Disease relevance of C1r

• We have expressed a truncated fragment of C1r protein without the N-terminal hydrophobic sequence in Escherichia coli and generated a polyclonal antibody against it [1].
• FUT-175 also inhibited complement-mediated hemolysis, including both classical and alternative pathways, sites of inhibition being on C1r and C1s as evidenced by the intermediate-cell technique [2].

High impact information on C1r

• This similarity extends to the serine protease component, which shares a similar modular construction and about 40% sequence identity with the C1r and C1s subcomponents of C1 [3].
• Although homology in the amino acid sequence of P100 with that of human C1r and C1s subcomponents of C was less than 40%, a striking similarity in domain organization was found among these proteins, indicating that P100 is a new C4-activating serine protease structurally similar to C1r and C1s [4].
• C1-Inh, which probably binds to C1r through the open end of the C1 cone, is too long asymmetric to be included within the cage [5].
• One of these showed significant sequence homology with human complement C1r precursor [1].
• Assignment of the complement serine protease genes C1r and C1s to chromosome 12 region 12p13 [6].

Biological context of C1r

• The C1r and C1s loci also provide useful polymorphic DNA markers for the short arm of chromosome 12 [6].
• Recent comparisons indicate a significant degree of sequence similarity between C1r and C1s and support the hypothesis that they are related by gene duplication [6].
• The open reading frame of full-length cDNA clones encodes a pre-protein with a calculated molecular mass of 50.6 kDa which, except for an internal deletion of several modules, has a modular organization similar to that of C1r and shows 51% overall amino acid identity to corresponding regions of C1rA [7].
• This review will initially summarize current information on the structure and function of C1r, with particular emphasis on the three-dimensional structure of its catalytic domain, which provides new insights into the activation mechanism of C1 [8].
• C1r and C1s are highly specific serine proteases that initiate the classical pathway of complement activation [7].

Associations of C1r with chemical compounds

• C1r and C1s are the serine proteases that form the catalytic unit of the C1 complex, the first component of complement [9].
• A 100-kDa protein in the C4-activating component of Ra-reactive factor is a new serine protease having module organization similar to C1r and C1s [4].

References