PROSITE documentation PDOC50190

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 α-helices. The helices are arranged in a right-handed superhelix reminiscent of that found in the armadillo-repeat (see <PDOC50176>). 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.