TBC1D4

Description

The TBC1D4 (TBC1 domain family member 4) is a protein-coding gene located on chromosome 13.

AS160 (Akt substrate of 160 kDa), originally known as TBC1 domain family member 4 (TBC1D4), is a Rab GTPase-activating protein encoded by the TBC1D4 gene. It was discovered as a substrate of the serine-threonine kinase Akt2, which phosphorylates AS160 at Thr-642 and Ser-588 after insulin stimulation. Insulin stimulation of fat and muscle cells leads to translocation of the glucose transporter GLUT4 to the plasma membrane, a process dependent on AS160 phosphorylation. AS160's role in GLUT4 translocation is mediated by its GTPase activating domain and interactions with Rab proteins involved in vesicle formation. Inhibition of AS160's GTPase activity by Akt phosphorylation activates RAB2A, RAB8A, RAB10 and RAB14, increasing GLUT4 translocation. AS160 also contains a calmodulin-binding domain that mediates phosphorylation-independent glucose uptake in muscle cells.

Acts as a GTPase-activating protein for RAB2A, RAB8A, RAB10 and RAB14. Isoform 2 promotes insulin-induced glucose transporter SLC2A4/GLUT4 translocation at the plasma membrane, thus increasing glucose uptake. (PMID:15971998, PMID:18771725, PMID:22908308)

TBC1D4 is also known as AS160, NIDDM5.

Associated Diseases

Comprehensive carrier screening

WES Whole Exome Sequencing

Clinical Exome Sequencing