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. The SEA domain is closely associated with regions receiving extensive O-glycosylation. It has been proposed that carbohydrates are required to stabilise SEA domains and protect them against proteolytic degradation and that the extent of substitution may control proteolytic processing [ (PUBMED:7670383) (PUBMED:9762901) ].
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 beta sheets and alpha helices for the SEA domain [ (PUBMED:7670383) (PUBMED:9030729) ].
Some proteins known to contain a SEA domain include:
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 catalyses the conversion of trypsinogen to trypsin which in turn activates other proenzymes, including chymotrypsinogen, procarboxypeptidases, and proelastases.
63kDa 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.
Family alignment:
There are 6947 SEA domains in 4988 proteins in SMART's nrdb database.
Click on the following links for more information.
Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing SEA domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with SEA domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing SEA domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
The SEA module: a new extracellular domain associated with O-glycosylation.
Protein Sci. 1995; 4: 1421-5
Display abstract
Using a variety of homology search methods and multiple alignments, a new extracellular module was identified in (1) agrin, (2) enterokinase, (3) a 63-kDa sea urchin sperm protein, (4) perlecan, (5) the breast cancer marker MUCI (episialin), (6) the cell surface antigen 114/A10, and (7/8) two functionally uncharacterized, probably extracellular, Caenorhabditis elegans proteins. Despite the functional diversity of these adhesive proteins, a common denominator seems to be their existence in heavily glycosylated environments. In addition, the better characterized proteins mentioned above contain all O-glycosidic-linked carbohydrates such as heparan sulfate that contribute considerably to their molecular masses. The common module might regulate or assist binding to neighboring carbohydrate moieties.
Enterokinase, the initiator of intestinal digestion, is a mosaic protease composed of a distinctive assortment of domains.
Proc Natl Acad Sci U S A. 1994; 91: 7588-92
Display abstract
Enterokinase is a protease of the intestinal brush border that specifically cleaves the acidic propeptide from trypsinogen to yield active trypsin. This cleavage initiates a cascade of proteolytic reactions leading to the activation of many pancreatic zymogens. The full-length cDNA sequence for bovine enterokinase and partial cDNA sequence for human enterokinase were determined. The deduced amino acid sequences indicate that active two-chain enterokinase is derived from a single-chain precursor. Membrane association may be mediated by a potential signal-anchor sequence near the amino terminus. The amino terminus of bovine enterokinase also meets the known sequence requirements for protein N-myristoylation. The amino-terminal heavy chain contains domains that are homologous to segments of the low density lipoprotein receptor, complement components C1r and C1s, the macrophage scavenger receptor, and a recently described motif shared by the metalloprotease meprin and the Xenopus A5 neuronal recognition protein. The carboxyl-terminal light chain is homologous to the trypsin-like serine proteases. Thus, enterokinase is a mosaic protein with a complex evolutionary history. The amino acid sequence surrounding the amino terminus of the enterokinase light chain is ITPK-IVGG (human) or VSPK-IVGG (bovine), suggesting that single-chain enterokinase is activated by an unidentified trypsin-like protease that cleaves the indicated Lys-Ile bond. Therefore, enterokinase may not be the "first" enzyme of the intestinal digestive hydrolase cascade. The specificity of enterokinase for the DDDDK-I sequence of trypsinogen may be explained by complementary basic-amino acid residues clustered in potential S2-S5 subsites.
Metabolism (metabolic pathways involving proteins which contain this domain)
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with SEA domain which could be assigned to a KEGG orthologous group, and not all proteins containing SEA domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
