Sec12

Sec12 is a protein that functions as a guanine nucleotide exchange factor (GEF) for the small GTPase Sar1, playing a central role in COPII vesicle formation at the endoplasmic reticulum (ER). The SEC12 gene encodes this protein in budding yeast, and homologous Sec12 proteins are found in many eukaryotes, illustrating a conserved mechanism for initiating ER-to-Golgi transport.

Mechanistically, Sec12 activates Sar1 by promoting the exchange of GDP for GTP on Sar1. Activated Sar1-GTP associates with the ER membrane and recruits other COPII coat components, triggering the budding of COPII vesicles that carry secretory and membrane cargo toward the Golgi apparatus.

Localization and structure of Sec12 support its function. It is an ER-resident membrane protein, typically described as a type II membrane protein, with the catalytic, cytosolic region facing the cytosol to enable Sar1 activation at ER exit sites. Sec12 often localizes to ER exit sites in close proximity to Sec16 and other COPII factors, coordinating coat assembly with membrane remodeling.

Genetic and functional importance is demonstrated in Saccharomyces cerevisiae, where SEC12 is essential for viability. Loss or impairment of Sec12 blocks ER-to-Golgi transport, causing accumulation of secretory cargo in the ER and disrupting secretion. The role of Sec12 is broadly conserved, underscoring its fundamental place in the secretory pathway.

Sec12 activity is integrated with the broader COPII machinery and can be influenced by its interactions with Sec16 and other components that organize ER exit sites. See also COPII, Sar1, Sec16, and ER-to-Golgi transport.