AKTS1_MOUSE
ID AKTS1_MOUSE Reviewed; 257 AA.
AC Q9D1F4; A2RT52;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Proline-rich AKT1 substrate 1;
DE Short=Proline-rich AKT substrate;
GN Name=Akt1s1 {ECO:0000312|MGI:MGI:1914855};
GN Synonyms=Pras {ECO:0000303|PubMed:14973226};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000312|EMBL:BAB22905.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAB22905.1}, and
RC NOD {ECO:0000312|EMBL:BAE32383.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:BAB22905.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3] {ECO:0000305}
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=14973226; DOI=10.1523/jneurosci.5209-03.2004;
RA Saito A., Narasimhan P., Hayashi T., Okuno S., Ferrand-Drake M., Chan P.H.;
RT "Neuroprotective role of a proline-rich Akt substrate in apoptotic neuronal
RT cell death after stroke: relationships with nerve growth factor.";
RL J. Neurosci. 24:1584-1593(2004).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=16397181; DOI=10.1161/01.str.0000198826.56611.a2;
RA Saito A., Hayashi T., Okuno S., Nishi T., Chan P.H.;
RT "Modulation of proline-rich akt substrate survival signaling pathways by
RT oxidative stress in mouse brains after transient focal cerebral ischemia.";
RL Stroke 37:513-517(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203; SER-204; SER-212 AND
RP SER-213, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-92; SER-117; SER-184;
RP SER-203; SER-204; SER-212; SER-213 AND THR-247, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-51, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Subunit of mTORC1, which regulates cell growth and survival
CC in response to nutrient and hormonal signals. mTORC1 is activated in
CC response to growth factors or amino acids. Growth factor-stimulated
CC mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-
CC TSC2, which leads to the activation of the RHEB GTPase that potently
CC activates the protein kinase activity of mTORC1. Amino acid-signaling
CC to mTORC1 requires its relocalization to the lysosomes mediated by the
CC Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates
CC protein synthesis by phosphorylating key regulators of mRNA translation
CC and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it
CC from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1
CC phosphorylates and activates S6K1 at 'Thr-389', which then promotes
CC protein synthesis by phosphorylating PDCD4 and targeting it for
CC degradation. Within mTORC1, AKT1S1 negatively regulates mTOR activity
CC in a manner that is dependent on its phosphorylation state and binding
CC to 14-3-3. Inhibits RHEB-GTP-dependent mTORC1 activation. Substrate for
CC AKT1 phosphorylation, but can also be activated by AKT1-independent
CC mechanisms. May also play a role in nerve growth factor-mediated
CC neuroprotection. {ECO:0000269|PubMed:14973226,
CC ECO:0000269|PubMed:16397181}.
CC -!- SUBUNIT: Part of the mammalian target of rapamycin complex 1 (mTORC1)
CC which contains MTOR, MLST8, RPTOR, AKT1S1/PRAS40 and DEPTOR. mTORC1
CC binds to and is inhibited by FKBP12-rapamycin. Interacts directly with
CC RPTOR. The phosphorylated form interacts with 14-3-3 proteins and with
CC phosphorylated AKT1 following transient focal cerebral ischemia in
CC vivo. {ECO:0000269|PubMed:14973226}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:14973226}.
CC Note=Found in the cytosolic fraction of the brain. Colocalizes with
CC cortical neurons following ischemic/reperfusion injury.
CC -!- PTM: Phosphorylated by AKT1. Phosphorylation at Thr-247 by DYRK3
CC relieves inhibitory function on mTORC1. {ECO:0000250|UniProtKB:Q96B36}.
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DR EMBL; AK003638; BAB22905.1; -; mRNA.
DR EMBL; AK141771; BAE24829.1; -; mRNA.
DR EMBL; AK154110; BAE32383.1; -; mRNA.
DR EMBL; BC132372; AAI32373.1; -; mRNA.
DR EMBL; BC132374; AAI32375.1; -; mRNA.
DR CCDS; CCDS21218.1; -.
DR RefSeq; NP_001240849.1; NM_001253920.1.
DR RefSeq; NP_001277623.1; NM_001290694.1.
