TABLE 1.

Characteristics of proteins that activate the complement cascade

Category and componentApprox serum concn (μg/ml)Mol mass (kDa)StructureaNo. of genetic lociChromosomal assignment
Complement activator proteins
    Classical pathway proteins
        C1q7045918 polypeptide chains; 6A, 6B, 6C; A-B and C-C linked by disulfides3 (A, B, C)1p34-1p36.3
        C1r34173Comprises a CUB (C1r/C1s, uEGF, bone morphogenetic protein) module, an epidermal growth factor (EGF)-like module, a second CUB module, two complement control protein (CCP) modules, and a C-terminal chymotrypsin-like serine protease domain; dimer (A and B chains linked by disulfide bond)112p13
        C1s3180Dimer (A and B chains linked by disulfide bond); modular structure described for C1r112p13
        C4600206β-α-γ; 1 β-α and 2 α-γ disulfide bonds2 (C4A, C4B)6p21.3
        C211-351001 chain16p21.3
    Alternative pathway proteins
        Factor B200901 chain16p21.3
        Factor D (adipsin)1-2251 chain119p13.3
    Lectin pathway proteins
        Mannan-binding lectin (MBL)1-5∼25 (subunit monomer)Subunit, trimers of identical polypeptides; subunits organized into larger oligomers (n ∼ 2 for variant [B, C, and D] alleles and n = 4-6 for wild-type [A] allele)110q11.2-q21
        Ficolin-1 (M-ficolin; ficolin/P35-related protein)0.04-0.1 (monocytes and PMNs main source)∼32 (subunit monomer)Subunit, trimers of identical polypeptides; subunits organized into larger oligomers19q34
        Ficolin-2 (L-ficolin; hucolin; EBP-37; ficolin/P35)3-434 (subunit monomer)As with ficolin-119q34
        Ficolin-3 (H-ficolin; Hakata antigen; thermolabile β-2 macroglycoprotein; thermolabile substance)1835 (subunit monomer)As with ficolin-11Chr 1
        MASP-1697Active form consists of heavy and light chains linked by disulfide bond13q27-28
        MASP-20.02-0.883Active form consists of A and B chains linked by disulfide bond11p36.3-p36.2
        MASP-32-12.9105Activation splits 105-kDa disulfide-linked dimer into A (58 kDa) and B (42 kDa); B chain is serine protease domain13q27-28
        MAp190.519Alternatively spliced version of MASP-2, contains first 2 domains and 4 additional C-terminal amino acids; head-to-tail homodimer11p36.3-p36.2
    C31,000-1,500190β-α, linked by disulfide bond; crystal structure shows organization into 13 domains (8 macroglobulin domains, CUB, thioester [TED], anaphylatoxin, linker, and C345c domain)119p13.3-p13.2
    Terminal complement components
        C575190β-α, linked by disulfide bond19q34.1
        C6451001 chain15p13
        C790951 chain15p13
        C855-80151α-γ dimer linked by disulfide, noncovalently associated with β3(α,β)1p32; (γ) 9q34.3
        C960711 chain15p13
Complement-regulatory proteins
    Positive regulator
        Properdin5-1055Cyclic polymers in head-to-tail orientation; dimers-trimers-tetramers in 26:54:20 ratio; each monomer comprises 6 thrombospondin-like repeats (TSRs) and has 14 sites of C-mannosylation1Xp11.4-p11.23
    Negative regulators
        C1 inhibitor1501041 chain; highly glycosylated111q11-q13.1
        C4b-binding protein (C4BP)150-300∼5507 disulfide-linked α-chains (8 SCRs) linked to β-chain (3 SCRs) via disulfide (major isoform, α7/β1); minor isoforms α7/β0 and α6/β12(α,β) 1q32
        Factor H5001551 chain (20 SCRs)11q32
        Factor H-like protein-1 (FHL-1)25431 chain (7 SCRs; identical to 7 N-terminal SCRs of factor H, plus 4 unique C-terminal amino acids)11q32
        Factor H-related molecule-1 (FHR-1)70-100371 chain (5 SCRs; the 3 C-terminal SCRs bear 100, 100, and 97% homology with the three C-terminal SCRs of fH, respectively)11q32
        Vitronectin (S-protein)50075 (65-kDa proteolytic1 chain117q11
    fragment also seen)
        Clusterin (SP-40,40; apolipoprotein J)100-30060 (predicted); 80 (observed)Heterodimer linked by 5-disulfide bond motif18p21-p12
        Factor J∼5∼24Highly glycosylated cationic protein (pI > 9.6)??
  • a SCRs, short consensus repeats.