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Information on EC 3.4.21.42 - complement subcomponent C1s and Organism(s) Homo sapiens and UniProt Accession P09871

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EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.21 Serine endopeptidases
                3.4.21.42 complement subcomponent C1s
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Select one or more organisms in this record: ?
This record set is specific for:
Homo sapiens
UNIPROT: P09871 not found.
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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
Cleavage of Arg-/-Ala bond in complement component C4 to form C4a and C4b, and Lys(or Arg)-/-Lys bond in complement component C2 to form C2a and C2b: the "classical" pathway C3 convertase
Synonyms
masp-2, c1 esterase, c1-esterase, mbl-associated serine protease-2, complement c1s, complement component c1s, c1s protease, serine protease c1s, complement protease, protease c1s, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C1 esterase
-
complement component 1 subcomponent s
UniProt
complement component C1s
-
complement protease
-
complement subcomponent 1s
-
multiprotein complex C1
the multiprotein complex C1 is formed from the recognition subcomponent C1q and a tetramer of proteases C1r2C1s2
protease C1s
-
serine protease C1s
-
activated complement C1s
-
-
-
-
C1 esterase
C1-esterase
-
-
-
-
C1s protease
-
-
C1s serine protease
-
-
complement 1s
-
-
complement C.hivin. 1s
-
-
-
-
complement C1s
-
-
complement C1s, activated
-
-
-
-
complement component 1 s
-
-
complement protease C1s
-
-
complement subcomponent C1sbar
-
-
-
-
esterase, C1
-
-
-
-
mannan-binding lectin-associated serine protease-2
-
-
MBL-associated serine protease-2
-
-
protease C1s
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
80295-70-1
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-aminobenzoyl-GLQRALEI-Lys(dinitrophenol)-NH2 + H2O
?
show the reaction diagram
the Abz-GLQRALEI-Lys(Dnp)fluorescence quenched peptide representing the P4-P4' sequence of complement C4
-
-
?
benzoyl-beta-Ala-Gly-L-Arg 4-nitroanilide + H2O
benzoyl-beta-Ala-Gly-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
benzoyl-L-Pro-L-Phe-L-Arg 4-nitroanilide + H2O
benzoyl-L-Pro-L-Phe-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
benzoyl-L-Val-Gly-L-Arg 4-nitroaniline + H2O
benzoyl-L-Val-Gly-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-Gly-D-Ala-L-Arg 4-nitroanilide + H2O
benzyloxycarbonyl-Gly-D-Ala-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-Gly-L-Pro-L-Arg 4-nitroanilide + H2O
benzyloxycarbonyl-Gly-L-Pro-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-L-Arg 4-nitroanilide + H2O
benzyloxycarbonyl-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-L-Arg-L-Arg 4-nitroanilide + H2O
benzyloxycarbonyl-L-Arg-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-L-Lys 4-nitroanilide + H2O
benzyloxycarbonyl-L-Lys + 4-nitroaniline
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-L-Lys-L-Arg 4-nitroanilide + H2O
benzyloxycarbonyl-L-Lys-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-L-Phe-L-Arg 4-nitroanilide + H2O
benzyloxycarbonyl-L-Phe-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-L-Tyr-L-Lys-L-Arg 4-nitroanilide + H2O
benzyloxycarbonyl-L-Tyr-L-Lys-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-L-Val-Gly-L-Arg 4-nitroanilide + H2O
benzyloxycarbonyl-L-Val-Gly-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
Boc-Leu-Ser-Thr-Arg-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
?
butyloxycarbonyl-L-Leu-Gly-L-Arg 4-nitroanilide + H2O
butyloxycarbonyl-L-Leu-Gly-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
butyloxycarbonyl-O-benzoyl-L-Ser-Gly-Arg 4-nitroanilide + H2O
butyloxycarbonyl-O-benzoyl-L-Ser-Gly-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
C4 complement + H2O
?
show the reaction diagram
-
-
-
?
complement C1q zymogen + H2O
?
show the reaction diagram
C1s-C1q Collagen interface, the three collagen-like peptides form a right-handed helix with a characteristic one residue stagger between adjacent strands, overview
-
-
?
complement C1q zymogen + H2O
active complement C1q + ?
show the reaction diagram
complement C4 + H2O
?
show the reaction diagram
-
-
-
?
complement C4 zymogen + H2O
active complement C4 + ?
show the reaction diagram
-
-
-
?
complement C4-bound C2 zymogen + H2O
C4a + C2b
show the reaction diagram
-
the fragments associate to form a C3 convertase enzyme
-
?
complement C4b-bound C2 + H2O
?
show the reaction diagram
-
-
-
?
D-CHG-L-Pro-L-Arg 4-nitroanilide + H2O
D-CHG-L-Pro-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
D-Ile-L-Phe-L-Lys 4-nitroanilide + H2O
D-Ile-L-Phe-L-Lys + 4-nitroaniline
show the reaction diagram
-
-
-
?
D-Ile-L-Pro-L-Arg 4-nitroanilide + H2O
D-Ile-L-Pro-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
D-Pro-L-hexahydrotyrosine-L-Arg 4-nitroanilide + H2O
D-Pro-L-hexahydrotyrosine-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
D-Pro-L-Phe-L-Arg 4-nitroanilide + H2O
D-Pro-L-Phe-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
D-Val-L-cyclohexylalanine-L-Arg 4-nitroanilide + H2O
D-Val-L-cyclohexylalanine-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
D-Val-L-Leu-L-Arg 4-nitroanilide + H2O
D-Val-L-Leu-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
D-Val-L-Leu-L-Lys 4-nitroanilide + H2O
D-Val-L-Leu-L-Lys + 4-nitroaniline
show the reaction diagram
-
-
-
?
D-Val-L-Phe-L-Lys 4-nitroanilide + H2O
D-Val-L-Phe-L-Lys + 4-nitroaniline
show the reaction diagram
-
-
-
?
Gly-Arg 4-nitroanilide + H2O
Gly-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
L-Glu-Gly-L-Arg 4-nitroanilide + H2O
L-Glu-Gly-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
L-Glu-L-Pro-L-Arg 4-nitroanilide + H2O
L-Glu-L-Pro-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
methyloxycarbonyl-D-L-hexahydrotyrosine-Gly-L-Arg 4-nitroaniline + H2O
methyloxycarbonyl-D-L-hexahydrotyrosine-Gly-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
methyloxycarbonyl-D-Nle-Gly-L-Arg 4-nitroaniline + H2O
methyloxycarbonyl-D-Nle-Gly-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
methyloxycarbonyl-L-cyclohexylglycine-Gly-L-Arg 4-nitroaniline + H2O
methyloxycarbonyl-L-cyclohexylglycine-Gly-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
N2-acetyl-L-Lys-N6-benzyloxycarbonyl-Gly-L-Arg 4-nitroanilide + H2O
N2-acetyl-L-Lys-N6-benzyloxycarbonyl-Gly-L-Arg + 4-nitroaniline
show the reaction diagram
best substrate
-
-
?
N2-acetyl-N6-benzyloxycarbonyl-L-Lys-Gly-L-Arg 4-nitroanilide + H2O
N2-acetyl-N6-benzyloxycarbonyl-L-Lys-Gly-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
N6-benzyloxycarbonyl-D-Lys-L-Pro-L-Arg 4-nitroanilide + H2O
N6-benzyloxycarbonyl-D-Lys-L-Pro-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
Sar-L-Pro-L-Arg 4-nitroanilide + H2O
Sar-L-Pro-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
tosyl-Gly-L-Pro-L-Arg 4-nitroanilide + H2O
tosyl-Gly-L-Pro-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
tosyl-Gly-L-Pro-L-Lys 4-nitroanilide + H2O
tosyl-Gly-L-Pro-L-Lys + 4-nitroaniline
show the reaction diagram
-
-
-
?
Z-AGLQR-7-amido-4-methylcoumarin + H2O
Z-AGLQR + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
Z-LGR-7-amido-4-methylcoumarin + H2O
Z-LGR + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
2-aminobenzoyl-Gly-Leu-Gln-Arg-Ala-Leu-Glu-Ile-Lys(dinitrophenyl)-NH2 + H2O
2-aminobenzoyl-Gly-Leu-Gln-Arg + Ala-Leu-Glu-Ile-Lys(dinitrophenyl)-NH2
show the reaction diagram
2-aminobenzoyl-Gly-Tyr-Leu-Gly-Arg-Ser-Tyr-Lys-Val-Gly-Lys(dinitrophenyl)-Asp-OH + H2O
2-aminobenzoyl-Gly-Tyr-Leu-Gly-Arg + Ser-Tyr-Lys-Val-Gly-Lys(dinitrophenyl)-Asp-OH + H2O
show the reaction diagram
-
substrate obtained from phage display analysis, 4.7fold higher procession than the natural C1s protease substrate (SLGRKIQI)
-
-
?
2-aminobenzoyl-Ser-Leu-Gly-Arg-Lys-Ile-Gln-Ile-Lys(dinitrophenyl)-NH2 + H2O
2-aminobenzoyl-Ser-Leu-Gly-Arg + Lys-Ile-Gln-Ile-Lys(dinitrophenyl)-NH2
show the reaction diagram
2-aminobenzoyl-Ser-Val-Ala-Arg-Thr-Leu-Leu-Lys(dinitrophenyl)-NH2 + H2O
2-aminobenzoyl-Ser-Val-Ala-Arg + Thr-Leu-Leu-Lys(dinitrophenyl)-NH2 + H2O
show the reaction diagram
-
-
-
-
?
Ac-Ala-P3-P2-P1-7-amino-4-carbamoylmethylcoumarin + H2O
?
show the reaction diagram
-
a 722-member substrate library with combinations of all proteogenic amino acids at positions P3 and P2 was screened for cleavage, C1s preferred the small polar residues Ser, Ala and Gly at the P2 position and had a broad specificity at P3 position
-
-
?
Benzoyl-Arg ethyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
benzyloxycarbonyl-Gly-Leu-Gln-Arg-4-methylcoumaryl-7-amide + H2O
benzyloxycarbonyl-Gly-Leu-Gln-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-Ser-Leu-Gly-Arg-4-methylcoumaryl-7-amide + H2O
benzyloxycarbonyl-Ser-Leu-Gly-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
C1-inhibitor P4-P1 fragment + H2O
?
show the reaction diagram
-
-
-
-
?
C1-inhibitor P4-P4' fragment + H2O
?
show the reaction diagram
-
-
-
-
?
C2H5CO-Lys-(epsilon-Cbz)-Gly-Arg-4-nitroanilide + H2O
C2H5CO-Lys-(epsilon-Cbz)-Gly-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
?
complement component C2 + H2O
?
show the reaction diagram
-
-
-
-
?
complement component C2 + H2O
complement component C2a + complement component C2b
show the reaction diagram
complement component C2 P4-P1 fragment + H2O
?
show the reaction diagram
-
-
-
-
?
complement component C2 P4-P4' fragment + H2O
?
show the reaction diagram
-
-
-
-
?
complement component C4 + H2O
?
show the reaction diagram
-
-
-
-
?
complement component C4 + H2O
complement component C4a + complement component C4b
show the reaction diagram
complement component C4 P4-P1 fragment + H2O
?
show the reaction diagram
-
-
-
-
?
complement component C4 P4-P4' fragment + H2O
?
show the reaction diagram
-
-
-
-
?
GLQRA + H2O
GLQR + Ala
show the reaction diagram
-
-
-
?
GLQRAAEI + H2O
GLQR + AAEI
show the reaction diagram
-
-
-
?
GLQRAEEI + H2O
GLQR + AEEI
show the reaction diagram
-
-
-
?
GLQRAFEI + H2O
GLQR + AFEI
show the reaction diagram
-
-
-
?
GLQRAHEI + H2O
GLQR + AHEI
show the reaction diagram
-
-
-
?
GLQRAL + H2O
GLQR + Ala-Leu
show the reaction diagram
-
-
-
?
GLQRALAI + H2O
GLQR + ALAI
show the reaction diagram
-
-
-
?
GLQRALE + H2O
GLQR + ALE
show the reaction diagram
-
-
-
?
GLQRALEA + H2O
GLQR + ALEA
show the reaction diagram
-
-
-
?
GLQRALEE + H2O
GLQR + ALEE
show the reaction diagram
-
-
-
?
GLQRALEF + H2O
GLQR + ALEF
show the reaction diagram
-
-
-
?
GLQRALEH + H2O
GLQR + ALEH
show the reaction diagram
-
-
-
?
GLQRALEI + H2O
GLQR + ALEI
show the reaction diagram
-
-
-
?
GLQRALEK + H2O
GLQR + ALEK
show the reaction diagram
-
-
-
?
GLQRALEL + H2O
GLQR + ALEL
show the reaction diagram
-
-
-
?
GLQRALEM + H2O
GLQR + ALEM
show the reaction diagram
-
-
-
?
GLQRALEP + H2O
GLQR + ALEP
show the reaction diagram
-
-
-
?
GLQRALEQ + H2O
GLQR + ALEQ
show the reaction diagram
-
-
-
?
GLQRALET + H2O
GLQR + ALET
show the reaction diagram
-
-
-
?
GLQRALFI + H2O
GLQR + ALFI
show the reaction diagram
-
-
-
?
GLQRALHI + H2O
GLQR + ALHI
show the reaction diagram
-
-
-
?
GLQRALKI + H2O
GLQR + ALKI
show the reaction diagram
-
-
-
?
GLQRALLI + H2O
GLQR + ALLI
show the reaction diagram
-
-
-
?
GLQRALMI + H2O
GLQR + ALMI
show the reaction diagram
-
-
-
?
GLQRALPI + H2O
GLQR + ALPI
show the reaction diagram
-
-
-
?
GLQRALQI + H2O
GLQR + ALQI
show the reaction diagram
-
-
-
?
GLQRALTI + H2O
GLQR + ALTI
show the reaction diagram
-
-
-
?
GLQRAMEI + H2O
GLQR + AMEI
show the reaction diagram
-
-
-
?
GLQRAPEI + H2O
GLQR + APEI
show the reaction diagram
-
-
-
?
GLQRAQEI + H2O
GLQR + AQEI
show the reaction diagram
-
-
-
?
GLQRATEI + H2O
GLQR + ATEI
show the reaction diagram
-
-
-
?
GLQRELEI + H2O
GLQR + ELEI
show the reaction diagram
-
-
-
?
GLQRFLEI + H2O
GLQR + FLEI
show the reaction diagram
-
-
-
?
GLQRHLEI + H2O
GLQR + HLEI
show the reaction diagram
-
-
-
?
