The SEA domain has been named after the first three proteins in which it was identified (Sperm protein, Enterokinase and Agrin). The SEA domain has around 120 residues, it is an extracellular domain whose function is not known. It is found in one or two copies in mosaic extracellular or transmembrane proteins [E1]. The SEA domain is closely associated with regions receiving extensive O-glycosylation. It has been proposed that carbohydrates are required to stabilize SEA domains and protect them against proteolytic degradation and that the extent of substitution may control proteolytic processing [1,2].

The SEA domain contains an about 80-residue conserved region and an about 40-residue segment that separates the conserved region from the subsequent C-terminal domains. Secondary structure predictions and circular dichroism suggest an alternating conformation of β sheets and α helices for the SEA domain [1,3].

Some proteins known to contain a SEA domain are listed below:

• Vertebrate agrin, an heparan sulfate proteoglycan of the basal lamina of the neuromuscular junction. It is responsible for the clustering of acetylcholine receptors (AChRs) and other proteins at the neuromuscular junction.
• Mammalian enterokinase. It catalyzes the conversion of trypsinogen to trypsin which in turn activates other proenzymes including chymotrypsinogen, procarboxypeptidases, and proelastases.
• 63 kDa sea urchin sperm protein (SP63). It might mediate sperm-egg or sperm-matrix interactions.
• Animal perlecan, a heparan sulfate containing proteoglycan found in all basement membranes. It interacts with other basement membrane components such as laminin and collagen type IV and serves as an attachment substrate for cells.
• Some vertebrate epithelial mucins. They form a family of secreted and cell surface glycoproteins expressed by epithelial tissues and implicated in epithelial cell protection, adhesion modulation and signaling.
• Mammalian cell surface antigen 114/A10, an integral transmembrane protein that is highly expressed in hematopoietic progenitor cells and IL-3- dependent cell lines.

The profile we have developed covers the entire SEA domain, e.g. the conserved region and the less conserved extension following it.