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 24-JAN-2024, entry version 141. 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 NOD RC {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, 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, RC Pancreas, 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: Negative regulator of the mechanistic target of rapamycin CC complex 1 (mTORC1), an evolutionarily conserved central nutrient sensor CC that stimulates anabolic reactions and macromolecule biosynthesis to CC promote cellular biomass generation and growth (By similarity). In CC absence of insulin and nutrients, AKT1S1 associates with the mTORC1 CC complex and directly inhibits mTORC1 activity by blocking the MTOR CC substrate-recruitment site (By similarity). In response to insulin and CC nutrients, AKT1S1 dissociates from mTORC1 (By similarity). Its activity CC is dependent on its phosphorylation state and binding to 14-3-3 (By CC similarity). May also play a role in nerve growth factor-mediated CC neuroprotection (PubMed:14973226, PubMed:16397181). CC {ECO:0000250|UniProtKB:Q96B36, ECO:0000269|PubMed:14973226, CC ECO:0000269|PubMed:16397181}. CC -!- SUBUNIT: Associated component of the mechanistic target of rapamycin CC complex 1 (mTORC1), which contains core MTOR, MLST8 and RPTOR (By CC similarity). Dissociates from mTORC1 in response to insulin treatment CC (By similarity). mTORC1 binds to and is inhibited by FKBP12-rapamycin CC (By similarity). Interacts (via TOS motif) with RPTOR; interaction is CC direct (By similarity). The phosphorylated form interacts with 14-3-3 CC proteins (By similarity). {ECO:0000250|UniProtKB:Q96B36}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:14973226}. CC Note=Found in the cytosolic fraction of the brain (PubMed:14973226). CC Colocalizes with cortical neurons following ischemic/reperfusion injury CC (PubMed:14973226). {ECO:0000269|PubMed:14973226}. CC -!- DOMAIN: The TOS motif mediates interaction with RPTOR, leading to CC promote phosphorylation by mTORC1 complex. CC {ECO:0000250|UniProtKB:Q96B36}. CC -!- PTM: Phosphorylated by AKT1; phosphorylation takes place in response to CC insulin treatment and promotes AKT1S1 interaction with 14-3-3 proteins, CC leading to relieve its inhibitor activity (By similarity). CC Phosphorylated by MTOR following mTORC1 activation, inhibiting AKT1S1 CC inhibitor activity: phosphorylation by MTOR probably serves as a CC feedback loop that relieves inhibition from AKT1S1 in response to CC mTORC1 inactivation (By similarity). Phosphorylation at Thr-247 by CC DYRK3 relieves inhibitory function on mTORC1 (By similarity). CC {ECO:0000250|UniProtKB:Q96B36}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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.ENSMUSP00000103514; -. DR GlyGen; Q9D1F4; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9D1F4; -. DR PhosphoSitePlus; Q9D1F4; -. DR EPD; Q9D1F4; -. DR jPOST; Q9D1F4; -. DR MaxQB; Q9D1F4; -. DR PaxDb; 10090-ENSMUSP00000103512; -. DR ProteomicsDB; 296391; -. DR Pumba; Q9D1F4; -. DR Antibodypedia; 32195; 662 antibodies from 39 providers. DR DNASU; 67605; -. DR Ensembl; ENSMUST00000054343.15; ENSMUSP00000049764.9; ENSMUSG00000011096.18. DR Ensembl; ENSMUST00000107880.9; ENSMUSP00000103512.2; ENSMUSG00000011096.18. DR GeneID; 67605; -. DR KEGG; mmu:67605; -. DR UCSC; uc009grd.2; mouse. DR AGR; MGI:1914855; -. 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; VPVWGCK; -. DR OrthoDB; 4215423at2759; -. 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 76 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 235 other cell types or tissues. DR ExpressionAtlas; Q9D1F4; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0031931; C:TORC1 complex; ISO:MGI. DR GO; GO:0004860; F:protein kinase inhibitor activity; ISO:MGI. DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; ISS:UniProtKB. DR GO; GO:0045792; P:negative regulation of cell size; ISO:MGI. DR GO; GO:0032007; P:negative regulation of TOR signaling; ISO:MGI. DR GO; GO:1904262; P:negative regulation of TORC1 signaling; ISS:UniProtKB. 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; AKT1 SUBSTRATE 1 PROTEIN; 1. DR PANTHER; PTHR21844:SF2; PROLINE-RICH AKT1 SUBSTRATE 1; 1. DR Pfam; PF15798; PRAS; 1. DR Genevisible; Q9D1F4; MM. 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 MOTIF 130..134 FT /note="TOS motif" FT /evidence="ECO:0000250|UniProtKB:Q96B36" 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 222 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q96B36" 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 //