Genomes and Genes
Summary: A 63-kDa serum glycoprotein encoded by gene C9. Monomeric C9 (mC9) binds the C5b-8 complex to form C5b-9 which catalyzes the polymerization of C9 forming C5b-p9 (MEMBRANE ATTACK COMPLEX) and transmembrane channels leading to lysis of the target cell. Patients with C9 deficiency suffer from recurrent bacterial infections.
- Turnberg D, Botto M, Lewis M, Zhou W, Sacks S, Morgan B, et al. CD59a deficiency exacerbates ischemia-reperfusion injury in mice. Am J Pathol. 2004;165:825-32 pubmed
- Kazantzi A, Sfyroera G, Holland M, Lambris J, Zarkadis I. Molecular cloning of the beta subunit of complement component eight of rainbow trout. Dev Comp Immunol. 2003;27:167-74 pubmed..The protein encoded by the gene was identified by Western blotting using an anti-peptide antibody and was approximately 65kDa...
- LaChapelle S, Tweten R, Hotze E. Intermedilysin-receptor interactions during assembly of the pore complex: assembly intermediates increase host cell susceptibility to complement-mediated lysis. J Biol Chem. 2009;284:12719-26 pubmed publisher..We further show that the assembly intermediates increase the sensitivity of the host cell to lysis by its complement membrane attack complex, apparently by blocking the hCD59-binding site for complement proteins C8alpha and C9. ..
- Happonen K, Saxne T, Aspberg A, Morgelin M, Heinegard D, Blom A. Regulation of complement by cartilage oligomeric matrix protein allows for a novel molecular diagnostic principle in rheumatoid arthritis. Arthritis Rheum. 2010;62:3574-83 pubmed publisher..It can activate one complement pathway at the same time as it has the potential to inhibit another. The net outcome of these interactions is most likely determined by the type of released COMP fragments, which may be disease specific. ..
- Murakoshi Y, Honda K, Sasazuki S, Ono M, Negishi A, Matsubara J, et al. Plasma biomarker discovery and validation for colorectal cancer by quantitative shotgun mass spectrometry and protein microarray. Cancer Sci. 2011;102:630-8 pubmed publisher..01×10(-3) and P=1.13×10(-5) , respectively). Although the significance of the present study must be validated in an independent clinical study, the increment of plasma C9 may be applicable to the early detection of colorectal cancer. ..
- Kusner L, Kaminski H. The role of complement in experimental autoimmune myasthenia gravis. Ann N Y Acad Sci. 2012;1274:127-32 pubmed publisher..Inhibition of complement-mediated lysis is an attractive therapeutic in MG. ..
- Polihronis M, Paizis K, Carter G, Sedal L, Murphy B. Elevation of human cerebrospinal fluid clusterin concentration is associated with acute neuropathology. J Neurol Sci. 1993;115:230-3 pubmed..Determination of CSF clusterin concentration may be of clinical value in neurological diagnosis. ..
- Kong C, Huang Z, Chen J, Shi Y, Lu X. [Molecular cloning, sequence analysis and expression of ayu complement component C9 gene]. Dongwuxue Yanjiu. 2012;33:151-7 pubmed publisher..Western blotting analysis revealed that serum aC9 significantly increased in Listonella anguillarum infected ayu fish. Our results suggested that aC9 may play an important role in fish immune response of anti-bacteria. ..
- Huang Y, Fedarovich A, Tomlinson S, Davies C. Crystal structure of CD59: implications for molecular recognition of the complement proteins C8 and C9 in the membrane-attack complex. Acta Crystallogr D Biol Crystallogr. 2007;63:714-21 pubmed..This higher resolution structure of CD59 will facilitate a more precise dissection of its interactions with C8 and C9 and thus increase the likelihood of designing enhanced CD59-based therapeutics. ..
- 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..Efficient C9-AF488 vesiculation was observed in cells expressing low CD59 levels, suggesting that the protective impact of MAC elimination by vesiculation increases as the level of expression of CD59 decreases. ..
- Howard O, Rao A, Sodetz J. Complementary DNA and derived amino acid sequence of the beta subunit of human complement protein C8: identification of a close structural and ancestral relationship to the alpha subunit and C9. Biochemistry. 1987;26:3565-70 pubmed..For beta and alpha, the overall homology is 33% on the basis of identity and 53% when conserved substitutions are allowed. For beta and C9, the values are 26% and 47%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) ..
- 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..These results indicate that both N-terminal modules in C8alpha have a role in forming the principal binding site for C9 and that binding may be dependent on a cooperative interaction between these modules and the C8alpha MACPF domain. ..
- 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..These findings are discussed in comparison with the strongly related components C6, C7, C8alpha, and C8beta. ..
- 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..Of these, six have actually be found. These data provide strong evidence that several mutation and recombination events occurred in the course of C9 gene evolution. ..
- Sawant Mane S, Piddlesden S, Morgan B, Holers V, Koski C. CD59 homologue regulates complement-dependent cytolysis of rat Schwann cells. J Neuroimmunol. 1996;69:63-71 pubmed
- Høgåsen A, Overlie I, Hansen T, Abrahamsen T, Finne P, Høgåsen K. The analysis of the complement activation product SC5 b-9 is applicable in neonates in spite of their profound C9 deficiency. J Perinat Med. 2000;28:39-48 pubmed..3% (0.1%-3.0%) of the values obtained after CVF activation of the same samples. Therefore, we suggest that the analysis of SC5 b-9 is applicable also in neonates, in spite of their extremely low C9 levels. ..
- Perforation of membranes and pore formation is mediated by polymerization of proteins of the immune system, complement C9 and Perforin, which share the conserved MACPF domain. In this issue of Immunity, Baran et al...
- Gong Y, Xi G, Wan S, Gu Y, Keep R, Hua Y. Effects of aging on complement activation and neutrophil infiltration after intracerebral hemorrhage. Acta Neurochir Suppl. 2008;105:67-70 pubmed..Western blot analysis showed that complement C9 and clusterin levels in ipsilateral basal ganglia after ICH were higher in aged rats than in young rats (p <..
- Seddon J, Yu Y, Miller E, Reynolds R, Tan P, Gowrisankar S, et al. Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration. Nat Genet. 2013;45:1366-70 pubmed publisher..These results implicate loss of C3 protein regulation and excessive alternative complement activation in AMD pathogenesis, thus informing both the direction of effect and mechanistic underpinnings of this disorder...
- Li L, Li J, Zhu Y, Fan G. Soluble complement receptor type 1 inhibits complement system activation and improves motor function in acute spinal cord injury. Spinal Cord. 2010;48:105-11 pubmed publisher..Soluble CR1 decreases inflammation reactions by inhibiting activation of the complement system and improves motor function after acute SCI. ..
- Lin T, Zhou W, Farrar C, Hargreaves R, Sheerin N, Sacks S. Deficiency of C4 from donor or recipient mouse fails to prevent renal allograft rejection. Am J Pathol. 2006;168:1241-8 pubmed
- Devlin L, Nguyen M, Figueroa E, Gordon L, Feldhoff P, Lassiter H. Effects of endotoxin administration and cerebral hypoxia-ischemia on complement activity and local transcriptional regulation in neonatal rats. Neurosci Lett. 2005;390:109-13 pubmed..These observations support the theory that previously reported C9-mediated neurotoxicity following cerebral HI is induced by circulating, rather than locally synthesized C9. ..
- Hatanaka M, Shimizu A. [Immunologic tests: C6, C7, C8 and C9]. Nihon Rinsho. 2005;63 Suppl 7:92-4 pubmed
- Scolding N, Houston W, Morgan B, Campbell A, Compston D. Reversible injury of cultured rat oligodendrocytes by complement. Immunology. 1989;67:441-6 pubmed..Reversible and/or lytic complement-mediated oligodendrocyte injury has implications for the pathogenesis of human and experimental demyelinating diseases. ..
- 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..Our results indicate that a novel mutation, R95X, is present in most cases of C9D in Japan. ..
- DiScipio R, Berlin C. The architectural transition of human complement component C9 to poly(C9). Mol Immunol. 1999;36:575-85 pubmed..As a consequence of circular polymerization the midsection of the polypeptide chain becomes exposed as each C9 lengths to fashion a volute form. reserved. ..
- Park T, Kang J, Na B, Sohn W. Molecular cloning and characterization of a paramyosin from Clonorchis sinensis. Korean J Parasitol. 2009;47:359-67 pubmed publisher..Successful induction of host IgG production also suggests that CsPmy can be applied as a diagnostic antigen and/or vaccine candidate for clonorchiasis...
- Agostinis C, Biffi S, Garrovo C, Durigutto P, Lorenzon A, Bek A, et al. In vivo distribution of ?2 glycoprotein I under various pathophysiologic conditions. Blood. 2011;118:4231-8 pubmed publisher..These findings indicate that ?2GPI binding to EC requires priming with pro-inflammatory factors which is not needed for uterine and placental localization probably dependent on hormonal changes. ..
- Yeo G, Elgar G, Sandford R, Brenner S. Cloning and sequencing of complement component C9 and its linkage to DOC-2 in the pufferfish Fugu rubripes. Gene. 1997;200:203-11 pubmed..Sequence scanning of overlapping cosmids has identified two other genes, GAS-1 and FBP, both of which map to human chromosome 9q22, and lie adjacent to the Fugu C9/DOC-2 locus, indicating the boundary between two syntenic regions...
- Soltys J, Kusner L, Young A, Richmonds C, Hatala D, Gong B, et al. Novel complement inhibitor limits severity of experimentally myasthenia gravis. Ann Neurol. 2009;65:67-75 pubmed publisher..Inhibition of complement significantly reduced weakness in two models of EAMG. C5 inhibition could prove to be of significant therapeutic value in human myasthenia gravis. ..
- Ratnoff W, Brockman W, Hasty L. Immunohistochemical localization of C9 neoantigen and the terminal complement inhibitory protein CD59 in human endometrium. Am J Reprod Immunol. 1995;34:72-9 pubmed..These analyses further support the presence of a functionally active complement system in normal human endometrium. ..
- Da Costa L, Garcia Bailo B, Borchers C, BADAWI A, El Sohemy A. Association between the plasma proteome and serum ascorbic acid concentrations in humans. J Nutr Biochem. 2013;24:842-7 pubmed publisher..Levels of complement C9, ceruloplasmin, alpha-1-anti-trypsin, angiotensinogen, complement C3, vitamin D binding protein and ..
- Schultz S, Aly H, Hasanen B, Khashaba M, Lear S, Bendon R, et al. Complement component 9 activation, consumption, and neuronal deposition in the post-hypoxic-ischemic central nervous system of human newborn infants. Neurosci Lett. 2005;378:1-6 pubmed..C9 was deposited on neurons, including morphologically apoptotic neurons. Further investigations into a possible role of complement in the pathogenesis of neonatal hypoxic-ischemic cerebral injury are warranted. ..
- Wang S, Wang R, Xu T. The evolutionary analysis on complement genes reveals that fishes C3 and C9 experience different evolutionary patterns. Fish Shellfish Immunol. 2013;35:2040-5 pubmed publisher..In conclusion, different living environments lead to different evolutionary patterns on C3 and C9 in mammals and fishes. Besides, different complement components may have different evolutionary patterns on mammals and fishes. ..
- 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
- Watts M, Dankert J, Morgan E. Isolation and characterization of a membrane-attack-complex-inhibiting protein present in human serum and other biological fluids. Biochem J. 1990;265:471-7 pubmed..Depletion of MIP from plasma resulted in enhancement of the lytic capacity of the plasma on heterologous erythrocytes. ..
- Hatanaka M, Seya T, Yoden A, Fukamoto K, Semba T, Inai S. Analysis of C5b-8 binding sites in the C9 molecule using monoclonal antibodies: participation of two separate epitopes of C9 in C5b-8 binding. Mol Immunol. 1992;29:911-6 pubmed..These mAbs may be useful in clarifying the conformational states of C9 and in analyzing the molecular interaction between C9 and its inhibitors. ..
- Kraiczy P, Hunfeld K, Breitner Ruddock S, Wurzner R, Acker G, Brade V. Comparison of two laboratory methods for the determination of serum resistance in Borrelia burgdorferi isolates. Immunobiology. 2000;201:406-19 pubmed..The IFA, however, is regarded as superior to the GIA owing to the obvious ease of performance and its rapid capability for the classification of even very slow growing isolates. ..
- Okamoto K, Wang W, Rounds J, Chambers E, Jacobs D. Sublytic complement attack increases intracellular sodium in rat skeletal muscle. J Surg Res. 2000;90:174-82 pubmed..Sublytic amounts of MAC formed as a result of complement activation can directly alter [Na(+)](i) in ex vivo skeletal muscle. ..
- Falcão D, Reis E, Paixao Cavalcante D, Amano M, Delcolli M, Florido M, et al. Deficiency of the human complement regulatory protein factor H associated with low levels of component C9. Scand J Immunol. 2008;68:445-55 pubmed publisher..Low concentrations of C9 were detected in the proband serum but no mutations in the patient's C9 gene or promoter have been identified, suggesting that this is a consequence of uncontrolled complement activation and high C9 consumption. ..
- Leath K, Johnson S, Roversi P, Hughes T, Smith R, Mackenzie L, et al. High-resolution structures of bacterially expressed soluble human CD59. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2007;63:648-52 pubmed..The presence/absence of this ligand is linked to alternate conformations of the amino acids implicated in C8/C9 binding. ..
- Pilzer D, Fishelson Z. Mortalin/GRP75 promotes release of membrane vesicles from immune attacked cells and protection from complement-mediated lysis. Int Immunol. 2005;17:1239-48 pubmed..These results suggest that mortalin/GRP75 promotes the shedding of membrane vesicles loaded with complement MAC and protects cells from complement-mediated lysis. ..
- Xi G, Hua Y, Keep R, Younger J, Hoff J. Systemic complement depletion diminishes perihematomal brain edema in rats. Stroke. 2001;32:162-7 pubmed..Complement depletion by CVF attenuates brain edema in ICH, indicating that complement activation plays an important role in ICH-induced brain edema. Preventing complement activation may be effective in the treatment of ICH. ..
- Ramaglia V, King R, Morgan B, Baas F. Deficiency of the complement regulator CD59a exacerbates Wallerian degeneration. Mol Immunol. 2009;46:1892-6 pubmed publisher..The number of endoneurial macrophages was significantly higher in CD59a deficient mice compared to wildtypes at 1 day post-injury. These findings are relevant to the understanding of the mechanisms of axon loss in injury and disease...
- Lin F, Salant D, Meyerson H, Emancipator S, Morgan B, Medof M. Respective roles of decay-accelerating factor and CD59 in circumventing glomerular injury in acute nephrotoxic serum nephritis. J Immunol. 2004;172:2636-42 pubmed..The results support the proposition that in autoantibody-mediated nephritis, DAF serves as the primary barrier to classical pathway-mediated injury, while CD59 limits consequent C5b-9-mediated cell damage. ..
- McLin V, Hu C, Shah R, Jamrich M. Expression of complement components coincides with early patterning and organogenesis in Xenopus laevis. Int J Dev Biol. 2008;52:1123-33 pubmed publisher..The expression patterns of these molecules suggest that these components of the complement system may have in Xenopus a so far undefined developmental role. ..
- Matsuo S, Nishikage H, Yoshida F, Nomura A, Piddlesden S, Morgan B. Role of CD59 in experimental glomerulonephritis in rats. Kidney Int. 1994;46:191-200 pubmed..The glomeruli in Group III appeared normal throughout experiments. These data indicate that the functional inhibition of a rat analogue of human CD59 worsens complement-mediated glomerular injury in vivo. ..
- Podack E, Deyev V, Shiratsuchi M. Pore formers of the immune system. Adv Exp Med Biol. 2007;598:325-41 pubmed
- Zhang N, Womack J. Synteny mapping in the bovine: genes from human chromosome 5. Genomics. 1992;14:126-30 pubmed
- Xiong Z, Qian W, Suzuki K, McNamara J. Formation of complement membrane attack complex in mammalian cerebral cortex evokes seizures and neurodegeneration. J Neurosci. 2003;23:955-60 pubmed..Deposition of the complement MAC in cortical gray matter may contribute to epileptic seizures and cell death in diverse diseases of the human brain. ..
- Watanabe N, Suzuki T, Kitano E, Kitamura H, Hatanaka M, Sago H. Successful pregnancy in a patient suffering from recurrent mid-trimester miscarriage with C9 deficiency after receiving cervical cerclage followed by clindamycin and progesterone: a case report. J Obstet Gynaecol Res. 2012;38:562-6 pubmed publisher..C9 protein and activity were undetectable in the patient's serum. We suggest that an immunologic disorder such as C9 deficiency should be considered as a potential complication of undiagnosed recurrent miscarriages. ..
- 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..The amino-terminal half of C9 is rich in cysteine residues and contains a region with a high level of homology to the LDL receptor cysteine-rich domains. A model for C9 topology based on these findings is proposed. ..