AKT1_MOUSE
ID AKT1_MOUSE Reviewed; 480 AA.
AC P31750; Q62274; Q6GSA6;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 229.
DE RecName: Full=RAC-alpha serine/threonine-protein kinase;
DE EC=2.7.11.1 {ECO:0000269|PubMed:22057101, ECO:0000269|PubMed:26440888};
DE AltName: Full=AKT1 kinase;
DE AltName: Full=Protein kinase B;
DE Short=PKB;
DE AltName: Full=Protein kinase B alpha;
DE Short=PKB alpha;
DE AltName: Full=Proto-oncogene c-Akt;
DE AltName: Full=RAC-PK-alpha;
DE AltName: Full=Thymoma viral proto-oncogene;
GN Name=Akt1; Synonyms=Akt, Rac;
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]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=AKR/J; TISSUE=Thymus;
RX PubMed=8437858;
RA Bellacosa A., Franke T.F., Gonzalez-Portal M.E., Datta K., Taguchi T.,
RA Gardner J., Cheng J.Q., Testa J.R., Tsichlis P.N.;
RT "Structure, expression and chromosomal mapping of c-akt: relationship to v-
RT akt and its implications.";
RL Oncogene 8:745-754(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, PHOSPHORYLATION AT SER-473,
RP DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RC STRAIN=129/SvJ;
RX PubMed=12783884; DOI=10.1074/jbc.m302847200;
RA Yang Z.Z., Tschopp O., Hemmings-Mieszczak M., Feng J., Brodbeck D.,
RA Perentes E., Hemmings B.A.;
RT "Protein kinase B alpha/Akt1 regulates placental development and fetal
RT growth.";
RL J. Biol. Chem. 278:32124-32131(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Bousquets X., Powell C.T.;
RT "Complete nucleotide coding sequence for murine rac (related to A and C
RT kinases) protein kinase.";
RL Submitted (JUN-1992) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=129/SvJ;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [8]
RP FUNCTION, AND MUTAGENESIS OF LYS-179.
RX PubMed=9415393; DOI=10.1210/mend.11.13.0027;
RA Cong L.N., Chen H., Li Y., Zhou L., McGibbon M.A., Taylor S.I., Quon M.J.;
RT "Physiological role of Akt in insulin-stimulated translocation of GLUT4 in
RT transfected rat adipose cells.";
RL Mol. Endocrinol. 11:1881-1890(1997).
RN [9]
RP FUNCTION IN PHOSPHORYLATION OF PDE3B.
RX PubMed=10454575; DOI=10.1128/mcb.19.9.6286;
RA Kitamura T., Kitamura Y., Kuroda S., Hino Y., Ando M., Kotani K.,
RA Konishi H., Matsuzaki H., Kikkawa U., Ogawa W., Kasuga M.;
RT "Insulin-induced phosphorylation and activation of cyclic nucleotide
RT phosphodiesterase 3B by the serine-threonine kinase Akt.";
RL Mol. Cell. Biol. 19:6286-6296(1999).
RN [10]
RP PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
RX PubMed=11090077;
RA Mizuki M., Fenski R., Halfter H., Matsumura I., Schmidt R., Muller C.,
RA Gruning W., Kratz-Albers K., Serve S., Steur C., Buchner T., Kienast J.,
RA Kanakura Y., Berdel W.E., Serve H.;
RT "Flt3 mutations from patients with acute myeloid leukemia induce
RT transformation of 32D cells mediated by the Ras and STAT5 pathways.";
RL Blood 96:3907-3914(2000).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=10716693; DOI=10.1073/pnas.97.7.3028;
RA Pekarsky Y., Koval A., Hallas C., Bichi R., Tresini M., Malstrom S.,
RA Russo G., Tsichlis P., Croce C.M.;
RT "Tcl1 enhances Akt kinase activity and mediates its nuclear
RT translocation.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:3028-3033(2000).
RN [12]
RP FUNCTION.
RX PubMed=11282895; DOI=10.1161/01.res.88.6.609;
RA Yamashita K., Kajstura J., Discher D.J., Wasserlauf B.J., Bishopric N.H.,
RA Anversa P., Webster K.A.;
RT "Reperfusion-activated Akt kinase prevents apoptosis in transgenic mouse
RT hearts overexpressing insulin-like growth factor-1.";
RL Circ. Res. 88:609-614(2001).
RN [13]
RP FUNCTION IN PHOSPHORYLATION OF PTPN1.
RX PubMed=11579209; DOI=10.1210/mend.15.10.0711;
RA Ravichandran L.V., Chen H., Li Y., Quon M.J.;
RT "Phosphorylation of PTP1B at Ser(50) by Akt impairs its ability to
RT dephosphorylate the insulin receptor.";
RL Mol. Endocrinol. 15:1768-1780(2001).
RN [14]
RP INTERACTION WITH THEM4.
RX PubMed=11598301; DOI=10.1126/science.1062030;
RA Maira S.-M., Galetic I., Brazil D.P., Kaech S., Ingley E., Thelen M.,
RA Hemmings B.A.;
RT "Carboxyl-terminal modulator protein (CTMP), a negative regulator of
RT PKB/Akt and v-Akt at the plasma membrane.";
RL Science 294:374-380(2001).
RN [15]
RP FUNCTION IN PHOSPHORYLATION OF TBC1D4.
RX PubMed=11994271; DOI=10.1074/jbc.c200198200;
RA Kane S., Sano H., Liu S.C.H., Asara J.M., Lane W.S., Garner C.C.,
RA Lienhard G.E.;
RT "A method to identify serine kinase substrates. Akt phosphorylates a novel
RT adipocyte protein with a Rab GTPase-activating protein (GAP) domain.";
RL J. Biol. Chem. 277:22115-22118(2002).
RN [16]
RP SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF ASP-434;
RP ASP-456 AND ASP-462.
RX PubMed=12124386; DOI=10.1074/jbc.m203805200;
RA Xu J., Liu D., Songyang Z.;
RT "The role of Asp-462 in regulating Akt activity.";
RL J. Biol. Chem. 277:35561-35566(2002).
RN [17]
RP INTERACTION WITH CCDC88A, AND PHOSPHORYLATION AT THR-308 AND SER-473.
