{PDOC50190} {PS50190; SEC7} {BEGIN} *********************** * SEC7 domain profile * *********************** The SEC7 domain was named after the first protein found to contain such a region [1]. SEC7 family proteins are guanine nucleotide exchange factor (GEF) specific for the ADP-rybosylation factors (ARF), a Ras-like GTPases which is important for vesicular protein trafficking. Although SEC7 proteins are highly divergent in their overall sequence they share a common region of roughly 200 amino acids known as the SEC7 domain. Proteins containing a SEC7 domain are found in fungi, animals and plants. SEC7 domains mediate interaction with ARF and catalyses GDP to GTP exchange [2,3,4]. Crystal structure of the human ARNO SEC7 domain has been solved [5,6] and consist of 10 alpha-helices. The helices are arranged in a right-handed superhelix reminiscent of that found in the armadillo-repeat (see ). The C-terminal part of the domain mediates interaction with Arf-1 through hydrophobic and polar residues. The nucleotide exchange activity is dependent on a conserved glutamate residue located in the loop between helix f and g [5,6]. The corresponding residue in Arabidopsis Emb30 protein is mutated to a lysine in a deficient allele [7]. Some proteins known to contain a SEC7 domain are listed below. - Yeast SEC7 protein. Associated with ER, essential for fusion of vesicles to the Golgi. - Mammalian cytohesin 1. - Mammalian cytohesin 2 (ARF nucleotide-binding site opener; ARNO). - Mammalian cytohesin 3. - Mammalian cytohesin 4. - Mammalian brefeldin A-inhibited guanine nucleotide-exchange proteins 1 and 2 (ARFGEP1 and ARFGEP2). - Mammalian golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1). We developed a profile that spans the whole domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: December 2001 / First entry. [ 1] Achstetter T., Franzusoff A., Field C., Schekman R. "SEC7 encodes an unusual, high molecular weight protein required for membrane traffic from the yeast Golgi apparatus." J. Biol. Chem. 263:11711-11717(1988). PubMed=3042778 [ 2] Klarlund J.K., Guilherme A., Holik J.J., Virbasius J.V., Chawla A., Czech M.P. "Signaling by phosphoinositide-3,4,5-trisphosphate through proteins containing pleckstrin and Sec7 homology domains." Science 275:1927-1930(1997). PubMed=9072969 [ 3] Klarlund J.K., Rameh L.E., Cantley L.C., Buxton J.M., Holik J.J., Sakelis C., Patki V., Corvera S., Czech M.P. "Regulation of GRP1-catalyzed ADP ribosylation factor guanine nucleotide exchange by phosphatidylinositol 3,4,5-trisphosphate." J. Biol. Chem. 273:1859-1862(1998). PubMed=9442017 [ 4] Abergel C., Chavrier P., Claverie J.-M. "Triple association of CDC25-, Dbl- and Sec7-related domains in mammalian guanine-nucleotide-exchange factors." Trends Biochem. Sci. 23:472-473(1998). PubMed=9868368 [ 5] Cherfils J., Menetrey J., Mathieu M., Le Bras G., Robineau S., Beraud-Dufour S., Antonny B., Chardin P. "Structure of the Sec7 domain of the Arf exchange factor ARNO." Nature 392:101-105(1998). PubMed=9510256; DOI=10.1038/32210 [ 6] Mossessova E., Gulbis J.M., Goldberg J. "Structure of the guanine nucleotide exchange factor Sec7 domain of human arno and analysis of the interaction with ARF GTPase." Cell 92:415-423(1998). PubMed=9476900 [ 7] Shevell D.E., Leu W.M., Gillmor C.S., Xia G., Feldmann K.A., Chua N.H. "EMB30 is essential for normal cell division, cell expansion, and cell adhesion in Arabidopsis and encodes a protein that has similarity to Sec7." Cell 77:1051-1062(1994). PubMed=8020095 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}