The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

C2  -  complement component 2

Homo sapiens

Synonyms: ARMD14, C3/C5 convertase, CO2, Complement C2
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of C2


Psychiatry related information on C2


High impact information on C2


Chemical compound and disease context of C2


Biological context of C2

  • The complete genomic DNA sequence between C2 and TNX is now available [14].
  • Deficiencies in complement C2 are either due to abolition of C2 protein synthesis by mini-deletions that caused frameshift mutations, or blocked secretion of the C2 protein by single amino acid substitutions [14].
  • Two cDNA clones for complement component C2 have been isolated from a high-complexity human liver cDNA library by using a mixture of 64 synthetic oligonucleotides as a probe [15].
  • In studies of eight kindred, the 28-base pair deletion was observed in all C2Q0 alleles associated with the common type I deficient complotype/haplotype; this deletion was not present in normal C2 nor in type II C2-deficient genes [16].
  • Human complement proteins D, C2, and B. Active site mapping with peptide thioester substrates [17].

Anatomical context of C2

  • To examine the molecular basis of this deficiency, we established cultures of blood monocytes from four families with C2-deficient members [1].
  • Pulse-chase biosynthetic labeling experiments indicated that the C111Y mutant C2 was retained by transfected COS cells and secreted only in minimal amounts [18].
  • As a result Sh-TOR-ed1 pre-incubated with C2 inhibits classical pathway (CP)-mediated haemolysis of sheep erythrocytes in a dose-dependent manner [19].
  • Using metabolic labeling with [35S]methionine, immunoprecipitation, and SDS-polyacrylamide gel electrophoresis, we examined the effects of LPS on synthesis of C3 by human mononuclear phagocytes as well as synthesis of the second component of complement (C2), factor B, lysozyme, and total protein [20].
  • The relationship of the genes coding for HLA to those coding for properdin Factor B allotypes and for deficiency of the second component of complement (C2) was studied in families of patients with connective tissue disorders [21].

Associations of C2 with chemical compounds

  • MASP-2 is the protease responsible for activating C4 and C2 to generate the C3 convertase, C4bC2b [22].
  • The binding of MBL to microbial carbohydrates activates the MBL-associated serine proteases (MASPs), which recruit the complement factors, C4 and C2, to generate the C3 convertase or directly activate C3 [23].
  • This part of C2 is 34% homologous to the corresponding region of the related serine protease factor B and additional similarity is evident from a number of conservative amino acid replacements in this region [15].
  • C2 and fragment C2a had comparable reactivities and hydrolyzed peptides containing Leu-Ala-Arg and Leu-Gly-Arg, which have the same sequence as the cleavage sites of C3 and C5, respectively [17].
  • Two clusters of acidic amino acids near the NH2 terminus of complement component C4 alpha'-chain are important for C2 binding [24].

Enzymatic interactions of C2

  • MASP-3 downregulate the C4 and C2 cleaving activity of MASP-2 [23].
  • MASP-1 can cleave C2, and with low efficiency also C3, and may serve a function through direct C3 activation [25].

Regulatory relationships of C2

  • Mannan-binding lectin (MBL) activates the complement system through cleavage of C4 and C2 [26].
  • Recombinant IFN-gamma in concentrations ranging from 0.1 to 300 U/ml (0.003 to 8.8 ng/ml) stimulates C2 production by both cell populations [27].
  • The ability of gold sodium thiomalate to inhibit production of the second complement component (C2) by monocytes stimulated by a lymphokine (monocyte complement stimulator is demonstrated [28].
  • In contrast to PBL, lymphocytes isolated from the synovial membranes (SML) of patients with rheumatoid arthritis and their culture supernatants were able to stimulate C2 synthesis without exposure to mitogens or antigens [29].

Other interactions of C2

  • Design, synthesis and biological activity of novel C2-C3' N-Linked macrocyclic taxoids [30].
  • IFN-gamma produced dose-dependent stimulation of C2, factor B, C1-inh, C4-bp and factor H synthesis by all cell types expressing these proteins, but decreased C3 synthesis in all four cell types [4].
  • The addition of lymphoblastoid interferon alpha, fibroblast interferon beta and recombinant interferon gamma to in vitro monocyte cultures produced dose-dependent increases in transcription rates of the genes encoding the second component of complement (C2), factor B (B) and C1 inhibitor, and the abundance of their respective mRNA [31].
  • A lod score of 13 was calculated for linkage between C2 deficiency and HLA-B at a maximum likelihood value of the recombinant fraction of 0.04 [21].
  • Detailed analysis of these haplotypes suggests that a susceptibility gene or genes for both immunodeficiencies are located within the class III region of the MHC, possibly between the C4B and C2 genes [32].

Analytical, diagnostic and therapeutic context of C2

  • Southern blot analysis of genomic DNA of unrelated individuals identified a single C2 locus and showed no cross-hybridization with the factor B locus [15].
  • Western blot analysis indicated that secreted rC2 had the same apparent m.w. as C2 in human serum [33].
  • Site-directed mutagenesis experiments revealed that replacing subsets of the charged residues by their isosteric amides within either acidic cluster resulted in molecules having reduced C2 binding activity [24].
  • Northern blot analysis of total RNA isolated from transfected COS cells showed two bands of C2 mRNA, both of which were longer than human liver C2 mRNA and represent transcripts generated by the vector-C2 construct [33].
  • Subsequent molecular biology, biosynthetic, and immunofluorescence studies demonstrated that C2 secretion is impaired in Type II C2 deficiency because of different missense mutations at highly conserved residues in each of the C2Q0 alleles [34].


  1. The molecular basis for genetic deficiency of the second component of human complement. Cole, F.S., Whitehead, A.S., Auerbach, H.S., Lint, T., Zeitz, H.J., Kilbridge, P., Colten, H.R. N. Engl. J. Med. (1985) [Pubmed]
  2. A variable number of tandem repeats locus within the human complement C2 gene is associated with a retroposon derived from a human endogenous retrovirus. Zhu, Z.B., Hsieh, S.L., Bentley, D.R., Campbell, R.D., Volanakis, J.E. J. Exp. Med. (1992) [Pubmed]
  3. Human immunodeficiency virus type 1 induces expression of complement factors in human astrocytes. Speth, C., Stöckl, G., Mohsenipour, I., Würzner, R., Stoiber, H., Lass-Flörl, C., Dierich, M.P. J. Virol. (2001) [Pubmed]
  4. Effect of interferon-gamma on complement gene expression in different cell types. Lappin, D.F., Guc, D., Hill, A., McShane, T., Whaley, K. Biochem. J. (1992) [Pubmed]
  5. Inherited deficiency of the second component of complement. Rheumatic disease associations. Glass, D., Raum, D., Gibson, D., Stillman, J.S., Schur, P.H. J. Clin. Invest. (1976) [Pubmed]
  6. Genetic association study between senile dementia of Alzheimer's type and APOE/C1/C2 gene cluster. Kamino, K., Yoshiiwa, A., Nishiwaki, Y., Nagano, K., Yamamoto, H., Kobayashi, T., Nonomura, Y., Yoneda, H., Sakai, T., Imagawa, M., Miki, T., Ogihara, T. Gerontology. (1996) [Pubmed]
  7. Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Gold, B., Merriam, J.E., Zernant, J., Hancox, L.S., Taiber, A.J., Gehrs, K., Cramer, K., Neel, J., Bergeron, J., Barile, G.R., Smith, R.T., Hageman, G.S., Dean, M., Allikmets, R., Chang, S., Yannuzzi, L.A., Merriam, J.C., Barbazetto, I., Lerner, L.E., Russell, S., Hoballah, J., Hageman, J., Stockman, H. Nat. Genet. (2006) [Pubmed]
  8. Cell-specific expression of the human complement protein factor B gene: evidence for the role of two distinct 5'-flanking elements. Wu, L.C., Morley, B.J., Campbell, R.D. Cell (1987) [Pubmed]
  9. Kinin formation in hereditary angioedema plasma: evidence against kinin derivation from C2 and in support of "spontaneous" formation of bradykinin. Fields, T., Ghebrehiwet, B., Kaplan, A.P. J. Allergy Clin. Immunol. (1983) [Pubmed]
  10. Increased expression of proteasome subunits in skeletal muscle of cancer patients with weight loss. Khal, J., Hine, A.V., Fearon, K.C., Dejong, C.H., Tisdale, M.J. Int. J. Biochem. Cell Biol. (2005) [Pubmed]
  11. Development and use of PCR primers for the investigation of C1, C2 and C3 enterotoxin types of Staphylococcus aureus strains isolated from food-borne outbreaks. Chen, T.R., Hsiao, M.H., Chiou, C.S., Tsen, H.Y. Int. J. Food Microbiol. (2001) [Pubmed]
  12. Effects of vitamin D3 and IFN-gamma on the synthesis of the second complement component, C2, by a human myeloid leukemia (HL-60) cell line. Littman, B.H., Sanders, K.M. J. Immunol. (1988) [Pubmed]
  13. Association of systemic lupus erythematosus and SLE-like syndromes with hereditary and acquired complement deficiency states. Agnello, V. Arthritis Rheum. (1978) [Pubmed]
  14. Molecular genetics of the human MHC complement gene cluster. Yu, C.Y. Exp. Clin. Immunogenet. (1998) [Pubmed]
