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A more recent version of this article appeared on April 1, 2004
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Submitted on June 26, 2003
Revised on December 29, 2003
Accepted on December 31, 2003
1 Departments of Biochemistry and Molecular Genetics, University of Illinois at Chicago
2 Department of Biological Sciences-Section of Ecology and Evolution, University of Illinois at Chicago
3 Cell Biology and Metabolism Branch, NICHD, NIH
4 Biological Sciences-Laboratory for Molecular Biology, University of Illinois at Chicago
* Corresponding author. E-mail address: nava{at}uic.edu.
The eukaryotic family of Arf GTPases plays a key role in the regulation of protein trafficking, and guanine-nucleotide exchange is crucial for Arf function. Exchange is stimulated by members of another family of proteins characterized by a 200 amino acid Sec7 domain, which alone is sufficient to catalyze exchange on Arf. Here, we analyzed the phylogeny of Sec7-domain containing proteins in seven model organisms, representing fungi, plants and animals. The phylogenetic tree has seven main groups, of which two include members from all seven model systems. Three groups are specific for animals, while two are specific for fungi. Based on this grouping, we propose a phylogenetically consistent set of names for members of the Sec7-domain family. Each group, except for one, contains proteins with known Arf exchange activity, implying that all members of this family have this activity. Contrary to the current convention, the sensitivity of Arf exchange activity to the inhibitor Brefeldin A probably cannot be predicted by group membership. Multiple alignment reveals group-specific domains outside the Sec7 domain and a set of highly conserved amino acids within it. Determination of the importance of these conserved elements in Arf exchange activity and other cellular functions is now possible.
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