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RAC-alpha serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase B) (PKB) (Protein kinase B alpha) (PKB alpha) (Proto-oncogene c-Akt) (RAC-PK-alpha)

 AKT1_HUMAN              Reviewed;         480 AA.
P31749; B2RAM5; B7Z5R1; Q9BWB6;
01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
01-FEB-2005, sequence version 2.
30-AUG-2017, entry version 216.
RecName: Full=RAC-alpha serine/threonine-protein kinase;
EC=2.7.11.1;
AltName: Full=Protein kinase B;
Short=PKB;
AltName: Full=Protein kinase B alpha;
Short=PKB alpha;
AltName: Full=Proto-oncogene c-Akt;
AltName: Full=RAC-PK-alpha;
Name=AKT1; Synonyms=PKB, RAC;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CATALYTIC ACTIVITY.
PubMed=1851997; DOI=10.1073/pnas.88.10.4171;
Jones P.F., Jakubowicz T., Pitossi F.J., Maurer F., Hemmings B.A.;
"Molecular cloning and identification of a serine/threonine protein
kinase of the second-messenger subfamily.";
Proc. Natl. Acad. Sci. U.S.A. 88:4171-4175(1991).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=11508278; DOI=10.1007/s001250100577;
Matsubara A., Wasson J.C., Donelan S.S., Welling C.M., Glaser B.,
Permutt M.A.;
"Isolation and characterization of the human AKT1 gene, identification
of 13 single nucleotide polymorphisms (SNPs), and their lack of
association with Type II diabetes.";
Diabetologia 44:910-913(2001).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
TISSUE=Adrenal gland;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
PubMed=19054851; DOI=10.1038/nmeth.1273;
Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H.,
Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M.,
Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T.,
Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A.,
Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K.,
Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S.,
Isogai T., Imai J., Watanabe S., Nomura N.;
"Human protein factory for converting the transcriptome into an in
vitro-expressed proteome.";
Nat. Methods 5:1011-1017(2008).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=12508121; DOI=10.1038/nature01348;
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
Quetier F., Waterston R., Hood L., Weissenbach J.;
"The DNA sequence and analysis of human chromosome 14.";
Nature 421:601-607(2003).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Muscle, and Ovary;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 63-480 (ISOFORM 1), FUNCTION, CATALYTIC
ACTIVITY, AND TISSUE SPECIFICITY.
TISSUE=Foreskin;
PubMed=1718748; DOI=10.1111/j.1432-1033.1991.tb16305.x;
Coffer P.J., Woodgett J.R.;
"Molecular cloning and characterisation of a novel putative protein-
serine kinase related to the cAMP-dependent and protein kinase C
families.";
Eur. J. Biochem. 201:475-481(1991).
[8]
ERRATUM, AND SEQUENCE REVISION.
PubMed=1533586;
Coffer P.J., Woodgett J.R.;
Eur. J. Biochem. 205:1217-1218(1992).
[9]
FUNCTION IN PHOSPHORYLATION OF CREB1.
PubMed=9829964; DOI=10.1074/jbc.273.49.32377;
Du K., Montminy M.;
"CREB is a regulatory target for the protein kinase Akt/PKB.";
J. Biol. Chem. 273:32377-32379(1998).
[10]
ENZYME REGULATION, AND PHOSPHORYLATION AT SER-473.
PubMed=9736715; DOI=10.1073/pnas.95.19.11211;
Delcommenne M., Tan C., Gray V., Rue L., Woodgett J.R., Dedhar S.;
"Phosphoinositide-3-OH kinase-dependent regulation of glycogen
synthase kinase 3 and protein kinase B/AKT by the integrin-linked
kinase.";
Proc. Natl. Acad. Sci. U.S.A. 95:11211-11216(1998).
[11]
MUTAGENESIS OF THR-308 AND SER-473, AND PHOSPHORYLATION AT THR-308 AND
SER-473.
PubMed=8978681;
Alessi D.R., Andjelkovic M., Caudwell F.B., Cron P., Morrice N.,
Cohen P., Hemmings B.A.;
"Mechanism of activation of protein kinase B by insulin and IGF-1.";
EMBO J. 15:6541-6551(1996).
[12]
FUNCTION, ENZYME REGULATION, AND PHOSPHORYLATION AT THR-308 BY PDPK1.
PubMed=9512493; DOI=10.1042/bj3310299;
Walker K.S., Deak M., Paterson A., Hudson K., Cohen P., Alessi D.R.;
"Activation of protein kinase B beta and gamma isoforms by insulin in
vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro:
comparison with protein kinase B alpha.";
Biochem. J. 331:299-308(1998).
[13]
FUNCTION IN PHOSPHORYLATION OF FOXO1.
PubMed=10358075; DOI=10.1074/jbc.274.24.17179;
Rena G., Guo S., Cichy S.C., Unterman T.G., Cohen P.;
"Phosphorylation of the transcription factor forkhead family member
FKHR by protein kinase B.";
J. Biol. Chem. 274:17179-17183(1999).
[14]
FUNCTION IN PHOSPHORYLATION OF RAF1, AND INTERACTION WITH RAF1.
