Information on EC 3.4.21.42 - complement subcomponent C1s

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.21.42
-
RECOMMENDED NAME
GeneOntology No.
complement subcomponent C1s
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
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
show the reaction diagram
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
80295-70-1
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
hereditary angioedema is caused by C1 esterase inhibitor deficiency
metabolism
physiological function
additional information
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
-
-
?
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
-
-
?
acetyl-Gly-Lys-naphthyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-Lys-(gamma-benzyloxycarbonyl)-Gly-Arg + H2O
?
show the reaction diagram
-
-
-
-
?
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
-
-
-
?
Boc-Leu-Ser-Thr-Arg-7-amido-4-methylcoumarin + H2O
?
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
-
-
-
?
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
-
-
-
-
?
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
-
-
-
?
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 + ALMI
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
-
-
-
?
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
-
-
-
-
?
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
-
-
-
-
-
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
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
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
-
-
-
-
?
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
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,10-phenanthroline
-
-
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
-
-
3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-carboxylic acid
-
-
3,4-dichloroisocoumarin
-
-
4-(biphenyl-3-ylsulfonyl)-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
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
-
-
4-[(2'-chlorobiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
4-[(2'-ethenylbiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
4-[(2'-hydroxybiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
4-[(2'-methoxybiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
4-[(2'-methylbiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
4-[(2-amino-6-methylphenyl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
4-[(3'-hydroxybiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
4-[(3'-methoxybiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
4-[(3'-methylbiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
4-[(3-bromophenyl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
4-[(4'-hydroxybiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
4-[(4'-methoxybiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
4-[(4'-methylbiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
4-[[2'-(hydroxymethyl)-6'-methylbiphenyl-3-yl]sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
4-[[2'-(hydroxymethyl)biphenyl-3-yl]sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
4-[[3-(3-methylpyridin-2-yl)phenyl]sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
5-(methylsulfanyl)-4-[[2'-methyl-6'-([[2-(2H-tetrazol-5-yl)ethyl]carbamoyl]amino)biphenyl-3-yl]sulfonyl]thiophene-2-carboximidamide
-
-
6-[(3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)amino]-6-oxohexanoic acid
-
-
6-[[(3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)carbamoyl]amino]hexanoic acid
-
-
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
-
C1-inhibitor
-
C1bar inhibitor
-
C1s-INH-248
-
CP-013043
-
-
-
CP-143217
-
-
CP-349547
-
-
FUT175
-
potent C1s inhibitor
Guanidines
-
-
-
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
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N-(3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)-2-(methylsulfonyl)acetamide
-
-
N-(3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)-4-(methylsulfonyl)butanamide
-
-
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
-
PEG size 10 kDa; PEG size 20 kDa
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
