UniProtKB - Q96B36 (AKTS1_HUMAN)
(max 400 entries)x
Your basket is currently empty. i
Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)
Protein
Proline-rich AKT1 substrate 1
Gene
AKT1S1
Organism
Homo sapiens (Human)
Status
Functioni
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.3 Publications
GO - Biological processi
- negative regulation of cell size Source: UniProtKB
- negative regulation of protein kinase activity Source: UniProtKB
- negative regulation of TOR signaling Source: UniProtKB
- neurotrophin TRK receptor signaling pathway Source: InterPro
- protein kinase B signaling Source: Reactome
- regulation of apoptotic process Source: UniProtKB
- regulation of cellular response to heat Source: Reactome
- regulation of neuron apoptotic process Source: UniProtKB
- TORC1 signaling Source: GO_Central
Enzyme and pathway databases
Reactomei | R-HSA-165159. mTOR signalling. R-HSA-166208. mTORC1-mediated signalling. R-HSA-198323. AKT phosphorylates targets in the cytosol. R-HSA-3371571. HSF1-dependent transactivation. R-HSA-5674400. Constitutive Signaling by AKT1 E17K in Cancer. |
SABIO-RKi | Q96B36. |
SignaLinki | Q96B36. |
SIGNORi | Q96B36. |
Names & Taxonomyi
Protein namesi | Recommended name: Proline-rich AKT1 substrate 1Alternative name(s): 40 kDa proline-rich AKT substrate |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000204673.10. |
HGNCi | HGNC:28426. AKT1S1. |
MIMi | 610221. gene. |
neXtProti | NX_Q96B36. |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 246 | T → A: Suppresses S6K1 phosphorylation by mTORC1. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 84335. |
OpenTargetsi | ENSG00000204673. |
PharmGKBi | PA134943587. |
Chemistry databases
ChEMBLi | CHEMBL1255161. |
Polymorphism and mutation databases
DMDMi | 74731194. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000253446 | 1 – 256 | Proline-rich AKT1 substrate 1Add BLAST | 256 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 51 | Omega-N-methylarginineCombined sources | 1 | |
Modified residuei | 88 | PhosphoserineCombined sources | 1 | |
Modified residuei | 92 | PhosphoserineCombined sources | 1 | |
Modified residuei | 116 | PhosphoserineBy similarity | 1 | |
Modified residuei | 183 | PhosphoserineCombined sources | 1 | |
Modified residuei | 202 | PhosphoserineCombined sources | 1 | |
Modified residuei | 203 | PhosphoserineCombined sources | 1 | |
Modified residuei | 211 | PhosphoserineCombined sources | 1 | |
Modified residuei | 212 | PhosphoserineCombined sources | 1 | |
Modified residuei | 246 | Phosphothreonine; by PKB/AKT1 and DYRK3Combined sources2 Publications | 1 |
Post-translational modificationi
Phosphorylated by AKT1 (PubMed:12524439). Phosphorylation at Thr-246 by DYRK3 relieves inhibitory function on mTORC1 (PubMed:23415227).2 Publications
Keywords - PTMi
Methylation, PhosphoproteinProteomic databases
EPDi | Q96B36. |
MaxQBi | Q96B36. |
PaxDbi | Q96B36. |
PeptideAtlasi | Q96B36. |
PRIDEi | Q96B36. |
PTM databases
iPTMneti | Q96B36. |
PhosphoSitePlusi | Q96B36. |
Expressioni
Tissue specificityi
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).2 Publications
Gene expression databases
Bgeei | ENSG00000204673. |
CleanExi | HS_AKT1S1. |
ExpressionAtlasi | Q96B36. baseline and differential. |
Genevisiblei | Q96B36. HS. |
Organism-specific databases
HPAi | CAB021903. HPA043590. HPA064427. |
Interactioni
Subunit structurei
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.3 Publications
Binary interactionsi
Protein-protein interaction databases
BioGridi | 124059. 18 interactors. |
IntActi | Q96B36. 15 interactors. |
