Complement C1S

Complement C1s, a highly specific SP (EC 3.4.21.42), mediates proteolytic activity of the C1 complex towards its complement substrates C4 and C2. C1s cleaves a single Arg-Ala bond in C4 and lead to the formation of C4a and C4b, it also results in a single Arg-Lys bond in C2 to produce C2a and C2b. Besides, the generation of the C3 convertase C4bC2a requires binding of C2 to C4b before cleavage by C1s. In addition, there are some noncomplement C1s protein substrates, such as heavy chain of the major histocompatibility complex class I antigens, β2-microglobulin, low-density lipoprotein receptor-related protein 6 (LRP6) and insulin-like growth factor-binding protein. C1s has also been proven to cleave the nuclear protein high-mobility group box 1, which is an alarmin released from apoptotic cells.

C1r binds to C1s and become the C1r2, C1s2 complex, which then binds to C1q. In the previous studies, it has demonstrated that patients with C1r or C1s deficiency have obviously decreased concentrations of the deficient protein (<1% of normal) and levels of the related protein that are 20% to 50% of normal. What’s more, C1r- or C1s-deficient patients are unable to activate C3 and C5 via C9 by the classical pathway therefore have decreased C3b-dependent opsonizing activity.

Reference

1. From Wikipedia: By Rantes, oringinally at pl.wikipedia, CC BY-SA 3.0 https://commons.wikimedia.org/wiki/File:Droga_klasyczna.png