TBC1D1 is the founding member of a family of proteins sharing a 180- to 200-amino acid TBC domain and presumed to have a role in regulating cell growth and differentiation. These proteins share significant homology with TRE2/USP6, yeast Bub2, and CDC16. TBC1D1 and TBC1D4 (AS160) have been demonstrated to be Rab GAPs (GTPase-activating proteins) that link upstream to Akt and phosphoinositide 3-kinase and downstream to Rabs involved in trafficking of GLUT4 vesicles. TBC1D1 regulates insulin-mediated GLUT4 translocation through its GAP activity, and is a likely Akt substrate. Mutations in the Tbc1d1 gene lead to some cases of severe human obesity.
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