Information on EC 3.4.21.45 - complement factor I

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
3.4.21.45
-
RECOMMENDED NAME
GeneOntology No.
complement factor I
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
Inactivates complement subcomponents C3b, iC3b and C4b by proteolytic cleavage
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
endopeptidase
-
CAS REGISTRY NUMBER
COMMENTARY hide
80295-66-5
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
single-copied gene in the catfish genome
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
UniProt
Manually annotated by BRENDA team
sand bass
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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
benzoyl-Arg-4-methylcoumaryl-7-amide + H2O
benzoyl-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
low activity
-
?
benzyloxycarbonyl-Gly-Gly-Arg-4-methylcoumaryl-7-amide + H2O
benzyloxycarbonyl-Gly-Gly-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
low activity
-
?
benzyloxycarbonyl-Gly-Pro-Arg-4-methylcoumaryl-7-amide + H2O
benzyloxycarbonyl-Gly-Pro-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-Leu-Leu-Arg-4-methylcoumaryl-7-amide + H2O
benzyloxycarbonyl-Leu-Leu-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
benzyloxycarbonyl-Phe-Arg-4-methylcoumaryl-7-amide + H2O
benzyloxycarbonyl-Phe-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
low activity
-
?
Boc-Asp(benzyl)-Pro-Arg-4-methylcoumarin 7-amide + H2O
?
show the reaction diagram
-
-
-
-
?
complement component C3 + H2O
?
show the reaction diagram
structural but not functional roles for the three N-linked oligosaccharide chains indicated, N-linked glycan pool composition of the heavy and light chains indicated
-
-
?
complement component C3(NH3) + H2O
?
show the reaction diagram
-
cleaved by SP domain-form
-
-
-
complement component C3b + H2O
?
show the reaction diagram
complement component C3b + H2O
complement component C3c + ?
show the reaction diagram
complement component C3b + H2O
complement component iC3b
show the reaction diagram
-
-
a major opsonin
-
?
complement component C3b + H2O
complement component iC3b + ?
show the reaction diagram
complement component C3b + H2O
inactivated C3b + ?
show the reaction diagram
complement component C3bi + H2O
?
show the reaction diagram
-
the breakdown of human erythrocyte-bound C3bi molecules in serum or plasma is mediated only by factor I
-
-
-
complement component C3bi + H2O
complement component C3c + ?
show the reaction diagram
-
complement component C3bi bound to human erythrocytes is rapidly cleaved, unlike complement component C3bi bound to other species
-
?
complement component C4b + H2O
?
show the reaction diagram
complement component C4b + H2O
complement component C4c + C4d
show the reaction diagram
complement factor C3b + H2O
?
show the reaction diagram
-
-
-
-
?
complement factor C4b + H2O
?
show the reaction diagram
-
-
-
-
?
FGR-7-amido-4-methylcoumarin + H2O
FGR + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
methylsulfonyl-D-Phe-Gly-Arg-4-methylcoumaryl-7-amide + H2O
methylsulfonyl-D-Phe-Gly-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
N-alpha-tert-butyloxycarbonyl-Val-Leu-Lys-4-methylcoumaryl-7-amide + H2O
N-alpha-tert-butyloxycarbonyl-Val-Pro-Lys + 7-amino-4-methylcoumarin
show the reaction diagram
-
low activity
-
?
N-alpha-tert-butyloxycarbonyl-Val-Pro-Arg-4-methylcoumaryl-7-amide + H2O
N-alpha-tert-butyloxycarbonyl-Val-Pro-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
Phe-Gly-Arg-4-methylcoumaryl-7-amide + H2O
Phe-Gly-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
Pro-Phe-Arg-4-methylcoumaryl-7-amide + H2O
Pro-Phe-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
low activity
-
?
tert-butyloxycarbonyl-Asp(benzyl ester)-Pro-Arg-4-methylcoumaryl-7-amide + H2O
tert-butyloxycarbonyl-Asp(benzyl ester)-Pro-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
tert-butyloxycarbonyl-Ile-Glu-Gly-Arg-4-methylcoumaryl-7-amide + H2O
tert-butyloxycarbonyl-Ile-Glu-Gly-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
low activity
-
?
tert-butyloxycarbonyl-Phe-Ser-Arg-4-methylcoumaryl-7-amide + H2O
tert-butyloxycarbonyl-Phe-Ser-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
low activity
-
?
