PROSITE documentation PDOC50024

SEA domain profile

The SEA domain has been named after the first three proteins in which it was identified (Sperm protein, Enterokinase and Agrin). SEA domains consist of about 120 residues, of which about 80 residues are highly conserved. The SEA domains always exist in the extracellular region and often are accompanied by an-O-linked glycochain at the N-terminal side. The SEA domain is found in one or more copies in mosaic extracellular or transmembrane proteins [1,2,3]. A subclass of proteins with the SEA domain fold exists as heterodimers generated by autoproteolytic cleavage between a serine and a glycine at a characteristic GSVVV sequence. The result is a heterodimerix yet single-domain structure. For the SEA domains, this cleavage reaction may have evolved as a membrane protective function and/or to serve as a receptor-ligand entity. It seems that the GSVVV-containing SEA domains have evolved to enable their own dissociation, whereas SEA domains without the proteolytic sequence and with a conserved disulfid have evolved to be stable [4,5].

The SEA domain forms a unique α/β sandwich fold, with the N and C termini on the same side of the molecule (see <PDB:1IVZ>). The α/β sandwich fold can be divided into two layers. One layer consists of four-stranded antiparallel β sheets and a short α helix, whereas the other layer consists of two long α helices and two-stranded short β sheets [5,6].

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.