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Commun.710588STRUCTURE BY ELECTRON MICROSCOPY (6.70 ANGSTROMS) OF 39-544FUNCTIONSUBUNITSUBCELLULAR LOCATIONThe first transmembrane region of complement component-9 acts as a brake on its self-assembly.Spicer B.A.Law R.H.P.Caradoc-Davies T.T.Ekkel S.M.Bayly-Jones C.Pang S.S.Conroy P.J.Ramm G.Radjainia M.Venugopal H.Whisstock J.C.Dunstone M.A.doi:10.1038/s41467-018-05717-02018Nat. Commun.93266STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS) OF 22-559FUNCTIONSUBCELLULAR LOCATIONSUBUNITDISULFIDE BONDSMUTAGENESIS OF PHE-283 AND VAL-426Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration.Seddon J.M.Yu Y.Miller E.C.Reynolds R.Tan P.L.Gowrisankar S.Goldstein J.I.Triebwasser M.Anderson H.E.Zerbib J.Kavanagh D.Souied E.Katsanis N.Daly M.J.Atkinson J.P.Raychaudhuri S.doi:10.1038/ng.27412013Nat. Genet.451366-1370VARIANT ARMD15 SER-167C9base; C9 mutation dbC9HU6.70A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=39-5443.90A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=22-5595.60G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X=22-5595.60G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X=22-5593.50G/H/I=22-5593.30G/H=22-5593.30H/I/J=1-5593.30H/I=1-5593.20A/C/G=21-55918Membrane attack complex6Copper8 N-Linked glycans (2 sites)8 sites, 12 glycans11 sites, 10 N-linked glycans (2 sites), 4 O-linked glycans (5 sites)761 antibodies from 39 providershumanC9Tissue enriched (liver)genephenotypephenotypeImmunodeficiency due to a late component of complement deficiencyNON RARE IN EUROPE: Age-related macular degenerationEukaryotaTerminal pathway of complementRegulation of Complement cascade9 hits in 1140 CRISPR screenshumanTchemProteinExpressed in right lobe of liver and 94 other cell types or tissuesLDLaLamininLow-density Lipoprotein ReceptorThrombospondin type-1 (TSP1) repeatGrowth_fac_rcpt_cys_sfLDL_receptor-like_sfLDLR_class-A_CSLDrepeatLR_classA_rptMAC_perforinMACPFMACPF_CSTSP1_rptTSP1_rpt_sfCOMPLEMENT COMPONENT C6COMPLEMENT COMPONENT C9Ldl_recept_aMACPFTSP_1COMPLEMENTC9LDLaMACPFTSP1Growth factor receptor domainLDL receptor-like moduleTSP-1 type 1 repeatEGF_1EGF_2LDLRA_1LDLRA_2MACPF_1MACPF_2TSP1HSComplement component C9Complement component C9aComplement component C9bC9Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells (PubMed:9634479, PubMed:9212048, PubMed:26841934). C9 is the pore-forming subunit of the MAC (PubMed:4055801, PubMed:26841934, PubMed:30111885).Component of the membrane attack complex (MAC). MAC assembly is initiated by proteolytic cleavage of C5 into C5a and C5b. C5b binds sequentially C6, C7, C8 and multiple copies of the pore-forming subunit C9 (PubMed:22832194). 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).Secreted as soluble monomer. Oligomerizes at target membranes, forming a pre-pore. A conformation change then leads to the formation of a 100 Angstrom diameter pore.Plasma (at protein level).Thrombin cleaves factor C9 to produce C9a and C9b.Phosphorylation sites are present in the extracellular medium.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 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.Belongs to the complement C6/C7/C8/C9 family.121Complement component C96097922559Complement component C9a27825265Complement component C9b33171266Beta stranded314330Beta stranded335354TSP type-14295LDL-receptor class A99136MACPF138509EGF-like510540Cleavage; by thrombinC-linked (Man) tryptophan48C-linked (Man) tryptophan; partial51N-linked (GlcNAc...) asparagine277N-linked (GlcNAc...) (complex) asparagine415437854885794101112107125119134142181526513528530539W5In C9D.GY127In ARMD15.S167V203S279T427Creates an artifactual disulfide bond that prevents the conformation change required for oligomerization and pore formation; when associated with C-427.C283Creates an artifactual disulfide bond that prevents the conformation change required for oligomerization and pore formation; when associated with C-283.C426RP41741455658606467728287102106108110115117122124126131133135137141144153155159161162165166168199207225282308310312317324332342344373375381414432434443452461462464467475476479482484487503507520522525527531533false3SOD11996-02-012true63173fa38085049000e392f731b053a5505f4MSACRSFAVAICILEISILTAQYTTSYDPELTESSGSASHIDCRMSPWSEWSQCDPCLRQMFRSRSIEVFGQFNGKRCTDAVGDRRQCVPTEPCEDAEDDCGNDFQCSTGRCIKMRLRCNGDNDCGDFSDEDDCESEPRPPCRDRVVEESELARTAGYGINILGMDPLSTPFDNEFYNGLCNRDRDGNTLTYYRRPWNVASLIYETKGEKNFRTEHYEEQIEAFKSIIQEKTSNFNAAISLKFTPTETNKAEQCCEETASSISLHGKGSFRFSYSKNETYQLFLSYSSKKEKMFLHVKGEIHLGRFVMRNRDVVLTTTFVDDIKALPTTYEKGEYFAFLETYGTHYSSSGSLGGLYELIYVLDKASMKRKGVELKDIKRCLGYHLDVSLAFSEISVGAEFNKDDCVKRGEGRAVNITSENLIDDVVSLIRGGTRKYAFELKEKLLRGTVIDVTDFVNWASSINDAPVLISQKLSPIYNLVPVKMKNAHLKKQNLERAIEDYINEFSVRKCHTCQNGGTVILMDGKCLCACPFKFEGIACEISKQKISEGLPALEFPNEKtruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetrue