InterPro domain: IPR032914

This entry includes fungal Vam6/Vps3 and animal Vps39/TRAP1. Vps39 is also known as Vam6 or TRAP1-Like-Protein (TLP) [ 1 ]. Vam6/Vps39 acts as a component of the HOPS complex that functions during the docking stage of vacuole fusion. It is required for late endosomal-lysosomal fusion events and the delivery of endocytic cargo to lysosomes [ 2 , 3 ]. In addition to its regulatory role in homotypic vacuolar fusion and vacuole protein sorting within the HOPS complex, Vam6 also controls the function of the central regulator of eukaryotic cell growth TORC1 by activating the Gtr1 subunit of the EGO complex [ 4 , 5 ].

TRAP1 plays a role in vesicle-mediated protein trafficking of the endocytic membrane transport pathway [ 6 ].

1. The TGF-β signaling modulators TRAP1/TGFBRAP1 and VPS39/Vam6/TLP are essential for early embryonic development. Immunobiology 216, 343-50
2. Human Vam6p promotes lysosome clustering and fusion in vivo. J. Cell Biol. 154, 109-22
3. The HOPS proteins hVps41 and hVps39 are required for homotypic and heterotypic late endosome fusion. Traffic 14, 219-32
4. Amino acid signaling to TOR activation: Vam6 functioning as a Gtr1 GEF. Mol. Cell 35, 543-5
5. The Vam6 GEF controls TORC1 by activating the EGO complex. Mol. Cell 35, 563-73
6. Mammalian CORVET is required for fusion and conversion of distinct early endosome subpopulations. Traffic 15, 1366-89