ID AKTS1_HUMAN Reviewed; 256 AA.
AC Q96B36; A8MTQ1; B2RE93; J3KPM3; Q96BI4; Q96IK7; Q96NG2; Q9BWR5;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 27-MAR-2024, entry version 168.
DE RecName: Full=Proline-rich AKT1 substrate 1;
DE AltName: Full=40 kDa proline-rich AKT substrate;
GN Name=AKT1S1 {ECO:0000312|EMBL:AAH16043.1};
GN Synonyms=PRAS40 {ECO:0000303|PubMed:12524439, ECO:0000303|PubMed:16174443};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000305, ECO:0000312|EMBL:BAB70937.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Prostate, and Synovium;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Coronary artery;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAH16043.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP PRO-47.
RC TISSUE=Brain {ECO:0000312|EMBL:AAH00031.2},
RC Eye {ECO:0000312|EMBL:AAH16043.1}, and Skin {ECO:0000312|EMBL:AAH51844.1};
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 [6] {ECO:0000305}
RP INTERACTION WITH 14-3-3, TISSUE SPECIFICITY, AND PHOSPHORYLATION AT
RP THR-246.
RX PubMed=12524439; DOI=10.1074/jbc.m210837200;
RA Kovacina K.S., Park G.Y., Bae S.S., Guzzetta A.W., Schaefer E.,
RA Birnbaum M.J., Roth R.A.;
RT "Identification of a proline-rich Akt substrate as a 14-3-3 binding
RT partner.";
RL J. Biol. Chem. 278:10189-10194(2003).
RN [7] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16174443; DOI=10.1111/j.1745-7254.2005.00184.x;
RA Huang B., Porter G.;
RT "Expression of proline-rich Akt-substrate PRAS40 in cell survival pathway
RT and carcinogenesis.";
RL Acta Pharmacol. Sin. 26:1253-1258(2005).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [9]
RP FUNCTION, INTERACTION WITH RPTOR, TOS MOTIF, AND MUTAGENESIS OF PHE-129.
RX PubMed=17510057; DOI=10.1074/jbc.m702376200;
RA Wang L., Harris T.E., Roth R.A., Lawrence J.C. Jr.;
RT "PRAS40 regulates mTORC1 kinase activity by functioning as a direct
RT inhibitor of substrate binding.";
RL J. Biol. Chem. 282:20036-20044(2007).
RN [10]
RP INTERACTION WITH RPTOR, PHOSPHORYLATION AT SER-183, AND MUTAGENESIS OF
RP PHE-129 AND SER-183.
RX PubMed=17517883; DOI=10.1074/jbc.m702636200;
RA Oshiro N., Takahashi R., Yoshino K., Tanimura K., Nakashima A., Eguchi S.,
RA Miyamoto T., Hara K., Takehana K., Avruch J., Kikkawa U., Yonezawa K.;
RT "The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological
RT substrate of mammalian target of rapamycin complex 1.";
RL J. Biol. Chem. 282:20329-20339(2007).
RN [11]
RP FUNCTION, IDENTIFICATION IN THE TORC1 COMPLEX, AND INTERACTION WITH RPTOR.
RX PubMed=17386266; DOI=10.1016/j.molcel.2007.03.003;
RA Sancak Y., Thoreen C.C., Peterson T.R., Lindquist R.A., Kang S.A.,
RA Spooner E., Carr S.A., Sabatini D.M.;
RT "PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase.";
RL Mol. Cell 25:903-915(2007).
RN [12]
RP FUNCTION, IDENTIFICATION IN THE TORC1 COMPLEX, AND MUTAGENESIS OF THR-246.
RX PubMed=17277771; DOI=10.1038/ncb1547;
RA Vander Haar E., Lee S.-I., Bandhakavi S., Griffin T.J., Kim D.-H.;
RT "Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40.";
RL Nat. Cell Biol. 9:316-323(2007).
RN [13]
RP FUNCTION, PHOSPHORYLATION AT SER-183; SER-212 AND SER-221, AND MUTAGENESIS
RP OF PHE-129; SER-183; SER-212 AND SER-221.
RX PubMed=18372248; DOI=10.1074/jbc.m800723200;
RA Wang L., Harris T.E., Lawrence J.C. Jr.;
RT "Regulation of proline-rich Akt substrate of 40 kDa (PRAS40) function by
RT mammalian target of rapamycin complex 1 (mTORC1)-mediated
RT phosphorylation.";
RL J. Biol. Chem. 283:15619-15627(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-92; SER-183; SER-202;
RP SER-203; SER-211; SER-212 AND THR-246, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-92; SER-183; SER-202;
RP SER-212 AND THR-246, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183; SER-202; SER-203;
RP SER-211; SER-212 AND THR-246, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-92; SER-183 AND
RP THR-246, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP PHOSPHORYLATION AT THR-246, AND MUTAGENESIS OF THR-246.
RX PubMed=23415227; DOI=10.1016/j.cell.2013.01.033;
RA Wippich F., Bodenmiller B., Trajkovska M.G., Wanka S., Aebersold R.,
RA Pelkmans L.;
RT "Dual specificity kinase DYRK3 couples stress granule
RT condensation/dissolution to mTORC1 signaling.";
RL Cell 152:791-805(2013).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183; SER-203 AND SER-212, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-88; SER-92; SER-202 AND
RP SER-203, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [23]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-51, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
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).
RN [24]
RP PHOSPHORYLATION AT THR-246.
RX PubMed=29634919; DOI=10.1016/j.jmb.2018.04.001;
RA Kim K., Cha J.S., Cho Y.S., Kim H., Chang N., Kim H.J., Cho H.S.;
RT "Crystal structure of human dual-specificity tyrosine-regulated kinase 3
RT reveals new structural features and insights into its auto-
RT phosphorylation.";
RL J. Mol. Biol. 430:1521-1530(2018).
RN [25] {ECO:0007744|PDB:5WBL, ECO:0007744|PDB:5WBU, ECO:0007744|PDB:5WBY}
RP X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 114-207 IN COMPLEX WITH MTOR AND
RP MLST8, FUNCTION, IDENTIFICATION IN THE MTORC1 COMPLEX, AND MUTAGENESIS OF
RP 215-LEU--LEU-225.
RX PubMed=29236692; DOI=10.1038/nature25023;
RA Yang H., Jiang X., Li B., Yang H.J., Miller M., Yang A., Dhar A.,
RA Pavletich N.P.;
RT "Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40.";
RL Nature 552:368-373(2017).
RN [26] {ECO:0007744|PDB:6SB0}
RP STRUCTURE BY ELECTRON MICROSCOPY (5.50 ANGSTROMS) IN COMPLEX WITH RRAGA;
RP RRAGC; RPTOR; MLST8 AND MTOR, AND IDENTIFICATION IN THE MTORC1 COMPLEX.
RX PubMed=31601764; DOI=10.1126/science.aax3939;
RA Anandapadamanaban M., Masson G.R., Perisic O., Berndt A., Kaufman J.,
RA Johnson C.M., Santhanam B., Rogala K.B., Sabatini D.M., Williams R.L.;
RT "Architecture of human Rag GTPase heterodimers and their complex with
RT mTORC1.";
RL Science 366:203-210(2019).
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 (PubMed:17510057,
CC PubMed:17386266, PubMed:17277771, PubMed:29236692). In absence of
CC insulin and nutrients, AKT1S1 associates with the mTORC1 complex and
CC directly inhibits mTORC1 activity by blocking the MTOR substrate-
CC recruitment site (PubMed:29236692). In response to insulin and
CC nutrients, AKT1S1 dissociates from mTORC1 (PubMed:17386266,
CC PubMed:18372248). Its activity is dependent on its phosphorylation
CC state and binding to 14-3-3 (PubMed:16174443, PubMed:18372248). May
CC also play a role in nerve growth factor-mediated neuroprotection (By
CC similarity). {ECO:0000250|UniProtKB:Q9D1F4,
CC ECO:0000269|PubMed:16174443, ECO:0000269|PubMed:17277771,
CC ECO:0000269|PubMed:17386266, ECO:0000269|PubMed:17510057,
CC ECO:0000269|PubMed:18372248, ECO:0000269|PubMed:29236692}.
CC -!- SUBUNIT: Associated component of the mechanistic target of rapamycin
CC complex 1 (mTORC1), which contains core MTOR, MLST8 and RPTOR
CC (PubMed:17510057, PubMed:17386266, PubMed:17277771, PubMed:29236692,
CC PubMed:31601764). Dissociates from mTORC1 in response to insulin
CC treatment (PubMed:17386266, PubMed:18372248). mTORC1 binds to and is
CC inhibited by FKBP12-rapamycin (PubMed:31601764, PubMed:17277771).