PubMed=10576742; DOI=10.1126/science.286.5445.1741;
Zimmermann S., Moelling K.;
"Phosphorylation and regulation of Raf by Akt (protein kinase B).";
Science 286:1741-1744(1999).
[15]
FUNCTION IN PHOSPHORYLATION OF BAD, AND INTERACTION WITH BAD AND PKN2.
PubMed=10926925; DOI=10.1074/jbc.M001753200;
Koh H., Lee K.H., Kim D., Kim S., Kim J.W., Chung J.;
"Inhibition of Akt and its anti-apoptotic activities by tumor necrosis
factor-induced protein kinase C-related kinase 2 (PRK2) cleavage.";
J. Biol. Chem. 275:34451-34458(2000).
[16]
INTERACTION WITH MTCP1; TCL1A AND TCL1B.
PubMed=10983986; DOI=10.1016/S1097-2765(00)00039-3;
Laine J., Kuenstle G., Obata T., Sha M., Noguchi M.;
"The protooncogene TCL1 is an Akt kinase coactivator.";
Mol. Cell 6:395-407(2000).
[17]
INTERACTION WITH TCL1A.
PubMed=10716693; DOI=10.1073/pnas.97.7.3028;
Pekarsky Y., Koval A., Hallas C., Bichi R., Tresini M., Malstrom S.,
Russo G., Tsichlis P., Croce C.M.;
"Tcl1 enhances Akt kinase activity and mediates its nuclear
translocation.";
Proc. Natl. Acad. Sci. U.S.A. 97:3028-3033(2000).
[18]
FUNCTION IN PHOSPHORYLATION OF MAP3K5, AND INTERACTION WITH MAP3K5.
PubMed=11154276; DOI=10.1128/MCB.21.3.893-901.2001;
Kim A.H., Khursigara G., Sun X., Franke T.F., Chao M.V.;
"Akt phosphorylates and negatively regulates apoptosis signal-
regulating kinase 1.";
Mol. Cell. Biol. 21:893-901(2001).
[19]
INTERACTION WITH THEM4, AND SUBCELLULAR LOCATION.
PubMed=11598301; DOI=10.1126/science.1062030;
Maira S.-M., Galetic I., Brazil D.P., Kaech S., Ingley E., Thelen M.,
Hemmings B.A.;
"Carboxyl-terminal modulator protein (CTMP), a negative regulator of
PKB/Akt and v-Akt at the plasma membrane.";
Science 294:374-380(2001).
[20]
FUNCTION IN PHOSPHORYLATION OF TBC1D4.
PubMed=11994271; DOI=10.1074/jbc.C200198200;
Kane S., Sano H., Liu S.C.H., Asara J.M., Lane W.S., Garner C.C.,
Lienhard G.E.;
"A method to identify serine kinase substrates. Akt phosphorylates a
novel adipocyte protein with a Rab GTPase-activating protein (GAP)
domain.";
J. Biol. Chem. 277:22115-22118(2002).
[21]
INTERACTION WITH CDKN1B, AND FUNCTION.
PubMed=12042314; DOI=10.1074/jbc.M203668200;
Fujita N., Sato S., Katayama K., Tsuruo T.;
"Akt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3
and cytoplasmic localization.";
J. Biol. Chem. 277:28706-28713(2002).
[22]
PHOSPHORYLATION AT TYR-474, AND MUTAGENESIS OF TYR-474.
PubMed=12149249; DOI=10.1074/jbc.M203387200;
Conus N.M., Hannan K.M., Cristiano B.E., Hemmings B.A., Pearson R.B.;
"Direct identification of tyrosine 474 as a regulatory phosphorylation
site for the Akt protein kinase.";
J. Biol. Chem. 277:38021-38028(2002).
[23]
FUNCTION IN PHOSPHORYLATION OF TSC2.
PubMed=12150915; DOI=10.1016/S1097-2765(02)00568-3;
Manning B.D., Tee A.R., Logsdon M.N., Blenis J., Cantley L.C.;
"Identification of the tuberous sclerosis complex-2 tumor suppressor
gene product tuberin as a target of the phosphoinositide 3-kinase/akt
pathway.";
Mol. Cell 10:151-162(2002).
[24]
INTERACTION WITH TCL1A.
PubMed=11839817; DOI=10.1128/MCB.22.5.1513-1525.2002;
Kuenstle G., Laine J., Pierron G., Kagami S., Nakajima H., Hoh F.,
Roumestand C., Stern M.H., Noguchi M.;
"Identification of Akt association and oligomerization domains of the
Akt kinase coactivator TCL1.";
Mol. Cell. Biol. 22:1513-1525(2002).
[25]
INTERACTION WITH CDKN1B, FUNCTION, AND MUTAGENESIS OF THR-308 AND
SER-473.
