InnateDB Protein
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IDBP-63693.6
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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AKT1S1
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Protein Name
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AKT1 substrate 1 (proline-rich)
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Synonyms
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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000341698
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InnateDB Gene
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IDBG-63691 (AKT1S1)
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Protein Structure
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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. {ECO:0000269PubMed:16174443, ECO:0000269PubMed:17277771, ECO:0000269PubMed:17386266}.
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Subcellular Localization |
Cytoplasm, cytosol {ECO:0000250}. Note=Found in the cytosolic fraction of the brain. {ECO:0000250}.
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Disease Associations |
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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). {ECO:0000269PubMed:12524439, ECO:0000269PubMed:16174443}.
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 38 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.
Experimentally validated |
Total |
38
[view]
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Protein-Protein |
37
[view]
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Protein-DNA |
1
[view]
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Predicted by orthology |
Total |
2 [view]
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Molecular Function |
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Biological Process |
GO:0006469
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negative regulation of protein kinase activity
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GO:0007173
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epidermal growth factor receptor signaling pathway
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GO:0008543
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fibroblast growth factor receptor signaling pathway
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GO:0032007
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negative regulation of TOR signaling
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GO:0038095
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Fc-epsilon receptor signaling pathway
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GO:0043523
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regulation of neuron apoptotic process
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GO:0045087
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innate immune response
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GO:0045792
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negative regulation of cell size
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GO:0048011
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neurotrophin TRK receptor signaling pathway
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GO:0048015
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phosphatidylinositol-mediated signaling
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Cellular Component |
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PDB ID |
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InterPro |
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PFAM |
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PRINTS |
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PIRSF |
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SMART |
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TIGRFAMs |
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Modification |
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SwissProt |
Q96B36
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PhosphoSite |
PhosphoSite-Q96B36
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TrEMBL |
M0R2V8
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UniProt Splice Variant |
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Entrez Gene |
84335
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UniGene |
Hs.628396
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RefSeq |
NP_001092103
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HUGO |
HGNC:28426
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OMIM |
610221
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CCDS |
CCDS12784
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HPRD |
12441
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IMGT |
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EMBL |
AC118341
AK055511
AK092610
AK226004
AK316603
BC000031
BC007416
BC015562
BC016043
BC051844
CH471177
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GenPept |
AAH00031
AAH07416
AAH15562
AAH16043
AAH51844
BAB70937
BAG38190
BAG52583
EAW52568
EAW52569
EAW52570
EAW52571
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