complement c1


Summary: The first complement component to act in the activation of CLASSICAL COMPLEMENT PATHWAY. It is a calcium-dependent trimolecular complex made up of three subcomponents: COMPLEMENT C1Q; COMPLEMENT C1R; and COMPLEMENT C1S at 1:2:2 ratios. When the intact C1 binds to at least two antibodies (involving C1q), C1r and C1s are sequentially activated, leading to subsequent steps in the cascade of COMPLEMENT ACTIVATION.

Top Publications

  1. Muller Eberhard H. Complement. Annu Rev Biochem. 1975;44:697-724 pubmed
  2. Ramirez G, Valck C, Molina M, Ribeiro C, López N, Sanchez G, et al. Trypanosoma cruzi calreticulin: a novel virulence factor that binds complement C1 on the parasite surface and promotes infectivity. Immunobiology. 2011;216:265-73 pubmed publisher
    ..We propose herein that the parasite uses this molecule to capture complement C1, in an infective apoptotic mimicry strategy...
  3. Wallis R, Mitchell D, Schmid R, Schwaeble W, Keeble A. Paths reunited: Initiation of the classical and lectin pathways of complement activation. Immunobiology. 2010;215:1-11 pubmed publisher
    ..Here, we develop and expand these concepts and delineate their implications towards the key aspects of complement activation via the classical and lectin pathways. ..
  4. Ling W, Biro A, Bally I, Tacnet P, Deniaud A, Doris E, et al. Proteins of the innate immune system crystallize on carbon nanotubes but are not activated. ACS Nano. 2011;5:730-7 pubmed publisher
    ..Our results raise caution in the applications of carbon nanotubes in biomedicine but may also open possibilities of novel applications concerning the many biochemical processes involving the versatile C1 macromolecule. ..
  5. Subasinghe N, Ali F, Illig C, Jonathan Rudolph M, Klein S, Khalil E, et al. A novel series of potent and selective small molecule inhibitors of the complement component C1s. Bioorg Med Chem Lett. 2004;14:3043-7 pubmed
    ..A series of thiopheneamidine-based inhibitors of C1s has been optimized to give a 70 nM inhibitor that inhibits the classical pathway of complement activation in vitro. ..
  6. Swanson S, Dombrink Kurtzman M, Voss E. C1q binding by a high affinity anti-fluorescein murine monoclonal IgM antibody and monomeric subunits. Mol Immunol. 1988;25:545-54 pubmed
    ..At low concn of IgM, when fluorescein was bound by antigen-binding sites on adjacent subunits of an intact pentamer, C1q appeared to bind IgM intramolecularly. ..
  7. Jackson J, Sim R, Whaley K, Feighery C. Autoantibody facilitated cleavage of C1-inhibitor in autoimmune angioedema. J Clin Invest. 1989;83:698-707 pubmed
    ..These findings contribute to our understanding of protease/C1-Inh interactions and document important observations on pathogenic mechanisms in autoimmune disease. ..
  8. Vakeva A, Morgan B, Tikkanen I, Helin K, Laurila P, Meri S. Time course of complement activation and inhibitor expression after ischemic injury of rat myocardium. Am J Pathol. 1994;144:1357-68 pubmed
    ..Deposition of C1 and late C components also starts during the early hours (2 to 4 hours) after ischemia. Subsequent loss of the protective CD59 antigen may initiate postinjury clearance of the irreversibly damaged tissue. ..
  9. Arlaud G, Willis A, Gagnon J. Complete amino acid sequence of the A chain of human complement-classical-pathway enzyme C1r. Biochem J. 1987;241:711-20 pubmed
    ..Combined with the previously determined sequence of C1r B chain [Arlaud & Gagnon (1983) Biochemistry 22, 1758-1764], these data give the complete sequence of human C1r. ..

More Information


  1. Martin H, Loos M. Guinea pig macrophages synthesize a low molecular weight form of C1q with affinity for the C1r2C1s2-complex but which does not bind to Fc in immunoglobulin aggregates. Mol Immunol. 1988;25:1231-7 pubmed
    ..This LMW-C1q was covalently associated with two additional polypeptides of mol. wt 46 and 50 kDa. ..
