C9

Summary

Gene Symbol: C9
Description: complement C9
Alias: ARMD15, C9D, complement component C9, complement component 9
Species: human
Products:     C9

Top Publications

  1. Ninomiya H, Sims P. The human complement regulatory protein CD59 binds to the alpha-chain of C8 and to the "b"domain of C9. J Biol Chem. 1992;267:13675-80 pubmed
    ..between 125I-CD59 and the isolated components of human complement membrane attack complex, C5b6, C7, C8, and C9. By density gradient analysis, we were unable to detect interaction of 125I-CD59 with any of these isolated ..
  2. Ichikawa E, Furuta J, Kawachi Y, Imakado S, Otsuka F. Hereditary complement (C9) deficiency associated with dermatomyositis. Br J Dermatol. 2001;144:1080-3 pubmed
    A 28-year-old Japanese woman with hereditary complement (C9) deficiency and dermatomyositis is reported. She had a 3-year history of facial erythema and a 1-month history of progressive muscle weakness...
  3. Khajoee V, Ihara K, Kira R, Takemoto M, Torisu H, Sakai Y, et al. Founder effect of the C9 R95X mutation in Orientals. Hum Genet. 2003;112:244-8 pubmed
    A nonsense mutation at codon 95 (R95X) in the C9 gene is responsible for most Japanese C9 deficiency (C9D) cases, with a carrier frequency of 6.7%...
  4. Hamad O, Nilsson P, Wouters D, Lambris J, Ekdahl K, Nilsson B. Complement component C3 binds to activated normal platelets without preceding proteolytic activation and promotes binding to complement receptor 1. J Immunol. 2010;184:2686-92 pubmed publisher
    ..C1q, C4, C3, and C9 were found to bind to thrombin receptor-activating peptide-activated platelets in lepirudin-anticoagulated platelet-..
  5. Moskovich O, Herzog L, Ehrlich M, Fishelson Z. Caveolin-1 and dynamin-2 are essential for removal of the complement C5b-9 complex via endocytosis. J Biol Chem. 2012;287:19904-15 pubmed publisher
    ..Our results show that Cav-1 and dynamin-2 (but not clathrin) support cell resistance to CDC, probably by facilitating purging of the C5b-9 complexes by endocytosis and exo-vesiculation. ..
  6. Shi H, Williams J, Guo L, Stampoulis D, Francesca Cordeiro M, Moss S. Exposure to the complement C5b-9 complex sensitizes 661W photoreceptor cells to both apoptosis and necroptosis. Apoptosis. 2015;20:433-43 pubmed publisher
    ..Our observations provide new insight into the potential role of the complement system in photoreceptor loss, with implications for the molecular aetiology of retinal disease. ..
  7. Witzel Schlömp K, Rittner C, Schneider P. The human complement C9 gene: structural analysis of the 5' gene region and genetic polymorphism studies. Eur J Immunogenet. 2001;28:515-22 pubmed
    b>C9 is the last of the human complement components creating the membrane attack complex. The single chain serum protein is encoded by a gene located on chromosome 5p13 that is composed of 11 exons...
  8. Stewart J, Kolb W, Sodetz J. Evidence that C5b recognizes and mediates C8 incorporation into the cytolytic complex of complement. J Immunol. 1987;139:1960-4 pubmed
    ..Simultaneous interaction of C8 with C5 and C9 in solution suggests that during assembly of the cytolytic C5b-9 complex on membranes, C8 binds to C5b-7 through ..
  9. Kim H, Meyer K, Di Bisceglie A, Ray R. Hepatitis C virus suppresses C9 complement synthesis and impairs membrane attack complex function. J Virol. 2013;87:5858-67 pubmed publisher
    ..In this study, we examined whether HCV regulates the membrane attack complex (MAC) via complement component C9. MAC is composed of C5b to C9 (C5b-9) and mediates cell lysis of invaded pathogens...