RX PubMed=15753085; DOI=10.1074/jbc.m500586200;
RA Anai M., Shojima N., Katagiri H., Ogihara T., Sakoda H., Onishi Y., Ono H.,
RA Fujishiro M., Fukushima Y., Horike N., Viana A., Kikuchi M., Noguchi N.,
RA Takahashi S., Takata K., Oka Y., Uchijima Y., Kurihara H., Asano T.;
RT "A novel protein kinase B (PKB)/AKT-binding protein enhances PKB kinase
RT activity and regulates DNA synthesis.";
RL J. Biol. Chem. 280:18525-18535(2005).
RN [18]
RP INTERACTION WITH GRB10.
RX PubMed=15722337; DOI=10.1074/jbc.m501477200;
RA Urschel S., Bassermann F., Bai R.Y., Munch S., Peschel C., Duyster J.;
RT "Phosphorylation of grb10 regulates its interaction with 14-3-3.";
RL J. Biol. Chem. 280:16987-16993(2005).
RN [19]
RP INTERACTION WITH WDFY2.
RX PubMed=16792529; DOI=10.1042/bj20060511;
RA Fritzius T., Burkard G., Haas E., Heinrich J., Schweneker M., Bosse M.,
RA Zimmermann S., Frey A.D., Caelers A., Bachmann A.S., Moelling K.;
RT "A WD-FYVE protein binds to the kinases Akt and PKCzeta/lambda.";
RL Biochem. J. 399:9-20(2006).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, AND IDENTIFICATION BY
RP 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 [21]
RP INTERACTION WITH BTBD10.
RX PubMed=18160256; DOI=10.1016/j.cellsig.2007.11.004;
RA Nawa M., Kanekura K., Hashimoto Y., Aiso S., Matsuoka M.;
RT "A novel Akt/PKB-interacting protein promotes cell adhesion and inhibits
RT familial amyotrophic lateral sclerosis-linked mutant SOD1-induced neuronal
RT death via inhibition of PP2A-mediated dephosphorylation of Akt/PKB.";
RL Cell. Signal. 20:493-505(2008).
RN [22]
RP COMPLEX FORMATION WITH WDFY2 AND FOXO1, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=18388859; DOI=10.1038/emboj.2008.67;
RA Fritzius T., Moelling K.;
RT "Akt- and Foxo1-interacting WD-repeat-FYVE protein promotes adipogenesis.";
RL EMBO J. 27:1399-1410(2008).
RN [23]
RP GLYCOSYLATION AT SER-473.
RX PubMed=18570920; DOI=10.1016/j.yexcr.2008.04.014;
RA Kang E.S., Han D., Park J., Kwak T.K., Oh M.A., Lee S.A., Choi S.,
RA Park Z.Y., Kim Y., Lee J.W.;
RT "O-GlcNAc modulation at Akt1 Ser473 correlates with apoptosis of murine
RT pancreatic beta cells.";
RL Exp. Cell Res. 314:2238-2248(2008).
RN [24]
RP FUNCTION, GLYCOSYLATION AT SER-473, AND PHOSPHORYLATION AT THR-308.
RX PubMed=18288188; DOI=10.1038/nature06668;
RA Yang X., Ongusaha P.P., Miles P.D., Havstad J.C., Zhang F., So W.V.,
RA Kudlow J.E., Michell R.H., Olefsky J.M., Field S.J., Evans R.M.;
RT "Phosphoinositide signalling links O-GlcNAc transferase to insulin
RT resistance.";
RL Nature 451:964-969(2008).
RN [25]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PKHM3.
RX PubMed=19028694; DOI=10.1074/jbc.m807000200;
RA Virtanen C., Paris J., Takahashi M.;
RT "Identification and characterization of a novel gene, dapr, involved in
RT skeletal muscle differentiation and protein kinase B signaling.";
RL J. Biol. Chem. 284:1636-1643(2009).
RN [26]
RP FUNCTION.
RX PubMed=19778506; DOI=10.1016/j.neuron.2009.08.008;
RA Kim J.Y., Duan X., Liu C.Y., Jang M.H., Guo J.U., Pow-anpongkul N.,
RA Kang E., Song H., Ming G.L.;
RT "DISC1 regulates new neuron development in the adult brain via modulation
RT of AKT-mTOR signaling through KIAA1212.";
RL Neuron 63:761-773(2009).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, AND IDENTIFICATION BY
RP MASS 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 [28]
RP INTERACTION WITH CLK2.
RX PubMed=20074525; DOI=10.1016/j.cmet.2009.11.006;
RA Rodgers J.T., Haas W., Gygi S.P., Puigserver P.;
RT "Cdc2-like kinase 2 is an insulin-regulated suppressor of hepatic
RT gluconeogenesis.";
RL Cell Metab. 11:23-34(2010).
RN [29]
RP PHOSPHORYLATION AT THR-450.
RX PubMed=21045808; DOI=10.1038/emboj.2010.271;
RA Oh W.J., Wu C.C., Kim S.J., Facchinetti V., Julien L.A., Finlan M.,
RA Roux P.P., Su B., Jacinto E.;
RT "mTORC2 can associate with ribosomes to promote cotranslational
RT phosphorylation and stability of nascent Akt polypeptide.";
RL EMBO J. 29:3939-3951(2010).
RN [30]
RP INTERACTION WITH WDFY2, AND SUBCELLULAR LOCATION.
RX PubMed=20189988; DOI=10.1074/jbc.m110.110536;
RA Walz H.A., Shi X., Chouinard M., Bue C.A., Navaroli D.M., Hayakawa A.,
RA Zhou Q.L., Nadler J., Leonard D.M., Corvera S.;
RT "Isoform-specific regulation of Akt signaling by the endosomal protein
RT WDFY2.";
RL J. Biol. Chem. 285:14101-14108(2010).
RN [31]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-176; THR-308 AND SER-473,
RP MUTAGENESIS OF TYR-176, AND INTERACTION WITH TNK2.
RX PubMed=20333297; DOI=10.1371/journal.pone.0009646;
RA Mahajan K., Coppola D., Challa S., Fang B., Chen Y.A., Zhu W., Lopez A.S.,
RA Koomen J., Engelman R.W., Rivera C., Muraoka-Cook R.S., Cheng J.Q.,
RA Schoenbrunn E., Sebti S.M., Earp H.S., Mahajan N.P.;
RT "Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its
RT activation.";
RL PLoS ONE 5:E9646-E9646(2010).
