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Information on EC 3.4.21.B26 - proprotein convertase 5 and Organism(s) Mus musculus and UniProt Accession Q04592

for references in articles please use BRENDA:EC3.4.21.B26
preliminary BRENDA-supplied EC number
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EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.21 Serine endopeptidases
                3.4.21.B26 proprotein convertase 5
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This record set is specific for:
Mus musculus
UNIPROT: Q04592
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Word Map
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
cleavage at the RX(K/R)R consensus motif. Release of mature proteins from their proproteins by cleavage of Arg-Xaa-Yaa-Arg-/-Zaa bonds, where Xaa can be any amino acid and Yaa is Arg or Lys.
Synonyms
pc5/6, pcsk5, pc5/6a, pc5-a, proprotein convertase 5/6, prohormone convertase 5, pc5-b, proprotein convertase subtilisin/kexin type 5, pc5/6b, proprotein convertase 5, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
convertase PC5/6
-
PC5/6A
proprotein convertase 5/6 (PC5/6) has two splice variants: soluble PC5/6A and membrane-bound PC5/6B
PC5/6B
proprotein convertase 5/6 (PC5/6) has two splice variants: soluble PC5/6A and membrane-bound PC5/6B
prohormone convertase 5
-
prohormone convertase 5/6
-
proprotein convertase 5/6
-
proprotein convertase PC5/6
-
PC5-A
-
-
PC5-B
-
-
PC5/6A
-
-
PC5A
-
-
PC5B
-
-
PCSK5
-
-
proprotein convertase 5/6
-
-
proprotein convertase PC5/6
-
-
S08.076
-
Merops ID
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
cleavage of C-N-linkage
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
99676-46-7
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ADAMTS-4 + H2O
?
show the reaction diagram
-
-
-
?
endothelial lipase + H2O
?
show the reaction diagram
-
-
-
?
human immunodeficiency virus type 1 Vpr + H2O
?
show the reaction diagram
undergoes proteolytic processing at a very well conserved proprotein convertase cleavage site, R85QRR88-/-, proprotein convertases PC5 and PACE4 can efficiently process extracellular Vpr
-
-
?
Lefty protein + H2O
?
show the reaction diagram
-
-
-
?
osteopontin + H2O
?
show the reaction diagram
PCSK9 + H2O
truncated PCSK9-DELTAN218 + ?
show the reaction diagram
-
-
-
?
preprohepcidin + H2O
?
show the reaction diagram
key role of the convertases furin, PACE4, PC5 and/or PC7 in the generation and secretion of active hepcidin
-
-
?
pro-cocaine- and amphetamine-regulated transcript precursor + H2O
bioactive pro-cocaine- and amphetamine-regulated transcript I + bioactive pro-cocaine- and amphetamine-regulated transcript II + ?
show the reaction diagram
PC5/6A preferentially cleaves the pairs of basic sites, KR/KK, of the CART precursor isoforms
-
-
?
pyroglutamic acid-RTKR-7-amido-4-methylcoumarin + H2O
pyroglutamic acid-RTKR + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
2-aminobenzoic acid-SKKRKRRFLG-(3-nitro)-Tyr-A + H2O
2-aminobenzoic acid-SKKRKRR + FLG-(3-nitro)-Tyr-A
show the reaction diagram
-
fluorogenic substrate encompassing the processing site of envelope glycoproteins of respiratory syncytial virus
-
?
2-aminobenzoyl-GGRRTRREAI-(3-nitro)-Tyr-A + H2O
2-aminobenzoyl-GGRRTRR + EAI-(3-nitro)-Tyr-A
show the reaction diagram
-
fluorogenic substrate encompassing the processing site of envelope glycoproteins of ebola virus
-
?
2-aminobenzoyl-RNTPRERKKRGL-(3-nitro)-Tyr-A + H2O
2-aminobenzoyl-RNTPRERKKR + GL-(3-nitro)-Tyr-A
show the reaction diagram
-
-
-
?
2-aminobenzoyl-RNTPRERRRKKRGL-(3-nitro)-Tyr-A + H2O
2-aminobenzoyl-RNTPRERRRKKR + GL-(3-nitro)-Tyr-A
show the reaction diagram
-
fluorogenic substrate encompassing the processing site of envelope glycoproteins of Hong Kong virus
-
?
