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,E1]. 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
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
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
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
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.
December 2013 / Profile and text revised.
PROSITE method (with tools and information) covered by this documentation:
Bork P. Patthy L.
The SEA module: a new extracellular domain associated with O-glycosylation.
Maeda T. Inoue M. Koshiba S. Yabuki T. Aoki M. Nunokawa E. Seki E. Matsuda T. Motoda Y. Kobayashi A. Hiroyasu F. Shirouzu M. Terada T. Hayami N. Ishizuka Y. Shinya N. Tatsuguchi A. Yoshida M. Hirota H. Matsuo Y. Tani K. Arakawa T. Carninci P. Kawai J. Hayashizaki Y. Kigawa T. Yokoyama S.
Solution structure of the SEA domain from the murine homologue of ovarian cancer antigen CA125 (MUC16).
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