MINTi | Q96B36. |
STRINGi | 9606.ENSP00000341698. |
Chemistry databases
BindingDBi | Q96B36. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Beta strandi | 190 – 192 | Combined sources | 3 | |
Helixi | 213 – 231 | Combined sources | 19 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5WBL | X-ray | 3.35 | T | 124-139 | [»] | |
5WBU | X-ray | 3.42 | O/P/Q/R | 173-256 | [»] | |
5WBY | X-ray | 3.10 | O/P | 114-207 | [»] | |
ProteinModelPortali | Q96B36. | |||||
SMRi | Q96B36. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Family & Domainsi
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 35 – 43 | Poly-ProSequence analysis | 9 | |
Compositional biasi | 77 – 96 | Pro-richSequence analysisAdd BLAST | 20 |
Phylogenomic databases
eggNOGi | ENOG410IXEE. Eukaryota. ENOG41121RI. LUCA. |
GeneTreei | ENSGT00390000017397. |
HOVERGENi | HBG059465. |
InParanoidi | Q96B36. |
KOi | K16184. |
OMAi | RDCEPFF. |
OrthoDBi | EOG091G0IBG. |
PhylomeDBi | Q96B36. |
Family and domain databases
InterProi | View protein in InterPro IPR026682. AKT1S1. |
PANTHERi | PTHR21844. PTHR21844. 2 hits. |
Pfami | View protein in Pfam PF15798. PRAS. 1 hit. |
s (3)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basket
Isoform 12 Publications (identifier: Q96B36-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MASGRPEELW EAVVGAAERF RARTGTELVL LTAAPPPPPR PGPCAYAAHG
60 70 80 90 100
RGALAEAARR CLHDIALAHR AATAARPPAP PPAPQPPSPT PSPPRPTLAR
110 120 130 140 150
EDNEEDEDEP TETETSGEQL GISDNGGLFV MDEDATLQDL PPFCESDPES
160 170 180 190 200
TDDGSLSEET PAGPPTCSVP PASALPTQQY AKSLPVSVPV WGFKEKRTEA
210 220 230 240 250
RSSDEENGPP SSPDLDRIAA SMRALVLREA EDTQVFGDLP RPRLNTSDFQ
KLKRKY
Sequence cautioni
The sequence AAH00031 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 108 | D → G in BAB70937 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 196 | K → M in BAB70937 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 233 | T → A in BAB70937 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_028239 | 47 | A → P1 PublicationCorresponds to variant dbSNP:rs17850191Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_052182 | 1 – 130 | Missing in isoform 2. 1 PublicationAdd BLAST | 130 | |
Alternative sequenceiVSP_047536 | 1 | M → MSFEGGDGAGPAMLATGTAR M in isoform 3. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK055511 mRNA. Translation: BAB70937.1. AK092610 mRNA. Translation: BAG52583.1. AK316603 mRNA. Translation: BAG38190.1. AK226004 mRNA. No translation available. AC118341 Genomic DNA. No translation available. CH471177 Genomic DNA. Translation: EAW52570.1. CH471177 Genomic DNA. Translation: EAW52568.1. BC000031 mRNA. Translation: AAH00031.2. Different initiation. BC007416 mRNA. Translation: AAH07416.1. BC015562 mRNA. Translation: AAH15562.1. BC016043 mRNA. Translation: AAH16043.1. BC051844 mRNA. Translation: AAH51844.1. |
CCDSi | CCDS12784.1. [Q96B36-1] CCDS59410.1. [Q96B36-3] |
RefSeqi | NP_001092102.1. NM_001098632.2. [Q96B36-1] NP_001092103.1. NM_001098633.3. [Q96B36-1] NP_001265088.1. NM_001278159.1. [Q96B36-1] NP_001265089.1. NM_001278160.1. [Q96B36-1] NP_115751.3. NM_032375.5. [Q96B36-3] |
UniGenei | Hs.515542. Hs.610819. |
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | AKTS1_HUMAN | |
Accessioni | Q96B36Primary (citable) accession number: Q96B36 Secondary accession number(s): A8MTQ1 Q9BWR5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 17, 2006 |
Last sequence update: | December 1, 2001 | |
Last modified: | March 28, 2018 | |
This is version 131 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |