Complement component 3

Complement component 3, often simply called C3, is a is_associated_with::protein of the is_associated_with::immune system. It plays a central role in the is_associated_with::complement system and contributes to is_associated_with::innate immunity. In humans it is encoded on is_associated_with::chromosome 19 by a is_associated_with::gene called C3.

Function
C3 plays a central role in the activation of is_associated_with::complement system. Its activation is required for both classical and alternative complement activation pathways. People with C3 deficiency are susceptible to bacterial infection.

One form of is_associated_with::C3-convertase, also known as C4b2a, is formed by a heterodimer of activated forms of C4 and C2. It catalyzes the is_associated_with::proteolytic cleavage of C3 into C3a and is_associated_with::C3b, generated during activation through the classical pathway as well as the is_associated_with::lectin pathway. C3a is an is_associated_with::anaphylotoxin and the precursor of some cytokines such as ASP, and C3b serves as an opsonizing agent. Factor I can cleave C3b into C3c and C3d, the latter of which plays a role in enhancing is_associated_with::B cell responses. In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 (C3b) and is_associated_with::factor B (Bb). Once C3 is activated to C3b, it exposes a reactive is_associated_with::thioester that allows the peptide to covalently attach to any surface that can provide a is_associated_with::nucleophile such as a primary amine or a hydroxyl group. Activated C3 can then interact with factor B. Factor B is then activated by factor D, to form Bb. The resultant complex, C3bBb, is called the alternative pathway (AP) C3 convertase.

C3bBb is deactivated in steps. First, the proteolytic component of the convertase, Bb, is removed by complement regulatory proteins having is_associated_with::decay-accelerating factor (DAF) activity. Next, C3b is broken down progressively to first iC3b, then C3c + C3dg, and then finally C3d. Factor I is the protease that performs these cuts but it requires the help of another protein (is_associated_with::Factor H, CR1, MCP or C4BP) to supply cofactor activity.

Structure
Several crystallographic structures of C3 have been determined and reveal that this protein contains 13 domains.

Clinical use
Levels of C3 in the is_associated_with::blood may be measured to support or refute a particular medical diagnosis. For example, low C3 levels are associated with some types of kidney disease such as is_associated_with::post-infectious glomerulonephritis, is_associated_with::membranoproliferative glomerulonephritis, and is_associated_with::shunt nephritis.

Interactions
Complement component 3 has been shown to interact with is_associated_with::Factor H.