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Gene Review

C1S  -  complement component 1, s subcomponent

Homo sapiens

Synonyms: C1 esterase, Complement C1s subcomponent, Complement component 1 subcomponent s
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Disease relevance of C1S

  • Hereditary angioneurotic edema (HAE) is an autosomal dominant disorder characterized by episodic local subcutaneous and submucosal edema caused by the deficiency of activated C1 esterase inhibitor protein (C1-INH, type I (C1NH): reduced serum antigen level, type II: reduced activity and normal serum antigen level) [1].
  • C1-Esterase inhibitor: an anti-inflammatory agent and its potential use in the treatment of diseases other than hereditary angioedema [2].
  • Potentiation of C1 esterase inhibitor by StcE, a metalloprotease secreted by Escherichia coli O157:H7 [3].
  • This study evaluates in dogs the effect of the C1-esterase inhibitor (C1-INH), a main inhibitor of the blood coagulation contact system, on the cardiovascular and respiratory dysfunction associated with endotoxic shock [4].
  • Combined treatment with C1 esterase inhibitor and antithrombin III improves survival in severe acute experimental pancreatitis [5].

Psychiatry related information on C1S

  • Concomitantly plasminogen increased from 113 +/- 14% to 142 +/- 18% (p less than 0.001), urokinase inhibiting activity fell from 105 +/- 10% to 90 +/- 9% (p less than 0.001) and C1-esterase inhibitor fell from 110 +/- 17% to 86 +/- 22% (p less than 0.05) in the oestrogen therapy group [6].

High impact information on C1S

  • C1 esterase-inhibitor concentrate prevents hypotension from plasma-protein solutions [7].
  • C1-esterase inhibitor (C1-Inh) therapy was introduced in clinical medicine about 25 years ago as a replacement therapy for patients with hereditary angioedema caused by a deficiency of C1-Inh [2].
  • Both siblings became symptom free after receiving danazol treatment, accompanied by a subnormal rise in C1 esterase inhibitor and C4 levels [8].
  • Evidence is given showing that the e region, but not the c or d, is released from a negatively charged surface when bound Hageman factor is exposed to proteolytic enzymes or whole plasma and that when this occurs in the presence of normal plasma, the e fragment becomes bound to C1 esterase inhibitor [9].
  • Infusion of C1-esterase inhibitor (the deficient factor in both HA and AA) immediately lowered bradykinin concentrations [10].

Chemical compound and disease context of C1S

  • We have identified a protein of previously unknown function encoded on the pO157 virulence plasmid of E. coli O157:H7, which is the first described protease that specifically cleaves C1 esterase inhibitor (C1-INH), a member of the serine protease inhibitor family [11].
  • Therefore we measured serum levels of C3, C4, and C1-esterase inhibitor (C1-INH) as well as C-reactive protein (CRP) in 167 patients with Crohn's disease (CD) and 111 patients with ulcerative colitis (UC) [12].
  • A 51-year-old man with recurrent episodes of angioedema was diagnosed as having autoimmune acquired angioedema, based on adult onset, lack of apparent family history, decreased activity of C1 esterase inhibitor (C1 INH) and CH50, decreased levels of serum C4 and Clq and the presence of autoantibodies to C1 INH [13].
  • The effect of conditioned media of 3-day cultures of blast cells from peripheral blood of 5 patients with acute myeloid leukemia (CM-AML) was studied on the synthesis of C2, factor B (Bf) and C1 esterase inhibitor (C1-INH) by human monocyte-macrophage cultures and HepG2 hepatoma cell line [14].
  • Because initial studies showed a functional deficiency of C1 esterase inhibitor and low C4 levels, he was treated with danazol, an attenuated androgen that has proven to be effective in the treatment of angioedema associated with C1 esterase inhibitor deficiency [15].