PubMed=12244301; DOI=10.1038/nm759;
Shin I., Yakes F.M., Rojo F., Shin N.-Y., Bakin A.V., Baselga J.,
Arteaga C.L.;
"PKB/Akt mediates cell-cycle progression by phosphorylation of
p27(Kip1) at threonine 157 and modulation of its cellular
localization.";
Nat. Med. 8:1145-1152(2002).
[26]
FUNCTION IN PARTICIPATION IN KIT SIGNALING.
PubMed=12878163; DOI=10.1016/S0014-4827(03)00206-4;
Lennartsson J., Wernstedt C., Engstrom U., Hellman U., Ronnstrand L.;
"Identification of Tyr900 in the kinase domain of c-Kit as a Src-
dependent phosphorylation site mediating interaction with c-Crk.";
Exp. Cell Res. 288:110-118(2003).
[27]
INTERACTION WITH AGAP2, AND PHOSPHORYLATION AT SER-473.
PubMed=14761976; DOI=10.1074/jbc.M312175200;
Ahn J.-Y., Rong R., Kroll T.G., Van Meir E.G., Snyder S.H., Ye K.;
"PIKE (phosphatidylinositol 3-kinase enhancer)-A GTPase stimulates Akt
activity and mediates cellular invasion.";
J. Biol. Chem. 279:16441-16451(2004).
[28]
PHOSPHORYLATION AT SER-473.
PubMed=15047712; DOI=10.1074/jbc.M314192200;
Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.;
"LGI1, a putative tumor metastasis suppressor gene, controls in vitro
invasiveness and expression of matrix metalloproteinases in glioma
cells through the ERK1/2 pathway.";
J. Biol. Chem. 279:23151-23157(2004).
[29]
ERRATUM.
Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.;
J. Biol. Chem. 282:2752-2752(2007).
[30]
INTERACTION WITH AKTIP.
PubMed=14749367; DOI=10.1128/MCB.24.4.1493-1504.2004;
Remy I., Michnick S.W.;
"Regulation of apoptosis by the Ft1 protein, a new modulator of
protein kinase B/Akt.";
Mol. Cell. Biol. 24:1493-1504(2004).
[31]
INTERACTION WITH AGAP2.
PubMed=15118108; DOI=10.1073/pnas.0400921101;
Ahn J.-Y., Hu Y., Kroll T.G., Allard P., Ye K.;
"PIKE-A is amplified in human cancers and prevents apoptosis by up-
regulating Akt.";
Proc. Natl. Acad. Sci. U.S.A. 101:6993-6998(2004).
[32]
PHOSPHORYLATION AT SER-473 IN RESPONSE TO FLT3 SIGNALING.
PubMed=16266983; DOI=10.1158/0008-5472.CAN-05-0422;
Brandts C.H., Sargin B., Rode M., Biermann C., Lindtner B.,
Schwable J., Buerger H., Muller-Tidow C., Choudhary C., McMahon M.,
Berdel W.E., Serve H.;
"Constitutive activation of Akt by Flt3 internal tandem duplications
is necessary for increased survival, proliferation, and myeloid
transformation.";
Cancer Res. 65:9643-9650(2005).
[33]
FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH CCDC88A.
PubMed=16139227; DOI=10.1016/j.devcel.2005.08.001;
Enomoto A., Murakami H., Asai N., Morone N., Watanabe T., Kawai K.,
Murakumo Y., Usukura J., Kaibuchi K., Takahashi M.;
"Akt/PKB regulates actin organization and cell motility via
Girdin/APE.";
Dev. Cell 9:389-402(2005).
[34]
PHOSPHORYLATION AT THR-308, AND PHOSPHORYLATION AT SER-473 BY MTOR.
PubMed=15718470; DOI=10.1126/science.1106148;
Sarbassov D.D., Guertin D.A., Ali S.M., Sabatini D.M.;
"Phosphorylation and regulation of Akt/PKB by the rictor-mTOR
complex.";
Science 307:1098-1101(2005).
[35]
PHOSPHORYLATION AT SER-473.
PubMed=17013611; DOI=10.1007/s00401-006-0128-y;
Schick V., Majores M., Engels G., Spitoni S., Koch A., Elger C.E.,
Simon M., Knobbe C., Bluemcke I., Becker A.J.;
"Activation of Akt independent of PTEN and CTMP tumor-suppressor gene
mutations in epilepsy-associated Taylor-type focal cortical
dysplasias.";
Acta Neuropathol. 112:715-725(2006).
[36]
INTERACTION WITH WDFY2, AND SUBCELLULAR LOCATION.
PubMed=16792529; DOI=10.1042/BJ20060511;
Fritzius T., Burkard G., Haas E., Heinrich J., Schweneker M.,
Bosse M., Zimmermann S., Frey A.D., Caelers A., Bachmann A.S.,
Moelling K.;
"A WD-FYVE protein binds to the kinases Akt and PKCzeta/lambda.";
Biochem. J. 399:9-20(2006).
