IRGM Human

The Immunity-Related GTPase Family, M (IRGM), also known as interferon-inducible protein 1 (IFI1), is an enzyme encoded by the IRGM gene in humans . This protein is a member of the interferon-inducible GTPase family, which plays a crucial role in the innate immune response by regulating autophagy formation in response to intracellular pathogens .

The IRGM gene is located on chromosome 5 in humans . The protein encoded by this gene is involved in various cellular processes, including the remodeling and trafficking of intracellular membranes . This dynamin-like protein binds to intracellular membranes and promotes their remodeling, which is essential for the clearance of acute protozoan and bacterial infections .

IRGM is required for the efficient degradation of intracellular pathogens through autophagy. It interacts with autophagy and lysosome regulatory proteins to promote the fusion of phagosomes with lysosomes . This process ensures the degradation of microbial cargo, thereby playing a vital role in antimicrobial defense .

IRGM also regulates selective autophagy, including xenophagy and mitophagy, both directly and indirectly . It acts as a molecular adapter that promotes the coassembly of the core autophagy machinery. This includes activating AMPK, which phosphorylates ULK1 and BECN1 to induce autophagy . Additionally, IRGM influences the composition of the BECN1 complex by competing with negative regulators like BCL2 and RUBCN .

Polymorphisms affecting the normal expression of the IRGM gene are associated with susceptibility to Crohn’s disease and tuberculosis . Elevated expression of IRGM has also been linked to the development of several cancers . Understanding the role of IRGM in these diseases can provide insights into potential therapeutic targets for treating these conditions.