Biological context of C1S


Anatomical context of C1S


Associations of C1S with chemical compounds

  • The c.d. spectra of the complex between C1s and C1-esterase inhibitor indicate that tryptophan residues are affected by the complex-formation [25].
  • By N-terminal amino acid analysis, a newly formed threonine residue is found in the complex, suggesting that the inhibitor peptide chain is cleaved in the complex between C1s and C1-esterase inhibitor [25].
  • The reaction between complement factor C1s and C1-esterase inhibitor has been investigated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, N-terminal amino acid analysis and c.d. studies [25].
  • The assay is sensitive to inhibition by ethylene glycol bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) (which allows alternative pathway activation), ethylene diamine tetraacetic acid (EDTA), mannose, N-acetylglucosamine and C1 esterase inhibitor (C1-INH), whereas it was not inhibited by galactose [26].
  • In this study we investigated the exon-intron organization of the human C1R gene, which spans 11 kb from the initiation codon to the stop codon, and is very similar in exon-intron structure to the C1S gene [27].

Physical interactions of C1S

  • Our results indicated that they represented free t-PA and t-PA in complex with respectively C1-esterase inhibitor and alpha 2-antiplasmin [28].

Regulatory relationships of C1S

  • Initial studies on the administration of C1-esterase inhibitor to patients with septic shock or with a vascular leak syndrome induced by interleukin-2 therapy [29].
  • Results to date indicate that antithrombin III controls the activity of both thrombin and Factor Xa, C-1-esterase inhibitor controls kallikrein and probably activated Hageman Factor (Factor XIIa), and alpha-2-antiplasmin controls plasmin activity [30].

Other interactions of C1S


Analytical, diagnostic and therapeutic context of C1S


  1. Mutation screening of the C1 inhibitor gene among Hungarian patients with hereditary angioedema. Kalmár, L., Bors, A., Farkas, H., Vas, S., Fandl, B., Varga, L., Füst, G., Tordai, A. Hum. Mutat. (2003) [Pubmed]
  2. C1-Esterase inhibitor: an anti-inflammatory agent and its potential use in the treatment of diseases other than hereditary angioedema. Caliezi, C., Wuillemin, W.A., Zeerleder, S., Redondo, M., Eisele, B., Hack, C.E. Pharmacol. Rev. (2000) [Pubmed]
  3. Potentiation of C1 esterase inhibitor by StcE, a metalloprotease secreted by Escherichia coli O157:H7. Lathem, W.W., Bergsbaken, T., Welch, R.A. J. Exp. Med. (2004) [Pubmed]
  4. Endotoxin-induced pulmonary dysfunction is prevented by C1-esterase inhibitor. Guerrero, R., Velasco, F., Rodriguez, M., Lopez, A., Rojas, R., Alvarez, M.A., Villalba, R., Rubio, V., Torres, A., del Castillo, D. J. Clin. Invest. (1993) [Pubmed]
  5. Combined treatment with C1 esterase inhibitor and antithrombin III improves survival in severe acute experimental pancreatitis. Yamaguchi, H., Weidenbach, H., Lührs, H., Lerch, M.M., Dickneite, G., Adler, G. Gut (1997) [Pubmed]
  6. Activators and inhibitors of coagulation and fibrinolysis in patients with prostatic cancer treated with oestrogen or orchidectomy. Henriksson, P., Blombäck, M., Bratt, G., Edhag, O., Eriksson, A. Thromb. Res. (1986) [Pubmed]
  7. C1 esterase-inhibitor concentrate prevents hypotension from plasma-protein solutions. Van der Starre, P., Sinclair, D., Damen, J., Brummelhuis, H. N. Engl. J. Med. (1979) [Pubmed]
  8. Familial angioedema associated with C1 esterase-inhibitor deficiency. A new genetic variant in hereditary angioedema? Chiu, J.T. JAMA (1982) [Pubmed]
  9. The relationship of structure and function in human Hageman factor. The association of enzymatic and binding activities with separate regions of the molecule. Revak, S.D., Cochrane, C.G. J. Clin. Invest. (1976) [Pubmed]
  10. Plasma bradykinin in angio-oedema. Nussberger, J., Cugno, M., Amstutz, C., Cicardi, M., Pellacani, A., Agostoni, A. Lancet (1998) [Pubmed]
  11. StcE, a metalloprotease secreted by Escherichia coli O157:H7, specifically cleaves C1 esterase inhibitor. Lathem, W.W., Grys, T.E., Witowski, S.E., Torres, A.G., Kaper, J.B., Tarr, P.I., Welch, R.A. Mol. Microbiol. (2002) [Pubmed]
  12. High normal serum levels of C3 and C1 inhibitor, two acute-phase proteins belonging to the complement system, occur more frequently in patients with Crohn's disease than ulcerative colitis. Bene, L., Füst, G., Fekete, B., Kovács, A., Horváth, L., Prohászka, Z., Miklós, K., Pálos, G., Daha, M., Farkas, H., Varga, L. Dig. Dis. Sci. (2003) [Pubmed]
  13. Autoimmune acquired form of angioedema that responded to danazol therapy. Higa, S., Hirata, H., Minami, S., Hashimoto, S., Suemura, M., Saeki, Y., Kawase, I., Tanaka, T. Intern. Med. (2002) [Pubmed]
  14. Effect of conditioned media of acute myeloid leukemia blast cells on complement synthesis by cultured human cells of monocyte and hepatocyte origin. Gyapay, G., Schmidt, B., Válay, M., Falus, A., Anh-Tuan, N., Pánya, A., Kókai, M., Onody, K., Mód, A., Füst, G. Complement and inflammation. (1991) [Pubmed]
  15. Exacerbation of a lupus-erythematosus-like syndrome during treatment of non-C1-esterase-inhibitor-dependent angioedema with danazol. Fretwell, M.D., Altman, L.C. J. Allergy Clin. Immunol. (1982) [Pubmed]
  16. Genetic studies of low-abundance human plasma proteins. XI. Linkage analysis and population genetics of the C1S subcomponent of the first complement component. Lyons, L.A., Kamboh, M.I., Ferrell, R.E. Complement and inflammation. (1989) [Pubmed]
  17. C1 esterase inhibitor (C1-INH) can reduce plasma concentrations of the complement activation product C5a. Nürnberger, W., Petrik, K., Burdach, S., Göbel, U. Intensive care medicine. (1994) [Pubmed]
  18. Hereditary angioneurotic edema (HANE): Lack of close linkage between HLA haplotypes and C1 esterase inhibitor deficiency. Ohela, K., Tiilikainen, A., Kaakinen, A., Räsänen, J. Tissue Antigens (1977) [Pubmed]
  19. Rapid fibrinolysis, augmented Hageman factor (factor XII) titers, and decreased C1 esterase inhibitor titers in women taking oral contraceptives. Gordon, E.M., Ratnoff, O.D., Saito, H., Donaldson, V.H., Pensky, J., Jones, P.K. J. Lab. Clin. Med. (1980) [Pubmed]
