A novel human complement-related protein, C1r-like protease (C1r-LP), specifically cleaves pro-C1s.

The availability of the human genome sequence allowed us to identify a human complement-related, C1r-like protease gene (c1r-LP) located 2 kb centromeric of the C1r gene (c1r). Compared with c1r, c1r-LP carries a large deletion corresponding to exons 4-8 of c1r. The open reading frame of the C1r-LP cDNA predicts a 50 kDa modular protein displaying 52% amino acid residue identity with the corresponding regions of C1r and 75% identity with a previously described murine C1r-LP.

A novel murine complement-related gene encoding a C1r-like serum protein.

C1r and C1s are highly specific serine proteases that initiate the classical pathway of complement activation. We recently demonstrated that, in the mouse, the genes encoding these proteins are duplicated. Analysis of the 5'-flanking region of the murine C1rA gene, the homologue of human C1r, revealed the presence of a novel gene encoding a C1r-like protein (c1r-LP).

Complement C1r and C1s genes are duplicated in the mouse: differential expression generates alternative isomorphs in the liver and in the male reproductive system.

C1r and C1s are the serine proteases that form the catalytic unit of the C1 complex, the first component of complement. In the present study, we found that the genes encoding murine C1r and C1s are duplicated. One set of these genes, referred to as c1rA and c1sA, are primarily expressed in the liver and are therefore the homologues of the human C1r and C1s genes.

Structure, function and molecular genetics of human and murine C1r.

C1r, the enzyme responsible for intrinsic activation of the C1 complex of complement, is a modular serine protease featuring an overall structural organization homologous to those of C1s and the mannan-binding lectin-associated serine proteases (MASPs). 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. The second part of this review will focus on recent discoveries dealing with a truncated, C1r-related protein, and the occurrence in the mouse of two isoforms, C1rA and C1rB, exhibiting tissue-specific expression patterns.

Calnexin is associated with and induced by overexpressed human complement protein C2.

C2 is a serum glycoprotein that is essential for activation of the classical and lectin pathways of the complement system. We reported previously that in transiently transfected COS cells, C2 accumulates in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC). Transfection with a cDNA corresponding to a variant C2 mRNA in which exon 17 is spliced out, C2Delta(17), resulted in retention of the mutant polypeptide in the ER.