CO9_HUMAN
ID CO9_HUMAN Reviewed; 559 AA.
AC P02748;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Complement component C9;
DE Contains:
DE RecName: Full=Complement component C9a;
DE Contains:
DE RecName: Full=Complement component C9b;
DE Flags: Precursor;
GN Name=C9;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=4018030; DOI=10.1002/j.1460-2075.1985.tb03639.x;
RA Stanley K.K., Kocher H.-P., Luzio J.P., Jackson P., Tschopp J.;
RT "The sequence and topology of human complement component C9.";
RL EMBO J. 4:375-382(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-559, AND PROTEIN SEQUENCE OF N-TERMINUS.
RX PubMed=6095282; DOI=10.1073/pnas.81.23.7298;
RA Discipio R.G., Gehring M.R., Podack E.R., Kan C.C., Hugli T.E., Fey G.H.;
RT "Nucleotide sequence of cDNA and derived amino acid sequence of human
RT complement component C9.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:7298-7302(1984).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 62-159.
RX PubMed=3219351; DOI=10.1021/bi00417a050;
RA Marazziti D., Eggertsen G., Fey G.H., Stanley K.K.;
RT "Relationships between the gene and protein structure in human complement
RT component C9.";
RL Biochemistry 27:6529-6534(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 27-559, VARIANT C9D GLY-119, FUNCTION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9634479; DOI=10.1007/s002510050415;
RA Witzel-Schloemp K., Hobart M.J., Fernie B.A., Orren A., Wuerzner R.,
RA Rittner C., Kaufmann T., Schneider P.M.;
RT "Heterogeneity in the genetic basis of human complement C9 deficiency.";
RL Immunogenetics 48:144-147(1998).
RN [6]
RP PARTIAL PROTEIN SEQUENCE, ELECTRON MICROSCOPY, FUNCTION, SUBCELLULAR
RP LOCATION, PROTEOLYTIC CLEAVAGE, AND GLYCOSYLATION AT ASN-277 AND ASN-415.
RX PubMed=4055801; DOI=10.1016/s0021-9258(17)38643-x;
RA DiScipio R.G., Hugli T.E.;
RT "The architecture of complement component C9 and poly(C9).";
RL J. Biol. Chem. 260:14802-14809(1985).
RN [7]
RP DISULFIDE BONDS, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=8603752; DOI=10.1016/0014-5793(95)01541-8;
RA Lengweiler S., Schaller J., Rickli E.E.;
RT "Identification of disulfide bonds in the ninth component (C9) of human
RT complement.";
RL FEBS Lett. 380:8-12(1996).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9212048; DOI=10.1203/00006450-199707000-00021;
RA Lassiter H.A., Walz B.M., Wilson J.L., Jung E., Calisi C.R.,
RA Goldsmith L.J., Wilson R.A., Morgan B.P., Feldhoff R.C.;
RT "The administration of complement component C9 enhances the survival of
RT neonatal rats with Escherichia coli sepsis.";
RL Pediatr. Res. 42:128-136(1997).
RN [9]
RP GLYCOSYLATION AT TRP-48 AND TRP-51.
RX PubMed=10551839; DOI=10.1074/jbc.274.46.32786;
RA Hofsteenge J., Blommers M., Hess D., Furmanek A., Miroshnichenko O.;
RT "The four terminal components of the complement system are C-mannosylated
RT on multiple tryptophan residues.";
RL J. Biol. Chem. 274:32786-32794(1999).
RN [10]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-415.
RC TISSUE=Plasma;
RX PubMed=14760718; DOI=10.1002/pmic.200300556;
RA Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.;
RT "Screening for N-glycosylated proteins by liquid chromatography mass
RT spectrometry.";
RL Proteomics 4:454-465(2004).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-277 AND ASN-415.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-415.