RN [32]
RP PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
RX PubMed=21262971; DOI=10.1074/jbc.m110.205021;
RA Arora D., Stopp S., Bohmer S.A., Schons J., Godfrey R., Masson K.,
RA Razumovskaya E., Ronnstrand L., Tanzer S., Bauer R., Bohmer F.D.,
RA Muller J.P.;
RT "Protein-tyrosine phosphatase DEP-1 controls receptor tyrosine kinase FLT3
RT signaling.";
RL J. Biol. Chem. 286:10918-10929(2011).
RN [33]
RP FUNCTION, CATALYTIC ACTIVITY, UBIQUITINATION BY ZNRF1, AND MUTAGENESIS OF
RP THR-308 AND SER-473.
RX PubMed=22057101; DOI=10.1038/ncb2373;
RA Wakatsuki S., Saitoh F., Araki T.;
RT "ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B-
RT dependent CRMP2 phosphorylation.";
RL Nat. Cell Biol. 13:1415-1423(2011).
RN [34]
RP REVIEW ON FUNCTION.
RX PubMed=11882383; DOI=10.1016/s0898-6568(01)00271-6;
RA Nicholson K.M., Anderson N.G.;
RT "The protein kinase B/Akt signalling pathway in human malignancy.";
RL Cell. Signal. 14:381-395(2002).
RN [35]
RP REVIEW ON FUNCTION.
RX PubMed=21620960; DOI=10.1016/j.cellsig.2011.05.004;
RA Hers I., Vincent E.E., Tavare J.M.;
RT "Akt signalling in health and disease.";
RL Cell. Signal. 23:1515-1527(2011).
RN [36]
RP REVIEW ON FUNCTION.
RX PubMed=21432781; DOI=10.14670/hh-26.651;
RA Heron-Milhavet L., Khouya N., Fernandez A., Lamb N.J.;
RT "Akt1 and Akt2: differentiating the aktion.";
RL Histol. Histopathol. 26:651-662(2011).
RN [37]
RP INTERACTION WITH KCTD20.
RX PubMed=24156551; DOI=10.1186/1471-2091-14-27;
RA Nawa M., Matsuoka M.;
RT "KCTD20, a relative of BTBD10, is a positive regulator of Akt.";
RL BMC Biochem. 14:27-27(2013).
RN [38]
RP INTERACTION WITH SYAP1.
RX PubMed=23300339; DOI=10.1126/scisignal.2003295;
RA Yao Y., Suraokar M., Darnay B.G., Hollier B.G., Shaiken T.E., Asano T.,
RA Chen C.H., Chang B.H., Lu Y., Mills G.B., Sarbassov D., Mani S.A.,
RA Abbruzzese J.L., Reddy S.A.;
RT "BSTA promotes mTORC2-mediated phosphorylation of Akt1 to suppress
RT expression of FoxC2 and stimulate adipocyte differentiation.";
RL Sci. Signal. 6:RA2-RA2(2013).
RN [39]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-179.
RX PubMed=26440888; DOI=10.1016/j.celrep.2015.09.007;
RA Seo G.J., Yang A., Tan B., Kim S., Liang Q., Choi Y., Yuan W., Feng P.,
RA Park H.S., Jung J.U.;
RT "Akt kinase-mediated checkpoint of cGAS DNA sensing pathway.";
RL Cell Rep. 13:440-449(2015).
RN [40]
RP PHOSPHORYLATION AT THR-308 AND SER-473.
RX PubMed=26359501; DOI=10.1074/jbc.m115.678433;
RA Cattin M.E., Wang J., Weldrick J.J., Roeske C.L., Mak E., Thorn S.L.,
RA DaSilva J.N., Wang Y., Lusis A.J., Burgon P.G.;
RT "Deletion of MLIP (muscle-enriched A-type lamin-interacting protein) leads
RT to cardiac hyperactivation of Akt/mammalian target of rapamycin (mTOR) and
RT impaired cardiac adaptation.";
RL J. Biol. Chem. 290:26699-26714(2015).
RN [41]
RP FUNCTION.
RX PubMed=32228865; DOI=10.7554/elife.53430;
RA Oh S., Paknejad N., Hite R.K.;
RT "Gating and selectivity mechanisms for the lysosomal K+ channel TMEM175.";
RL Elife 9:0-0(2020).
CC -!- FUNCTION: AKT1 is one of 3 closely related serine/threonine-protein
CC kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate
CC many processes including metabolism, proliferation, cell survival,
CC growth and angiogenesis. This is mediated through serine and/or
CC threonine phosphorylation of a range of downstream substrates. Over 100
CC substrate candidates have been reported so far, but for most of them,
CC no isoform specificity has been reported (PubMed:11882383,
CC PubMed:21620960, PubMed:21432781). AKT is responsible of the regulation
CC of glucose uptake by mediating insulin-induced translocation of the
CC SLC2A4/GLUT4 glucose transporter to the cell surface (PubMed:9415393).
CC Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its
CC phosphatase activity preventing dephosphorylation of the insulin
CC receptor and the attenuation of insulin signaling (PubMed:11579209).
CC Phosphorylation of TBC1D4 triggers the binding of this effector to
CC inhibitory 14-3-3 proteins, which is required for insulin-stimulated
CC glucose transport (PubMed:11994271). AKT regulates also the storage of
CC glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21'
CC and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity
CC (PubMed:22057101). Phosphorylation of GSK3 isoforms by AKT is also
CC thought to be one mechanism by which cell proliferation is driven
CC (PubMed:22057101). AKT regulates also cell survival via the
CC phosphorylation of MAP3K5 (apoptosis signal-related kinase).
CC Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated
CC by oxidative stress and thereby prevents apoptosis. AKT mediates
CC insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-
CC 939' and 'Thr-1462', thereby activating the TORC1 signaling pathway,
CC and leading to both phosphorylation of 4E-BP1 and in activation of
CC RPS6KB1. Also regulates the TORC1 signaling pathway by catalyzing
CC phosphorylation of CASTOR1. AKT is involved in the phosphorylation of
CC members of the FOXO factors (Forkhead family of transcription factors),
CC leading to binding of 14-3-3 proteins and cytoplasmic localization. In
CC particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-
CC 319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has
CC an important role in the regulation of NF-kappa-B-dependent gene
CC transcription and positively regulates the activity of CREB1 (cyclic
CC AMP (cAMP)-response element binding protein). The phosphorylation of
CC CREB1 induces the binding of accessory proteins that are necessary for
CC the transcription of pro-survival genes such as BCL2 and MCL1 (By
CC similarity). AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY),
CC thereby potentially regulating ACLY activity and fatty acid synthesis
CC (By similarity). Activates the 3B isoform of cyclic nucleotide
CC phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting
CC in reduced cyclic AMP levels and inhibition of lipolysis
CC (PubMed:10454575). Phosphorylates PIKFYVE on 'Ser-318', which results
CC in increased PI(3)P-5 activity (By similarity). The Rho GTPase-
CC activating protein DLC1 is another substrate and its phosphorylation is
CC implicated in the regulation cell proliferation and cell growth (By
CC similarity). AKT plays a role as key modulator of the AKT-mTOR
CC signaling pathway controlling the tempo of the process of newborn
CC neurons integration during adult neurogenesis, including correct neuron
CC positioning, dendritic development and synapse formation
CC (PubMed:19778506). Signals downstream of phosphatidylinositol 3-kinase
CC (PI(3)K) to mediate the effects of various growth factors such as
CC platelet-derived growth factor (PDGF), epidermal growth factor (EGF),
CC insulin and insulin-like growth factor I (IGF-I) (PubMed:11282895,
CC PubMed:18288188). AKT mediates the antiapoptotic effects of IGF-I
CC (PubMed:11282895). Essential for the SPATA13-mediated regulation of
CC cell migration and adhesion assembly and disassembly (By similarity).
CC May be involved in the regulation of the placental development
CC (PubMed:12783884). Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387'
CC leading to inhibition of its: kinase activity, nuclear translocation,
CC autophosphorylation and ability to phosphorylate FOXO3. Phosphorylates
CC STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its:
CC cleavage, kinase activity, autophosphorylation at Thr-180, binding to
CC RASSF1 and nuclear translocation. Phosphorylates SRPK2 and enhances its
CC kinase activity towards SRSF2 and ACIN1 and promotes its nuclear
CC translocation. Phosphorylates RAF1 at 'Ser-259' and negatively
CC regulates its activity. Phosphorylation of BAD stimulates its pro-
CC apoptotic activity. Phosphorylates KAT6A at 'Thr-369' and this
CC phosphorylation inhibits the interaction of KAT6A with PML and
CC negatively regulates its acetylation activity towards p53/TP53.
CC Phosphorylates palladin (PALLD), modulating cytoskeletal organization
CC and cell motility. Phosphorylates prohibitin (PHB), playing an
CC important role in cell metabolism and proliferation. Phosphorylates
CC CDKN1A, for which phosphorylation at 'Thr-145' induces its release from
CC CDK2 and cytoplasmic relocalization. These recent findings indicate
CC that the AKT1 isoform has a more specific role in cell motility and
CC proliferation. Phosphorylates CLK2 thereby controlling cell survival to
CC ionizing radiation (By similarity). Phosphorylates PCK1 at 'Ser-90',
CC reducing the binding affinity of PCK1 to oxaloacetate and changing PCK1
CC into an atypical protein kinase activity using GTP as donor (By
CC similarity). Also acts as an activator of TMEM175 potassium channel
CC activity in response to growth factors: forms the lysoK(GF) complex
CC together with TMEM175 and acts by promoting TMEM175 channel activation,
CC independently of its protein kinase activity (PubMed:32228865). Acts as
CC a negative regulator of the cGAS-STING pathway by mediating
CC phosphorylation of CGAS during mitosis, leading to its inhibition
CC (PubMed:26440888). {ECO:0000250|UniProtKB:P31749,
CC ECO:0000250|UniProtKB:P47196, ECO:0000269|PubMed:10454575,
CC ECO:0000269|PubMed:11282895, ECO:0000269|PubMed:11579209,
CC ECO:0000269|PubMed:11994271, ECO:0000269|PubMed:12783884,
CC ECO:0000269|PubMed:18288188, ECO:0000269|PubMed:19778506,
CC ECO:0000269|PubMed:22057101, ECO:0000269|PubMed:26440888,
CC ECO:0000269|PubMed:32228865, ECO:0000269|PubMed:9415393,
CC ECO:0000303|PubMed:11882383, ECO:0000303|PubMed:21432781,
CC ECO:0000303|PubMed:21620960}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:22057101, ECO:0000269|PubMed:26440888};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:P47196};
CC -!- ACTIVITY REGULATION: Three specific sites, one in the kinase domain
CC (Thr-308) and the two other ones in the C-terminal regulatory region
CC (Ser-473 and Tyr-474), need to be phosphorylated for its full
CC activation. {ECO:0000250|UniProtKB:P31749}.
CC -!- SUBUNIT: Interacts with and phosphorylated by PDPK1 (By similarity).
CC Interacts with AGAP2 (isoform 2/PIKE-A); the interaction occurs in the
CC presence of guanine nucleotides. Interacts with AKTIP. Interacts (via
CC PH domain) with MTCP1, TCL1A AND TCL1B. Interacts with CDKN1B; the
CC interaction phosphorylates CDKN1B promoting 14-3-3 binding and cell-
CC cycle progression. Interacts with MAP3K5 and TRAF6. Interacts with BAD,
CC PPP2R5B, STK3 and STK4. Interacts (via PH domain) with SIRT1. Interacts
CC with SRPK2 in a phosphorylation-dependent manner. Interacts with
CC TRIM13; the interaction ubiquitinates AKT1 leading to its proteasomal
CC degradation. Interacts with RAF1 (By similarity). Interacts (via the C-
CC terminus) with CCDC88A (via its C-terminus) and THEM4 (via its C-
CC terminus). Interacts with GRB10; the interaction leads to GRB10
CC phosphorylation thus promoting YWHAE-binding. Interacts with KCTD20
CC (PubMed:24156551). Interacts with BTBD10 (PubMed:18160256). Interacts
CC with PA2G4 (By similarity). Interacts with KIF14; the interaction is
CC detected in the plasma membrane upon INS stimulation and promotes AKT1
CC phosphorylation (By similarity). Interacts with FAM83B; activates the
CC PI3K/AKT signaling cascade (By similarity). Interacts with WDFY2 (via
CC WD repeats 1-3) (PubMed:16792529, PubMed:20189988). Forms a complex
CC with WDFY2 and FOXO1 (PubMed:18388859). Interacts with FAM168A (By
CC similarity). Interacts with SYAP1 (via phosphorylated form and BSD
CC domain); this interaction is enhanced in a mTORC2-mediated manner in
CC response to epidermal growth factor (EGF) stimulation and activates
CC AKT1 (PubMed:23300339). Interacts with PKHM3 (PubMed:19028694).
