Autophagy-related protein 101 (ATG101)

Autophagy-related protein 101 (ATG101) is a highly conserved cytoplasmic protein encoded by the *C12orf44* gene in humans[1]. ATG101 is a core component of the ULK (unc-51-like kinase) initiation complex that orchestrates the early steps of autophagy, a catabolic process critical for cellular homeostasis, stress response, and degradation of cytoplasmic constituents[1][2][3]. ATG101 contains a HORMA domain that adopts an open conformation and forms a stable heterodimer with ATG13, another ULK complex subunit[2][4]. Through this interaction, ATG101 protects ATG13 from proteasomal degradation and thus maintains ULK1 complex integrity, which is necessary for autophagosome formation in response to nutrient deprivation or cellular stress[1][2][3][4]. Structural studies reveal that ATG101's unique HORMA fold and a specialized WF finger motif make it an interaction hub within the autophagy machinery, recruiting downstream effectors to the site of autophagosome initiation[3][4]. Recent research links altered ATG101 expression to several cancers, including cholangiocarcinoma, colon cancer, and hepatocellular carcinoma, suggesting its utility as a disease biomarker and its conceptual potential as a drug target[3]. However, to date, no specific drugs or small molecules are known to directly target ATG101 in clinical or experimental settings. Perturbation of ATG101 or the entire ULK complex can severely disrupt autophagy, raising concerns about cell viability if targeted indiscriminately[3].

Other names

C12orf44PP894FLJ11773Atg13-interacting proteinATG101autophagy-related protein 101Atg101