DEPTOR
Identifiers
AliasesDEPTOR, DEP.6, DEPDC6, DEP domain containing MTOR-interacting protein, DEP domain containing MTOR interacting protein
External IDsOMIM: 612974 MGI: 2146322 HomoloGene: 32551 GeneCards: DEPTOR
Orthologs
SpeciesHumanMouse
Entrez

64798

97998

Ensembl

ENSG00000155792

ENSMUSG00000022419

UniProt

Q8TB45

Q570Y9

RefSeq (mRNA)

NM_022783
NM_001283012

NM_001037937
NM_145470

RefSeq (protein)

NP_001269941
NP_073620

NP_001033026
NP_663445

Location (UCSC)Chr 8: 119.87 – 120.05 MbChr 15: 54.98 – 55.12 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5]

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.[6] Human DEPTOR contains two N-terminal DEP domains and a C-terminal PDZ domain.[7]

Function

DEPTOR is involved in mTOR signaling pathway as an endogenous regulator. A direct interaction between DEPTOR and mTOR has been shown. [7] Overexpression of DEPTOR downregulates the activity of mTORC1 and mTORC2 in vitro. mTORC1 and mTORC2 can both inhibit DEPTOR through phosphorylation.[7]

Metabolism

DEPTOR cell-autonomously regulates adipogenesis.[8] In the muscle, Baf60c promotes a switch from oxidative to glycolytic myofiber type through DEPTOR-mediated Akt/PKB activation.[9] Within the brain, DEPTOR is highly expressed in the hippocampus, the medio-basal hypothalamus and the circumventricular organs.[10] Overexpression of DEPTOR in the medio-basal hypothalamus protects mice against high-fat diet-induced obesity by modulating Akt/PKB signaling.[11]

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.[7]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000155792 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022419 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: DEPDC6 DEP domain containing 6".
  6. ^ "Homo sapiens - Ensembl protein families - Gene: DEPTOR (ENSG00000155792)". Ensembl genome browser 78.
  7. ^ a b c d 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. PMC 2758791. PMID 19446321.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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. S2CID 205683672.
  11. ^ Caron, Alexandre; Labbé, Sébastien M.; Lanfray, Damien; Blanchard, Pierre-Gilles; Villot, Romain; Roy, Christian; Sabatini, David M.; Richard, Denis; Laplante, Mathieu (2016). "Mediobasal Hypothalamic Overexpression of Deptor Protects Against High-Fat Diet-Induced Obesity". Molecular Metabolism. 5 (2): 102–112. doi:10.1016/j.molmet.2015.11.005. PMC 4735664. PMID 26909318.

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