Atg12/ATG12 and Atg8/LC3 proteins are ubiquitin-like proteins. The conjugation systems of these two proteins are interconnected and they ultimately covalently link Atg8/LC3 proteins to the PE present in the phagophore membrane during autophagy. Amino acids at the C-terminus of Atg8/LC3 proteins (indicated with a X in the draw) are post-translationally cleaved by the Atg4/ATG4 proteases to expose a C-terminal glycine (G). Processed Atg8/LC3 proteins are activated and finally conjugated to the amino group of PE through the sequential action of the E1 enzyme Atg7/ATG7 and the E2 enzyme Atg3/ATG3. The last step of this reaction is mediated by the Atg12–Atg5–Atg16/ATG12–ATG5–ATG16L1 complex, which is formed by the Atg12/ATG12 conjugation system and acts as an E3 enzyme. The Atg12/ATG12 conjugation system involves the sequential action of Atg7/ATG7 and the E2 enzyme Atg10/ATG10, and covalently links Atg12/ATG12 to Atg5/ATG5. The Atg12/ATG12–Atg5/ATG5 conjugate binds to Atg16/ATG16L1, which subsequently multimerizes to form the Atg12–Atg5–Atg16/ATG12–ATG5–ATG16L1 complex. This complex associates with the phagophore via interaction with both Atg21/WIPI2B and PtdIns3P.