InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: AKT1S1

Summary

InnateDB Protein

IDBP-246895.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

AKT1S1

Protein Name

AKT1 substrate 1 (proline-rich)

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000375708

InnateDB Gene

IDBG-63691 (AKT1S1)

Protein Structure

UniProt Annotation

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}.

Subcellular Localization

Cytoplasm, cytosol {ECO:0000250}. Note=Found in the cytosolic fraction of the brain. {ECO:0000250}.

Disease Associations

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}.

Comments

Interactions

Number of Interactions

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]
Protein-Protein	37 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding

Biological Process

GO:0006469	negative regulation of protein kinase activity
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0032007	negative regulation of TOR signaling
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0043523	regulation of neuron apoptotic process
GO:0045087	innate immune response
GO:0045792	negative regulation of cell size
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling