Any feedback?
Information on EC 3.4.21.69 - Protein C (activated) and Organism(s) Bos taurus and UniProt Accession P00745
for references in articles please use BRENDA:EC3.4.21.69Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
3.4.21.69 Protein C (activated)Specify your search results
Word Map
- 3.4.21.69
- thrombosis
- venous
- leiden
- sepsis
- endothelial
- antithrombin
- thromboembolism
- thrombophilia
- clot
- thrombomodulin
- platelet
-
procoagulant
- heparin
- arterial
- vein
-
bleeding
- plasminogen
-
hypercoagulable
- thromboplastin
-
lupus
- fibrinogen
-
fibrinolysis
-
hemostatic
- viiia
- epcr
-
intravascular
-
contraceptive
-
antiphospholipid
-
antithrombotic
-
prothrombotic
- fibrin
-
k-dependent
-
anticardiolipin
-
d-dimers
- coagulopathy
- embolism
- prothrombinase
-
amidolytic
-
thrombin-antithrombin
-
haemostasis
- par1
-
profibrinolytic
- pharmacology
-
goal-directed
- diagnostics
- drug development
-
gamma-carboxyglutamic
-
deep-vein
-
time-based
- tafi
-
hypofibrinolysis
-
thromboprophylaxis
- medicine
- protac
The taxonomic range for the selected organisms is: Bos taurus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
activated protein c, rhapc, protein ca, anticoagulant activated protein c, autoprothrombin ii-a, anticoagulant-activated protein c, anticoagulant serine protease-activated protein c, ghrelin endopeptidase, protein c (activated), 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Activated blood coagulation factor XIV
-
-
-
-
Activated protein C
APC
Autoprothrombin II-A
-
-
-
-
Autoprothrombin IIA
-
-
-
-
Blood coagulation factor XIV
-
-
-
-
Blood-coagulation factor XIV, activated
-
-
-
-
Blood-coagulation factor XIVa
-
-
-
-
GSAPC
-
-
-
-
Protein Ca
-
-
-
-
Activated protein C
-
-
-
-
APC
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
42617-41-4
-
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
Boc-Leu-Ser-Thr-Arg-4-nitroanilide + H2O
Boc-Leu-Ser-Thr-Arg + 4-nitroaniline
-
amidolytic activity
-
-
?
ghrelin + H2O
?
-
ghrelin is converted into smaller fragments in blood plasma in circulation under thrombotic and inflammatory conditions
-
-
?
Nalpha-benzoyl-L-Arg 4-nitroanilide + H2O
Nalpha-benzoyl-L-Arg + 4-nitroaniline
-
amidase activity
-
-
?
octanoyl-truncated ghrelin + H2O
?
-
preferred substrate, synthetic human substrate, octanoyl-truncated ghrelin(1-15) activates GHSR1a-dependent signaling similar to the full-length peptide
-
-
?
additional information
?
-
-
no effect on the coagulation activity of factor XII, factor XI, factor X, factor IX, factor VII or prothrombin
-
-
?
additional information
?
-
-
identification of the binding site for activated protein C on the light chains of factors V and VIII
-
-
?
additional information
?
-
-
role of protein C in the regulation of blood coagulation
-
-
?
additional information
?
-
-
activated protein C complexes with protein S on the surface of either platelets or the endothelium, these complexes catalyze the proteolytic inactivation of factors Va and VIIIa
-
-
?
additional information
?
-
-
potential role of the enzyme in blood coagulation and hemostasis
-
-
?
additional information
?
-
-
the enzyme is one of the gamma-carboxyglutamic acid-containing coagulation factors. It is formed by protein C, the proenzyme that circulates in plasma, by the action of a complex of thrombin with thrombomodulin or by serine endopeptidases present in several snake venoms
-
-
?
additional information
?
-
-
the enzyme is one of the gamma-carboxyglutamic acid-containing coagulation factors. It is formed by protein C, the proenzyme that circulates in plasma, by the action of a complex of thrombin with thrombomodulin or by serine endopeptidases present in several snake venoms
-
-
?
additional information
?
-
-
the enzyme is one of the gamma-carboxyglutamic acid-containing coagulation factors. It is formed by protein C, the proenzyme that circulates in plasma, by the action of a complex of thrombin with thrombomodulin or by serine endopeptidases present in several snake venoms
-
-
?
additional information
?
-
-
does not seem to be necessary for blood coagulation
-
-
?
additional information
?