2-aminobenzoyl-RNTPRKKRGL-(3-nitro)-Tyr-A + H2O
2-aminobenzoyl-RNTPRKKR + GL-(3-nitro)-Tyr-A
show the reaction diagram
-
-
-
?
2-aminobenzoyl-RNTPRRRKKRGL-(3-nitro)-Tyr-A + H2O
2-aminobenzoyl-RNTPRRRKKR + GL-(3-nitro)-Tyr-A
show the reaction diagram
-
-
-
?
2-aminobenzoyl-SKKRKRRFLG-(3-nitro)-Tyr-A + H2O
2-aminobenzoyl-SKKRKRR + FLG-(3-nitro)-Tyr-A
show the reaction diagram
-
-
-
-
?
pro-von Willebrand factor + H2O
von Willebrand factor + ?
show the reaction diagram
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
human immunodeficiency virus type 1 Vpr + H2O
?
show the reaction diagram
undergoes proteolytic processing at a very well conserved proprotein convertase cleavage site, R85QRR88-/-, proprotein convertases PC5 and PACE4 can efficiently process extracellular Vpr
-
-
?
osteopontin + H2O
?
show the reaction diagram
Pcsk5/PCSK5 is temporally and spatially expressed with Opn/OPN (Spp1/SPP1) in osteoblasts and osteocytes, indicating that osteopontin could be a physiologically relevant substrate for PC5/6 or PC5/6-activated proteases in bone. Cleavage of osteopontin may modify the function of osteopontin in bone and/or modulate other enzymatic cleavages of osteopontin, leading to alterations in the bone phenotype
-
-
?
preprohepcidin + H2O
?
show the reaction diagram
key role of the convertases furin, PACE4, PC5 and/or PC7 in the generation and secretion of active hepcidin
-
-
?
additional information
?
-
death at birth of the PC5/6-deficient embryos
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
0.2-1 mM required for maximal activity of both isoforms
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
prosegment of human furin
-
-
14-dehydroandrographolide succinoyl monoester
-
syn: SEA, 0.25 mM
antitrypsin-Portland
-
alpha1-antitrypsin-PDX
-
decanonyl-RVKR-chloromethylketone
-
-
hexa-D-arginine
-
-
nona-D-arginine
-
-
transforming growth factor beta-binding protein-2
-
-
-
transforming growth factor beta-binding protein-3
-
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
the activation of PC5A is stimulated by incubation of Y1 cells with adrenocorticotropic hormone or 8-Br-cAMP
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0031
2-aminobenzoyl-GGRRTRREAI-(3-nitro)-Tyr-A
-
pH 7, 37°C
0.0021
2-aminobenzoyl-RNTPRERKKRGL-(3-nitro)-Tyr-A
-
pH 7, 37°C
0.0051
2-aminobenzoyl-RNTPRERRRKKRGL-(3-nitro)-Tyr-A
-
pH 7, 37°C
0.0042
2-aminobenzoyl-RNTPRKKRGL-(3-nitro)-Tyr-A
-
pH 7, 37°C
0.0033
2-aminobenzoyl-RNTPRRRKKRGL-(3-nitro)-Tyr-A
-
pH 7, 37°C
0.0031
2-aminobenzoyl-SKKRKRRFLG-(3-nitro)-Tyr-A
-
pH 7, 37°C
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
expressed during mouse development in many tissues including bone and tooth
Manually annotated by BRENDA team
primary culture
Manually annotated by BRENDA team
expressed in the telencephalon at embryonic day E15.5
Manually annotated by BRENDA team
expressed during mouse development in many tissues including bone and tooth
Manually annotated by BRENDA team
-
PC5A dominates
Manually annotated by BRENDA team
-
PC5A dominates
Manually annotated by BRENDA team
-
in the small intestine PC5/6 is mainly expressed in enterocytes
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
PC5A dominates
Manually annotated by BRENDA team
-
furture hippocampus, CA3 region
Manually annotated by BRENDA team
-
richest source of PC5B
Manually annotated by BRENDA team
-
both isoforms equally expressed
Manually annotated by BRENDA team
-
PC5A dominates
Manually annotated by BRENDA team
-
PC5A dominates
Manually annotated by BRENDA team
-
PC5A dominates
Manually annotated by BRENDA team
-
pancreatic and adrenal primordium
Manually annotated by BRENDA team