More Information

Publications49

  1. Narayanasamy A, Ahn J, Sung H, Kong D, Ha K, Lee S, et al. Fucosylated glycoproteomic approach to identify a complement component 9 associated with squamous cell lung cancer (SQLC). J Proteomics. 2011;74:2948-58 pubmed publisher
    ..From comparative proteomic analysis, we selected the C9 protein...
  2. Hallström T, Siegel C, Morgelin M, Kraiczy P, Skerka C, Zipfel P. CspA from Borrelia burgdorferi inhibits the terminal complement pathway. MBio. 2013;4: pubmed publisher
    ..Borrelial CspA binds the human terminal complement components C7 and C9 and blocks assembly and membrane insertion of the terminal complement complex (TCC)...
  3. Chang C, Husler T, Zhao J, Wiedmer T, Sims P. Identity of a peptide domain of human C9 that is bound by the cell-surface complement inhibitor, CD59. J Biol Chem. 1994;269:26424-30 pubmed
    ..in the alpha-chain subunit of human C8, as well as within the C9b domain (amino acid residues 245-538) of human C9, during assembly of the C5b-9 complex on the target membrane (Ninomiya, H., and Sims, P. J. (1992) J. Biol. Chem...
  4. Lengweiler S, Schaller J, Rickli E. Identification of disulfide bonds in the ninth component (C9) of human complement. FEBS Lett. 1996;380:8-12 pubmed
    b>C9 is the most abundant protein of the membrane attack complex of complement...
  5. Slade D, Chiswell B, Sodetz J. Functional studies of the MACPF domain of human complement protein C8alpha reveal sites for simultaneous binding of C8beta, C8gamma, and C9. Biochemistry. 2006;45:5290-6 pubmed
    ..C8alpha, C8beta, and complement components C6, C7, and C9 form the MAC family of proteins...
  6. Wickham S, Hotze E, Farrand A, Polekhina G, Nero T, Tomlinson S, et al. Mapping the intermedilysin-human CD59 receptor interface reveals a deep correspondence with the binding site on CD59 for complement binding proteins C8alpha and C9. J Biol Chem. 2011;286:20952-62 pubmed publisher
    ..a remarkably deep correspondence between the hCD59 binding site for ILY and that for the MAC proteins C8? and C9. ILY disengages from hCD59 during the prepore to pore transition, suggesting that loss of this interaction is ..
  7. Hofsteenge J, Blommers M, Hess D, Furmanek A, Miroshnichenko O. The four terminal components of the complement system are C-mannosylated on multiple tryptophan residues. J Biol Chem. 1999;274:32786-94 pubmed
    ..and to learn more about its mechanism, the terminal components of the human complement system (C6, C7, C8,and C9), which contain multiple and complex recognition motifs, were examined...
  8. Coto E, Martinez Naves E, Dominguez O, DiScipio R, Urra J, Lopez Larrea C. DNA polymorphisms and linkage relationship of the human complement component C6, C7, and C9 genes. Immunogenetics. 1991;33:184-7 pubmed
    In this report we describe the linkage between genes encoding human complement components C6, C7, and C9. Polymorphisms have been described at the DNA level for the C7 and C9 genes...
  9. Bae J, Pasaje C, Park B, Cheong H, Kim J, Park T, et al. Genetic analysis of complement component 9 (C9) polymorphisms with clearance of hepatitis B virus infection. Dig Dis Sci. 2011;56:2735-41 pubmed publisher
    The complement component 9 (C9), a major cytolytic protein in the complement system, plays an important role in the immunological process...
  10. Yang L, Li R, Meri S, Rogers J, Shen Y. Deficiency of complement defense protein CD59 may contribute to neurodegeneration in Alzheimer's disease. J Neurosci. 2000;20:7505-9 pubmed
    ..and hippocampus of Alzheimer's disease (AD) compared with nondemented elderly (ND) patients, whereas complement component 9, a final component to form MAC, is significantly increased...