[37]
FUNCTION, AND INTERACTION WITH RARA.
PubMed=16417524; DOI=10.1042/BJ20051794;
Srinivas H., Xia D., Moore N.L., Uray I.P., Kim H., Ma L.,
Weigel N.L., Brown P.H., Kurie J.M.;
"Akt phosphorylates and suppresses the transactivation of retinoic
acid receptor alpha.";
Biochem. J. 395:653-662(2006).
[38]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in
signaling networks.";
Cell 127:635-648(2006).
[39]
BIOPHYSICOCHEMICAL PROPERTIES.
PubMed=16540465; DOI=10.1074/jbc.M601384200;
Zhang X., Zhang S., Yamane H., Wahl R., Ali A., Lofgren J.A.,
Kendall R.L.;
"Kinetic mechanism of AKT/PKB enzyme family.";
J. Biol. Chem. 281:13949-13956(2006).
[40]
FUNCTION IN PHOSPHORYLATION OF CDKN1A.
PubMed=16982699; DOI=10.1128/MCB.00201-06;
Heron-Milhavet L., Franckhauser C., Rana V., Berthenet C., Fisher D.,
Hemmings B.A., Fernandez A., Lamb N.J.;
"Only Akt1 is required for proliferation, while Akt2 promotes cell
cycle exit through p21 binding.";
Mol. Cell. Biol. 26:8267-8280(2006).
[41]
INTERACTION WITH STK4/MST1, SUBCELLULAR LOCATION, AND TISSUE
SPECIFICITY.
PubMed=17932490; DOI=10.1038/sj.emboj.7601872;
Cinar B., Fang P.K., Lutchman M., Di Vizio D., Adam R.M., Pavlova N.,
Rubin M.A., Yelick P.C., Freeman M.R.;
"The pro-apoptotic kinase Mst1 and its caspase cleavage products are
direct inhibitors of Akt1.";
EMBO J. 26:4523-4534(2007).
[42]
FUNCTION, AND INTERACTION WITH STK4/MST1.
PubMed=17726016; DOI=10.1074/jbc.M704542200;
Jang S.W., Yang S.J., Srinivasan S., Ye K.;
"Akt phosphorylates MstI and prevents its proteolytic activation,
blocking FOXO3 phosphorylation and nuclear translocation.";
J. Biol. Chem. 282:30836-30844(2007).
[43]
FUNCTION IN PHOSPHORYLATION OF PROHIBITIN.
PubMed=18507042;
Han E.K., Mcgonigal T., Butler C., Giranda V.L., Luo Y.;
"Characterization of Akt overexpression in MiaPaCa-2 cells: prohibitin
is an Akt substrate both in vitro and in cells.";
Anticancer Res. 28:957-963(2008).
[44]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124; SER-126 AND
SER-129, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18669648; DOI=10.1073/pnas.0805139105;
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[45]
UBIQUITINATION BY TTC3.
PubMed=20059950; DOI=10.1016/j.devcel.2009.09.007;
Suizu F., Hiramuki Y., Okumura F., Matsuda M., Okumura A.J.,
Hirata N., Narita M., Kohno T., Yokota J., Bohgaki M., Obuse C.,
Hatakeyama S., Obata T., Noguchi M.;
"The E3 ligase TTC3 facilitates ubiquitination and degradation of
phosphorylated Akt.";
Dev. Cell 17:800-810(2009).
[46]
FUNCTION IN PHOSPHORYLATION OF SRPK2, AND INTERACTION WITH SRPK2.
PubMed=19592491; DOI=10.1074/jbc.M109.026237;
Jang S.W., Liu X., Fu H., Rees H., Yepes M., Levey A., Ye K.;
"Interaction of Akt-phosphorylated SRPK2 with 14-3-3 mediates cell
cycle and cell death in neurons.";
J. Biol. Chem. 284:24512-24525(2009).
[47]
FUNCTION.
PubMed=19934221; DOI=10.1242/jcs.053728;
Bristow J.M., Sellers M.H., Majumdar D., Anderson B., Hu L.,
Webb D.J.;
"The Rho-family GEF Asef2 activates Rac to modulate adhesion and actin
dynamics and thereby regulate cell migration.";
J. Cell Sci. 122:4535-4546(2009).
[48]
UBIQUITINATION, INTERACTION WITH TRAF6, MUTAGENESIS OF LYS-8 AND
LYS-14, AND CHARACTERIZATION OF VARIANT BREAST CANCER LYS-17.
PubMed=19713527; DOI=10.1126/science.1175065;
Yang W.-L., Wang J., Chan C.-H., Lee S.-W., Campos A.D., Lamothe B.,
Hur L., Grabiner B.C., Lin X., Darnay B.G., Lin H.-K.;
"The E3 ligase TRAF6 regulates Akt ubiquitination and activation.";
Science 325:1134-1138(2009).
[49]
FUNCTION, AND INTERACTION WITH STK3/MST2.