  2. Patel V, Chu C. Decreased SIRT2 activity leads to altered microtubule dynamics in oxidatively-stressed neuronal cells: implications for Parkinson's disease. Exp Neurol. 2014;257:170-81 pubmed publisher
  3. Gibson J, Hakobyan S, Cree A, Collins A, Harris C, Ennis S, et al. Variation in complement component C1 inhibitor in age-related macular degeneration. Immunobiology. 2012;217:251-5 pubmed publisher
    ..This suggests that genetic variation in the promoter region of the SERPING1 gene may influence expression of the gene. ..
  4. Calabrese G, Recondo E, Fernandez de Recondo M. Antithrombin and first complement protein recognize the same active heparin fraction. Thromb Res. 2002;105:537-41 pubmed
    ..The differences with early results could be explained by our experimental conditions of low ionic strength and the presence of calcium ions used for the interaction of the protein and the glycosaminoglycan. ..
  5. Janulis L, Nemeth J, Yang T, Lang S, Lee C. Prostatic luminal cell differentiation and prostatic steroid-binding protein (PBP) gene expression are differentially affected by neonatal castration. Prostate. 2000;43:195-204 pubmed
    ..This investigation establishes that the cytological and the physiological differentiation of the rat prostate are differentially regulated. ..
  6. Soda K, Ando M, Sakata T, Sugimoto M, Nakashima H, Araki S. C1q and C3 in bronchoalveolar lavage fluid from patients with summer-type hypersensitivity pneumonitis. Chest. 1988;93:76-80 pubmed
    ..These findings are indicative of local secretion or concentration mechanism of C1q and C3, supporting the involvement of immune complexes in the respiratory tract of the patients. ..
  7. Laurell A, Martensson U, Sjoholm A. C1 dissociation. Spontaneous generation in human serum of a trimer complex containing C1 inactivator, activated C1r, and zymogen C1s. J Immunol. 1987;139:4145-51 pubmed
    ..Consistent with results obtained by size exclusion chromatography, analysis by crossed immunoelectrophoresis and by electroimmunoassay showed that C1s could be released from C1 IA-C1r-C1s in the presence of EDTA. ..
  8. Nguyen V, Tosi M, Gross M, Cohen Haguenauer O, Jegou Foubert C, de Tand M, et al. Assignment of the complement serine protease genes C1r and C1s to chromosome 12 region 12p13. Hum Genet. 1988;78:363-8 pubmed
    ..These data suggest that the homologous C1r and C1s genes have remained closely linked after duplication of a common ancestor. The C1r and C1s loci also provide useful polymorphic DNA markers for the short arm of chromosome 12. ..
  9. Heinz H, Rubin K, Laurell A, Loos M. Common epitopes in Clq and collagen type II. Mol Immunol. 1989;26:163-9 pubmed
    ..The present findings raise the question of the pathogenetic significance of the presence of anti-collagen type II antibodies and free Clq, both of which are frequently seen in high amounts in rheumatoid arthritis. ..
  10. Welters I, Menzebach A, Langefeld T, Menzebach M, Hempelmann G. Inhibitory effects of S-(-) and R-(+) bupivacaine on neutrophil function. Acta Anaesthesiol Scand. 2001;45:570-5 pubmed
    ..Enantiomer-specific effects of bupivacaine may play a minor role in the inhibition of these leukocyte functions. ..
  11. Folkerd E, Gardner B, Hughes Jones N. The relationship between the binding ability and the rate of activation of the complement component C1. Immunology. 1980;41:179-85 pubmed
    ..C1 bound to immune complexes was not activated in the presence of C1 inhibitor, indicating that the inhibitor can prevent the hydrolysis of C1r under the test conditions. ..
