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FUNCTION Pore-forming component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane rupture and cell lysis (PubMed:22832194, PubMed:26841837, PubMed:26841934, PubMed:27052168, PubMed:30552328, PubMed:6177822, PubMed:9212048, PubMed:9634479). The MAC is initiated by proteolytic cleavage of C5 into complement C5b in response to the classical, alternative, lectin and GZMK complement pathways (PubMed:39914456, PubMed:39814882, PubMed:9212048, PubMed:9634479). The complement pathways consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:9212048, PubMed:9634479). Constitutes the pore-forming subunit of the MAC complex: during MAC assembly, C9 associates with the C5b8 intermediate complex, and polymerizes to complete the pore (PubMed:26841934, PubMed:30111885, PubMed:30552328, PubMed:34752492, PubMed:4055801, PubMed:6177822).ACTIVITY REGULATION Membrane attack complex (MAC) assembly is inhibited by CD59, thereby protecting self-cells from damage during complement activation (PubMed:36797260). CD59 acts by preventing incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore (PubMed:36797260). MAC assembly is also inhibited by clusterin (CLU) chaperones that inhibit polymerization of C9 (PubMed:34667172). Specifically inhibited by the antibody aE11, thereby inhibiting MAC assembly (PubMed:36639734).SUBUNIT Homooligomer; about 20 C9 chains oligomerize to give rise to a huge beta-barrel that forms a 100 Angstrom diameter pore in target membranes (PubMed:26841934, PubMed:30111885, PubMed:34752492). Component of the membrane attack complex (MAC), composed of complement C5b, C6, C7, C8A, C8B, C8G and multiple copies of the pore-forming subunit C9 (PubMed:22832194, PubMed:26841837, PubMed:26841934, PubMed:27052168, PubMed:30552328, PubMed:31061395, PubMed:34752492, PubMed:6177822).INTERACTION Secreted as soluble monomer (PubMed:26841934, PubMed:30111885, PubMed:4055801, PubMed:9634479). Oligomerizes at target membranes, forming a pre-pore (PubMed:26841934, PubMed:30111885, PubMed:31061395, PubMed:4055801, PubMed:9634479). A conformation change then leads to the formation of a 100 Angstrom diameter pore (PubMed:26841934, PubMed:30111885, PubMed:31061395, PubMed:4055801, PubMed:9634479).TISSUE SPECIFICITY Plasma (at protein level).PTM Thrombin cleaves factor C9 to produce C9a and C9b.PTM Phosphorylation sites are present in the extracellular medium.PTM Initially, positions and connectivity of disulfide bonds were based on peptide sequencing done for the human protein (PubMed:8603752). The crystal structures for the human and mouse proteins corrected the positions and connectivities of the disulfide bonds (PubMed:30111885). The distance between Cys-57 and Cys-94 in the monomeric mouse protein precludes formation of a disulfide bond, contrary to what is seen in the structure of the human polymeric form of the protein (Probable).DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.SIMILARITY Belongs to the complement C6/C7/C8/C9 family.ONLINE INFORMATION C9 mutation db
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