PubMed=20086174; DOI=10.1158/0008-5472.CAN-09-3147;
Romano D., Matallanas D., Weitsman G., Preisinger C., Ng T., Kolch W.;
"Proapoptotic kinase MST2 coordinates signaling crosstalk between
RASSF1A, Raf-1, and Akt.";
Cancer Res. 70:1195-1203(2010).
[50]
FUNCTION.
PubMed=19940129; DOI=10.1074/jbc.M109.059675;
Yuan Z., Kim D., Shu S., Wu J., Guo J., Xiao L., Kaneko S.,
Coppola D., Cheng J.Q.;
"Phosphoinositide 3-kinase/Akt inhibits MST1-mediated pro-apoptotic
signaling through phosphorylation of threonine 120.";
J. Biol. Chem. 285:3815-3824(2010).
[51]
FUNCTION, AND INTERACTION WITH CLK2.
PubMed=20682768; DOI=10.1074/jbc.M110.122044;
Nam S.Y., Seo H.H., Park H.S., An S., Kim J.Y., Yang K.H., Kim C.S.,
Jeong M., Jin Y.W.;
"Phosphorylation of CLK2 at serine 34 and threonine 127 by AKT
controls cell survival after ionizing radiation.";
J. Biol. Chem. 285:31157-31163(2010).
[52]
FUNCTION IN PHOSPHORYLATION OF PALLD.
PubMed=20471940; DOI=10.1016/j.molcel.2010.02.031;
Chin Y.R., Toker A.;
"The actin-bundling protein palladin is an Akt1-specific substrate
that regulates breast cancer cell migration.";
Mol. Cell 38:333-344(2010).
[53]
FUNCTION, AND INTERACTION WITH STK3/MST2.
PubMed=20231902; DOI=10.1371/journal.pone.0009616;
Kim D., Shu S., Coppola M.D., Kaneko S., Yuan Z.Q., Cheng J.Q.;
"Regulation of proapoptotic mammalian ste20-like kinase MST2 by the
IGF1-Akt pathway.";
PLoS ONE 5:E9616-E9616(2010).
[54]
FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-176; THR-308
AND SER-473, MUTAGENESIS OF TYR-176, INTERACTION WITH TNK2, AND TISSUE
SPECIFICITY.
PubMed=20333297; DOI=10.1371/journal.pone.0009646;
Mahajan K., Coppola D., Challa S., Fang B., Chen Y.A., Zhu W.,
Lopez A.S., Koomen J., Engelman R.W., Rivera C., Muraoka-Cook R.S.,
Cheng J.Q., Schoenbrunn E., Sebti S.M., Earp H.S., Mahajan N.P.;
"Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its
activation.";
PLoS ONE 5:E9646-E9646(2010).
[55]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21269460; DOI=10.1186/1752-0509-5-17;
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
"Initial characterization of the human central proteome.";
BMC Syst. Biol. 5:17-17(2011).
[56]
INTERACTION WITH TRIM13, AND UBIQUITINATION.
PubMed=21333377; DOI=10.1016/j.ejcb.2010.12.001;
Joo H.M., Kim J.Y., Jeong J.B., Seong K.M., Nam S.Y., Yang K.H.,
Kim C.S., Kim H.S., Jeong M., An S., Jin Y.W.;
"Ret finger protein 2 enhances ionizing radiation-induced apoptosis
via degradation of AKT and MDM2.";
Eur. J. Cell Biol. 90:420-431(2011).
[57]
INTERACTION WITH PPP2R5B, AND DEPHOSPHORYLATION.
PubMed=21329884; DOI=10.1016/j.molcel.2011.02.007;
Rodgers J.T., Vogel R.O., Puigserver P.;
"Clk2 and B56-beta mediate insulin-regulated assembly of the PP2A
phosphatase holoenzyme complex on Akt.";
Mol. Cell 41:471-479(2011).
[58]
INTERACTION WITH FAM168A.
PubMed=23251525; DOI=10.1371/journal.pone.0051413;
Peng B., Gu Y., Xiong Y., Zheng G., He Z.;
"Microarray-assisted pathway analysis identifies MT1X & NFkappaB as
mediators of TCRP1-associated resistance to cisplatin in oral squamous
cell carcinoma.";
PLoS ONE 7:E51413-E51413(2012).
[59]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma, and Erythroleukemia;
PubMed=23186163; DOI=10.1021/pr300630k;
Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
Mohammed S.;
"Toward a comprehensive characterization of a human cancer cell
phosphoproteome.";
J. Proteome Res. 12:260-271(2013).
[60]
INTERACTION WITH FAM83B.
PubMed=23676467;
Cipriano R., Miskimen K.L., Bryson B.L., Foy C.R., Bartel C.A.,
Jackson M.W.;
"FAM83B-mediated activation of PI3K/AKT and MAPK signaling cooperates
to promote epithelial cell transformation and resistance to targeted
therapies.";
Oncotarget 4:729-738(2013).
[61]
REVIEW ON ROLE IN KIT SIGNALING.
