Complement Component 1, R Subcomponent Like Protein (C1rL)

C1RL has an N-terminal signal peptide, a conserved CUB domain, a truncated complement control protein module, and a trypsin-like serine protease domain. It also has 2 N-glycosylation sites and 3 conserved cysteines in the CUB domain, but it lacks a consensus sequence for activation by upstream trypsin-like proteases. C1RL shares sequence similarity with C1r, C1s, and MASPs. C1RL mediates this cleavage. Coexpression of the proform of HP (proHP) and C1RL in COS-1 cells resulted in the cleavage of proHP in the endoplasmic reticulum. C1RL showed specificity for proHP, in that it did not cleave the proform of complement C1s, a protein similar to HP, particularly around the cleavage site. Suppression of C1RL expression by RNA interference reduced the cleavage of proHP by up to 45%.