p-nitrophenyl-p'-guanidinobenzoate
-
-
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
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PHA-00737785
-
-
PMSF
-
-
serine protease inhibitor 1
-
-
-
serine protease inhibitor 2
-
-
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tert-butyl [[4-[(3-bromophenyl)sulfonyl]-5-(methylsulfanyl)thiophen-2-yl](imino)methyl]carbamate
-
binding mode in the active site, structure, overview
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
-
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
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
-
-
0.0654 - 0.245
Z-AGLQR-7-amido-4-methylcoumarin
0.0762 - 0.212
Z-LGR-7-amido-4-methylcoumarin
additional information
2-[5-Amino-2-(4-fluoro-phenyl)-6-oxo-6H-pyrimidin-1-yl]-N-(1-benzyl-2-oxo-2-thiazol-2-yl-ethyl)-acetamide
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00139
2-aminobenzoyl -Ser-Leu-Gly-Arg-Lys-Ile-Gln-Ile-Lys(dinitrophenyl)-NH2
Homo sapiens
-
pH 7.4, 37°C
1.14 - 1.3
2-aminobenzoyl-GLQRALEI-Lys(dinitrophenol)-NH2
0.00021
2-aminobenzoyl-Gly-Leu-Gln-Arg-Ala-Leu-Glu-Ile-Lys(dinitrophenyl)-NH2
Homo sapiens
-
pH 7.4, 37°C
0.38
benzyloxycarbonyl-Gly-Leu-Gln-Arg-4-methylcoumaryl-7-amide
Homo sapiens
-
pH 7.4, 37°C
0.5
benzyloxycarbonyl-Ser-Leu-Gly-Arg-4-methylcoumaryl-7-amide
Homo sapiens
-
pH 7.4, 37°C
0.313
C1-inhibitor P4-P1 fragment
Homo sapiens
-
pH 7.4, 37°C
-
0.0388
C1-inhibitor P4-P4' fragment
Homo sapiens
-
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
Homo sapiens
-
pH 7.4, 37°C
-
1.9 - 6.7
Complement component C4
-
0.38
complement component C4 P4-P1 fragment
Homo sapiens
-
pH 7.4, 37°C
-
0.015
complement component C4 P4-P4' fragment
Homo sapiens
-
pH 7.4, 37°C
-
0.0000394
GLQRA
Homo sapiens
-
pH 7.4, 37°C
0.000169
GLQRAAEI
Homo sapiens
-
pH 7.4, 37°C
0.0000421
GLQRAEEI
Homo sapiens
-
pH 7.4, 37°C
0.00033
GLQRAFEI
Homo sapiens
-
pH 7.4, 37°C
0.000683
GLQRAL
Homo sapiens
-
pH 7.4, 37°C
0.00274
GLQRALAI
Homo sapiens
-
pH 7.4, 37°C
0.000319
GLQRALE
Homo sapiens
-
pH 7.4, 37°C
0.000392
GLQRALEA
Homo sapiens
-
pH 7.4, 37°C
0.0000978
GLQRALEE
Homo sapiens
-
pH 7.4, 37°C
0.00022
GLQRALEF
Homo sapiens
-
pH 7.4, 37°C
0.000244
GLQRALEH
Homo sapiens
-
pH 7.4, 37°C
0.000205
GLQRALEI
Homo sapiens
-
pH 7.4, 37°C
0.000867
GLQRALEK
Homo sapiens
-
pH 7.4, 37°C
0.0000978
GLQRALEL
Homo sapiens
-
pH 7.4, 37°C
0.000171
GLQRALEM
Homo sapiens
-
pH 7.4, 37°C
0.000807
GLQRALEP
Homo sapiens
-
pH 7.4, 37°C
0.0000978
GLQRALEQ
Homo sapiens
-
pH 7.4, 37°C
0.00044
GLQRALET
Homo sapiens
-
pH 7.4, 37°C
0.00288
GLQRALFI
Homo sapiens
-
pH 7.4, 37°C
0.00821
GLQRALHI
Homo sapiens
-
pH 7.4, 37°C
0.000136
GLQRALKI
Homo sapiens
-
pH 7.4, 37°C
0.00296
GLQRALLI
Homo sapiens
-
pH 7.4, 37°C
0.00227
GLQRALMI
Homo sapiens
-
pH 7.4, 37°C
0.00244
GLQRALPI
Homo sapiens
-
pH 7.4, 37°C
0.00279
GLQRALTI
Homo sapiens
-
pH 7.4, 37°C
0.000119
GLQRAMEI
Homo sapiens
-
pH 7.4, 37°C
0.0000189
GLQRAPEI
Homo sapiens
-
pH 7.4, 37°C
0.000183 - 0.00232
GLQRAQEI
0.000147
GLQRATEI
Homo sapiens
-
pH 7.4, 37°C
0.0000205
GLQRELEI
Homo sapiens
-
pH 7.4, 37°C
0.000155
GLQRFLEI
Homo sapiens
-
pH 7.4, 37°C
0.000415
GLQRHLEI
Homo sapiens
-
pH 7.4, 37°C
0.0000762
GLQRKLEI
Homo sapiens
-
pH 7.4, 37°C
0.0000702
GLQRLLEI
Homo sapiens
-
pH 7.4, 37°C
0.000239
GLQRMLEI
Homo sapiens
-
pH 7.4, 37°C
0.0000702
GLQRQLEI
Homo sapiens
-
pH 7.4, 37°C
0.00155
GLQRTLEI
Homo sapiens
-
pH 7.4, 37°C
5.7
N-benzoyl-Phe-Val-Arg p-nitroanilide
Homo sapiens
-
-
20.8
N-benzyloxycarbonyl-Lys p-nitrophenyl ester
Homo sapiens
-
-
0.73
tert-butyloxycarbonyl-Tyr p-nitrophenyl ester
Homo sapiens
-
-
-
1.3 - 116.5
Z-AGLQR-7-amido-4-methylcoumarin
1.77 - 6
Z-LGR-7-amido-4-methylcoumarin
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
82 - 110
2-aminobenzoyl-GLQRALEI-Lys(dinitrophenol)-NH2
202407
12 - 1800
Z-AGLQR-7-amido-4-methylcoumarin
202406
8.3 - 79
Z-LGR-7-amido-4-methylcoumarin
202405
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00015
3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-carboxylic acid
-
-
0.00026
4-(biphenyl-3-ylsulfonyl)-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
0.00004
