AKT1_HUMAN
ID AKT1_HUMAN Reviewed; 480 AA.
AC P31749; B2RAM5; B7Z5R1; Q9BWB6;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 255.
DE RecName: Full=RAC-alpha serine/threonine-protein kinase;
DE EC=2.7.11.1 {ECO:0000269|PubMed:32322062, ECO:0000269|PubMed:33594058};
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;
GN Name=AKT1; Synonyms=PKB, RAC;
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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CATALYTIC ACTIVITY.
RX PubMed=1851997; DOI=10.1073/pnas.88.10.4171;
RA Jones P.F., Jakubowicz T., Pitossi F.J., Maurer F., Hemmings B.A.;
RT "Molecular cloning and identification of a serine/threonine protein kinase
RT of the second-messenger subfamily.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:4171-4175(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11508278; DOI=10.1007/s001250100577;
RA Matsubara A., Wasson J.C., Donelan S.S., Welling C.M., Glaser B.,
RA Permutt M.A.;
RT "Isolation and characterization of the human AKT1 gene, identification of
RT 13 single nucleotide polymorphisms (SNPs), and their lack of association
RT with Type II diabetes.";
RL Diabetologia 44:910-913(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Adrenal gland;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle, and Ovary;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 63-480 (ISOFORM 1), FUNCTION, CATALYTIC
RP ACTIVITY, AND TISSUE SPECIFICITY.
RC TISSUE=Foreskin;
RX PubMed=1718748; DOI=10.1111/j.1432-1033.1991.tb16305.x;
RA Coffer P.J., Woodgett J.R.;
RT "Molecular cloning and characterisation of a novel putative protein-serine
RT kinase related to the cAMP-dependent and protein kinase C families.";
RL Eur. J. Biochem. 201:475-481(1991).
RN [8]
RP ERRATUM OF PUBMED:1718748, AND SEQUENCE REVISION.
RX PubMed=1533586;
RA Coffer P.J., Woodgett J.R.;
RL Eur. J. Biochem. 205:1217-1218(1992).
RN [9]
RP FUNCTION IN PHOSPHORYLATION OF CREB1.
RX PubMed=9829964; DOI=10.1074/jbc.273.49.32377;
RA Du K., Montminy M.;
RT "CREB is a regulatory target for the protein kinase Akt/PKB.";
RL J. Biol. Chem. 273:32377-32379(1998).
RN [10]
RP ACTIVITY REGULATION, AND PHOSPHORYLATION AT SER-473.
RX PubMed=9736715; DOI=10.1073/pnas.95.19.11211;
RA Delcommenne M., Tan C., Gray V., Rue L., Woodgett J.R., Dedhar S.;
RT "Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase
RT kinase 3 and protein kinase B/AKT by the integrin-linked kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:11211-11216(1998).
RN [11]
RP MUTAGENESIS OF THR-308 AND SER-473, AND PHOSPHORYLATION AT THR-308 AND
RP SER-473.
RX PubMed=8978681; DOI=10.1002/j.1460-2075.1996.tb01045.x;
RA Alessi D.R., Andjelkovic M., Caudwell F.B., Cron P., Morrice N., Cohen P.,
RA Hemmings B.A.;
RT "Mechanism of activation of protein kinase B by insulin and IGF-1.";
RL EMBO J. 15:6541-6551(1996).
RN [12]
RP FUNCTION, ACTIVITY REGULATION, AND PHOSPHORYLATION AT THR-308 BY PDPK1.
RX PubMed=9512493; DOI=10.1042/bj3310299;
RA Walker K.S., Deak M., Paterson A., Hudson K., Cohen P., Alessi D.R.;
RT "Activation of protein kinase B beta and gamma isoforms by insulin in vivo
RT and by 3-phosphoinositide-dependent protein kinase-1 in vitro: comparison
RT with protein kinase B alpha.";
RL Biochem. J. 331:299-308(1998).
RN [13]
RP FUNCTION IN PHOSPHORYLATION OF FOXO1.
RX PubMed=10358075; DOI=10.1074/jbc.274.24.17179;
RA Rena G., Guo S., Cichy S.C., Unterman T.G., Cohen P.;
RT "Phosphorylation of the transcription factor forkhead family member FKHR by
RT protein kinase B.";
RL J. Biol. Chem. 274:17179-17183(1999).
RN [14]
RP FUNCTION IN PHOSPHORYLATION OF RAF1, AND INTERACTION WITH RAF1.
RX PubMed=10576742; DOI=10.1126/science.286.5445.1741;
RA Zimmermann S., Moelling K.;
RT "Phosphorylation and regulation of Raf by Akt (protein kinase B).";
RL Science 286:1741-1744(1999).
RN [15]
RP FUNCTION IN PHOSPHORYLATION OF BAD, AND INTERACTION WITH BAD AND PKN2.
RX PubMed=10926925; DOI=10.1074/jbc.m001753200;
RA Koh H., Lee K.H., Kim D., Kim S., Kim J.W., Chung J.;
RT "Inhibition of Akt and its anti-apoptotic activities by tumor necrosis
RT factor-induced protein kinase C-related kinase 2 (PRK2) cleavage.";
RL J. Biol. Chem. 275:34451-34458(2000).
RN [16]
RP INTERACTION WITH MTCP1; TCL1A AND TCL1B.
RX PubMed=10983986; DOI=10.1016/s1097-2765(00)00039-3;
RA Laine J., Kuenstle G., Obata T., Sha M., Noguchi M.;
RT "The protooncogene TCL1 is an Akt kinase coactivator.";
RL Mol. Cell 6:395-407(2000).
RN [17]
RP INTERACTION WITH TCL1A.
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 [18]
RP FUNCTION IN PHOSPHORYLATION OF MAP3K5, AND INTERACTION WITH MAP3K5.
RX PubMed=11154276; DOI=10.1128/mcb.21.3.893-901.2001;
RA Kim A.H., Khursigara G., Sun X., Franke T.F., Chao M.V.;
RT "Akt phosphorylates and negatively regulates apoptosis signal-regulating
RT kinase 1.";
RL Mol. Cell. Biol. 21:893-901(2001).
RN [19]
RP INTERACTION WITH THEM4, AND SUBCELLULAR LOCATION.
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 [20]
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 [21]
RP INTERACTION WITH CDKN1B, AND FUNCTION.
RX PubMed=12042314; DOI=10.1074/jbc.m203668200;
RA Fujita N., Sato S., Katayama K., Tsuruo T.;
RT "Akt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3 and
RT cytoplasmic localization.";
RL J. Biol. Chem. 277:28706-28713(2002).
RN [22]
RP PHOSPHORYLATION AT TYR-474, AND MUTAGENESIS OF TYR-474.
RX PubMed=12149249; DOI=10.1074/jbc.m203387200;
RA Conus N.M., Hannan K.M., Cristiano B.E., Hemmings B.A., Pearson R.B.;
RT "Direct identification of tyrosine 474 as a regulatory phosphorylation site
RT for the Akt protein kinase.";
RL J. Biol. Chem. 277:38021-38028(2002).
RN [23]
RP FUNCTION IN PHOSPHORYLATION OF TSC2.
RX PubMed=12150915; DOI=10.1016/s1097-2765(02)00568-3;
RA Manning B.D., Tee A.R., Logsdon M.N., Blenis J., Cantley L.C.;
RT "Identification of the tuberous sclerosis complex-2 tumor suppressor gene
RT product tuberin as a target of the phosphoinositide 3-kinase/akt pathway.";
RL Mol. Cell 10:151-162(2002).
RN [24]
RP INTERACTION WITH TCL1A.
RX PubMed=11839817; DOI=10.1128/mcb.22.5.1513-1525.2002;
RA Kuenstle G., Laine J., Pierron G., Kagami S., Nakajima H., Hoh F.,
RA Roumestand C., Stern M.H., Noguchi M.;
RT "Identification of Akt association and oligomerization domains of the Akt
RT kinase coactivator TCL1.";
RL Mol. Cell. Biol. 22:1513-1525(2002).
RN [25]
RP INTERACTION WITH CDKN1B, FUNCTION, AND MUTAGENESIS OF THR-308 AND SER-473.
RX PubMed=12244301; DOI=10.1038/nm759;
RA Shin I., Yakes F.M., Rojo F., Shin N.-Y., Bakin A.V., Baselga J.,
RA Arteaga C.L.;
RT "PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at
RT threonine 157 and modulation of its cellular localization.";
RL Nat. Med. 8:1145-1152(2002).
RN [26]
RP FUNCTION IN PARTICIPATION IN KIT SIGNALING.
RX PubMed=12878163; DOI=10.1016/s0014-4827(03)00206-4;
RA Lennartsson J., Wernstedt C., Engstrom U., Hellman U., Ronnstrand L.;
RT "Identification of Tyr900 in the kinase domain of c-Kit as a Src-dependent
RT phosphorylation site mediating interaction with c-Crk.";
RL Exp. Cell Res. 288:110-118(2003).
RN [27]
RP INTERACTION WITH AGAP2, AND PHOSPHORYLATION AT SER-473.
RX PubMed=14761976; DOI=10.1074/jbc.m312175200;
RA Ahn J.-Y., Rong R., Kroll T.G., Van Meir E.G., Snyder S.H., Ye K.;
RT "PIKE (phosphatidylinositol 3-kinase enhancer)-A GTPase stimulates Akt
RT activity and mediates cellular invasion.";
RL J. Biol. Chem. 279:16441-16451(2004).
RN [28]
RP PHOSPHORYLATION AT SER-473.
RX PubMed=15047712; DOI=10.1074/jbc.m314192200;
RA Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.;
RT "LGI1, a putative tumor metastasis suppressor gene, controls in vitro
RT invasiveness and expression of matrix metalloproteinases in glioma cells
RT through the ERK1/2 pathway.";
RL J. Biol. Chem. 279:23151-23157(2004).
RN [29]
RP ERRATUM OF PUBMED:15047712.
RA Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.;
RL J. Biol. Chem. 282:2752-2752(2007).
RN [30]
RP INTERACTION WITH AKTIP.
RX PubMed=14749367; DOI=10.1128/mcb.24.4.1493-1504.2004;
RA Remy I., Michnick S.W.;
RT "Regulation of apoptosis by the Ft1 protein, a new modulator of protein
RT kinase B/Akt.";
RL Mol. Cell. Biol. 24:1493-1504(2004).
RN [31]
RP INTERACTION WITH AGAP2.
RX PubMed=15118108; DOI=10.1073/pnas.0400921101;
RA Ahn J.-Y., Hu Y., Kroll T.G., Allard P., Ye K.;
RT "PIKE-A is amplified in human cancers and prevents apoptosis by up-
RT regulating Akt.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:6993-6998(2004).
RN [32]
RP PHOSPHORYLATION AT SER-473 IN RESPONSE TO FLT3 SIGNALING.
RX PubMed=16266983; DOI=10.1158/0008-5472.can-05-0422;
RA Brandts C.H., Sargin B., Rode M., Biermann C., Lindtner B., Schwable J.,
RA Buerger H., Muller-Tidow C., Choudhary C., McMahon M., Berdel W.E.,
RA Serve H.;
RT "Constitutive activation of Akt by Flt3 internal tandem duplications is
RT necessary for increased survival, proliferation, and myeloid
RT transformation.";
RL Cancer Res. 65:9643-9650(2005).
RN [33]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH CCDC88A.
RX PubMed=16139227; DOI=10.1016/j.devcel.2005.08.001;
RA Enomoto A., Murakami H., Asai N., Morone N., Watanabe T., Kawai K.,
RA Murakumo Y., Usukura J., Kaibuchi K., Takahashi M.;
RT "Akt/PKB regulates actin organization and cell motility via Girdin/APE.";
RL Dev. Cell 9:389-402(2005).
RN [34]
RP PHOSPHORYLATION AT THR-308, AND PHOSPHORYLATION AT SER-473 BY MTOR.
RX PubMed=15718470; DOI=10.1126/science.1106148;
RA Sarbassov D.D., Guertin D.A., Ali S.M., Sabatini D.M.;
RT "Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex.";
RL Science 307:1098-1101(2005).
RN [35]
RP PHOSPHORYLATION AT SER-473.
