{PDOC51399}
{PS51399; SEP}
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* SEP domain profile *
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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  beta-sheet  composed of four
strands, and two alpha-helices (see <PDB:1VAZ; A>). 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 [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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: August 2008 / First entry.

[ 1] Yuan X., Simpson P., Mckeown C., Kondo H., Uchiyama K., Wallis R.,
     Dreveny I., Keetch C., Zhang X., Robinson C., Freemont P.,
     Matthews S.
     "Structure, dynamics and interactions of p47, a major adaptor of the
     AAA ATPase, p97."
     EMBO J. 23:1463-1473(2004).
     PubMed=15029246; DOI=10.1038/sj.emboj.7600152
[ 2] Soukenik M., Diehl A., Leidert M., Sievert V., Buessow K., Leitner D.,
     Labudde D., Ball L.J., Lechner A., Naegler D.K., Oschkinat H.
     "The SEP domain of p47 acts as a reversible competitive inhibitor of
     cathepsin L."
     FEBS Lett. 576:358-362(2004).
     PubMed=15498563; DOI=10.1016/j.febslet.2004.09.037

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