Domain: The C-terminal part of the protein is essential for the dimerization and interaction with ATG3 and ATG12. The N-terminal FAP motif (residues 15 to 17) is essential for the formation of the ATG89-PE and ATG5-ATG12 conjugates. Function: E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 family proteins for their conjugation with phosphatidylethanolamine. Both systems are needed for the ATG8 association to Cvt vesicles and autophagosomes membranes. Required for autophagic death induced by caspase-8 inhibition. Required for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Modulates p53/TP53 activity to regulate cell cycle and survival during metabolic stress. Plays also a key role in the maintenance of axonal homeostasis, the prevention of axonal degeneration, the maintenance of hematopoietic stem cells, the formation of Paneth cell granules, as well as in adipose differentiation. PTM: Acetylated by EP300. Similarity: Belongs to the ATG7 family. Tissue specificity: Widely expressed, especially in kidney, liver, lymph nodes and bone marrow.