome, OMIM

IUBMB Enzyme Nomenclature

PROSITE Database of protein families and domains

SYSTERS

Protein Mutant Database

InterPro (database of protein families, domains and functional sites)

Mark a special word or phrase in this record:
Select one or more organisms in this record: