Complement component 5 (C5) (C5)

Complement component 5 (C5) is a central protein in the complement cascade, representing the initiator of the terminal pathway in the innate immune system (UniProt: P01031). It is primarily synthesized in the liver and circulates in the blood as a 190 kDa glycoprotein composed of alpha and beta polypeptide chains (NCBI Gene: 727). Upon activation by C5 convertase enzymes from the classical, alternative, or lectin pathways, C5 is proteolytically cleaved into C5a and C5b (PubMed: 30224934). C5a acts as a powerful pro-inflammatory mediator and chemoattractant, while C5b serves as the foundation for the assembly of the membrane attack complex (MAC), which creates pores in target cell membranes to induce lysis (StatPearls: NBK534867). Pathological overactivation of C5 is a key driver in diseases characterized by intravascular hemolysis and microvascular thrombosis, such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) (DrugBank: DB01257). Therapeutic strategies targeting C5, including monoclonal antibodies and small peptides, focus on blocking its cleavage to prevent terminal complement-mediated damage while leaving the upstream opsonization functions of the complement system intact (PubMed: 31647320).

Other names

C5CPAMD4Complement C5C5a anaphylatoxinC5bPrepro-C5

C5 inhibitors bind to the C5 protein, sterically blocking its cleavage by C5 convertases into C5a and C5b, which prevents the assembly of the membrane attack complex and the release of pro-inflammatory mediators (PubMed: 31647320).