-
PC5A dominates
Manually annotated by BRENDA team
-
PC5A dominates
Manually annotated by BRENDA team
-
PC5A dominates
Manually annotated by BRENDA team
-
most highly expressing PC5 line
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
proprotein convertase 5/6 (PC5/6) has two splice variants: soluble PC5/6A and membrane-bound PC5/6B
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
PC5/6-knockout mouse embryos show developmental abnormalities, and reduced overall mineralization
physiological function
Pcsk5/PCSK5 is temporally and spatially expressed with Opn/OPN (Spp1/SPP1) in osteoblasts and osteocytes, indicating that osteopontin could be a physiologically relevant substrate for PC5/6 or PC5/6-activated proteases in bone. Cleavage of osteopontin may modify the function of osteopontin in bone and/or modulate other enzymatic cleavages of osteopontin, leading to alterations in the bone phenotype
malfunction
physiological function
-
the proprotein convertase PC5/6 is protective against intestinal tumorigenesis
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PCSK5_MOUSE
1877
0
209257
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
65000
SDS-PAGE
110000
-
Western blot analysis, PC5A isoform
117000
-
isoform PC5-A, SDS-PAGE
69000
-
SDS-PAGE, PC5 of a stable transfectant in AtT-20 cells
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
-
COOH-terminal cleavage of the membrane-bound PC5-B occurs along the secretory pathway, intracellular zymogen cleavage of pro-PC5-A
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
Pcsk5delta4-deficient allele missing exon 4 that encodes the catalytic Asp173, delta4/delta4 genotype is embryonic lethal, heterozygote mice are healthy and fertile
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in GH3-CART cells
expressed in Y1 cells
2 isoforms: PC5-A and PC5-B, expressed in AtT-20 cells
-
expressed in AtT-20 cells
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Basak, A.; Zhong, M.; Munzer, J.S.; Chretien, M.; Seidah, N.G.
Implication of the proprotein convertases furin, PC5 and PC7 in the cleavage of surface glycoproteins of Hong Kong, Ebola and respiratory syncytial viruses: a comparative analysis with fluorogenic peptides
Biochem. J.
353
537-545
2001
Mus musculus
Manually annotated by BRENDA team
De Strooper, B.; Creemers, J.W.; Moechars, D.; Huylebroeck, D.; Van De Ven, W.J.; Van Leuven, F.; Van den Berghe, H.
Amyloid precursor protein is not processed by furin, PACE 4, PC1/3, PC2, PC4 and PC5/6 of the furin family of proprotein processing enzymes
Biochim. Biophys. Acta
1246
185-188
1995
Mus musculus
Manually annotated by BRENDA team
De Bie, I.; Marcinkiewicz, M.; Malide, D.; Lazure, C.; Nakayama, K.; Bendayan, M.; Seidah, N.G.
The isoforms of proprotein convertase PC5 are sorted to different subcellular compartments
J. Cell. Biol.
135
1261-1275
1996
Mus musculus
Manually annotated by BRENDA team
Tang, M.; Mikhailik, A.; Pauli, I.; Giudice, L.C.; Fazelabas, A.T.; Tulac, S.; Carson, D.D.; Kaufman, D.G.; Barbier, C.; Creemers, J.W.; Tabibzadeh, S.
Decidual differentiation of stromal cells promotes proprotein convertase 5/6 expression and lefty processing
Endocrinology
146
5313-5320
2005
Mus musculus (Q04592), Mus musculus
Manually annotated by BRENDA team
Seidah, N.G.; Chretien, M.
Proprotein convertase 5
Handbook of Proteolytic Enzymes (Barrett, A. J. , Rawlings, N. D. , Woessner, J. F. , Eds. ) Academic Press
2
1874-1877
2004
Homo sapiens, Mus musculus, Rattus norvegicus
-
Manually annotated by BRENDA team
Essalmani, R.; Hamelin, J.; Marcinkiewicz, J.; Chamberland, A.; Mbikay, M.; Chretien, M.; Seidah, N.G.; Prat, A.
