complement c6

Summary

Summary: A 105-kDa serum glycoprotein with significant homology to the other late complement components, C7-C9. It is a polypeptide chain cross-linked by 32 disulfide bonds. C6 is the next complement component to bind to the membrane-bound COMPLEMENT C5B in the assembly of MEMBRANE ATTACK COMPLEX. It is encoded by gene C6.

Top Publications

  1. Zhou W, Farrar C, Abe K, Pratt J, Marsh J, Wang Y, et al. Predominant role for C5b-9 in renal ischemia/reperfusion injury. J Clin Invest. 2000;105:1363-71 pubmed
    ..The membrane attack complex of complement is a potential target for prevention of I/R injury in this model. ..
  2. Fondevila C, Shen X, Tsuchihashi S, Uchida Y, Freitas M, Ke B, et al. The membrane attack complex (C5b-9) in liver cold ischemia and reperfusion injury. Liver Transpl. 2008;14:1133-41 pubmed publisher
    ..This is the first report using a clinically relevant liver cold ischemia model to show that local MAC inhibition attenuates IRI cascade in OLT recipients. ..
  3. Aleshin A, Schraufstatter I, Stec B, Bankston L, Liddington R, DiScipio R. Structure of complement C6 suggests a mechanism for initiation and unidirectional, sequential assembly of membrane attack complex (MAC). J Biol Chem. 2012;287:10210-22 pubmed publisher
    ..Our model of the assembled pore resembles those of the cholesterol-dependent cytolysins but is distinct from that recently proposed for perforin. ..
  4. Scacchi R, Corbo R, Cossu G, Mureddu L, Mulas G, Pascone R. Distribution of ORM1, C6, C7 and APO C-II allele frequencies in populations from mainland Italy and Sardinia. Hum Hered. 1992;42:309-15 pubmed
    ..The two populations showed a significant difference in the gene frequencies distribution for ORM1. ..
  5. 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
    ..We propose that the clusters involving the C8A and C8B and the C6, C7, and C9 genes be referred to as MACI and MACII, respectively. ..
  6. Moya Quiles M, Bernardo Pisa M, Martinez P, Gimeno L, Bosch A, Salgado G, et al. Complement component C6 deficiency in a Spanish family: implications for clinical and molecular diagnosis. Gene. 2013;521:204-6 pubmed publisher
    ..In this work we report the immunochemical and molecular characterization of complement C6 deficiency in a Spanish patient showing no detectable functional activity of either the classical or ..
  7. Hobart M, Fernie B, Stanley K, Lachmann P. C6 epitope expression by an unrelated antisense cDNA clone: an inadvertent surface-simulation mimotope. Proc Biol Sci. 1993;252:157-62 pubmed
  8. Elvington A, Atkinson C, Zhu H, Yu J, Takahashi K, Stahl G, et al. The alternative complement pathway propagates inflammation and injury in murine ischemic stroke. J Immunol. 2012;189:4640-7 pubmed publisher
    ..We additionally show that the protective effect of factor B deficiency and CR2-fH treatment is sustained in the subacute stage of infarct development, adding to the clinical relevance of these findings. ..
  9. Multerer K, Smith L. Two cDNAs from the purple sea urchin, Strongylocentrotus purpuratus, encoding mosaic proteins with domains found in factor H, factor I, and complement components C6 and C7. Immunogenetics. 2004;56:89-106 pubmed
    ..Based on the domains present in SpCRL and SpCRS, they might be either examples of complement regulatory proteins or members of the terminal pathway of complement. ..

More Information

Publications62

  1. Thai C, Ogata R. Complement components C5 and C7: recombinant factor I modules of C7 bind to the C345C domain of C5. J Immunol. 2004;173:4547-52 pubmed
    ..Based on available evidence, we suggest a model for an irreversible membrane attack complex assembly in which the C7 FIMs, but not those in C6, are bound to the C345C domain of C5 within the fully assembled complex. ..
