Human Gene AKT1S1 (ENST00000344175.10_12) from GENCODE V47lift37
  Description: AKT1 substrate 1, transcript variant 3 (from RefSeq NM_001098633.4)
Gencode Transcript: ENST00000344175.10_12
Gencode Gene: ENSG00000204673.11_16
Transcript (Including UTRs)
   Position: hg19 chr19:50,372,296-50,380,612 Size: 8,317 Total Exon Count: 5 Strand: -
Coding Region
   Position: hg19 chr19:50,373,174-50,376,552 Size: 3,379 Coding Exon Count: 4 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr19:50,372,296-50,380,612)mRNA (may differ from genome)Protein (256 aa)
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-  Comments and Description Text from UniProtKB
  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;

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: AKT1S1
Diseases sorted by gene-association score: diaphragmatic eventration (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 18.04 RPKM in Adrenal Gland
Total median expression: 593.00 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -46.50126-0.369 Picture PostScript Text
3' UTR -351.70878-0.401 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR026682 - AKT1S1

Pfam Domains:
PF15798 - Proline-rich AKT1 substrate 1

ModBase Predicted Comparative 3D Structure on Q96B36
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding

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

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0032991 macromolecular complex
GO:0031931 TORC1 complex


-  Descriptions from all associated GenBank mRNAs
  BC022241 - Homo sapiens AKT1 substrate 1 (proline-rich), mRNA (cDNA clone IMAGE:4399397), with apparent retained intron.
BC000031 - Homo sapiens AKT1 substrate 1 (proline-rich), mRNA (cDNA clone IMAGE:3509274), partial cds.
BC016043 - Homo sapiens AKT1 substrate 1 (proline-rich), mRNA (cDNA clone MGC:20246 IMAGE:4635389), complete cds.
BC007416 - Homo sapiens AKT1 substrate 1 (proline-rich), mRNA (cDNA clone MGC:2865 IMAGE:2988648), complete cds.
BC051844 - Homo sapiens AKT1 substrate 1 (proline-rich), mRNA (cDNA clone MGC:60158 IMAGE:6164197), complete cds.
BC015562 - Homo sapiens AKT1 substrate 1 (proline-rich), mRNA (cDNA clone IMAGE:3955201), complete cds.
AK092610 - Homo sapiens cDNA FLJ35291 fis, clone PROST2008447, highly similar to Homo sapiens AKT1 substrate 1 (proline-rich) (AKT1S1), mRNA.
AX747627 - Sequence 1152 from Patent EP1308459.
AK055511 - Homo sapiens cDNA FLJ30949 fis, clone HCASM1000021, weakly similar to Plasmodium berghei strain NYU2 merozoite surface protein-1 mRNA.
AK123687 - Homo sapiens cDNA FLJ41693 fis, clone HCHON2000244.
JD483950 - Sequence 464974 from Patent EP1572962.
JD283107 - Sequence 264131 from Patent EP1572962.
JD121091 - Sequence 102115 from Patent EP1572962.
JD338034 - Sequence 319058 from Patent EP1572962.
JD275793 - Sequence 256817 from Patent EP1572962.
JD134408 - Sequence 115432 from Patent EP1572962.
JD411335 - Sequence 392359 from Patent EP1572962.
JD208057 - Sequence 189081 from Patent EP1572962.
JD486901 - Sequence 467925 from Patent EP1572962.
JD406373 - Sequence 387397 from Patent EP1572962.
JD129277 - Sequence 110301 from Patent EP1572962.
JD403149 - Sequence 384173 from Patent EP1572962.
JD325014 - Sequence 306038 from Patent EP1572962.
AK226004 - Homo sapiens mRNA for AKT1 substrate 1 variant, clone: FCC109B07.
JD389306 - Sequence 370330 from Patent EP1572962.
AK316603 - Homo sapiens cDNA, FLJ96719.
KJ903421 - Synthetic construct Homo sapiens clone ccsbBroadEn_12815 AKT1S1 gene, encodes complete protein.
AK074097 - Homo sapiens mRNA for FLJ00168 protein.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q96B36 (Reactome details) participates in the following event(s):

R-HSA-200143 AKT phosphorylates AKT1S1 (PRAS40)
R-HSA-2399977 AKT1 E17K mutant phosphorylates AKT1S1 (PRAS40)
R-HSA-5672843 AKT1S1 (PRAS40) binds mTORC1
R-HSA-377186 Activated Akt1 phosphorylates AKT1S1 (PRAS40)
R-HSA-5672824 Phosphorylated AKT1S1:mTORC1 binds YWHAB
R-HSA-5672828 mTORC1 phosphorylates AKT1S1
R-HSA-5082405 Phosphorylation of HSF1 at Ser326 induces transactivation
R-HSA-198323 AKT phosphorylates targets in the cytosol
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-165159 mTOR signalling
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-2219528 PI3K/AKT Signaling in Cancer
R-HSA-162582 Signal Transduction
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-5663202 Diseases of signal transduction
R-HSA-1643685 Disease
R-HSA-3371571 HSF1-dependent transactivation
R-HSA-3371556 Cellular response to heat stress
R-HSA-2262752 Cellular responses to stress
R-HSA-8953897 Cellular responses to external stimuli

-  Other Names for This Gene
  Alternate Gene Symbols: A8MTQ1, AKT1S1 , AKTS1_HUMAN, B2RE93, ENST00000344175.1, ENST00000344175.2, ENST00000344175.3, ENST00000344175.4, ENST00000344175.5, ENST00000344175.6, ENST00000344175.7, ENST00000344175.8, ENST00000344175.9, J3KPM3, NM_001098633, PRAS40 , Q96B36, Q96BI4, Q96IK7, Q96NG2, Q9BWR5, uc317wwc.1, uc317wwc.2
UCSC ID: ENST00000344175.10_12
RefSeq Accession: NM_001098633.4
Protein: Q96B36 (aka AKTS1_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.