ATG16L1

The protein encoded by this gene is part of a large protein complex that is necessary for autophagy, the major process by which intracellular components are targeted to lysosomes for degradation. Defects in this gene are a cause of susceptibility to inflammatory bowel disease type 10 (IBD10). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jun 2010]

Full Name

Autophagy Related 16 Like 1

Function

Plays an essential role in autophagy: interacts with ATG12-ATG5 to mediate the conjugation of phosphatidylethanolamine (PE) to LC3 (MAP1LC3A, MAP1LC3B or MAP1LC3C), to produce a membrane-bound activated form of LC3 named LC3-II. Thereby, controls the elongation of the nascent autophagosomal membrane (PubMed:24553140, PubMed:23376921, PubMed:24954904, PubMed:27273576, PubMed:23392225).
Regulates mitochondrial antiviral signaling (MAVS)-dependent type I interferon (IFN-I) production (PubMed:25645662).
Negatively regulates NOD1- and NOD2-driven inflammatory cytokine response (PubMed:24238340).
Instead, promotes with NOD2 an autophagy-dependent antibacterial pathway (PubMed:20637199).
Plays a role in regulating morphology and function of Paneth cell (PubMed:18849966).

Biological Process

Autophagosome assembly Source: GO_Central
Macroautophagy Source: Reactome
Negative stranded viral RNA replication Source: GO_Central
Protein transport Source: UniProtKB-KW

Cellular Location

Cytoplasm; Preautophagosomal structure membrane. Recruited to omegasomes membranes by WIPI2. Omegasomes are endoplasmic reticulum connected strutures at the origin of preautophagosomal structures. Localized to preautophagosomal structure (PAS) where it is involved in the membrane targeting of ATG5. Localizes also to discrete punctae along the ciliary axoneme.

Involvement in disease

Inflammatory bowel disease 10 (IBD10): A chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints.

PTM

Proteolytic cleavage by activated CASP3 leads to degradation and may regulate autophagy upon cellular stress and apoptotic stimuli.
Phosphorylation at Ser-139 promotes association with the ATG12-ATG5 conjugate to form the ATG12-ATG5-ATG16L1 complex.