GLQRKLEI + H2O
GLQR + KLEI
show the reaction diagram
-
-
-
?
GLQRLLEI + H2O
GLQR + LLEI
show the reaction diagram
-
-
-
?
GLQRMLEI + H2O
GLQR + MLEI
show the reaction diagram
-
-
-
?
GLQRQLEI + H2O
GLQR + QLEI
show the reaction diagram
-
-
-
?
GLQRTLEI + H2O
GLQR + TLEI
show the reaction diagram
-
-
-
?
gp120 + H2O
?
show the reaction diagram
-
-
-
-
?
insulin-like growth factor-binding protein-5 + H2O
?
show the reaction diagram
insulin-like growth factor-I binding protein-5 + H2O
?
show the reaction diagram
-
C1s accounts for the proteolytic activity in human osteoarthritis fluid for insulin-like growth factor-I binding protein-5
-
-
?
kininogen I + H2O
kinin
show the reaction diagram
-
very slow activity
-
?
N-acetyl-Arg methyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
N-acetyl-Gly-Lys methyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
N-acetyl-Tyr ethyl ester + H2O
N-acetyl-Tyr + ethanol
show the reaction diagram
-
-
-
-
?
N-benzoyl-Phe-Val-Arg p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
N-benzyloxycarbonyl-Gly-Arg thiobenzyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
N-benzyloxycarbonyl-Lys-p-nitrophenyl ester + H2O
?
show the reaction diagram
N-benzyloxycarbonyl-Tyr-p-nitrophenyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
N2-acetyl-N6-benzyloxycarbonyl-Lys-Gly-Arg 4-nitroanilide + H2O
N2-acetyl-N6-benzyloxycarbonyl-Lys-Gly-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
Nalpha-acetyl-Tyr ethyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
Nalpha-tosyl-Arg methyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
tert-butyloxycarbonyl-Lys p-nitrophenyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
tert-butyloxycarbonyl-Phe p-nitrophenyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
tert-butyloxycarbonyl-Tyr p-nitrophenyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
Tosyl-Arg methyl ester + H2O
?
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
complement C1q zymogen + H2O
?
show the reaction diagram
C1s-C1q Collagen interface, the three collagen-like peptides form a right-handed helix with a characteristic one residue stagger between adjacent strands, overview
-
-
?
complement C1q zymogen + H2O
active complement C1q + ?
show the reaction diagram
-
-
-
?
complement C4 + H2O
?
show the reaction diagram
-
-
-
?
complement C4 zymogen + H2O
active complement C4 + ?
show the reaction diagram
-
-
-
?
complement C4-bound C2 zymogen + H2O
C4a + C2b
show the reaction diagram
-
the fragments associate to form a C3 convertase enzyme
-
?
complement C4b-bound C2 + H2O
?
show the reaction diagram
-
-
-
?
complement component C2 + H2O
?
show the reaction diagram
-
-
-
-
?
complement component C2 + H2O
complement component C2a + complement component C2b
show the reaction diagram
-
-
-
-
?
complement component C4 + H2O
?
show the reaction diagram
-
-
-
-
?
complement component C4 + H2O
complement component C4a + complement component C4b
show the reaction diagram
-
-
-
-
?
gp120 + H2O
?
show the reaction diagram
-
-
-
-
?
insulin-like growth factor-binding protein-5 + H2O
?
show the reaction diagram
-
the enzyme accounts for cleavage of insulin-like growth factor-binding protein-5 in fibroblast medium
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
the NH2-terminal alpha fragment of the enzyme contains one high affinity Ca2+ binding site
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-bromo-N-(3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-2-methylbiphenyl-4-yl)acetamide
-
2-bromo-N-(3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)acetamide
-
4-[(2'-methylbiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
C1-inhibitor
-
-
human C1-esterase inhibitor
C1-INH, a multifunctional plasma protein with a wide range of inhibitory and non-inhibitory properties, mainly recognized as a key downregulator of the complement and contact cascades. Potentiation of C1-INH by heparin and other glycosaminoglycans regulating a broad spectrum of C1-INH activities in vivo both in normal and disease states, interaction analysis via double capture SPR approach, surface plasmon resonance (using a CM5 sensor chip through amine coupling) and circular dichroism, overview. Heparin binding does not alter C1-INH secondary structure and does not affect the amidolytic activity of C1s, but does accelerate its consumption due to C1-INH potentiation
-
N-PEG2000 6-[[(3'-[[5-carbamimidoyl-2-(methylsulfanyl)-2,3-dihydrothiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)carbamoyl]amino]hexanamide
PEG size 20 kDa
N-PEG2000 N-(3'-[[5-carbamimidoyl-2-(methylsulfanyl)-2,3-dihydrothiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)dodecanediamide
PEG size 20 kDa
N-PEG4000 6-[[(3'-[[5-carbamimidoyl-2-(methylsulfanyl)-2,3-dihydrothiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)carbamoyl]amino]hexanamide
PEG size 40 kDa
N-PEG750 2-[(2-amino-2-oxoethyl)sulfanyl]-N-(3'-[[5-carbamimidoyl-2-(methylsulfanyl)-2,3-dihydrothiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)acetamide
N-PEG750 2-[(2-amino-2-oxoethyl)sulfanyl]-N-(3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-2-methylbiphenyl-4-yl)acetamide
-
N-PEG750 2-[(2-amino-2-oxoethyl)sulfanyl]-N-(3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)acetamide
PEG size 0.75 kDa
PEG-linked bis(6-[[(4-carbamimidamido-3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)carbamoyl]amino]hexanamide)
PEG size 20 kDa
PEG-linked bis(N-[6-amino-5-[(4-carbamimidamido-3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)amino]hept-6-en-1-yl]-6-[[(4-carbamimidamido-3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfanyl]biphenyl-2-yl)carbamoyl]amino]hexanamide)
-
-
PEG-linked tetrakis(4-[[4'-carbamimidamido-2'-(carbamoylamino)biphenyl-3-yl]sulfanyl]-5-(methylsulfanyl)thiophene-2-carboximidamide)
PEG size 20 kDa
-
TNT003
a mouse monoclonal antibody targeting the CP-specific serine protease C1s. TNT003 prevents cold agglutinin-mediated deposition of complement opsonins that promote phagocytosis of red blood cells. By preventing classical pathway activation, TNT003 also prevents cold agglutinin-driven generation of anaphylatoxins
-
1,10-phenanthroline
-
-
3,4-dichloroisocoumarin
-
-
4-chloro-3-(3-isothiureidopropoxy)isocoumarin
-
best inhibitor among substituted isocoumarins
4-chloro-3-ethoxy-7-guanidinoisocoumarin
-
-
4-chloro-7-guanidino-3-(2-phenylethoxy)isocoumarin
-
-
4-chloro-7-guanidino-3-methoxyisocoumarin
-
-
7-amino-4-chloro-3-(3-isothiureidopropoxy)isocoumarin
-
-
amidines
-
-
C-1 esterase inhibitor
-
main inhibitor of C1r and C1s of the complement system
-
C1 esterase inhibitor
