3.4.21.47 923DELTADG mutation in complement factor 3 gene identified in patients with dense deposit disease. Mutant C3923DELTADG, which lacks 2 amino acids, cannot be cleaved to C3b by the alternative pathway C3-convertase and is therefore the predominant circulating C3 protein in the patients. Upon activation to C3b by proteases, or to C3(H2O) by spontaneous thioester hydrolysis, mutant C3 generates an active C3-convertase that is regulated normally by decay accelerating factor but is resistant to decay by factor H. Activated C3b923DELTADG and C3(H2O)923DELTADG are resistant to proteolysis by factor I in the presence of factor H, but are efficiently inactivated in the presence of membrane cofactor protein, causing a fluid phase-restricted alternative pathway dysregulation in the patients that continuously activates and consumes C3 produced by the normal C3 allele 717907 3.4.21.47 D254G mutation in the Bb component decreases sensitivity to DAF to 9% of the wild-type value, sensitivity to CR1 to 4% of the wild-type value and sensitivity to Factor H to 48% of the wild-type value 652225 3.4.21.47 D382A mutation in the Bb component decreases sensitivity to DAF to 36% of the wild-type value, sensitivity to CR1 to 41% of the wild-type value 652225 3.4.21.47 D382N mutation in the Bb component decreases sensitivity to DAF to 54% of the wild-type value 652225 3.4.21.47 D445A mutation in the Bb component decreases sensitivity to CR1 to 71% of the wild-type value 652225 3.4.21.47 D715A factor B mutation, severly reduces hemolytic activity, in complex with C3b no cleavage of C3 36600 3.4.21.47 D715E factor B mutation, severly reduces hemolytic activity, in complex with C3b no cleavage of C3 36600 3.4.21.47 D715N factor B mutation, severly reduces hemolytic activity, in complex with C3b no cleavage of C3 36600 3.4.21.47 D715S factor B mutation, severly reduces hemolytic activity 36600 3.4.21.47 D715Y factor B mutation, severly reduces hemolytic activity 36600 3.4.21.47 E207A mutation in proenzyme factor B. Mutation disrupts salt bridge R234-E207, with little effects on the cleavage of proenzyme factor B 717849 3.4.21.47 E301A mutation in the Bb component decreases sensitivity to DAF to 75% of the wild-type value 652225 3.4.21.47 E316A mutation in the Bb component decreases sensitivity to DAF to 71% of the wild-type value 652225 3.4.21.47 E379A mutation in the Bb component decreases sensitivity to DAF to 52% of the wild-type value, sensitivity to CR1 to 50% of the wild-type value 652225 3.4.21.47 E434A mutation in the Bb component decreases sensitivity to CR1 to 65% of the wild-type value 652225 3.4.21.47 E446V mutation in proenzyme factor B. Mutation disrupts salt bridge R234-E446 which partly stabilizes the complex C3bB(Mg2+) thereby inhibiting activation of the proenzyme 717849 3.4.21.47 F716A factor B mutation, severly reduces hemolytic activity 36600 3.4.21.47 K265A/K266A Mutation in the Bb component decreases sensitivity to DAF to 18% of the wild-type value, sensitivity to CR1 to 18% of the wild-type value and sensitivity to Factor H to 19% of the wild-type value 652225 3.4.21.47 K294A mutation in the Bb component decreases sensitivity to CR1 to 44% of the wild-type value 652225 3.4.21.47 M341A mutation in the Bb component decreases sensitivity to Factor H to 75% of the wild-type value 652225 3.4.21.47 additional information enzyme component C3 deletion mutant. Acute lung inflammatory injury is greatly attenuated in lungs of mutant animals, and C5a levels in broncheolar lavage fluids of mutants greatly reduced in presence of antithrombin III or hirudin, compared to wild-type. Plasma from mutant animals contains threefold higher levels of thrombin activity and higher levels of prothrombin mRNA, prothrombin and thrombin protein in liver of mutants 670361 3.4.21.47 additional information introduction of Cys-residues to form a disulfide bond at positions 428 and 435 of von Willebrandt factor type A domain of subunit Bb. Adaption of an active conformation by the domain, which is not sufficient to activate the enzyme catalytic apparatus 670220 3.4.21.47 additional information replacement of C-terminal sequences of enzyme compoment C3 by the corresponding sequences of cobra venom factor from Naja kaouthia. Major role of NTR/C345C motiv in regulation of enzyme half-life 668899 3.4.21.47 additional information substitution of enzyme component C3 domains by corresponding domains of cobra venom factor. Structural domains of cobra venom factor gamma- or beta-chains confer stability to C3 convertase complex. Replacement of terminal C-275 amino acids by those of cobra venom factor beta-chain results in a catalytic activity of C3 convertase similar to wild-type, but with a half-life of 5-6 h compared to 1-2 min for wild-type 669714 3.4.21.47 N260D mutation in the Bb component decreases sensitivity to DAF to 32% of the wild-type value, sensitivity to CR1 to 31% of the wild-type value and sensitivity to Factor H to 24% of the wild-type value 652225 3.4.21.47 Q335A mutation in the Bb component decreases sensitivity to DAF to 20% of the wild-type value 652225 3.4.21.47 S339A mutation in the Bb component decreases sensitivity to DAF to 32% of the wild-type value, sensitivity to CR1 to 50% of the wild-type value 652225 3.4.21.47 W343A mutation in the Bb component decreases sensitivity to DAF to 55% of the wild-type value, sensitivity to CR1 to 56% of the wild-type value 652225 3.4.21.47 Y338A mutation in the Bb component decreases sensitivity to DAF to 9% of the wild-type value, sensitivity to CR1 to 4% of the wild-type value and sensitivity to Factor H to 48% of the wild-type value 652225 3.4.21.47 Y338F mutation in the Bb component decreases sensitivity to DAF to 18% of the wild-type value, sensitivity to CR1 to 20% of the wild-type value and sensitivity to Factor H to 61% of the wild-type value 652225 3.4.21.47 Y338S mutation in the Bb component decreases sensitivity to DAF to 5% of the wild-type value, sensitivity to CR1 to 24% of the wild-type value 652225