RX PubMed=17013611; DOI=10.1007/s00401-006-0128-y;
RA Schick V., Majores M., Engels G., Spitoni S., Koch A., Elger C.E.,
RA Simon M., Knobbe C., Bluemcke I., Becker A.J.;
RT "Activation of Akt independent of PTEN and CTMP tumor-suppressor gene
RT mutations in epilepsy-associated Taylor-type focal cortical dysplasias.";
RL Acta Neuropathol. 112:715-725(2006).
RN [36]
RP INTERACTION WITH WDFY2, AND SUBCELLULAR LOCATION.
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 [37]
RP FUNCTION, AND INTERACTION WITH RARA.
RX PubMed=16417524; DOI=10.1042/bj20051794;
RA Srinivas H., Xia D., Moore N.L., Uray I.P., Kim H., Ma L., Weigel N.L.,
RA Brown P.H., Kurie J.M.;
RT "Akt phosphorylates and suppresses the transactivation of retinoic acid
RT receptor alpha.";
RL Biochem. J. 395:653-662(2006).
RN [38]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, 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 [39]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16540465; DOI=10.1074/jbc.m601384200;
RA Zhang X., Zhang S., Yamane H., Wahl R., Ali A., Lofgren J.A., Kendall R.L.;
RT "Kinetic mechanism of AKT/PKB enzyme family.";
RL J. Biol. Chem. 281:13949-13956(2006).
RN [40]
RP FUNCTION IN PHOSPHORYLATION OF CDKN1A.
RX PubMed=16982699; DOI=10.1128/mcb.00201-06;
RA Heron-Milhavet L., Franckhauser C., Rana V., Berthenet C., Fisher D.,
RA Hemmings B.A., Fernandez A., Lamb N.J.;
RT "Only Akt1 is required for proliferation, while Akt2 promotes cell cycle
RT exit through p21 binding.";
RL Mol. Cell. Biol. 26:8267-8280(2006).
RN [41]
RP INTERACTION WITH STK4/MST1, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17932490; DOI=10.1038/sj.emboj.7601872;
RA Cinar B., Fang P.K., Lutchman M., Di Vizio D., Adam R.M., Pavlova N.,
RA Rubin M.A., Yelick P.C., Freeman M.R.;
RT "The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct
RT inhibitors of Akt1.";
RL EMBO J. 26:4523-4534(2007).
RN [42]
RP FUNCTION, AND INTERACTION WITH STK4/MST1.
RX PubMed=17726016; DOI=10.1074/jbc.m704542200;
RA Jang S.W., Yang S.J., Srinivasan S., Ye K.;
RT "Akt phosphorylates MstI and prevents its proteolytic activation, blocking
RT FOXO3 phosphorylation and nuclear translocation.";
RL J. Biol. Chem. 282:30836-30844(2007).
RN [43]
RP FUNCTION IN PHOSPHORYLATION OF PROHIBITIN.
RX PubMed=18507042;
RA Han E.K., Mcgonigal T., Butler C., Giranda V.L., Luo Y.;
RT "Characterization of Akt overexpression in MiaPaCa-2 cells: prohibitin is
RT an Akt substrate both in vitro and in cells.";
RL Anticancer Res. 28:957-963(2008).
RN [44]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124; SER-126 AND SER-129, AND
RP IDENTIFICATION BY MASS 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 [45]
RP UBIQUITINATION BY TTC3.
RX PubMed=20059950; DOI=10.1016/j.devcel.2009.09.007;
RA Suizu F., Hiramuki Y., Okumura F., Matsuda M., Okumura A.J., Hirata N.,
RA Narita M., Kohno T., Yokota J., Bohgaki M., Obuse C., Hatakeyama S.,
RA Obata T., Noguchi M.;
RT "The E3 ligase TTC3 facilitates ubiquitination and degradation of
RT phosphorylated Akt.";
RL Dev. Cell 17:800-810(2009).
RN [46]
RP FUNCTION IN PHOSPHORYLATION OF SRPK2, AND INTERACTION WITH SRPK2.
RX PubMed=19592491; DOI=10.1074/jbc.m109.026237;
RA Jang S.W., Liu X., Fu H., Rees H., Yepes M., Levey A., Ye K.;
RT "Interaction of Akt-phosphorylated SRPK2 with 14-3-3 mediates cell cycle
RT and cell death in neurons.";
RL J. Biol. Chem. 284:24512-24525(2009).
RN [47]
RP FUNCTION.
RX PubMed=19934221; DOI=10.1242/jcs.053728;
RA Bristow J.M., Sellers M.H., Majumdar D., Anderson B., Hu L., Webb D.J.;
RT "The Rho-family GEF Asef2 activates Rac to modulate adhesion and actin
RT dynamics and thereby regulate cell migration.";
RL J. Cell Sci. 122:4535-4546(2009).
RN [48]
RP UBIQUITINATION, INTERACTION WITH TRAF6, MUTAGENESIS OF LYS-8 AND LYS-14,
RP AND CHARACTERIZATION OF VARIANT BREAST CANCER LYS-17.
RX PubMed=19713527; DOI=10.1126/science.1175065;
RA Yang W.-L., Wang J., Chan C.-H., Lee S.-W., Campos A.D., Lamothe B.,
RA Hur L., Grabiner B.C., Lin X., Darnay B.G., Lin H.-K.;
RT "The E3 ligase TRAF6 regulates Akt ubiquitination and activation.";
RL Science 325:1134-1138(2009).
RN [49]
RP FUNCTION, AND INTERACTION WITH STK3/MST2.
RX PubMed=20086174; DOI=10.1158/0008-5472.can-09-3147;
RA Romano D., Matallanas D., Weitsman G., Preisinger C., Ng T., Kolch W.;
RT "Proapoptotic kinase MST2 coordinates signaling crosstalk between RASSF1A,
RT Raf-1, and Akt.";
RL Cancer Res. 70:1195-1203(2010).
RN [50]
RP RETRACTED PAPER.
RX PubMed=19940129; DOI=10.1074/jbc.m109.059675;
RA Yuan Z., Kim D., Shu S., Wu J., Guo J., Xiao L., Kaneko S., Coppola D.,
RA Cheng J.Q.;
RT "Phosphoinositide 3-kinase/Akt inhibits MST1-mediated pro-apoptotic
RT signaling through phosphorylation of threonine 120.";
RL J. Biol. Chem. 285:3815-3824(2010).
RN [51]
RP RETRACTION NOTICE OF PUBMED:19940129.
RX PubMed=27825096; DOI=10.1074/jbc.a109.059675;
RA Yuan Z., Kim D., Shu S., Wu J., Guo J., Xiao L., Kaneko S., Coppola D.,
RA Cheng J.Q.;
RL J. Biol. Chem. 291:22858-22858(2016).
RN [52]
RP FUNCTION, AND INTERACTION WITH CLK2.
RX PubMed=20682768; DOI=10.1074/jbc.m110.122044;
RA Nam S.Y., Seo H.H., Park H.S., An S., Kim J.Y., Yang K.H., Kim C.S.,
RA Jeong M., Jin Y.W.;
RT "Phosphorylation of CLK2 at serine 34 and threonine 127 by AKT controls
RT cell survival after ionizing radiation.";
RL J. Biol. Chem. 285:31157-31163(2010).
RN [53]
RP FUNCTION IN PHOSPHORYLATION OF PALLD.
RX PubMed=20471940; DOI=10.1016/j.molcel.2010.02.031;
RA Chin Y.R., Toker A.;
RT "The actin-bundling protein palladin is an Akt1-specific substrate that
RT regulates breast cancer cell migration.";
RL Mol. Cell 38:333-344(2010).
RN [54]
RP FUNCTION, AND INTERACTION WITH STK3/MST2.
RX PubMed=20231902; DOI=10.1371/journal.pone.0009616;
RA Kim D., Shu S., Coppola M.D., Kaneko S., Yuan Z.Q., Cheng J.Q.;
RT "Regulation of proapoptotic mammalian ste20-like kinase MST2 by the IGF1-
RT Akt pathway.";
RL PLoS ONE 5:E9616-E9616(2010).
RN [55]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-176; THR-308 AND
RP SER-473, MUTAGENESIS OF TYR-176, INTERACTION WITH TNK2, AND TISSUE
RP SPECIFICITY.
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 [56]
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 [57]
RP INTERACTION WITH TRIM13, AND UBIQUITINATION.
RX PubMed=21333377; DOI=10.1016/j.ejcb.2010.12.001;
RA Joo H.M., Kim J.Y., Jeong J.B., Seong K.M., Nam S.Y., Yang K.H., Kim C.S.,
RA Kim H.S., Jeong M., An S., Jin Y.W.;
RT "Ret finger protein 2 enhances ionizing radiation-induced apoptosis via
RT degradation of AKT and MDM2.";
RL Eur. J. Cell Biol. 90:420-431(2011).
RN [58]
RP INTERACTION WITH PPP2R5B, AND DEPHOSPHORYLATION.
RX PubMed=21329884; DOI=10.1016/j.molcel.2011.02.007;
RA Rodgers J.T., Vogel R.O., Puigserver P.;
RT "Clk2 and B56-beta mediate insulin-regulated assembly of the PP2A
RT phosphatase holoenzyme complex on Akt.";
RL Mol. Cell 41:471-479(2011).
RN [59]
RP INTERACTION WITH FAM168A.
RX PubMed=23251525; DOI=10.1371/journal.pone.0051413;
RA Peng B., Gu Y., Xiong Y., Zheng G., He Z.;
RT "Microarray-assisted pathway analysis identifies MT1X & NFkappaB as
RT mediators of TCRP1-associated resistance to cisplatin in oral squamous cell
RT carcinoma.";
RL PLoS ONE 7:E51413-E51413(2012).
RN [60]
RP PROTEOLYTIC CLEAVAGE.
RX PubMed=23152800; DOI=10.1371/journal.pone.0048770;
RA Sen T., Sen N., Noordhuis M.G., Ravi R., Wu T.C., Ha P.K., Sidransky D.,
RA Hoque M.O.;
RT "OGDHL is a modifier of AKT-dependent signaling and NF-kappaB function.";
RL PLoS ONE 7:e48770-e48770(2012).
RN [61]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, AND IDENTIFICATION BY
RP 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 [62]
RP INTERACTION WITH FAM83B.
RX PubMed=23676467; DOI=10.18632/oncotarget.1027;
RA Cipriano R., Miskimen K.L., Bryson B.L., Foy C.R., Bartel C.A.,
RA Jackson M.W.;
RT "FAM83B-mediated activation of PI3K/AKT and MAPK signaling cooperates to
RT promote epithelial cell transformation and resistance to targeted
RT therapies.";
RL Oncotarget 4:729-738(2013).
RN [63]
RP REVIEW ON ROLE IN KIT SIGNALING.
RX PubMed=15526160; DOI=10.1007/s00018-004-4189-6;
RA Ronnstrand L.;
RT "Signal transduction via the stem cell factor receptor/c-Kit.";
RL Cell. Mol. Life Sci. 61:2535-2548(2004).
RN [64]
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 [65]
RP PHOSPHORYLATION AT SER-473.
RX PubMed=20978158; DOI=10.1158/1535-7163.mct-10-0730;
RA Kunoh T., Noda T., Koseki K., Sekigawa M., Takagi M., Shin-ya K.,
RA Goshima N., Iemura S., Natsume T., Wada S., Mukai Y., Ohta S., Sasaki R.,
RA Mizukami T.;
RT "A novel human dynactin-associated protein, dynAP, promotes activation of
RT Akt, and ergosterol-related compounds induce dynAP-dependent apoptosis of
RT human cancer cells.";
RL Mol. Cancer Ther. 9:2934-2942(2010).
RN [66]
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 [67]
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 [68]
RP PHOSPHORYLATION AT THR-308 AND SER-473.
RX PubMed=21464307; DOI=10.1073/pnas.1016132108;
RA Xie X., Zhang D., Zhao B., Lu M.K., You M., Condorelli G., Wang C.Y.,
RA Guan K.L.;
RT "IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct
RT phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:6474-6479(2011).