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 component C3(NH3) + H2O
?
show the reaction diagram
-
cleaved by SP domain-form
-
-
-
complement component C3b + H2O
?
show the reaction diagram
complement component C3b + H2O
complement component C3c + ?
show the reaction diagram
complement component C3b + H2O
complement component iC3b
show the reaction diagram
-
-
a major opsonin
-
?
complement component C3b + H2O
complement component iC3b + ?
show the reaction diagram
-
the complement C3 fragments C3b and iC3b appear on the surface of several virulent Staphylococcus aureus strains of capsule polysaccharide type 5 and 8. Factor I mediates the cleavage of C3b to iC3b on the surface of Staphylococcus aureus and appears to be able to function without the serum cofactor, factor H
-
?
complement component C3bi + H2O
?
show the reaction diagram
-
the breakdown of human erythrocyte-bound C3bi molecules in serum or plasma is mediated only by factor I
-
-
-
complement component C4b + H2O
?
show the reaction diagram
complement component C4b + H2O
complement component C4c + C4d
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
Staphylococcus aureus expressing clumping factor A (ClfA) (P336A Y338S) is more susceptible to complement-mediated phagocytosis than a ClfA-null mutant or the wild type. Unlike clumping factor A, the mutant ClfA(P336A Y338S) does not enhance factor I cleavage of C3b to iC3b and inhibits the cofactor function of factor H. Fibrinogen enhances factor I binding to clumping factor A and the Staphylococcus aureus surface
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
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10 mM, strong
4-(2-aminoethyl)benzenesulfonyl fluoride
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0.25 mM, inhibits SP domain form and fI
amyloid beta
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antipain
Aprotinin
benzamidine
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20 mM, 82% inhibition of amidolytic activity
benzenesulfonyl fluorides
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inhibits amidolytic activity
benzyloxycarbonyl-D-Phe-Pro-methoxypropylboroglycinepinanediol ester
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0.05 mM, 82% inhibition; inhibits amidolytic activity
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Cr2+
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inhibition of proteolytic and amidolytic activity, 54% inhibition of amidolytic activity at 1 mM, 43% inhibition of proteolytic activity at 0.1 mM
Cu2+
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23% inhibition of amidolytic activity at 1 mM
diisopropylfluorophosphate
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-
dithiothreitol
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1 mM, strong
epsilon-aminocaproic acid
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20 mM, 10% inhibition of amidolytic activity
factor H
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inhibits SP domain form
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Fe3+
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inhibition of proteolytic and amidolytic activity, 59% inhibition of amidolytic activity at 1 mM, 23% inhibition of proteolytic activity at 0.1 mM
Hg2+
-
26% inhibition of amidolytic activity at 1 mM
Hirudin
-
-
-
K-76COOH
leupeptin
Lima bean trypsin inhibitor
-
0.05 mM, 20% inhibition of amidolytic activity
-
NEM
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1 mM, partial inhibition
Pefabloc TH
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0.25 mM, 58% inhibition of amidolytic activity
Pefabloc-SC
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0.00025 mM, complete inhibition of amidolytic activity
Pefabloc-Xa
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0.00025 mM, 93% inhibition of amidolytic activity
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PMSF
-
1 mM, 42% inhibition of amidolytic activity
Soybean trypsin inhibitor
-
0.05 mM, 37% inhibition of amidolytic activity
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suramin
Zn2+
-
0.1 mM, 59% inhibition of proteolytic activity
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
beta1H
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C3b receptor
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obligate cofactor for factor I-mediated cleavage of cell bound C3bi
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C4-binding protein
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C4b binding protein
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C4BP, required for activity, dependent on
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C4bC3bINACo
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complement component CR1
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soluble, required for activity, dependent on
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factor H
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JM4C8-Ag
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.128
methylsulfonyl-D-Phe-Gly-Arg-4-methylcoumaryl-7-amide
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pH 8.3, 37C
0.027
N-alpha-tert-butyloxycarbonyl-Val-Pro-Arg-4-methylcoumaryl-7-amide
-
pH 8.3, 37C
0.0146
tert-butyloxycarbonyl-Asp(benzyl ester)-Pro-Arg-4-methylcoumaryl-7-amide
-
pH 8.3, 37C
0.041 - 0.203
tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.25
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assay at