RC TISSUE=Platelet;
RX PubMed=16263699; DOI=10.1074/mcp.m500324-mcp200;
RA Lewandrowski U., Moebius J., Walter U., Sickmann A.;
RT "Elucidation of N-glycosylation sites on human platelet proteins: a
RT glycoproteomic approach.";
RL Mol. Cell. Proteomics 5:226-233(2006).
RN [13]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-277 AND ASN-415.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [14]
RP GLYCOSYLATION AT ASN-415.
RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core fucosylated
RT glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP 3D-STRUCTURE MODELING OF MEMBRANE-SPANNING DOMAIN (MSB).
RX PubMed=2395434; DOI=10.1016/0161-5890(90)90001-g;
RA Peitsch M.C., Amiguet P., Guy R., Brunner J., Maizel J.V. Jr., Tschopp J.;
RT "Localization and molecular modelling of the membrane-inserted domain of
RT the ninth component of human complement and perforin.";
RL Mol. Immunol. 27:589-602(1990).
RN [17]
RP ELECTRON MICROSCOPY, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22832194; DOI=10.1016/j.celrep.2012.02.003;
RA Hadders M.A., Bubeck D., Roversi P., Hakobyan S., Forneris F., Morgan B.P.,
RA Pangburn M.K., Llorca O., Lea S.M., Gros P.;
RT "Assembly and regulation of the membrane attack complex based on structures
RT of C5b6 and sC5b9.";
RL Cell Rep. 1:200-207(2012).
RN [18]
RP STRUCTURE BY ELECTRON MICROSCOPY (6.70 ANGSTROMS) OF 39-544, FUNCTION,
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=26841934; DOI=10.1038/ncomms10588;
RA Dudkina N.V., Spicer B.A., Reboul C.F., Conroy P.J., Lukoyanova N.,
RA Elmlund H., Law R.H., Ekkel S.M., Kondos S.C., Goode R.J., Ramm G.,
RA Whisstock J.C., Saibil H.R., Dunstone M.A.;
RT "Structure of the poly-C9 component of the complement membrane attack
RT complex.";
RL Nat. Commun. 7:10588-10588(2016).
RN [19] {ECO:0007744|PDB:6DLW}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS) OF 22-559, FUNCTION,
RP SUBCELLULAR LOCATION, SUBUNIT, DISULFIDE BONDS, AND MUTAGENESIS OF PHE-283
RP AND VAL-426.
RX PubMed=30111885; DOI=10.1038/s41467-018-05717-0;
RA Spicer B.A., Law R.H.P., Caradoc-Davies T.T., Ekkel S.M., Bayly-Jones C.,
RA Pang S.S., Conroy P.J., Ramm G., Radjainia M., Venugopal H.,
RA Whisstock J.C., Dunstone M.A.;
RT "The first transmembrane region of complement component-9 acts as a brake
RT on its self-assembly.";
RL Nat. Commun. 9:3266-3266(2018).
RN [20]
RP VARIANT ARMD15 SER-167.
RX PubMed=24036952; DOI=10.1038/ng.2741;
RA Seddon J.M., Yu Y., Miller E.C., Reynolds R., Tan P.L., Gowrisankar S.,
RA Goldstein J.I., Triebwasser M., Anderson H.E., Zerbib J., Kavanagh D.,
RA Souied E., Katsanis N., Daly M.J., Atkinson J.P., Raychaudhuri S.;
RT "Rare variants in CFI, C3 and C9 are associated with high risk of advanced
RT age-related macular degeneration.";
RL Nat. Genet. 45:1366-1370(2013).
CC -!- FUNCTION: Constituent of the membrane attack complex (MAC) that plays a
CC key role in the innate and adaptive immune response by forming pores in
CC the plasma membrane of target cells (PubMed:9634479, PubMed:9212048,
CC PubMed:26841934). C9 is the pore-forming subunit of the MAC
CC (PubMed:4055801, PubMed:26841934, PubMed:30111885).
