Domain

DG-type SEA domain (IPR030398)

Short name: SEA_DG_dom

Domain relationships

None.

Description

This entry represents the DG-type SEA domain.

Dystroglycan (DG) is an integral membrane receptor linking the extracellular matrix (ECM) and cytoskeleton. Through widespread expression in a variety of cell types, including muscle, neural and epithelial cells, DG plays diverse and important roles in cell functions from basement membrane assembly to tissue morphogenesis and structural integrity. DG is encoded by a single gene and posttranslationally cleaved into two noncovalently associated subunits by autoproteolysis within a distinctive protein motif called an sea urchin- enterokinase-agrin (SEA) domain. The resulting heterodimer is composed of a transmembrane subunit that tethers to the cell surface an extracellular subunit bearing extensive O-linked glycosylation. O-linked glycosylation of the extracellular DG subunit (alpha-DG) mediates binding to several ECM ligands, including laminins and perlecan. The cleavage of DG elicits a conspicuous change in its ligand-binding activity. Extensive work has demonstrated the importance of alpha-DG glycosylation for DG functions and how altered alpha-DG glycosylation leads to receptor dysfunction with direct implications for human diseases. However, functions contained within the DG transmembrane subunit (beta-DG), and the roles of this subunit in human disease, are poorly understood [PMID: 17905726, PMID: 18764929]. The DG-type SEA domain forms the peptidase S72 family.

The ~120-residue DG-type SEA domain is predicted to display a four-stranded antiparallel beta sheet (beta1-beta4) backed by alpha helices (alpha1-alpha4). The cleavage occurs at a bend between the beta2 and beta3 sheets. The cleavage of the DG precursor requires the sequence GSIVV, where cleavage occurs between the glycine and serine [PMID: 17905726, PMID: 18764929].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles