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] See more...

Aliases for AKT1S1 Gene

Aliases for AKT1S1 Gene

  • AKT1 Substrate 1 2 3 5
  • PRAS40 2 3 4
  • 40 KDa Proline-Rich AKT Substrate 3 4
  • Proline-Rich AKT1 Substrate 1 3 4
  • Lobe 2 3
  • Proline-Rich Akt Substrate, 40 KDa 2
  • AKT1 Substrate 1 (Proline-Rich) 2
  • AKT1 Substrate 1 (Proline Rich) 3
  • MGC2865 2
  • AKT1S1 5

External Ids for AKT1S1 Gene

Previous GeneCards Identifiers for AKT1S1 Gene

  • GC19M055067
  • GC19M055071
  • GC19M055073
  • GC19M050372
  • GC19M046748

Summaries for AKT1S1 Gene

Entrez Gene Summary for AKT1S1 Gene

  • 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]

GeneCards Summary for AKT1S1 Gene

AKT1S1 (AKT1 Substrate 1) is a Protein Coding gene. Diseases associated with AKT1S1 include Breast Papillomatosis and Tuberous Sclerosis 1. Among its related pathways are RET signaling and Development HGF signaling pathway.

UniProtKB/Swiss-Prot Summary for AKT1S1 Gene

  • 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.

Gene Wiki entry for AKT1S1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for AKT1S1 Gene

Genomics for AKT1S1 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for AKT1S1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around AKT1S1 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for AKT1S1

Top Transcription factor binding sites by QIAGEN in the AKT1S1 gene promoter:
  • p300
  • Sp1
  • SRY

Genomic Locations for AKT1S1 Gene

Latest Assembly
chr19:49,869,033-49,878,459
(GRCh38/hg38)
Size:
9,427 bases
Orientation:
Minus strand

Previous Assembly
chr19:50,372,290-50,381,613
(GRCh37/hg19 by Entrez Gene)
Size:
9,324 bases
Orientation:
Minus strand

chr19:50,372,295-50,381,716
(GRCh37/hg19 by Ensembl)
Size:
9,422 bases
Orientation:
Minus strand

Genomic View for AKT1S1 Gene

Genes around AKT1S1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
AKT1S1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for AKT1S1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for AKT1S1 Gene

Proteins for AKT1S1 Gene

  • Protein details for AKT1S1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96B36-AKTS1_HUMAN
    Recommended name:
    Proline-rich AKT1 substrate 1
    Protein Accession:
    Q96B36
    Secondary Accessions:
    • A8MTQ1
    • B2RE93
    • J3KPM3
    • Q96BI4
    • Q96IK7
    • Q96NG2
    • Q9BWR5

    Protein attributes for AKT1S1 Gene

    Size:
    256 amino acids
    Molecular mass:
    27383 Da
    Quaternary structure:
    • 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.
    SequenceCaution:
    • Sequence=AAH00031.2; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for AKT1S1 Gene

    Alternative splice isoforms for AKT1S1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for AKT1S1 Gene

Post-translational modifications for AKT1S1 Gene

  • Phosphorylated by AKT1 (PubMed:12524439). Phosphorylation at Thr-246 by DYRK3 relieves inhibitory function on mTORC1 (PubMed:23415227).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for AKT1S1 Gene

Domains & Families for AKT1S1 Gene

Gene Families for AKT1S1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for AKT1S1 Gene

InterPro:

Suggested Antigen Peptide Sequences for AKT1S1 Gene

GenScript: Design optimal peptide antigens:
  • 40 kDa proline-rich AKT substrate (AKTS1_HUMAN)
genes like me logo Genes that share domains with AKT1S1: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for AKT1S1 Gene

Function for AKT1S1 Gene

Molecular function for AKT1S1 Gene

UniProtKB/Swiss-Prot 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.

Phenotypes From GWAS Catalog for AKT1S1 Gene

Gene Ontology (GO) - Molecular Function for AKT1S1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 12524439
genes like me logo Genes that share ontologies with AKT1S1: view
genes like me logo Genes that share phenotypes with AKT1S1: view

Animal Models for AKT1S1 Gene

MGI Knock Outs for AKT1S1:

miRNA for AKT1S1 Gene

miRTarBase miRNAs that target AKT1S1

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for AKT1S1

Clone products for research

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for AKT1S1 Gene

Localization for AKT1S1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for AKT1S1 Gene

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

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for AKT1S1 gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
endosome 2
lysosome 2
peroxisome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for AKT1S1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IBA 21873635
GO:0005829 cytosol TAS --
GO:0031931 colocalizes_with TORC1 complex IDA 17386266
genes like me logo Genes that share ontologies with AKT1S1: view

Pathways & Interactions for AKT1S1 Gene

genes like me logo Genes that share pathways with AKT1S1: view

SIGNOR curated interactions for AKT1S1 Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for AKT1S1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006469 negative regulation of protein kinase activity IBA,IDA 17386266
GO:0032007 negative regulation of TOR signaling IDA 17386266
GO:0042981 regulation of apoptotic process ISS --
GO:0043523 regulation of neuron apoptotic process ISS --
GO:0045792 negative regulation of cell size IDA 17386266
genes like me logo Genes that share ontologies with AKT1S1: view

Drugs & Compounds for AKT1S1 Gene

(3) Drugs for AKT1S1 Gene - From: DGIdb

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
OSI-027 Investigational Pharma inhibitor MTORC1/ mTORC2 inhibitor, Kinase Inhibitors 0
AZD8055 Pharma inhibitor MTOR inhibitor, Kinase Inhibitors 0
MLN0128 Pharma inhibitor Kinase Inhibitors 0
genes like me logo Genes that share compounds with AKT1S1: view

