SEA

Domain found in sea urchin sperm protein, enterokinase, agrin

• SMART accession number: SM00200
• Description: Proposed function of regulating or binding carbohydrate sidechains.
• Interpro abstract (IPR000082): SEA is an extracellular domain associated with O-glycosylation [(PUBMED:7670383)]. Proteins found to contain SEA-modules include, agrin, enterokinase, 63 kDa Strongylocentrotus purpuratus (Purple sea urchin) sperm protein, perlecan (heparan sulphate proteoglycan core, mucin 1 and the cell surface antigen, 114/A10, and two functionally uncharacterised, 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 characterised proteins all contain O-glycosidic-linked carbohydrates such as heparan sulphate that contribute considerably to their molecular masses. The common module might regulate or assist binding to neighbouring carbohydrate moieties.

  Enterokinase, the initiator of intestinal digestion, is a mosaic protease composed of a distinctive assortment of domains [(PUBMED:8052624)].

There are 572 SEA domains in 438 proteins in SMART's nrdb database.

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Bork P, Patthy L
• The SEA module: a new extracellular domain associated with O-glycosylation.
• Protein Sci. 1995; 4: 1421-5

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.

• Kitamoto Y, Yuan X, Wu Q, McCourt DW, Sadler JE
• 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

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)

% proteins involved	KEGG pathway ID	Description
100.00	map04512	ECM-receptor interaction

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%.

Structure (3D structures containing this domain)

3D Structures of SEA domains in PDB

PDB code	Title
1ivz	Solution structure of the sea domain from murine hypothetical protein homologous to human mucin 16
2e7v	Crystal structure of sea domain of transmembrane protease from mus musculus

Links (links to other resources describing this domain)

• INTERPRO: IPR000082