Protein: Autophagy-related protein 16-1 (APG16-like 1) (Q676U5)
Organism: Homo sapiens (Human)
Function: Plays an essential role in both canonical and non-canonical autophagy: interacts with ATG12-ATG5 to mediate the lipidation to ATG8 family proteins (MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAPL1, GABARAPL2 and GABARAP). Acts as a molecular hub, coordinating autophagy pathways via distinct domains that support either canonical or non-canonical signaling. During canonical autophagy, interacts with ATG12-ATG5 to mediate the conjugation of phosphatidylethanolamine (PE) to ATG8 proteins, to produce a membrane-bound activated form of ATG8. Thereby, controls the elongation of the nascent autophagosomal membrane. Also involved in non-canonical autophagy, a parallel pathway involving conjugation of ATG8 proteins to single membranes at endolysosomal compartments, probably by catalyzing conjugation of phosphatidylserine (PS) to ATG8. Non-canonical autophagy plays a key role in epithelial cells to limit lethal infection by influenza A (IAV) virus (By similarity). Regulates mitochondrial antiviral signaling (MAVS)-dependent type I interferon (IFN-I) production. Negatively regulates NOD1- and NOD2-driven inflammatory cytokine response. Instead, promotes with NOD2 an autophagy-dependent antibacterial pathway. Plays a role in regulating morphology and function of Paneth cell.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:23392225}. Preautophagosomal structure membrane {ECO:0000269|PubMed:20639872, ECO:0000269|PubMed:23392225}; Peripheral membrane protein {ECO:0000305}. Endosome membrane {ECO:0000269|PubMed:29317426}; Peripheral membrane protein {ECO:0000305}. Lysosome membrane {ECO:0000269|PubMed:29317426}; Peripheral membrane protein {ECO:0000305}. Note=Recruited to omegasomes membranes by WIPI2 (By similarity). Omegasomes are endoplasmic reticulum connected strutures at the origin of preautophagosomal structures (By similarity). Localized to preautophagosomal structure (PAS) where it is involved in the membrane targeting of ATG5 (By similarity). Also localizes to discrete punctae along the ciliary axoneme (By similarity). Upon activation of non-canonical autophagy, recruited to single-membrane endolysosomal compartments (PubMed:29317426). {ECO:0000250|UniProtKB:Q8C0J2, ECO:0000269|PubMed:29317426}.
Interaction partners:
- Ubiquitin-like-conjugating enzyme ATG3
- Nucleotide-binding oligomerization domain-containing protein 2
- Autophagy protein 5
- Ras-related protein Rab-33B
- WD repeat domain phosphoinositide-interacting protein 2
- Nucleotide-binding oligomerization domain-containing protein 1
- RB1-inducible coiled-coil protein 1
- Ubiquitin-like protein ATG12
- Ubiquitin-like modifier-activating enzyme ATG7
- GABA type A receptor associated protein like 1
Sequence:
MSSGLRAADFPRWKRHISEQLRRRDRLQRQAFEEIILQYNKLLEKSDLHSVLAQKLQAEKHDVPNRHEISPGHDGTWNDNQLQEMAQLRIKHQEELTELHKKRGELAQLVIDLNNQMQRKDREMQMNEAKIAECLQTISDLETECLDLRTKLCDLERANQTLKDEYDALQITFTALEGKLRKTTEENQELVTRWMAEKAQEANRLNAENEKDSRRRQARLQKELAEAAKEPLPVEQDDDIEVIVDETSDHTEETSPVRAISRAATKRLSQPAGGLLDSITNIFGRRSVSSFPVPQDNVDTHPGSGKEVRVPATALCVFDAHDGEVNAVQFSPGSRLLATGGMDRRVKLWEVFGEKCEFKGSLSGSNAGITSIEFDSAGSYLLAASNDFASRIWTVDDYRLRHTLTGHSGKVLSAKFLLDNARIVSGSHDRTLKLWDLRSKVCIKTVFAGSSCNDIVCTEQCVMSGHFDKKIRFWDIRSESIVREMELLGKITALDLNPERTELLSCSRDDLLKVIDLRTNAIKQTFSAPGFKCGSDWTRVVFSPDGSYVAAGSAEGSLYIWSVLTGKVEKVLSKQHSSSINAVAWSPSGSHVVSVDKGCKAVLWAQY