HpARI (CCP1/2) (rec.) (His)

HpARI is a protein secreted by the mouse parasite Heligmosomoides polygyrus. The mature protein HpARI, containing three predicted Complement Control Protein (CCP)-like modules (also known as Short Consensus Repeats (SCRs) or sushi-domains), suppresses type 2 (allergic) immune responses through interference in the interleukin-33 (IL-33) pathway. During cell damage, HpARI gains access to the nucleus of necrotic cells, where it binds directly to IL-33 and nuclear DNA, preventing secretion and binding of IL-33 to its receptor. A non-natural truncation consisting of the first 2 domains of HpARI (CCP1/2) retains IL-33 and DNA binding capacity. HpARI (CCP1/2) is able to stabilize IL-33, increasing its half-life and amplifying its effects. HpARI (CCP1/2) increases IL-33 activity by protecting it from oxidation and proteolytic degradation. HpARI (CCP1/2) (rec.) (His) is a new type of reagent to study IL-33-mediated pathology in vivo. Protein function: Secreted protein which suppresses the host allergic response by inhibiting the interaction of host IL33 with its receptor in order to maintain parasitic infection (PubMed:29045903). Binds to both host IL33 and host nuclear DNA and this dual binding blocks the interaction of IL33 with its receptor, and tethers IL33 within necrotic cells, preventing its release, and blocking allergic response initiation (PubMed:29045903). [The UniProt Consortium]