RN [69]
RP INTERACTION WITH SIRT1, ACETYLATION AT LYS-14 AND LYS-20, DEACETYLATION AT
RP LYS-14 AND LYS-20, AND MUTAGENESIS OF LYS-14; GLU-17 AND LYS-20.
RX PubMed=21775285; DOI=10.1126/scisignal.2001465;
RA Sundaresan N.R., Pillai V.B., Wolfgeher D., Samant S., Vasudevan P.,
RA Parekh V., Raghuraman H., Cunningham J.M., Gupta M., Gupta M.P.;
RT "The deacetylase SIRT1 promotes membrane localization and activation of Akt
RT and PDK1 during tumorigenesis and cardiac hypertrophy.";
RL Sci. Signal. 4:RA46-RA46(2011).
RN [70]
RP UBIQUITINATION AT LYS-284.
RX PubMed=22410793; DOI=10.1038/cr.2012.38;
RA Bae S., Kim S.Y., Jung J.H., Yoon Y., Cha H.J., Lee H., Kim K., Kim J.,
RA An I.S., Kim J., Um H.D., Park I.C., Lee S.J., Nam S.Y., Jin Y.W.,
RA Lee J.H., An S.;
RT "Akt is negatively regulated by the MULAN E3 ligase.";
RL Cell Res. 22:873-885(2012).
RN [71]
RP GLYCOSYLATION AT SER-126; SER-129; THR-305 AND THR-312, SUBCELLULAR
RP LOCATION, INTERACTION WITH PDPK1, AND MUTAGENESIS OF THR-305 AND THR-312.
RX PubMed=22629392; DOI=10.1371/journal.pone.0037427;
RA Wang S., Huang X., Sun D., Xin X., Pan Q., Peng S., Liang Z., Luo C.,
RA Yang Y., Jiang H., Huang M., Chai W., Ding J., Geng M.;
RT "Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates
RT Akt signaling.";
RL PLoS ONE 7:E37427-E37427(2012).
RN [72]
RP PHOSPHORYLATION AT SER-473, AND DEPHOSPHORYLATION BY CPPED1.
RX PubMed=23799035; DOI=10.1371/journal.pone.0065679;
RA Zhuo D.X., Zhang X.W., Jin B., Zhang Z., Xie B.S., Wu C.L., Gong K.,
RA Mao Z.B.;
RT "CSTP1, a novel protein phosphatase, blocks cell cycle, promotes cell
RT apoptosis, and suppresses tumor growth of bladder cancer by directly
RT dephosphorylating Akt at Ser473 site.";
RL PLoS ONE 8:E65679-E65679(2013).
RN [73]
RP FUNCTION.
RX PubMed=23431171; DOI=10.1073/pnas.1300490110;
RA Rokudai S., Laptenko O., Arnal S.M., Taya Y., Kitabayashi I., Prives C.;
RT "MOZ increases p53 acetylation and premature senescence through its complex
RT formation with PML.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:3895-3900(2013).
RN [74]
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 [75]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-448 AND THR-450, AND
RP 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 [76]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 [77]
RP INTERACTION WITH KIF14.
RX PubMed=24784001; DOI=10.1016/j.neo.2014.03.008;
RA Singel S.M., Cornelius C., Zaganjor E., Batten K., Sarode V.R.,
RA Buckley D.L., Peng Y., John G.B., Li H.C., Sadeghi N., Wright W.E., Lum L.,
RA Corson T.W., Shay J.W.;
RT "KIF14 promotes AKT phosphorylation and contributes to chemoresistance in
RT triple-negative breast cancer.";
RL Neoplasia 16:247-256(2014).
RN [78]
RP PHOSPHORYLATION AT SER-473, DEPHOSPHORYLATION, AND INTERACTION WITH PHLPP1
RP AND FKBP5.
RX PubMed=28147277; DOI=10.1016/j.celrep.2017.01.009;
RA Yu J., Qin B., Wu F., Qin S., Nowsheen S., Shan S., Zayas J., Pei H.,
RA Lou Z., Wang L.;
RT "Regulation of serine-threonine kinase Akt activation by NAD+-dependent
RT deacetylase SIRT7.";
RL Cell Rep. 18:1229-1240(2017).
RN [79]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=32322062; DOI=10.1038/s41586-020-2183-2;
RA Xu D., Wang Z., Xia Y., Shao F., Xia W., Wei Y., Li X., Qian X., Lee J.H.,
RA Du L., Zheng Y., Lv G., Leu J.S., Wang H., Xing D., Liang T., Hung M.C.,
RA Lu Z.;
RT "The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis.";
RL Nature 580:530-535(2020).
RN [80]
RP INTERACTION WITH TMEM175, AND 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).
RN [81]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-179.
RX PubMed=33594058; DOI=10.1038/s41467-021-21206-3;
RA Li T., Wang X., Ju E., da Silva S.R., Chen L., Zhang X., Wei S., Gao S.J.;
RT "RNF167 activates mTORC1 and promotes tumorigenesis by targeting CASTOR1
RT for ubiquitination and degradation.";
RL Nat. Commun. 12:1055-1055(2021).
RN [82]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 1-123, FUNCTION, INTERACTION WITH
RP PTDINS(3,4,5)P3 AND PTDINS(3,4)P2, AND MUTAGENESIS OF LYS-14; ARG-25 AND
RP ARG-86.
RX PubMed=12176338; DOI=10.1016/s0960-9822(02)00972-7;
RA Thomas C.C., Deak M., Alessi D.R., van Aalten D.M.;
RT "High-resolution structure of the pleckstrin homology domain of protein
RT kinase b/akt bound to phosphatidylinositol (3,4,5)-trisphosphate.";
RL Curr. Biol. 12:1256-1262(2002).
RN [83]
RP X-RAY CRYSTALLOGRAPHY (0.98 ANGSTROMS) OF 1-121, FUNCTION, AND INTERACTION
RP WITH PTDINS(1,3,4,5)P4.
RX PubMed=12964941; DOI=10.1042/bj20031229;
RA Milburn C.C., Deak M., Kelly S.M., Price N.C., Alessi D.R.,
RA Van Aalten D.M.;
RT "Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin
RT homology domain of protein kinase B induces a conformational change.";
RL Biochem. J. 375:531-538(2003).
RN [84] {ECO:0007744|PDB:3CQU, ECO:0007744|PDB:3CQW}
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 144-480, PHOSPHORYLATION AT
RP THR-308, AND ACTIVITY REGULATION.
RX PubMed=18456494; DOI=10.1016/j.bmcl.2008.04.034;
RA Lippa B., Pan G., Corbett M., Li C., Kauffman G.S., Pandit J., Robinson S.,
RA Wei L., Kozina E., Marr E.S., Borzillo G., Knauth E., Barbacci-Tobin E.G.,
RA Vincent P., Troutman M., Baker D., Rajamohan F., Kakar S., Clark T.,
RA Morris J.;
RT "Synthesis and structure based optimization of novel Akt inhibitors.";
RL Bioorg. Med. Chem. Lett. 18:3359-3363(2008).
RN [85] {ECO:0007744|PDB:3OCB}
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 144-480, AND ACTIVITY REGULATION.
RX PubMed=20810279; DOI=10.1016/j.bmcl.2010.08.053;
RA Blake J.F., Kallan N.C., Xiao D., Xu R., Bencsik J.R., Skelton N.J.,
RA Spencer K.L., Mitchell I.S., Woessner R.D., Gloor S.L., Risom T.,
RA Gross S.D., Martinson M., Morales T.H., Vigers G.P., Brandhuber B.J.;
RT "Discovery of pyrrolopyrimidine inhibitors of Akt.";
RL Bioorg. Med. Chem. Lett. 20:5607-5612(2010).
RN [86] {ECO:0007744|PDB:3MV5, ECO:0007744|PDB:3MVH}
RP X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 144-480, PHOSPHORYLATION AT
RP THR-308, AND ACTIVITY REGULATION.
RX PubMed=20481595; DOI=10.1021/jm1003842;
RA Freeman-Cook K.D., Autry C., Borzillo G., Gordon D., Barbacci-Tobin E.,
RA Bernardo V., Briere D., Clark T., Corbett M., Jakubczak J., Kakar S.,
RA Knauth E., Lippa B., Luzzio M.J., Mansour M., Martinelli G., Marx M.,
RA Nelson K., Pandit J., Rajamohan F., Robinson S., Subramanyam C., Wei L.,
RA Wythes M., Morris J.;
RT "Design of selective, ATP-competitive inhibitors of Akt.";
RL J. Med. Chem. 53:4615-4622(2010).
RN [87] {ECO:0007744|PDB:3O96}
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 2-443, AND DISULFIDE BOND.
RX PubMed=20886116; DOI=10.1371/journal.pone.0012913;
RA Wu W.I., Voegtli W.C., Sturgis H.L., Dizon F.P., Vigers G.P.,
RA Brandhuber B.J.;
RT "Crystal structure of human AKT1 with an allosteric inhibitor reveals a new
RT mode of kinase inhibition.";
RL PLoS ONE 5:E12913-E12913(2010).
RN [88] {ECO:0007744|PDB:3QKK, ECO:0007744|PDB:3QKL}
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 144-480, AND ACTIVITY REGULATION.
RX PubMed=21392984; DOI=10.1016/j.bmcl.2011.02.073;
RA Kallan N.C., Spencer K.L., Blake J.F., Xu R., Heizer J., Bencsik J.R.,
RA Mitchell I.S., Gloor S.L., Martinson M., Risom T., Gross S.D.,
RA Morales T.H., Wu W.I., Vigers G.P., Brandhuber B.J., Skelton N.J.;
RT "Discovery and SAR of spirochromane Akt inhibitors.";
RL Bioorg. Med. Chem. Lett. 21:2410-2414(2011).
RN [89]
RP VARIANT BREAST CANCER LYS-17, AND CHARACTERIZATION OF VARIANT BREAST CANCER
RP LYS-17.
RX PubMed=17611497; DOI=10.1038/nature05933;
RA Carpten J.D., Faber A.L., Horn C., Donoho G.P., Briggs S.L., Robbins C.M.,
RA Hostetter G., Boguslawski S., Moses T.Y., Savage S., Uhlik M., Lin A.,
RA Du J., Qian Y.-W., Zeckner D.J., Tucker-Kellogg G., Touchman J., Patel K.,
RA Mousses S., Bittner M., Schevitz R., Lai M.-H.T., Blanchard K.L.,
RA Thomas J.E.;
RT "A transforming mutation in the pleckstrin homology domain of AKT1 in
RT cancer.";
RL Nature 448:439-444(2007).
RN [90]
RP CHARACTERIZATION OF VARIANT PROTEUSS LYS-17.
RX PubMed=18954143; DOI=10.1021/bi801683k;
RA Landgraf K.E., Pilling C., Falke J.J.;
RT "Molecular mechanism of an oncogenic mutation that alters membrane
RT targeting: Glu17Lys modifies the PIP lipid specificity of the AKT1 PH
RT domain.";
RL Biochemistry 47:12260-12269(2008).
RN [91]
RP VARIANT PROTEUSS LYS-17.
RX PubMed=21793738; DOI=10.1056/nejmoa1104017;
RA Lindhurst M.J., Sapp J.C., Teer J.K., Johnston J.J., Finn E.M., Peters K.,
RA Turner J., Cannons J.L., Bick D., Blakemore L., Blumhorst C., Brockmann K.,
RA Calder P., Cherman N., Deardorff M.A., Everman D.B., Golas G.,
RA Greenstein R.M., Kato B.M., Keppler-Noreuil K.M., Kuznetsov S.A.,
RA Miyamoto R.T., Newman K., Ng D., O'Brien K., Rothenberg S.,
RA Schwartzentruber D.J., Singhal V., Tirabosco R., Upton J., Wientroub S.,
RA Zackai E.H., Hoag K., Whitewood-Neal T., Robey P.G., Schwartzberg P.L.,
RA Darling T.N., Tosi L.L., Mullikin J.C., Biesecker L.G.;
RT "A mosaic activating mutation in AKT1 associated with the Proteus
RT syndrome.";
RL N. Engl. J. Med. 365:611-619(2011).
RN [92]
RP VARIANTS CWS6 CYS-25 AND PRO-435.