  12. Tassani P, Kunkel R, Richter J, Oechsler H, Lorenz H, Braun S, et al. Effect of C1-esterase-inhibitor on capillary leak and inflammatory response syndrome during arterial switch operations in neonates. J Cardiothorac Vasc Anesth. 2001;15:469-73 pubmed
    ..This difference may have contributed to improved clinical parameters, including less weight gain postoperatively. ..
  13. Castellheim A, Lindenskov P, Pharo A, Fung M, Saugstad O, Mollnes T. Meconium is a potent activator of complement in human serum and in piglets. Pediatr Res. 2004;55:310-8 pubmed
    ..In conclusion, meconium is a potent activator of the complement system both in vitro and in vivo. Complement may be important in the pathogenesis of MAS, and specific complement inhibition might be a possible treatment approach in MAS. ..
  14. Monteferrante G, Brioschi S, Caprioli J, Pianetti G, Bettinaglio P, Bresin E, et al. Genetic analysis of the complement factor H related 5 gene in haemolytic uraemic syndrome. Mol Immunol. 2007;44:1704-8 pubmed
    ..Based on these data, we conclude that, though not causative, CFHR5 genetic alterations may play a secondary role in the pathogenesis of HUS. ..
  15. Stangel M, Compston A, Scolding N. Oligodendroglia are protected from antibody-mediated complement injury by normal immunoglobulins ("IVIg"). J Neuroimmunol. 2000;103:195-201 pubmed
    ..Inhibition of inflammatory mechanisms, as opposed to a direct effect on remyelinating cells, may underlie the role of IVIg in promoting myelin repair in experimental models. ..
  16. Brier S, Pflieger D, Le Mignon M, Bally I, Gaboriaud C, Arlaud G, et al. Mapping surface accessibility of the C1r/C1s tetramer by chemical modification and mass spectrometry provides new insights into assembly of the human C1 complex. J Biol Chem. 2010;285:32251-63 pubmed publisher
    ..These results provide further structural insights into the architecture of the C1 complex, allowing significant improvement of our current C1 model. ..
  17. Tas S, Klickstein L, Barbashov S, Nicholson Weller A. C1q and C4b bind simultaneously to CR1 and additively support erythrocyte adhesion. J Immunol. 1999;163:5056-63 pubmed
  18. Gao B, Clermont A, Rook S, Fonda S, Srinivasan V, Wojtkowski M, et al. Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation. Nat Med. 2007;13:181-8 pubmed
    ..Inhibition of extracellular CA-I and kallikrein-mediated innate inflammation could provide new therapeutic opportunities for the treatment of hemorrhage-induced retinal and cerebral edema. ..
  19. Ziccardi R, Cooper N. Activation of C1r by proteolytic cleavage. J Immunol. 1976;116:504-9 pubmed
    ..Liquoid, an inhibitor of C1 activation, inhibited C1r cleavage. Thus, proteolytic cleavage of C1r appears to be a biologically meaningful event occurring during the activation of C1. ..
  20. Mattsson P, Morgan B, Svensson M. Complement activation and CD59 expression in the motor facial nucleus following intracranial transection of the facial nerve in the adult rat. J Neuroimmunol. 1998;91:180-9 pubmed
    ..We propose a neuroprotective role for the complement regulators CD59 and clusterin against homologous attack of complement to facial motor neurons. ..
  21. Parsons J, Dianova I, Boswell E, Weinfeld M, Dianov G. End-damage-specific proteins facilitate recruitment or stability of X-ray cross-complementing protein 1 at the sites of DNA single-strand break repair. FEBS J. 2005;272:5753-63 pubmed
  22. Traunecker A, Schneider J, Kiefer H, Karjalainen K. Highly efficient neutralization of HIV with recombinant CD4-immunoglobulin molecules. Nature. 1989;339:68-70 pubmed
    ..Deletion of the CH1 domain may allow the association and secretion of heavy chains in the absence of light chains, and we suggest that the basic design of our constructs may be generally and usefully applied. ..
  23. McAdam R, Goundis D, Reid K. A homozygous point mutation results in a stop codon in the C1q B-chain of a C1q-deficient individual. Immunogenetics. 1988;27:259-64 pubmed
    ..No material corresponding to the A or C chains, or a truncated B chain, could be identified by antigenic analysis of the patient's serum, indicating that a complete B chain is required for secretion of a C1q molecule. ..
