Disease relevance of C1RL

• C1r-LP accounts for at least part of the endogenous proHp-cleavage activity because suppression of the C1r-LP expression by RNA interference reduced the cleavage of proHp by up to 45% in the cells of a human hepatoma cell line (HepG2) [1].

High impact information on C1RL

• This cleavage depended on proteolytic activity of C1r-LP because mutation of the putative active-site Ser residue abolished the reaction [1].
• We demonstrate that coexpression of the proform of Hp (proHp) and C1r-LP in COS-1 cells effected cleavage of proHp in the endoplasmic reticulum [1].
• The 487-residue CLSPa protein contains a CUB domain and a serine protease domain, possessing characteristic catalytic triad but lacking typical activation/cleavage sequence [2].
• Here we report a novel human C1r-like serine protease analog, CLSPa, derived from dendritic cells (DC) [2].
• Upon stimulation by agonistic anti-CD40 Ab, TNF-alpha, or LPS, CLSPa mRNA expression was significantly up-regulated in monocytic cells and monocyte-derived immature DC [2].

Biological context of C1RL

• 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 [3].

Anatomical context of C1RL

• When overexpressed in 293T cells, CLSPa protein was synthesized into the culture supernatants as a secretory protein, which had an inhibitory effect on complement-mediated cytotoxicity to antibody-sensitized erythrocytes [2].
• CLSPa mRNA is widely expressed, especially abundant in placenta, liver, kidney, pancreas, and myeloid cells, which are a major resources of serine proteases [2].

Associations of C1RL with chemical compounds

• Immunoprecipitation experiments failed to demonstrate an association of C1r-LP with the C1 complex in serum [3].
• Recombinant C1r-LP exhibits esterolytic activity against peptide thioesters with arginine at the P1 position, but its catalytic efficiency (kcat/K(m)) is lower than that of C1r and C1s [3].
• Thus C1r-LP may provide a novel means for the formation of the classical pathway C3/C5 convertase [3].
• The enzymic activity of C1r-LP is inhibited by di-isopropyl fluorophosphate and also by C1 inhibitor, which forms stable complexes with the protease [3].

Analytical, diagnostic and therapeutic context of C1RL

• Northern blotting demonstrated the expression of C1r-LP mRNA mainly in the liver and ELISA demonstrated the presence of the protein in human serum at a concentration of 5.5+/-0.9 microg/ml [3].

References