8.3
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reaction with Phe-Gly-Arg-4-methylcoumarin-7-amide
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 10
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pH 7.0: about 45% of maximal activity, pH 10.0: about 45% of maximal activity, reaction with Phe-Gly-Arg-4-methylcoumaryl-7-amide
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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no mRNA of complement factor I detected in carcinoid cells H720, H727
Manually annotated by BRENDA team
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RPE-Bruch's membrane-choriocapillaris complex from eyes of 12-month-old neprilysin gene-disrupted mice and age-matched wild-type mice
Manually annotated by BRENDA team
expression shown by RT-PCR
Manually annotated by BRENDA team
expression shown by RT-PCR
Manually annotated by BRENDA team
-
transfected with mutant and wild-type forms of complement factor I
Manually annotated by BRENDA team
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only isolated hepatocytes but neither Kupffer cells, hepatic stellate cells or sinusoidal endothelial cells express FI-specific mRNA
Manually annotated by BRENDA team
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incubation of foreskin with thermolysin followed by trypsinization
Manually annotated by BRENDA team
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LCC, no mRNA expression detected in LCC H661
Manually annotated by BRENDA team
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AC, mRNA of complement factor I detected in H2087 and H358 but not in H1264 and A549
Manually annotated by BRENDA team
-
SCC, squamous cell carcinoma, mRNA of complement factor I detected in H226 but not in H157, H1385
Manually annotated by BRENDA team
expression shown by RT-PCR
Manually annotated by BRENDA team
expression shown by RT-PCR
Manually annotated by BRENDA team
-
SCLC, no mRNA of complement factor I detected in H69, H82, H187, H209, H345, N417, H510
Manually annotated by BRENDA team
expression shown by RT-PCR
Manually annotated by BRENDA team
expression shown by RT-PCR
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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upon EndoH digestion, a large fraction of wild-type complement factor I is EndoH sensitive and displays faster mobility upon electrophoresis representing protein in endoplasmic reticulum still undergoing processing, but significant amount of wild-type complement factor I is resistant to EndoH indicates transport to late secretory compartments and beyond
Manually annotated by BRENDA team
-
upon EndoH digestion, a large fraction of wild-type complement factor I is EndoH sensitive and displays faster mobility upon electrophoresis representing protein in endoplasmic reticulum still undergoing processing, but significant amount of wild-type complement factor I is resistant to EndoH indicates transport to late secretory compartments and beyond
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Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
892
-
Man3GlcNAc2 core, deduced molecular weight of N-linked glycan structure
1622
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A2G2, deduced molecular weight of N-linked glycan structure
1824
-
A3G2, deduced molecular weight of N-linked glycan structure
1912
-
A2G2S1, deduced molecular weight of N-linked glycan structure
2115
-
A3G2S1, deduced molecular weight of N-linked glycan structure
2202
-
A2G2S2, deduced molecular weight of N-linked glycan structure
2277
-
A3G3S1, deduced molecular weight of N-linked glycan structure
2405
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A3G2S2, deduced molecular weight of N-linked glycan structure
2567
-
A3G3S2, deduced molecular weight of N-linked glycan structure
3569
-
approximate reduction of molecular weight for the heavy chain after partial deglycosylation of native protein with ABS, BTG and GuH exoglycosidases
5632
-
approximate reduction of molecular weight for the light chain after partial deglycosylation of native protein with ABS, BTG and GuH exoglycosidases
9201
-
approximate reduction of molecular weight for total molecule of factor I after partial deglycosylation of native protein with ABS, BTG and GuH exoglycosidases
27000
-
1 * 27000 + 1 * 37500, calculation from nucleotide sequence
27590
-
calculated for non-glycosylated light chain, estimated basing upon results of the N-linked glycan analysis
28500
-
1 * 28500 + 1 * 38000, calculation from nucleotide sequence
30270
-
estimated for light chain of a partially deglycosylated factor I bearing a single N-linked Man3GlcNAc2 core structure at each glycosylation site
35290
-
calculated for non-glycosylated heavy chain, estimated basing upon results of the N-linked glycan analysis
35900
-
native light chain, estimated basing upon results from the N-linked glycan analysis
37000
-
light chain of
37500
-
1 * 27000 + 1 * 37500, calculation from nucleotide sequence
37960
-
estimated for heavy chain of a partially deglycosylated factor I bearing a single N-linked Man3GlcNAc2 core structure at each glycosylation site
41530
-
native heavy chain, estimated basing upon results from the N-linked glycan analysis
58000
-
SDS-PAGE
62880
-
total calculated molecular weight for non-glycosylated factor I, estimated basing upon results of the N-linked glycan analysis
66000
-
nonglycosylated proenzyme
68230
-