CC Interacts (via TOS motif) with RPTOR; interaction is direct
CC (PubMed:17510057, PubMed:17517883, PubMed:17386266). The phosphorylated
CC form interacts with 14-3-3 proteins (PubMed:12524439, PubMed:18372248).
CC {ECO:0000269|PubMed:12524439, ECO:0000269|PubMed:17277771,
CC ECO:0000269|PubMed:17386266, ECO:0000269|PubMed:17510057,
CC ECO:0000269|PubMed:17517883, ECO:0000269|PubMed:18372248,
CC ECO:0000269|PubMed:29236692, ECO:0000269|PubMed:31601764}.
CC -!- INTERACTION:
CC Q96B36; P31946: YWHAB; NbExp=3; IntAct=EBI-720593, EBI-359815;
CC Q96B36; Q04917: YWHAH; NbExp=5; IntAct=EBI-720593, EBI-306940;
CC Q96B36; P29311: BMH1; Xeno; NbExp=3; IntAct=EBI-720593, EBI-3661;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9D1F4}. Note=Found in the cytosolic fraction of
CC the brain. {ECO:0000250|UniProtKB:Q9D1F4}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1 {ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334};
CC IsoId=Q96B36-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:15489334};
CC IsoId=Q96B36-2; Sequence=VSP_052182;
CC Name=3;
CC IsoId=Q96B36-3; Sequence=VSP_047536;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels of expression
CC in liver and heart. Expressed at higher levels in cancer cell lines
CC (e.g. A-549 and HeLa) than in normal cell lines (e.g. HEK293).
CC {ECO:0000269|PubMed:12524439, ECO:0000269|PubMed:16174443}.
CC -!- DOMAIN: The TOS motif mediates interaction with RPTOR, leading to
CC promote phosphorylation by mTORC1 complex.
CC {ECO:0000269|PubMed:17510057, ECO:0000269|PubMed:17517883}.
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 (PubMed:12524439,
CC PubMed:17386266). Phosphorylated by MTOR following mTORC1 activation,
CC inhibiting AKT1S1 inhibitor activity: phosphorylation by MTOR probably
CC serves as a feedback loop that relieves inhibition from AKT1S1 in
CC response to mTORC1 inactivation (PubMed:17517883). Phosphorylation at
CC Thr-246 by DYRK3 relieves inhibitory function on mTORC1
CC (PubMed:23415227). {ECO:0000269|PubMed:12524439,
CC ECO:0000269|PubMed:17386266, ECO:0000269|PubMed:17517883,
CC ECO:0000269|PubMed:23415227}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH00031.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK055511; BAB70937.1; -; mRNA.
DR EMBL; AK092610; BAG52583.1; -; mRNA.
DR EMBL; AK316603; BAG38190.1; -; mRNA.
DR EMBL; AK226004; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC118341; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471177; EAW52570.1; -; Genomic_DNA.
DR EMBL; CH471177; EAW52568.1; -; Genomic_DNA.
DR EMBL; BC000031; AAH00031.2; ALT_INIT; mRNA.
DR EMBL; BC007416; AAH07416.1; -; mRNA.
DR EMBL; BC015562; AAH15562.1; -; mRNA.
DR EMBL; BC016043; AAH16043.1; -; mRNA.
DR EMBL; BC051844; AAH51844.1; -; mRNA.
DR CCDS; CCDS12784.1; -. [Q96B36-1]
DR CCDS; CCDS59410.1; -. [Q96B36-3]
DR RefSeq; NP_001092102.1; NM_001098632.2. [Q96B36-1]
DR RefSeq; NP_001092103.1; NM_001098633.3. [Q96B36-1]
DR RefSeq; NP_001265088.1; NM_001278159.1. [Q96B36-1]
DR RefSeq; NP_001265089.1; NM_001278160.1. [Q96B36-1]
DR RefSeq; NP_115751.3; NM_032375.5. [Q96B36-3]
DR PDB; 5WBL; X-ray; 3.35 A; T=124-139.
DR PDB; 5WBU; X-ray; 3.42 A; O/P/Q/R=173-256.
DR PDB; 5WBY; X-ray; 3.10 A; O/P=114-207.
DR PDB; 6SB0; EM; 5.50 A; O/T=1-256.
DR PDBsum; 5WBL; -.
DR PDBsum; 5WBU; -.