CC {ECO:0000269|PubMed:26841934, ECO:0000269|PubMed:30111885,
CC ECO:0000269|PubMed:4055801, ECO:0000269|PubMed:9212048,
CC ECO:0000269|PubMed:9634479}.
CC -!- SUBUNIT: Component of the membrane attack complex (MAC). MAC assembly
CC is initiated by proteolytic cleavage of C5 into C5a and C5b. C5b binds
CC sequentially C6, C7, C8 and multiple copies of the pore-forming subunit
CC C9 (PubMed:22832194). About 20 C9 chains oligomerize to give rise to a
CC huge beta-barrel that forms a 100 Angstrom diameter pore in target
CC membranes (PubMed:26841934, PubMed:30111885).
CC {ECO:0000269|PubMed:22832194, ECO:0000269|PubMed:26841934,
CC ECO:0000269|PubMed:30111885}.
CC -!- INTERACTION:
CC P02748; P00441: SOD1; NbExp=3; IntAct=EBI-6677628, EBI-990792;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22832194,
CC ECO:0000269|PubMed:26841934, ECO:0000269|PubMed:8603752,
CC ECO:0000269|PubMed:9212048, ECO:0000269|PubMed:9634479}. Target cell
CC membrane {ECO:0000269|PubMed:26841934, ECO:0000269|PubMed:30111885,
CC ECO:0000269|PubMed:9212048}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:26841934}. Note=Secreted as soluble monomer.
CC Oligomerizes at target membranes, forming a pre-pore. A conformation
CC change then leads to the formation of a 100 Angstrom diameter pore.
CC {ECO:0000269|PubMed:26841934, ECO:0000269|PubMed:30111885,
CC ECO:0000269|PubMed:4055801, ECO:0000269|PubMed:9634479}.
CC -!- TISSUE SPECIFICITY: Plasma (at protein level).
CC {ECO:0000269|PubMed:22832194, ECO:0000269|PubMed:26841934,
CC ECO:0000269|PubMed:8603752, ECO:0000269|PubMed:9212048,
CC ECO:0000269|PubMed:9634479}.
CC -!- PTM: Thrombin cleaves factor C9 to produce C9a and C9b.
CC {ECO:0000269|PubMed:4055801}.
CC -!- PTM: Phosphorylation sites are present in the extracellular medium.
CC -!- PTM: Initially, positions and connectivity of disulfide bonds were
CC based on peptide sequencing done for the human protein
CC (PubMed:8603752). The crystal structures for the human and mouse
CC proteins corrected the positions and connectivities of the disulfide
CC bonds (PubMed:30111885). The distance between Cys-57 and Cys-94 in the
CC monomeric mouse protein precludes formation of a disulfide bond,
CC contrary to what is seen in the structure of the human polymeric form
CC of the protein (Probable). {ECO:0000269|PubMed:30111885,
CC ECO:0000269|PubMed:8603752, ECO:0000305|PubMed:30111885}.
CC -!- DISEASE: Complement component 9 deficiency (C9D) [MIM:613825]: A rare
CC defect of the complement classical pathway associated with
CC susceptibility to severe recurrent infections predominantly by
CC Neisseria gonorrhoeae or Neisseria meningitidis. Some patients may
CC develop dermatomyositis. {ECO:0000269|PubMed:9634479}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- DISEASE: Macular degeneration, age-related, 15 (ARMD15) [MIM:615591]: A
CC form of age-related macular degeneration, a multifactorial eye disease
CC and the most common cause of irreversible vision loss in the developed
CC world. In most patients, the disease is manifest as ophthalmoscopically
CC visible yellowish accumulations of protein and lipid that lie beneath
CC the retinal pigment epithelium and within an elastin-containing
CC structure known as Bruch membrane. {ECO:0000269|PubMed:24036952}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the complement C6/C7/C8/C9 family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=C9base; Note=C9 mutation db;
CC URL="http://structure.bmc.lu.se/idbase/C9base/";
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DR EMBL; X02176; CAA26117.1; -; mRNA.
