Table 1.
Proteins involved in the core complement cascade
| Pattern-Recognition | Alternative Names | Function |
|---|---|---|
| C1q | Part of the C1 complex; recognizes surface-bound IgG, IgM, CRP, and PAMP.; initiates CP | |
| MBL (mannose-binding lectin) | Recognizes carbohydrate patterns; initiates LP | |
| Ficolin-1 | M-Ficolin | Recognizes carbohydrate patterns; initiates LP |
| Ficolin-2 | L-Ficolin; Hucolin | Recognizes carbohydrate patterns; initiates LP |
| Ficolin-3 | H-Ficolin; HAKA1 | Recognizes carbohydrate patterns; initiates LP |
| Properdin | Factor P | Recognizes PAMP and DAMP; initiates AP; stabilizes AP convertases |
| CRP (C-reactive protein)1 | Recognizes DAMP/PAMP on apoptotic and microbial cell cells; binds C1q | |
| CFHR-4 (Factor H-related protein 4) | FHR-4 | Recruits monomeric CRP to necrotic cells; facilitates activation of CP via C1q |
| Proteases | Alternative Names | Function |
|---|---|---|
| C1r | Part of the C1 complex; cleaves C1s | |
| C1s | Part of the C1 complex; cleaves C2 and C4 | |
| MASP-1 (MBL-associated serine protease 1) | Binds to MBL/Ficolins; cleaves C2 (but not C4); may cleave MASP-2 and C3; activates pro-FD; potential role in coagulation cascade? | |
| MASP-2 (MBL-associated serine protease 2) | Binds to MBL/Ficolins; cleaves C2 and C4 | |
| MASP-3 (MBL-associated serine protease 3) | Unknown (binds to MBL/Ficolins, does not cleave C2 or C4) | |
| C2 | Part of the CP/LP convertases; cleaves C3/C5 | |
| fB (Factor B) | CFB | Part of the AP C3/C5 convertases; cleaves C3/C5 |
| fD (Factor D) | CFD | Cleaves C3b-bound FB to form the AP C3/C5 convertases |
| fI (Factor I) | CFI | Degrades C3b and C4b |
| Complement Components | Alternative Names | Function |
|---|---|---|
| C3 | Progenitor for anaphylatoxin C3a, opsonin C3b and signaling fragments (iC3b, C3c, C3d); part of the AP C3 and all C5 convertases | |
| C4 | Progenitor for opsonin C4b; part of the CP/LP convertases | |
| C5 | Progenitor for anaphylatoxin C5a and C5b/TCC | |
| C6 | Part of TCC (membrane-insertion) | |
| C7 | Part of TCC (membrane-insertion) | |
| C8 | Part of TCC (induction of pore formation) | |
| C9 | Part of TCC (forms lytic pore) |
| Receptors2 | Alternative Names | Function |
|---|---|---|
| CR1 (complement receptor 1) | CD35; C3b/C4b-receptor | Binds C3b/iC3b; Induces phagocytosis: accelerates decay of convertases; cofactor for fI |
| CR2 (complement receptor 2) | CD21; C3d-receptor | Binds iC3b/C3d; lowers threshold for B-cell stimulation |
| CR3 (complement receptor 3) | CD11b/CD18; Mac-1 (Macrophage-1 antigen); integrin aMb2 | Induces phagocytosis via interaction with iC3b; modulates IL-12 family in APC |
| CR4 (complement receptor 4) | CD11c/CD18; p150/95; integrin aXb2 | Induces phagocytosis via interaction with iC3b |
| C3aR (C3a receptor) | Binds C3a; triggers proinflammatory signaling | |
| C5aR (C5a receptor) | CD88 | Binds C5a; triggers proinflammatory signaling |
| C5L2 (C5a receptor 2) | GPR77 | Binds C5a / C5adesArg (may bind C3a/C3adesArg); function controversial |
| CRIg (Complement receptor of the immunoglobulin family) | Z93Ig, VSIG4 | Induces phagocytosis via interaction with iC3b/C3c; regulatory effect on C5 convertases |
| cC1qR (C1q receptor for collagen region) | Calreticulin; collectin receptor | Recognizes bound C1q; induces phagocytic signaling via CD91 |
| gC1qR (C1q receptor for globular heads) | C1qbp (C1q-binding protein); p33 | Recognizes C1q; potential role in phagocytosis and signaling; modulates IL-12 on APC |
| C1qRp | (CD93 + unknown mediator) | Part of receptor complex that binds C1q and mediates phagocytosis |
| Regulators | Alternative Names | Function |
|---|---|---|
| C1-INH (C1 esterase inhibitor) | SERPIN1 (Serine protease inhibitor 1) | Inhibits C1r/s and MASPs |
| sMAP (small MBL-associated protein) | MAp19 (MBL-associated protein 19) | Binds to MBL, competes with MASPs |
| MAP-1 (MBL/ficolin-associated protein 1) | MAp44 ((MBL-associated protein 44) | Binds to MBL/ficolins; inhibits C4 deposition |
| C4BP (C4b-binding protein) | C4-binding protein | Accelerates decay of LC/CP convertases; cofactor for fI |
| fH (Factor H) | CFH | Recognizes self-surfaces; accelerates convertase decay; cofactor for fI |
| FHL-1 (Factor H-like protein 1) | Reconectin, CFHL1 | Accelerates convertase decay; cofactor for fI |
| MCP (Membrane Cofactor Protein) | CD46 | Cofactor for fI |
| DAF (Decay Accelerating Factor) | CD55 | Accelerates decay of convertases |
| CFHR-1 (Factor H-related protein 1) | FHR-1 | Recognizes self-surfaces and C5; inhibits C5 cleavage and TCC formation |
| CD59 | Protectin | Binds to C8 and C9; prevents assembly of TCC |
| VTN (Vitronectin) | S-protein; S40 | Binds to C5b-9; prevents assembly of TCC |
| CLU (Clusterin) | Apolipoprotein J; SP-40,40 | Binds to C7–C9; prevents assembly of TCC |
| CPN (Carboxypeptidase-N) | Degrades C3a and C5a to their desArg forms | |
| CRIT (C2 receptor inhibitor trispanning) | Binds to C2; prevents cleavage by C1s |
1
Although CRP is the best-described representative mediator of this category, other pentraxins may exert similar functions
2
Additional receptor for C1q (e.g. CR1, integrin α2β1, murine SIGN-R1) have been proposed but not yet been confirmed.