CC Interacts with FKBP5/FKBP51; promoting interaction between Akt/AKT1 and
CC PHLPP1, thereby enhancing dephosphorylation and subsequent activation
CC of Akt/AKT1 (By similarity). Interacts with TMEM175; leading to
CC formation of the lysoK(GF) complex (By similarity).
CC {ECO:0000250|UniProtKB:P31749, ECO:0000250|UniProtKB:P47196,
CC ECO:0000269|PubMed:11598301, ECO:0000269|PubMed:15722337,
CC ECO:0000269|PubMed:15753085, ECO:0000269|PubMed:16792529,
CC ECO:0000269|PubMed:18160256, ECO:0000269|PubMed:18388859,
CC ECO:0000269|PubMed:19028694, ECO:0000269|PubMed:20074525,
CC ECO:0000269|PubMed:20189988, ECO:0000269|PubMed:20333297,
CC ECO:0000269|PubMed:23300339, ECO:0000269|PubMed:24156551}.
CC -!- INTERACTION:
CC P31750; Q9Z2V5: Hdac6; NbExp=2; IntAct=EBI-298707, EBI-1009256;
CC P31750; P07901: Hsp90aa1; NbExp=6; IntAct=EBI-298707, EBI-78930;
CC P31750; P05480: Src; NbExp=3; IntAct=EBI-298707, EBI-298680;
CC P31750; Q8K4K2: Trib3; NbExp=5; IntAct=EBI-298707, EBI-448962;
CC P31750; P62991: Ubc; NbExp=3; IntAct=EBI-298707, EBI-413074;
CC P31750; P32121: ARRB2; Xeno; NbExp=3; IntAct=EBI-298707, EBI-714559;
CC P31750; Q1W6H9: FAM110C; Xeno; NbExp=3; IntAct=EBI-298707, EBI-3942563;
CC P31750; Q8TCU6: PREX1; Xeno; NbExp=2; IntAct=EBI-298707, EBI-1046542;
CC P31750; P03165: X; Xeno; NbExp=2; IntAct=EBI-298707, EBI-7683985;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12124386,
CC ECO:0000269|PubMed:18388859, ECO:0000269|PubMed:19028694,
CC ECO:0000269|PubMed:20189988}. Nucleus {ECO:0000269|PubMed:18388859,
CC ECO:0000269|PubMed:20189988}. Cell membrane
CC {ECO:0000269|PubMed:19028694}. Note=Nucleus after activation by
CC integrin-linked protein kinase 1 (ILK1) (By similarity). Nuclear
CC translocation is enhanced by interaction with TCL1A. Phosphorylation on
CC Tyr-176 by TNK2 results in its localization to the cell membrane where
CC it is targeted for further phosphorylations on Thr-308 and Ser-473
CC leading to its activation and the activated form translocates to the
CC nucleus. Colocalizes with WDFY2 in intracellular vesicles.
CC {ECO:0000250|UniProtKB:P31749}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Low levels found in liver with
CC slightly higher levels present in thymus and testis.
CC {ECO:0000269|PubMed:8437858}.
CC -!- DEVELOPMENTAL STAGE: Expressed in trophoblast and vessel endothelial
CC cells of the placenta and in the brain at 14.5 dpc (at protein level).
CC {ECO:0000269|PubMed:12783884}.
CC -!- DOMAIN: Binding of the PH domain to phosphatidylinositol 3,4,5-
CC trisphosphate (PI(3,4,5)P3) following phosphatidylinositol 3-kinase
CC alpha (PIK3CA) activity results in its targeting to the plasma
CC membrane. The PH domain mediates interaction with TNK2 and Tyr-176 is
CC also essential for this interaction. {ECO:0000250|UniProtKB:P31749}.
CC -!- DOMAIN: The AGC-kinase C-terminal mediates interaction with THEM4.
CC {ECO:0000250|UniProtKB:P31749}.
CC -!- PTM: O-GlcNAcylation at Thr-305 and Thr-312 inhibits activating
CC phosphorylation at Thr-308 via disrupting the interaction between AKT1
CC and PDPK1 (By similarity). O-GlcNAcylation at Ser-473 also probably
CC interferes with phosphorylation at this site (PubMed:18570920,
CC PubMed:18288188). {ECO:0000250|UniProtKB:P31749,
CC ECO:0000269|PubMed:18288188, ECO:0000269|PubMed:18570920}.
CC -!- PTM: Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required for
CC full activity. Activated TNK2 phosphorylates it on Tyr-176 resulting in
CC its binding to the anionic plasma membrane phospholipid PA. This
CC phosphorylated form localizes to the plasma membrane, where it is
CC targeted by PDPK1 and PDPK2 for further phosphorylations on Thr-308 and
CC Ser-473 leading to its activation. Ser-473 phosphorylation by mTORC2
CC favors Thr-308 phosphorylation by PDPK1. Phosphorylated at Thr-308 and
CC Ser-473 by IKBKE and TBK1. Ser-473 phosphorylation is enhanced by
CC signaling through activated FLT3. Ser-473 is dephosphorylated by PHLPP
CC (By similarity). Dephosphorylated at Thr-308 and Ser-473 by PP2A
CC phosphatase. The phosphorylated form of PPP2R5B is required for
CC bridging AKT1 with PP2A phosphatase. Ser-473 is dephosphorylated by
CC CPPED1, leading to termination of signaling (By similarity).
CC {ECO:0000250|UniProtKB:P31749}.
CC -!- PTM: Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked
CC polyubiquitination. TRAF6-induced 'Lys-63'-linked AKT1 ubiquitination
CC is critical for phosphorylation and activation. When ubiquitinated, it
CC translocates to the plasma membrane, where it becomes phosphorylated.
CC When fully phosphorylated and translocated into the nucleus, undergoes
CC 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its
CC degradation by the proteasome. Also ubiquitinated by TRIM13 leading to
CC its proteasomal degradation. Ubiquitinated via 'Lys-48'-linked
CC polyubiquitination by ZNRF1, leading to its degradation by the
CC proteasome. Phosphorylated, undergoes 'Lys-48'-linked
CC polyubiquitination preferentially at Lys-284 catalyzed by MUL1, leading
CC to its proteasomal degradation. {ECO:0000269|PubMed:11090077,
CC ECO:0000269|PubMed:12783884, ECO:0000269|PubMed:15753085,
CC ECO:0000269|PubMed:18288188, ECO:0000269|PubMed:20333297,
CC ECO:0000269|PubMed:21045808, ECO:0000269|PubMed:21262971,
CC ECO:0000269|PubMed:22057101}.
