DEPTOR

DEP domain containing MTOR-interacting protein
Identifiers
Symbols DEPTOR ; DEP.6; DEPDC6
External IDs OMIM: 612974 MGI: 2146322 HomoloGene: 32551 GeneCards: DEPTOR Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 64798 97998
Ensembl ENSG00000155792 ENSMUSG00000022419
UniProt Q8TB45 Q570Y9
RefSeq (mRNA) NM_001283012 NM_001037937
RefSeq (protein) NP_001269941 NP_001033026
Location (UCSC) Chr 8:
119.87 – 120.05 Mb		 Chr 15:
55.11 – 55.26 Mb
PubMed search

DEP domain-containing mTOR-interacting protein (DEPTOR) also known as DEP domain-containing protein 6 (DEPDC6) is a protein that in humans is encoded by the DEPTOR gene.[1]

Structure

The gene DEPTOR can be found only in vertebrates. In human, DEPTOR gene locates at chromosome 8, 8q24.12 with protein size 409 a.a.[2] Human DEPTOR contains two N-terminal DEP domains and a C-terminal PDZ domain.[3]

Function

DEPTOR is involved in mTOR signaling pathway as an endogenous regulator. A direct interaction between DEPTOR and mTOR has been shown.[3] Overexpression of DEPTOR downregulates the activity of mTORC1 and mTORC2 in vitro. mTORC1 and mTORC2 can both inhibit DEPTOR through phosphorylation.[3]

Metabolism

DEPTOR cell-autonomously regulates adipogenesis.[4] In the muscle, Baf60c promotes a switch from oxidative to glycolytic myofiber type through DEPTOR-mediated Akt/PKB activation.[5] Within the brain, DEPTOR is highly express in the hippocampus, the medio-basal hypothalamus and the circumventricular organs.[6] Overexpression of DEPTOR in the medio-basal hypothalamus protects mice against high-fat diet-induced obesity by modulating Akt/PKB signaling.[7]

Clinical cancer

Although in most cancer, mTOR pathway is constitutively activated and the expression of DEPTOR is low, one study has found that DEPTOR is overexpressed in multiple myeloma cells and is necessary for their survival.[3]

References

  1. ↑ "Entrez Gene: DEPDC6 DEP domain containing 6".
  2. ↑ "Homo sapiens - Ensembl protein families - Gene: DEPTOR (ENSG00000155792)". Ensembl genome browser 78.
  3. 1 2 3 4 Peterson TR, Laplante M, Thoreen CC, Sancak Y, Kang SA, Kuehl WM, Gray NS, Sabatini DM (May 2009). "DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival". Cell 137 (5): 873–86. doi:10.1016/j.cell.2009.03.046. PMID 19446321.
  4. ↑ Laplante M, Horvat S, Festuccia WT, Birsoy K, Prevorsek Z, Efeyan A, Sabatini DM (Aug 2012). "DEPTOR cell-autonomously promotes adipogenesis, and its expression is associated with obesity". Cell Metabolism 16 (2): 202–12. doi:10.1016/j.cmet.2012.07.008. PMC 3463374. PMID 22883231.
  5. ↑ Meng ZX, Li S, Wang L, Ko HJ, Lee Y, Jung DY, Okutsu M, Yan Z, Kim JK, Lin JD (May 2013). "Baf60c drives glycolytic metabolism in the muscle and improves systemic glucose homeostasis through Deptor-mediated Akt activation". Nature Medicine 19 (5): 640–5. doi:10.1038/nm.3144. PMC 3650110. PMID 23563706.
  6. ↑ Caron A, Baraboi ED, Laplante M, Richard D (Jan 2015). "DEP domain-containing mTOR-interacting protein in the rat brain: distribution of expression and potential implication". The Journal of Comparative Neurology 523 (1): 93–107. doi:10.1002/cne.23668. PMID 25159114.
  7. ↑ Caron, Alexandre; Labbé, Sébastien M.; Lanfray, Damien; Blanchard, Pierre-Gilles; Villot, Romain; Roy, Christian; Sabatini, David M.; Richard, Denis; Laplante, Mathieu. "Mediobasal Hypothalamic Overexpression of Deptor Protects Against High-Fat Diet-Induced Obesity". Molecular Metabolism. doi:10.1016/j.molmet.2015.11.005.

Further reading


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