ATG9A

Domain

Forms a homotrimer with a solvated central pore, which is connected laterally to the cytosol through the cavity within each protomer (PubMed:32610138, PubMed:33106659). Acts as a lipid scramblase that uses its central pore to function: the central pore opens laterally to accommodate lipid headgroups, thereby enabling lipid flipping and redistribution of lipids added to the outer leaflet of ATG9A-containing vesicles, thereby enabling growth into autophagosomes (PubMed:33106659).

The tyrosine-based sorting signal motif, also named YXX-psi motif, promotes interaction with the AP-4 complex.

Function

Phospholipid scramblase involved in autophagy by mediating autophagosomal membrane expansion (PubMed:22456507, PubMed:27510922, PubMed:29437695, PubMed:32513819, PubMed:32610138, PubMed:33106659, PubMed:33468622, PubMed:33850023). Cycles between the preautophagosomal structure/phagophore assembly site (PAS) and the cytoplasmic vesicle pool and supplies membrane for the growing autophagosome (PubMed:16940348, PubMed:22456507, PubMed:33106659). Lipid scramblase activity plays a key role in preautophagosomal structure/phagophore assembly by distributing the phospholipids that arrive through ATG2 (ATG2A or ATG2B) from the cytoplasmic to the luminal leaflet of the bilayer, thereby driving autophagosomal membrane expansion (PubMed:33106659). Also required to supply phosphatidylinositol 4-phosphate to the autophagosome initiation site by recruiting the phosphatidylinositol 4-kinase beta (PI4KB) in a process dependent on ARFIP2, but not ARFIP1 (PubMed:30917996). In addition to autophagy, also plays a role in necrotic cell death (By similarity).

Post-translational modifications

Ufmylated in a DDRGK1 dependent manner.

Sequence Similarities

Belongs to the ATG9 family.

Cellular localization

• Preautophagosomal structure membrane
• Multi-pass membrane protein
• Cytoplasmic vesicle
• Autophagosome membrane
• Multi-pass membrane protein
• Golgi apparatus
• trans-Golgi network membrane
• Multi-pass membrane protein
• Late endosome membrane
• Multi-pass membrane protein
• Recycling endosome membrane
• Multi-pass membrane protein
• Endoplasmic reticulum membrane
• Multi-pass membrane protein
• Mitochondrion membrane
• Multi-pass membrane protein
• Mainly localizes to the trans-Golgi network (TGN) and the endosomal system; cycles between them though vesicle trafficking (PubMed:27316455, PubMed:27663665). Export from the TGN to promote formation of autophagosomes is mediated by the AP-4 complex (PubMed:29180427, PubMed:30262884). Under amino acid starvation or rapamycin treatment, redistributes to preautophagosomal structure/phagophore assembly site (PAS) (PubMed:16940348). The starvation-induced redistribution depends on ULK1, ATG13, as well as SH3GLB1 (PubMed:16940348). Upon autophagy induction, a small portion transiently localizes to the autophagic membranes (PubMed:22456507). Recruited to damaged mitochondria during mitophagy in a RIMOC1-dependent manner (PubMed:34432599).

Alternative names

APG9L1, ATG9A, Autophagy-related protein 9A, APG9-like 1, mATG9

Database links

swissprot:Q7Z3C6 omim:612204 entrezGene:79065

Other research areas

• Neuroscience