DR RefSeq; NP_001277624.1; NM_001290695.1.
DR RefSeq; NP_080546.1; NM_026270.4.
DR RefSeq; XP_006541182.1; XM_006541119.3.
DR RefSeq; XP_006541183.1; XM_006541120.3.
DR RefSeq; XP_006541184.1; XM_006541121.3.
DR RefSeq; XP_006541185.1; XM_006541122.2.
DR AlphaFoldDB; Q9D1F4; -.
DR BioGRID; 212306; 8.
DR IntAct; Q9D1F4; 1.
DR MINT; Q9D1F4; -.
DR STRING; 10090.ENSMUSP00000103512; -.
DR iPTMnet; Q9D1F4; -.
DR PhosphoSitePlus; Q9D1F4; -.
DR EPD; Q9D1F4; -.
DR jPOST; Q9D1F4; -.
DR MaxQB; Q9D1F4; -.
DR PaxDb; Q9D1F4; -.
DR PRIDE; Q9D1F4; -.
DR ProteomicsDB; 296391; -.
DR Antibodypedia; 32195; 586 antibodies from 39 providers.
DR DNASU; 67605; -.
DR Ensembl; ENSMUST00000054343; ENSMUSP00000049764; ENSMUSG00000011096.
DR Ensembl; ENSMUST00000107880; ENSMUSP00000103512; ENSMUSG00000011096.
DR GeneID; 67605; -.
DR KEGG; mmu:67605; -.
DR UCSC; uc009grd.2; mouse.
DR CTD; 84335; -.
DR MGI; MGI:1914855; Akt1s1.
DR VEuPathDB; HostDB:ENSMUSG00000011096; -.
DR eggNOG; ENOG502RY6G; Eukaryota.
DR GeneTree; ENSGT00390000017397; -.
DR HOGENOM; CLU_067112_0_0_1; -.
DR InParanoid; Q9D1F4; -.
DR OMA; AYCQKSG; -.
DR OrthoDB; 927670at2759; -.
DR PhylomeDB; Q9D1F4; -.
DR Reactome; R-MMU-165159; MTOR signalling.
DR Reactome; R-MMU-166208; mTORC1-mediated signalling.
DR Reactome; R-MMU-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-MMU-3371571; HSF1-dependent transactivation.
DR BioGRID-ORCS; 67605; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Akt1s1; mouse.
DR PRO; PR:Q9D1F4; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9D1F4; protein.
DR Bgee; ENSMUSG00000011096; Expressed in hindlimb stylopod muscle and 231 other tissues.
DR ExpressionAtlas; Q9D1F4; baseline and differential.
DR Genevisible; Q9D1F4; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0031931; C:TORC1 complex; ISO:MGI.
DR GO; GO:0045792; P:negative regulation of cell size; ISO:MGI.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISO:MGI.
DR GO; GO:0032007; P:negative regulation of TOR signaling; ISO:MGI.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; IEA:InterPro.
DR GO; GO:0007219; P:Notch signaling pathway; ISA:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; IDA:UniProtKB.
DR InterPro; IPR026682; AKT1S1.
DR PANTHER; PTHR21844; PTHR21844; 2.
DR Pfam; PF15798; PRAS; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Methylation; Phosphoprotein; Reference proteome.
FT CHAIN 1..257
FT /note="Proline-rich AKT1 substrate 1"
FT /id="PRO_0000253447"
FT REGION 64..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 197..217
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 75..97
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 51
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 184
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 203
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 204
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 213
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 247
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 257 AA; 27483 MW; 4BFFC8630DBBA5EC CRC64;
MASGRPEELW EAVVGAAERF QARTGTELVL LTAAPPPPPR PGPCAYAAHG RGALAEAARR
CLHDIAQAHR AATATRPPGP PPAPQPPSPA PSPPPRPALA REDEEEDEDE PTETETSGER
LGGSDNGGLF MMDEDATLQD LPPFCESDPE STDDGSLSEE TPAGPTACPQ PPATALPTQQ
YAKSLPVSVP VWAFKEKRTE ARSSDEENGP PSSPDLDRIA ASMRALVLRE AEDTQVFGDL
PRPRLNTSDF QKLKRKY
