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UniProtKB - Q96B36 (AKTS1_HUMAN)

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Protein

Proline-rich AKT1 substrate 1

Gene

AKT1S1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-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.
SignaLinkiQ96B36.
SIGNORiQ96B36.

Names & Taxonomyi

Protein namesi
Recommended name:
Proline-rich AKT1 substrate 1
Alternative name(s):
40 kDa proline-rich AKT substrate
Gene namesi
Name:AKT1S1Imported
Synonyms:PRAS402 Publications
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:28426. AKT1S1.

Subcellular locationi

  • Cytoplasm › cytosol By similarity

    • Note: Found in the cytosolic fraction of the brain.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi246T → A: Suppresses S6K1 phosphorylation by mTORC1. 2 Publications1

Organism-specific databases

DisGeNETi84335.
OpenTargetsiENSG00000204673.
PharmGKBiPA134943587.

Chemistry databases

ChEMBLiCHEMBL1255161.

Polymorphism and mutation databases

DMDMi74731194.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002534461 – 256Proline-rich AKT1 substrate 1Add BLAST256

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei51Omega-N-methylarginineCombined sources1
Modified residuei88PhosphoserineCombined sources1
Modified residuei92PhosphoserineCombined sources1
Modified residuei116PhosphoserineBy similarity1
Modified residuei183PhosphoserineCombined sources1
Modified residuei202PhosphoserineCombined sources1
Modified residuei203PhosphoserineCombined sources1
Modified residuei211PhosphoserineCombined sources1
Modified residuei212PhosphoserineCombined sources1
Modified residuei246Phosphothreonine; by PKB/AKT1 and DYRK3Combined sources2 Publications1

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, Phosphoprotein

Proteomic databases

EPDiQ96B36.
MaxQBiQ96B36.
PaxDbiQ96B36.
PeptideAtlasiQ96B36.
PRIDEiQ96B36.

PTM databases

iPTMnetiQ96B36.
PhosphoSitePlusiQ96B36.

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

BgeeiENSG00000204673.
CleanExiHS_AKT1S1.
ExpressionAtlasiQ96B36. baseline and differential.
GenevisibleiQ96B36. HS.

Organism-specific databases

HPAiCAB021903.
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

Show more details

Protein-protein interaction databases

BioGridi124059. 14 interactors.
IntActiQ96B36. 12 interactors.
MINTiMINT-3317903.
STRINGi9606.ENSP00000341698.

Chemistry databases

BindingDBiQ96B36.

Structurei

3D structure databases

ProteinModelPortaliQ96B36.
SMRiQ96B36.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi35 – 43Poly-ProSequence analysis9
Compositional biasi77 – 96Pro-richSequence analysisAdd BLAST20

Phylogenomic databases

eggNOGiENOG410IXEE. Eukaryota.
ENOG41121RI. LUCA.
GeneTreeiENSGT00390000017397.
HOVERGENiHBG059465.
InParanoidiQ96B36.
KOiK16184.
OMAiRDCEPFF.
OrthoDBiEOG091G0IBG.
PhylomeDBiQ96B36.

Family and domain databases

InterProiView protein in InterPro
IPR026682. AKT1S1.
PANTHERiPTHR21844. PTHR21844. 1 hit.
PfamiView protein in Pfam
PF15798. PRAS. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative 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.

« Hide

        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
Length:256
Mass (Da):27,383
Last modified:December 1, 2001 - v1
Checksum:iF6CB195CBB54326C
GO
Isoform 21 Publication (identifier: Q96B36-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-130: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:126
Mass (Da):13,807
Checksum:i2E34744BBEFEC1E9
GO
Isoform 3 (identifier: Q96B36-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MSFEGGDGAGPAMLATGTARM

Note: No experimental confirmation available.
Show »
Length:276
Mass (Da):29,262
Checksum:i3866EE718A29CC48
GO

Sequence cautioni

The sequence AAH00031 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti108D → G in BAB70937 (PubMed:14702039).Curated1
Sequence conflicti196K → M in BAB70937 (PubMed:14702039).Curated1
Sequence conflicti233T → A in BAB70937 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02823947A → P1 PublicationCorresponds to variant dbSNP:rs17850191Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0521821 – 130Missing in isoform 2. 1 PublicationAdd BLAST130
Alternative sequenceiVSP_0475361M → MSFEGGDGAGPAMLATGTAR M in isoform 3. 1 Publication1

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.
CCDSiCCDS12784.1. [Q96B36-1]
CCDS59410.1. [Q96B36-3]
RefSeqiNP_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]
UniGeneiHs.515542.
Hs.610819.

Genome annotation databases

EnsembliENST00000344175; ENSP00000341698; ENSG00000204673. [Q96B36-1]
ENST00000391831; ENSP00000375707; ENSG00000204673. [Q96B36-1]
ENST00000391832; ENSP00000375708; ENSG00000204673. [Q96B36-1]
ENST00000391833; ENSP00000375709; ENSG00000204673. [Q96B36-1]
ENST00000391834; ENSP00000375710; ENSG00000204673. [Q96B36-1]
ENST00000391835; ENSP00000375711; ENSG00000204673. [Q96B36-3]
GeneIDi84335.
KEGGihsa:84335.
UCSCiuc002pql.6. human. [Q96B36-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiAKTS1_HUMAN
AccessioniPrimary (citable) accession number: Q96B36
Secondary accession number(s): A8MTQ1
, B2RE93, J3KPM3, Q96BI4, Q96IK7, Q96NG2, Q9BWR5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: December 1, 2001
Last modified: June 7, 2017
This is version 125 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot