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Information on EC 3.4.21.B24 - proprotein convertase 4 and Organism(s) Homo sapiens and UniProt Accession Q6UW60

for references in articles please use BRENDA:EC3.4.21.B24
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.B24 proprotein convertase 4
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Homo sapiens
UNIPROT: Q6UW60
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
cleaves hormones at pairs of basic amino acid residues
Synonyms
pcsk4, proprotein convertase 4, proprotein convertase subtilisin/kexin type 4, proprotein convertase pc4, proprotein convertase subtilisin/kexin-like 4, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proprotein convertase subtilisin/kexin type 4
-
PCSK4
Q6KW60
-
proprotein convertase PC4/PCSK4
Q6KW60
-
additional information
the enzyme belongs to a family of endoproteinases involved in the proteolytic conversion of secretory precursor proteins to their active forms
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
pro-insulin growth factor-II + H2O
insulin growth factor-II
show the reaction diagram
PC4 cleaves pro-insulin growth factor-II to generate the intermediate processed form insulin growth factor-II (1-102) and, subsequently, mature insulin-growth factor-II (1-67)
-
-
?
Boc-RVRR-7-amido-4-methylcoumarin + H2O
Boc-RVRR + 7-amino-4-methylcoumarin
show the reaction diagram
Q6KW60
-
-
-
?
proform IGF-2 + H2O
mature IGF-2 + ?
show the reaction diagram
Q6KW60
-
-
-
?
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
proform IGF-2 + H2O
mature IGF-2 + ?
show the reaction diagram
Q6KW60
-
-
-
?
additional information
?
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cystatin related epididymal spermatogenic dimer
Q6KW60
i.e. CRES, an epididymal serpin, the recombinant protein inhibits the enzyme activity in vitro in a differential manner depending on its oligomeric state, overview
-
cystatin related epididymal spermatogenic monomer
Q6KW60
i.e. CRES, an epididymal serpin, the recombinant protein inhibits the enzyme activity in vitro in a differential manner depending on its oligomeric state, overview
-
additional information
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.008
cystatin related epididymal spermatogenic dimer
Q6KW60
pH and temperature not specified in the publication
-
0.1
cystatin related epididymal spermatogenic monomer
Q6KW60
pH and temperature not specified in the publication
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
PC4 predominantely present during the first trimester, to a lesser extent during the third trimester
Manually annotated by BRENDA team
PC4 predominantely present during the third trimester
Manually annotated by BRENDA team
PC4 predominantely present during the third trimester
Manually annotated by BRENDA team
Q6KW60
-
Manually annotated by BRENDA team
Q6KW60
-
Manually annotated by BRENDA team
Q6KW60
-
Manually annotated by BRENDA team
Q6KW60
placental
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
the enzyme belongs to a family of endoproteinases involved in the proteolytic conversion of secretory precursor proteins to their active forms. PCSK4 appears to be a crucial enzyme for reproduction. It stimulates the invasiveness of human placental trophoblasts in culture, suggesting that it may facilitate placentation in vivo
evolution
Q6KW60
the enzyme belongs to the 9-member superfamily of mammalian subtilases collectively called proprotein convertases or proprotein convertase subtilisin/kexins that convert inactive precursor proteins into their active mature forms by endoproteolytic cleavage
physiological function
Q6KW60
the enzyme activity plays a crucial role in mammalian fertilization via activation of sperm surface proteins
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PCSK4_HUMAN
755
0
82795
Swiss-Prot
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
54000
Western blot analysis, mature PC4
72000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
proteolytic modification
after cotranslational removal of the signal peptide, the resulting proPCSK undergoes maturation by autocatalytic cleavage between the pro and the catalytic domains, within a cleavage motif that is also recognized by the fully activated enzyme in the primary sequence of its physiological substrates, mechanism
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in HEK-293 cells
PCSK4 is the product of a 9 kb, 15 exon gene located on chromosome 19
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
abnormal processing of insulin growth factor-II by PC4 is involved in the pathophysiology of fetoplacental growth restriction
medicine
-
manifold effects of proprotein convertases, influencing tumor cell proliferation, motility, adhesiveness, and invasiveness, should be exploited by further developing competitive or inhibitory therapeutic strategies that would be able to neutralize simultaneously the most salient cancer cell properties
additional information
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bassi, D.E.; Fu, J.; Lopez de Cicco, R.; Klein-Szanto, A.J.
Proprotein convertases: "master switches" in the regulation of tumor growth and progression
Mol. Carcinog.
44
151-161
2005
Homo sapiens
Manually annotated by BRENDA team
Qiu, Q.; Basak, A.; Mbikay, M.; Tsang, B.K.; Gruslin, A.
Role of pro-IGF-II processing by proprotein convertase 4 in human placental development
Proc. Natl. Acad. Sci. USA
102
11047-11052
2005
Homo sapiens (Q6UW60), Homo sapiens
Manually annotated by BRENDA team
Freyer, C.; Kilpatrick, L.M.; Salamonsen, L.A.; Nie, G.
Pro-protein convertases (PCs) other than PC6 are not tightly regulated for implantation in the human endometrium
Reproduction
133
1189-1197
2007
Homo sapiens (Q6UW60)
Manually annotated by BRENDA team
Gyamera-Acheampong, C.; Mbikay, M.
Proprotein convertase subtilisin/kexin type 4 in mammalian fertility: a review.
Hum. Reprod. Update
15
237-247
2009
Homo sapiens (Q6UW60), Homo sapiens, Mus musculus (P29121), Mus musculus
Manually annotated by BRENDA team
Gyamera-Acheampong, C.; Sirois, F.; Denis, N.J.; Mishra, P.; Figeys, D.; Basak, A.; Mbikay, M.
The precursor to the germ cell-specific PCSK4 proteinase is inefficiently activated in transfected somatic cells: evidence of interaction with the BiP chaperone
Mol. Cell. Biochem.
348
43-52
2011
Homo sapiens (Q6UW60), Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Mishra, P.; Qiu, Q.; Gruslin, A.; Hidaka, Y.; Mbikay, M.; Basak, A.
In vitro regulatory effect of epididymal serpin CRES on protease activity of proprotein convertase PC4/PCSK4
Curr. Mol. Med.
12
1050-1067
2012
Homo sapiens (Q6KW60), Homo sapiens, Mus musculus (P29121)
Manually annotated by BRENDA team