  2. Murata K, Iwata T, Nakashima S, Fox Talbot K, Qian Z, Wilkes D, et al. C4d deposition and cellular infiltrates as markers of acute rejection in rat models of orthotopic lung transplantation. Transplantation. 2008;86:123-9 pubmed publisher
    ..Furthermore, the histological features of our allografts support the concept that posttransplant capillaritis is a form of humoral rejection. ..
  3. Hobart M, Fernie B, DiScipio R. Structure of the human C7 gene and comparison with the C6, C8A, C8B, and C9 genes. J Immunol. 1995;154:5188-94 pubmed
    ..With the exception of exon 1, all intron/exon boundaries are preserved with respect to phase when compared with C6. ..
  4. Shen Y, Zhang J, Xu X, Fu J, Li J. A new haplotype variability in complement C6 is marginally associated with resistance to Aeromonas hydrophila in grass carp. Fish Shellfish Immunol. 2013;34:1360-5 pubmed publisher
    ..hydrophila in grass carp. These findings suggest a lack of strong association of the C6 polymorphisms with the A. hydrophila resistance in grass carp. ..
  5. DiScipio R, Hugli T. The molecular architecture of human complement component C6. J Biol Chem. 1989;264:16197-206 pubmed
    ..The combined results are discussed and comparisons made with the other late acting components of complement and perforin. ..
  6. Xiao H, Dairaghi D, Powers J, Ertl L, BAUMGART T, Wang Y, et al. C5a receptor (CD88) blockade protects against MPO-ANCA GN. J Am Soc Nephrol. 2014;25:225-31 pubmed publisher
    ..These observations suggest that blockade of C5aR/CD88 might have therapeutic benefit in patients with ANCA-associated vasculitis and GN. ..
  7. Thai C, Ogata R. Expression and characterization of the C345C/NTR domains of complement components C3 and C5. J Immunol. 2003;171:6565-73 pubmed
    ..The high binding affinities suggest that complexes composed of C5 bound to C6 or C7 exist in plasma before activation and may facilitate assembly of the complement membrane attack complex. ..
  8. Tramontini N, Huber C, Liu Bryan R, Terkeltaub R, Kilgore K. Central role of complement membrane attack complex in monosodium urate crystal-induced neutrophilic rabbit knee synovitis. Arthritis Rheum. 2004;50:2633-9 pubmed
    ..C6 and MAC activation may represent novel therapeutic targets for suppression of neutrophil-mediated joint inflammation in gout. ..
  9. Leggiadro R. Systemic meningococcal infection and complement deficiency. Pediatr Infect Dis J. 2003;22:760-1 pubmed
  10. Rangan G, Pippin J, Couser W. C5b-9 regulates peritubular myofibroblast accumulation in experimental focal segmental glomerulosclerosis. Kidney Int. 2004;66:1838-48 pubmed
    ..Adriamycin nephropathy was induced in complement C6-sufficient (C6+) and C6-deficient (C6-) piebold viral glaxo (PVG) rats...
  11. Tran G, Hodgkinson S, Carter N, Killingsworth M, Nomura M, Verma N, et al. Membrane attack complex of complement is not essential for immune mediated demyelination in experimental autoimmune neuritis. J Neuroimmunol. 2010;229:98-106 pubmed publisher
  12. Holtman L, van Vliet E, Baas F, Aronica E, Gorter J. Complement protein 6 deficiency in PVG/c rats does not lead to neuroprotection against seizure induced cell death. Neuroscience. 2011;188:109-16 pubmed publisher
    ..Whether complement components upstream of MAC play a crucial role in neuronal death and/or epileptogenesis needs to be further investigated. ..