  20. Synthesis and expression of C1 inhibitor by human umbilical vein endothelial cells. Schmaier, A.H., Murray, S.C., Heda, G.D., Farber, A., Kuo, A., McCrae, K., Cines, D.B. J. Biol. Chem. (1989) [Pubmed]
  21. A phase I study of recombinant human C1 inhibitor in asymptomatic patients with hereditary angioedema. van Doorn, M.B., Burggraaf, J., van Dam, T., Eerenberg, A., Levi, M., Hack, C.E., Schoemaker, R.C., Cohen, A.F., Nuijens, J. J. Allergy Clin. Immunol. (2005) [Pubmed]
  22. Characterization of the StcE protease activity of Escherichia coli O157:H7. Grys, T.E., Walters, L.L., Welch, R.A. J. Bacteriol. (2006) [Pubmed]
  23. Inhibition of activation of human T lymphocytes by the complement C1 esterase inhibitor. Eriksson, H., Sjögren, H.O. Immunology (1995) [Pubmed]
  24. Trimer and tetramer complexes containing C1 esterase inhibitor, C1r and C1s, in serum and synovial fluid of patients with rheumatic disease. Laurell, A.B., Mårtensson, U., Sjöholm, A.G. J. Immunol. Methods (1990) [Pubmed]
  25. Structural and circular-dichroism studies on the interaction between human C1-esterase inhibitor and C1s. Nilsson, T., Sjöholm, I., Wiman, B. Biochem. J. (1983) [Pubmed]
  26. A hemolytic assay for the estimation of functional mannose-binding lectin levels in human serum. Kuipers, S., Aerts, P.C., Sjöholm, A.G., Harmsen, T., van Dijk, H. J. Immunol. Methods (2002) [Pubmed]
  27. The human complement component C1R gene: the exon-intron structure and the molecular basis of allelic diversity. Nakagawa, M., Yuasa, I., Irizawa, Y., Umetsu, K. Ann. Hum. Genet. (2003) [Pubmed]
  28. Isolation of tissue-type plasminogen activator-inhibitor complexes from human plasma. Evidence for a rapid plasminogen activator inhibitor. Thorsen, S., Philips, M. Biochim. Biophys. Acta (1984) [Pubmed]
  29. Initial studies on the administration of C1-esterase inhibitor to patients with septic shock or with a vascular leak syndrome induced by interleukin-2 therapy. Hack, C.E., Ogilvie, A.C., Eisele, B., Jansen, P.M., Wagstaff, J., Thijs, L.G. Prog. Clin. Biol. Res. (1994) [Pubmed]
  30. Control of coagulation and fibrinolysis by plasma proteinase inhibitors. Travis, J., Salvesen, G. Behring Inst. Mitt. (1983) [Pubmed]
  31. Postburn edema and related changes in interleukin-2, leukocytes, platelet activation, endothelin-1, and C1 esterase inhibitor. Kowal-Vern, A., Walenga, J.M., Sharp-Pucci, M., Hoppensteadt, D., Gamelli, R.L. The Journal of burn care & rehabilitation. (1997) [Pubmed]
  32. Plasma levels of prekallikrein, alpha-2-macroglobulin and C1-esterase inhibitor in patients with urticarial reaction to contrast media. Mikkonen, R., Aronen, H.J., Kivisaari, L., Piilonen, A., Syrjälä, M. Acta radiologica (Stockholm, Sweden : 1987) (1997) [Pubmed]
  33. Serum concentrations of C reactive protein, alpha1 antitrypsin, and complement (C3, C4, C1 esterase inhibitor) before and during the Vuelta a Espańa. Semple, S.J., Smith, L.L., McKune, A.J., Hoyos, J., Mokgethwa, B., San Juan, A.F., Lucia, A., Wadee, A.A. British journal of sports medicine. (2006) [Pubmed]
  34. Inhibition of plasmin, urokinase, tissue plasminogen activator, and C1S by a myxoma virus serine proteinase inhibitor. Lomas, D.A., Evans, D.L., Upton, C., McFadden, G., Carrell, R.W. J. Biol. Chem. (1993) [Pubmed]
  35. Molecular investigation of interspousal transmission of hepatitis C virus in two Japanese patients who acquired acute hepatitis C after 40 or 42 years of marriage. Nakayama, H., Sugai, Y., Ikeya, S., Inoue, J., Nishizawa, T., Okamoto, H. J. Med. Virol. (2005) [Pubmed]
  36. Complement and contrast material reactors. Lasser, E.C., Lang, J.H., Lyon, S.G., Hamblin, A.E. J. Allergy Clin. Immunol. (1979) [Pubmed]
  37. A surface-bound form of human C1 esterase inhibitor improves xenograft rejection. Matsunami, K., Miyagawa, S., Yamada, M., Yoshitatsu, M., Shirakura, R. Transplantation (2000) [Pubmed]
  38. Rescue therapy with C1-esterase inhibitor concentrate after emergency coronary surgery for failed PTCA. Bauernschmitt, R., Böhrer, H., Hagl, S. Intensive care medicine. (1998) [Pubmed]
  39. Septic shock after liver transplantation for Caroli's disease: clinical improvement after treatment with C1-esterase inhibitor. Marx, G., Nashan, B., Cobas Meyer, M., Vangerow, B., Schlitt, H.J., Ziesing, S., Leuwer, M., Piepenbrock, S., Rueckoldt, H. Intensive care medicine. (1999) [Pubmed]
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