DR EMBL; BC020721; AAH20721.1; -; mRNA.
DR EMBL; K02766; AAA51889.1; -; mRNA.
DR EMBL; J02833; AAA51890.1; -; Genomic_DNA.
DR EMBL; Y08545; CAA69849.1; -; Genomic_DNA.
DR EMBL; Y08546; CAA69849.1; JOINED; Genomic_DNA.
DR EMBL; Y08547; CAA69849.1; JOINED; Genomic_DNA.
DR EMBL; Y08548; CAA69849.1; JOINED; Genomic_DNA.
DR EMBL; Y08549; CAA69849.1; JOINED; Genomic_DNA.
DR EMBL; Y08550; CAA69849.1; JOINED; Genomic_DNA.
DR EMBL; Y08551; CAA69849.1; JOINED; Genomic_DNA.
DR EMBL; Y08552; CAA69849.1; JOINED; Genomic_DNA.
DR EMBL; Y08553; CAA69849.1; JOINED; Genomic_DNA.
DR EMBL; Y08554; CAA69849.1; JOINED; Genomic_DNA.
DR CCDS; CCDS3929.1; -.
DR PIR; A59363; C9HU.
DR RefSeq; NP_001728.1; NM_001737.4.
DR PDB; 5FMW; EM; 6.70 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=39-544.
DR PDB; 6DLW; EM; 3.90 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=22-559.
DR PDB; 6H03; EM; 5.60 A; G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X=22-559.
DR PDB; 6H04; EM; 5.60 A; G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X=22-559.
DR PDB; 7NYC; EM; 3.50 A; G/H/I=22-559.
DR PDB; 7NYD; EM; 3.30 A; G/H=22-559.
DR PDBsum; 5FMW; -.
DR PDBsum; 6DLW; -.
DR PDBsum; 6H03; -.
DR PDBsum; 6H04; -.
DR PDBsum; 7NYC; -.
DR PDBsum; 7NYD; -.
DR AlphaFoldDB; P02748; -.
DR SMR; P02748; -.
DR BioGRID; 107196; 18.
DR ComplexPortal; CPX-6159; Membrane attack complex.
DR DIP; DIP-1124N; -.
DR ELM; P02748; -.
DR IntAct; P02748; 5.
DR STRING; 9606.ENSP00000263408; -.
DR BindingDB; P02748; -.
DR ChEMBL; CHEMBL4295693; -.
DR DrugBank; DB09130; Copper.
DR GlyConnect; 1150; 8 N-Linked glycans (2 sites).
DR GlyGen; P02748; 11 sites, 10 N-linked glycans (2 sites), 4 O-linked glycans (5 sites).
DR iPTMnet; P02748; -.
DR PhosphoSitePlus; P02748; -.
DR BioMuta; C9; -.
DR DMDM; 1352108; -.
DR CPTAC; non-CPTAC-1110; -.
DR CPTAC; non-CPTAC-1111; -.
DR CPTAC; non-CPTAC-2656; -.
DR jPOST; P02748; -.
DR MassIVE; P02748; -.
DR MaxQB; P02748; -.
DR PaxDb; P02748; -.
DR PeptideAtlas; P02748; -.
DR PRIDE; P02748; -.
DR ProteomicsDB; 51564; -.
DR Antibodypedia; 3685; 551 antibodies from 39 providers.
DR DNASU; 735; -.
DR Ensembl; ENST00000263408.5; ENSP00000263408.4; ENSG00000113600.11.
DR GeneID; 735; -.
DR KEGG; hsa:735; -.
DR MANE-Select; ENST00000263408.5; ENSP00000263408.4; NM_001737.5; NP_001728.1.
DR UCSC; uc003jlv.5; human.
DR CTD; 735; -.
DR DisGeNET; 735; -.
DR GeneCards; C9; -.
DR HGNC; HGNC:1358; C9.
DR HPA; ENSG00000113600; Tissue enriched (liver).
