Guided entry of tail-anchored protein factor 3 (Get3, or ATPase Get3) (GET3 (or TRC40 in mammals))

Guided entry of tail-anchored protein factor 3 (GET3, ASNA1, or TRC40 in mammals) is a conserved ATPase responsible for the post-translational targeting and insertion of tail-anchored (TA) membrane proteins into the endoplasmic reticulum (ER)[1][3][4]. TA proteins, which contain a single C-terminal transmembrane domain, are critical for a variety of cellular processes including membrane fusion, apoptosis, and protein translocation[1][3]. GET3 cycles between cytosol and ER, binding to TA proteins and then interacting with the ER-localized Get1/Get2 receptor complex to facilitate their insertion into the ER membrane in an ATP-dependent manner[1][4]. Structural and functional analyses have shown that GET3 undergoes conformational changes linked to ATP binding and hydrolysis, coupling energy consumption to TA protein delivery and release[1][2][3]. In addition to its canonical targeting function, GET3 can act as an ATP-independent chaperone under oxidative stress, protecting cells from protein unfolding and aggregation[4]. Knockout of GET3 in yeast leads to various stress sensitivities and impaired ER-targeted protein trafficking[4]. In mammals, its homolog ASNA1/TRC40 is essential for viability and proper organization of the secretory pathway[4].

Other names

ATPase GET3ASNA1TRC40Arsenical pump-driving ATPaseArsenite-stimulated ATPaseTransmembrane domain recognition complex 40 kDa ATPase subunitgolgi to ER traffic 3 homologTRC40 (Transmembrane recognition complex 40 kDa subunit)ArsaCMD2HhARSA-I, hASNA-I (human forms)Guided entry of tail-anchored proteins factor 3