2.A.1.1.29
Glucosamine/glucose/fructose uniporter, Glut-2, Glut2 or ATG9A; it may also transport dehydroascorbate (Mardones et al., 2011; Maulén et al., 2003), and cotransports water against an osmotic gradient (Naftalin, 2008).  Mutations may give rise to the rare autosomal recessive Fanconi-Bickel syndrome (Batool et al. 2019). It mediates intestinal transport of quercetrin (Li et al. 2020) and can transport the drug gastrodin, a seditive with a strcture of a phenolic glucoside (Huang et al. 2023). It also functions in autophagy. The cryoEM structure of the human ATG9A isoform at 2.9-Å resolution has been solved (Guardia et al. 2020). The structure reveals a fold with a homotrimeric domain-swapped architecture, multiple membrane spans, and a network of branched cavities, consistent with ATG9A being a membrane transporter. Mutational analyses support a role for the cavities in the functions of ATG9A. Structure-guided molecular simulations predict that ATG9A causes membrane bending, explaining the localization of this protein to small vesicles and highly curved edges of growing autophagosomes (Guardia et al. 2020). Both GLUT2 and GLUT3 have been expressed in yeast and exhibit most of the characteristics of the proteins expressed in humans (Schmidl et al. 2020). Autophagy is a highly conserved pathway that the cell uses to maintain homeostasis, degrade damaged organelles, combat invading pathogens, and survive pathological conditions. A set of proteins, called ATG proteins, comprise the core autophagy machinery and work together in a defined hierarchy. ATG9A vesicles are at the heart of autophagy, as they control the rapid de novo synthesis of an organelle called the phagophore. ATG9A is present in different membrane compartments (van Vliet et al. 2023).  Metformin increases the uptake of glucose into the gut from the circulation in high-fat diet-fed male mice, which is enhanced by a reduction in whole-body Slc2a2 expression (Morrice et al. 2023).  Increased expression of Glucose Transporter 2 (GLUT2) is observed on the peripheral blood insulin-producing cells (PB-IPC) in type 1 diabetic patients after receiving stem cell educator therapy (Zhao et al. 2024).