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Autophagy-related 5 (ATG5), formerly known as apoptosis specific protein (ASP), is a protein that is essential to autophagosome elongation.1,2,3 ATG5 is covalently conjugated to the C-terminal glycine residue of ATG12 (ATG12-ATG5) and forms a non-covalent complex with ATG16 (ATG12-ATG5-ATG16), which functions as an E3 ubiquitin ligase-like enzyme to facilitate LC3 transfer from ATG3 to phosphatidylethanolamine in canonical autophagy. ATG12-ATG5 also binds to the ATG12-ATG5-interaction region of the lysosomal localized protein TECPR1, freeing the TECPR1 pleckstrin homology domain to interact with phosphatidylinositol 3-phosphate components in the autophagosome membrane, promoting autophagosome-lysosome fusion.3 Polymorphisms in ATG5 have been associated with various autoimmune diseases, including lupus nephritis and Behcet's disease, gastrointestinal and colorectal cancers, as well as sporadic Parkinson's disease and childhood asthma.
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1. Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy. Nat. Struct. Mol. Biol. 20(1), 59-66 (2013).
2. Insights into autophagosome maturation revealed by the structures of ATG5 with its interacting partners. Autophagy 11(1), 75-87 (2015).
3. Exploring the role of autophagy-