ADP-ribosylation factor guanine nucleotide exchange factor 1 (ARFGEF1)

ADP-ribosylation factor guanine nucleotide exchange factor 1 (ARFGEF1, also known as BIG1) is a large protein (∼209 kDa) that catalyzes the exchange of GDP for GTP on ADP-ribosylation factors (ARFs), thereby activating them during intracellular vesicular trafficking. ARFGEF1 possesses a Sec7 domain responsible for this exchange activity, which is also the target for inhibition by Brefeldin A. This protein is essential for the maintenance of Golgi apparatus structure, maturation of key glycoproteins such as integrin beta-1, and regulation of cell polarity and movement. Mutations in ARFGEF1 cause a spectrum of neurodevelopmental disorders, marked by developmental delay, intellectual disability, and epilepsy, through mechanisms likely involving haploinsufficiency or loss of function[1][3][5]. ARFGEF1 is thus considered a critical regulator of membrane trafficking and neuronal development.

Other names

Brefeldin A-inhibited guanine nucleotide-exchange protein 1BIG1ARFGEP1p200DKFZP434L057DEDISBP200Brefeldin A-inhibited GEP 1

Inhibition of guanine nucleotide exchange factor activity (e.g., by Brefeldin A; blocks ARF activation by stabilizing GDP-bound form) Potential kinase interactions (as A kinase-anchoring protein, mediating crosstalk between ARF and PKA pathways)