AKTS1_HUMAN
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 03-AUG-2022, entry version 159.
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, 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 [10]
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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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).
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 proteins. Inhibits RHEB-GTP-dependent mTORC1 activation.
CC Substrate for AKT1 phosphorylation, but can also be activated by AKT1-
CC independent mechanisms. May also play a role in nerve growth factor-
CC mediated neuroprotection. {ECO:0000269|PubMed:16174443,
CC ECO:0000269|PubMed:17277771, ECO:0000269|PubMed:17386266}.
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.
CC {ECO:0000269|PubMed:12524439, ECO:0000269|PubMed:17277771,
CC ECO:0000269|PubMed:17386266}.
CC -!- INTERACTION:
CC Q96B36; Q04917: YWHAH; NbExp=4; IntAct=EBI-720593, EBI-306940;
CC Q96B36; P29311: BMH1; Xeno; NbExp=3; IntAct=EBI-720593, EBI-3661;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Note=Found in
CC the cytosolic fraction of the brain. {ECO:0000250}.
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 -!- PTM: Phosphorylated by AKT1 (PubMed:12524439). Phosphorylation at Thr-
CC 246 by DYRK3 relieves inhibitory function on mTORC1 (PubMed:23415227).
CC {ECO:0000269|PubMed:12524439, 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 SMR; Q96B36; -.
DR BioGRID; 124059; 30.
DR IntAct; Q96B36; 15.
DR MINT; Q96B36; -.
DR STRING; 9606.ENSP00000375711; -.
DR BindingDB; Q96B36; -.
DR ChEMBL; CHEMBL1255161; -.
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 EPD; Q96B36; -.
DR jPOST; Q96B36; -.
DR MassIVE; Q96B36; -.
DR MaxQB; Q96B36; -.
DR PaxDb; Q96B36; -.
DR PeptideAtlas; Q96B36; -.
DR PRIDE; Q96B36; -.
DR ProteomicsDB; 76040; -. [Q96B36-1]
DR ProteomicsDB; 76041; -. [Q96B36-2]
DR Antibodypedia; 32195; 586 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 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 OMA; AYCQKSG; -.
DR OrthoDB; 927670at2759; -.
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; 20 hits in 1087 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 153 other 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: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: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; PTHR21844; 2.
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 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"
FT /evidence="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"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
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 246
FT /note="T->A: Suppresses S6K1 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
