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 27-MAR-2024, entry version 264. DE RecName: Full=RAC-alpha serine/threonine-protein kinase; DE EC=2.7.11.1 {ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:15861136, 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 FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-179. RX PubMed=12172553; DOI=10.1038/ncb839; RA Inoki K., Li Y., Zhu T., Wu J., Guan K.L.; RT "TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR RT signalling."; RL Nat. Cell Biol. 4:648-657(2002). RN [26] 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 [27] 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 [28] 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 [29] 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 [30] 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 [31] 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 [32] 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 [33] 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 [34] 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 [35] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=15861136; DOI=10.1038/sj.emboj.7600648; RA Cartlidge R.A., Knebel A., Peggie M., Alexandrov A., Phizicky E.M., RA Cohen P.; RT "The tRNA methylase METTL1 is phosphorylated and inactivated by PKB and RSK RT in vitro and in cells."; RL EMBO J. 24:1696-1705(2005). RN [36] 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 [37] 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 [38] 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 [39] 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 [40] 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 [41] 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 [42] 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 [43] 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 [44] 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 [45] 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 [46] 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 [47] 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 [48] 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 [49] 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 [50] 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 [51] 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 [52] 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 [53] 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 [54] 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 [55] 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 [56] 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 [57] 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 [58] 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 [59] 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 [60] 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 [61] 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 [62] 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 [63] 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 [64] 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 [65] 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 [66] 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 [67] 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 [68] 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 [69] 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 [70] 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 [71] 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 [72] 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 [73] 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 [74] 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 [75] 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 [76] 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 [77] 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 [78] 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 [79] 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 [80] 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 [81] RP FUNCTION. RX PubMed=31204173; DOI=10.1016/j.devcel.2019.05.022; RA Walia V., Cuenca A., Vetter M., Insinna C., Perera S., Lu Q., Ritt D.A., RA Semler E., Specht S., Stauffer J., Morrison D.K., Lorentzen E., RA Westlake C.J.; RT "Akt Regulates a Rab11-Effector Switch Required for Ciliogenesis."; RL Dev. Cell 50:229-246(2019). RN [82] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=31548394; DOI=10.1073/pnas.1904774116; RA Padi S.K.R., Singh N., Bearss J.J., Olive V., Song J.H., Cardo-Vila M., RA Kraft A.S., Okumura K.; RT "Phosphorylation of DEPDC5, a component of the GATOR1 complex, releases RT inhibition of mTORC1 and promotes tumor growth."; RL Proc. Natl. Acad. Sci. U.S.A. 116:20505-20510(2019). RN [83] 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 [84] 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 [85] 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 [86] 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 [87] 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 [88] {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 [89] {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 [90] {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 [91] {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 [92] {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 [93] 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 [94] 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 [95] 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 [96] 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:15861136, PubMed:15526160, CC PubMed:11882383, PubMed:21620960, PubMed:21432781, PubMed:31204173). CC This is mediated through serine and/or threonine phosphorylation of a CC range of downstream substrates (PubMed:15526160, PubMed:11882383, CC PubMed:21620960, PubMed:21432781, PubMed:31204173). Over 100 substrate CC candidates have been reported so far, but for most of them, no isoform CC specificity has been reported (PubMed:15526160, PubMed:11882383, CC PubMed:21620960, PubMed:21432781). AKT is responsible of the regulation CC of glucose uptake by mediating insulin-induced translocation of the CC SLC2A4/GLUT4 glucose transporter to the cell surface (By similarity). CC Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its CC phosphatase activity preventing dephosphorylation of the insulin CC receptor and the attenuation of insulin signaling (By similarity). CC Phosphorylation of TBC1D4 triggers the binding of this effector to CC inhibitory 14-3-3 proteins, which is required for insulin-stimulated CC glucose transport (PubMed:11994271). AKT regulates also the storage of CC glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' CC and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity CC (By similarity). Phosphorylation of GSK3 isoforms by AKT is also CC thought to be one mechanism by which cell proliferation is driven (By CC similarity). AKT regulates also cell survival via the phosphorylation CC of MAP3K5 (apoptosis signal-related kinase) (PubMed:11154276). CC Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated CC by oxidative stress and thereby prevents apoptosis (PubMed:11154276). CC AKT mediates insulin-stimulated protein synthesis by phosphorylating CC TSC2 at 'Ser-939' and 'Thr-1462', thereby activating the mTORC1 CC signaling pathway, and leading to both phosphorylation of 4E-BP1 and in CC activation of RPS6KB1 (PubMed:12150915, PubMed:12172553). Also CC regulates the mTORC1 signaling pathway by catalyzing phosphorylation of CC CASTOR1 and DEPDC5 (PubMed:31548394, PubMed:33594058). AKT is involved CC in the phosphorylation of members of the FOXO factors (Forkhead family CC of transcription factors), leading to binding of 14-3-3 proteins and CC cytoplasmic localization (PubMed:10358075). In particular, FOXO1 is CC phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319' (PubMed:10358075). CC FOXO3 and FOXO4 are phosphorylated on equivalent sites CC (PubMed:10358075). AKT has an important role in the regulation of NF- CC kappa-B-dependent gene transcription and positively regulates the CC activity of CREB1 (cyclic AMP (cAMP)-response element binding protein) CC (PubMed:9829964). The phosphorylation of CREB1 induces the binding of CC accessory proteins that are necessary for the transcription of pro- CC survival genes such as BCL2 and MCL1 (PubMed:9829964). AKT CC phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby CC potentially regulating ACLY activity and fatty acid synthesis (By CC similarity). Activates the 3B isoform of cyclic nucleotide CC phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting CC in reduced cyclic AMP levels and inhibition of lipolysis (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 (By similarity). CC AKT plays a role as key modulator of the AKT-mTOR signaling pathway CC controlling the tempo of the process of newborn neurons integration CC during adult neurogenesis, including correct neuron positioning, CC dendritic development and synapse formation (By similarity). Signals CC downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the CC effects of various growth factors such as platelet-derived growth CC factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like CC growth factor I (IGF-I) (PubMed:12176338, PubMed:12964941). AKT CC mediates the antiapoptotic effects of IGF-I (By similarity). Essential CC for the SPATA13-mediated regulation of cell migration and adhesion CC assembly and disassembly (PubMed:19934221). May be involved in the CC regulation of the placental development (By similarity). Phosphorylates CC STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: CC kinase activity, nuclear translocation, autophosphorylation and ability CC to phosphorylate FOXO3 (PubMed:17726016). Phosphorylates STK3/MST2 at CC 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase CC activity, 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). Acts as an inhibitor CC of tRNA methylation by mediating phosphorylation of the N-terminus of CC METTL1, thereby inhibiting METTL1 methyltransferase activity CC (PubMed:15861136). In response to LPAR1 receptor pathway activation, CC phosphorylates Rabin8/RAB3IP which alters its activity and CC phosphorylates WDR44 which induces WDR44 binding to Rab11, thereby CC switching Rab11 vesicular function from preciliary trafficking to CC endocytic recycling (PubMed:31204173). {ECO:0000250|UniProtKB:P31750, CC ECO:0000250|UniProtKB:P47196, ECO:0000269|PubMed:10358075, CC ECO:0000269|PubMed:10576742, ECO:0000269|PubMed:10926925, CC ECO:0000269|PubMed:11154276, ECO:0000269|PubMed:11994271, CC ECO:0000269|PubMed:12150915, ECO:0000269|PubMed:12172553, CC ECO:0000269|PubMed:12176338, ECO:0000269|PubMed:12964941, CC ECO:0000269|PubMed:15861136, ECO:0000269|PubMed:16139227, CC ECO:0000269|PubMed:16982699, ECO:0000269|PubMed:17726016, CC ECO:0000269|PubMed:18507042, ECO:0000269|PubMed:19592491, CC ECO:0000269|PubMed:19934221, ECO:0000269|PubMed:20086174, CC ECO:0000269|PubMed:20231902, ECO:0000269|PubMed:20471940, CC ECO:0000269|PubMed:20682768, ECO:0000269|PubMed:23431171, CC ECO:0000269|PubMed:31204173, ECO:0000269|PubMed:31548394, CC ECO:0000269|PubMed:32228865, ECO:0000269|PubMed:32322062, CC ECO:0000269|PubMed:33594058, ECO:0000269|PubMed:9829964, CC ECO:0000303|PubMed:11882383, ECO:0000303|PubMed:15526160, CC ECO:0000303|PubMed:21432781, 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:12172553, ECO:0000269|PubMed:15861136, CC ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:1718748, CC ECO:0000269|PubMed:1851997, ECO:0000269|PubMed:26440888, CC ECO:0000269|PubMed:31548394, ECO:0000269|PubMed:32322062, CC 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:12172553, CC ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:1718748, CC 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=5; 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; Q8WUY3: PRUNE2; NbExp=3; IntAct=EBI-296087, EBI-743880; 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). AIM2 acts as an CC inhibitor of AKT1 by inhibiting phosphorylation Ser-473: AIM2 acts both CC by inhibiting the activity of PRKDC/DNA-PK kinase and promoting CC dephosphorylation by PP2A phosphatase (By similarity). CC {ECO:0000250|UniProtKB:P31750, ECO:0000250|UniProtKB:Q01314, CC ECO:0000269|PubMed:12149249, 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:21329884, ECO:0000269|PubMed:21464307, CC ECO:0000269|PubMed:23799035, ECO:0000269|PubMed:28147277, CC ECO:0000269|PubMed:8978681, ECO:0000269|PubMed:9512493, CC 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="https://atlasgeneticsoncology.org/gene/355/AKT1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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; 7MYX; X-ray; 1.39 A; A=1-121. 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; 7MYX; -. DR PDBsum; 7NH4; -. DR PDBsum; 7NH5; -. DR AlphaFoldDB; P31749; -. DR SMR; P31749; -. DR BioGRID; 106710; 572. DR CORUM; P31749; -. DR DIP; DIP-24269N; -. DR ELM; P31749; -. DR IntAct; P31749; 214. 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 GlyCosmos; P31749; 6 sites, 1 glycan. 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-3162; -. DR CPTAC; CPTAC-3163; -. DR CPTAC; CPTAC-3164; -. DR CPTAC; CPTAC-3165; -. DR CPTAC; CPTAC-3166; -. DR CPTAC; CPTAC-3167; -. DR CPTAC; CPTAC-5758; -. DR CPTAC; CPTAC-5759; -. DR CPTAC; CPTAC-5805; -. DR CPTAC; CPTAC-5806; -. DR CPTAC; CPTAC-5807; -. DR CPTAC; CPTAC-5808; -. DR CPTAC; CPTAC-783; -. DR CPTAC; CPTAC-784; -. DR CPTAC; non-CPTAC-5328; -. DR CPTAC; non-CPTAC-5329; -. DR CPTAC; non-CPTAC-5332; -. DR CPTAC; non-CPTAC-5527; -. DR CPTAC; non-CPTAC-5528; -. DR CPTAC; non-CPTAC-5719; -. DR CPTAC; non-CPTAC-5720; -. DR EPD; P31749; -. DR jPOST; P31749; -. DR MassIVE; P31749; -. DR MaxQB; P31749; -. DR PaxDb; 9606-ENSP00000451828; -. DR PeptideAtlas; P31749; -. DR ProteomicsDB; 54800; -. [P31749-1] DR ProteomicsDB; 6712; -. DR Pumba; P31749; -. DR ABCD; P31749; 12 sequenced antibodies. DR Antibodypedia; 135; 6272 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 AGR; HGNC:391; -. 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; QDESMEM; -. DR OrthoDB; 3028764at2759; -. 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; 54 hits in 1212 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 189 other cell types or tissues. DR ExpressionAtlas; P31749; baseline and differential. DR GO; GO:0005938; C:cell cortex; NAS:BHF-UCL. 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:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0030027; C:lamellipodium; NAS:BHF-UCL. DR GO; GO:0016020; C:membrane; IDA:UniProt. 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; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl. DR GO; GO:0106310; F:protein serine kinase activity; IEA:Ensembl. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; ISS:BHF-UCL. 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:0007249; P:canonical NF-kappaB signal transduction; IMP:CAFA. 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; IDA:UniProtKB. 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; IDA:UniProtKB. 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; IEA:Ensembl. 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: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: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:0022605; P:mammalian oogenesis stage; IEA:Ensembl. 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:0160049; P:negative regulation of cGAS/STING signaling pathway; IDA:UniProt. DR GO; GO:1902018; P:negative regulation of cilium assembly; IDA:UniProtKB. 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: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:0150033; P:negative regulation of protein localization to lysosome; IDA:UniProtKB. 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:0006809; P:nitric oxide biosynthetic process; TAS:ProtInc. DR GO; GO:0038061; P:non-canonical NF-kappaB signal transduction; IMP:CAFA. 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:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:BHF-UCL. 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: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:0045893; P:positive regulation of DNA-templated transcription; IMP:CAFA. 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: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; IDA:UniProt. DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; IEA:Ensembl. DR GO; GO:1905552; P:positive regulation of protein localization to endoplasmic reticulum; IDA:UniProt. 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:1904263; P:positive regulation of TORC1 signaling; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. 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: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:0099175; P:regulation of postsynapse organization; IEA:Ensembl. 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:0110002; P:regulation of tRNA methylation; IDA:UniProt. 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 GO; GO:0019049; P:virus-mediated perturbation of host defense response; IDA:UniProt. DR CDD; cd01241; PH_PKB; 1. DR CDD; cd05594; STKc_PKB_alpha; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR24351:SF200; NON-SPECIFIC SERINE_THREONINE PROTEIN KINASE; 1. DR PANTHER; PTHR24351; RIBOSOMAL PROTEIN S6 KINASE; 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; SSF50729; PH domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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. DR Genevisible; P31749; HS. 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 FT T-308 and S-473, loss of AKT activation, and 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 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 FT T-308 and S-473, reduced AKT activation, and reduced FT binding to PIP3 as well as IGF1-induced membrane FT recruitment. Loss of membrane localization; when associated FT 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:12172553, FT 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 //