RX PubMed=23246288; DOI=10.1016/j.ajhg.2012.10.021;
RA Orloff M.S., He X., Peterson C., Chen F., Chen J.L., Mester J.L., Eng C.;
RT "Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes.";
RL Am. J. Hum. Genet. 92:76-80(2013).
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 (PubMed:15526160, PubMed:11882383,
CC PubMed:21620960, PubMed:21432781). This is mediated through serine
CC and/or threonine phosphorylation of a range of downstream substrates
CC (PubMed:15526160, PubMed:11882383, PubMed:21620960, PubMed:21432781).
CC Over 100 substrate candidates have been reported so far, but for most
CC of them, no isoform specificity has been reported (PubMed:15526160,
CC PubMed:11882383, PubMed:21620960, PubMed:21432781). AKT is responsible
CC of the regulation of glucose uptake by mediating insulin-induced
CC translocation of the SLC2A4/GLUT4 glucose transporter to the cell
CC surface (By similarity). Phosphorylation of PTPN1 at 'Ser-50'
CC negatively modulates its phosphatase activity preventing
CC dephosphorylation of the insulin receptor and the attenuation of
CC insulin signaling (By similarity). Phosphorylation of TBC1D4 triggers
CC the binding of this effector to inhibitory 14-3-3 proteins, which is
CC required for insulin-stimulated glucose transport (PubMed:11994271).
CC AKT regulates also the storage of glucose in the form of glycogen by
CC phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in
CC inhibition of its kinase activity (By similarity). Phosphorylation of
CC GSK3 isoforms by AKT is also thought to be one mechanism by which cell
CC proliferation is driven (By similarity). AKT regulates also cell
CC survival via the phosphorylation of MAP3K5 (apoptosis signal-related
CC kinase) (PubMed:11154276). Phosphorylation of 'Ser-83' decreases MAP3K5
CC kinase activity stimulated by oxidative stress and thereby prevents
CC apoptosis (PubMed:11154276). AKT mediates insulin-stimulated protein
CC synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby
CC activating the TORC1 signaling pathway, and leading to both
CC phosphorylation of 4E-BP1 and in activation of RPS6KB1
CC (PubMed:12150915). Also regulates the TORC1 signaling pathway by
CC catalyzing phosphorylation of CASTOR1 (PubMed:33594058). AKT is
CC involved in the phosphorylation of members of the FOXO factors
CC (Forkhead family of transcription factors), leading to binding of 14-3-
CC 3 proteins and cytoplasmic localization (PubMed:10358075). In
CC particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-
CC 319' (PubMed:10358075). FOXO3 and FOXO4 are phosphorylated on
CC equivalent sites (PubMed:10358075). AKT has an important role in the
CC regulation of NF-kappa-B-dependent gene transcription and positively
CC regulates the activity of CREB1 (cyclic AMP (cAMP)-response element
CC binding protein) (PubMed:9829964). The phosphorylation of CREB1 induces
CC the binding of accessory proteins that are necessary for the
CC transcription of pro-survival genes such as BCL2 and MCL1
CC (PubMed:9829964). AKT phosphorylates 'Ser-454' on ATP citrate lyase
CC (ACLY), thereby potentially regulating ACLY activity and fatty acid
CC synthesis (By similarity). Activates the 3B isoform of cyclic
CC nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273',
CC resulting in reduced cyclic AMP levels and inhibition of lipolysis (By
CC similarity). Phosphorylates PIKFYVE on 'Ser-318', which results in
CC increased PI(3)P-5 activity (By similarity). The Rho GTPase-activating
CC protein DLC1 is another substrate and its phosphorylation is implicated
CC in the regulation cell proliferation and cell growth. AKT plays a role
CC as key modulator of the AKT-mTOR signaling pathway controlling the
CC tempo of the process of newborn neurons integration during adult
CC neurogenesis, including correct neuron positioning, dendritic
CC development and synapse formation (By similarity). Signals downstream
CC of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of
CC various growth factors such as platelet-derived growth factor (PDGF),
CC epidermal growth factor (EGF), insulin and insulin-like growth factor I
CC (IGF-I) (PubMed:12176338, PubMed:12964941). AKT mediates the
CC antiapoptotic effects of IGF-I (By similarity). Essential for the
CC SPATA13-mediated regulation of cell migration and adhesion assembly and
CC disassembly (PubMed:19934221). May be involved in the regulation of the
CC placental development (By similarity). Phosphorylates STK4/MST1 at
CC 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity,
CC nuclear translocation, autophosphorylation and ability to phosphorylate
CC FOXO3 (PubMed:17726016). Phosphorylates STK3/MST2 at 'Thr-117' and
CC 'Thr-384' leading to inhibition of its: cleavage, kinase activity,
CC autophosphorylation at Thr-180, binding to RASSF1 and nuclear
CC translocation (PubMed:20086174, PubMed:20231902). Phosphorylates SRPK2
CC and enhances its kinase activity towards SRSF2 and ACIN1 and promotes
CC its nuclear translocation (PubMed:19592491). Phosphorylates RAF1 at
CC 'Ser-259' and negatively regulates its activity (PubMed:10576742).
CC Phosphorylation of BAD stimulates its pro-apoptotic activity
CC (PubMed:10926925). 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 (PubMed:23431171). Phosphorylates palladin (PALLD), modulating
CC cytoskeletal organization and cell motility (PubMed:20471940).
CC Phosphorylates prohibitin (PHB), playing an important role in cell
CC metabolism and proliferation (PubMed:18507042). Phosphorylates CDKN1A,
CC for which phosphorylation at 'Thr-145' induces its release from CDK2
CC and cytoplasmic relocalization (PubMed:16982699). These recent findings
CC indicate that the AKT1 isoform has a more specific role in cell
CC motility and proliferation (PubMed:16139227). Phosphorylates CLK2
CC thereby controlling cell survival to ionizing radiation
CC (PubMed:20682768). Phosphorylates PCK1 at 'Ser-90', reducing the
CC binding affinity of PCK1 to oxaloacetate and changing PCK1 into an
CC atypical protein kinase activity using GTP as donor (PubMed:32322062).
CC Also acts as an activator of TMEM175 potassium channel activity in
CC response to growth factors: forms the lysoK(GF) complex together with
CC TMEM175 and acts by promoting TMEM175 channel activation, independently
CC of its protein kinase activity (PubMed:32228865).
CC {ECO:0000250|UniProtKB:P31750, ECO:0000250|UniProtKB:P47196,
CC ECO:0000269|PubMed:10358075, ECO:0000269|PubMed:10576742,
CC ECO:0000269|PubMed:10926925, ECO:0000269|PubMed:11154276,
CC ECO:0000269|PubMed:11994271, ECO:0000269|PubMed:12150915,
CC ECO:0000269|PubMed:12176338, ECO:0000269|PubMed:12964941,
CC ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:16982699,
CC ECO:0000269|PubMed:17726016, ECO:0000269|PubMed:18507042,
CC ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:19934221,
CC ECO:0000269|PubMed:20086174, ECO:0000269|PubMed:20231902,
CC ECO:0000269|PubMed:20471940, ECO:0000269|PubMed:20682768,
CC ECO:0000269|PubMed:23431171, ECO:0000269|PubMed:32228865,
CC ECO:0000269|PubMed:32322062, ECO:0000269|PubMed:33594058,
CC ECO:0000269|PubMed:9829964, ECO:0000303|PubMed:11882383,
CC ECO:0000303|PubMed:15526160, 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:16139227, ECO:0000269|PubMed:1718748,
CC ECO:0000269|PubMed:1851997, ECO:0000269|PubMed:26440888,
CC ECO:0000269|PubMed:32322062, ECO:0000269|PubMed:33594058};
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:0000269|PubMed:16139227,
CC ECO:0000269|PubMed:1718748, ECO:0000269|PubMed:1851997};
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 (PubMed:20481595, PubMed:21392984, PubMed:9512493,
CC PubMed:9736715). Inhibited by pyrrolopyrimidine inhibitors like aniline
CC triazole and spiroindoline (PubMed:18456494, PubMed:20810279).
CC {ECO:0000269|PubMed:18456494, ECO:0000269|PubMed:20481595,
CC ECO:0000269|PubMed:20810279, ECO:0000269|PubMed:21392984,
CC ECO:0000269|PubMed:9512493, ECO:0000269|PubMed:9736715,
CC ECO:0000305|PubMed:20810279}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=52.8 uM for ATP (for purified and in vitro activated AKT1)
CC {ECO:0000269|PubMed:16540465};
CC KM=0.5 uM for peptide substrate (for purified and in vitro activated
CC AKT1) {ECO:0000269|PubMed:16540465};
CC KM=143.3 uM for ATP (for recombinant myristoylated AKT1 expressed and
CC immunoprecipitated from Rat-1 cells) {ECO:0000269|PubMed:16540465};
CC KM=2.9 uM for peptide substrate (for recombinant myristoylated AKT1
CC expressed and immunoprecipitated from Rat-1 cells)
CC {ECO:0000269|PubMed:16540465};
CC -!- SUBUNIT: Interacts with BTBD10 (By similarity). Interacts with KCTD20
CC (By similarity). Interacts (via the C-terminus) with CCDC88A (via its
CC C-terminus). Interacts with GRB10; the interaction leads to GRB10
CC phosphorylation thus promoting YWHAE-binding (By similarity). Interacts
CC with AGAP2 (isoform 2/PIKE-A); the interaction occurs in the presence
CC of guanine nucleotides. Interacts with AKTIP. Interacts (via PH domain)
CC with MTCP1, TCL1A AND TCL1B. Interacts with CDKN1B; the interaction
CC phosphorylates CDKN1B promoting 14-3-3 binding and cell-cycle
CC 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 RAF1.
CC Interacts with TRIM13; the interaction ubiquitinates AKT1 leading to
CC its proteasomal degradation. Interacts with TNK2 and CLK2. Interacts
CC (via the C-terminus) with THEM4 (via its C-terminus). Interacts with
CC and phosphorylated by PDPK1. Interacts with PA2G4 (By similarity).
CC Interacts with KIF14; the interaction is detected in the plasma
CC membrane upon INS stimulation and promotes AKT1 phosphorylation
CC (PubMed:24784001). Interacts with FAM83B; activates the PI3K/AKT
CC signaling cascade (PubMed:23676467). Interacts with WDFY2 (via WD
CC repeats 1-3) (PubMed:16792529). Forms a complex with WDFY2 and FOXO1
CC (By similarity). Interacts with FAM168A (PubMed:23251525). Interacts
CC with SYAP1 (via phosphorylated form and BSD domain); this interaction
CC is enhanced in a mTORC2-mediated manner in response to epidermal growth
CC factor (EGF) stimulation and activates AKT1 (PubMed:23300339).
CC Interacts with PKHM3 (By similarity). Interacts with FKBP5/FKBP51;
CC promoting interaction between Akt/AKT1 and PHLPP1, thereby enhancing
CC dephosphorylation and subsequent activation of Akt/AKT1
CC (PubMed:28147277). Interacts with TMEM175; leading to formation of the
CC lysoK(GF) complex (PubMed:32228865). Acts as a negative regulator of
CC the cGAS-STING pathway by mediating phosphorylation of CGAS during
CC mitosis, leading to its inhibition (PubMed:26440888).
CC {ECO:0000250|UniProtKB:P31750, ECO:0000250|UniProtKB:P47196,
CC ECO:0000269|PubMed:10576742, ECO:0000269|PubMed:10716693,
CC ECO:0000269|PubMed:10926925, ECO:0000269|PubMed:10983986,
CC ECO:0000269|PubMed:11154276, ECO:0000269|PubMed:11598301,
CC ECO:0000269|PubMed:11839817, ECO:0000269|PubMed:12042314,
CC ECO:0000269|PubMed:12176338, ECO:0000269|PubMed:12244301,
CC ECO:0000269|PubMed:12964941, ECO:0000269|PubMed:14749367,
CC ECO:0000269|PubMed:14761976, ECO:0000269|PubMed:15118108,
CC ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:16417524,
CC ECO:0000269|PubMed:16792529, ECO:0000269|PubMed:17726016,
CC ECO:0000269|PubMed:17932490, ECO:0000269|PubMed:19592491,
CC ECO:0000269|PubMed:19713527, ECO:0000269|PubMed:20086174,
CC ECO:0000269|PubMed:20231902, ECO:0000269|PubMed:20333297,
CC ECO:0000269|PubMed:20682768, ECO:0000269|PubMed:21329884,
CC ECO:0000269|PubMed:21333377, ECO:0000269|PubMed:21775285,
CC ECO:0000269|PubMed:22629392, ECO:0000269|PubMed:23251525,
CC ECO:0000269|PubMed:23300339, ECO:0000269|PubMed:23676467,
CC ECO:0000269|PubMed:24784001, ECO:0000269|PubMed:26440888,
CC ECO:0000269|PubMed:28147277, ECO:0000269|PubMed:32228865}.
CC -!- INTERACTION:
CC P31749; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-296087, EBI-10173507;
CC P31749; P31749: AKT1; NbExp=3; IntAct=EBI-296087, EBI-296087;
CC P31749; Q86V81: ALYREF; NbExp=5; IntAct=EBI-296087, EBI-347640;
CC P31749; Q8IXJ9: ASXL1; NbExp=2; IntAct=EBI-296087, EBI-1646500;
CC P31749; P54253: ATXN1; NbExp=6; IntAct=EBI-296087, EBI-930964;
CC P31749; O95999: BCL10; NbExp=5; IntAct=EBI-296087, EBI-958922;
CC P31749; Q9H0C5: BTBD1; NbExp=3; IntAct=EBI-296087, EBI-935503;
CC P31749; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-296087, EBI-1383687;
CC P31749; P20248: CCNA2; NbExp=2; IntAct=EBI-296087, EBI-457097;
CC P31749; Q16543: CDC37; NbExp=4; IntAct=EBI-296087, EBI-295634;
CC P31749; Q8TAP6: CEP76; NbExp=3; IntAct=EBI-296087, EBI-742887;
CC P31749; Q92793: CREBBP; NbExp=3; IntAct=EBI-296087, EBI-81215;
CC P31749; Q15438: CYTH1; NbExp=3; IntAct=EBI-296087, EBI-997830;
CC P31749; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-296087, EBI-742054;
CC P31749; P26358: DNMT1; NbExp=6; IntAct=EBI-296087, EBI-719459;
CC P31749; Q1W6H9: FAM110C; NbExp=2; IntAct=EBI-296087, EBI-3942563;
CC P31749; Q12778: FOXO1; NbExp=2; IntAct=EBI-296087, EBI-1108782;
CC P31749; O43524: FOXO3; NbExp=3; IntAct=EBI-296087, EBI-1644164;
CC P31749; P06241: FYN; NbExp=3; IntAct=EBI-296087, EBI-515315;
CC P31749; P22466: GAL; NbExp=3; IntAct=EBI-296087, EBI-6624768;
CC P31749; P49841: GSK3B; NbExp=4; IntAct=EBI-296087, EBI-373586;
CC P31749; Q96LI6-3: HSFY2; NbExp=3; IntAct=EBI-296087, EBI-25830912;
CC P31749; P08238: HSP90AB1; NbExp=3; IntAct=EBI-296087, EBI-352572;
CC P31749; P42858: HTT; NbExp=3; IntAct=EBI-296087, EBI-466029;
CC P31749; Q5S007: LRRK2; NbExp=6; IntAct=EBI-296087, EBI-5323863;
CC P31749; Q99683: MAP3K5; NbExp=2; IntAct=EBI-296087, EBI-476263;
CC P31749; P10636: MAPT; NbExp=2; IntAct=EBI-296087, EBI-366182;
CC P31749; Q00987: MDM2; NbExp=4; IntAct=EBI-296087, EBI-389668;
CC P31749; Q14696: MESD; NbExp=3; IntAct=EBI-296087, EBI-6165891;
CC P31749; P42345: MTOR; NbExp=4; IntAct=EBI-296087, EBI-359260;
CC P31749; Q9BZQ8: NIBAN1; NbExp=2; IntAct=EBI-296087, EBI-6916466;
CC P31749; P04150: NR3C1; NbExp=5; IntAct=EBI-296087, EBI-493507;
CC P31749; O15530: PDPK1; NbExp=4; IntAct=EBI-296087, EBI-717097;
CC P31749; Q96S96: PEBP4; NbExp=2; IntAct=EBI-296087, EBI-8563667;
CC P31749; P19174: PLCG1; NbExp=9; IntAct=EBI-296087, EBI-79387;
CC P31749; O60437: PPL; NbExp=2; IntAct=EBI-296087, EBI-368321;
CC P31749; P62136: PPP1CA; NbExp=4; IntAct=EBI-296087, EBI-357253;
CC P31749; P67775: PPP2CA; NbExp=4; IntAct=EBI-296087, EBI-712311;
CC P31749; P30153: PPP2R1A; NbExp=2; IntAct=EBI-296087, EBI-302388;
CC P31749; P17612: PRKACA; NbExp=3; IntAct=EBI-296087, EBI-476586;
CC P31749; Q05513: PRKCZ; NbExp=2; IntAct=EBI-296087, EBI-295351;
CC P31749; A0A0C4DFM3: PRUNE2; NbExp=3; IntAct=EBI-296087, EBI-25830870;
CC P31749; Q15047: SETDB1; NbExp=9; IntAct=EBI-296087, EBI-79691;
CC P31749; Q96EB6: SIRT1; NbExp=5; IntAct=EBI-296087, EBI-1802965;
CC P31749; Q13043: STK4; NbExp=13; IntAct=EBI-296087, EBI-367376;
CC P31749; Q9UNE7-1: STUB1; NbExp=5; IntAct=EBI-296087, EBI-15687717;
CC P31749; P56279: TCL1A; NbExp=8; IntAct=EBI-296087, EBI-749995;
CC P31749; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-296087, EBI-750109;
CC P31749; Q5T1C6: THEM4; NbExp=4; IntAct=EBI-296087, EBI-7684443;
CC P31749; Q92547: TOPBP1; NbExp=2; IntAct=EBI-296087, EBI-308302;
CC P31749; P53804: TTC3; NbExp=4; IntAct=EBI-296087, EBI-2681313;
CC P31749; P10599: TXN; NbExp=3; IntAct=EBI-296087, EBI-594644;
CC P31749; P08670: VIM; NbExp=29; IntAct=EBI-296087, EBI-353844;
CC P31749; Q6GPH4: XAF1; NbExp=3; IntAct=EBI-296087, EBI-2815120;
CC P31749; A0A024RC47: ZNF24; NbExp=3; IntAct=EBI-296087, EBI-25830832;
CC P31749; P29067: Arrb2; Xeno; NbExp=2; IntAct=EBI-296087, EBI-1636616;
CC P31749; Q83730: m005R; Xeno; NbExp=3; IntAct=EBI-296087, EBI-6859930;
CC P31749; P03165: X; Xeno; NbExp=3; IntAct=EBI-296087, EBI-7683985;
CC P31749-1; Q15118-1: PDK1; NbExp=2; IntAct=EBI-12562306, EBI-12562315;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P31750}. Nucleus
CC {ECO:0000269|PubMed:20333297}. Cell membrane
CC {ECO:0000269|PubMed:20333297}. Note=Nucleus after activation by
CC integrin-linked protein kinase 1 (ILK1). Nuclear translocation is
CC enhanced by interaction with TCL1A. Phosphorylation on Tyr-176 by TNK2
CC results in its localization to the cell membrane where it is targeted
CC for further phosphorylations on Thr-308 and Ser-473 leading to its
CC activation and the activated form translocates to the nucleus.
CC Colocalizes with WDFY2 in intracellular vesicles (PubMed:16792529).
CC {ECO:0000269|PubMed:16792529}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P31749-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P31749-2; Sequence=VSP_056180;
CC -!- TISSUE SPECIFICITY: Expressed in prostate cancer and levels increase
CC from the normal to the malignant state (at protein level). Expressed in
CC all human cell types so far analyzed. The Tyr-176 phosphorylated form
CC shows a significant increase in expression in breast cancers during the
CC progressive stages i.e. normal to hyperplasia (ADH), ductal carcinoma
CC in situ (DCIS), invasive ductal carcinoma (IDC) and lymph node
CC metastatic (LNMM) stages. {ECO:0000269|PubMed:1718748,
CC ECO:0000269|PubMed:17932490, ECO:0000269|PubMed:20333297}.
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:0000269|PubMed:12176338,
CC ECO:0000269|PubMed:12964941}.
CC -!- DOMAIN: The AGC-kinase C-terminal mediates interaction with THEM4.
CC {ECO:0000269|PubMed:11598301}.
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. O-GlcNAcylation at Ser-473 also probably interferes with
CC phosphorylation at this site. {ECO:0000269|PubMed:14761976,
CC ECO:0000269|PubMed:15047712, ECO:0000269|PubMed:15718470,
CC ECO:0000269|PubMed:16266983, ECO:0000269|PubMed:17013611,
CC ECO:0000269|PubMed:18456494, ECO:0000269|PubMed:20333297,
CC ECO:0000269|PubMed:20481595, ECO:0000269|PubMed:20978158,
CC ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:23799035,
CC ECO:0000269|PubMed:8978681, ECO:0000269|PubMed:9512493,
CC ECO:0000269|PubMed:9736715}.
CC -!- PTM: Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required for
CC full activity (PubMed:12149249, PubMed:14761976, PubMed:15047712,
CC PubMed:16266983, PubMed:17013611, PubMed:20978158, PubMed:9736715,
CC PubMed:23799035, PubMed:8978681, PubMed:28147277). Activated TNK2
CC phosphorylates it on Tyr-176 resulting in its binding to the anionic
CC plasma membrane phospholipid PA (PubMed:20333297). This phosphorylated
CC form localizes to the cell membrane, where it is targeted by PDPK1 and
CC PDPK2 for further phosphorylations on Thr-308 and Ser-473 leading to
CC its activation (PubMed:9512493). Ser-473 phosphorylation by mTORC2
CC favors Thr-308 phosphorylation by PDPK1 (PubMed:21464307,
CC PubMed:8978681). Phosphorylated at Thr-308 and Ser-473 by IKBKE and
CC TBK1 (PubMed:15718470, PubMed:18456494, PubMed:20481595,
CC PubMed:8978681). Ser-473 phosphorylation is enhanced by interaction
CC with AGAP2 isoform 2 (PIKE-A) (PubMed:14761976). Ser-473
CC phosphorylation is enhanced in focal cortical dysplasias with Taylor-
CC type balloon cells (PubMed:17013611). Ser-473 phosphorylation is
CC enhanced by signaling through activated FLT3 (By similarity). Ser-473
CC is dephosphorylated by PHLPP (PubMed:28147277). Dephosphorylated at
CC Thr-308 and Ser-473 by PP2A phosphatase (PubMed:21329884). The
CC phosphorylated form of PPP2R5B is required for bridging AKT1 with PP2A
CC phosphatase (PubMed:21329884). Ser-473 is dephosphorylated by CPPED1,
CC leading to termination of signaling (PubMed:9512493).
CC {ECO:0000250|UniProtKB:Q01314, ECO:0000269|PubMed:12149249,
CC ECO:0000269|PubMed:14761976, ECO:0000269|PubMed:15047712,
CC ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:16266983,
CC ECO:0000269|PubMed:17013611, ECO:0000269|PubMed:18456494,
CC ECO:0000269|PubMed:20333297, ECO:0000269|PubMed:20481595,
CC ECO:0000269|PubMed:20978158, ECO:0000269|PubMed:21329884,
CC ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:23799035,
CC ECO:0000269|PubMed:28147277, ECO:0000269|PubMed:8978681,
CC ECO:0000269|PubMed:9512493, ECO:0000269|PubMed:9736715}.
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 (PubMed:19713527). When
CC ubiquitinated, it translocates to the plasma membrane, where it becomes
CC phosphorylated (PubMed:20059950). When fully phosphorylated and
CC translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination
CC catalyzed by TTC3, leading to its degradation by the proteasome
CC (PubMed:20059950). Also ubiquitinated by TRIM13 leading to its
CC proteasomal degradation (PubMed:21333377). Phosphorylated, undergoes
CC 'Lys-48'-linked polyubiquitination preferentially at Lys-284 catalyzed
CC by MUL1, leading to its proteasomal degradation (PubMed:22410793).
