AKT1S1 (AKT1 Substrate 1)
Proline-rich AKT1 substrate 1 (PRAS40) – a key regulator of mTORC1 signaling and cell growth
Gene Information Card
| Symbol | AKT1S1 |
|---|---|
| Full Name | AKT1 substrate 1 (proline-rich) |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 84335 ncbi.nlm.nih.gov/gene/84335 |
| Ensembl ID | ENSG00000105669 |
| UniProt ID | Q96B36 |
| OMIM ID | 610221 |
| HGNC ID | 28426 |
| Aliases | PRAS40, Lobe, FLJ14268 |
Description
AKT1S1 (AKT1 substrate 1) encodes the proline-rich AKT1 substrate 1 (PRAS40), a component of the mTORC1 signaling pathway. PRAS40 binds to Raptor and inhibits mTORC1 activity under basal conditions. Upon AKT1-mediated phosphorylation at Thr246, PRAS40 dissociates from mTORC1, relieving inhibition and promoting cell growth, proliferation, and survival. The gene is located on chromosome 19q13.33 and is widely expressed.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various) | PRAS40 overexpression or altered phosphorylation contributes to aberrant mTORC1 activation, promoting tumorigenesis | PMID: 20010870, COSMIC |
| Diabetes (type 2) | Impaired AKT1S1 phosphorylation in insulin-resistant tissues leads to dysregulated mTORC1 signaling and metabolic dysfunction | PMID: 21788567 |
| Tuberous sclerosis complex | PRAS40 phosphorylation status is altered in TSC1/TSC2-deficient cells, contributing to mTORC1 hyperactivation | PMID: 18316744 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 9.8 | Medium |
| Liver | 7.2 | Low |
| Kidney | 10.1 | Medium |
| Lung | 8.5 | Medium |
| Pancreas | 6.3 | Low |
| Skeletal muscle | 11.0 | Medium |
| Testis | 14.2 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.3 | High expression |
| HeLa | 12.1 | Medium expression |
| MCF7 | 10.8 | Medium expression |
| A549 | 9.5 | Medium expression |
| HepG2 | 7.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.737C>T (p.Thr246Met) | Missense | <0.1% (COSMIC) | Alters AKT1 phosphorylation site, potentially affecting mTORC1 regulation |
| c.1A>G (p.Met1Val) | Missense | <0.1% (ClinVar) | Start codon loss, likely loss of function |
| c.454_455insA | Frameshift | <0.1% (COSMIC) | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and start-loss mutations are predicted to result in loss of PRAS40 protein function, reducing mTORC1 inhibition.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported; Thr246 mutations may alter phosphorylation dynamics but not clearly activating.
Dominant Negative (DN)
No dominant-negative mutations described in literature or databases.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005515 (protein binding) | • GO:0031932 (TORC1 complex) |
| • GO:0043517 (negative regulation of TORC1 signaling) | • GO:0046777 (protein autophosphorylation) |
| • GO:0004672 (protein kinase activity | • indirect) |
Pathways
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• mTOR signaling pathway (KEGG: hsa04150)
• Insulin signaling pathway (KEGG: hsa04910)
Protein Summary
PRAS40 (proline-rich AKT1 substrate 1) is a 40 kDa protein that acts as a negative regulator of mTORC1. It contains an N-terminal proline-rich domain and a C-terminal TOR signaling (TOS) motif that mediates binding to Raptor. Phosphorylation at Thr246 by AKT1 promotes 14-3-3 binding and cytoplasmic retention, relieving mTORC1 inhibition. PRAS40 also interacts with other signaling molecules and is implicated in cell growth, metabolism, and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AKT1S1 Knockout HEK293 Cell Line | EDJ-KQ613 | Human | 84335 | Details Get a Quote |
| AKT1S1 Knockout A-549 Cell Line | EDJ-KQ20424 | Human | 84335 | Details Get a Quote |
| AKT1S1 Knockout HCT 116 Cell Line | EDJ-KQ20425 | Human | 84335 | Details Get a Quote |
| AKT1S1 Knockout HeLa Cell Line | EDJ-KQ20426 | Human | 84335 | Details Get a Quote |
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