complement c2


Summary: A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).

Top Publications

  1. Jonsson G, Truedsson L, Sturfelt G, Oxelius V, Braconier J, Sjöholm A. Hereditary C2 deficiency in Sweden: frequent occurrence of invasive infection, atherosclerosis, and rheumatic disease. Medicine (Baltimore). 2005;84:23-34 pubmed
    ..In addition, we confirm the well-known association between C2D and systemic lupus erythematosus. ..
  2. Jakobsdottir J, Conley Y, Weeks D, Ferrell R, Gorin M. C2 and CFB genes in age-related maculopathy and joint action with CFH and LOC387715 genes. PLoS ONE. 2008;3:e2199 pubmed publisher
  3. Alper C, Xu J, Cosmopoulos K, Dolinski B, Stein R, Uko G, et al. Immunoglobulin deficiencies and susceptibility to infection among homozygotes and heterozygotes for C2 deficiency. J Clin Immunol. 2003;23:297-305 pubmed
  4. Inal J, Hui K, Miot S, Lange S, Ramirez M, Schneider B, et al. Complement C2 receptor inhibitor trispanning: a novel human complement inhibitory receptor. J Immunol. 2005;174:356-66 pubmed
    ..We describe complement C2 receptor inhibitor trispanning (CRIT), a novel human complement regulatory receptor, expressed on hemopoietic ..
  5. Zhu Z, Atkinson T, Volanakis J. A novel type II complement C2 deficiency allele in an African-American family. J Immunol. 1998;161:578-84 pubmed
  6. Seddon J, Reynolds R, Maller J, Fagerness J, Daly M, Rosner B. Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables. Invest Ophthalmol Vis Sci. 2009;50:2044-53 pubmed publisher
    ..831 for progression to advanced AMD. Factors reflective of nature and nurture are independently related to prevalence and incidence of advanced AMD, with excellent predictive power. ..
  7. Zhu Z, Hsieh S, Bentley D, Campbell R, Volanakis J. A variable number of tandem repeats locus within the human complement C2 gene is associated with a retroposon derived from a human endogenous retrovirus. J Exp Med. 1992;175:1783-7 pubmed
    ..SINE-R.C2 is a member of a previously described large retroposon family of the human genome, apparently derived from the human endogenous retrovirus, (HERV) K10, which is homologous to the mouse mammary tumor virus. ..
  8. Johnson C, Densen P, Hurford R, Colten H, Wetsel R. Type I human complement C2 deficiency. A 28-base pair gene deletion causes skipping of exon 6 during RNA splicing. J Biol Chem. 1992;267:9347-53 pubmed
    ..These data demonstrate that: 1) type I human complement C2 deficiency is caused by a 28-base pair genomic deletion that causes skipping of exon 6 during RNA splicing, ..
  9. Wetsel R, Kulics J, Lokki M, Kiepiela P, Akama H, Johnson C, et al. Type II human complement C2 deficiency. Allele-specific amino acid substitutions (Ser189 --> Phe; Gly444 --> Arg) cause impaired C2 secretion. J Biol Chem. 1996;271:5824-31 pubmed
    ..Each mutant C2 gene product is retained early in the secretory pathway. These mutants provide models for elucidating the C2 secretory pathway. ..

More Information


  1. Huda R, Tuzun E, Christadoss P. Complement C2 siRNA mediated therapy of myasthenia gravis in mice. J Autoimmun. 2013;42:94-104 pubmed publisher
    ..Therefore, C2 siRNA mediated therapy can be applied in all complement mediated autoimmune diseases. ..
  2. Gold B, Merriam J, Zernant J, Hancox L, Taiber A, Gehrs K, et al. Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nat Genet. 2006;38:458-62 pubmed
    ..These data expand and refine our understanding of the genetic risk for AMD. ..
  3. Jonsson G, Oxelius V, Truedsson L, Braconier J, Sturfelt G, Sjöholm A. Homozygosity for the IgG2 subclass allotype G2M(n) protects against severe infection in hereditary C2 deficiency. J Immunol. 2006;177:722-8 pubmed
    ..In conclusion, the findings indicated that efficient Ab responses to polysaccharides are protective against severe infection in C2D. Implications with regard to vaccination should be considered. ..
  4. Wallis R, Dodds A, Mitchell D, Sim R, Reid K, Schwaeble W. Molecular interactions between MASP-2, C4, and C2 and their activation fragments leading to complement activation via the lectin pathway. J Biol Chem. 2007;282:7844-51 pubmed
  5. Spencer K, Hauser M, Olson L, Schmidt S, Scott W, Gallins P, et al. Protective effect of complement factor B and complement component 2 variants in age-related macular degeneration. Hum Mol Genet. 2007;16:1986-92 pubmed
    ..21, 95% confidence interval 0.11-0.39; P < 10(-4)). Likelihood ratio testing and conditional analyses in the case-control data set suggest that a weaker, independent protective effect exists for CC2 E318D. ..
  6. Yuste J, Sen A, Truedsson L, Jonsson G, Tay L, Hyams C, et al. Impaired opsonization with C3b and phagocytosis of Streptococcus pneumoniae in sera from subjects with defects in the classical complement pathway. Infect Immun. 2008;76:3761-70 pubmed publisher
    ..These data confirm that the classical pathway is vital for complement-mediated phagocytosis of S. pneumoniae and demonstrate why subjects with a C2 deficiency have a marked increase in susceptibility to S. pneumoniae infections. ..
  7. Bentley D. Primary structure of human complement component C2. Homology to two unrelated protein families. Biochem J. 1986;239:339-45 pubmed
    ..The repeats are also found in the non-complement proteins beta 2-glycoprotein I and interleukin-2 receptor, and this repeat family may be widespread. ..
  8. Muller Eberhard H. Complement. Annu Rev Biochem. 1975;44:697-724 pubmed
  9. Sun L, Shao X, Wu Y, Li J, Zhou Q, Lin B, et al. Ontogenetic expression and 17?-estradiol regulation of immune-related genes in early life stages of Japanese medaka (Oryzias latipes). Fish Shellfish Immunol. 2011;30:1131-7 pubmed publisher
    ..In addition, the expression profiles of immune-related genes can be developed for use as biomarkers for future immunotoxicological studies. ..
  10. Shah S, Mertz T, Craig T. Recurrent septic shock in a 34-year-old woman. Allergy Asthma Proc. 2012;33:437-40 pubmed publisher
    ..History revealed this was her third episode of such a presentation with asymptomatic periods in between. She responded well to medical interventions but reported persistent joint pain. Immunologic workup revealed her diagnosis. ..
  11. LaBonte M, McKay P, Letvin N. Evidence of NK cell dysfunction in SIV-infected rhesus monkeys: impairment of cytokine secretion and NKG2C/C2 expression. Eur J Immunol. 2006;36:2424-33 pubmed
  12. Amara U, Rittirsch D, Flierl M, Bruckner U, Klos A, Gebhard F, et al. Interaction between the coagulation and complement system. Adv Exp Med Biol. 2008;632:71-9 pubmed
    ..Moreover, functional C5a and C3a are generated, both of which are known to be crucially involved in the inflammatory response. ..
  13. Cliff J, Lee J, Constantinou N, Cho J, Clark T, Ronacher K, et al. Distinct phases of blood gene expression pattern through tuberculosis treatment reflect modulation of the humoral immune response. J Infect Dis. 2013;207:18-29 pubmed publisher
    ..Measurement of biosignatures during clinical trials of new drugs could be useful predictors of rapid bactericidal or sterilizing drug activity, and would expedite the licensing of new treatment regimens. ..
  14. Maher B, Mackinnon R, Bai J, Chapman E, Kelly P. Activation of postsynaptic Ca(2+) stores modulates glutamate receptor cycling in hippocampal neurons. J Neurophysiol. 2005;93:178-88 pubmed
    ..These results suggest that IP(3)R-mediated Ca(2+) release can enhance AMPAR EPSC amplitudes through mechanisms that involve AMPAR-PDZ interactions and/or synaptotagmin-SNARE-mediated receptor trafficking. ..
  15. Bergeron Sawitzke J, Gold B, Olsh A, Schlotterbeck S, Lemon K, Visvanathan K, et al. Multilocus analysis of age-related macular degeneration. Eur J Hum Genet. 2009;17:1190-9 pubmed publisher
    ..These results also support previous findings that variants in the region of 10q26 exert an independent risk for AMD. ..