estimated for total protein bearing a single N-linked Man3GlcNAc2 core structure at each glycosylation site
75000
-
x * 75000, SDS-PAGE
77430
-
deduced for total protein of the native factor I basing upon results from the N-linked glycan analysis
155000
-
gel filtration
additional information
-
mutant protein reveals a slightly different migration pattern during electrophoresis under reducing conditions, due to proximity of the mutation to a cysteine residue
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 75000, SDS-PAGE
heterodimer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
proteolytic modification
CFI mRNA is translated in both a heavy and light chain which is further cleaved at a tetrapeptide processing site
side-chain modification
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
to 2.7 A resolution. The shape of factor I is bilobal, with the heavy and light chains making up the two halves of a brick. The arrangement of the domains in the larger heavy-chain lobe forms a ring structure, with the N-terminal FIMAC domain contacting the C-terminal LDLRA domains. This contact is linked covalently by a disulfide bridge between Cys15 and Cys237. Mapping of disease-associated gene polymorphisms and mutations known to alter cofactor-assisted C3b/C4b cleavage by factor I onto the factor I structure implies allosteric regulation of light-chain activity by contact of the heavy chain. Modeling of the ternary complex of factor I, factor H, and C3b
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2.2
-
stable
95489
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
56
-
30 min, stable
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
stable to 0.15 M hydrazine or 2 M guanidine-HCl
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4C, neutral pH, stable for several weeks
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
by size-exclusion chromatography
-
extracellular enzyme from serum
-
gel filtration
gel filtration, recombinant protein
-
gel filtration, SDS-PAGE
-
generation of intact form of SP domain, purifiaction by affinity chromatography on MRC-OX21-Sepharose
-
on Ni-NTA resin
-
recombinant and native proteins, gel filtration, SDS-PAGE
-
using Ni-NTA chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloned in Escherichia coli
cloned into the eukaryotic expression vector pcDNA3 with addition of an N-terminal His-tag and transiently expressed in human embryonic kidney 293 cells; expressed as an N-terminal His-tagged fusion protein in human embryonic kidney cells
-
expressed in Escherichia coli, generation of mice strains deficient of complement factor I
expressed in Escherichia coli, mutant and unmodified proteins
-
expressed in Escherichia coli; expressed in Escherichia coli; expressed in Escherichia coli; expressed in Escherichia coli
expression of His6-tagged wild-type and mutant enzymes in HEK-293 cells
-
HEK-293 cells transiently transfected with wild-type CFI or recombinant mutant constructs
-
serine protease region of factor I flanked by the Xho I site and cloned into vector pCXN2L/FLAG-PI. Plasmid transformed into Escherichia coli C600 and amplified. Expression in CHO cells
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A222G
-
secretion of mutant protein significantly lower compared to wild-type when expressed in human embryonic kidney cells. Mutant cleaves the alpha'-chains of complement factor C4b and C3b as efficiently as wild-type in solution. Compared to wild-type mutant A22G shows impaired cleavage of complement factor C3b on the surface of sheep erythrocytes. Mutant cleaves C3b alpha'chain on the surface of endothelial cells (HUVEV-cells) as efficiently as wild-type
C196S
-
naturally occuring mutation, causes a failure in secretion of the enzyme
C237Y
-
mutation affects secretion, is expressed in smaller amounts as the wild-type. Does not degrade C4b and C3b as efficiently as the wild-type
C25F
-
mutant is as efficiently expressed in human embryonic kidney cells as wild-type, mutant protein is not secreted. Mutant is sensitive to EndoH digestion, indicating that it does not reach the late Golgi compartment and is retained in the endoplasmic reticulum
D104S
-
site-directed mutagenesis, altered kinetics compared to the wild-type
D207N/Q219A
-
Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) and Vmax similar to wild-type
D207N/Q219A/M220A/K221Q
-
Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) and Vmax similar to wild-type
D26N/K27Q/F29A/Q31A
-
Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) similar to wild-type, Vmax significantly increased compared to wild-type. Compared to wild-type mutant shows strongly impaired activity in degradation of fluid-phase complement factor C4b or C3b and in the degradation of surface-bound C3b deposited on sheep erythrocytes
D385N/K387S
-
site-directed mutagenesis, altered kinetics compared to the wild-type
D420N/N422T
-
site-directed mutagenesis, the mutation in the serine protease domain decreases the binding of the enzyme to substrate analogue C3met
D497N
-
site-directed mutagenesis, altered kinetics compared to the wild-type
F29A/Q31A
-
Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) similar to wild-type, Vmax significantly increased compared to wild-type. Compared to wild-type mutant shows strongly impaired activity in degradation of fluid-phase complement factor C4b or C3b
F82N/N84T
-
site-directed mutagenesis, the mutation in the FIMAC domain impairs enzyme activity, which is rescued by deglycosylation of the mutant
