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Target of Myb protein 1

Domain

The GAT domain and the VHS domain are required for the interaction with polyubiquitinated proteins.

The VHS domain binds to phosphatidylinositol monophosphates (PubMed:25588840). The KRKK motif within the VHS domain is required for binding to phosphatidylinositol monophosphates, with a preference for phosphatidylinositol 5-phosphate (PtdIns(5)P) (PubMed:25588840).

Function

Adapter protein that plays a role in the intracellular membrane trafficking of ubiquitinated proteins, thereby participating in autophagy, ubiquitination-dependent signaling and receptor recycling pathways (PubMed:14563850, PubMed:15047686, PubMed:23023224, PubMed:25588840, PubMed:26320582, PubMed:31371777). Acts as a MYO6/Myosin VI adapter protein that targets MYO6 to endocytic structures (PubMed:23023224). Together with MYO6, required for autophagosomal delivery of endocytic cargo, the maturation of autophagosomes and their fusion with lysosomes (PubMed:23023224). MYO6 links TOM1 with autophagy receptors, such as TAX1BP1; CALCOCO2/NDP52 and OPTN (PubMed:31371777). Binds to polyubiquitinated proteins via its GAT domain (PubMed:14563850). In a complex with TOLLIP, recruits ubiquitin-conjugated proteins onto early endosomes (PubMed:15047686). The Tom1-Tollip complex may regulate endosomal trafficking by linking polyubiquitinated proteins to clathrin (PubMed:14563850, PubMed:15047686). Mediates clathrin recruitment to early endosomes by ZFYVE16 (PubMed:15657082). Modulates binding of TOLLIP to phosphatidylinositol 3-phosphate (PtdIns(3)P) via binding competition; the association with TOLLIP may favor the release of TOLLIP from endosomal membranes, allowing TOLLIP to commit to cargo trafficking (PubMed:26320582). Acts as a phosphatidylinositol 5-phosphate (PtdIns(5)P) effector by binding to PtdIns(5)P, thereby regulating endosomal maturation (PubMed:25588840). PtdIns(5)P-dependent recruitment to signaling endosomes may block endosomal maturation (PubMed:25588840). Also inhibits Toll-like receptor (TLR) signaling and participates in immune receptor recycling (PubMed:15047686, PubMed:26320582).

Involvement in disease

Immunodeficiency 85

IMD85

An autosomal dominant immunologic disorder characterized by early-onset autoimmunity and features of combined immunodeficiency such as hypogammaglobulinemia and abnormal T-cell function. Clinical manifestations include atopic eczema and recurrent respiratory infections in the first decade of life, autoimmune enteropathy, growth failure, autoimmune oligoarthritis, interstitial pneumonitis, and EBV viremia.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

Post-translational modifications

Monoubiquitinated.

Sequence Similarities

Belongs to the TOM1 family.

Tissue Specificity

Widely expressed. Highly expressed in skeletal muscle, heart, placenta and liver.

Cellular localization

Alternative names

Target of Myb1 membrane trafficking protein, Target of Myb protein 1, TOM1

swissprot:O60784 swissprot:Q15582 entrezGene:7045 omim:601692