DR PDBsum; 5WBY; -.
DR PDBsum; 6SB0; -.
DR AlphaFoldDB; Q96B36; -.
DR EMDB; EMD-10132; -.
DR SMR; Q96B36; -.
DR BioGRID; 124059; 36.
DR IntAct; Q96B36; 16.
DR MINT; Q96B36; -.
DR STRING; 9606.ENSP00000375711; -.
DR BindingDB; Q96B36; -.
DR ChEMBL; CHEMBL1255161; -.
DR GlyGen; Q96B36; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q96B36; -.
DR PhosphoSitePlus; Q96B36; -.
DR BioMuta; AKT1S1; -.
DR DMDM; 74731194; -.
DR CPTAC; CPTAC-1038; -.
DR CPTAC; CPTAC-785; -.
DR CPTAC; CPTAC-787; -.
DR CPTAC; non-CPTAC-5333; -.
DR CPTAC; non-CPTAC-5698; -.
DR EPD; Q96B36; -.
DR jPOST; Q96B36; -.
DR MassIVE; Q96B36; -.
DR MaxQB; Q96B36; -.
DR PaxDb; 9606-ENSP00000375711; -.
DR PeptideAtlas; Q96B36; -.
DR ProteomicsDB; 76040; -. [Q96B36-1]
DR ProteomicsDB; 76041; -. [Q96B36-2]
DR Pumba; Q96B36; -.
DR Antibodypedia; 32195; 662 antibodies from 39 providers.
DR DNASU; 84335; -.
DR Ensembl; ENST00000344175.10; ENSP00000341698.5; ENSG00000204673.11. [Q96B36-1]
DR Ensembl; ENST00000391831.5; ENSP00000375707.1; ENSG00000204673.11. [Q96B36-1]
DR Ensembl; ENST00000391832.7; ENSP00000375708.3; ENSG00000204673.11. [Q96B36-1]
DR Ensembl; ENST00000391833.5; ENSP00000375709.1; ENSG00000204673.11. [Q96B36-1]
DR Ensembl; ENST00000391834.6; ENSP00000375710.2; ENSG00000204673.11. [Q96B36-1]
DR Ensembl; ENST00000391835.1; ENSP00000375711.1; ENSG00000204673.11. [Q96B36-3]
DR GeneID; 84335; -.
DR KEGG; hsa:84335; -.
DR MANE-Select; ENST00000344175.10; ENSP00000341698.5; NM_001098633.4; NP_001092103.1.
DR UCSC; uc002pql.6; human. [Q96B36-1]
DR AGR; HGNC:28426; -.
DR CTD; 84335; -.
DR DisGeNET; 84335; -.
DR GeneCards; AKT1S1; -.
DR HGNC; HGNC:28426; AKT1S1.
DR HPA; ENSG00000204673; Low tissue specificity.
DR MIM; 610221; gene.
DR neXtProt; NX_Q96B36; -.
DR OpenTargets; ENSG00000204673; -.
DR PharmGKB; PA134943587; -.
DR VEuPathDB; HostDB:ENSG00000204673; -.
DR eggNOG; ENOG502RY6G; Eukaryota.
DR GeneTree; ENSGT00390000017397; -.
DR HOGENOM; CLU_067112_0_0_1; -.
DR InParanoid; Q96B36; -.
DR OrthoDB; 4215423at2759; -.
DR PhylomeDB; Q96B36; -.
DR PathwayCommons; Q96B36; -.
DR Reactome; R-HSA-165159; MTOR signalling.
DR Reactome; R-HSA-166208; mTORC1-mediated signalling.
DR Reactome; R-HSA-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-HSA-3371571; HSF1-dependent transactivation.
DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer.
DR SABIO-RK; Q96B36; -.
DR SignaLink; Q96B36; -.
DR SIGNOR; Q96B36; -.
DR BioGRID-ORCS; 84335; 23 hits in 1163 CRISPR screens.
DR ChiTaRS; AKT1S1; human.
DR GeneWiki; AKT1S1; -.
DR GenomeRNAi; 84335; -.
DR Pharos; Q96B36; Tchem.
DR PRO; PR:Q96B36; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q96B36; Protein.
DR Bgee; ENSG00000204673; Expressed in gastrocnemius and 155 other cell types or tissues.
DR ExpressionAtlas; Q96B36; baseline and differential.