  24. Horváth Z, Csuka D, Vargova K, Kovacs A, Molnár A, Gulácsi Bárdos P, et al. Elevated C1rC1sC1inh levels independently predict atherosclerotic coronary heart disease. Mol Immunol. 2013;54:8-13 pubmed publisher
    ..3, CI: 1.628-2616.284). Activation of the classical complement pathway can be observed in angiographically proven coronary atherosclerosis. Elevated C1rC1sC1inh levels might represent an useful biomarker for coronary artery disease. ..
  25. Tuzun E, Saini S, Ghosh S, Rowin J, Meriggioli M, Christadoss P. Predictive value of serum anti-C1q antibody levels in experimental autoimmune myasthenia gravis. Neuromuscul Disord. 2006;16:137-43 pubmed
    ..The serum levels of anti-C1q antibodies but not C1q, C3 and CIC are significantly correlated with the clinical severity in the experimental myasthenia mice. However, this correlation is not observed in myasthenia gravis patients. ..
  26. Strife C, Leahy A, West C. Antibody to a cryptic, solid phase C1Q antigen in membranoproliferative nephritis. Kidney Int. 1989;35:836-42 pubmed
    ..SpClq-binding IgG was detected in 54% of 68 MPGN patients. These results indicate that the 7S spClq-binding IgG represents antibody to a cryptic antigen revealed only when Clq fixes to a solid surface. ..
  27. Leu R, Kriet D, Zhou A, Herriott M, Rummage J, Shannon B. Reconstitution of murine resident peritoneal macrophages for antibody-dependent cellular cytotoxicity by homologous serum Clq. Cell Immunol. 1989;122:48-61 pubmed
    ..Our findings indicate that Clq may provide an essential second signal in concert with Fc receptor binding of IgG to initiate ADCC activation of macrophages. ..
  28. Sasaki T, Yonemasu K, Matsumoto M, Nagaki K. Characterization of C1q found in a patient with hypocomplementemic vasculitis-urticaria syndrome. Microbiol Immunol. 1989;33:413-22 pubmed
    ..The probable structural change of the hypofunctional C1q in the case of this HVUS is discussed. ..
  29. Gompels M, Lock R. Cinryze (C1-inhibitor) for the treatment of hereditary angioedema. Expert Rev Clin Immunol. 2011;7:569-73 pubmed publisher
    ..Cinryze and other similar products are going to change the future management of hereditary angioedema and have potential in other areas of medicine. ..
  30. Bi B, Lin H, Cheng Y, Zhou H, Lin T, Zhang M, et al. Promotion of ?-amyloid production by C-reactive protein and its implications in the early pathogenesis of Alzheimer's disease. Neurochem Int. 2012;60:257-66 pubmed publisher
    ..These results suggest that CRP cytotoxicity is associated with A? formation and A?-related markers expressions; CRP and A? were relevant in early-stage AD; CRP may be an important trigger in AD pathogenesis. ..
  31. Carpentier N, Lange G, Fiere D, Fournie G, Lambert P, Miescher P. Clinical relevance of circulating immune complexes in human leukemia. Association in acute leukemia of the presence of immune complexes with unfavorable prognosis. J Clin Invest. 1977;60:874-84 pubmed
    ..The corresponding median survival times in the latter patient group were 64, 135, and 90 days. These findings were unrelated to prognostic features already known. ..
  32. Oyeyinka G, Bello C, Elegba O, Nsofor B. Levels of some complement components in azoospermic, oligospermic and normospermic Nigerian men. J Reprod Med. 1987;32:774-6 pubmed
    ..Generally, the individual sera from the azoospermic men did not show abnormally lowered levels of any of the complement components when compared with values obtained for the normospermic group. ..
  33. Bruggemann M, Williams G, Bindon C, Clark M, Walker M, Jefferis R, et al. Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. J Exp Med. 1987;166:1351-61 pubmed
    ..These results suggest that IgG1 might be the favoured IgG subclass for therapeutic applications. ..
  34. Erdei A, Reid K. Characterization of C1q-binding material released from the membranes of Raji and U937 cells by limited proteolysis with trypsin. Biochem J. 1988;255:493-9 pubmed
    ..Evidence for the synthesis of the C1q-binding material by both Raji and U937 cells was obtained by biosynthetic-labelling studies using [35S]cysteine and [35S]methionine. ..
  35. Bianchino A, Poon P, Schumaker V. A mechanism for the spontaneous activation of the first component of complement, C1, and its regulation by C1-inhibitor. J Immunol. 1988;141:3930-6 pubmed
    ..When C1s was added to normal human serum, activation at 37 degrees C was also sigmoidal, similar to that of reconstituted C1. ..
  36. Prellner K, Sjoholm A, Truedsson L. Concentrations of C1q, factor B, factor D and properdin in healthy children, and the age-related presence of circulating C1r-C1s complexes. Acta Paediatr Scand. 1987;76:939-43 pubmed
    ..Since the concentrations of C1q are influenced by those of IgG, the presence of C1r-C1s complexes might partly have reflected maturation of immunoglobulin synthesis during ontogeny. ..
  37. Rosano C, Braun C, Hechemy K, Parhami N, Satoh P, Hurwitz C. Inhibition of C1q functions by RHP, a protein elevated in sera from patients with rheumatoid arthritis. Complement. 1988;5:57-64 pubmed
    ..We now show that RHP inhibits the hemolytic activity of C1q, disaggregates C1, and inhibits the ability of C1q bound to latex beads or to aggregated IgG to enhance the oxidative metabolism of neutrophils. ..
  38. Larsson A, Jonsson L, Sjoquist J. Determination of circulating immune complexes by chicken anti-human C3 and anti-human C1q microELISA. J Immunol Methods. 1988;113:93-9 pubmed
    ..They are therefore suitable as capture antibodies in CIC assays. We have tested Bell's palsy patients and found an increase in both anti-C3- and anti-C1q-containing CIC in acute and convalescent sera compared with the normal. ..
  39. Tschank G, Raghunath M, Gunzler V, Hanauske Abel H. Pyridinedicarboxylates, the first mechanism-derived inhibitors for prolyl 4-hydroxylase, selectively suppress cellular hydroxyprolyl biosynthesis. Decrease in interstitial collagen and Clq secretion in cell culture. Biochem J. 1987;248:625-33 pubmed
  40. Caycı F, Cakar N, Hancer V, Uncu N, Acar B, Gur G. Eculizumab therapy in a child with hemolytic uremic syndrome and CFI mutation. Pediatr Nephrol. 2012;27:2327-31 pubmed publisher
    ..It is our belief that eculizumab can be the treatment of choice in children who have plasma exchange-refractory HUS with defective regulation of the alternative complement pathway. ..
  41. Rosenberg A, Prokopchuk P, Lee J. The binding of native DNA to the collagen-like segment of Clq. J Rheumatol. 1988;15:1091-6 pubmed
    ..Our results indicate the dsDNA binds to CLS. Since CLS is the binding site for Clr and then Clr2Cls2, molecules which bind to CLS, such as dsDNA, could be important factors affecting Cl activation. ..
  42. Trifonova O, Pastushkova L, Samenkova N, Chernobrovkin A, Karuzina I, Lisitsa A, et al. The study of the proteome of healthy human blood plasma under conditions of long-term confinement in an isolation chamber. Bull Exp Biol Med. 2013;155:37-9 pubmed
    ..These changes probably reflect the adaptive response to altered conditions of life. ..
