Tchem AKT1S1 Proline-rich AKT1 substrate 1

Protein Summary

Description

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. AKT1S1 is a proline-rich substrate of AKT (MIM 164730) that binds 14-3-3 protein (see YWHAH, MIM 113508) when phosphorylated (Kovacina et al., 2003 [PubMed 12524439]).[supplied by OMIM, Mar 2008]

Uniprot Accession IDs

• Q96B36
• A8MTQ1
• B2RE93
• J3KPM3
• Q96BI4
• Q96IK7
• Q96NG2
• Q9BWR5

Gene Name

• AKT1S1

Ensembl ID

• ENST00000344175
• ENSP00000341698
• ENSG00000204673
• ENST00000391831
• ENSP00000375707
• ENST00000391832
• ENSP00000375708
• ENST00000391833
• ENSP00000375709
• ENST00000391834
• ENSP00000375710
• ENST00000391835
• ENSP00000375711

Symbol

• PRAS40
• Lobe
• PRAS40

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
ligand (protein) perturbation	0.99
transcription factor binding site profile	0.93
histone modification site profile	0.84
interacting protein	0.77
transcription factor	0.76

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 113.89   (req: < 5)

Gene RIFs: 35   (req: <= 3)

Antibodies: 538   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 113.89   (req: >= 5)

Gene RIFs: 35   (req: > 3)

Antibodies: 538   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 8

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 1

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0