C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates. Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. In chronic inflammation, acts as a chemoattractant for neutrophils (By similarity). It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. Acts as a chemoattractant for neutrophils in chronic inflammation. Adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for C5AR2. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of C5AR2 (PubMed:8376604, PubMed:2909530, PubMed:9059512, PubMed:10432298, PubMed:15833747, PubMed:16333141, PubMed:19615750). 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, PubMed:31507604). The interaction with Bb is dependent on Mg2+ (PubMed:31507604). C3b interacts with CR1 (via Sushi 8 and Sushi 9 domains) (PubMed:8175757, PubMed:2972794). C3b interacts with CFH (PubMed:21285368). C3d interacts with CFH (PubMed:21285368, PubMed: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. Plasma. The acylation stimulating protein (ASP) is expressed in adipocytes and released into the plasma during both the fasting and postprandial periods. C3b is rapidly split in two positions by factor I and a cofactor to form iC3b (inactivated C3b) and C3f which is released. Then iC3b is slowly cleaved (possibly by factor I) to form C3c (beta chain + alpha' chain fragment 1 + alpha' chain fragment 2), C3dg and C3f. Other proteases produce other fragments such as C3d or C3g. C3a is further processed by carboxypeptidases to release the C-terminal arginine residue generating the acylation stimulating protein (ASP). Levels of ASP are increased in adipocytes in the postprandial period and by insulin and dietary chylomicrons. (Microbial infection) C3 is cleaved by Staphylococcus aureus aureolysin; this cleavage renders C3a and C3b inactive. C3b is rapidly degraded by host factors CFH and CFI preventing its deposition on the bacterial surface while C3a is further inactivated by aureolysin. Phosphorylated by FAM20C in the extracellular medium. There are two alleles: C3S (C3 slow), the most common allele in all races and C3F (C3 fast), relatively frequent in Caucasians, less common in Black Americans, extremely rare in Orientals. The disease is caused by variants affecting the gene represented in this entry. Disease susceptibility is associated with variants affecting the gene represented in this entry. Disease susceptibility is associated with variants affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype. Increased levels of C3 and its cleavage product ASP, are associated with obesity, diabetes and coronary heart disease. Short-term endurance training reduces baseline ASP levels and subsequently fat storage. An article reported the interaction surface between C3 and CR2 (PubMed:11387479). According to a another paper, it is however an artifact and can be ascribed to the presence of zinc acetate in the buffer (PubMed:21527715). The difference between allele C3S (C3 slow) and allele C3F (C3 fast) was reported to be caused by a an Asn at position 1216 instead of an Asp (PubMed:2473125). The paper was however retracted (PubMed:2584723). C3 mutation db Complement C3 entry