Target of Myb1 membrane trafficking protein

TOM1 (Target of Myb1 membrane trafficking protein) is an adapter protein that mediates intracellular membrane trafficking of ubiquitinated proteins through interactions with the myosin motor protein MYO6 (UniProt: O60784). It functions in autophagy, ubiquitin-dependent signaling, receptor recycling, and endosomal maturation by binding polyubiquitinated cargo via its GAT domain and regulating phosphatidylinositol lipid interactions.

TOM1 localizes to endocytic structures and early endosomes, where it coordinates with TOLLIP and other autophagy receptors to facilitate autophagosomal maturation and lysosomal fusion. The protein also inhibits Toll-like receptor signaling and supports immune receptor recycling. A monogenic immunodeficiency (IMD85, MIM 619510) has been associated with TOM1 mutations (UniProt: O60784).

In Alzheimer's disease, TOM1 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.82 across subcellular fractions (Chaparral AD proteomics). This reduction may reflect impaired autophagosomal trafficking and endosomal dysfunction, processes increasingly implicated in AD pathogenesis.