This subfamily is composed of Tom1 (Target of myb1 - retroviral oncogene) protein, Tom1L1 (Tom1-like1), Tom1L2 (Tom1-like2), and similar proteins. Proteins belonging to this subfamily are characterized by the presence of a VHS (Vps27p/Hrs/Stam) domain in the N-terminal portion followed by a GAT (GGA and Tom) domain. They are novel regulators for post-Golgi trafficking and signaling. Yeast do not contain homologous proteins of the Tom1 subfamily, suggesting these proteins have evolved to accommodate more complex cellular processes. Tom1 is essential for the negative regulation of Interleukin-1 and Tumor Necrosis Factor-induced signaling pathways. The VHS domain has a superhelical structure similar to the structure of the ARM repeats and is present at the very N-termini of proteins. It is a right-handed superhelix of eight alpha helices. The VHS domain has been found in a number of proteins, some of which have been implicated in intracellular trafficking and sorting.
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