This is a family of eukaryotic proteins found in animals, plants, and yeasts that includes Atg7p (YHR171W) from Saccharomyces cerevisiae (Baker's yeast) and ATG7 from Pichia angusta. Members are about 650 to 700 residues in length and include a central domain of about 150 residues shared with the ThiF/MoeB/HesA family of proteins. A low level of similarity toubiquitin-activating enzyme E1 is described in a paper on peroxisome autophagy mediated by ATG7 [], and is the basis of the name ubiquitin activating enzyme E1-like protein. Members of the family are involved in protein lipidation events analogous to ubiquitination and required for membrane fusion events during autophagy.This protein is important for several processes. It plays 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 [[cite22291845]], as well as in adipose differentiation []. It is involved in circadian clock regulation in the liver and glucose metabolism through the autophagic degradation of CRY1 (clock repressor) in a time-dependent manner [].
This entry represents a group of ubiquitin-like-conjugating enzymes, including Atg3 and Atg10.Atg3 is the E2 enzyme for the LC3 lipidation process []. It is essential for autophagocytosis. The super protein complex, the Atg16L complex, consists of multiple Atg12-Atg5 conjugates. Atg16L has an E3-like role in the LC3 lipidation reaction. The activated intermediate, LC3-Atg3 (E2), is recruited to the site where the lipidation takes place []. Atg3 catalyses the conjugation of Atg8 and phosphatidylethanolamine (PE). Atg3 has an alpha/β-fold, and its core region is topologically similar to canonical E2 enzymes. Atg3 has two regions inserted in the core region and another with a long α-helical structure that protrudes from the core region as far as 30 A []. It interacts with atg8 through an intermediate thioester bond between Cys-288 and the C-terminal Gly of atg8. It also interacts with the C-terminal region of the E1-like atg7 enzyme.Atg10 acts as an E2-like enzyme that catalyzes the conjugation of ATG12 to ATG5 [].
This is a family of E1-like enzymes that contain the NAD/FAD-binding fold []. Proteins in this entry include ThiF/MoeB/HesA from bacteria and E1-like enzymes from eukaryotes. ThiF/MoeB/HesA are involved in molybdopterin and thiamine biosynthesis. The common reaction mechanism catalysed by MoeB and ThiF, like other E1 enzymes, begins with a nucleophilic attack of the C-terminal carboxylate of MoaD and ThiS, respectively, on the alpha-phosphate of an ATP molecule bound at the active site of the activating enzymes, leading to the formation of a high-energy acyladenylate intermediate and subsequently to the formation of a thiocarboxylate at the C termini of MoaD and ThiS. MoeB, as the MPT synthase (MoaE/MoaD complex) sulfurase, is involved in the biosynthesis of the molybdenum cofactor, a derivative of the tricyclic pterin, molybdopterin (MPT) []. ThiF catalyses the adenylation of ThiS, as part of the biosynthesis pathway of thiamin pyrophosphate (vitamin B1) []. Some ThiF/MoeB/HesA family members such as Atg7, MOCS3 andSAE1/2, have different functions. For instance, Atg7 is a protein-activating enzyme for multiple substrates [], while SAE1/2 acts as an E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4 []. MOCS3 is a adenylyltransferase and sulfurtransferase involved in 2-thiolation of mcm5S2U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln) [].