Transcripts for AKT1S1 Gene

mRNA/cDNA for AKT1S1 Gene

5 REFSEQ mRNAs :
15 NCBI additional mRNA sequence :
9 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for AKT1S1

Clone products for research

Alternative Splicing Database (ASD) splice patterns (SP) for AKT1S1 Gene

No ASD Table

Relevant External Links for AKT1S1 Gene

GeneLoc Exon Structure for
AKT1S1

Expression for AKT1S1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for AKT1S1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for AKT1S1 Gene

This gene is overexpressed in Adrenal (22.8), Bone marrow stromal cell (12.0), and Lung (8.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for AKT1S1 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for AKT1S1

SOURCE GeneReport for Unigene cluster for AKT1S1 Gene:

Hs.515542

mRNA Expression by UniProt/SwissProt for AKT1S1 Gene:

Q96B36-AKTS1_HUMAN
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).

Evidence on tissue expression from TISSUES for AKT1S1 Gene

  • Liver(4.5)
  • Nervous system(4.1)
  • Skin(3.7)
  • Lung(2.8)
  • Muscle(2.7)
  • Intestine(2.6)
  • Kidney(2.5)
  • Heart(2.4)
  • Pancreas(2.3)
  • Blood(2.2)
  • Lymph node(2.1)
  • Eye(2)
genes like me logo Genes that share expression patterns with AKT1S1: view

Primer products for research

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for AKT1S1 Gene

Orthologs for AKT1S1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for AKT1S1 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia AKT1S1 29 30
  • 98.96 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia AKT1S1 29 30
  • 89.98 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia AKT1S1 29 30
  • 88.54 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Akt1s1 29 16 30
  • 83.59 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Akt1s1 29
  • 82.81 (n)
Oppossum
(Monodelphis domestica)
Mammalia AKT1S1 30
  • 64 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia AKT1S1 30
  • 55 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia akt1s1 29
  • 62.06 (n)
Str.8926 29
African clawed frog
(Xenopus laevis)
Amphibia Xl.7177 29
Zebrafish
(Danio rerio)
Actinopterygii akt1s1 30
  • 27 (a)
OneToOne
Species where no ortholog for AKT1S1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for AKT1S1 Gene

ENSEMBL:
Gene Tree for AKT1S1 (if available)
TreeFam:
Gene Tree for AKT1S1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for AKT1S1: view image
Alliance of Genome Resources:
Additional Orthologs for AKT1S1

Paralogs for AKT1S1 Gene

No data available for Paralogs for AKT1S1 Gene

Variants for AKT1S1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for AKT1S1 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
rs149454204 Benign: not provided 49,872,948(-) G/A
NM_001098633.4(AKT1S1):c.348C>T (p.Ser116=)
SYNONYMOUS
rs201965042 Benign: not provided 49,873,131(-) C/T
NM_001098633.4(AKT1S1):c.165G>A (p.Ala55=)
SYNONYMOUS
rs17850191 -- p.Ala47Pro

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for AKT1S1 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for AKT1S1 Gene

Variant ID Type Subtype PubMed ID
dgv53n68 CNV loss 17160897
dgv54n68 CNV loss 17160897
esv2718724 CNV deletion 23290073
esv2718725 CNV deletion 23290073
esv3644628 CNV gain 21293372
esv3644630 CNV gain 21293372
nsv1111553 CNV deletion 24896259
nsv1121196 CNV deletion 24896259
nsv1140251 OTHER inversion 24896259
nsv1152384 CNV deletion 26484159
nsv138068 CNV deletion 16902084
nsv2519 CNV deletion 18451855
nsv524068 CNV loss 19592680
nsv526372 CNV loss 19592680
nsv953600 CNV deletion 24416366
nsv9739 CNV gain+loss 18304495

Variation tolerance for AKT1S1 Gene

Gene Damage Index Score: 1.17; 23.65% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for AKT1S1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
AKT1S1
Leiden Open Variation Database (LOVD)
AKT1S1

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for AKT1S1 Gene

Disorders for AKT1S1 Gene

MalaCards: The human disease database

(8) MalaCards diseases for AKT1S1 Gene - From: COP

Disorder Aliases PubMed IDs
breast papillomatosis
  • papillomatosis of the breast
tuberous sclerosis 1
  • tsc1
cowden syndrome 1
  • cws1
subependymal glioma
  • mixed subependymoma-ependymoma
tuberous sclerosis 2
  • tsc2
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for AKT1S1

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with AKT1S1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for AKT1S1 Gene

Publications for AKT1S1 Gene

  1. Identification of a proline-rich Akt substrate as a 14-3-3 binding partner. (PMID: 12524439) Kovacina KS … Roth RA (The Journal of biological chemistry 2003) 2 3 4
  2. PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. (PMID: 17386266) Sancak Y … Sabatini DM (Molecular cell 2007) 3 4
  3. Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. (PMID: 17277771) Vander Haar E … Kim DH (Nature cell biology 2007) 3 4
  4. Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. (PMID: 17081983) Olsen JV … Mann M (Cell 2006) 3 4
  5. Expression of proline-rich Akt-substrate PRAS40 in cell survival pathway and carcinogenesis. (PMID: 16174443) Huang B … Porter G (Acta pharmacologica Sinica 2005) 3 4

Products for AKT1S1 Gene

Sources for AKT1S1 Gene