CC Ubiquitinated via 'Lys-48'-linked polyubiquitination by ZNRF1, leading
CC to its degradation by the proteasome (By similarity).
CC {ECO:0000250|UniProtKB:P31750, ECO:0000269|PubMed:19713527,
CC ECO:0000269|PubMed:20059950, ECO:0000269|PubMed:21333377,
CC ECO:0000269|PubMed:22410793}.
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.
CC {ECO:0000269|PubMed:21775285}.
CC -!- PTM: Cleavage by caspase-3/CASP3 (By similarity). 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:23152800). {ECO:0000250|UniProtKB:P31750,
CC ECO:0000269|PubMed:23152800}.
CC -!- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy
CC originating from breast epithelial tissue. Breast neoplasms can be
CC distinguished by their histologic pattern. Invasive ductal carcinoma is
CC by far the most common type. Breast cancer is etiologically and
CC genetically heterogeneous. Important genetic factors have been
CC indicated by familial occurrence and bilateral involvement. Mutations
CC at more than one locus can be involved in different families or even in
CC the same case. {ECO:0000269|PubMed:17611497}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease
CC characterized by malignant lesions arising from the inner wall of the
CC large intestine (the colon) and the rectum. Genetic alterations are
CC often associated with progression from premalignant lesion (adenoma) to
CC invasive adenocarcinoma. Risk factors for cancer of the colon and
CC rectum include colon polyps, long-standing ulcerative colitis, and
CC genetic family history. Note=The gene represented in this entry may be
CC involved in disease pathogenesis.
CC -!- DISEASE: Note=Genetic variations in AKT1 may play a role in
CC susceptibility to ovarian cancer.
CC -!- DISEASE: Proteus syndrome (PROTEUSS) [MIM:176920]: A highly variable,
CC severe disorder of asymmetric and disproportionate overgrowth of body
CC parts, connective tissue nevi, epidermal nevi, dysregulated adipose
CC tissue, and vascular malformations. Many features of Proteus syndrome
CC overlap with other overgrowth syndromes. {ECO:0000269|PubMed:18954143,
CC ECO:0000269|PubMed:21793738}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Cowden syndrome 6 (CWS6) [MIM:615109]: A form of Cowden
CC syndrome, a hamartomatous polyposis syndrome with age-related
CC penetrance. Cowden syndrome is characterized by hamartomatous lesions
CC affecting derivatives of ectodermal, mesodermal and endodermal layers,
CC macrocephaly, facial trichilemmomas (benign tumors of the hair follicle
CC infundibulum), acral keratoses, papillomatous papules, and elevated
CC risk for development of several types of malignancy, particularly
CC breast carcinoma in women and thyroid carcinoma in both men and women.
CC Colon cancer and renal cell carcinoma have also been reported.
CC Hamartomas can be found in virtually every organ, but most commonly in
CC the skin, gastrointestinal tract, breast and thyroid.
CC {ECO:0000269|PubMed:23246288}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. RAC subfamily. {ECO:0000305}.
CC -!- CAUTION: PUBMED:19940129 has been retracted because the same data were
CC used to represent different experimental conditions.
CC {ECO:0000305|PubMed:19940129, ECO:0000305|PubMed:27825096}.
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}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/AKT1ID355ch14q32.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
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DR EMBL; M63167; AAA36539.1; -; mRNA.
DR EMBL; AF283830; AAL55732.1; -; Genomic_DNA.
DR EMBL; AF283819; AAL55732.1; JOINED; Genomic_DNA.
DR EMBL; AF283820; AAL55732.1; JOINED; Genomic_DNA.
DR EMBL; AF283821; AAL55732.1; JOINED; Genomic_DNA.
DR EMBL; AF283822; AAL55732.1; JOINED; Genomic_DNA.
DR EMBL; AF283823; AAL55732.1; JOINED; Genomic_DNA.
DR EMBL; AF283824; AAL55732.1; JOINED; Genomic_DNA.
DR EMBL; AF283825; AAL55732.1; JOINED; Genomic_DNA.
DR EMBL; AF283826; AAL55732.1; JOINED; Genomic_DNA.
DR EMBL; AF283827; AAL55732.1; JOINED; Genomic_DNA.
DR EMBL; AF283828; AAL55732.1; JOINED; Genomic_DNA.
DR EMBL; AF283829; AAL55732.1; JOINED; Genomic_DNA.
DR EMBL; AK299310; BAH12997.1; -; mRNA.
DR EMBL; AK314256; BAG36922.1; -; mRNA.
DR EMBL; AB451242; BAG70056.1; -; mRNA.
DR EMBL; AB451367; BAG70181.1; -; mRNA.
DR EMBL; AL583722; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590327; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000479; AAH00479.1; -; mRNA.
DR EMBL; BC084538; AAH84538.1; -; mRNA.
DR EMBL; X61037; CAA43372.1; -; mRNA.
DR CCDS; CCDS9994.1; -. [P31749-1]
DR PIR; A39360; A39360.
DR RefSeq; NP_001014431.1; NM_001014431.1. [P31749-1]
DR RefSeq; NP_001014432.1; NM_001014432.1. [P31749-1]
DR RefSeq; NP_005154.2; NM_005163.2. [P31749-1]
DR RefSeq; XP_005267458.1; XM_005267401.1.
DR PDB; 1H10; X-ray; 1.40 A; A=1-123.
DR PDB; 1UNP; X-ray; 1.65 A; A=1-121.
DR PDB; 1UNQ; X-ray; 0.98 A; A=1-123.
DR PDB; 1UNR; X-ray; 1.25 A; A=1-123.
DR PDB; 2UVM; X-ray; 1.94 A; A=1-123.
DR PDB; 2UZR; X-ray; 1.94 A; A=1-123.
DR PDB; 2UZS; X-ray; 2.46 A; A=1-123.
DR PDB; 3CQU; X-ray; 2.20 A; A=144-480.
DR PDB; 3CQW; X-ray; 2.00 A; A=144-480.
DR PDB; 3MV5; X-ray; 2.47 A; A=144-480.
DR PDB; 3MVH; X-ray; 2.01 A; A=144-480.
DR PDB; 3O96; X-ray; 2.70 A; A=2-443.
DR PDB; 3OCB; X-ray; 2.70 A; A/B=144-480.
DR PDB; 3OW4; X-ray; 2.60 A; A/B=144-480.
DR PDB; 3QKK; X-ray; 2.30 A; A=144-480.
DR PDB; 3QKL; X-ray; 1.90 A; A=144-480.
DR PDB; 3QKM; X-ray; 2.20 A; A=144-480.
DR PDB; 4EJN; X-ray; 2.19 A; A=2-446.
DR PDB; 4EKK; X-ray; 2.80 A; A/B=144-480.
DR PDB; 4EKL; X-ray; 2.00 A; A=144-480.
DR PDB; 4GV1; X-ray; 1.49 A; A=144-480.
DR PDB; 5KCV; X-ray; 2.70 A; A=2-446.
DR PDB; 6BUU; X-ray; 2.40 A; A/B=144-480.
DR PDB; 6CCY; X-ray; 2.18 A; A=144-466.
DR PDB; 6HHF; X-ray; 2.90 A; A=2-446.
DR PDB; 6HHG; X-ray; 2.30 A; A=2-446.
DR PDB; 6HHH; X-ray; 2.70 A; A=2-446.
DR PDB; 6HHI; X-ray; 2.70 A; A=2-446.
DR PDB; 6HHJ; X-ray; 2.30 A; A=2-446.
DR PDB; 6NPZ; X-ray; 2.12 A; A/B=123-480, A/B=144-480.
DR PDB; 6S9W; X-ray; 2.30 A; A=2-446.
DR PDB; 6S9X; X-ray; 2.60 A; A=2-446.
DR PDB; 7APJ; X-ray; 2.05 A; A=1-119, A=136-445.
DR PDB; 7NH4; X-ray; 2.30 A; A=2-446.
DR PDB; 7NH5; X-ray; 1.90 A; A=2-446.
DR PDBsum; 1H10; -.
DR PDBsum; 1UNP; -.
DR PDBsum; 1UNQ; -.
DR PDBsum; 1UNR; -.
DR PDBsum; 2UVM; -.
DR PDBsum; 2UZR; -.
DR PDBsum; 2UZS; -.
DR PDBsum; 3CQU; -.
DR PDBsum; 3CQW; -.
DR PDBsum; 3MV5; -.
DR PDBsum; 3MVH; -.
DR PDBsum; 3O96; -.
DR PDBsum; 3OCB; -.
DR PDBsum; 3OW4; -.
DR PDBsum; 3QKK; -.
DR PDBsum; 3QKL; -.
DR PDBsum; 3QKM; -.
DR PDBsum; 4EJN; -.
DR PDBsum; 4EKK; -.
DR PDBsum; 4EKL; -.
DR PDBsum; 4GV1; -.
DR PDBsum; 5KCV; -.
DR PDBsum; 6BUU; -.
DR PDBsum; 6CCY; -.
DR PDBsum; 6HHF; -.
DR PDBsum; 6HHG; -.
DR PDBsum; 6HHH; -.
DR PDBsum; 6HHI; -.
DR PDBsum; 6HHJ; -.
DR PDBsum; 6NPZ; -.
DR PDBsum; 6S9W; -.
DR PDBsum; 6S9X; -.
DR PDBsum; 7APJ; -.
DR PDBsum; 7NH4; -.
DR PDBsum; 7NH5; -.
DR AlphaFoldDB; P31749; -.
DR SMR; P31749; -.
DR BioGRID; 106710; 468.
DR CORUM; P31749; -.
DR DIP; DIP-24269N; -.
DR ELM; P31749; -.
DR IntAct; P31749; 208.
DR MINT; P31749; -.
DR STRING; 9606.ENSP00000451828; -.
DR BindingDB; P31749; -.
DR ChEMBL; CHEMBL4282; -.
DR DrugBank; DB07585; 5-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine.
DR DrugBank; DB05971; Archexin.
DR DrugBank; DB01169; Arsenic trioxide.
DR DrugBank; DB00171; ATP.
DR DrugBank; DB06486; Enzastaurin.
DR DrugBank; DB01645; Genistein.
DR DrugBank; DB01863; Inositol 1,3,4,5-Tetrakisphosphate.
DR DrugBank; DB07584; N-[2-(5-methyl-4H-1,2,4-triazol-3-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine.
DR DrugBank; DB06641; Perifosine.
DR DrugBank; DB02709; Resveratrol.
DR DrugCentral; P31749; -.
DR GuidetoPHARMACOLOGY; 1479; -.
DR TCDB; 8.A.104.1.10; the 5'-amp-activated protein kinase (ampk) family.
DR GlyGen; P31749; 6 sites, 1 O-linked glycan (6 sites).
DR iPTMnet; P31749; -.
DR MetOSite; P31749; -.
DR PhosphoSitePlus; P31749; -.
DR BioMuta; AKT1; -.
DR DMDM; 60391226; -.
DR CPTAC; CPTAC-783; -.
DR CPTAC; CPTAC-784; -.
DR EPD; P31749; -.
DR jPOST; P31749; -.
DR MassIVE; P31749; -.
DR MaxQB; P31749; -.
DR PaxDb; P31749; -.
DR PeptideAtlas; P31749; -.
DR PRIDE; P31749; -.
DR ProteomicsDB; 54800; -. [P31749-1]
DR ProteomicsDB; 6712; -.
DR ABCD; P31749; 12 sequenced antibodies.
DR Antibodypedia; 135; 5359 antibodies from 56 providers.
DR CPTC; P31749; 6 antibodies.
DR DNASU; 207; -.