4-[(2'-chlorobiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
0.00014
4-[(2'-ethenylbiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
0.00046
4-[(2'-hydroxybiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
0.00061
4-[(2'-methoxybiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
0.00003
4-[(2'-methylbiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
0.00002
4-[(2-amino-6-methylphenyl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
0.00015
4-[(3'-hydroxybiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
0.00049
4-[(3'-methoxybiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
0.00185
4-[(3'-methylbiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
0.00036
4-[(3-bromophenyl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
0.00019
4-[(4'-hydroxybiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
0.00035
4-[(4'-methoxybiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
0.00025
4-[(4'-methylbiphenyl-3-yl)sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
0.00005
4-[[2'-(hydroxymethyl)-6'-methylbiphenyl-3-yl]sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
0.00012
4-[[2'-(hydroxymethyl)biphenyl-3-yl]sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
0.00004
4-[[3-(3-methylpyridin-2-yl)phenyl]sulfonyl]-5-(methylsulfanyl)thiophene-2-carboximidamide
-
-
0.000064
5-(methylsulfanyl)-4-[[2'-methyl-6'-([[2-(2H-tetrazol-5-yl)ethyl]carbamoyl]amino)biphenyl-3-yl]sulfonyl]thiophene-2-carboximidamide
-
-
0.000042
6-[(3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)amino]-6-oxohexanoic acid
-
-
0.000022
6-[[(3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)carbamoyl]amino]hexanoic acid
-
-
0.000012
N-(3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)-2-(methylsulfonyl)acetamide
-
-
0.000014
N-(3'-[[5-carbamimidoyl-2-(methylsulfanyl)thiophen-3-yl]sulfonyl]-6-methylbiphenyl-2-yl)-4-(methylsulfonyl)butanamide
-
-
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 - 8
-
-
7 - 8.5
-
acetyl-Tyr ethyl ester
7.5
-
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
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30000
sequence analysis, the L chain of C1s derived from the maternal abnormal allele
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
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
92000
-
nondenaturing PAGE
113000
-
gel filtration
200000
gel filtration, wild-type and mutant G630E
790000
-
-
SUBUNITS
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
heteropentamer
-
C1q, 2 * C1s, 2 * C1r
homodimer
-
monomer
-
1 * 88000 ,immunoblotting, both joint fluid and purified material, 1 * 90000, SDS-PAGE and 1 * 86000, SDS-PAGE
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
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
-
-
no modification
-
no beta-hydroxy-Asn is found in the recombinant enzyme
proteolytic modification
side-chain modification
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structure analysis, PDB IDs 1NZI
-
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
-
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
-
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 gel filtration and on affinity column
-
by Ni-NTA affinity chromatography
C1s and C1sbar
-
commercial preparation
-
from human plasma
-
one-step affinity chromatography
-
partially purified
-
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
-
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
-
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
-
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
-
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
-
wild-type and mutant expressed in Drosophila S2 cells
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
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
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
R423H
-
loss of activity
S617T
-
loss of activity
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
-
further probing for cooperativity may be of great value in the development of a peptide inhibitor for the C1s protease in the treatment of inflammatory disease
medicine
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