CC -!- PTM: Acetylated on Lys-14 and Lys-20 by the histone acetyltransferases
CC EP300 and KAT2B. Acetylation results in reduced phosphorylation and
CC inhibition of activity. Deacetylated at Lys-14 and Lys-20 by SIRT1.
CC SIRT1-mediated deacetylation relieves the inhibition (By similarity).
CC {ECO:0000250|UniProtKB:P31749}.
CC -!- PTM: Cleavage by caspase-3/CASP3 (PubMed:12124386). Cleaved at the
CC caspase-3 consensus site Asp-462 during apoptosis, resulting in down-
CC regulation of the AKT signaling pathway and decreased cell survival
CC (PubMed:12124386). {ECO:0000269|PubMed:12124386}.
CC -!- DISRUPTION PHENOTYPE: Show fetal growth impairment and reduced
CC vascularization in the placenta; majority of pups died within 10 days.
CC {ECO:0000269|PubMed:12783884}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. RAC subfamily. {ECO:0000305}.
CC -!- CAUTION: In light of strong homologies in the primary amino acid
CC sequence, the 3 AKT kinases were long surmised to play redundant and
CC overlapping roles. More recent studies has brought into question the
CC redundancy within AKT kinase isoforms and instead pointed to isoform
CC specific functions in different cellular events and diseases. AKT1 is
CC more specifically involved in cellular survival pathways, by inhibiting
CC apoptotic processes; whereas AKT2 is more specific for the insulin
CC receptor signaling pathway. Moreover, while AKT1 and AKT2 are often
CC implicated in many aspects of cellular transformation, the 2 isoforms
CC act in a complementary opposing manner. The role of AKT3 is less clear,
CC though it appears to be predominantly expressed in brain.
CC {ECO:0000305}.
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DR EMBL; X65687; CAA46620.1; -; mRNA.
DR EMBL; AF534134; AAN04036.1; -; Genomic_DNA.
DR EMBL; M94335; AAA18254.1; -; mRNA.
DR EMBL; AK154936; BAE32937.1; -; mRNA.
DR EMBL; CH466549; EDL18586.1; -; Genomic_DNA.
DR EMBL; BC066018; AAH66018.1; -; mRNA.
DR CCDS; CCDS26194.1; -.
DR PIR; S33364; S33364.
DR RefSeq; NP_001159366.1; NM_001165894.1.
DR RefSeq; NP_001318036.1; NM_001331107.1.
DR RefSeq; NP_033782.1; NM_009652.3.
DR RefSeq; XP_006515478.1; XM_006515415.1.
DR AlphaFoldDB; P31750; -.
DR SMR; P31750; -.
DR BioGRID; 198056; 67.
DR CORUM; P31750; -.
DR DIP; DIP-736N; -.
DR ELM; P31750; -.
DR IntAct; P31750; 27.
DR MINT; P31750; -.
DR STRING; 10090.ENSMUSP00000001780; -.
DR BindingDB; P31750; -.
DR ChEMBL; CHEMBL5859; -.
DR GlyGen; P31750; 5 sites.
DR iPTMnet; P31750; -.
DR PhosphoSitePlus; P31750; -.
DR SwissPalm; P31750; -.
DR EPD; P31750; -.
DR jPOST; P31750; -.
DR MaxQB; P31750; -.
DR PaxDb; P31750; -.
DR PeptideAtlas; P31750; -.
DR PRIDE; P31750; -.
DR ProteomicsDB; 282066; -.
DR ABCD; P31750; 2 sequenced antibodies.
DR Antibodypedia; 135; 5359 antibodies from 56 providers.
DR DNASU; 11651; -.
DR Ensembl; ENSMUST00000001780; ENSMUSP00000001780; ENSMUSG00000001729.
DR GeneID; 11651; -.
DR KEGG; mmu:11651; -.
DR UCSC; uc007pex.2; mouse.
DR CTD; 207; -.
DR MGI; MGI:87986; Akt1.
DR VEuPathDB; HostDB:ENSMUSG00000001729; -.
DR eggNOG; KOG0690; Eukaryota.
DR GeneTree; ENSGT00940000158752; -.
DR HOGENOM; CLU_000288_11_0_1; -.
DR InParanoid; P31750; -.
DR OMA; CIDNERR; -.
DR OrthoDB; 614710at2759; -.
DR PhylomeDB; P31750; -.
DR TreeFam; TF102004; -.
DR BRENDA; 2.7.11.1; 3474.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-1358803; Downregulation of ERBB2:ERBB3 signaling.
DR Reactome; R-MMU-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR Reactome; R-MMU-165159; MTOR signalling.
DR Reactome; R-MMU-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-MMU-198693; AKT phosphorylates targets in the nucleus.
DR Reactome; R-MMU-199418; Negative regulation of the PI3K/AKT network.
DR Reactome; R-MMU-203615; eNOS activation.
DR Reactome; R-MMU-211163; AKT-mediated inactivation of FOXO1A.
DR Reactome; R-MMU-354192; Integrin signaling.
DR Reactome; R-MMU-3769402; Deactivation of the beta-catenin transactivating complex.
DR Reactome; R-MMU-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-MMU-389513; CTLA4 inhibitory signaling.
DR Reactome; R-MMU-392451; G beta:gamma signalling through PI3Kgamma.
DR Reactome; R-MMU-450385; Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
DR Reactome; R-MMU-450604; KSRP (KHSRP) binds and destabilizes mRNA.
DR Reactome; R-MMU-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-MMU-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-MMU-6804757; Regulation of TP53 Degradation.
DR Reactome; R-MMU-6804758; Regulation of TP53 Activity through Acetylation.
DR Reactome; R-MMU-6804759; Regulation of TP53 Activity through Association with Co-factors.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-MMU-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR Reactome; R-MMU-8849469; PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1.
DR Reactome; R-MMU-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR Reactome; R-MMU-8948751; Regulation of PTEN stability and activity.
DR Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-MMU-9604323; Negative regulation of NOTCH4 signaling.