DR Ensembl; ENST00000349310.7; ENSP00000270202.4; ENSG00000142208.18. [P31749-1]
DR Ensembl; ENST00000402615.6; ENSP00000385326.2; ENSG00000142208.18. [P31749-1]
DR Ensembl; ENST00000407796.7; ENSP00000384293.2; ENSG00000142208.18. [P31749-1]
DR Ensembl; ENST00000554581.5; ENSP00000451828.1; ENSG00000142208.18. [P31749-1]
DR Ensembl; ENST00000554848.5; ENSP00000451166.1; ENSG00000142208.18. [P31749-1]
DR Ensembl; ENST00000555528.5; ENSP00000450688.1; ENSG00000142208.18. [P31749-1]
DR Ensembl; ENST00000649815.2; ENSP00000497822.1; ENSG00000142208.18. [P31749-1]
DR Ensembl; ENST00000683722.1; ENSP00000507879.1; ENSG00000142208.18. [P31749-1]
DR GeneID; 207; -.
DR KEGG; hsa:207; -.
DR MANE-Select; ENST00000649815.2; ENSP00000497822.1; NM_001382430.1; NP_001369359.1.
DR UCSC; uc001ypk.4; human. [P31749-1]
DR CTD; 207; -.
DR DisGeNET; 207; -.
DR GeneCards; AKT1; -.
DR GeneReviews; AKT1; -.
DR HGNC; HGNC:391; AKT1.
DR HPA; ENSG00000142208; Low tissue specificity.
DR MalaCards; AKT1; -.
DR MIM; 114480; phenotype.
DR MIM; 114500; phenotype.
DR MIM; 164730; gene.
DR MIM; 176920; phenotype.
DR MIM; 615109; phenotype.
DR neXtProt; NX_P31749; -.
DR OpenTargets; ENSG00000142208; -.
DR Orphanet; 201; Cowden syndrome.
DR Orphanet; 2495; Meningioma.
DR Orphanet; 744; Proteus syndrome.
DR PharmGKB; PA24684; -.
DR VEuPathDB; HostDB:ENSG00000142208; -.
DR eggNOG; KOG0690; Eukaryota.
DR GeneTree; ENSGT00940000158752; -.
DR HOGENOM; CLU_000288_11_0_1; -.
DR InParanoid; P31749; -.
DR OMA; MQHKFFT; -.
DR PhylomeDB; P31749; -.
DR TreeFam; TF102004; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; P31749; -.
DR Reactome; R-HSA-111447; Activation of BAD and translocation to mitochondria.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-1358803; Downregulation of ERBB2:ERBB3 signaling.
DR Reactome; R-HSA-1445148; Translocation of SLC2A4 (GLUT4) to the plasma membrane.
DR Reactome; R-HSA-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
DR Reactome; R-HSA-165159; MTOR signalling.
DR Reactome; R-HSA-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-HSA-198693; AKT phosphorylates targets in the nucleus.
DR Reactome; R-HSA-199418; Negative regulation of the PI3K/AKT network.
DR Reactome; R-HSA-203615; eNOS activation.
DR Reactome; R-HSA-211163; AKT-mediated inactivation of FOXO1A.
DR Reactome; R-HSA-354192; Integrin signaling.
DR Reactome; R-HSA-3769402; Deactivation of the beta-catenin transactivating complex.
DR Reactome; R-HSA-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-HSA-389513; CTLA4 inhibitory signaling.
DR Reactome; R-HSA-392451; G beta:gamma signalling through PI3Kgamma.
DR Reactome; R-HSA-450385; Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
DR Reactome; R-HSA-450604; KSRP (KHSRP) binds and destabilizes mRNA.
DR Reactome; R-HSA-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer.
DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-HSA-6804757; Regulation of TP53 Degradation.
DR Reactome; R-HSA-6804758; Regulation of TP53 Activity through Acetylation.
DR Reactome; R-HSA-6804759; Regulation of TP53 Activity through Association with Co-factors.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-HSA-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-HSA-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR Reactome; R-HSA-8849469; PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR Reactome; R-HSA-8941332; RUNX2 regulates genes involved in cell migration.
DR Reactome; R-HSA-8948751; Regulation of PTEN stability and activity.
DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-HSA-9604323; Negative regulation of NOTCH4 signaling.
DR Reactome; R-HSA-9607240; FLT3 Signaling.
DR Reactome; R-HSA-9614399; Regulation of localization of FOXO transcription factors.
DR Reactome; R-HSA-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR Reactome; R-HSA-9755511; KEAP1-NFE2L2 pathway.
DR Reactome; R-HSA-9755779; SARS-CoV-2 targets host intracellular signalling and regulatory pathways.
DR SABIO-RK; P31749; -.
DR SignaLink; P31749; -.
DR SIGNOR; P31749; -.
DR BioGRID-ORCS; 207; 51 hits in 1123 CRISPR screens.
DR ChiTaRS; AKT1; human.
DR EvolutionaryTrace; P31749; -.
DR GeneWiki; AKT1; -.
DR GenomeRNAi; 207; -.
DR Pharos; P31749; Tchem.
DR PRO; PR:P31749; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P31749; protein.
DR Bgee; ENSG00000142208; Expressed in stromal cell of endometrium and 187 other tissues.
DR ExpressionAtlas; P31749; baseline and differential.
DR Genevisible; P31749; HS.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0036064; C:ciliary basal body; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; NAS:BHF-UCL.
DR GO; GO:0030027; C:lamellipodium; NAS:BHF-UCL.
DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0098794; C:postsynapse; IEA:GOC.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0005819; C:spindle; IEA:Ensembl.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0071889; F:14-3-3 protein binding; IPI:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISS:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016301; F:kinase activity; IDA:MGI.
DR GO; GO:0030235; F:nitric-oxide synthase regulator activity; IMP:BHF-UCL.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB.
DR GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0099104; F:potassium channel activator activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
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; IDA:MGI.
DR GO; GO:0006924; P:activation-induced cell death of T cells; IMP:MGI.
DR GO; GO:0043276; P:anoikis; NAS:ParkinsonsUK-UCL.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; IEA:Ensembl.
DR GO; GO:0048266; P:behavioral response to pain; IEA:Ensembl.
DR GO; GO:0008643; P:carbohydrate transport; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; TAS:UniProtKB.
DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; IMP:BHF-UCL.
DR GO; GO:0008283; P:cell population proliferation; TAS:UniProtKB.
DR GO; GO:0071276; P:cellular response to cadmium ion; IMP:CAFA.
DR GO; GO:0036294; P:cellular response to decreased oxygen levels; IEA:Ensembl.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IEA:Ensembl.
DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; IEA:Ensembl.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IMP:BHF-UCL.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IMP:UniProtKB.
DR GO; GO:0140052; P:cellular response to oxidised low-density lipoprotein particle stimulus; IMP:BHF-UCL.
DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; IEA:Ensembl.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:CAFA.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IMP:UniProtKB.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IEA:Ensembl.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0072655; P:establishment of protein localization to mitochondrion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0060079; P:excitatory postsynaptic potential; NAS:ParkinsonsUK-UCL.
DR GO; GO:0097194; P:execution phase of apoptosis; IEA:Ensembl.
DR GO; GO:0010761; P:fibroblast migration; NAS:BHF-UCL.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0007281; P:germ cell development; IEA:Ensembl.
DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0005978; P:glycogen biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0060709; P:glycogen cell differentiation involved in embryonic placenta development; IEA:Ensembl.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IMP:CAFA.
DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0035655; P:interleukin-18-mediated signaling pathway; IDA:BHF-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:MGI.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IEA:Ensembl.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0072656; P:maintenance of protein location in mitochondrion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0060644; P:mammary gland epithelial cell differentiation; TAS:UniProtKB.
DR GO; GO:0001893; P:maternal placenta development; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0010507; P:negative regulation of autophagy; IMP:BHF-UCL.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IMP:BHF-UCL.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; TAS:BHF-UCL.
DR GO; GO:0031999; P:negative regulation of fatty acid beta-oxidation; IMP:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:1903038; P:negative regulation of leukocyte cell-cell adhesion; IMP:BHF-UCL.
DR GO; GO:0010748; P:negative regulation of long-chain fatty acid import across plasma membrane; IMP:BHF-UCL.
DR GO; GO:2000402; P:negative regulation of lymphocyte migration; IMP:BHF-UCL.
DR GO; GO:0016242; P:negative regulation of macroautophagy; NAS:ParkinsonsUK-UCL.
DR GO; GO:1901215; P:negative regulation of neuron death; NAS:ParkinsonsUK-UCL.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; TAS:Reactome.
DR GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; NAS:BHF-UCL.
DR GO; GO:0032091; P:negative regulation of protein binding; IMP:ARUK-UCL.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IMP:BHF-UCL.
DR GO; GO:0100002; P:negative regulation of protein kinase activity by protein phosphorylation; TAS:ParkinsonsUK-UCL.
DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; TAS:ARUK-UCL.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IMP:ARUK-UCL.
DR GO; GO:0045861; P:negative regulation of proteolysis; IMP:BHF-UCL.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISS:UniProtKB.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; IMP:CAFA.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; TAS:ProtInc.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB.
DR GO; GO:0032287; P:peripheral nervous system myelin maintenance; IEA:Ensembl.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IMP:CAFA.
DR GO; GO:0016310; P:phosphorylation; IDA:UniProtKB.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:DFLAT.
DR GO; GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; IMP:BHF-UCL.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0032079; P:positive regulation of endodeoxyribonuclease activity; IDA:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:BHF-UCL.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IMP:BHF-UCL.
DR GO; GO:0010763; P:positive regulation of fibroblast migration; IEA:Ensembl.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IMP:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0046326; P:positive regulation of glucose import; IMP:BHF-UCL.
DR GO; GO:0010907; P:positive regulation of glucose metabolic process; IMP:BHF-UCL.
DR GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; IMP:BHF-UCL.
DR GO; GO:1903721; P:positive regulation of I-kappaB phosphorylation; IMP:CAFA.
DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; IMP:UniProtKB.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; IMP:BHF-UCL.
DR GO; GO:0046622; P:positive regulation of organ growth; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; IEA:Ensembl.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IMP:UniProtKB.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IMP:BHF-UCL.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; ISS:BHF-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:BHF-UCL.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:CAFA.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; TAS:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; IMP:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IEA:Ensembl.
DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0005979; P:regulation of glycogen biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0043488; P:regulation of mRNA stability; TAS:Reactome.
DR GO; GO:0031641; P:regulation of myelination; IEA:Ensembl.
DR GO; GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR GO; GO:2000074; P:regulation of type B pancreatic cell development; TAS:Reactome.
DR GO; GO:0034405; P:response to fluid shear stress; IMP:BHF-UCL.
DR GO; GO:0032094; P:response to food; IEA:Ensembl.
DR GO; GO:0070848; P:response to growth factor; IDA:UniProtKB.
DR GO; GO:0060416; P:response to growth hormone; ISS:AgBase.
DR GO; GO:0009408; P:response to heat; TAS:ProtInc.
DR GO; GO:1990418; P:response to insulin-like growth factor stimulus; ISS:AgBase.
DR GO; GO:0006979; P:response to oxidative stress; ISS:ParkinsonsUK-UCL.
DR GO; GO:0070141; P:response to UV-A; IDA:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; TAS:UniProtKB.
DR GO; GO:0003376; P:sphingosine-1-phosphate receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0051146; P:striated muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome.
DR GO; GO:0031929; P:TOR signaling; NAS:ParkinsonsUK-UCL.
DR CDD; cd01241; PH_PKB; 1.
DR CDD; cd05594; STKc_PKB_alpha; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR IDEAL; IID00412; -.
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 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding;
KW Carbohydrate metabolism; Cell membrane; Cytoplasm; Developmental protein;
KW Disease variant; Disulfide bond; Glucose metabolism; Glycogen biosynthesis;
KW Glycogen metabolism; Glycoprotein; Isopeptide bond; Kinase; Membrane;
KW Neurogenesis; Nucleotide-binding; Nucleus; Phosphoprotein; Proto-oncogene;
KW Reference proteome; Serine/threonine-protein kinase; Sugar transport;
KW Transferase; Translation regulation; Transport; Ubl conjugation.
