Sec7

Sec7 refers to a family of guanine nucleotide exchange factors (GEFs) for ARF family small GTPases, named after the Saccharomyces cerevisiae gene Sec7. Sec7p encodes a Golgi-localized ARF-GEF essential for the secretory pathway, and its discovery helped establish the role of ARF activation in vesicle formation.

The defining feature of Sec7 family proteins is the Sec7 domain, a conserved catalytic module of about 200 amino acids that accelerates GDP-to-GTP exchange on ARF GTPases. Activation of ARF GTPases by Sec7-domain GEFs promotes recruitment of coat proteins and the assembly of vesicles at Golgi membranes, thereby regulating trafficking between the Golgi, endosomes, and the ER-Golgi cycle. Localization and activity are often controlled by additional domains and interactions with lipids such as phosphoinositides, as well as other small GTPases.

Diversity and distribution: The Sec7 family includes several subtypes with distinct cellular roles. In yeast, Gea1 and Gea2 are prominent ARF-GEFs. In mammals, the best known Sec7-domain GEFs are GBF1 and GBF2 (also referred to as BIG1 and BIG2), which function at the Golgi and endosomal systems. Other Sec7-domain proteins in vertebrates and invertebrates include members that serve as ARF-GEFs for different ARF paralogs and cellular compartments; some are related to cytohesins and other Sec7-domain-containing proteins that act on ARF6 and related GTPases.

Clinical and research relevance: Sec7-domain ARF-GEFs are targets of brefeldin A, a compound that inhibits Sec7 activity and disrupts Golgi trafficking. Abnormal Sec7-GEF signaling has been implicated in certain diseases, and researchers study Sec7p in yeast as a model for understanding vesicular transport and ARF regulation.