  16. Wenda S, Dauber E, Stadlbacher S, Glock B, Fischer M, Körmöczi G, et al. C2_4_4 microheterogeneity and HLA Class I. Tissue Antigens. 2003;61:484-6 pubmed
    ..No clear cut association could be observed in C2_4_4*16 and *18. The results of this study demonstrate that the exclusive use of microsatellite polymorphisms for the definition of HLA haplotypes is generally not possible. ..
  17. Inal J, Schifferli J. Complement C2 receptor inhibitor trispanning and the beta-chain of C4 share a binding site for complement C2. J Immunol. 2002;168:5213-21 pubmed
    b>Complement C2 receptor inhibitor trispanning (CRIT) of the Schistosoma parasite binds human C2 via the C2a segment. The receptor in vivo functions as C2 decoy receptor by directly competing with C4b for binding to C2...
  18. Niemann M, Bhown A, Miller E. The principal site of glycation of human complement factor B. Biochem J. 1991;274 ( Pt 2):473-80 pubmed
  19. Whiteman L, Purkall D, Ruddy S. Covalent linkage of C3 to properdin during complement activation. Eur J Immunol. 1995;25:1481-4 pubmed
    ..These data are consistent with a covalent linkage of C3 to P via the C3 alpha chain, producing the 160-kDa complex. ..
  20. Hutchinson W, Herbert J, Botto M, Pepys M. Classical and alternative pathway complement activation are not required for reactive systemic AA amyloid deposition in mice. Immunology. 2004;112:250-4 pubmed
    ..Complement activation by either the classical or alternative pathways is thus not apparently necessary for the experimental induction of systemic AA amyloid in mice. ..
  21. Brodsky F, Parham P, Barnstable C, Crumpton M, Bodmer W. Monoclonal antibodies for analysis of the HLA system. Immunol Rev. 1979;47:3-61 pubmed
  22. Grob S, Luo J, Hughes G, Lee C, Zhou X, Lee J, et al. Genetic analysis of simultaneous geographic atrophy and choroidal neovascularization. Eye (Lond). 2012;26:1106-13 pubmed publisher
    ..Clinical and genetic results may support the fact that GA and CNV fit on an age-related macular degeneration (AMD)-disease continuum and may clarify the disease processes in AMD. ..
  23. Sun C, Zhao M, Li X. CFB/C2 gene polymorphisms and risk of age-related macular degeneration: a systematic review and meta-analysis. Curr Eye Res. 2012;37:259-71 pubmed publisher
    ..The disease risk descended to nearly one half for individuals carrying at least one copy of the rare alleles. The protective effects seemed to be stronger in Caucasians, of which the genotype frequencies were also higher. ..
  24. Sargent C, Dunham I, Campbell R. Identification of multiple HTF-island associated genes in the human major histocompatibility complex class III region. EMBO J. 1989;8:2305-12 pubmed
    ..The location of so many new genes in this region raises the question as to whether they play any role in the observed HLA associations with an individual's susceptibility to develop autoimmune disease. ..
  25. Liu X, Zhao P, Tang S, Lu F, Hu J, Lei C, et al. Association study of complement factor H, C2, CFB, and C3 and age-related macular degeneration in a Han Chinese population. Retina. 2010;30:1177-84 pubmed publisher
  26. Passwell J, Schreiner G, Nonaka M, Beuscher H, Colten H. Local extrahepatic expression of complement genes C3, factor B, C2, and C4 is increased in murine lupus nephritis. J Clin Invest. 1988;82:1676-84 pubmed
    ..These results suggest that in SLE local expression of complement genes plays a role in the pathogenesis of chronic glomerulonephritis and in the autoimmune arteritis of other organs. ..
  27. Bentley D, Porter R. Isolation of cDNA clones for human complement component C2. Proc Natl Acad Sci U S A. 1984;81:1212-5 pubmed
    ..9 kilobases. Southern blot analysis of genomic DNA of unrelated individuals identified a single C2 locus and showed no cross-hybridization with the factor B locus. ..
