ID:AKTS1_HUMAN DESCRIPTION: RecName: Full=Proline-rich AKT1 substrate 1; AltName: Full=40 kDa proline-rich AKT substrate; FUNCTION: Subunit of mTORC1, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, AKT1S1 negatively regulates mTOR activity in a manner that is dependent on its phosphorylation state and binding to 14-3-3 proteins. Inhibits RHEB-GTP-dependent mTORC1 activation. Substrate for AKT1 phosphorylation, but can also be activated by AKT1-independent mechanisms. May also play a role in nerve growth factor-mediated neuroprotection. SUBUNIT: Part of the mammalian target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8, RPTOR, AKT1S1/PRAS40 and DEPTOR. mTORC1 binds to and is inhibited by FKBP12-rapamycin. Interacts directly with RPTOR. The phosphorylated form interacts with 14-3-3 proteins. SUBCELLULAR LOCATION: Cytoplasm, cytosol (By similarity). Note=Found in the cytosolic fraction of the brain (By similarity). TISSUE SPECIFICITY: Widely expressed with highest levels of expression in liver and heart. Expressed at higher levels in cancer cell lines (e.g. A-549 and HeLa) than in normal cell lines (e.g. HEK293). PTM: Phosphorylated by AKT1. Phosphorylation relieves inhibitory function on mTORC1. SEQUENCE CAUTION: Sequence=AAH00031.2; Type=Erroneous initiation;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q96B36
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006469 negative regulation of protein kinase activity GO:0032007 negative regulation of TOR signaling GO:0038202 TORC1 signaling GO:0042981 regulation of apoptotic process GO:0043523 regulation of neuron apoptotic process GO:0045792 negative regulation of cell size GO:0048011 neurotrophin TRK receptor signaling pathway GO:1900034 regulation of cellular response to heat
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