Protein: Autophagy-related protein 9A (APG9-like 1) (mATG9) (Q7Z3C6)
Organism: Homo sapiens (Human)
Function: Phospholipid scramblase involved in autophagy by mediating autophagosomal membrane expansion. Cycles between the preautophagosomal structure/phagophore assembly site (PAS) and the cytoplasmic vesicle pool and supplies membrane for the growing autophagosome. 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. 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. In addition to autophagy, also plays a role in necrotic cell death (By similarity).
Subcellular location: Preautophagosomal structure membrane {ECO:0000269|PubMed:18936157, ECO:0000269|PubMed:32073997, ECO:0000269|PubMed:33106659}; Multi-pass membrane protein {ECO:0000269|PubMed:32610138, ECO:0000269|PubMed:33106659}. Cytoplasmic vesicle, autophagosome membrane {ECO:0000269|PubMed:19910472}; Multi-pass membrane protein {ECO:0000269|PubMed:32610138, ECO:0000269|PubMed:33106659}. Golgi apparatus, trans-Golgi network membrane {ECO:0000269|PubMed:16940348, ECO:0000269|PubMed:20124090, ECO:0000269|PubMed:21068542, ECO:0000269|PubMed:27316455, ECO:0000269|PubMed:27663665, ECO:0000269|PubMed:29180427, ECO:0000269|PubMed:33468622, ECO:0000305|PubMed:34432599}; Multi-pass membrane protein {ECO:0000269|PubMed:32610138, ECO:0000269|PubMed:33106659}. Late endosome membrane {ECO:0000269|PubMed:16940348, ECO:0000269|PubMed:20124090, ECO:0000269|PubMed:22456507, ECO:0000269|PubMed:32513819, ECO:0000269|PubMed:33468622}; Multi-pass membrane protein {ECO:0000269|PubMed:32610138, ECO:0000269|PubMed:33106659}. Recycling endosome membrane {ECO:0000269|PubMed:22456507, ECO:0000269|PubMed:29437695}; Multi-pass membrane protein {ECO:0000269|PubMed:32610138, ECO:0000269|PubMed:33106659}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:20124090, ECO:0000269|PubMed:27316455, ECO:0000269|PubMed:27663665}; Multi-pass membrane protein {ECO:0000269|PubMed:32610138, ECO:0000269|PubMed:33106659}. Mitochondrion membrane {ECO:0000305|PubMed:34432599}; Multi-pass membrane protein {ECO:0000255}. Note=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). {ECO:0000269|PubMed:16940348, ECO:0000269|PubMed:22456507, ECO:0000269|PubMed:27316455, ECO:0000269|PubMed:27663665, ECO:0000269|PubMed:29180427, ECO:0000269|PubMed:30262884, ECO:0000269|PubMed:34432599}.
Interaction partners:
- Serine/threonine-protein kinase ULK1
- Transcription factor SPT20 homolog
- Autophagy-related protein 2 homolog A
- Autophagy-related protein 9B
- WD repeat domain phosphoinositide-interacting protein 1
- Serine/threonine-protein kinase ULK2
- Autophagy-related protein 16-1
- Autophagy-related protein 13
- Beclin 1-associated autophagy-related key regulator
- Microtubule-associated protein 1 light chain 3 alpha
Sequence:
MAQFDTEYQRLEASYSDSPPGEEDLLVHVAEGSKSPWHHIENLDLFFSRVYNLHQKNGFTCMLIGEIFELMQFLFVVAFTTFLVSCVDYDILFANKMVNHSLHPTEPVKVTLPDAFLPAQVCSARIQENGSLITILVIAGVFWIHRLIKFIYNICCYWEIHSFYLHALRIPMSALPYCTWQEVQARIVQTQKEHQICIHKRELTELDIYHRILRFQNYMVALVNKSLLPLRFRLPGLGEAVFFTRGLKYNFELILFWGPGSLFLNEWSLKAEYKRGGQRLELAQRLSNRILWIGIANFLLCPLILIWQILYAFFSYAEVLKREPGALGARCWSLYGRCYLRHFNELEHELQSRLNRGYKPASKYMNCFLSPLLTLLAKNGAFFAGSILAVLIALTIYDEDVLAVEHVLTTVTLLGVTVTVCRSFIPDQHMVFCPEQLLRVILAHIHYMPDHWQGNAHRSQTRDEFAQLFQYKAVFILEELLSPIVTPLILIFCLRPRALEIIDFFRNFTVEVVGVGDTCSFAQMDVRQHGHPQWLSAGQTEASVYQQAEDGKTELSLMHFAITNPGWQPPRESTAFLGFLKEQVQRDGAAASLAQGGLLPENALFTSIQSLQSESEPLSLIANVVAGSSCRGPPLPRDLQGSRHRAEVASALRSFSPLQPGQAPTGRAHSTMTGSGVDARTASSGSSVWEGQLQSLVLSEYASTEMSLHALYMHQLHKQQAQAEPERHVWHRRESDESGESAPDEGGEGARAPQSIPRSASYPCAAPRPGAPETTALHGGFQRRYGGITDPGTVPRVPSHFSRLPLGGWAEDGQSASRHPEPVPEEGSEDELPPQVHKV