DR MalaCards; C9; -.
DR MIM; 120940; gene.
DR MIM; 613825; phenotype.
DR MIM; 615591; phenotype.
DR neXtProt; NX_P02748; -.
DR OpenTargets; ENSG00000113600; -.
DR Orphanet; 169150; Immunodeficiency due to a late component of complement deficiency.
DR Orphanet; 279; NON RARE IN EUROPE: Age-related macular degeneration.
DR PharmGKB; PA25968; -.
DR VEuPathDB; HostDB:ENSG00000113600; -.
DR eggNOG; ENOG502QWHM; Eukaryota.
DR GeneTree; ENSGT00940000159777; -.
DR HOGENOM; CLU_032453_2_0_1; -.
DR InParanoid; P02748; -.
DR OMA; WASSIND; -.
DR OrthoDB; 787014at2759; -.
DR PhylomeDB; P02748; -.
DR TreeFam; TF330498; -.
DR PathwayCommons; P02748; -.
DR Reactome; R-HSA-166665; Terminal pathway of complement.
DR Reactome; R-HSA-977606; Regulation of Complement cascade.
DR SignaLink; P02748; -.
DR SIGNOR; P02748; -.
DR BioGRID-ORCS; 735; 8 hits in 1063 CRISPR screens.
DR ChiTaRS; C9; human.
DR GenomeRNAi; 735; -.
DR Pharos; P02748; Tchem.
DR PRO; PR:P02748; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P02748; protein.
DR Bgee; ENSG00000113600; Expressed in right lobe of liver and 93 other tissues.
DR Genevisible; P02748; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005579; C:membrane attack complex; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0001906; P:cell killing; IDA:UniProtKB.
DR GO; GO:0006956; P:complement activation; IBA:GO_Central.
DR GO; GO:0006957; P:complement activation, alternative pathway; IEA:UniProtKB-KW.
DR GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR GO; GO:0050778; P:positive regulation of immune response; IC:ComplexPortal.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR CDD; cd00112; LDLa; 1.
DR Gene3D; 2.20.100.10; -; 1.
DR Gene3D; 4.10.400.10; -; 1.
DR InterPro; IPR037567; Complement_C9.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR023415; LDLR_class-A_CS.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR InterPro; IPR001862; MAC_perforin.
DR InterPro; IPR020864; MACPF.
DR InterPro; IPR020863; MACPF_CS.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR PANTHER; PTHR45742:SF3; PTHR45742:SF3; 1.
DR Pfam; PF00057; Ldl_recept_a; 1.
DR Pfam; PF01823; MACPF; 1.
DR Pfam; PF00090; TSP_1; 1.
DR PRINTS; PR00764; COMPLEMENTC9.
DR SMART; SM00192; LDLa; 1.
DR SMART; SM00457; MACPF; 1.
DR SMART; SM00209; TSP1; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR SUPFAM; SSF57424; SSF57424; 1.
DR SUPFAM; SSF82895; SSF82895; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS01209; LDLRA_1; 1.
DR PROSITE; PS50068; LDLRA_2; 1.
DR PROSITE; PS00279; MACPF_1; 1.
DR PROSITE; PS51412; MACPF_2; 1.