DR Reactome; R-MMU-9607240; FLT3 Signaling.
DR Reactome; R-MMU-9614399; Regulation of localization of FOXO transcription factors.
DR Reactome; R-MMU-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR Reactome; R-MMU-9755511; KEAP1-NFE2L2 pathway.
DR BioGRID-ORCS; 11651; 7 hits in 77 CRISPR screens.
DR ChiTaRS; Akt1; mouse.
DR PRO; PR:P31750; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P31750; protein.
DR Bgee; ENSMUSG00000001729; Expressed in ectoplacental cone and 268 other tissues.
DR ExpressionAtlas; P31750; baseline and differential.
DR Genevisible; P31750; MM.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0036064; C:ciliary basal body; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0005819; C:spindle; IDA:MGI.
DR GO; GO:0031982; C:vesicle; ISO:MGI.
DR GO; GO:0071889; F:14-3-3 protein binding; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0032794; F:GTPase activating protein binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0016301; F:kinase activity; ISO:MGI.
DR GO; GO:0030235; F:nitric-oxide synthase regulator activity; ISO:MGI.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; ISO:MGI.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; ISO:MGI.
DR GO; GO:0099104; F:potassium channel activator activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0005080; F:protein kinase C binding; ISO:MGI.
DR GO; GO:0051721; F:protein phosphatase 2A binding; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; ISO:MGI.
DR GO; GO:0006924; P:activation-induced cell death of T cells; ISO:MGI.
DR GO; GO:0007568; P:aging; ISO:MGI.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; IDA:MGI.
DR GO; GO:0048266; P:behavioral response to pain; IGI:MGI.
DR GO; GO:0008643; P:carbohydrate transport; IEA:UniProtKB-KW.
DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; ISO:MGI.
DR GO; GO:0030030; P:cell projection organization; ISO:MGI.
DR GO; GO:0071276; P:cellular response to cadmium ion; ISO:MGI.
DR GO; GO:0036294; P:cellular response to decreased oxygen levels; IDA:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:MGI.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; IDA:MGI.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IDA:MGI.
DR GO; GO:0071456; P:cellular response to hypoxia; ISO:MGI.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:MGI.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; ISO:MGI.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:MGI.
DR GO; GO:0140052; P:cellular response to oxidised low-density lipoprotein particle stimulus; ISO:MGI.
DR GO; GO:1901653; P:cellular response to peptide; IDA:MGI.
DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; IDA:MGI.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISO:MGI.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:MGI.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IDA:MGI.
DR GO; GO:0007010; P:cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISO:MGI.
DR GO; GO:0072655; P:establishment of protein localization to mitochondrion; ISO:MGI.
DR GO; GO:0097194; P:execution phase of apoptosis; IDA:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0007281; P:germ cell development; IDA:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
DR GO; GO:0006006; P:glucose metabolic process; IMP:MGI.
DR GO; GO:0005978; P:glycogen biosynthetic process; ISO:MGI.
DR GO; GO:0060709; P:glycogen cell differentiation involved in embryonic placenta development; IMP:MGI.
DR GO; GO:0005977; P:glycogen metabolic process; IMP:MGI.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; IDA:MGI.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0035655; P:interleukin-18-mediated signaling pathway; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IMP:MGI.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:MGI.
DR GO; GO:0072656; P:maintenance of protein location in mitochondrion; ISO:MGI.
DR GO; GO:0001893; P:maternal placenta development; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0010507; P:negative regulation of autophagy; ISO:MGI.
DR GO; GO:0110099; P:negative regulation of calcium import into the mitochondrion; ISO:MGI.
DR GO; GO:0045792; P:negative regulation of cell size; ISO:MGI.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; ISO:MGI.
DR GO; GO:0031999; P:negative regulation of fatty acid beta-oxidation; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0046329; P:negative regulation of JNK cascade; ISO:MGI.
DR GO; GO:1903038; P:negative regulation of leukocyte cell-cell adhesion; ISO:MGI.
DR GO; GO:0010748; P:negative regulation of long-chain fatty acid import across plasma membrane; ISO:MGI.
DR GO; GO:2000402; P:negative regulation of lymphocyte migration; ISO:MGI.
DR GO; GO:0032091; P:negative regulation of protein binding; ISO:MGI.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISO:MGI.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0045861; P:negative regulation of proteolysis; ISO:MGI.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IDA:UniProtKB.
DR GO; GO:0032929; P:negative regulation of superoxide anion generation; ISO:MGI.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IGI:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:MGI.
DR GO; GO:0032287; P:peripheral nervous system myelin maintenance; IMP:MGI.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; ISO:MGI.
DR GO; GO:0016310; P:phosphorylation; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:MGI.
DR GO; GO:0030307; P:positive regulation of cell growth; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0032079; P:positive regulation of endodeoxyribonuclease activity; ISO:MGI.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:MGI.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISO:MGI.
DR GO; GO:0010763; P:positive regulation of fibroblast migration; IMP:MGI.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0046326; P:positive regulation of glucose import; ISO:MGI.
DR GO; GO:0010907; P:positive regulation of glucose metabolic process; ISO:MGI.
DR GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; ISO:MGI.
DR GO; GO:1903721; P:positive regulation of I-kappaB phosphorylation; ISO:MGI.
DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; ISO:MGI.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:MGI.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; ISO:MGI.
DR GO; GO:0046622; P:positive regulation of organ growth; IMP:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:MGI.
DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; IMP:UniProtKB.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:MGI.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; ISO:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:MGI.
DR GO; GO:0030163; P:protein catabolic process; IDA:MGI.
DR GO; GO:0006606; P:protein import into nucleus; ISO:MGI.
DR GO; GO:0043491; P:protein kinase B signaling; IGI:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:MGI.
DR GO; GO:1903715; P:regulation of aerobic respiration; ISO:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0005979; P:regulation of glycogen biosynthetic process; ISO:MGI.
DR GO; GO:0031641; P:regulation of myelination; IMP:MGI.
DR GO; GO:0010975; P:regulation of neuron projection development; IDA:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IDA:MGI.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR GO; GO:0034405; P:response to fluid shear stress; ISO:MGI.
DR GO; GO:0032094; P:response to food; IDA:MGI.
DR GO; GO:0070848; P:response to growth factor; ISO:MGI.
DR GO; GO:0060416; P:response to growth hormone; ISS:AgBase.
