Complement C3

Function

Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system.

Classification

Family (Pfam)

PF00207 A2M, PF07703 A2M_BRD, PF07677 A2M_recep, PF01821 ANATO, PF21406 C3_CUB1, PF21308 C3_CUB2, PF17790 MG1, PF01835 MG2, PF17791 MG3, PF17789 MG4, PF01759 NTR, PF07678 TED_complement

InterPro

A-macroglobulin_rcpt-bd, A-macroglobulin_rcpt-bd_sf, A2M/Complement_sys, A2M_N_BRD, Alpha-macroglob_thiol-ester_cl, Alpha-macroglobulin_TED, Anaphylatoxin/fibulin, Anaphylatoxin_comp_syst, Anaphylatoxn_comp_syst_dom, C3/4/5_MG1, C3_CUB1, C3_CUB2, Ig-like_fold, Macroglobln_a2, MacrogloblnA2_CS, MG2, MG3, MG4, Netrin_domain, Netrin_module_non-TIMP, NTR_complement_C3, Terpenoid_cyclase/PrenylTrfase, TIMP-like_OB-fold

Functional cluster

Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 74

• 1C3D X-ray 1.80A
• 1GHQ X-ray 2.04A
• 1W2S X-ray
• 2A73 X-ray 3.30A
• 2A74 X-ray 2.40A
• 2GOX X-ray 2.20A
• 2I07 X-ray 4.00A
• 2ICE X-ray 3.10A
• 2ICF X-ray 4.10A
• 2NOJ X-ray 2.70A
• 2QKI X-ray 2.40A
• 2WII X-ray 2.70A
• … and 62 more

A predicted model is available from AlphaFold.

Gene Ontology · 40

• GO:0035578 azurophil granule lumen
• GO:0072562 blood microparticle
• GO:0009986 cell surface
• GO:0005788 endoplasmic reticulum lumen
• GO:0070062 extracellular exosome
• GO:0005576 extracellular region
• GO:0005615 extracellular space
• GO:0005886 plasma membrane
• GO:0032991 protein-containing complex
• GO:0034774 secretory granule lumen
• GO:0031715 C5L2 anaphylatoxin chemotactic receptor binding
• GO:0004866 endopeptidase inhibitor activity
• GO:0048018 receptor ligand activity
• GO:0005102 signaling receptor binding
• GO:0097242 amyloid-beta clearance
• GO:0042113 B cell activation
• GO:0006956 complement activation
• GO:0006957 complement activation, alternative pathway
• GO:0006958 complement activation, classical pathway
• GO:0160257 complement activation, GZMK pathway
• GO:0002430 complement receptor mediated signaling pathway
• GO:0150062 complement-mediated synapse pruning
• GO:0006631 fatty acid metabolic process
• GO:0007186 G protein-coupled receptor signaling pathway
• GO:0006955 immune response
• GO:0006954 inflammatory response
• GO:0016322 neuron remodeling
• GO:0001970 positive regulation of activation of membrane attack complex
• GO:0045766 positive regulation of angiogenesis
• GO:2000427 positive regulation of apoptotic cell clearance
• GO:0010828 positive regulation of D-glucose transmembrane transport
• GO:0045745 positive regulation of G protein-coupled receptor signaling pathway
• GO:0010884 positive regulation of lipid storage
• GO:0060100 positive regulation of phagocytosis, engulfment
• GO:0001934 positive regulation of protein phosphorylation
• GO:0048260 positive regulation of receptor-mediated endocytosis
• GO:0010575 positive regulation of vascular endothelial growth factor production
• GO:0010866 regulation of triglyceride biosynthetic process
• GO:0007165 signal transduction
• GO:0150064 vertebrate eye-specific patterning

Disease associations

• age related macular degeneration 9 MONDO:0012659
• atypical hemolytic-uremic syndrome with C3 anomaly MONDO:0013043
• complement component 3 deficiency MONDO:0013417

Drugs targeting this protein · 1

• AMY-101 inhibitor

Related proteins · sequence + function similarity

• Complement C3 0.98
• Complement C3 0.98
• Complement C3 0.98
• Complement C3 0.98
• Complement C3 0.96
• Ophiophagus venom factor 0.92
• Venom factor 0.92
• A.superbus venom factor 2 0.92
• Complement C3 0.91
• Cobra venom factor 0.91
• A.superbus venom factor 1 0.91
• Complement C5 0.90

Co-cited proteins · studied together in the literature

• C5a anaphylatoxin chemotactic receptor 2 4 shared papers
• Complement factor B 10 shared papers
• Complement factor I 4 shared papers
• V-set and immunoglobulin domain-containing protein 4 1 shared papers
• Fibrinogen-binding protein 1 shared papers
• Complement C5 11 shared papers
• Complement factor H 6 shared papers
• Neisserial autotransporter lipoprotein NalP 1 shared papers
• Zinc metalloproteinase aureolysin 1 shared papers
• Complement receptor type 2 2 shared papers
• C3a anaphylatoxin chemotactic receptor 3 shared papers
• Properdin 3 shared papers

Literature · 96 cited papers

• Granzyme K activates the entire complement cascade. Nature · 2025
• GZMK-expressing CD8+ T cells promote recurrent airway inflammatory diseases. Nature · 2025
• Molecular basis of anaphylatoxin binding, activation, and signaling bias at complement receptors. Cell · 2023
• Revealing the signaling of complement receptors C3aR and C5aR1 by anaphylatoxins. Nat. Chem. Biol. · 2023
• Structural Basis for Properdin Oligomerization and Convertase Stimulation in the Human Complement System. Front. Immunol. · 2019
• Bacterial killing by complement requires membrane attack complex formation via surface-bound C5 convertases. EMBO J. · 2019
• Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses. Nat. Struct. Mol. Biol. · 2017
• Functional and structural insight into properdin control of complement alternative pathway amplification. EMBO J. · 2017
• A single kinase generates the majority of the secreted phosphoproteome. Cell · 2015
• Neisseria meningitidis NalP cleaves human complement C3, facilitating degradation of C3b and survival in human serum. Proc. Natl. Acad. Sci. U.S.A. · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration. Nat. Genet. · 2013
• … and 84 more in the literature graph