  28. Rawal N, Pangburn M. Formation of high affinity C5 convertase of the classical pathway of complement. J Biol Chem. 2003;278:38476-83 pubmed
  29. Jing H, Xu Y, Carson M, Moore D, Macon K, Volanakis J, et al. New structural motifs on the chymotrypsin fold and their potential roles in complement factor B. EMBO J. 2000;19:164-73 pubmed
    ..The bottom of the S1 pocket has a negative charge at residue 226 instead of the typical 189 position. These unique structural features may play different roles in domain-domain interaction, cofactor binding and substrate binding. ..
  30. Selander B, Martensson U, Weintraub A, Holmström E, Matsushita M, Thiel S, et al. Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2. J Clin Invest. 2006;116:1425-34 pubmed
    ..MBL-dependent C2 bypass activation could be particularly important in various inherited and acquired complement deficiency states. ..
  31. Yu R, Chadban S, Svara F, Sen S, Eris J. Two cases of delayed cyclosporin absorption leading to CsA exposure higher than that predicted by C2 monitoring alone. Nephrol Dial Transplant. 2005;20:1745-7 pubmed
  32. Hinterseher I, Erdman R, Donoso L, Vrabec T, Schworer C, Lillvis J, et al. Role of complement cascade in abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 2011;31:1653-60 pubmed publisher
    ..The overrepresented binding sites of transcription factor STAT5A in the complement cascade gene promoters suggest a role for STAT5A in the coordinated regulation of complement cascade gene expression. ..
  33. Lipsker D, Hauptmann G. Cutaneous manifestations of complement deficiencies. Lupus. 2010;19:1096-106 pubmed publisher
    ..The genetic background and the clinical associations of the different components of the complement system will be detailed. ..
  34. Robson M, Cook H, Botto M, Taylor P, Busso N, Salvi R, et al. Accelerated nephrotoxic nephritis is exacerbated in C1q-deficient mice. J Immunol. 2001;166:6820-8 pubmed
    ..The increased IgG deposits and apoptotic cells in the glomeruli of C1q-deficient mice suggest that the exacerbation of disease may be due to a defect in the clearance of immune complexes and/or apoptotic cells from their kidneys. ..
  35. Cole F, Whitehead A, Auerbach H, Lint T, Zeitz H, Kilbridge P, et al. The molecular basis for genetic deficiency of the second component of human complement. N Engl J Med. 1985;313:11-6 pubmed
  36. Francis P, Hamon S, Ott J, Weleber R, Klein M. Polymorphisms in C2, CFB and C3 are associated with progression to advanced age related macular degeneration associated with visual loss. J Med Genet. 2009;46:300-7 pubmed publisher
    ..Five genes have now been shown to be independently involved in progression from intermediate disease (before vision loss has occurred) to advanced disease in which blindness is frequent. ..
  37. Lappin D, Birnie G, Whaley K. Interferon-mediated transcriptional and post-transcriptional modulation of complement gene expression in human monocytes. Eur J Biochem. 1990;194:177-84 pubmed
    ..They also suggest that the synergistic effects of interferon alpha together with interferon gamma on C1-inhibitor and factor B synthesis is also dependent upon increased transcription and increased mRNA stability. ..
  38. Speth C, Stockl G, Mohsenipour I, Wurzner R, Stoiber H, Lass Florl C, et al. Human immunodeficiency virus type 1 induces expression of complement factors in human astrocytes. J Virol. 2001;75:2604-15 pubmed
    ..The C3 protein which is secreted after incubation of the cells with HIV was shown to be biologically active as it can participate in the complement cascade. ..
  39. Lee K, Vithana E, Mathur R, Yong V, Yeo I, Thalamuthu A, et al. Association analysis of CFH, C2, BF, and HTRA1 gene polymorphisms in Chinese patients with polypoidal choroidal vasculopathy. Invest Ophthalmol Vis Sci. 2008;49:2613-9 pubmed publisher
    ..Variants in the C2 and BF genes have been found to confer a significantly reduced risk of AMD. This study was undertaken to determine whether these associations occur in Chinese patients with PCV...
  40. Triglia R, Linscott W. Titers of nine complement components, conglutinin and C3b-inactivator in adult and fetal bovine sera. Mol Immunol. 1980;17:741-8 pubmed
  41. Ji Y, Matsushita M, Okada H, Fujita T, Kawakami M. The C4 and C2 but not C1 components of complement are responsible for the complement activation triggered by the Ra-reactive factor. J Immunol. 1988;141:4271-5 pubmed
    ..Activities of C4 and C2 remained on the sensitized cells even after washing the cells, suggesting that the classical C3 convertase, C4b2a, is generated on the RaRF-sensitized ELPS. ..
