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Q96B36 (AKTS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Proline-rich AKT1 substrate 1
Alternative name(s):
40 kDa proline-rich AKT substrate
Gene names
Name:AKT1S1
Synonyms:PRAS40
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length256 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.7 Ref.9 Ref.10

Subunit 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. Ref.6 Ref.9 Ref.10

Subcellular location

Cytoplasmcytosol 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). Ref.6 Ref.7

Post-translational modification

Phosphorylated by AKT1. Phosphorylation relieves inhibitory function on mTORC1. Ref.6

Sequence caution

The sequence AAH00031.2 differs from that shown. Reason: Erroneous initiation.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

BMH1P293113EBI-720593,EBI-3661From a different organism.
YWHAHQ049173EBI-720593,EBI-306940

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.1 Ref.5 (identifier: Q96B36-1)

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.
Isoform 2 Ref.5 (identifier: Q96B36-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-130: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q96B36-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MSFEGGDGAGPAMLATGTARM
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 256256Proline-rich AKT1 substrate 1
PRO_0000253446

Regions

Compositional bias35 – 439Poly-Pro
Compositional bias77 – 9620Pro-rich

Amino acid modifications

Modified residue881Phosphoserine Ref.11 Ref.13 Ref.16
Modified residue921Phosphoserine Ref.11 Ref.13 Ref.16
Modified residue1831Phosphoserine Ref.8 Ref.11 Ref.13 Ref.14 Ref.16
Modified residue2021Phosphoserine Ref.11 Ref.13 Ref.14
Modified residue2031Phosphoserine Ref.11 Ref.14
Modified residue2111Phosphoserine Ref.11 Ref.13 Ref.14
Modified residue2121Phosphoserine Ref.11 Ref.13 Ref.14
Modified residue2461Phosphothreonine; by PKB/AKT1 Ref.6 Ref.11 Ref.13 Ref.14 Ref.16

Natural variations

Alternative sequence1 – 130130Missing in isoform 2. Ref.5
VSP_052182
Alternative sequence11M → MSFEGGDGAGPAMLATGTAR M in isoform 3.
VSP_047536
Natural variant471A → P. Ref.5
Corresponds to variant rs17850191 [ dbSNP | Ensembl ].
VAR_028239

Experimental info

Mutagenesis2461T → A: Suppresses S6K1 phosphorylation by mTORC1. Ref.10
Sequence conflict1081D → G in BAB70937. Ref.1
Sequence conflict1961K → M in BAB70937. Ref.1
Sequence conflict2331T → A in BAB70937. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: F6CB195CBB54326C

FASTA25627,383
        10         20         30         40         50         60 
MASGRPEELW EAVVGAAERF RARTGTELVL LTAAPPPPPR PGPCAYAAHG RGALAEAARR 

        70         80         90        100        110        120 
CLHDIALAHR AATAARPPAP PPAPQPPSPT PSPPRPTLAR EDNEEDEDEP TETETSGEQL 

       130        140        150        160        170        180 
GISDNGGLFV MDEDATLQDL PPFCESDPES TDDGSLSEET PAGPPTCSVP PASALPTQQY 

       190        200        210        220        230        240 
AKSLPVSVPV WGFKEKRTEA RSSDEENGPP SSPDLDRIAA SMRALVLREA EDTQVFGDLP 

       250 
RPRLNTSDFQ KLKRKY 

« Hide

Isoform 2 [UniParc].

Checksum: 2E34744BBEFEC1E9
Show »

FASTA12613,807
Isoform 3 [UniParc].

Checksum: 3866EE718A29CC48
Show »

FASTA27629,262

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Prostate and Synovium.
[2]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Coronary artery.
[3]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT PRO-47.
Tissue: Brain, Eye and Skin.
[6]"Identification of a proline-rich Akt substrate as a 14-3-3 binding partner."
Kovacina K.S., Park G.Y., Bae S.S., Guzzetta A.W., Schaefer E., Birnbaum M.J., Roth R.A.
J. Biol. Chem. 278:10189-10194(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH 14-3-3, TISSUE SPECIFICITY, PHOSPHORYLATION AT THR-246.
[7]"Expression of proline-rich Akt-substrate PRAS40 in cell survival pathway and carcinogenesis."
Huang B., Porter G.
Acta Pharmacol. Sin. 26:1253-1258(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[8]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase."
Sancak Y., Thoreen C.C., Peterson T.R., Lindquist R.A., Kang S.A., Spooner E., Carr S.A., Sabatini D.M.
Mol. Cell 25:903-915(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN THE TORC1 COMPLEX, INTERACTION WITH RPTOR.
[10]"Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40."
Vander Haar E., Lee S.-I., Bandhakavi S., Griffin T.J., Kim D.-H.
Nat. Cell Biol. 9:316-323(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN THE TORC1 COMPLEX, MUTAGENESIS OF THR-246.
[11]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-92; SER-183; SER-202; SER-203; SER-211; SER-212 AND THR-246, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-92; SER-183; SER-202; SER-211; SER-212 AND THR-246, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[14]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183; SER-202; SER-203; SER-211; SER-212 AND THR-246, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-92; SER-183 AND THR-246, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001092102.1. NM_001098632.2.
NP_001092103.1. NM_001098633.3.
NP_001265088.1. NM_001278159.1.
NP_001265089.1. NM_001278160.1.
NP_115751.3. NM_032375.5.
UniGeneHs.515542.
Hs.610819.

3D structure databases

ProteinModelPortalQ96B36.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124059. 10 interactions.
IntActQ96B36. 11 interactions.
MINTMINT-3317903.
STRING9606.ENSP00000341698.

Chemistry

BindingDBQ96B36.
ChEMBLCHEMBL1255161.

PTM databases

PhosphoSiteQ96B36.

Polymorphism databases

DMDM74731194.

Proteomic databases

PaxDbQ96B36.
PRIDEQ96B36.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000344175; 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]
GeneID84335.
KEGGhsa:84335.
UCSCuc002pqm.5. human. [Q96B36-1]

Organism-specific databases

CTD84335.
GeneCardsGC19M050372.
HGNCHGNC:28426. AKT1S1.
HPACAB021903.
HPA043590.
MIM610221. gene.
neXtProtNX_Q96B36.
PharmGKBPA134943587.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40718.
HOVERGENHBG059465.
InParanoidQ96B36.
KOK16184.
OMACLHDIAQ.
OrthoDBEOG7X3QRW.
PhylomeDBQ96B36.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.
SignaLinkQ96B36.

Gene expression databases

ArrayExpressQ96B36.
BgeeQ96B36.
CleanExHS_AKT1S1.
GenevestigatorQ96B36.

Family and domain databases

InterProIPR026682. AKT1S1.
[Graphical view]
PANTHERPTHR21844. PTHR21844. 1 hit.
ProtoNetSearch...

Other

ChiTaRSAKT1S1. human.
GeneWikiAKT1S1.
GenomeRNAi84335.
NextBio35535165.
PROQ96B36.
SOURCESearch...

Entry information

Entry nameAKTS1_HUMAN
AccessionPrimary (citable) accession number: Q96B36
Secondary accession number(s): A8MTQ1 expand/collapse secondary AC list , B2RE93, J3KPM3, Q96BI4, Q96IK7, Q96NG2, Q9BWR5
Entry history
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: December 1, 2001
Last modified: April 16, 2014
This is version 96 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM