Atg12 activating enzyme activity

Definition

Target type: molecularfunction

Catalysis of the activation of the small ubiquitin-related modifier APG12, through the formation of an ATP-dependent high-energy thiolester bond. [GOC:mah]

Atg12 activating enzyme activity is a crucial step in the autophagy pathway, a cellular process that involves the breakdown and recycling of cellular components. This activity is catalyzed by the Atg7 enzyme, which specifically activates the Atg12 protein. Here is a detailed description of the molecular function of Atg12 activating enzyme activity:

1. **Activation of Atg12:** Atg7, an E1-like enzyme, initiates the process by activating Atg12. This activation involves two key steps:
* **Adenylation:** Atg7 utilizes ATP to adenylate Atg12, forming a high-energy thioester bond between Atg12 and the enzyme. This adenylated Atg12 intermediate is crucial for the next step.
* **Transfer to Atg7:** The adenylated Atg12 is then transferred from Atg7 to a cysteine residue within the active site of the enzyme, forming a second thioester bond.

2. **Conjugation of Atg12 to Atg5:** Once Atg12 is activated on Atg7, it can be conjugated to Atg5. This process requires the assistance of Atg10, an E2-like enzyme:
* **Transfer to Atg10:** Activated Atg12 is transferred from Atg7 to a cysteine residue on Atg10, forming a thioester bond.
* **Transfer to Atg5:** Atg10 then catalyzes the transfer of Atg12 from its own cysteine residue to the amino group of a lysine residue (Lys150) on Atg5. This forms an irreversible isopeptide bond, creating the Atg12-Atg5 conjugate.

3. **Formation of the Atg12-Atg5-Atg16L1 Complex:** The Atg12-Atg5 conjugate then associates with another protein, Atg16L1, forming a larger complex. This complex plays a pivotal role in the elongation and closure of the phagophore, a double-membrane vesicle that engulfs cellular components destined for degradation.

4. **Role in Autophagy:** The Atg12-Atg5-Atg16L1 complex is essential for the proper functioning of the autophagy pathway. It helps to:
* **Recruit other autophagy proteins:** The complex acts as a scaffold, recruiting other autophagy proteins to the phagophore membrane, including the Atg8/LC3 family of proteins.
* **Control phagophore dynamics:** The complex contributes to the elongation and closure of the phagophore, ensuring that the engulfed material is effectively isolated within the autophagosome.
* **Regulate autophagy flux:** The complex indirectly regulates the overall efficiency of autophagy by controlling the availability of Atg8/LC3 for autophagosome formation.

In summary, Atg12 activating enzyme activity is a critical step in the autophagy pathway, enabling the conjugation of Atg12 to Atg5. This conjugation is essential for the formation of the Atg12-Atg5-Atg16L1 complex, which plays a crucial role in the elongation, closure, and overall function of the phagophore.'
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Proteins (1)

Compounds (1)