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Protein

Proline-rich AKT1 substrate 1

Gene

AKT1S1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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
SABIO-RKiQ96B36
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000204673.10
HGNCiHGNC:28426 AKT1S1
MIMi610221 gene
neXtProtiNX_Q96B36

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 sources3 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
ProteomicsDBi76040
76041 [Q96B36-2]

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 Expressed in 169 organ(s), highest expression level in gastrocnemius
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

Protein-protein interaction databases

BioGridi124059, 19 interactors
IntActiQ96B36, 13 interactors
MINTiQ96B36
STRINGi9606.ENSP00000341698

Chemistry databases

BindingDBiQ96B36

Structurei

Secondary structure

1256
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

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, 2 hits
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

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H9KV91H9KV91_HUMAN
Proline-rich AKT1 substrate 1
AKT1S1
108Annotation score:
M0R2V8M0R2V8_HUMAN
Proline-rich AKT1 substrate 1
AKT1S1
33Annotation score:

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

Cross-referencesi

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5WBLX-ray3.35T124-139[»]
5WBUX-ray3.42O/P/Q/R173-256[»]
5WBYX-ray3.10O/P114-207[»]
ProteinModelPortaliQ96B36
SMRiQ96B36
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124059, 19 interactors
IntActiQ96B36, 13 interactors
MINTiQ96B36
STRINGi9606.ENSP00000341698

Chemistry databases

BindingDBiQ96B36
ChEMBLiCHEMBL1255161

PTM databases

iPTMnetiQ96B36
PhosphoSitePlusiQ96B36

Polymorphism and mutation databases

DMDMi74731194

Proteomic databases

EPDiQ96B36
MaxQBiQ96B36
PaxDbiQ96B36
PeptideAtlasiQ96B36
PRIDEiQ96B36
ProteomicsDBi76040
76041 [Q96B36-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi84335
DisGeNETi84335
EuPathDBiHostDB:ENSG00000204673.10
GeneCardsiAKT1S1
HGNCiHGNC:28426 AKT1S1
HPAiCAB021903
HPA043590
HPA064427
MIMi610221 gene
neXtProtiNX_Q96B36
OpenTargetsiENSG00000204673
PharmGKBiPA134943587
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IXEE Eukaryota
ENOG41121RI LUCA
GeneTreeiENSGT00390000017397
HOVERGENiHBG059465
InParanoidiQ96B36
KOiK16184
OMAiRDCEPFF
OrthoDBiEOG091G0IBG
PhylomeDBiQ96B36

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
SABIO-RKiQ96B36
SignaLinkiQ96B36
SIGNORiQ96B36

Miscellaneous databases

ChiTaRSiAKT1S1 human
GeneWikiiAKT1S1
GenomeRNAii84335
PROiPR:Q96B36
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000204673 Expressed in 169 organ(s), highest expression level in gastrocnemius
CleanExiHS_AKT1S1
ExpressionAtlasiQ96B36 baseline and differential
GenevisibleiQ96B36 HS

Family and domain databases

InterProiView protein in InterPro
IPR026682 AKT1S1
PANTHERiPTHR21844 PTHR21844, 2 hits
PfamiView protein in Pfam
PF15798 PRAS, 1 hit
ProtoNetiSearch...

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: November 7, 2018
This is version 138 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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