C3

Candidate cardiovascular disease genes, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins

Intracellular, Secreted (different isoforms)

Cell type enriched (Hepatocytes)

Immune cell enriched (non-classical monocyte)

Group enriched (BJ hTERT+, EFO-21, Hep G2, HSkMC, SiHa)

C3 precursor is first processed by the removal of 4 Arg residues, forming two chains, beta and alpha, linked by a disulfide bond. C3 convertase activates C3 by cleaving the alpha chain, releasing C3a anaphylatoxin and generating C3b (beta chain + alpha' chain). Forms the pro-C3-convertase enzyme complex by interacting with Complement factor B Bb fragment (Bb), which is then stabilized by binding CFP, allowing the complex to become active (PubMed:28264884, 31507604). The interaction with Bb is dependent on Mg2+ (PubMed:31507604). C3b interacts with CR1 (via Sushi 8 and Sushi 9 domains) (PubMed:8175757, 2972794). C3b interacts with CFH (PubMed:21285368). C3d interacts with CFH (PubMed:21285368, 21317894). C3dg interacts with CR2 (via the N-terminal Sushi domains 1 and 2). During pregnancy, C3dg exists as a complex (probably a 2:2:2 heterohexamer) with AGT and the proform of PRG2. Interacts with VSIG4. Interacts (both C3a and ASP) with C5AR2; the interaction occurs with higher affinity for ASP, enhancing the phosphorylation and activation of C5AR2, recruitment of ARRB2 to the cell surface and endocytosis of GRP77. (Microbial infection) C3b interacts with herpes simplex virus 1 (HHV-1) and herpes simplex virus 2 (HHV-2) envelope glycoprotein C; this interaction inhibits the activation of the complement system. (Microbial infection) Interacts with Staphylococcus aureus immunoglobulin-binding protein Sbi; this interaction prevents the association between C3dg and CR2. (Microbial infection) Interacts with Staphylococcus aureus protein Fib.