PubMed=15526160; DOI=10.1007/s00018-004-4189-6;
Ronnstrand L.;
"Signal transduction via the stem cell factor receptor/c-Kit.";
Cell. Mol. Life Sci. 61:2535-2548(2004).
[62]
REVIEW ON FUNCTION.
PubMed=11882383; DOI=10.1016/S0898-6568(01)00271-6;
Nicholson K.M., Anderson N.G.;
"The protein kinase B/Akt signalling pathway in human malignancy.";
Cell. Signal. 14:381-395(2002).
[63]
PHOSPHORYLATION AT SER-473.
PubMed=20978158; DOI=10.1158/1535-7163.MCT-10-0730;
Kunoh T., Noda T., Koseki K., Sekigawa M., Takagi M., Shin-ya K.,
Goshima N., Iemura S., Natsume T., Wada S., Mukai Y., Ohta S.,
Sasaki R., Mizukami T.;
"A novel human dynactin-associated protein, dynAP, promotes activation
of Akt, and ergosterol-related compounds induce dynAP-dependent
apoptosis of human cancer cells.";
Mol. Cancer Ther. 9:2934-2942(2010).
[64]
REVIEW ON FUNCTION.
PubMed=21620960; DOI=10.1016/j.cellsig.2011.05.004;
Hers I., Vincent E.E., Tavare J.M.;
"Akt signalling in health and disease.";
Cell. Signal. 23:1515-1527(2011).
[65]
REVIEW ON FUNCTION.
PubMed=21432781; DOI=10.14670/HH-26.651;
Heron-Milhavet L., Khouya N., Fernandez A., Lamb N.J.;
"Akt1 and Akt2: differentiating the aktion.";
Histol. Histopathol. 26:651-662(2011).
[66]
PHOSPHORYLATION AT THR-308 AND SER-473.
PubMed=21464307; DOI=10.1073/pnas.1016132108;
Xie X., Zhang D., Zhao B., Lu M.K., You M., Condorelli G., Wang C.Y.,
Guan K.L.;
"IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by
direct phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 108:6474-6479(2011).
[67]
INTERACTION WITH SIRT1, ACETYLATION AT LYS-14 AND LYS-20,
DEACETYLATION AT LYS-14 AND LYS-20, AND MUTAGENESIS OF LYS-14; GLU-17
AND LYS-20.
PubMed=21775285; DOI=10.1126/scisignal.2001465;
Sundaresan N.R., Pillai V.B., Wolfgeher D., Samant S., Vasudevan P.,
Parekh V., Raghuraman H., Cunningham J.M., Gupta M., Gupta M.P.;
"The deacetylase SIRT1 promotes membrane localization and activation
of Akt and PDK1 during tumorigenesis and cardiac hypertrophy.";
Sci. Signal. 4:RA46-RA46(2011).
[68]
UBIQUITINATION AT LYS-284.
PubMed=22410793; DOI=10.1038/cr.2012.38;
Bae S., Kim S.Y., Jung J.H., Yoon Y., Cha H.J., Lee H., Kim K.,
Kim J., An I.S., Kim J., Um H.D., Park I.C., Lee S.J., Nam S.Y.,
Jin Y.W., Lee J.H., An S.;
"Akt is negatively regulated by the MULAN E3 ligase.";
Cell Res. 22:873-885(2012).
[69]
GLYCOSYLATION AT SER-126; SER-129; THR-305 AND THR-312, SUBCELLULAR
LOCATION, INTERACTION WITH PDPK1, AND MUTAGENESIS OF THR-305 AND
THR-312.
PubMed=22629392; DOI=10.1371/journal.pone.0037427;
Wang S., Huang X., Sun D., Xin X., Pan Q., Peng S., Liang Z., Luo C.,
Yang Y., Jiang H., Huang M., Chai W., Ding J., Geng M.;
"Extensive crosstalk between O-GlcNAcylation and phosphorylation
regulates Akt signaling.";
PLoS ONE 7:E37427-E37427(2012).
[70]
PHOSPHORYLATION AT SER-473, AND DEPHOSPHORYLATION BY CPPED1.
PubMed=23799035; DOI=10.1371/journal.pone.0065679;
Zhuo D.X., Zhang X.W., Jin B., Zhang Z., Xie B.S., Wu C.L., Gong K.,
Mao Z.B.;
"CSTP1, a novel protein phosphatase, blocks cell cycle, promotes cell
apoptosis, and suppresses tumor growth of bladder cancer by directly
dephosphorylating Akt at Ser473 site.";
PLoS ONE 8:E65679-E65679(2013).
[71]
FUNCTION.
PubMed=23431171; DOI=10.1073/pnas.1300490110;
Rokudai S., Laptenko O., Arnal S.M., Taya Y., Kitabayashi I.,
Prives C.;
"MOZ increases p53 acetylation and premature senescence through its
complex formation with PML.";
Proc. Natl. Acad. Sci. U.S.A. 110:3895-3900(2013).
