Critical Roles of SEA Domains

This mini-review delves into the multifaceted roles of SEA (sea urchin sperm protein, enterokinase, and agrin) domains, ubiquitous protein modules critical to the structure, and function of a wide range of membrane-associated and secreted proteins in organisms from yeast to humans. We explore the structural and functional characteristics of SEA domains based on their two types of fundamental characteristics: proteolytic and non-proteolytic SEA domains. We also examine the significance of SEA domains in different protein families, particularly in mucins and extracellular matrix proteins, emphasizing their roles in glycosylation, cell adhesion, and signal transduction. The review also highlights the crucial impact of SEA domains in health and disease contexts, with a focus on their implications in cancer progression and retinal health. Mutations within these domains are linked to a range of pathologies, including various cancers and congenital disorders, underscoring their clinical importance. Through this review, we aim to provide a deeper understanding of SEA domains, shedding light on their diverse biological functions and their potential as targets for therapeutic interventions in diseases where they play a pivotal role.