The SEP (after shp1, eyc and p47) domain is an eukaryotic domain, which occurs frequently and mainly in single units. Almost all proteins containing a SEP domain are succeeded closely by a UBX domain (see PDOC50033). The function of the SEP domain is as yet unknown but it has been proposed to act as a reversible competitive inhibitor of the lysosomal cysteine protease cathepsin L. Most SEP domains are succeeded closely by a UBX domain PMID:15029246,PMID:15498563.

The structure of the SEP domain comprises a beta-sheet composed of four strands, and two alpha-helices. One side of the beta-sheet faces alpha1 and alpha2. The longer helix alpha1 packs against the four-stranded beta-sheet, where as the shorter helix alpha2 is located at one edge of the globular structure formed by alpha1 and the four stranded beta sheet. A number of highly conserved hydrophobic residues are present in the SEP domain, which are predominantly buried and form the hydrophobic core PMID:15029246,PMID:15498563.

INTERPRO:IPR012989, PFAM:PF08059