TBC1D4

TBC1 domain family member 4, previously known as AS160 (Akt substrate of 160 kDa) is a is_associated_with::protein that in humans is encoded by the TBC1D4 is_associated_with::gene.

The 160 kD protein product was first discovered in a screen for novel substrates of the serine-threonine kinase is_associated_with::Akt, which phosphorylates TBC1D4 after insulin stimulation. is_associated_with::Insulin stimulation of fat and muscle cells results in translocation of the glucose transporter is_associated_with::GLUT4 to the plasma membrane, and this translocation process is dependent on phosphorylation of TBC1D4. The role of TBC1D4 in GLUT4 translocation is mediated by its GTPase activating domain and interactions with Rab proteins in vesicle formation, increasing GLUT4 translocation when its GTPase activity is inhibited by Akt phosphorylation. Specifically, this inhibition activates is_associated_with::RAB2A, is_associated_with::RAB8A, is_associated_with::RAB10 and is_associated_with::RAB14.

TBC1D4 also contains a calmodulin-binding domain, and this domain mediates phosphorylation-independent glucose uptake in muscle cells.