DR GO; GO:0009408; P:response to heat; IGI:MGI.
DR GO; GO:0009725; P:response to hormone; IDA:UniProtKB.
DR GO; GO:1990418; P:response to insulin-like growth factor stimulus; ISS:AgBase.
DR GO; GO:0010033; P:response to organic substance; IDA:MGI.
DR GO; GO:0006979; P:response to oxidative stress; ISS:ParkinsonsUK-UCL.
DR GO; GO:0070141; P:response to UV-A; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
DR GO; GO:0003376; P:sphingosine-1-phosphate receptor signaling pathway; ISO:MGI.
DR GO; GO:0021510; P:spinal cord development; ISO:MGI.
DR GO; GO:0051146; P:striated muscle cell differentiation; IGI:MGI.
DR GO; GO:0006412; P:translation; ISO:MGI.
DR CDD; cd01241; PH_PKB; 1.
DR CDD; cd05594; STKc_PKB_alpha; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR034676; Akt1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR039026; PH_PKB.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR039027; RAC_alpha.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24351:SF200; PTHR24351:SF200; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Acetylation; Apoptosis; ATP-binding; Carbohydrate metabolism;
KW Cell membrane; Cytoplasm; Developmental protein; Disulfide bond;
KW Glucose metabolism; Glycogen biosynthesis; Glycogen metabolism;
KW Glycoprotein; Isopeptide bond; Kinase; Membrane; Neurogenesis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Sugar transport; Transferase;
KW Translation regulation; Transport; Ubl conjugation.
FT CHAIN 1..480
FT /note="RAC-alpha serine/threonine-protein kinase"
FT /id="PRO_0000085606"
FT DOMAIN 5..108
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 150..408
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 409..480
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 114..137
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 450..480
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 274
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 14..19
FT /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate"
FT /ligand_id="ChEBI:CHEBI:57895"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT BINDING 23..25
FT /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate"
FT /ligand_id="ChEBI:CHEBI:57895"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT BINDING 53
FT /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate"
FT /ligand_id="ChEBI:CHEBI:57895"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT BINDING 86
FT /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate"
FT /ligand_id="ChEBI:CHEBI:57895"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT BINDING 156..164
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 179
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT SITE 462
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000269|PubMed:12124386"
FT MOD_RES 14
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT MOD_RES 20
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT MOD_RES 124
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT MOD_RES 126
FT /note="Phosphoserine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT MOD_RES 129
FT /note="Phosphoserine; alternate"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 176
FT /note="Phosphotyrosine; by TNK2"
FT /evidence="ECO:0000269|PubMed:20333297"
FT MOD_RES 308
FT /note="Phosphothreonine; by IKKE, PDPK1 and TBK1"
FT /evidence="ECO:0000269|PubMed:15753085,
FT ECO:0000269|PubMed:18288188, ECO:0000269|PubMed:20333297,
FT ECO:0000269|PubMed:26359501"
FT MOD_RES 448
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT MOD_RES 450
FT /note="Phosphothreonine; by MTOR"
FT /evidence="ECO:0000269|PubMed:21045808"
FT MOD_RES 473
FT /note="Phosphoserine; by IKKE, MTOR and TBK1; alternate"
FT /evidence="ECO:0000269|PubMed:26359501,
FT ECO:0000305|PubMed:12783884, ECO:0000305|PubMed:15753085,
FT ECO:0000305|PubMed:20333297"
FT MOD_RES 474
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT CARBOHYD 126
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT CARBOHYD 129
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT CARBOHYD 305
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT CARBOHYD 312
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT CARBOHYD 473
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000269|PubMed:18570920"
FT DISULFID 60..77
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT DISULFID 296..310
FT /evidence="ECO:0000250|UniProtKB:P31751"
FT CROSSLNK 284
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P31749"
FT MUTAGEN 176
FT /note="Y->F: Significant loss of interaction with TNK2.
FT Loss of membrane localization. Significant reduction in
FT phosphorylation on Ser-473."
FT /evidence="ECO:0000269|PubMed:20333297"
FT MUTAGEN 179
FT /note="K->A: In kinase dead mutant; lacks kinase activity.
FT Overexpression inhibits insulin-stimulated translocation of
FT SLC2A4/GLUT4 in a dominant negative manner."
FT /evidence="ECO:0000269|PubMed:26440888,
FT ECO:0000269|PubMed:9415393"
FT MUTAGEN 308
FT /note="T->A: Does not affect ubiquitination by ZNRF1."
FT /evidence="ECO:0000269|PubMed:22057101"
FT MUTAGEN 434
FT /note="D->N: Does not affect caspase-3 cleavage."
FT /evidence="ECO:0000269|PubMed:12124386"
FT MUTAGEN 456
FT /note="D->N: Does not affect caspase-3 cleavage."
FT /evidence="ECO:0000269|PubMed:12124386"
FT MUTAGEN 462
FT /note="D->N: Abolishes caspase-3 cleavage and increases
FT cell survival. Does not affect kinase activity."
FT /evidence="ECO:0000269|PubMed:12124386"
FT MUTAGEN 473
FT /note="S->A: Does not affect ubiquitination by ZNRF1."
FT /evidence="ECO:0000269|PubMed:22057101"
FT CONFLICT 367
FT /note="R -> A (in Ref. 3; AAA18254)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 480 AA; 55707 MW; 98DF28E5EFE03730 CRC64;
MNDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVDQRES PLNNFSVAQC
QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWA TAIQTVADGL KRQEEETMDF
RSGSPSDNSG AEEMEVSLAK PKHRVTMNEF EYLKLLGKGT FGKVILVKEK ATGRYYAMKI
LKKEVIVAKD EVAHTLTENR VLQNSRHPFL TALKYSFQTH DRLCFVMEYA NGGELFFHLS
RERVFSEDRA RFYGAEIVSA LDYLHSEKNV VYRDLKLENL MLDKDGHIKI TDFGLCKEGI
KDGATMKTFC GTPEYLAPEV LEDNDYGRAV DWWGLGVVMY EMMCGRLPFY NQDHEKLFEL
ILMEEIRFPR TLGPEAKSLL SGLLKKDPTQ RLGGGSEDAK EIMQHRFFAN IVWQDVYEKK
LSPPFKPQVT SETDTRYFDE EFTAQMITIT PPDQDDSMEC VDSERRPHFP QFSYSASGTA
