PROSITE documentation PDOC51699
DG-type SEA domain profile


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 (see <PDOC50024>). 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 (α-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 α-DG glycosylation for DG functions and how altered α-DG glycosylation leads to receptor dysfunction with direct implications for human diseases. However, functions contained within the DG transmembrane subunit (β-DG), and the roles of this subunit in human disease, are poorly understood [1,2]. The DG-type SEA domain forms the peptidase S72 family [E1].

The ~120-residue DG-type SEA domain is predicted to display a four-stranded antiparallel β sheet (β1-β4) backed by α helices (α1-α4). The cleavage occurs at a bend between the β2 and β3 sheets. The cleavage of the DG precursor requires the sequence GSIVV, where cleavage occurs between the glycine and serine [1,2].

The profile we developed covers the entire DG-type SEA domain.

Last update:

January 2014 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

SEA_DG, PS51699; DG-type SEA domain profile  (MATRIX)


1AuthorsAkhavan A. Crivelli S.N. Singh M. Lingappa V.R. Muschler J.L.
TitleSEA domain proteolysis determines the functional composition of dystroglycan.
SourceFASEB J. 22:612-621(2008).
PubMed ID17905726

2AuthorsOppizzi M.L. Akhavan A. Singh M. Fata J.E. Muschler J.L.
TitleNuclear translocation of beta-dystroglycan reveals a distinctive trafficking pattern of autoproteolyzed mucins.
SourceTraffic 9:2063-2072(2008).
PubMed ID18764929


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