DEP domain-containing protein 5 (DEPDC5)

DEP domain-containing protein 5 (DEPDC5) is the largest subunit of the trimeric GATOR1 complex, which also includes NPRL2 and NPRL3[1][3][6][7]. GATOR1 acts as a key negative regulator of the mechanistic target of rapamycin complex 1 (mTORC1) pathway by sensing amino acid sufficiency and inhibiting inappropriate mTORC1 activation, especially under conditions of nutrient deprivation[1][2][6]. DEPDC5 stabilizes the GATOR1 complex and mediates interaction with Rag GTPases, although the catalytic GAP activity is attributed primarily to NPRL2/NPRL3[7]. DEPDC5 is ubiquitously expressed and has a structure featuring a DEP domain, implicated in intracellular signaling localization, as well as other domains critical for GATOR1 assembly and function[6][7][4]. Germline or somatic mutations in DEPDC5 lead to hyperactivation of mTORC1 signaling, resulting in various pathologies including familial focal epilepsy, neurodevelopmental disorders, and some cancers (notably hepatocellular carcinoma)[1][3][4]. Currently, there are no drugs known to directly target DEPDC5, but genetic status of DEPDC5 serves as an important biomarker in several diseases.

Other names

GATOR1 complex protein DEPDC5KIAA0645DEP.5DEE111FFEVFFFEVF1FPEVFDEP domain-containing 5DEP domain-containing protein 5GATOR complex protein DEPDC5

Not directly drug-targeted; loss-of-function mutations disrupt GATOR1-mediated mTORC1 inhibition, leading to pathway hyperactivation; inhibitors of mTOR (such as rapamycin and its analogs) can partially compensate for pathway hyperactivity, but these do not act directly on DEPDC5