-
-
bovine enzyme preferentially hydrolyzes the major form of octanoylated ghrelin(28), i.e. about twice as much hydrolysis as is observed for a longer acyl chain of decanoylated ghrelin(28). But both acyl and desacyl ghrelin are hydrolyzed at the peptidebond between Arg15 and Lys16, generating an N-terminal peptide consisting of the first 15 residues
-
-
?
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
ghrelin + H2O
?
-
ghrelin is converted into smaller fragments in blood plasma in circulation under thrombotic and inflammatory conditions
-
-
?
additional information
?
-
-
role of protein C in the regulation of blood coagulation
-
-
?
additional information
?
-
-
activated protein C complexes with protein S on the surface of either platelets or the endothelium, these complexes catalyze the proteolytic inactivation of factors Va and VIIIa
-
-
?
additional information
?
-
-
potential role of the enzyme in blood coagulation and hemostasis
-
-
?
additional information
?
-
-
the enzyme is one of the gamma-carboxyglutamic acid-containing coagulation factors. It is formed by protein C, the proenzyme that circulates in plasma, by the action of a complex of thrombin with thrombomodulin or by serine endopeptidases present in several snake venoms
-
-
?
additional information
?
-
-
the enzyme is one of the gamma-carboxyglutamic acid-containing coagulation factors. It is formed by protein C, the proenzyme that circulates in plasma, by the action of a complex of thrombin with thrombomodulin or by serine endopeptidases present in several snake venoms
-
-
?
additional information
?
-
-
the enzyme is one of the gamma-carboxyglutamic acid-containing coagulation factors. It is formed by protein C, the proenzyme that circulates in plasma, by the action of a complex of thrombin with thrombomodulin or by serine endopeptidases present in several snake venoms
-
-
?
additional information
?
-
-
does not seem to be necessary for blood coagulation
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
additional information
Ca2+
-
contains gamma-carboxyglutamic acid residues required for Ca2+-dependent membrane binding
additional information
-
the divalent cation site is separate from the monovalent cation site and the active site of the enzyme
additional information
-
the enzyme displays a strict requirement for monovalent cations in its expression of amidolytic activity towards Nalpha-benzoyl-L-arginine 4-nitroanilide
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
alpha1-antitrypsin
APC anti-coagulant activity is eventually inhibited by the action of the serpins alpha1-antitrypsin and protein C inhibitor, which irreversibly bind and inactivate APC prior to clearance
-
Protein C inhibitor
APC anti-coagulant activity is eventually inhibited by the action of the serpins alpha1-antitrypsin and protein C inhibitor, which irreversibly bind and inactivate APC prior to clearance
-
Protein C inhibitor
-
bovine plasma protein C inhibitor is structural and functional homologous to human plasma protein C inhibitor
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.32
Nalpha-benzoyl-L-arginine 4-nitroanilide
-
with Na+ or Cs+ as activating cation
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
the anticoagulant-activated protein C (APC) acts not solely as a crucial regulator of thrombus formation following vascular injury, but also as a potent signalling enzyme with important functions in the control of both acute and chronic inflammatory disease
physiological function
-
the enzyme is a major regulator of blood coagulation by inactivating factors Va and VIIIa. O-ghrelin(15) has no effect
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). PROC_BOVIN
456
0
51409
Swiss-Prot
Secretory Pathway (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
21000
41000
-
1 * 41000 + 1 * 21000, bovine protein C, SDS-PAGE of reduced protein, heavy and light chain are connected by a disulfide bond, cleavage of Arg12-Leu13 in the heavy chain releases a small activation peptide, MW 1400 and protein Ca
54300
-
bovine, protein C, amino acid and carbohydrate composition data, conversion to protein Ca by hydrolysis of a specific peptide bond in the amino-terminal region of the heavy chain between Arg14 and Ile15, giving rise to protein Ca, MW 52650 and an activation peptide, MW 1650
additional information
21000
-
1 * 41000 + 1 * 21000, bovine protein C, SDS-PAGE of reduced protein, heavy and light chain are connected by a disulfide bond, cleavage of Arg12-Leu13 in the heavy chain releases a small activation peptide, MW 1400 and protein Ca
additional information
-
of the heavy chain of bovine protein C, on activation, an NH2-terminal tetradecapeptide is removed
additional information
-
amino acid sequence: of the light chain of bovine protein C
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
dimer
-
1 * 41000 + 1 * 21000, bovine protein C, SDS-PAGE of reduced protein, heavy and light chain are connected by a disulfide bond, cleavage of Arg12-Leu13 in the heavy chain releases a small activation peptide, MW 1400 and protein Ca
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
-
bovine protein C contains 14% carbohydrate, approximately 15 residues of hexose, 12 residues of hexosamine and 9 residues of sialic acid distributed in 3 carbohydrate chains, human protein C contains 23% carbohydrate, approximately 14 residues of galactose, 21 residues of mannose, 23 residues of glucosamine and 12 residues of sialic acid
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native enzyme from bovine plasma by gel filtration, mannose affinity and Blue Sepharose chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
protective effect of recombinant APC administration in animals subject to Escherichia coli-induced sepsis. Possible effects of APC administration may include attenuation of the proinflammatory cytokine storm, re-balancing dysregulated haemostasis or degradation of cytotoxic extracellular histones that circulate during sepsis. Successful pre-clinical animal studies indicate that the neuroprotective effects of recombinant APC do not require anti-coagulant activity for therapeutic benefit to be achieved
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Esmon, C.T.
