AS160 (Akt substrate of 160 kDa), which was originally known as TBC1 domain family member 4 (TBC1D4), is a

Rab Rab �âːb( dlm, Arba, la, Arba, it, Arbe, german: Arbey) is an island in the northern Dalmatia region in Croatia, located just off the northern Croatian coast in the Adriatic Sea. The island is long, has an area of and 9,328 inhabitants (2 ...

GTPase-activating

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the ''TBC1D4''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. The 160 kD protein product was first discovered in a screen for novel substrates of the serine-threonine kinase

Akt2 AKT2, also known as RAC-beta serine/threonine-protein kinase, is an enzyme that in humans is encoded by the ''AKT2'' gene. It influences metabolite storage as part of the insulin signal transduction pathway. Function This gene is a putative o ...

, which phosphorylates AS160 at Thr-642 and Ser-588 after insulin stimulation. Insulin stimulation of fat and muscle cells results in translocation of the glucose transporter

GLUT4 Glucose transporter type 4 (GLUT4), also known as solute carrier family 2, facilitated glucose transporter member 4, is a protein encoded, in humans, by the ''SLC2A4'' gene. GLUT4 is the insulin-regulated glucose transporter found primarily in a ...

to the plasma membrane, and this translocation process is dependent on phosphorylation of AS160. The role of AS160 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

RAB2A Ras-related protein Rab-2A is a protein that in humans is encoded by the ''RAB2A'' gene. Function Members of the Rab protein family are nontransforming monomeric GTP-binding proteins of the Ras superfamily that contain 4 highly conserved regio ...

RAB8A Ras-related protein Rab-8A is a protein that in humans is encoded by the ''RAB8A'' gene. Function The protein encoded by this gene is a member of the RAS superfamily which are small GTP/GDP-binding proteins with an average size of 200 amino ac ...

, RAB10 and RAB14. AS160 also contains a calmodulin-binding domain, and this domain mediates phosphorylation-independent glucose uptake in muscle cells.

References

Further reading