-
C1-esterase inhibitor
inhibitory effect is increased by addition of heparin (5-500 nM)
-
C1-inhibitor
-
a serpin
-
C1bar inhibitor
-
C1s-INH-248
-
highly selective small molecule inhibitor. Blocking the classical complement pathway with a highly specific and potent synthetic inhibitor of the classical C1 complex appears to be an effective mean to preserve ischemic myocardium from injury following reperfusion
-
CP-013043
-
-
-
CP-143217
-
-
CP-349547
-
-
FUT175
-
potent C1s inhibitor
Guanidines
-
-
-
p-nitrophenyl-p'-guanidinobenzoate
-
-
PHA-00737785
-
-
PMSF
-
-
serine protease inhibitor 1
-
-
-
serine protease inhibitor 2
-
-
-
sutimlimab
-
-
-
unconjugated bilirubin
-
inhibits C1 esterase activity at pathological concentrations (above 17 micromol) and in a dose-dependent manner, due to a direct pigment-protein interaction. Maximal inhibitory activity is reached at an 85 micromol concentration. Inhibitory action exerted by unconjugated bilirubin on the classical pathway is not only due to an impairment of the interaction of the C1q subcomponent with IgM or IgG but also to a diminished enzymatic activity of the C1 esterase
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.012 - 0.0138
2-aminobenzoyl-GLQRALEI-Lys(dinitrophenol)-NH2
0.0654 - 0.245
Z-AGLQR-7-amido-4-methylcoumarin
0.0762 - 0.212
Z-LGR-7-amido-4-methylcoumarin
19
acetyl-L-Tyr ethyl ester
-
-
2.5 - 5
benzoyl-Arg ethyl ester
-
-
0.3408
C1-inhibitor P4-P1 fragment
-
pH 7.4, 37°C
-
0.0077
C1-inhibitor P4-P4' fragment
-
pH 7.4, 37°C
-
0.0052 - 0.0061
Complement component C2
-
0.1369
complement component C2 P4-P1 fragment
-
pH 7.4, 37°C
-
0.0274
complement component C2 P4-P4' fragment
-
pH 7.4, 37°C
-
0.000085 - 0.0066
Complement component C4
-
0.3581
complement component C4 P4-P1 fragment
-
pH 7.4, 37°C
-
0.0136
complement component C4 P4-P4' fragment
-
pH 7.4, 37°C
-
0.36
N-benzoyl-Phe-Val-Arg p-nitroanilide
-
-
0.069
N-benzyloxycarbonyl-Gly-Arg thiobenzyl ester
-
-
0.8
N-benzyloxycarbonyl-Lys p-nitrophenyl ester
-
-
0.056 - 0.07
N-benzyloxycarbonyl-Tyr p-nitrophenyl ester
-
-
0.07
t-butyloxycarbonyl-Tyr p-nitrophenyl ester
-
-
1.7 - 2.8
tosyl-Arg methyl ester
-
-
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.14 - 1.3
2-aminobenzoyl-GLQRALEI-Lys(dinitrophenol)-NH2
1.3 - 116.5
Z-AGLQR-7-amido-4-methylcoumarin
1.77 - 6
Z-LGR-7-amido-4-methylcoumarin
0.00139
2-aminobenzoyl -Ser-Leu-Gly-Arg-Lys-Ile-Gln-Ile-Lys(dinitrophenyl)-NH2
-
pH 7.4, 37°C
0.00021
2-aminobenzoyl-Gly-Leu-Gln-Arg-Ala-Leu-Glu-Ile-Lys(dinitrophenyl)-NH2
-
pH 7.4, 37°C
0.38
benzyloxycarbonyl-Gly-Leu-Gln-Arg-4-methylcoumaryl-7-amide
-
pH 7.4, 37°C
0.5
benzyloxycarbonyl-Ser-Leu-Gly-Arg-4-methylcoumaryl-7-amide
-
pH 7.4, 37°C
0.313
C1-inhibitor P4-P1 fragment
-
pH 7.4, 37°C
-
0.0388
C1-inhibitor P4-P4' fragment
-
pH 7.4, 37°C
-
5.1 - 5.6
Complement component C2
-
0.5 - 12.89
complement component C2 P4-P1 fragment
-
0.069
complement component C2 P4-P4' fragment
-
pH 7.4, 37°C
-
1.9 - 6.7
Complement component C4
-
0.38
complement component C4 P4-P1 fragment
-
pH 7.4, 37°C
-
0.015
complement component C4 P4-P4' fragment
-
pH 7.4, 37°C
-
0.0000394
GLQRA
-
pH 7.4, 37°C
0.000169
GLQRAAEI
-
pH 7.4, 37°C
0.0000421
GLQRAEEI
-
pH 7.4, 37°C
0.00033
GLQRAFEI
-
pH 7.4, 37°C
0.000683
GLQRAL
-
pH 7.4, 37°C
0.00274
GLQRALAI
-
pH 7.4, 37°C
0.000319
GLQRALE
-
pH 7.4, 37°C
0.000392
GLQRALEA
-
pH 7.4, 37°C
0.0000978
GLQRALEE
-
pH 7.4, 37°C
0.00022
GLQRALEF
-
pH 7.4, 37°C
0.000244
GLQRALEH
-
pH 7.4, 37°C
0.000205
GLQRALEI
-
pH 7.4, 37°C
0.000867
GLQRALEK
-
pH 7.4, 37°C
0.0000978
GLQRALEL
-
pH 7.4, 37°C
0.000171
GLQRALEM
-
pH 7.4, 37°C
0.000807
GLQRALEP
-
pH 7.4, 37°C
0.0000978
GLQRALEQ
-
pH 7.4, 37°C
0.00044
GLQRALET
-
pH 7.4, 37°C
0.00288
GLQRALFI
-
pH 7.4, 37°C
0.00821
GLQRALHI
-
pH 7.4, 37°C
0.000136
GLQRALKI
-
pH 7.4, 37°C
0.00296
GLQRALLI
-
pH 7.4, 37°C
0.00227
GLQRALMI
-
pH 7.4, 37°C
0.00244
GLQRALPI
-
pH 7.4, 37°C
0.00279
GLQRALTI
-
pH 7.4, 37°C
0.000119
GLQRAMEI
-
pH 7.4, 37°C
0.0000189
GLQRAPEI
-
pH 7.4, 37°C
0.000183 - 0.00232
GLQRAQEI
0.000147
GLQRATEI
-
pH 7.4, 37°C
0.0000205
GLQRELEI
-
pH 7.4, 37°C
0.000155
GLQRFLEI
-
pH 7.4, 37°C
0.000415
GLQRHLEI
-
pH 7.4, 37°C
0.0000762
GLQRKLEI
-
pH 7.4, 37°C
0.0000702
GLQRLLEI
-
pH 7.4, 37°C
0.000239
GLQRMLEI
-
pH 7.4, 37°C
0.0000702
GLQRQLEI
-
pH 7.4, 37°C
0.00155
GLQRTLEI
-
pH 7.4, 37°C
5.7
N-benzoyl-Phe-Val-Arg p-nitroanilide
-
-
20.8
N-benzyloxycarbonyl-Lys p-nitrophenyl ester
-
-
0.73
tert-butyloxycarbonyl-Tyr p-nitrophenyl ester
-
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
82 - 110
2-aminobenzoyl-GLQRALEI-Lys(dinitrophenol)-NH2
12 - 1800
Z-AGLQR-7-amido-4-methylcoumarin
8.3 - 79
Z-LGR-7-amido-4-methylcoumarin
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00003
4-[(2'-methylbiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
pH and temperature not specified in the publication
0.000079
N-PEG2000 6-[[(3'-[[5-carbamimidoyl-2-(methylsulfanyl)-2,3-dihydrothiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)carbamoyl]amino]hexanamide
pH and temperature not specified in the publication
0.00006
N-PEG2000 N-(3'-[[5-carbamimidoyl-2-(methylsulfanyl)-2,3-dihydrothiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)dodecanediamide
pH and temperature not specified in the publication
0.000365
N-PEG4000 6-[[(3'-[[5-carbamimidoyl-2-(methylsulfanyl)-2,3-dihydrothiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)carbamoyl]amino]hexanamide
pH and temperature not specified in the publication
0.000095 - 0.00027
N-PEG750 2-[(2-amino-2-oxoethyl)sulfanyl]-N-(3'-[[5-carbamimidoyl-2-(methylsulfanyl)-2,3-dihydrothiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)acetamide
0.00026
N-PEG750 2-[(2-amino-2-oxoethyl)sulfanyl]-N-(3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-2-methylbiphenyl-4-yl)acetamide
pH and temperature not specified in the publication
0.000055
N-PEG750 2-[(2-amino-2-oxoethyl)sulfanyl]-N-(3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)acetamide
pH and temperature not specified in the publication
0.000039
PEG-linked bis(6-[[(4-carbamimidamido-3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)carbamoyl]amino]hexanamide)
pH and temperature not specified in the publication
0.000018
PEG-linked bis(N-[6-amino-5-[(4-carbamimidamido-3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)amino]hept-6-en-1-yl]-6-[[(4-carbamimidamido-3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfanyl]biphenyl-2-yl)carbamoyl]amino]hexanamide)
pH and temperature not specified in the publication
-
0.000029
PEG-linked tetrakis(4-[[4'-carbamimidamido-2'-(carbamoylamino)biphenyl-3-yl]sulfanyl]-5-(methylsulfanyl)thiophene-2-carboximidamide)
