PROSITE documentation PDOC51399
SEP domain profile


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 [1,2].

The sructure of the SEP domain comprises a β-sheet composed of four strands, and two α-helices (see <PDB:1VAZ; A>). One side of the β-sheet faces α1 and α2. The longer helix α1 packs against the four-stranded β-sheet, where as the shorter helix α2 is located at one edge of the globular structure formed by α1 and the four stranded β sheet. A number of highly conserved hydrophobic residues are present in the SEP domain, which are predominantly buried and form the hydrophobic core [1,2].

Some proteins known to contain a SEP domain are listed below:

  • Eukaryotic NSFL1 cofactor p37 (or p97 cofactor p37), an adapter protein required for Golgi and endoplasmic reticulum biogenesis. It is involved in Golgi and endoplasmic reticulum maintenance during interphase and in their reassembly at the end of mitosis.
  • Eukaryotic NSFL1 cofactor p47 (or p97 cofactor p47), a major adaptor molecule of the cytosolic AAA-type ATPase (ATPases associated with various cellular activities) p97. p47 is required for the p97-regulated membrane reassembly of the endoplasmic reticulum (ER), the nuclear envelope and the Golgi apparatus.
  • Vertebrate UBX domain-containing protein 4 (UBXD4).
  • Plant UBA and UBX domain-containing protein.
  • Saccharomyces cerevisiae UBX domain-containing protein 1 or Suppressor of high-copy PP1 protein (shp1), the homologue of p47.
  • Drosophila melanogaster eyes closed (eyc).

The profile we developed covers the entire SEP domain.

Last update:

August 2008 / First entry.


Technical section

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

SEP, PS51399; SEP domain profile  (MATRIX)


1AuthorsYuan X. Simpson P. Mckeown C. Kondo H. Uchiyama K. Wallis R. Dreveny I. Keetch C. Zhang X. Robinson C. Freemont P. Matthews S.
TitleStructure, dynamics and interactions of p47, a major adaptor of the AAA ATPase, p97.
SourceEMBO J. 23:1463-1473(2004).
PubMed ID15029246

2AuthorsSoukenik M. Diehl A. Leidert M. Sievert V. Buessow K. Leitner D. Labudde D. Ball L.J. Lechner A. Naegler D.K. Oschkinat H.
TitleThe SEP domain of p47 acts as a reversible competitive inhibitor of cathepsin L.
SourceFEBS Lett. 576:358-362(2004).
PubMed ID15498563

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