Deptor
Developmental stage
At postnatal day 1 (P1), in cartilage growth plate, primarily expressed in resting and proliferating chondrocytes. This expression pattern is maintained at least until P21 (at protein level).
Function
Negative regulator of the mTORC1 and mTORC2 complexes: inhibits the protein kinase activity of MTOR, thereby inactivating both complexes. DEPTOR inhibits mTORC1 and mTORC2 to induce autophagy. In contrast to AKT1S1/PRAS40, only partially inhibits mTORC1 activity.
Post-translational modifications
Phosphorylation weakens interaction with MTOR within mTORC1 and mTORC2 (By similarity). Phosphorylated at Ser-286, Ser-287 and Ser-291 in response to mitogenic stimulation by MTOR: DEPTOR is either directly phosphorylated by MTOR or indirectly via proteins kinases that are activated by MTOR, such as CK1/CSNK1A1 (By similarity). Phosphorylation at Ser-286, Ser-287 and Ser-291 promotes ubiquitination by the SCF(BTRC) complex, followed by degradation (By similarity). Phosphorylation at Ser-235 by MAPK3/ERK1 promotes deubiquitination by USP7, enhancing its stability (By similarity). Phosphorylation at Tyr-291 by SYK impairs its interaction with MTOR, promoting mTORC1 and mTORC2 signaling (By similarity).
Ubiquitinated; leading to proteasomal degradation (By similarity). Ubiquitination by the SCF(BTRC) and SCF(FBXW11) complexes following phosphorylation at Ser-286, Ser-287 and Ser-291 by MTOR, leads to its degradation by the proteasome (By similarity). Deubiquitinated by OTUB1 in response to amino acid via a non-canonical mechanism, leading to DEPTOR stability (By similarity). Deubiquitinated by USP7 following phosphorylation at Ser-235, promoting its stability (By similarity).
Cellular localization
- Lysosome membrane
- Localizes to the lysosomal membrane when associated with the mTORC1 and mTORC2 complexes.
Alternative names
Depdc6, Kiaa4200, DEP domain-containing mTOR-interacting protein, DEP domain-containing protein 6