  11. Witzel Schlömp K, Hobart M, Fernie B, Orren A, Wurzner R, Rittner C, et al. Heterogeneity in the genetic basis of human complement C9 deficiency. Immunogenetics. 1998;48:144-7 pubmed
  12. Fan W, Cheng J, Zhang S, Liu X. Cloning and functions of the HBxAg-binding protein XBP1. Mol Med Rep. 2013;7:618-22 pubmed publisher
  13. Saksens N, Geerlings M, Bakker B, Schick T, Daha M, Fauser S, et al. Rare Genetic Variants Associated With Development of Age-Related Macular Degeneration. JAMA Ophthalmol. 2016;134:287-93 pubmed publisher
    Rare variants in the complement genes CFH, CFI, C9, and C3 have been found to be highly associated with age-related macular degeneration (AMD); however, the effect on clinical characteristics and familial segregation by these variants is ..
  14. Abbott C, West L, Povey S, Jeremiah S, Murad Z, DiScipio R, et al. The gene for human complement component C9 mapped to chromosome 5 by polymerase chain reaction. Genomics. 1989;4:606-9 pubmed
    The gene for human complement component C9 has been mapped to chromosome 5...
  15. Rossi V, Wang Y, ESSER A. Topology of the membrane-bound form of complement protein C9 probed by glycosylation mapping, anti-peptide antibody binding, and disulfide modification. Mol Immunol. 2010;47:1553-60 pubmed publisher
    The two N-linked oligosaccharides in native human C9 were deleted by site-specific mutagenesis. This aglycosyl-C9 did not differ from its native form in hemolytic and bactericidal activity...
  16. Kabut J, Kondera Anasz Z, Sikora J, Mielczarek Palacz A. Levels of complement components iC3b, C3c, C4, and SC5b-9 in peritoneal fluid and serum of infertile women with endometriosis. Fertil Steril. 2007;88:1298-303 pubmed
    ..The impairment of the mechanisms involved in the regulation of activation of complement system may be an important factor in the pathogenesis of endometriosis and endometriosis-associated infertility. ..
  17. Pilzer D, Saar M, Koya K, Fishelson Z. Mortalin inhibitors sensitize K562 leukemia cells to complement-dependent cytotoxicity. Int J Cancer. 2010;126:1428-35 pubmed publisher
    ..In the presence of MKT-077, the direct binding of mortalin to complement C9, the major MAC component, is inhibited. The tumor suppressor protein p53 is a known mortalin client protein...
  18. Witzel Schlömp K, Spath P, Hobart M, Fernie B, Rittner C, Kaufmann T, et al. The human complement C9 gene: identification of two mutations causing deficiency and revision of the gene structure. J Immunol. 1997;158:5043-9 pubmed
    The ninth component of human complement (C9) is the last of the terminal complement components creating the membrane attack complex. C9 is a single-chain serum protein that is encoded by a gene located on chromosome 5p...
  19. Nishiguchi K, Yasuma T, Tomida D, Nakamura M, Ishikawa K, Kikuchi M, et al. C9-R95X polymorphism in patients with neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci. 2012;53:508-12 pubmed publisher
    A non-sense mutation at codon 95 in the gene encoding complement factor C9 (C9-R95X) is found most frequently among Japanese...
  20. Marazziti D, Eggertsen G, Fey G, Stanley K. Relationships between the gene and protein structure in human complement component C9. Biochemistry. 1988;27:6529-34 pubmed
    Human complement component C9 is a multidomain protein for which a large number of surface topographical features have been determined...
  21. DiScipio R, Gehring M, Podack E, Kan C, Hugli T, Fey G. Nucleotide sequence of cDNA and derived amino acid sequence of human complement component C9. Proc Natl Acad Sci U S A. 1984;81:7298-302 pubmed
    The nucleotide sequence coding for the ninth component of human complement (C9) has been determined and the corresponding amino acid sequence has been derived...