  15. Isolation of cDNA clones for human complement component C2. Bentley, D.R., Porter, R.R. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  16. Type I human complement C2 deficiency. A 28-base pair gene deletion causes skipping of exon 6 during RNA splicing. Johnson, C.A., Densen, P., Hurford, R.K., Colten, H.R., Wetsel, R.A. J. Biol. Chem. (1992) [Pubmed]
  17. Human complement proteins D, C2, and B. Active site mapping with peptide thioester substrates. Kam, C.M., McRae, B.J., Harper, J.W., Niemann, M.A., Volanakis, J.E., Powers, J.C. J. Biol. Chem. (1987) [Pubmed]
  18. A novel type II complement C2 deficiency allele in an African-American family. Zhu, Z.B., Atkinson, T.P., Volanakis, J.E. J. Immunol. (1998) [Pubmed]
  19. A Schistosoma protein, Sh-TOR, is a novel inhibitor of complement which binds human C2. Inal, J.M., Sim, R.B. FEBS Lett. (2000) [Pubmed]
  20. Pretranslational regulation of the synthesis of the third component of complement in human mononuclear phagocytes by the lipid A portion of lipopolysaccharide. Strunk, R.C., Whitehead, A.S., Cole, F.S. J. Clin. Invest. (1985) [Pubmed]
  21. The chromosomal order of genes controlling the major histocompatibility complex, properdin factor B, and deficiency of the second component of complement. Raum, D., Glass, D., Carpenter, C.B., Alper, C.A., Schur, P.H. J. Clin. Invest. (1976) [Pubmed]
  22. The mannan-binding lectin-associated serine proteases (MASPs) and MAp19: four components of the lectin pathway activation complex encoded by two genes. Schwaeble, W., Dahl, M.R., Thiel, S., Stover, C., Jensenius, J.C. Immunobiology (2002) [Pubmed]
  23. MASP-3 and its association with distinct complexes of the mannan-binding lectin complement activation pathway. Dahl, M.R., Thiel, S., Matsushita, M., Fujita, T., Willis, A.C., Christensen, T., Vorup-Jensen, T., Jensenius, J.C. Immunity (2001) [Pubmed]
  24. Two clusters of acidic amino acids near the NH2 terminus of complement component C4 alpha'-chain are important for C2 binding. Pan, Q., Ebanks, R.O., Isenman, D.E. J. Immunol. (2000) [Pubmed]
  25. Mannan-binding-lectin-associated serine proteases, characteristics and disease associations. Sørensen, R., Thiel, S., Jensenius, J.C. Springer Semin. Immunopathol. (2005) [Pubmed]
  26. MASP-2, the C3 convertase generating protease of the MBLectin complement activating pathway. Vorup-Jensen, T., Jensenius, J.C., Thiel, S. Immunobiology (1998) [Pubmed]
  27. Lymphokine stimulation of human macrophage C2 production is partially due to interferon-gamma. Sanders, K.M., Littman, B.H. J. Immunol. (1986) [Pubmed]
  28. Gold inhibition of the production of the second complement component by lymphokine-stimulated human monocytes. Littman, B.H., Schwartz, P. Arthritis Rheum. (1982) [Pubmed]
  29. Modulation of monocyte complement synthesis by lymphocytes and lymphocyte-conditioned media. Lappin, D., Whaley, K. Clin. Exp. Immunol. (1989) [Pubmed]
  30. Design, synthesis and biological activity of novel C2-C3' N-Linked macrocyclic taxoids. Ojima, I., Geng, X., Lin, S., Pera, P., Bernacki, R.J. Bioorg. Med. Chem. Lett. (2002) [Pubmed]
  31. Interferon-mediated transcriptional and post-transcriptional modulation of complement gene expression in human monocytes. Lappin, D.F., Birnie, G.D., Whaley, K. Eur. J. Biochem. (1990) [Pubmed]
  32. Major histocompatibility complex class III genes and susceptibility to immunoglobulin A deficiency and common variable immunodeficiency. Volanakis, J.E., Zhu, Z.B., Schaffer, F.M., Macon, K.J., Palermos, J., Barger, B.O., Go, R., Campbell, R.D., Schroeder, H.W., Cooper, M.D. J. Clin. Invest. (1992) [Pubmed]
  33. cDNA cloning and expression of human complement component C2. Horiuchi, T., Macon, K.J., Kidd, V.J., Volanakis, J.E. J. Immunol. (1989) [Pubmed]
  34. Type II human complement C2 deficiency. Allele-specific amino acid substitutions (Ser189 --> Phe; Gly444 --> Arg) cause impaired C2 secretion. Wetsel, R.A., Kulics, J., Lokki, M.L., Kiepiela, P., Akama, H., Johnson, C.A., Densen, P., Colten, H.R. J. Biol. Chem. (1996) [Pubmed]
WikiGenes - Universities