FT CHAIN 1..480
FT /note="RAC-alpha serine/threonine-protein kinase"
FT /id="PRO_0000085605"
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 113..138
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:0000269|PubMed:12176338,
FT ECO:0000269|PubMed:12964941"
FT BINDING 23..25
FT /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate"
FT /ligand_id="ChEBI:CHEBI:57895"
FT /evidence="ECO:0000269|PubMed:12176338,
FT ECO:0000269|PubMed:12964941"
FT BINDING 53
FT /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate"
FT /ligand_id="ChEBI:CHEBI:57895"
FT /evidence="ECO:0000269|PubMed:12176338,
FT ECO:0000269|PubMed:12964941"
FT BINDING 86
FT /ligand="1D-myo-inositol 1,3,4,5-tetrakisphosphate"
FT /ligand_id="ChEBI:CHEBI:57895"
FT /evidence="ECO:0000269|PubMed:12176338,
FT ECO:0000269|PubMed:12964941"
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 /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 462
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250|UniProtKB:P31750"
FT MOD_RES 14
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21775285"
FT MOD_RES 20
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21775285"
FT MOD_RES 124
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 126
FT /note="Phosphoserine; alternate"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 129
FT /note="Phosphoserine; alternate"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
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:15718470,
FT ECO:0000269|PubMed:18456494, ECO:0000269|PubMed:20333297,
FT ECO:0000269|PubMed:20481595, ECO:0000269|PubMed:21464307,
FT ECO:0000269|PubMed:8978681, ECO:0000269|PubMed:9512493"
FT MOD_RES 448
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 450
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 473
FT /note="Phosphoserine; by IKKE, MTOR and TBK1; alternate"
FT /evidence="ECO:0000269|PubMed:14761976,
FT ECO:0000269|PubMed:15047712, ECO:0000269|PubMed:15718470,
FT ECO:0000269|PubMed:16266983, ECO:0000269|PubMed:17013611,
FT ECO:0000269|PubMed:20333297, ECO:0000269|PubMed:20978158,
FT ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:23799035,
FT ECO:0000269|PubMed:8978681, ECO:0000269|PubMed:9736715"
FT MOD_RES 474
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12149249"
FT CARBOHYD 126
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000269|PubMed:22629392"
FT CARBOHYD 129
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000269|PubMed:22629392"
FT CARBOHYD 305
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000269|PubMed:22629392"
FT CARBOHYD 312
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000269|PubMed:22629392"
FT CARBOHYD 473
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P31750"
FT DISULFID 60..77
FT /evidence="ECO:0000269|PubMed:20886116"
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:0000269|PubMed:22410793"
FT VAR_SEQ 1..62
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056180"
FT VARIANT 17
FT /note="E -> K (in PROTEUSS and breast cancer; also detected
FT in colorectal and ovarian cancer; somatic mutation; results
FT in increased phosphorylation at T-308 and higher basal
FT ubiquitination; the mutant protein is more efficiently
FT recruited to the plasma membrane; alters
FT phosphatidylinositiol phosphates lipid specificity of the
FT AKT1 PH domain; dbSNP:rs121434592)"
FT /evidence="ECO:0000269|PubMed:17611497,
FT ECO:0000269|PubMed:18954143, ECO:0000269|PubMed:19713527,
FT ECO:0000269|PubMed:21793738"
FT /id="VAR_055422"
FT VARIANT 25
FT /note="R -> C (in CWS6; dbSNP:rs397514644)"
FT /evidence="ECO:0000269|PubMed:23246288"
FT /id="VAR_069791"
FT VARIANT 167
FT /note="V -> A (in dbSNP:rs11555433)"
FT /id="VAR_051617"
FT VARIANT 435
FT /note="T -> P (in CWS6; dbSNP:rs397514645)"
FT /evidence="ECO:0000269|PubMed:23246288"
FT /id="VAR_069792"
FT MUTAGEN 8
FT /note="K->R: Substantial reduction of ubiquitination,
FT phosphorylation at T-308 and S-473, AKT activation as well
FT as IGF1-induced membrane recruitment. Decrease in
FT ubiquitination and phosphorylation at T-308 as well as
FT impaired association with the membrane; when associated
FT with K-17."
FT /evidence="ECO:0000269|PubMed:19713527"
FT MUTAGEN 14
FT /note="K->A: Impairs interaction with PtdIns(3,4,5)P3 and
FT PtdIns(3,4)P2."
FT /evidence="ECO:0000269|PubMed:12176338,
FT ECO:0000269|PubMed:19713527, ECO:0000269|PubMed:21775285"
FT MUTAGEN 14
FT /note="K->Q: Substantial reduction of phosphorylation at T-
FT 308 and S-473, loss of AKT activation, and loss of binding
FT to PIP3 as well as IGF1-induced membrane recruitment."
FT /evidence="ECO:0000269|PubMed:12176338,
FT ECO:0000269|PubMed:19713527, ECO:0000269|PubMed:21775285"
FT MUTAGEN 14
FT /note="K->R: Substantial reduction of ubiquitination,
FT phosphorylation at T-308 and S-473, AKT activation, loss of
FT binding to PIP3 as well as IGF1-induced membrane
FT recruitment."
FT /evidence="ECO:0000269|PubMed:12176338,
FT ECO:0000269|PubMed:19713527, ECO:0000269|PubMed:21775285"
FT MUTAGEN 17
FT /note="E->K: No effect on membrane localization. Loss of
FT membrane localization; when associated with Q-20."
FT /evidence="ECO:0000269|PubMed:21775285"
FT MUTAGEN 20
FT /note="K->Q: Substantial reduction of phosphorylation at T-
FT 308 and S-473, reduced AKT activation, and reduced binding
FT to PIP3 as well as IGF1-induced membrane recruitment. Loss
FT of membrane localization; when associated with K-17."
FT /evidence="ECO:0000269|PubMed:21775285"
FT MUTAGEN 20
FT /note="K->R: Slight increase of phosphorylation at T-308
FT and S-473."
FT /evidence="ECO:0000269|PubMed:21775285"
FT MUTAGEN 25
FT /note="R->A,C: Impairs interaction with PtdIns(3,4,5)P3 and
FT PtdIns(3,4)P2."
FT /evidence="ECO:0000269|PubMed:12176338"
FT MUTAGEN 86
FT /note="R->A: Impairs interaction with PtdIns(3,4,5)P3 and
FT PtdIns(3,4)P2."
FT /evidence="ECO:0000269|PubMed:12176338"
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->M: Abolished serine/threonine-protein kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:33594058"
FT MUTAGEN 305
FT /note="T->A: Reduces O-GlcNAc levels; Reduces O-GlcNAc
FT levels even more; when associated with A-312."
FT /evidence="ECO:0000269|PubMed:22629392"
FT MUTAGEN 305
FT /note="T->Y: Abolishes phosphorylation at Thr-308."
FT /evidence="ECO:0000269|PubMed:22629392"
FT MUTAGEN 308
FT /note="T->D: 5-fold activation and 18-fold activation; when
FT associated with D-473."
FT /evidence="ECO:0000269|PubMed:12244301,
FT ECO:0000269|PubMed:8978681"
FT MUTAGEN 312
FT /note="T->A: Reduces O-GlcNAc levels; Reduces O-GlcNAc
FT levels even more; when associated with A-305."
FT /evidence="ECO:0000269|PubMed:22629392"
FT MUTAGEN 312
FT /note="T->Y: Abolishes phosphorylation at Thr-308."
FT /evidence="ECO:0000269|PubMed:22629392"
FT MUTAGEN 473
FT /note="S->D: 7-fold activation and 25-fold activation; when
FT associated with D-308."
FT /evidence="ECO:0000269|PubMed:12244301,
FT ECO:0000269|PubMed:8978681"
FT MUTAGEN 474
FT /note="Y->F: 55% inhibition of activation."
FT /evidence="ECO:0000269|PubMed:12149249"
FT CONFLICT 173..174
FT /note="GR -> A (in Ref. 7; CAA43372)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="L -> Q (in Ref. 7; CAA43372)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="A -> R (in Ref. 7; CAA43372)"
FT /evidence="ECO:0000305"
FT CONFLICT 246
FT /note="S -> A (in Ref. 7; CAA43372)"
FT /evidence="ECO:0000305"
FT CONFLICT 409
FT /note="A -> T (in Ref. 7; CAA43372)"
FT /evidence="ECO:0000305"
FT CONFLICT 476
FT /note="A -> P (in Ref. 7; CAA43372)"
FT /evidence="ECO:0000305"
FT CONFLICT 478
FT /note="G -> A (in Ref. 7; CAA43372)"
FT /evidence="ECO:0000305"
FT CONFLICT 478
FT /note="G -> S (in Ref. 1; AAA36539, 2; AAL55732, 3;
FT BAG36922 and 4; BAG70056/BAG70181)"
FT /evidence="ECO:0000305"
FT HELIX 2..4
FT /evidence="ECO:0007829|PDB:1UNQ"
FT STRAND 6..15
FT /evidence="ECO:0007829|PDB:1UNQ"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:1UNQ"
FT STRAND 22..30
FT /evidence="ECO:0007829|PDB:1UNQ"
FT STRAND 33..40
FT /evidence="ECO:0007829|PDB:1UNQ"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:7APJ"
FT HELIX 45..48
FT /evidence="ECO:0007829|PDB:1UNQ"
FT STRAND 52..56
FT /evidence="ECO:0007829|PDB:1UNQ"
FT STRAND 61..65
FT /evidence="ECO:0007829|PDB:1UNQ"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:1UNQ"
FT STRAND 72..79
FT /evidence="ECO:0007829|PDB:1UNQ"
FT STRAND 82..89
FT /evidence="ECO:0007829|PDB:1UNQ"
FT HELIX 93..115
FT /evidence="ECO:0007829|PDB:1UNQ"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:4GV1"
FT STRAND 150..158
FT /evidence="ECO:0007829|PDB:4GV1"
FT STRAND 160..169
FT /evidence="ECO:0007829|PDB:4GV1"
FT TURN 170..172
FT /evidence="ECO:0007829|PDB:4GV1"
FT STRAND 175..182
FT /evidence="ECO:0007829|PDB:4GV1"
FT HELIX 183..188
FT /evidence="ECO:0007829|PDB:4GV1"
FT HELIX 192..204
FT /evidence="ECO:0007829|PDB:4GV1"
FT STRAND 213..218
FT /evidence="ECO:0007829|PDB:4GV1"
FT STRAND 220..227
FT /evidence="ECO:0007829|PDB:4GV1"
FT HELIX 235..242
FT /evidence="ECO:0007829|PDB:4GV1"
FT HELIX 247..268
FT /evidence="ECO:0007829|PDB:4GV1"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:4GV1"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:4GV1"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:4EJN"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:4GV1"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:3MVH"
FT HELIX 313..315
FT /evidence="ECO:0007829|PDB:4GV1"
FT HELIX 318..322
FT /evidence="ECO:0007829|PDB:4GV1"
FT HELIX 330..344
FT /evidence="ECO:0007829|PDB:4GV1"
FT HELIX 354..363
FT /evidence="ECO:0007829|PDB:4GV1"
FT HELIX 374..383
FT /evidence="ECO:0007829|PDB:4GV1"
FT HELIX 388..390
FT /evidence="ECO:0007829|PDB:4GV1"
FT TURN 396..398
FT /evidence="ECO:0007829|PDB:4GV1"
FT HELIX 399..403
FT /evidence="ECO:0007829|PDB:4GV1"
FT HELIX 406..408
FT /evidence="ECO:0007829|PDB:4GV1"
FT HELIX 413..417
FT /evidence="ECO:0007829|PDB:4GV1"
FT STRAND 430..433
FT /evidence="ECO:0007829|PDB:3MVH"
FT TURN 436..438
FT /evidence="ECO:0007829|PDB:7NH5"
FT HELIX 440..443
FT /evidence="ECO:0007829|PDB:4GV1"
FT STRAND 464..466
FT /evidence="ECO:0007829|PDB:4GV1"
FT STRAND 473..475
FT /evidence="ECO:0007829|PDB:4GV1"
SQ SEQUENCE 480 AA; 55686 MW; 6EAFF4F8AD436714 CRC64;
MSDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVDQREA PLNNFSVAQC
QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWT TAIQTVADGL KKQEEEEMDF
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 SGLLKKDPKQ RLGGGSEDAK EIMQHRFFAG IVWQHVYEKK
LSPPFKPQVT SETDTRYFDE EFTAQMITIT PPDQDDSMEC VDSERRPHFP QFSYSASGTA