  22. Moskovich O, Fishelson Z. Live cell imaging of outward and inward vesiculation induced by the complement c5b-9 complex. J Biol Chem. 2007;282:29977-86 pubmed
    ..To gain an insight into the route of MAC removal, human C9 was tagged with Alexa Fluor 488 and traced within live cells...
  23. Fosbrink M, Cudrici C, Tegla C, Soloviova K, Ito T, Vlaicu S, et al. Response gene to complement 32 is required for C5b-9 induced cell cycle activation in endothelial cells. Exp Mol Pathol. 2009;86:87-94 pubmed publisher
    ..All these data together suggest that cell cycle induction by C5b-9 in AEC is RGC-32 dependent and this is in part through regulation of Akt and growth factor release. ..
  24. Hadders M, Bubeck D, Roversi P, Hakobyan S, Forneris F, Morgan B, et al. Assembly and regulation of the membrane attack complex based on structures of C5b6 and sC5b9. Cell Rep. 2012;1:200-7 pubmed publisher
    ..through sideways alignment of the central MAC-perforin (MACPF) domains, resulting in a C5b6-C7-C8β-C8α-C9 arc. Soluble regulatory proteins below the arc indicate a potential dual mechanism in protection from pore formation...
  25. Dudkina N, Spicer B, Reboul C, Conroy P, Lukoyanova N, Elmlund H, et al. Structure of the poly-C9 component of the complement membrane attack complex. Nat Commun. 2016;7:10588 pubmed publisher
    The membrane attack complex (MAC)/perforin-like protein complement component 9 (C9) is the major component of the MAC, a multi-protein complex that forms pores in the membrane of target pathogens...
  26. Kira R, Ihara K, Takada H, Gondo K, Hara T. Nonsense mutation in exon 4 of human complement C9 gene is the major cause of Japanese complement C9 deficiency. Hum Genet. 1998;102:605-10 pubmed
    Deficiency of the ninth component of human complement (C9) is the most common complement deficiency in Japan but is rare in other countries...
  27. Shiver J, Dankert J, Donovan J, Esser A. The ninth component of human complement (C9). Functional activity of the b fragment. J Biol Chem. 1986;261:9629-36 pubmed
    The domain structure of human complement protein C9 was investigated by determining the functional activities of the NH2-terminal (C9a) and COOH-terminal (C9b) fragments obtained by cleavage of C9 with alpha-thrombin...
  28. Horiuchi T, Nishizaka H, Kojima T, Sawabe T, Niho Y, Schneider P, et al. A non-sense mutation at Arg95 is predominant in complement 9 deficiency in Japanese. J Immunol. 1998;160:1509-13 pubmed
    Deficiency of the ninth component of complement (C9D) is one of the most common genetic abnormalities in Japan, with an incidence of one homozygote in 1000...
  29. Huang Y, Qiao F, Abagyan R, Hazard S, Tomlinson S. Defining the CD59-C9 binding interaction. J Biol Chem. 2006;281:27398-404 pubmed
    ..It functions by binding to C8 (alpha chain) and C9 after their structural rearrangement during MAC assembly...
  30. Stewart J, Sodetz J. Analysis of the specific association of the eighth and ninth components of human complement: identification of a direct role for the alpha subunit of C8. Biochemistry. 1985;24:4598-602 pubmed
    The basis for the physical association between C8 and C9 in solution was examined by isolating the noncovalently associated alpha-gamma and beta subunits of C8 and determining their respective affinities for C9...
  31. Susal C, Kirschfink M, Kröpelin M, Daniel V, Opelz G. Identification of complement activation sites in human immunodeficiency virus type-1 glycoprotein gp120. Blood. 1996;87:2329-36 pubmed
    ..In the current study, the complement proteins C4,C3,C5,C9, and properdin were found to bind to a synthetic peptide covering positions 233-251 of the gp120BRU sequence on ..