The roles of protein C and thrombomodulin in the regulation of blood coagulation
J. Biol. Chem.
264
4743-4746
1989
Bos taurus, Homo sapiens
Stenflo, J.
A new vitamin K-dependent protein. Purification from bovine plasma and preliminary characterization
J. Biol. Chem.
251
355-363
1976
Bos taurus
Esmon, C.T.; Stenflo, J.; Suttie, J.W.; Jackson, C.M.
A new vitamin K-dependent protein. A phospholipid-binding zymogen of a serine esterase
J. Biol. Chem.
251
3052-3056
1976
Bos taurus
Hill, K.A.W.; Castellino, F.J.
The binding of Mn2+ to bovine plasma protein C, des(1-41)-light chain protein C, and activated des(1-41)-light chain activated protein C
Arch. Biochem. Biophys.
254
196-202
1987
Bos taurus
Fernlund, P.; Stenflo, J.
Amino acid sequence of the light chain of bovine protein C
J. Biol. Chem.
257
12170-12179
1982
Bos taurus
Stenflo, J.; Fernlund, P.
Amino acid sequence of the heavy chain of bovine protein C
J. Biol. Chem.
257
12180-12190
1982
Bos taurus
Steiner, S.A.; Castellino.F.J.
Kinetic mechanism for stimulation by monovalent cations of the amidase activity of the plasma protease bovine activated protein C
Biochemistry
24
609-617
1985
Bos taurus
Kisiel, W.; Canfield, W.M.; Ericsson, L.H.; Davie, E.W.
Anticoagulant properties of bovine plasma protein C following activation by thrombin
Biochemistry
16
5824-5831
1977
Bos taurus
Chi, C.W.; Liu, H.Z.; Liu, C.Y.; Chibber, B.A.K.; Castellino, F.J.
The inhibition of the enzymic activity of blood coagulation and fibrinolytic serine proteases by a new leupeptin-like inhibitor, and its structural analogs, isolated from Streptomyces griseus
J. Antibiot.
17
1506-1512
1989
Bos taurus
-
Walker, F.J.; Scandella, D.; Fay, P.J.
Identification of the binding site for activated protein C on the light chain of factors V and VIII
J. Biol. Chem.
265
1484-1489
1990
Bos taurus
Suzuki, K.; Kusumoto, H.; Nishioka, J.; Komiyama, Y.
Bovine plasma protein C inhibitor with structural and functional homologous properties to human plasma protein C inhibitor
J. Biochem.
107
381-388
1990
Bos taurus, Homo sapiens
Mann, K.G.; Hockin, M.F.; Begin, K.J.; Kalafatis, M.
Activated protein C cleavage of factor Va leads to dissociation of the A2 domain
J. Biol. Chem.
272
20678-20683
1997
Bos taurus
Yegneswaran, S.; Deguchi, H.; Griffin, J.H.
Glucosylceramide, a neutral glycosphingolipid anticoagulant cofactor, enhances the interaction of human- and bovine-activated protein C with negatively charged phospholipid vesicles
J. Biol. Chem.
278
14614-14621
2003
Bos taurus, Homo sapiens
Satou, M.; Nishi, Y.; Hishinuma, A.; Hosoda, H.; Kangawa, K.; Sugimoto, H.
Identification of activated protein C as a ghrelin endopeptidase in bovine plasma
J. Endocrinol.
224
61-73
2015
Bos taurus, Homo sapiens, Mus musculus, Mus musculus C57/BL6J
EXTERNAL LINKS (specific for EC-Number 3.4.21.69)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
