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. 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 [ (PUBMED:15029246) (PUBMED:15498563) ].
The sructure 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 [ (PUBMED:15029246) (PUBMED:15498563) ].
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 (Baker's yeast) UBX domain-containing protein 1 or Suppressor of high-copy PP1 protein (shp1), the homologue of p47.
A Fas-associated protein factor, FAF1, potentiates Fas-mediated apoptosis.
Proc Natl Acad Sci U S A. 1995; 92: 11894-8
Display abstract
Fas, a member of the tumor necrosis factor receptor family, can induce apoptosis when activated by Fas ligand binding or anti-Fas antibody crosslinking. Genetic studies have shown that a defect in Fas-mediated apoptosis resulted in abnormal development and function of the immune system in mice. A point mutation in the cytoplasmic domain of Fas (a single base change from T to A at base 786), replacing isoleucine with asparagine, abolishes the signal transducing property of Fas. Mice homozygous for this mutant allele (lprcg/lprcg mice) develop lymphadenopathy and a lupus-like autoimmune disease. Little is known about the mechanism of signal transduction in Fas-mediated apoptosis. In this study, we used the two-hybrid screen in yeast to isolate a Fas-associated protein factor, FAF1, which specifically interacts with the cytoplasmic domain of wild-type Fas but not the lprcg-mutated Fas protein. This interaction occurs not only in yeast but also in mammalian cells. When transiently expressed in L cells, FAF1 potentiated Fas-induced apoptosis. A search of available DNA and protein sequence data banks did not reveal significant homology between FAF1 and known proteins. Therefore, FAF1 is an unusual protein that binds to the wild type but not the inactive point mutant of Fas. FAF1 potentiates Fas-induced cell killing and is a candidate signal transducing molecule in the regulation of apoptosis.
