E2 conjugating enzyme required for the cytoplasm to vacuole transport (Cvt), autophagy, and mitochondrial homeostasis. Responsible for the E2-like covalent binding of phosphatidylethanolamine to the C-terminal Gly of ATG8-like proteins (GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A). The ATG12-ATG5 conjugate plays a role of an E3 and promotes the transfer of ATG8-like proteins from ATG3 to phosphatidylethanolamine (PE). This step is required for the membrane association of ATG8-like proteins. The formation of the ATG8-phosphatidylethanolamine conjugates is essential for autophagy and for the cytoplasm to vacuole transport (Cvt). Preferred substrate is MAP1LC3A. Also acts as an autocatalytic E2-like enzyme, catalyzing the conjugation of ATG12 to itself, ATG12 conjugation to ATG3 playing a role in mitochondrial homeostasis but not in autophagy. ATG7 (E1-like enzyme) facilitates this reaction by forming an E1-E2 complex with ATG3 (By similarity). Interacts with ATG7 and ATG12. The complex composed of ATG3 and ATG7 plays a role in the conjugation of ATG12 to ATG5. Interacts with FNBP1L. Conjugated to ATG12 at Lys-243. ATG12-conjugation plays a role in regulation of mitochondrial homeostasis and cell death, while it is not involved in PE-conjugation to ATG8-like proteins and autophagy (By similarity). Cleaved by CASP8 upon death ligand binding such as tumor necrosis factor-alpha. CASP8 cleavage blocks survival-related autophagy and favors apoptosis (By similarity). Belongs to the ATG3 family.