Clip-domain serine proteinases and their homologs: Role in crustacean immunity

Abstract

Clip-domain serine proteinases (clip-SPs) and their non-catalytic serine proteinase homologs (SPHs) constitute a highly conserved protein family that plays a critical role in the innate immunity of crustaceans. These extracellular proteolytic enzymes contain one or more N-terminal clip domains and a C-terminal serine proteinase or proteinase-like domain. Their classification as either catalytically active clip-SPs or inactive SPHs is based on the presence or absence of a conserved catalytic triad (His-Asp-Ser). This review provides a comprehensive overview of their structural features, molecular classification, and occurrence across diverse crustacean species. Clip-SPs and SPHs act as key modulators of the innate immune system. They mediate proteolytic activation of the prophenoloxidase (proPO) cascade, which drives the melanization response, and coordinate antimicrobial and antiviral defenses to limit pathogen proliferation and promote immune clearance. They also influence the transcription of antimicrobial peptides (AMPs), likely via molecular cross-talk between the proPO cascade and Toll signaling pathway. This review summarizes current knowledge of clip-SPs and SPHs in crustaceans, emphasizing their integrative function and potential relevance to host defense mechanisms.