8fkm

Structural highlights

Function

ATG3_HUMAN 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.^{[1] [2] [3] [4] [5]}

References

1. ↑ Tanida I, Tanida-Miyake E, Komatsu M, Ueno T, Kominami E. Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple substrates, GATE-16, GABARAP, and MAP-LC3, and facilitates the conjugation of hApg12p to hApg5p. J Biol Chem. 2002 Apr 19;277(16):13739-44. Epub 2002 Feb 1. PMID:11825910 doi:http://dx.doi.org/10.1074/jbc.M200385200
2. ↑ Tanida I, Nishitani T, Nemoto T, Ueno T, Kominami E. Mammalian Apg12p, but not the Apg12p.Apg5p conjugate, facilitates LC3 processing. Biochem Biophys Res Commun. 2002 Sep 6;296(5):1164-70. PMID:12207896
3. ↑ Nemoto T, Tanida I, Tanida-Miyake E, Minematsu-Ikeguchi N, Yokota M, Ohsumi M, Ueno T, Kominami E. The mouse APG10 homologue, an E2-like enzyme for Apg12p conjugation, facilitates MAP-LC3 modification. J Biol Chem. 2003 Oct 10;278(41):39517-26. Epub 2003 Jul 30. PMID:12890687 doi:http://dx.doi.org/10.1074/jbc.C200334200
4. ↑ Tanida I, Sou YS, Minematsu-Ikeguchi N, Ueno T, Kominami E. Atg8L/Apg8L is the fourth mammalian modifier of mammalian Atg8 conjugation mediated by human Atg4B, Atg7 and Atg3. FEBS J. 2006 Jun;273(11):2553-62. PMID:16704426 doi:http://dx.doi.org/10.1111/j.1742-4658.2006.05260.x
5. ↑ Radoshevich L, Murrow L, Chen N, Fernandez E, Roy S, Fung C, Debnath J. ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death. Cell. 2010 Aug 20;142(4):590-600. doi: 10.1016/j.cell.2010.07.018. PMID:20723759 doi:http://dx.doi.org/10.1016/j.cell.2010.07.018