  43. Fu J, Lin G, Wu Z, Ceng B, Wu Y, Liang G, et al. Anti-apoptotic role for C1 inhibitor in ischemia/reperfusion-induced myocardial cell injury. Biochem Biophys Res Commun. 2006;349:504-12 pubmed
  44. Wallace E, Perkins S, Sim R, Willis A, Feighery C, Jackson J. Degradation of C1-inhibitor by plasmin: implications for the control of inflammatory processes. Mol Med. 1997;3:385-96 pubmed
    ..These findings may also explain the efficacy of anti-plasmin agents in the treatment of C1-Inh deficiency states, as they may diminish plasmin-mediated C1-Inh degradation. ..
  45. Uwatoko S, Aotsuka S, Okawa M, Egusa Y, Yokohari R, Aizawa C, et al. C1q solid-phase radioimmunoassay: evidence for detection of antibody directed against the collagen-like region of C1q in sera from patients with systemic lupus erythematosus. Clin Exp Immunol. 1987;69:98-106 pubmed
    ..These findings suggest that the Clq-binding IgG in SLE sera is, at least in part, antibody directed against the collagen-like region of C1q. ..
  46. Baldwin W, Kasper E, Zachary A, Wasowska B, Rodriguez E. Beyond C4d: other complement-related diagnostic approaches to antibody-mediated rejection. Am J Transplant. 2004;4:311-8 pubmed
    ..Understanding the mechanisms by which complement integrates the interactions of leukocytes, platelets and parenchymal cells offers opportunities to further refine the diagnosis of rejection. ..
  47. Roberts Thomson P, Neoh S, Kennedy A, Smith M, O DONNELL J, Bradley J. Measurement of immune complexes with the liquid phase C1q binding assay: ten years experience in a routine diagnostic laboratory. Asian Pac J Allergy Immunol. 1987;5:149-54 pubmed
    ..Sequential monitoring of IC in RA and IE reflects response to treatment. ..
  48. Hamada A, Young J, Chmielewski R, Greene B. C1q enhancement of antibody-dependent granulocyte-mediated killing of nonphagocytosable targets in vitro. J Clin Invest. 1988;82:945-9 pubmed
    ..25 +/- 0.07 to 0.68 +/- 0.07 nm/10(6) cells.10 min (P less than 0.01). These results describe a novel functional role for C1q in enhancement of antibody-dependent cellular cytotoxicity towards nonphagocytosable targets...
  49. Busby T, Ingham K. Domain structure, stability, and interactions of human complement C1s-: characterization of a derivative lacking most of the B chain. Biochemistry. 1988;27:6127-35 pubmed
    ..They also provide direct proof for the occurrence of Ca2+ binding sites on the A chain and demonstrate that all or most of the sites on C1-s that are responsible for its interaction with C1-r and C1q are located on the A chain. ..
  50. de la Barrera S, Fejes M, Riera N, Scaglione C, Pérez Blanco R, de Bracco M. [Cytotoxicity induced by the serum of patients with AIDS and at high risk of AIDS against cells infected with Epstein-Barr virus]. Rev Argent Microbiol. 1985;17:137-43 pubmed
    ..Fc receptor (FcR) bridging between target cells FcR and effector cells FcR may play a role in the outcome of total ADCC. ..
  51. Matsumoto M, Nagaki K, Kitamura H, Kuramitsu S, Nagasawa S, Seya T. Probing the C4-binding site on C1s with monoclonal antibodies. Evidence for a C4/C4b-binding site on the gamma-domain. J Immunol. 1989;142:2743-50 pubmed
    ..Based on these results, the gamma-domain and the L chain constitute the catalytic site of C1s to activate C4 to C4b. Moreover, the generated C4b, although it still has weak affinity for C1s, can be replaced by newly coming C4. ..
  52. Bruno J, Carrillo M, Phillips T. In vitro antibacterial effects of antilipopolysaccharide DNA aptamer-C1qrs complexes. Folia Microbiol (Praha). 2008;53:295-302 pubmed publisher
  53. Bordin S, Page R. Role of platelet factors and serum complement in growth of fibroblasts with high-affinity Clq complement receptors. In Vitro Cell Dev Biol. 1988;24:719-26 pubmed
    ..High-affinity receptor cells may comprise a rapidly dividing subpopulation giving rise only to like progeny or to other, more differentiated cells. ..