  42. Moulds J. Ethnic diversity of class III genes in autoimmune disease. Front Biosci. 2001;6:D986-91 pubmed
    ..The purpose of this review will be to briefly describe the class III region, identify the genetic polymorphism found in various ethnic groups and define their roles in autoimmune diseases. ..
  43. Ashfield R, Patel A, Bossone S, Brown H, Campbell R, Marcu K, et al. MAZ-dependent termination between closely spaced human complement genes. EMBO J. 1994;13:5656-67 pubmed
    ..The MAZ consensus sequence will facilitate the identification of further sites. ..
  44. Shibaguchi H, Tsuru H, Kuroki M, Kuroki M. Enhancement of the antitumor effect on combination therapy of an anticancer drug and its antibody against carcinoembryonic antigen. Chemotherapy. 2012;58:110-7 pubmed publisher
    ..A mechanism for the additive antitumor effect when an anticancer drug and C2-74 are combined is indicated mainly by CDC activity but is irrelevant to anoikis in tumor cells. ..
  45. Hussain A, Prasad K, Bhattacharyya D, el Bouri K. C2 deficiency primary meningococcal arthritis of the elbow by Neisseria meningitidis serogroup Y in a 12-year old girl. Infection. 2007;35:287-8 pubmed
  46. Li Q, Li Y, Stahl G, Thurman J, He Y, Tong H. Essential role of factor B of the alternative complement pathway in complement activation and opsonophagocytosis during acute pneumococcal otitis media in mice. Infect Immun. 2011;79:2578-85 pubmed publisher
  47. Kaplan A, Ghebrehiwet B. Does C-2 kinin exist?. J Allergy Clin Immunol. 2005;115:876 pubmed
  48. Tong H, Li Y, Stahl G, Thurman J. Enhanced susceptibility to acute pneumococcal otitis media in mice deficient in complement C1qa, factor B, and factor B/C2. Infect Immun. 2010;78:976-83 pubmed publisher
    ..pneumoniae from the middle ear and dissemination to the bloodstream during AOM. ..
  49. Bally I, Rossi V, Thielens N, Gaboriaud C, Arlaud G. Functional role of the linker between the complement control protein modules of complement protease C1s. J Immunol. 2005;175:4536-42 pubmed
  50. Kadam A, Sahu A. Identification of Complin, a novel complement inhibitor that targets complement proteins factor B and C2. J Immunol. 2010;184:7116-24 pubmed publisher
    ..Like inhibition of fB cleavage, the peptide also inhibited C2 cleavage by activated C1s and activation of the classical as well as lectin pathways. Based on its inhibitory activities, we named the peptide Complin. ..
  51. Ceribelli A, Andreoli L, Cavazzana I, Franceschini F, Radice A, Rimoldi L, et al. Complement cascade in systemic lupus erythematosus: analyses of the three activation pathways. Ann N Y Acad Sci. 2009;1173:427-34 pubmed publisher
    ..05). In conclusion, the ELISA assay can be considered well suited for testing SLE samples. We detected a significant link between the phases of lupus activity and the reduction of the CP. ..
  52. Richardson A, Islam F, Guymer R, Baird P. Analysis of rare variants in the complement component 2 (C2) and factor B (BF) genes refine association for age-related macular degeneration (AMD). Invest Ophthalmol Vis Sci. 2009;50:540-3 pubmed publisher
    ..96). Although the E318D and L9H variants have shown association with AMD in previous studies, the findings were not in agreement. This demonstrates a refined pattern of association of these rare variants with AMD. ..
  53. Brekke O, Christiansen D, Fure H, Fung M, Mollnes T. The role of complement C3 opsonization, C5a receptor, and CD14 in E. coli-induced up-regulation of granulocyte and monocyte CD11b/CD18 (CR3), phagocytosis, and oxidative burst in human whole blood. J Leukoc Biol. 2007;81:1404-13 pubmed
    ..coli-induced CD11b, phagocytosis, and oxidative burst in both cell types. ..