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3.4.21.45: complement factor I

This is an abbreviated version!
For detailed information about complement factor I, go to the full flat file.

Word Map on EC 3.4.21.45

Reaction

Inactivates complement subcomponents C3b, iC3b and C4b by proteolytic cleavage =

Synonyms

C3b inactivator, C3b/C4b inactivator, C3bINA, CFI, complement C3b inactivator, complement C3b/C4b inactivator, complement C4b inactivator, complement C4bi, complement compoment C3b inactivator, complement factor I, complement inhibitor factor I, complement regulator factor I, conglutinogen-activating factor C, factor I, factor I-like activity, fI, GcIf-1, GcIf-2, GcIf-3, GcIf-4, IF, plasma protease factor I, serine protease Factor I

ECTree

     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.21 Serine endopeptidases
                3.4.21.45 complement factor I

Engineering

Engineering on EC 3.4.21.45 - complement factor I

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PROTEIN VARIANTS
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
D501N
D506V
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
-
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
-
site-directed mutagenesis, altered kinetics compared to the wild-type
L289x
-
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
-
Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) and Vmax similar to wild-type
M120I
M120V
-
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
-
Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) and Vmax similar to wild-type
N133S
-
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
-
site-directed mutagenesis, the mutation in the serine protease domain decreases the binding of the enzyme to substrate analogues C3met and C4met
P32A
-
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
-
site-directed mutagenesis, altered kinetics compared to the wild-type
Q219N/K221S
-
site-directed mutagenesis, altered kinetics compared to the wild-type
Q232K
-
mutation affects secretion, is expressed in smaller amounts as the wild-type. Does degrade C4b and C3b
Q242N/K244S
-
site-directed mutagenesis, the mutation in the LDLr2 domain decreases the binding of the enzyme to substrate analogues C3met and C4met
Q257N/Q259S
-
site-directed mutagenesis, the mutation in the LDLr2 domain decreases the binding of the enzyme to substrate analogues C3met and C4met
Q336x
-
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
-
Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) and Vmax similar to wild-type
R150Q/F151A/K152Q
-
Km (tert-butyloxycarbonyl-Asp(benzyl)-Pro-Arg-7-amido-4-methylcoumarin) and Vmax similar to wild-type
R201S
-
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
R299W
R35N/I37T
-
site-directed mutagenesis, the mutation in the FIMAC domain impairs enzyme activity, which is rescued by deglycosylation of the mutant
R365N
-
site-directed mutagenesis, the mutation in the serine protease domain decreases the binding of the enzyme to substrate analogues C3met and C4met
R388H
cofactor function of complement components C3b and Cb4 not affected
R406H
-
present almost exclusively in East Asians and at highest frequencies in southern Chinese Han and Thais
R456x
-
point mutant leading to a premature stop codon. Mutant protein is not secreted when expressed in human embryonic kidney cells
R502L
-
must have arisen in a southeastern part of Asia and thereafter has spread to neighboring populations
R61N
-
site-directed mutagenesis, altered kinetics compared to the wild-type
S250L
-
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
-
site-directed mutagenesis, the mutation in the serine protease domain impairs enzyme activity, which is rescued by deglycosylation of the mutant
T520x
-
insertion mutant (c. 1610insAT) leading to a premature stop codon, mutant protein is not secreted when expressed in human embryonic kidney cells
T54N/V56T
-
site-directed mutagenesis, altered kinetics compared to the wild-type
V212A/L236A
-
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
-
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
W127X
W468x
-
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
-
point mutant leading to a premature stop codon. Mutant protein is not secreted when expressed in human embryonic kidney cells
Y369S
-
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