DR PROSITE; PS50092; TSP1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Age-related macular degeneration;
KW Complement alternate pathway; Complement pathway; Cytolysis;
KW Direct protein sequencing; Disease variant; Disulfide bond;
KW EGF-like domain; Glycoprotein; Immunity; Innate immunity; Membrane;
KW Membrane attack complex; Phosphoprotein; Reference proteome; Secreted;
KW Signal; Target cell membrane; Target membrane; Transmembrane;
KW Transmembrane beta strand.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:6095282"
FT CHAIN 22..559
FT /note="Complement component C9"
FT /id="PRO_0000023602"
FT CHAIN 22..265
FT /note="Complement component C9a"
FT /id="PRO_0000023603"
FT CHAIN 266..559
FT /note="Complement component C9b"
FT /id="PRO_0000023604"
FT TRANSMEM 314..330
FT /note="Beta stranded"
FT /evidence="ECO:0000255"
FT TRANSMEM 335..354
FT /note="Beta stranded"
FT /evidence="ECO:0000255"
FT DOMAIN 42..95
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 99..136
FT /note="LDL-receptor class A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 138..509
FT /note="MACPF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00745"
FT DOMAIN 510..540
FT /note="EGF-like"
FT SITE 265..266
FT /note="Cleavage; by thrombin"
FT CARBOHYD 48
FT /note="C-linked (Man) tryptophan"
FT /evidence="ECO:0000269|PubMed:10551839"
FT CARBOHYD 51
FT /note="C-linked (Man) tryptophan; partial"
FT /evidence="ECO:0000269|PubMed:10551839"
FT CARBOHYD 277
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:4055801"
FT CARBOHYD 415
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:14760718,
FT ECO:0000269|PubMed:16263699, ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:4055801"
FT DISULFID 43..78
FT /evidence="ECO:0000269|PubMed:30111885,
FT ECO:0000269|PubMed:8603752, ECO:0007744|PDB:6DLW"
FT DISULFID 54..88
FT /evidence="ECO:0000269|PubMed:30111885,
FT ECO:0007744|PDB:6DLW"
FT DISULFID 57..94
FT /evidence="ECO:0000269|PubMed:30111885,
FT ECO:0007744|PDB:6DLW"
FT DISULFID 101..112
FT /evidence="ECO:0000269|PubMed:30111885,
FT ECO:0000269|PubMed:8603752, ECO:0007744|PDB:6DLW"
FT DISULFID 107..125
FT /evidence="ECO:0000269|PubMed:30111885,
FT ECO:0000269|PubMed:8603752, ECO:0007744|PDB:6DLW"
FT DISULFID 119..134
FT /evidence="ECO:0000269|PubMed:30111885,
FT ECO:0000269|PubMed:8603752, ECO:0007744|PDB:6DLW"
FT DISULFID 142..181
FT /evidence="ECO:0000269|PubMed:30111885,
FT ECO:0000269|PubMed:8603752, ECO:0007744|PDB:6DLW"
FT DISULFID 510..526
FT /evidence="ECO:0000269|PubMed:30111885,
FT ECO:0000269|PubMed:8603752, ECO:0007744|PDB:6DLW"
FT DISULFID 513..528
FT /evidence="ECO:0000269|PubMed:30111885,
FT ECO:0000269|PubMed:8603752, ECO:0007744|PDB:6DLW"
FT DISULFID 530..539
FT /evidence="ECO:0000269|PubMed:30111885,
FT ECO:0000269|PubMed:8603752, ECO:0007744|PDB:6DLW"
FT VARIANT 5
FT /note="R -> W (in dbSNP:rs700233)"
FT /id="VAR_022024"
FT VARIANT 119
FT /note="C -> G (in C9D; dbSNP:rs121909593)"
FT /evidence="ECO:0000269|PubMed:9634479"
FT /id="VAR_012648"
FT VARIANT 127
FT /note="D -> Y (in dbSNP:rs696763)"
FT /id="VAR_050481"
FT VARIANT 167
FT /note="P -> S (in ARMD15; dbSNP:rs34882957)"
FT /evidence="ECO:0000269|PubMed:24036952"
FT /id="VAR_070940"
FT VARIANT 203
FT /note="I -> V (in dbSNP:rs13361416)"
FT /id="VAR_027651"
FT VARIANT 279
FT /note="T -> S (in dbSNP:rs34625111)"
FT /id="VAR_033802"
FT VARIANT 427
FT /note="S -> T (in dbSNP:rs34421659)"
FT /id="VAR_061503"
FT MUTAGEN 283
FT /note="F->C: Creates an artifactual disulfide bond that
FT prevents the conformation change required for
FT oligomerization and pore formation; when associated with C-
FT 427."