  13. Wang Z, Liao J, Wu S, Li C, Fan J, Peng Z. Recipient C6 rs9200 genotype is associated with hepatocellular carcinoma recurrence after orthotopic liver transplantation in a Han Chinese population. Cancer Gene Ther. 2016;23:157-61 pubmed publisher
    ..05) for predicting HCC recurrence after OLT. In conclusion, recipient C6 rs9200 polymorphism is associated with HCC recurrence after OLT, and improves the predictive value of clinical models. ..
  14. Mollnes T, Lea T, Frøland S, Harboe M. Quantification of the terminal complement complex in human plasma by an enzyme-linked immunosorbent assay based on monoclonal antibodies against a neoantigen of the complex. Scand J Immunol. 1985;22:197-202 pubmed
    ..The assay is easy to perform and can be used for examination of large numbers of plasma samples. ..
  15. Chakravarti D, Muller Eberhard H. Biochemical characterization of the human complement protein C6. Association with alpha-thrombin-like enzyme and absence of serine protease activity in cytolytically active C6. J Biol Chem. 1988;263:18306-12 pubmed
    ..A method for the isolation of homogeneous C6 in the hemolytically fully active form is described. No free sulfhydryl group was detected in C6. The amino acid sequence of 20 amino-terminal residues was determined. ..
  16. Hobart M, Lachmann P. Allotypes of complement components in man. Transplant Rev. 1976;32:26-42 pubmed
  17. Tramontini N, Kuipers P, Huber C, Murphy K, Naylor K, Broady A, et al. Modulation of leukocyte recruitment and IL-8 expression by the membrane attack complex of complement (C5b-9) in a rabbit model of antigen-induced arthritis. Inflammation. 2002;26:311-9 pubmed
    ..The results derived from this study provide evidence that the MAC has an important function in mediating leukocyte recruitment in antigen-induced arthritis but does not play a direct role in connective tissue breakdown. ..
  18. Orren A, Preece C, Dowdle E. Genetically determined molecular weight differences in murine complement component C6. Eur J Immunol. 1985;15:100-3 pubmed
    ..Results of breeding experiments demonstrated that the possession of the high Mr type B C6 was inherited in the manner of an autosomal phenotypically dominant characteristic. ..
  19. Gianni D, Zambrano N, Bimonte M, Minopoli G, Mercken L, Talamo F, et al. Platelet-derived growth factor induces the beta-gamma-secretase-mediated cleavage of Alzheimer's amyloid precursor protein through a Src-Rac-dependent pathway. J Biol Chem. 2003;278:9290-7 pubmed
  20. Hook L, Lubinski J, Jiang M, Pangburn M, Friedman H. Herpes simplex virus type 1 and 2 glycoprotein C prevents complement-mediated neutralization induced by natural immunoglobulin M antibody. J Virol. 2006;80:4038-46 pubmed
    ..These findings indicate that humans differ in the ability of their innate immune systems to neutralize HSV-1 or HSV-2 gC-null virus and that a critical function of gC1 and gC2 is to prevent C5 activation. ..
  21. Chondrou M, Mastellos D, Zarkadis I. cDNA cloning and phylogenetic analysis of the sixth complement component in rainbow trout. Mol Immunol. 2006;43:1080-7 pubmed publisher
    ..Finally, trout C6 gene appears to exist as a single copy in the trout genome, and is expressed in a wide range of trout tissues...
  22. Qian Z, Lee C, Murata K, Liu J, Fox Talbot K, Wasowska B, et al. Antibody and complement mediated injury in transplants following sensitization by allogeneic blood transfusion. Transplantation. 2006;82:857-64 pubmed
    ..In the absence of C6, macrophages colocalized with deposits of C4d and T cells accumulated in the periarterial lymphatics. ..
  23. van Oorschot R, Birmingham V, Porter P, Kammerer C, Vandeberg J. Linkage between complement components 6 and 7 and glutamic pyruvate transaminase in the marsupial Monodelphis domestica. Biochem Genet. 1993;31:215-22 pubmed
    ..The newly described C6 and C7 polymorphisms provide additional power for developing a linkage map for M. domestica and for localizing genes that confer susceptibility to diseases for which this species is used as a model. ..
  24. Lewis R, Jackson C, Morgan B, Hughes T. The membrane attack complex of complement drives the progression of atherosclerosis in apolipoprotein E knockout mice. Mol Immunol. 2010;47:1098-105 pubmed publisher
    ..Our results demonstrate that the MAC contributes to the development of atherosclerosis, C6 deficiency being protective and CD59a deficiency exacerbating disease. ..
  25. Schrag M, McAuley G, Pomakian J, Jiffry A, Tung S, Mueller C, et al. Correlation of hypointensities in susceptibility-weighted images to tissue histology in dementia patients with cerebral amyloid angiopathy: a postmortem MRI study. Acta Neuropathol. 2010;119:291-302 pubmed publisher
    ..Correlation of imaging findings to tissue pathology in our cases indicates that a variety of CAA-related pathologies produce MR-identified signal voids and further supports the use of SWI as a biomarker for this disease. ..
  26. Spicer S, Tran G, Killingsworth M, Carter N, Power D, Paizis K, et al. Induction of passive Heymann nephritis in complement component 6-deficient PVG rats. J Immunol. 2007;179:172-8 pubmed
    ..These studies showed proteinuria in PHN occurs without MAC and that other mechanisms, such as immune complex size, early complement components, CD4+ and CD8+ T cells, disrupt glomerular integrity and lead to proteinuria. ..
  27. Bhole D, Stahl G. Molecular basis for complement component 6 (C6) deficiency in rats and mice. Immunobiology. 2004;209:559-68 pubmed
    ..Further, adenosine diphosphate induced platelet aggregation were markedly reduced in C6 deficient rats. The molecular basis for these coagulations defects is unknown at present. ..
  28. Oka R, Sasagawa T, Ninomiya I, Miwa K, Tanii H, Saijoh K. Reduction in the local expression of complement component 6 (C6) and 7 (C7) mRNAs in oesophageal carcinoma. Eur J Cancer. 2001;37:1158-65 pubmed
    ..Our findings suggest a possible relationship between oesophageal tumorigenesis and reduced expression of C6 and C7 mRNAs, which is probably caused by a change in gene expression regulation and not by genetic loss of the locus. ..
  29. Kraiczy P, Hunfeld K, Peters S, Wurzner R, Ackert G, Wilske B, et al. Borreliacidal activity of early Lyme disease sera against complement-resistant Borrelia afzelii FEM1 wild-type and an OspC-lacking FEM1 variant. J Med Microbiol. 2000;49:917-28 pubmed
    ..These results provide direct evidence that anti-OspC antibodies, once developed during the immune response, are of critical importance for efficient killing of borreliae in the early phase of infection. ..
  30. Tran G, Hodgkinson S, Carter N, Killingsworth M, Spicer S, Hall B. Attenuation of experimental allergic encephalomyelitis in complement component 6-deficient rats is associated with reduced complement C9 deposition, P-selectin expression, and cellular infiltrate in spinal cords. J Immunol. 2002;168:4293-300 pubmed
  31. Høgåsen A, Wurzner R, Abrahamsen T, Dierich M. Human polymorphonuclear leukocytes store large amounts of terminal complement components C7 and C6, which may be released on stimulation. J Immunol. 1995;154:4734-40 pubmed
    ..This suggests a new role for the PMN as a C membrane attack modulator. ..
  32. Mead R, Singhrao S, Neal J, Lassmann H, Morgan B. The membrane attack complex of complement causes severe demyelination associated with acute axonal injury. J Immunol. 2002;168:458-65 pubmed
    ..In the absence of MAC deposition, complement activation leading to opsonization and generation of the anaphylatoxins C5a and C3a is insufficient to initiate demyelination. ..
