Disease relevance of C2

• Local extrahepatic expression of complement genes C3, factor B, C2, and C4 is increased in murine lupus nephritis [1].
• The results of this analysis suggest a selective pressure to conserve the intergenic sequence between C2 and Bf genes and that further studies of these sequences will be useful in elucidating mechanisms controlling the acute phase response [2].
• These results suggest that changes in the metabolism of estradiol via the C-2 pathway might play a significant role in decreasing risk for breast cancer in women [3].

High impact information on C2

• The complete gene structure of Factor B has been solved in man and rapid progress is being made with the C2 and C4 genes [4].
• Remarkably there are sequence homologies between these proteins and C2 and Factor B, probably related to the ability to bind to one or other of the structurally similar proteins C3b and C4b [4].
• As this gene is very closely spaced to the related Factor B gene [the C2 poly(A) site is only 421 bp from the transcription start site of Factor B] we have isolated this same intergenic sequence from four other mammals (mouse, cat, rabbit and cow) [5].
• Comparison of the maps orients the complement gene clusters in the S region with the 21-OHB gene pointing towards the K end and the C2 gene pointing towards the D end of the MHC [6].
• The distances between the E alpha and 21-OHB genes is 430 kb and between the C2 and TNF-alpha genes at least 420 kb [6].

Biological context of C2

• Like the human Bf gene, murine Bf and C2 each consist of 18 exons with similar intron-exon organizations [7].
• The resulting mouse is deficient in both factor B and C2, and hence the alternative and classical pathways of complement activation, and adds to the repertoire of models for studying the in vivo role of complement in the immune system [8].
• The down-regulation of C2 gene expression was sufficient to cause a complete loss of classical pathway function as determined by the failure of sera from the deficient mice to opsonize antibody-sensitized sheep erythrocytes and by impairment of immune complex processing in vivo [8].
• Evidence from cDNA clones shows that the two C2 transcripts are generated by an alternative splice at the donor site of exon 14 producing long and short C2 mRNA species that differ by 21 base pairs encoding a region within the binding pocket (amino acids 636-642 (GSTCKDH)) of the serine proteinase domain [7].
• The S region of the mouse major histocompatibility complex (MHC) encodes the class III proteins, the second (C2) and fourth (C4) components of complement, and factor B. Previously, the assignment of S-region haplotypes was based on analysis of protein polymorphisms [9].

Anatomical context of C2

• By contrast, specific mRNA content of C2 and factor B in macrophages differed significantly from those observed in liver for each strain [10].
• gamma-Interferon increases expression of class III complement genes C2 and factor B in human monocytes and in murine fibroblasts transfected with human C2 and factor B genes [11].
• The second component of complement (C2) and factor B are major histocompatibility complex class III gene products synthesized in mononuclear phagocytes [11].
• Cell-free biosynthesis in the presence of microsomes demonstrate that this intracellular C2 protein (70 kDa) is apparently capable of traversing the membrane of the endoplasmic reticulum [12].
• Further, the repeated immunisation with the C1/C2 mixture caused tendon calcification and bone irregularity, together with decreased NTPPH activity [13].

Associations of C2 with chemical compounds

• Ra-reactive factor (RaRF), a C-dependent bactericidal factor in mice, is composed of one polysaccharide-binding component and one C4/C2-activating component [14].
• 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 [15].
• The mouse cDNA homologues of the rat C2, C9, and C5 subunits of the multicatalytic proteinase have been cloned and expressed in bacteria [16].
• Human complement protein C2. Alternative splicing generates templates for secreted and intracellular C2 proteins [12].
• These results are consistent with the identification of a pool of unassembled C2 exon-containing NR1 subunits, i.e., NR1-1a, NR1-1b, NR1-2a, and NR1-2b, selectively solubilised by 1% Triton X-100/1 M NaCl [17].

Physical interactions of C2

• Complement C2 receptor inhibitor trispanning and the beta-chain of C4 share a binding site for complement C2 [18].

Other interactions of C2

• Further studies revealed that the two adjacent genes, complement component C2 and D17H6S45, had been down regulated as a result of the disruption [8].
• Structural polymorphism of mouse complement C2 detected by microscale peptide mapping: linkage to H-2 [19].
• They were assessed for their effect on the activation and stability of the cell-bound classical-pathway C3 convertase, EAC14b2a and on the binding of C2 and C4bp to EC4b [20].
• This effect is specific inasmuch as the expression of other genes (e.g. C3) is decreased by interferon-gamma, and interferon-alpha and beta at concentrations one to two logs greater have only a minimal effect on C2 and factor B gene expression [21].
• Three cDNA clones containing the mouse apolipoprotein C2 (Apoc2) gene were isolated from a mouse liver cDNA library [22].

Analytical, diagnostic and therapeutic context of C2

• Molecular cloning and linkage analysis of the Japanese medaka fish complement Bf/C2 gene [23].
• Complement C2 was isolated from 17 mouse strains by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and examined for structural polymorphism by using micro-peptide mapping [19].
• As assessed by Northern blot analysis, neither endotoxin nor IL 1 affected liver C2-specific mRNA but increased specific C2 mRNA levels in kidney and lung [10].

References