  32. Tomlinson S, Ueda E, Maruniak J, Garcia Canedo A, Bjes E, Esser A. The expression of hemolytically active human complement protein C9 in mammalian, insect, and yeast cells. Protein Expr Purif. 1993;4:141-8 pubmed
    The cDNA sequence encoding mature human C9 protein and its signal peptide was cloned into three expression vectors for expression in COS-7 (mammalian), Spodoptera frugiperda IPLB-SF-21AE (insect), and Saccharomyces cerevisiae (yeast) ..
  33. Saar Ray M, Moskovich O, Iosefson O, Fishelson Z. Mortalin/GRP75 binds to complement C9 and plays a role in resistance to complement-dependent cytotoxicity. J Biol Chem. 2014;289:15014-22 pubmed publisher
    ..mortalin, the ATPase domain, but not the substrate-binding domain, was found to bind to complement proteins C8 and C9 and to inhibit zinc-induced polymerization of C9...
  34. Stanley K, Kocher H, Luzio J, Jackson P, Tschopp J. The sequence and topology of human complement component C9. EMBO J. 1985;4:375-82 pubmed
    A partial nucleotide sequence of human complement component C9 cDNA representing 94% of the coding region of the mature protein is presented...
  35. Peitsch M, Amiguet P, Guy R, Brunner J, Maizel J, Tschopp J. Localization and molecular modelling of the membrane-inserted domain of the ninth component of human complement and perforin. Mol Immunol. 1990;27:589-602 pubmed
    Upon interaction with the membrane-bound C5b-8 complex, the ninth component of complement (C9) unfolds and inserts into the membrane of cells on which surface complement has been activated...
  36. Tschopp J, Chonn A, Hertig S, French L. Clusterin, the human apolipoprotein and complement inhibitor, binds to complement C7, C8 beta, and the b domain of C9. J Immunol. 1993;151:2159-65 pubmed
    ..the binding interactions between [125I]clusterin and the isolated components of the complex, C5b-6, C7, C8, and C9 and vitronectin...
  37. Shah A, Cao K, Choi E, Chen D, Gautier B, Nancarrow D, et al. Serum Glycoprotein Biomarker Discovery and Qualification Pipeline Reveals Novel Diagnostic Biomarker Candidates for Esophageal Adenocarcinoma. Mol Cell Proteomics. 2015;14:3023-39 pubmed publisher
    ..0231; AUROC = 0.71); BE versus EAC, Aleuria aurantia lectin (AAL)-reactive complement component C9 (p value = 0.0001; AUROC = 0...
  38. Gancz D, Donin N, Fishelson Z. Involvement of the c-jun N-terminal kinases JNK1 and JNK2 in complement-mediated cell death. Mol Immunol. 2009;47:310-7 pubmed publisher
    ..Our results demonstrate that complement C5b-9 induce a JNK/Bid-dependent and JNK-independent necrotic cell death. Both JNK1 and JNK2 have cytotoxic potential, however JNK2 is the primary signal transducer. ..
  39. Scibek J, Plumb M, Sodetz J. Binding of human complement C8 to C9: role of the N-terminal modules in the C8 alpha subunit. Biochemistry. 2002;41:14546-51 pubmed
    ..During MAC formation, C8alpha mediates binding and self-polymerization of C9 to form a pore-like structure on the membrane of target cells...
  40. Miura T, Goto S, Iguchi S, Shimada H, Ueno M, Nishi S, et al. Membranoproliferative pattern of glomerular injury associated with complement component 9 deficiency due to Arg95Stop mutation. Clin Exp Nephrol. 2011;15:86-91 pubmed publisher
    Arg95Stop mutation of exon 4 in complement component 9 (C9) gene is common in individuals in Japan with C9 deficiency (C9D); however, understanding of the influences of C9D on human glomerulonephritis remains elusive...