F94A/K182Q/R184Q
-
Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) similar to wild-type, Vmax significantly increased compared to wild-type. Compared to wild-type mutant shows strongly impaired activity in degradation of fluid-phase complement factor C4b or C3b. Mutant shows greatly impaired activity in the degradation of surface-bound C3b deposited on sheep erythrocytes
G170V
-
is expressed at low levels. Does degrade C4b and C3b
G243D
-
cofactor function of complement components C3b and Cb4 not affected
G261D
-
mutation in the complement factor I heavy chain associated with atypical hemolytic uremic syndrome, recombinant protein generated, activity tested
G71V
-
naturally occuring mutation, causes a failure in secretion of the enzyme
H165R
-
mutant is as efficiently expressed and secreted in human embryonic kidney cells as wild-type. Mutant cleaves the alpha'-chains of complement factor C4b and C3b more efficiently than wild-type in the presence of C4b-binding protein and factor H as cofactors in solution. Cleavage of complement factor C3b on the surface of sheep erythrocytes is similar to wild-type. In the presence of membrane cofactor protein mutant cleaves C3b alpha'chain on the surface of endothelial cells (HUVEV-cells) more efficiently than wild-type
H400L
-
mutation affects secretion, is expressed at low levels. Does degrade C4b and C3b
I322T
-
amino acid exchange in the serine protease domain, resulting in secreted proteins that lack cofactor function of complement components C3b and C4b
I339M
-
mutation affects secretion, is expressed at low levels
K124N
-
site-directed mutagenesis, altered kinetics compared to the wild-type
K124Q/R150Q/F151A/K152Q
-
Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) and Vmax similar to wild-type
K182N/R184S
-
site-directed mutagenesis, altered kinetics compared to the wild-type
K182Q/R184Q
-
Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) and Vmax similar to wild-type. Mutant shows similar activity to wild-type in degradation of fluid-phase complement factor C4b or C3b and in the degradation of surface-bound C3b deposited on sheep erythrocytes
K326N/A328T
-
site-directed mutagenesis, the mutation in the serine protease domain decreases the binding of the enzyme to substrate analogue C3met
K458N/N460T
-
site-directed mutagenesis, altered kinetics compared to the wild-type
K51A/R62A
-
Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) and Vmax similar to wild-type, only mutant in the FI and membrane attack complex domain (FIMAC) which shows some activity in degradation of fluid-phase complement factor C4b or C3b
K51A/R62A/L73A/L76A/F82A
-
Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) and Vmax similar to wild-type
K93Q/F94A
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Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) and Vmax similar to wild-type. Compared to wild-type mutant shows decreased but not abolished activity in degradation of fluid-phase complement factor C4b or C3b. Mutant shows impaired activity in the degradation of surface-bound C3b deposited on sheep erythrocytes
L171N
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site-directed mutagenesis, altered kinetics compared to the wild-type
L289x
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deletion mutant (c.893delC) leading to a premature stop codon. Mutant protein is not secreted when expressed in human embryonic kidney cells
L73A/L76A/F82A
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Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) and Vmax similar to wild-type
M120V
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mutant is as efficiently expressed in human embryonic kidney cells as wild-type, secretion is significantly lower compared to wild-type. Mutant cleaves the alpha'-chains of complement factor C4b and C3b more efficiently than wild-type in the presence of C4b-binding protein and factor H as cofactors in solution. Mutant cleaves complement factor C3b more efficiently in the presence of membrane cofactor protein in solution. Compared to wild-type mutant M120V shows enhanced cleavage of complement factor C3b on the surface of sheep erythrocytes. In the presence of membrane cofactor protein mutant cleaves C3b alpha'chain on the surface of endothelial cells (HUVEV-cells) more efficiently than wild-type
M220A/K221Q
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Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) and Vmax similar to wild-type
N133S
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mutant protein is not secreted when expressed in human embryonic kidney cells, mutant is sensitive to EndoH digestion, indicating that it does not reach the late Golgi compartment and is retained in the endoplasmic reticulum
N404T
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site-directed mutagenesis, the mutation in the serine protease domain decreases the binding of the enzyme to substrate analogues C3met and C4met
P32A
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mutant is as efficiently expressed and secreted in human embryonic kidney cells as wild-type. P32A mutant shows impaired function towards degradation of the alpha'-chains of complement factor C4b at the two highest concentrations and of the alpha'-chain of C3b at the highest concentration when factor H is used as cofactor. No significant impairment when complement receptor 1 and membrane cofactor protein 1 are used as cofactors. Compared to wild-type mutant P32A shows impaired cleavage of complement factor C3b on the surface of sheep erythrocytes. Mutant cleaves C3b alpha'chain on the surface of endothelial cells (HUVEV-cells) as efficiently as wild-type
