TBC1D5
Domain
The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site.
The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins. LIR 1 is also implicated in interaction with retromer; LIR 2 is only implicated in interaction with ATG8 family proteins.
Function
May act as a GTPase-activating protein (GAP) for Rab family protein(s). May act as a GAP for RAB7A. Can displace RAB7A and retromer CSC subcomplex from the endosomal membrane to the cytosol; at least retromer displacement seems to require its catalytic activity (PubMed:19531583, PubMed:20923837). Required for retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN); the function seems to require its catalytic activity. Involved in regulation of autophagy (PubMed:22354992). May act as a molecular switch between endosomal and autophagosomal transport and is involved in reprogramming vesicle trafficking upon autophagy induction. Involved in the trafficking of ATG9A upon activation of autophagy. May regulate the recruitment of ATG9A-AP2-containing vesicles to autophagic membranes (PubMed:24603492).
Cellular localization
- Endosome membrane
- Cytoplasmic vesicle
- Autophagosome
- During starvation induced autophagy is relocalized from endosomal localization to LC3-positive autophagosomes.
Alternative names
KIAA0210, TBC1D5, TBC1 domain family member 5