Deletion of the gene encoding proprotein convertase 5/6 causes early embryonic lethality in the mouse
Mol. Cell. Biol.
26
354-361
2006
Homo sapiens (Q92824), Mus musculus
Manually annotated by BRENDA team
Stein, J.; Shah, R.; Steiner, D.F.; Dey, A.
RNAi-mediated silencing of prohormone convertase (PC) 5/6 expression leads to impairment in processing of cocaine- and amphetamine-regulated transcript (CART) precursor
Biochem. J.
400
209-215
2006
Mus musculus (Q04592)
Manually annotated by BRENDA team
Dikeakos, J.D.; Mercure, C.; Lacombe, M.; Seidah, N.G.; Reudelhuber, T.L.
PC1/3, PC2 and PC5/6A are targeted to dense core secretory granules by a common mechanism
FEBS J.
274
4094-4102
2007
Mus musculus
Manually annotated by BRENDA team
Seidah, N.G.; Mayer, G.; Zaid, A.; Rousselet, E.; Nassoury, N.; Poirier, S.; Essalmani, R.; Prat, A.
The activation and physiological functions of the proprotein convertases
Int. J. Biochem. Cell Biol.
40
1111-1125
2008
Mus musculus (Q04592)
Manually annotated by BRENDA team
Mayer, G.; Hamelin, J.; Asselin, M.; Pasquato, A.; Marcinkiewicz, E.; Tang, M.; Tabibzadeh, S.; Seidah, N.G.
The regulated cell surface zymogen activation of the proprotein convertase PC5A directs the processing of its secretory substrates
J. Biol. Chem.
283
2373-2384
2008
Mus musculus (Q04592)
Manually annotated by BRENDA team
Reynolds Nicole , R.N.; Blum Aliss, B.A.; Kitagawa Kouk, K.K.; Beinfeld, M.C.
Inhibition of PC5 expression decreases CCK secretion and increases PC2 expression
Peptides
27
901-904
2006
Mus musculus (Q04592), Mus musculus
Manually annotated by BRENDA team
Padua, M.B.; Hansen, P.J.
Regulation of DNA synthesis and the cell cycle in human prostate cancer cells and lymphocytes by ovine uterine serpin
BMC Cell Biol.
9
5
2008
Mus musculus (Q04592)
Manually annotated by BRENDA team
Essalmani, R.; Zaid, A.; Marcinkiewicz, J.; Chamberland, A.; Pasquato, A.; Seidah, N.G.; Prat, A.
In vivo functions of the proprotein convertase PC5/6 during mouse development: Gdf11 is a likely substrate
Proc. Natl. Acad. Sci. USA
105
5750-5755
2008
Mus musculus (Q04592), Mus musculus
Manually annotated by BRENDA team
Xiao, Y.; Chen, G.; Richard, J.; Rougeau, N.; Li, H.; Seidah, N.G.; Cohen, E.A.
Cell-surface processing of extracellular human immunodeficiency virus type 1 Vpr by proprotein convertases
Virology
372
384-397
2008
Mus musculus (Q04592)
Manually annotated by BRENDA team
Sun, X.; Essalmani, R.; Seidah, N.G.; Prat, A.
The proprotein convertase PC5/6 is protective against intestinal tumorigenesis: in vivo mouse model
Mol. Cancer
8
73
2009
Mus musculus
Manually annotated by BRENDA team
Fritzsche, J.; Stawowy, P.
Time for endothelial cell proprotein convertase PC5/6 in cardiovascular medicine?
J. Mol. Med.
89
1061-1063
2011
Mus musculus
Manually annotated by BRENDA team
Hoac, B.; Susan-Resiga, D.; Essalmani, R.; Marcinkiweicz, E.; Seidah, N.G.; McKee, M.D.
Osteopontin as a novel substrate for the proprotein convertase 5/6 (PCSK5) in bone
Bone
107
45-55
2018
Mus musculus (Q04592)
Manually annotated by BRENDA team