pH and temperature not specified in the publication
-
additional information
additional information
-
first order rate inhibition kinetics
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.1
1,10-phenanthroline
Homo sapiens
-
-
0.001
CP-013043
Homo sapiens
-
-
-
0.00007
CP-143217
Homo sapiens
-
-
0.001
CP-349547
Homo sapiens
-
-
0.1
FUT175
Homo sapiens
-
-
0.0103
PHA-00737785
Homo sapiens
-
-
0.1
serine protease inhibitor 1, serine protease inhibitor 2
Homo sapiens
-
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
assay at
7 - 8
-
-
7 - 8.5
-
acetyl-Tyr ethyl ester
7.4
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 8.8
-
pH 6.5: about 60% of maximal activity, pH 8.8: about 75% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
levels of C1s in sera of two patients with C1s deficiency or abnormality in a Japanese family are approximately half that of healthy subjects
Manually annotated by BRENDA team
-
highest expression
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
physiological function
malfunction
-
hereditary angioedema is caused by C1 esterase inhibitor deficiency
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
C1S_HUMAN
688
0
76684
Swiss-Prot
Secretory Pathway (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
200000
gel filtration, wild-type and mutant G630E
30000
sequence analysis, the L chain of C1s derived from the maternal abnormal allele
81000
sequence analysis, proenzyme form of C1s generated by the paternal abnormal allele
90000
sequence analysis, proenzyme form of maternal mutated C1s
113000
-
gel filtration
27000
56000
-
x * 56000, A chain, + x * 27000, B chain, gel filtration under denaturing conditions
62000
-
x * 62000, A chain, + x * 27000, B chain, SDS-PAGE
77410
-
mass spectrometry
78900
-
x * 78900, monomer protein that forms Ca2+-dependent dimers, calculation from amino acid sequence and carbohydrate content
790000
-
-
81000
-
gel filtration
86000
-
1 * 88000 ,immunoblotting, both joint fluid and purified material, 1 * 90000, SDS-PAGE and 1 * 86000, SDS-PAGE
88000
-
1 * 88000 ,immunoblotting, both joint fluid and purified material, 1 * 90000, SDS-PAGE and 1 * 86000, SDS-PAGE
90000
-
1 * 88000 ,immunoblotting, both joint fluid and purified material, 1 * 90000, SDS-PAGE and 1 * 86000, SDS-PAGE
92000
-
nondenaturing PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
recombinant CUB1-EGF-CUB2 region of enzyme C1s, monomers associate to form an X-shaped dimer through lateral association of the CUB1 and EGF-like domains about the crystallographic symmetry axis. The interface features a number of hydrophobic side chains
homodimer
tetramer
in the absence of collagen peptide, C1s crystallizes to form a tetramer, similar to the native C1r-C1s-C1r-C1s complex. The tetramer is a flat ring with an outer diameter of about 120 A
heteropentamer
-
C1q, 2 * C1s, 2 * C1r
monomer
-
1 * 88000 ,immunoblotting, both joint fluid and purified material, 1 * 90000, SDS-PAGE and 1 * 86000, SDS-PAGE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
glycoprotein
-
-
no modification
-
no beta-hydroxy-Asn is found in the recombinant enzyme
proteolytic modification
side-chain modification
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
complex between the CUB1-EGF-CUB2 domains of C1r and C1s, sitting drop vapor diffusion method, in imidazole buffer at pH 8.0 with PEG 8000 as the precipitant
crystal structure analysis, PDB IDs 1NZI
in the absence of collagen peptide, C1s crystallizes to form a tetramer, similar to the native C1r-C1s-C1r-C1s complex. The tetramer is a flat ring with an outer diameter of about 120 A. The structure is assembled from two X-shaped dimers linked via a connecting interface at the center, structure overview
crystal structure of of a catalytic fragment comprising the second complement control protein (CCP2) module and the chymotrypsin-like serine protease domain determined and refined to 1.7 A resolution
-
crystallization of the whole C1 complex formed by C1q and 2 copies of each protease C1r and C1s
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C294R
the mutation is associated with periodontal Ehlers-Danlos syndrome
G630E
missense mutation, like normal C1s, the mutant has the ability to form a complex with rC1r. The activity of the mutant is significantly lower than that of wild-type, being only 60% of the activity of the wild-type rC1s. The mutant has a higher susceptibility to proteolysis than the wild-type, and prolonged proteolysis generates a truncated L chain with little or no protease activity
K628A
the mutant shows lower activity than wild-type enzyme against peptide substrates, cleavage of C4 is reduced by 5fold compared to the wild-type enzyme
K628Q
the mutant shows greater activity than wild-type enzyme against peptide substrates and peptide substrates containing physiological substrate sequences, unaltered activity with 2-aminobenzoyl-GLQRALEI-Lys(dinitrophenol)-NH2 substrate compared to the wild-type enzyme, but cleavage of C4 complement is reduced by 5fold compared to the wild-type enzyme
V316Del
the mutation is associated with periodontal Ehlers-Danlos syndrome
C1s(MASP-2 CCP1/2)
-
chimeric C1s protease containing the MASP-2 complement control protein domain, cleavage efficiency of C4 similar to MASP-2 protease
C1s(MASP-2 SP)
-
chimeric C1s protease containing the MASP-2 serine protease domain, cleavage efficiency similar to wild-type C1s
D275S/P276I/K405V
-
similar to wild-type C1s
D343N
-
complement component C4 cleavage activity below 50% compared to wild-type, complement component C2 cleavage activity similar to wild-type
P341I
-
complement component C4 cleavage activity below 50% compared to wild-type, complement component C2 cleavage activity similar to wild-type
Q340A
-
similar to wild-type
Q340D
-
complement component C4 cleavage activity below 50% compared to wild-type, complement component C2 cleavage activity similar to wild-type
Q340D/D343E
-
complement component C4 cleavage activity below 50% compared to wild-type, complement component C2 cleavage activity similar to wild-type
Q340E
-
activation by complement component C1r is impaired, enhanced glycosylation at N391
Q340E/D343N
-
complement component C4 cleavage activity below 50% compared to wild-type, complement component C2 cleavage activity similar to wild-type
Q340E/N391Q
-
similar to wild-type
Q340K
-
complement component C4 cleavage activity below 50% compared to wild-type, complement component C2 cleavage activity similar to wild-type
Q340K/D343N
-
complement component C4 cleavage activity below 50% compared to wild-type, complement component C2 cleavage activity similar to wild-type