[72]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-448 AND THR-450, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
Wang L., Ye M., Zou H.;
"An enzyme assisted RP-RPLC approach for in-depth analysis of human
liver phosphoproteome.";
J. Proteomics 96:253-262(2014).
[73]
INTERACTION WITH KIF14.
PubMed=24784001; DOI=10.1016/j.neo.2014.03.008;
Singel S.M., Cornelius C., Zaganjor E., Batten K., Sarode V.R.,
Buckley D.L., Peng Y., John G.B., Li H.C., Sadeghi N., Wright W.E.,
Lum L., Corson T.W., Shay J.W.;
"KIF14 promotes AKT phosphorylation and contributes to chemoresistance
in triple-negative breast cancer.";
Neoplasia 16:247-256(2014).
[74]
X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 1-123, INTERACTION WITH
PTDINS(3,4,5)P3 AND PTDINS(3,4)P2, AND MUTAGENESIS OF LYS-14; ARG-25
AND ARG-86.
PubMed=12176338; DOI=10.1016/S0960-9822(02)00972-7;
Thomas C.C., Deak M., Alessi D.R., van Aalten D.M.;
"High-resolution structure of the pleckstrin homology domain of
protein kinase b/akt bound to phosphatidylinositol (3,4,5)-
trisphosphate.";
Curr. Biol. 12:1256-1262(2002).
[75]
X-RAY CRYSTALLOGRAPHY (0.98 ANGSTROMS) OF 1-121, AND INTERACTION WITH
PTDINS(1,3,4,5)P4.
PubMed=12964941; DOI=10.1042/BJ20031229;
Milburn C.C., Deak M., Kelly S.M., Price N.C., Alessi D.R.,
Van Aalten D.M.;
"Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin
homology domain of protein kinase B induces a conformational change.";
Biochem. J. 375:531-538(2003).
[76]
X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 144-480, PHOSPHORYLATION AT
THR-308, AND ENZYME REGULATION.
PubMed=18456494; DOI=10.1016/j.bmcl.2008.04.034;
Lippa B., Pan G., Corbett M., Li C., Kauffman G.S., Pandit J.,
Robinson S., Wei L., Kozina E., Marr E.S., Borzillo G., Knauth E.,
Barbacci-Tobin E.G., Vincent P., Troutman M., Baker D., Rajamohan F.,
Kakar S., Clark T., Morris J.;
"Synthesis and structure based optimization of novel Akt inhibitors.";
Bioorg. Med. Chem. Lett. 18:3359-3363(2008).
[77]
X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 144-480, AND ENZYME
REGULATION.
PubMed=20810279; DOI=10.1016/j.bmcl.2010.08.053;
Blake J.F., Kallan N.C., Xiao D., Xu R., Bencsik J.R., Skelton N.J.,
Spencer K.L., Mitchell I.S., Woessner R.D., Gloor S.L., Risom T.,
Gross S.D., Martinson M., Morales T.H., Vigers G.P., Brandhuber B.J.;
"Discovery of pyrrolopyrimidine inhibitors of Akt.";
Bioorg. Med. Chem. Lett. 20:5607-5612(2010).
[78]
X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 144-480, PHOSPHORYLATION AT
THR-308, AND ENZYME REGULATION.
PubMed=20481595; DOI=10.1021/jm1003842;
Freeman-Cook K.D., Autry C., Borzillo G., Gordon D.,
Barbacci-Tobin E., Bernardo V., Briere D., Clark T., Corbett M.,
Jakubczak J., Kakar S., Knauth E., Lippa B., Luzzio M.J., Mansour M.,
Martinelli G., Marx M., Nelson K., Pandit J., Rajamohan F.,
Robinson S., Subramanyam C., Wei L., Wythes M., Morris J.;
"Design of selective, ATP-competitive inhibitors of Akt.";
J. Med. Chem. 53:4615-4622(2010).
[79]
X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 2-443, AND DISULFIDE BOND.
PubMed=20886116; DOI=10.1371/journal.pone.0012913;
Wu W.I., Voegtli W.C., Sturgis H.L., Dizon F.P., Vigers G.P.,
Brandhuber B.J.;
"Crystal structure of human AKT1 with an allosteric inhibitor reveals
a new mode of kinase inhibition.";
PLoS ONE 5:E12913-E12913(2010).
[80]
X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 144-480, AND ENZYME
REGULATION.
PubMed=21392984; DOI=10.1016/j.bmcl.2011.02.073;
Kallan N.C., Spencer K.L., Blake J.F., Xu R., Heizer J., Bencsik J.R.,
Mitchell I.S., Gloor S.L., Martinson M., Risom T., Gross S.D.,
Morales T.H., Wu W.I., Vigers G.P., Brandhuber B.J., Skelton N.J.;
"Discovery and SAR of spirochromane Akt inhibitors.";
Bioorg. Med. Chem. Lett. 21:2410-2414(2011).
[81]
VARIANT BREAST CANCER LYS-17, AND CHARACTERIZATION OF VARIANT BREAST
CANCER LYS-17.