  33. Orren A, Potter P. Complement component C6 deficiency and susceptibility to Neisseria meningitidis infections. S Afr Med J. 2004;94:345-6 pubmed
  34. Wurzner R, Witzel Schlömp K, Tokunaga K, Fernie B, Hobart M, Orren A. Reference typing report for complement components C6, C7 and C9 including mutations leading to deficiencies. Exp Clin Immunogenet. 1998;15:268-85 pubmed
    ..The results of the protein typing for C6 are published in the following paper of this issue. ..
  35. Laudisi F, Spreafico R, Evrard M, Hughes T, Mandriani B, Kandasamy M, et al. Cutting edge: the NLRP3 inflammasome links complement-mediated inflammation and IL-1? release. J Immunol. 2013;191:1006-10 pubmed publisher
    ..These findings provide insight into the molecular processes underlying complement-mediated inflammation and highlight the possibility of targeting IL-1? to control complement-induced disease and pathological inflammation. ..
  36. Fleming R, Marques A, Klempner M, Schmid C, Dally L, Martin D, et al. Pre-treatment and post-treatment assessment of the C(6) test in patients with persistent symptoms and a history of Lyme borreliosis. Eur J Clin Microbiol Infect Dis. 2004;23:615-8 pubmed
    ..The results indicate that C(6) antibody cannot be used to assess treatment outcome or the presence of active infection in this population. ..
  37. Wu G, Korsgren O, van Rooijen N, Tibell A. Suppression of T cells results in long-term survival of mouse heart xenografts in C6-deficient rats. Xenotransplantation. 2001;8:303-9 pubmed
    ..Our data indicate that MAC-mediated injury plays an essential role in concordant xenograft rejection. Once this mechanism has been prevented, suppression of T cells allows for long-term xenograft survival. ..
  38. Ikinciogullari A, Tekin M, Dogu F, Reisli I, Tanir G, Yi Z, et al. Meningococccal meningitis and complement component 6 deficiency associated with oculocutaneous albinism. Eur J Pediatr. 2005;164:177-9 pubmed
  39. Ota H, Fox Talbot K, Hu W, Qian Z, Sanfilippo F, Hruban R, et al. Terminal complement components mediate release of von Willebrand factor and adhesion of platelets in arteries of allografts. Transplantation. 2005;79:276-81 pubmed
    ..1U (C6+) recipients. Mononuclear cell infiltration of the arterial intima occurs in the absence of C6, but C6 deficiency limits the release of vWF from arterial endothelial cells. ..
  40. de Vries B, Matthijsen R, van Bijnen A, Wolfs T, Buurman W. Lysophosphatidic acid prevents renal ischemia-reperfusion injury by inhibition of apoptosis and complement activation. Am J Pathol. 2003;163:47-56 pubmed
    ..Moreover, exogenous LPA is capable of preventing organ failure because of an ischemic insult and thus may provide new means to treat clinical conditions associated with I/R injury in the kidney and potentially also in other organs. ..
  41. Blanchin S, Estienne V, Durand Gorde J, Carayon P, Ruf J. Complement activation by direct C4 binding to thyroperoxidase in Hashimoto's thyroiditis. Endocrinology. 2003;144:5422-9 pubmed
    ..Investigating this complement pathway, therefore, would provide an excellent means of reaching a better understanding of the etiology of other degenerative diseases. ..
  42. Owen E, Leisegang F, Whitelaw A, Simpson J, Baker S, Wurzner R, et al. Complement component C5 and C6 mutation screening indicated in meningococcal disease in South Africa. S Afr Med J. 2012;102:525-7 pubmed
    ..7% being either C5D or C6Q0. We strongly recommend diagnostic testing for complement C5 and C6 deficiency in the routine work-up of all MD cases in South Africa. Prophylactic treatment should be started in susceptible individuals. ..
  43. Malassagne B, Regimbeau J, Taboit F, Troalen F, Chereau C, Moire N, et al. Hypodermin A, a new inhibitor of human complement for the prevention of xenogeneic hyperacute rejection. Xenotransplantation. 2003;10:267-77 pubmed
    ..The mHA-PAEC11 cells were significantly more resistant to lysis by human C than control PAEC11 cells. These data suggest that transgenic HA could be used to prevent hyperacute xenogeneic rejection. ..