DR Genevisible; Q96B36; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0031931; C:TORC1 complex; IDA:UniProtKB.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0045792; P:negative regulation of cell size; IDA:UniProtKB.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:0032007; P:negative regulation of TOR signaling; IDA:UniProtKB.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IDA:UniProtKB.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; IEA:InterPro.
DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; ISS: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.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Methylation; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..256
FT /note="Proline-rich AKT1 substrate 1"
FT /id="PRO_0000253446"
FT REGION 69..189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 197..216
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 237..256
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 129..133
FT /note="TOS motif"
FT /evidence="ECO:0000269|PubMed:17510057"
FT COMPBIAS 75..96
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:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 116
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D1F4"
FT MOD_RES 183
FT /note="Phosphoserine; by MTOR"
FT /evidence="ECO:0000269|PubMed:17517883,
FT ECO:0000269|PubMed:18372248, ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 202
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 203
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 211
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 212
FT /note="Phosphoserine; by MTOR"
FT /evidence="ECO:0000269|PubMed:18372248,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 221
FT /note="Phosphoserine; by MTOR"
FT /evidence="ECO:0000269|PubMed:18372248"
FT MOD_RES 246
FT /note="Phosphothreonine; by PKB/AKT1 and DYRK3"
FT /evidence="ECO:0000269|PubMed:12524439,
FT ECO:0000269|PubMed:23415227, ECO:0000269|PubMed:29634919,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT VAR_SEQ 1..130
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_052182"
FT VAR_SEQ 1
FT /note="M -> MSFEGGDGAGPAMLATGTARM (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_047536"
FT VARIANT 47
FT /note="A -> P (in dbSNP:rs17850191)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_028239"
FT MUTAGEN 129
FT /note="F->A: Abolished association with the MTORC1 complex.
FT Does not affect phosphorylatiuon by MTOR."
FT /evidence="ECO:0000269|PubMed:17510057,
FT ECO:0000269|PubMed:17517883, ECO:0000269|PubMed:18372248"
FT MUTAGEN 183
FT /note="S->A: Reduced phosphorylation by MTOR."
FT /evidence="ECO:0000269|PubMed:17517883,
FT ECO:0000269|PubMed:18372248"
FT MUTAGEN 183
FT /note="S->D: Mimics phosphorylation; reduced interaction
FT with RPTOR."
FT /evidence="ECO:0000269|PubMed:17517883"
FT MUTAGEN 212
FT /note="S->A: Does not affect phosphorylation by MTOR."
FT /evidence="ECO:0000269|PubMed:18372248"
FT MUTAGEN 215..225
FT /note="LDRIAASMRAL->ADRAAGSARAA: Abolished ability to
FT inhibit the kinase activity of MTOR."
FT /evidence="ECO:0000269|PubMed:29236692"
FT MUTAGEN 221
FT /note="S->A: Decreased interaction with 14-3-3; increased
FT inhibitory activity toward mTORC1."
FT /evidence="ECO:0000269|PubMed:18372248"
FT MUTAGEN 246
FT /note="T->A: Suppresses RPS6KB1 phosphorylation by mTORC1."
FT /evidence="ECO:0000269|PubMed:17277771,
FT ECO:0000269|PubMed:23415227"
FT CONFLICT 108
FT /note="D -> G (in Ref. 1; BAB70937)"
FT /evidence="ECO:0000305"
FT CONFLICT 196
FT /note="K -> M (in Ref. 1; BAB70937)"
FT /evidence="ECO:0000305"
FT CONFLICT 233
FT /note="T -> A (in Ref. 1; BAB70937)"
FT /evidence="ECO:0000305"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:5WBY"
FT HELIX 213..231
FT /evidence="ECO:0007829|PDB:5WBU"
SQ SEQUENCE 256 AA; 27383 MW; F6CB195CBB54326C CRC64;
MASGRPEELW EAVVGAAERF RARTGTELVL LTAAPPPPPR PGPCAYAAHG RGALAEAARR
CLHDIALAHR AATAARPPAP PPAPQPPSPT PSPPRPTLAR EDNEEDEDEP TETETSGEQL
GISDNGGLFV MDEDATLQDL PPFCESDPES TDDGSLSEET PAGPPTCSVP PASALPTQQY
AKSLPVSVPV WGFKEKRTEA RSSDEENGPP SSPDLDRIAA SMRALVLREA EDTQVFGDLP
RPRLNTSDFQ KLKRKY
//