Q340K/P341I
-
complement component C4 cleavage activity below 50% compared to wild-type, complement component C2 cleavage activity similar to wild-type
Q340K/P341I/V342K
-
complement component C4 cleavage activity below 50% compared to wild-type, complement component C2 cleavage activity similar to wild-type
Q340R
-
complement component C4 cleavage activity below 50% compared to wild-type, complement component C2 cleavage activity similar to wild-type
Q340S
-
complement component C4 cleavage activity below 50% compared to wild-type, complement component C2 cleavage activity similar to wild-type
Q340S/P341I
-
complement component C4 cleavage activity below 50% compared to wild-type, complement component C2 cleavage activity similar to wild-type
V342K
-
complement component C4 cleavage activity below 50% compared to wild-type, complement component C2 cleavage activity similar to wild-type
additional information
-
only the fragment bearing the serine protease (SP) and the complement control protein (CCP) module 2 of MASP-2 were expressed and crystallized
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 9.5
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
49
-
10 min, 90% loss of activity
56
-
30 min, 50% loss of activity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
no autolytic cleavage
-
stable at concentrations of 1-2 mg/ml
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
2°C, pH 5.3-7.3, stable over weeks
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
by Ni-NTA affinity chromatography
nickel-Sepharose affinity column chromatography and Superdex 200 gel filtration
recombinant His-tagged enzyme fragment CCP2 and SP by nickel affinity chromatography and dialysis, activation by C1r
recombinant refolded and solubilized wild-type enzyme and K628Q and K628A mutants from Escherichia coli by anion exchange chromatography and gel filtration
by gel filtration and on affinity column
-
C1s and C1sbar
-
commercial preparation
from human plasma
-
one-step affinity chromatography
-
partially purified
-
to homogeneity
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
development and evaluation of a method for expression of recombinant full-length human C-terminally tagged C1q involving stable transfection of HEK 293-F mammalian cells
expressed in Chinese hamster ovary cells
expression of the CUB1-EGF-CUB2 region of enzyme C1s in CHO cells
recombinant expression of N-terminally His6-tagged enzyme fragment comprising the second CCP domain and the serine protease domain, CCP2-SP, amino acids 358-688
recombinant expression of wild-type enzyme and K628Q and K628A mutants in Escherichia coli as insoluble proteins in inclusion bodies
wild-type and mutant expressed in Drosophila S2 cells
expressed in CHO cells
-
expression in a baculovirus/insect cells system
-
expression in Escherichia coli BL-21 DE3 pLysS
-
expression in insect cells
-
expression of a 159 residue N-terminal fragment of C1s in a baculovirus insect cell system
-
the full length cDNA of C1s is placed under the control of the strong polyhedrin promoter of Autographa californica nuclear polyhedrosis virus, expression in Sf9, High5 cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
two patients with C1s deficiency or abnormality in a Japanese family that have distinct compound heterozygous genotypes derived from three distinct C1s gene mutations including a novel missense mutation in exon XII, and which share similar symptoms, but which are different from those of previously reported cases
pharmacology
inhibition of the complement pathway is of great therapeutic interest. The C1 complex is a very attractive target for selective inhibition of the classical complement pathway because it is the only member of the classical pathway that does not participate in the other complement pathways
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Gal, P.; Zavodzky, P.
Structure and function of the serine-protease subcomponents of C1: protein engineering studies
Immunobiology
199
317-326
1998
Homo sapiens
Manually annotated by BRENDA team
Sim, R.B.; Porter, R.R.; Reid, K.B.M.; Gigli, I.
The structure and enzymic activities of the C1r and C1s subcomponents of C1, the first component of human serum complement
Biochem. J.
163
219-227
1977
Homo sapiens
Manually annotated by BRENDA team
Sim, R.; Arlaud, G.J.; Colomb, M.G.
Kinetics of reaction of human C1bar-inhibitor with the human complement system proteases C1rbar and C1sbar
Biochim. Biophys. Acta
612
433-449
1980
Homo sapiens
Manually annotated by BRENDA team
Sim, R.B.
The human complement system serine proteases C1bar and C1sbar and their proenzymes
Methods Enzymol.
80
26-42
1981
Homo sapiens
Manually annotated by BRENDA team
Nilsson, T.; Wiman, B.
Kinetics of the reaction between human C1-esterase inhibitor and C1r or C1s
Eur. J. Biochem.
129
663-667
1983
Homo sapiens
Manually annotated by BRENDA team
Reboul, A.; Bensa, J.C.; Colomb, M.G.
Characteristics of complement subcomponents C1r and C1s synthesized by Hep G2 cells
Biochem. J.
233
559-564
1986
Homo sapiens
Manually annotated by BRENDA team
Thielens, N.M.; Aude, C.A.; Lacroix, M.B.; Gagnon, J.; Arlaud, G.J.
Ca2+ binding properties and Ca2+-dependent interactions of the isolated NH2-terminal alpha fragments of human complement proteases C1rbar and C1sbar
J. Biol. Chem.
265
14469-14475
1990
Homo sapiens
Manually annotated by BRENDA team
Katz, Y.; Guterman, M.; Lahat, E.
Regulation of synthesis of complement proteins in HEp2 cells
Clin. Immunol. Immunopathol.
67
117-123
1993
Homo sapiens
Manually annotated by BRENDA team
Zavodszky, P.; Gal, P.; Cseh, S.; Schumaker, V.N.
Protein engineering studies on C1r and C1s
Behring Inst. Mitt.
93
103-114
1993
Homo sapiens
Manually annotated by BRENDA team
Gulati, P.; Lemercier, C.; Guc, D.; Lappin, D.; Whaley, K.
Regulation of the synthesis of C1 subcomponents and C1-inhibitor
Behring Inst. Mitt.
93
196-203
1993
Homo sapiens
Manually annotated by BRENDA team
Arlaud, G.J.; Thielens, N.M.
Human complement serine proteases C1r and C1s and their proenzymes
Methods Enzymol.
223
61-82
1993
Homo sapiens
Manually annotated by BRENDA team
Kam, C.M.; Oglesby, T.J.; Pangburn, M.K.; Volanakis, J.E.; Powers, J.C.
Substituted isocoumarins as inhibitors of complement serine proteases
J. Immunol.
149
163-168
1992
Homo sapiens
Manually annotated by BRENDA team
Loos, M.; Heinz, H.P.; Clas, F.
C1sbar-esterase
Methods Enzym. Anal. , 3rd Ed. (Bergmeyer, H. U. , ed. )
5
527-536
1984
Homo sapiens
-
Manually annotated by BRENDA team
Morgan, P.H.; Nair, I.G.
Hydrolysis of a synthetic amide substrate by human C1 esterase (C1sbar)
J. Immunol.
119
19-25
1977
Homo sapiens
Manually annotated by BRENDA team
Sumi, H.; Muramatu, M.
Purification and partial characterization of human C1-esterase
Agric. Biol. Chem.
38
605-611
1974
Homo sapiens
-
Manually annotated by BRENDA team
Bing, D.H.
Purification of the first component of human complement and its subunit C1 esterase
Methods Enzymol.
34B
731-746
1974
Homo sapiens
Manually annotated by BRENDA team
Tsai, S.W.; Poon, P.H.; Schumaker, V.N.
Expression and characterization of a 159 amino acid, N-terminal fragment of human complement component C1s
Mol. Immunol.
34
1273-1280
1997
Homo sapiens
Manually annotated by BRENDA team
Skoog, M.T.; Mehdi, S.; Wiseman, J.S.; Bey, P.
The specificity of two proteinases that cleave adjacent to arginine, C1 esterase and acrosin, for peptide p-nitroanilide substrates
Biochim. Biophys. Acta
996
89-94
1989
Homo sapiens
Manually annotated by BRENDA team
O'Brien, G.; Quinsey, N.S.; Whisstock, J.C.; Pike, R.N.
Importance of the prime subsites of the C1s protease of the classical complement pathway for recognition of substrates
Biochemistry
42
14939-14945
2003
Homo sapiens
Manually annotated by BRENDA team
Subasinghe, N.L.; Ali, F.; Illig, C.R.; Jonathan Rudolph, M.; Klein, S.; Khalil, E.; Soll, R.M.; Bone, R.F.; Spurlino, J.C.; DesJarlais, R.L.; Crysler, C.S.; Cummings, M.D.; Morris, P.E., Jr.; Kilpatrick, J.M.; Sudhakara Babu, Y.
A novel series of potent and selective small molecule inhibitors of the complement component C1s
Bioorg. Med. Chem. Lett.
14
3043-3047
2004
Homo sapiens
Manually annotated by BRENDA team
Gaboriaud, C.; Rossi, V.; Bally, I.; Arlaud, G.J.; Fontecilla-Camps, J.C.
Crystal structure of the catalytic domain of human complement C1s: a serine protease with a handle
EMBO J.
19
1755-1765
2000
Homo sapiens
Manually annotated by BRENDA team
Busby, W.H., Jr.; Nam, T.J.; Moralez, A.; Smith, C.; Jennings, M.; Clemmons, D.R.
The complement component C1s is the protease that accounts for cleavage of insulin-like growth factor-binding protein-5 in fibroblast medium
J. Biol. Chem.
275
37638-37644
2000
Homo sapiens
Manually annotated by BRENDA team
Buerke, M.; Schwertz, H.; Seitz, W.; Meyer, J.; Darius, H.
Novel small molecule inhibitor of C1s exerts cardioprotective effects in ischemia-reperfusion injury in rabbits
J. Immunol.
167
5375-5380
2001
Oryctolagus cuniculus, Homo sapiens
Manually annotated by BRENDA team
Harmat, V.; Gal, P.; Kardos, J.; Szilagyi, K.; Ambrus, G.; Vegh, B.; Naray-Szabo, G.; Zavodszky, P.
The structure of MBL-associated serine protease-2 reveals that identical substrate specificities of C1s and MASP-2 are realized through different sets of enzyme-substrate interactions
J. Mol. Biol.
342
1533-1546
2004
Homo sapiens
Manually annotated by BRENDA team
Rossi, V.; Teillet, F.; Thielens, N.M.; Bally, I.; Arlaud, G.J.
Functional characterization of complement proteases C1s/mannan-binding lectin-associated serine protease-2 (MASP-2) chimeras reveals the higher C4 recognition efficacy of the MASP-2 complement control protein modules
J. Biol. Chem.
280
41811-41818
2005
Homo sapiens
Manually annotated by BRENDA team
Kerr, F.K.; OBrien, G.; Quinsey, N.S.; Whisstock, J.C.; Boyd, S.; de la Banda, M.G.; Kaiserman, D.; Matthews, A.Y.; Bird, P.I.; Pike, R.N.
Elucidation of the substrate specificity of the C1s protease of the classical complement pathway
J. Biol. Chem.
280
39510-39514
2005
Homo sapiens
Manually annotated by BRENDA team
Bally, I.; Rossi, V.; Thielens, N.M.; Gaboriaud, C.; Arlaud, G.J.
Functional role of the linker between the complement control protein modules of complement protease C1s
J. Immunol.
175
4536-4542
2005
Homo sapiens
Manually annotated by BRENDA team
Gosalia, D.N.; Salisbury, C.M.; Ellman, J.A.; Diamond, S.L.
High throughput substrate specificity profiling of serine and cysteine proteases using solution-phase fluorogenic peptide microarrays
Mol. Cell. Proteomics
4
626-636
2005
Homo sapiens
Manually annotated by BRENDA team
Gaboriaud, C.; Thielens, N.M.; Gregory, L.A.; Rossi, V.; Fontecilla-Camps, J.C.; Arlaud, G.J.
Structure and activation of the C1 complex of complement: unraveling the puzzle
Trends Immunol.
25
368-373
2004
Homo sapiens
Manually annotated by BRENDA team
Kerr, F.K.; Thomas, A.R.; Wijeyewickrema, L.C.; Whisstock, J.C.; Boyd, S.E.; Kaiserman, D.; Matthews, A.Y.; Bird, P.I.; Thielens, N.M.; Rossi, V.; Pike, R.N.
Elucidation of the substrate specificity of the MASP-2 protease of the lectin complement pathway and identification of the enzyme as a major physiological target of the serpin, C1-inhibitor
Mol. Immunol.
45
670-677
2008
Homo sapiens
Manually annotated by BRENDA team
Arriaga, S.M.; Basiglio, C.L.; Mottino, A.D.; Almara, A.M.
Unconjugated bilirubin inhibits C1 esterase activity
Clin. Biochem.
42
919-921
2009
Homo sapiens
Manually annotated by BRENDA team
Hong, S.B.; Kim, C.W.; Kim, J.H.; Kim, J.S.; Han, S.B.
A case of angioedema due to acquired C1 esterase inhibitor deficiency masquerading as suspected peritonitis: A case report
J. Emerg. Med.
41
e99-e101
2011
Homo sapiens
Manually annotated by BRENDA team
Abe, K.; Endo, Y.; Nakazawa, N.; Kanno, K.; Okubo, M.; Hoshino, T.; Fujita, T.
Unique phenotypes of C1s deficiency and abnormality caused by two compound heterozygosities in a Japanese family
J. Immunol.
182
1681-1688
2009
Homo sapiens (P09871)
Manually annotated by BRENDA team
Busby, W.H.; Yocum, S.A.; Rowland, M.; Kellner, D.; Lazerwith, S.; Sverdrup, F.; Yates, M.; Radabaugh, M.; Clemmons, D.R.
Complement 1s is the serine protease that cleaves IGFBP-5 in human osteoarthritic joint fluid
Osteoarthritis Cartilage
17
547-555
2009
Homo sapiens
Manually annotated by BRENDA team
Dagen, C.; Craig, T.J.
Treatment of hereditary angioedema: items that need to be addressed in practice parameters
Allergy Asthma Clin. Immunol.
6
11
2010
Homo sapiens
Manually annotated by BRENDA team
Craig, T.J.; Levy, R.J.; Wasserman, R.L.; Bewtra, A.K.; Hurewitz, D.; Obtulowicz, K.; Reshef, A.; Ritchie, B.; Moldovan, D.; Shirov, T.; Grivcheva-Panovska, V.; Kiessling, P.C.; Keinecke, H.O.; Bernstein, J.A.
Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks
J. Allergy Clin. Immunol.
124
801-808
2009
Homo sapiens
Manually annotated by BRENDA team
Grosskinsky, S.; Schott, M.; Brenner, C.; Cutler, S.J.; Simon, M.M.; Wallich, R.
Human complement regulators C4b-binding protein and C1 esterase inhibitor interact with a novel outer surface protein of Borrelia recurrentis
PLoS Negl. Trop. Dis.
4
e698
2010
Homo sapiens
Manually annotated by BRENDA team
Rajabi, M.; Struble, E.; Zhou, Z.; Karnaukhova, E.
Potentiation of C1-esterase inhibitor by heparin and interactions with C1s protease as assessed by surface plasmon resonance
Biochim. Biophys. Acta
1820
56-63
2011
Homo sapiens, Homo sapiens (P09871)
Manually annotated by BRENDA team
Brier, S.; Pflieger, D.; Le Mignon, M.; Bally, I.; Gaboriaud, C.; Arlaud, G.J.; Daniel, R.
Mapping surface accessibility of the C1r/C1s tetramer by chemical modification and mass spectrometry provides new insights into assembly of the human C1 complex
J. Biol. Chem.
285
32251-32263
2010
Homo sapiens
Manually annotated by BRENDA team
Subasinghe, N.L.; Khalil, E.; Travins, J.M.; Ali, F.; Ballentine, S.K.; Hufnagel, H.R.; Pan, W.; Leonard, K.; Bone, R.F.; Soll, R.M.; Crysler, C.S.; Ninan, N.; Kirkpatrick, J.; Kolpak, M.X.; Diloreto, K.A.; Eisennagel, S.H.; Huebert, N.D.; Molloy, C.J.; Tomczuk, B.E.; Gaul, M.D.
Design and synthesis of polyethylene glycol-modified biphenylsulfonyl-thiophene-carboxamidine inhibitors of the complement component C1s
Bioorg. Med. Chem. Lett.
22
5303-5307
2012
Homo sapiens (P09871)
Manually annotated by BRENDA team
Shi, J.; Rose, E.L.; Singh, A.; Hussain, S.; Stagliano, N.E.; Parry, G.C.; Panicker, S.
TNT003, an inhibitor of the serine protease C1s, prevents complement activation induced by cold agglutinins
Blood
123
4015-4022
2014
Homo sapiens (P09871), Homo sapiens
Manually annotated by BRENDA team
Wijeyewickrema, L.C.; Duncan, R.C.; Pike, R.N.
The role of the lys628 (192) residue of the complement protease, C1s, in interacting with peptide and protein substrates
Front. Immunol.
5
444
2014
Homo sapiens (P09871)
Manually annotated by BRENDA team
Carroll, S.; Georgiou, G.
Antibody-mediates inhibition of human C1s and the classical complement pathway
Immunobiology
218
1041-1048
2013
Homo sapiens (P09871), Homo sapiens
Manually annotated by BRENDA team
Wijeyewickrema, L.C.; Yongqing, T.; Tran, T.P.; Thompson, P.E.; Viljoen, J.E.; Coetzer, T.H.; Duncan, R.C.; Kass, I.; Buckle, A.M.; Pike, R.N.
Molecular determinants of the substrate specificity of the complement-initiating protease, C1r
J. Biol. Chem.
288
15571-15580
2013
Homo sapiens (P09871)
Manually annotated by BRENDA team
Venkatraman Girija, U.; Gingras, A.R.; Marshall, J.E.; Panchal, R.; Sheikh, M.A.; Gal, P.; Schwaeble, W.J.; Mitchell, D.A.; Moody, P.C.; Wallis, R.
Structural basis of the C1q/C1s interaction and its central role in assembly of the C1 complex of complement activation
Proc. Natl. Acad. Sci. USA
110
13916-13920
2013
Homo sapiens (P09871)
Manually annotated by BRENDA team
Bally, I.; Ancelet, S.; Moriscot, C.; Gonnet, F.; Mantovani, A.; Daniel, R.; Schoehn, G.; Arlaud, G.J.; Thielens, N.M.
Expression of recombinant human complement C1q allows identification of the C1r/C1s-binding sites
Proc. Natl. Acad. Sci. USA
110
8650-8655
2013
Homo sapiens (P09871)
Manually annotated by BRENDA team
Beveridge, A.J.; Wallis, R.; Samani, N.J.
A molecular dynamics study of C1r and C1s dimers: implications for the structure of the C1 complex
Proteins
80
1987-1997
2012
Homo sapiens (P09871)
Manually annotated by BRENDA team
Skoog, S.M.; Wiseman, J.S.; Bey, P.
The specificity of two proteinases that cleave adjacent to argirnine, Cl esterase and acrosin, for pepfide p-nitroanilide substrates
Biochim. Biophys. Acta
996
89.94
1989
Homo sapiens (P09871), Homo sapiens
Manually annotated by BRENDA team
Kapferer-Seebacher, I.; Pepin, M.; Werner, R.; Aitman, T.J.; Nordgren, A.; Stoiber, H.; Thielens, N.; Gaboriaud, C.; Amberger, A.; Schossig, A.; Gruber, R.; Giunta, C.; Bamshad, M.; Bjoerck, E.; Chen, C.; Chitayat, D.; Dorschner, M.; Schmitt-Egenolf, M.; Hale, C.J.; Hanna, D.; Hennies, H.C.; Heiss-Kisielewsky, I.
Periodontal Ehlers-Danlos syndrome is caused by mutations in C1R and C1S, which encode subcomponents C1r and C1s of complement
Am. J. Hum. Genet.
99
1005-1014
2016
Homo sapiens (P09871)
Manually annotated by BRENDA team
Li, S.; Yu, B.; Byrne, G.; Wright, M.; ORourke, S.; Mesa, K.; Berman, P.W.
Identification and CRISPR/Cas9 knockout of the endogenous C1s protease in CHO cells eliminates aberrant proteolysis of recombinantly expressed proteins
Biotechnol. Bioeng.
116
2130-2145
2019
Homo sapiens
Manually annotated by BRENDA team
Jaeger, U.; DSa, S.; Schoergenhofer, C.; Bartko, J.; Derhaschnig, U.; Sillaber, C.; Jilma-Stohlawetz, P.; Fillitz, M.; Schenk, T.; Patou, G.; Panicker, S.; Parry, G.C.; Gilbert, J.C.; Jilma, B.
Inhibition of complement C1s improves severe hemolytic anemia in cold agglutinin disease a first-in-human trial
Blood
133
893-901
2019
Homo sapiens
Manually annotated by BRENDA team
Almitairi, J.O.M.; Venkatraman Girija, U.; Furze, C.M.; Simpson-Gray, X.; Badakshi, F.; Marshall, J.E.; Schwaeble, W.J.; Mitchell, D.A.; Moody, P.C.E.; Wallis, R.
Structure of the C1r-C1s interaction of the C1 complex of complement activation
Proc. Natl. Acad. Sci. USA
115
768-773
2018
Homo sapiens (P09871)
Manually annotated by BRENDA team