The following text describes a protein:
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. As part of the ATG8 conjugation system with ATG5 and ATG12, required for recruitment of LRRK2 to stressed lysosomes and induction of LRRK2 kinase activity in response to lysosomal stress (By similarity). 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 an autophagy-dependent antibacterial pathway together with NOD1 or NOD2. Plays a role in regulating morphology and function of Paneth cell.
Miscellaneous:
MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Subcellular Localization:
Cytoplasm. Preautophagosomal structure membrane; Peripheral membrane protein. Endosome membrane; Peripheral membrane protein. Lysosome membrane; Peripheral membrane protein. 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. Under starved conditions, the ATG12-ATG5-ATG16L1 complex is translocated to phagophores driven by RAB33B.
Domain:
The WD repeats are required for non-canonical autophagy but not for canonical autophagy. The WD repeats are required for the recruitment of LRRK2 to stressed lysosomes (By similarity).
Sequence:
MSSGLRAADFPRWKRHISEQLRRRDRLQRQAFEEIILQYNKLLEKSDLHSVLAQKLQAEKHDVPNRHEISPGHDGTWNDNQLQEMAQLRIKHQEELTELHKKRGELAQLVIDLNNQMQRKDREMQMNEAKIAECLQTISDLETECLDLRTKLCDLERANQTLKDEYDALQITFTALEGKLRKTTEENQELVTRWMAEKAQEANRLNAENEKDSRRRQARLQKELAEAAKEPLPVEQDDDIEVIVDETSDHTEETSPVRAISRAATKRLSQPAGGLLDSITNIFGRRSVSSFPVPQDNVDTHPGSGKEVRVPATALCVFDAHDGEVNAVQFSPGSRLLATGGMDRRVKLWEVFGEKCEFKGSLSGSNAGITSIEFDSAGSYLLAASNDFASRIWTVDDYRLRHTLTGHSGKVLSAKFLLDNARIVSGSHDRTLKLWDLRSKVCIKTVFAGSSCNDIVCTEQCVMSGHFDKKIRFWDIRSESIVREMELLGKITALDLNPERTELLSCSRDDLLKVIDLRTNAIKQTFSAPGFKCGSDWTRVVFSPDGSYVAAGSAEGSLYIWSVLTGKVEKVLSKQHSSSINAVAWSPSGSHVVSVDKGCKAVLWAQY