FT /evidence="ECO:0000269|PubMed:30111885"
FT MUTAGEN 426
FT /note="V->C: Creates an artifactual disulfide bond that
FT prevents the conformation change required for
FT oligomerization and pore formation; when associated with C-
FT 283."
FT /evidence="ECO:0000269|PubMed:30111885"
FT CONFLICT 43
FT /note="C -> R (in Ref. 3; AAA51889)"
FT /evidence="ECO:0000305"
FT CONFLICT 314
FT /note="Missing (in Ref. 3; AAA51889)"
FT /evidence="ECO:0000305"
FT CONFLICT 417
FT /note="T -> P (in Ref. 3; AAA51889)"
FT /evidence="ECO:0000305"
FT STRAND 41..45
FT /evidence="ECO:0007829|PDB:7NYD"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 60..64
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 67..72
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 102..106
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:7NYD"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 119..122
FT /evidence="ECO:0007829|PDB:7NYD"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:7NYD"
FT TURN 131..133
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:7NYC"
FT STRAND 141..144
FT /evidence="ECO:0007829|PDB:7NYC"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:7NYD"
FT TURN 162..165
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 199..203
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 207..225
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 282..308
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 310..312
FT /evidence="ECO:0007829|PDB:7NYD"
FT HELIX 317..324
FT /evidence="ECO:0007829|PDB:7NYD"
FT HELIX 332..342
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 344..373
FT /evidence="ECO:0007829|PDB:7NYD"
FT HELIX 375..381
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 414..432
FT /evidence="ECO:0007829|PDB:7NYD"
FT HELIX 434..443
FT /evidence="ECO:0007829|PDB:7NYD"
FT HELIX 452..461
FT /evidence="ECO:0007829|PDB:7NYD"
FT TURN 462..464
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 467..475
FT /evidence="ECO:0007829|PDB:7NYD"
FT HELIX 476..479
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 482..484
FT /evidence="ECO:0007829|PDB:7NYC"
FT HELIX 487..503
FT /evidence="ECO:0007829|PDB:7NYD"
FT HELIX 507..509
FT /evidence="ECO:0007829|PDB:7NYC"
FT STRAND 520..522
FT /evidence="ECO:0007829|PDB:7NYD"
FT STRAND 525..527
FT /evidence="ECO:0007829|PDB:7NYD"
FT TURN 531..533
FT /evidence="ECO:0007829|PDB:7NYD"
SQ SEQUENCE 559 AA; 63173 MW; 7403F6AD77B3ECE1 CRC64;
MSACRSFAVA ICILEISILT AQYTTSYDPE LTESSGSASH IDCRMSPWSE WSQCDPCLRQ
MFRSRSIEVF GQFNGKRCTD AVGDRRQCVP TEPCEDAEDD CGNDFQCSTG RCIKMRLRCN
GDNDCGDFSD EDDCESEPRP PCRDRVVEES ELARTAGYGI NILGMDPLST PFDNEFYNGL
CNRDRDGNTL TYYRRPWNVA SLIYETKGEK NFRTEHYEEQ IEAFKSIIQE KTSNFNAAIS
LKFTPTETNK AEQCCEETAS SISLHGKGSF RFSYSKNETY QLFLSYSSKK EKMFLHVKGE
IHLGRFVMRN RDVVLTTTFV DDIKALPTTY EKGEYFAFLE TYGTHYSSSG SLGGLYELIY
VLDKASMKRK GVELKDIKRC LGYHLDVSLA FSEISVGAEF NKDDCVKRGE GRAVNITSEN
LIDDVVSLIR GGTRKYAFEL KEKLLRGTVI DVTDFVNWAS SINDAPVLIS QKLSPIYNLV
PVKMKNAHLK KQNLERAIED YINEFSVRKC HTCQNGGTVI LMDGKCLCAC PFKFEGIACE
ISKQKISEGL PALEFPNEK