  44. O Hanlon T, Li Z, Gan L, Gourley M, Rider L, Miller F. Plasma proteomic profiles from disease-discordant monozygotic twins suggest that molecular pathways are shared in multiple systemic autoimmune diseases. Arthritis Res Ther. 2011;13:R181 pubmed publisher
    ..An understanding of the mechanisms leading to the altered plasma proteomes common among these SAID may provide useful insights into their pathogeneses. ..
  45. Pasaje C, Bae J, Park B, Cheong H, Jang A, Uh S, et al. Association analysis of C6 genetic variations and aspirin hypersensitivity in Korean asthmatic patients. Hum Immunol. 2011;72:973-8 pubmed publisher
    ..However, these preliminary results may contribute to the etiology of aspirin hypersensitivity in Korean asthmatic patients. ..
  46. Fernie B, Orren A, Sheehan G, Schlesinger M, Hobart M. Molecular bases of C7 deficiency: three different defects. J Immunol. 1997;159:1019-26 pubmed
    ..However, one individual is heterozygous for markers at adjacent C6 loci, showing that there has been an intergenic recombination and suggesting that the deficiency mutation is of appreciable antiquity. ..
  47. Mikrou A, Zarkadis I. Cloning of the sixth complement component and, spatial and temporal expression profile of MAC structural and regulatory genes in chicken. Dev Comp Immunol. 2010;34:485-90 pubmed publisher
    ..On the other hand, MAC regulatory genes are expressed in all the developmental stages investigated. ..
  48. Ramaglia V, Tannemaat M, de Kok M, Wolterman R, Vigar M, King R, et al. Complement inhibition accelerates regeneration in a model of peripheral nerve injury. Mol Immunol. 2009;47:302-9 pubmed publisher
    ..We suggest that a destructive C-mediated event during nerve degeneration hampers the subsequent regenerative process. These findings provide a rationale for the testing of anti-complement agents in human nerve injury. ..
  49. Hobart M, Fernie B, Fijen K, Orren A. The molecular basis of C6 deficiency in the western Cape, South Africa. Hum Genet. 1998;103:506-12 pubmed
    ..We have also observed the 879delG defect in two Dutch C6-deficient kindreds, but the 879delG defect in the Cape probably did not come from The Netherlands. ..
  50. Qian Z, Liu J, Fox Talbot K, Wasowska B, Baldwin W. A rat model of pregnancy-induced sensitization to transplants. Transplant Proc. 2005;37:96-7 pubmed
    ..In summary, previous pregnancy leads to memory alloantibody responses that accelerate allograft rejection even with immunosuppression. Membrane attack complex is required for accelerated rejection induced by previous pregnancy. ..
  51. Hobart M, Fernie B, DiScipio R, Lachmann P. A physical map of the C6 and C7 complement component gene region on chromosome 5p13. Hum Mol Genet. 1993;2:1035-6 pubmed
  52. Binks M, Sriprakash K. Characterization of a complement-binding protein, DRS, from strains of Streptococcus pyogenes containing the emm12 and emm55 genes. Infect Immun. 2004;72:3981-6 pubmed
    ..Despite this, the recombinant DRS preparation showed no significant effect on complement function, as determined by lysis of sensitized sheep erythrocytes. Furthermore, the presence of DRS is not inhibitory to SIC activity. ..
  53. Sassi F, Bardi R, Neji T, Ayed K, Ben Dridi M. [Immunological study in sickle cell disease patients: importance of the complement system]. Tunis Med. 2003;81:195-9 pubmed
    ..Numeration of Band T cells revealed slight decrease in proportion of CD3 and CD4 at one patient associated with an increase in B cells, but normal or increased absolute numbers of all cells population. ..