Q210N/V212T
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site-directed mutagenesis, altered kinetics compared to the wild-type
Q219N/K221S
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site-directed mutagenesis, altered kinetics compared to the wild-type
Q232K
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mutation affects secretion, is expressed in smaller amounts as the wild-type. Does degrade C4b and C3b
Q242N/K244S
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site-directed mutagenesis, the mutation in the LDLr2 domain decreases the binding of the enzyme to substrate analogues C3met and C4met
Q257N/Q259S
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site-directed mutagenesis, the mutation in the LDLr2 domain decreases the binding of the enzyme to substrate analogues C3met and C4met
Q336x
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truncated mutant can be expressed, in vitro, at a level similar to that of the wild-type, but is not functional because it lacks the serine protease domain. Is not detected in serum of the patient
R130Q/R169Q
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Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) and Vmax similar to wild-type
R150Q/F151A/K152Q
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Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) and Vmax similar to wild-type
R201S
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present only in Far East populations with frequencies of about 0.03 in the main island of Japan and lower than 0.01 in Okinawa and Korea
R35N/I37T
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site-directed mutagenesis, the mutation in the FIMAC domain impairs enzyme activity, which is rescued by deglycosylation of the mutant
R365N
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site-directed mutagenesis, the mutation in the serine protease domain decreases the binding of the enzyme to substrate analogues C3met and C4met
R388H
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cofactor function of complement components C3b and Cb4 not affected
R406H
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present almost exclusively in East Asians and at highest frequencies in southern Chinese Han and Thais
R456x
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point mutant leading to a premature stop codon. Mutant protein is not secreted when expressed in human embryonic kidney cells
R502L
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must have arisen in a southeastern part of Asia and thereafter has spread to neighboring populations
R61N
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site-directed mutagenesis, altered kinetics compared to the wild-type
S250L
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mutation affects secretion, is expressed in smaller amounts as the wild-type. Cleaves C4b and C3b in the same manner as the wild-type
S561N/Y563T
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site-directed mutagenesis, the mutation in the serine protease domain impairs enzyme activity, which is rescued by deglycosylation of the mutant
T520x
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insertion mutant (c. 1610insAT) leading to a premature stop codon, mutant protein is not secreted when expressed in human embryonic kidney cells
T54N/V56T
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site-directed mutagenesis, altered kinetics compared to the wild-type
V212A/L236A
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Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) similar to wild-type, Vmax significantly increased compared to wild-type. Compared to wild-type mutant shows strongly impaired activity in degradation of fluid-phase complement factor C4b or C3b. Mutant shows no activity in the degradation of surface-bound C3b deposited on sheep erythrocytes
V252A/I267A
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Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) similar to wild-type, Vmax significantly increased compared to wild-type. Compared to wild-type mutant shows strongly impaired activity in degradation of fluid-phase complement factor C4b or C3b. Mutant shows no activity in the degradation of surface-bound C3b deposited on sheep erythrocytes
W468x
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deletion mutant (c.1446-1450 delTTCAC) leading to a premature stop codon, mutant is as efficiently expressed in human embryonic kidney cells as wild-type but protein is not secreted
W528x
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point mutant leading to a premature stop codon. Mutant protein is not secreted when expressed in human embryonic kidney cells
Y369S
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patient heterozygous for a novel missense mutation in CFI. This polymorphism is within a functional domain. It is located in the 38 kDa chain of the protein within the serine protease domain that is linked by a disulfide bond to the noncatalytic heavy chain of factor I
additional information
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UNIPROT
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medicine