PubMed=17611497; DOI=10.1038/nature05933;
Carpten J.D., Faber A.L., Horn C., Donoho G.P., Briggs S.L.,
Robbins C.M., Hostetter G., Boguslawski S., Moses T.Y., Savage S.,
Uhlik M., Lin A., Du J., Qian Y.-W., Zeckner D.J., Tucker-Kellogg G.,
Touchman J., Patel K., Mousses S., Bittner M., Schevitz R.,
Lai M.-H.T., Blanchard K.L., Thomas J.E.;
"A transforming mutation in the pleckstrin homology domain of AKT1 in
cancer.";
Nature 448:439-444(2007).
[82]
CHARACTERIZATION OF VARIANT PROTEUSS LYS-17.
PubMed=18954143; DOI=10.1021/bi801683k;
Landgraf K.E., Pilling C., Falke J.J.;
"Molecular mechanism of an oncogenic mutation that alters membrane
targeting: Glu17Lys modifies the PIP lipid specificity of the AKT1 PH
domain.";
Biochemistry 47:12260-12269(2008).
[83]
VARIANT PROTEUSS LYS-17.
PubMed=21793738; DOI=10.1056/NEJMoa1104017;
Lindhurst M.J., Sapp J.C., Teer J.K., Johnston J.J., Finn E.M.,
Peters K., Turner J., Cannons J.L., Bick D., Blakemore L.,
Blumhorst C., Brockmann K., Calder P., Cherman N., Deardorff M.A.,
Everman D.B., Golas G., Greenstein R.M., Kato B.M.,
Keppler-Noreuil K.M., Kuznetsov S.A., Miyamoto R.T., Newman K., Ng D.,
O'Brien K., Rothenberg S., Schwartzentruber D.J., Singhal V.,
Tirabosco R., Upton J., Wientroub S., Zackai E.H., Hoag K.,
Whitewood-Neal T., Robey P.G., Schwartzberg P.L., Darling T.N.,
Tosi L.L., Mullikin J.C., Biesecker L.G.;
"A mosaic activating mutation in AKT1 associated with the Proteus
syndrome.";
N. Engl. J. Med. 365:611-619(2011).
[84]
VARIANTS CWS6 CYS-25 AND PRO-435.
PubMed=23246288; DOI=10.1016/j.ajhg.2012.10.021;
Orloff M.S., He X., Peterson C., Chen F., Chen J.L., Mester J.L.,
Eng C.;
"Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like
syndromes.";
Am. J. Hum. Genet. 92:76-80(2013).
-!- FUNCTION: AKT1 is one of 3 closely related serine/threonine-
protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and
which regulate many processes including metabolism, proliferation,
cell survival, growth and angiogenesis. This is mediated through
serine and/or threonine phosphorylation of a range of downstream
substrates. Over 100 substrate candidates have been reported so
far, but for most of them, no isoform specificity has been
reported. AKT is responsible of the regulation of glucose uptake
by mediating insulin-induced translocation of the SLC2A4/GLUT4
glucose transporter to the cell surface. Phosphorylation of PTPN1
at 'Ser-50' negatively modulates its phosphatase activity
preventing dephosphorylation of the insulin receptor and the
attenuation of insulin signaling. Phosphorylation of TBC1D4
triggers the binding of this effector to inhibitory 14-3-3
proteins, which is required for insulin-stimulated glucose
transport. AKT regulates also the storage of glucose in the form
of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at
'Ser-9', resulting in inhibition of its kinase activity.
Phosphorylation of GSK3 isoforms by AKT is also thought to be one
mechanism by which cell proliferation is driven. AKT regulates
also cell survival via the phosphorylation of MAP3K5 (apoptosis
signal-related kinase). Phosphorylation of 'Ser-83' decreases
MAP3K5 kinase activity stimulated by oxidative stress and thereby
prevents apoptosis. AKT mediates insulin-stimulated protein
synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462',
thereby activating mTORC1 signaling and leading to both
phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is
involved in the phosphorylation of members of the FOXO factors
(Forkhead family of transcription factors), leading to binding of
14-3-3 proteins and cytoplasmic localization. In particular, FOXO1
is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and
FOXO4 are phosphorylated on equivalent sites. AKT has an important
role in the regulation of NF-kappa-B-dependent gene transcription
and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-
response element binding protein). The phosphorylation of CREB1
induces the binding of accessory proteins that are necessary for
the transcription of pro-survival genes such as BCL2 and MCL1. AKT
phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby
potentially regulating ACLY activity and fatty acid synthesis.
Activates the 3B isoform of cyclic nucleotide phosphodiesterase
(PDE3B) via phosphorylation of 'Ser-273', resulting in reduced
cyclic AMP levels and inhibition of lipolysis. Phosphorylates
PIKFYVE on 'Ser-318', which results in increased PI(3)P-5
activity. The Rho GTPase-activating protein DLC1 is another
substrate and its phosphorylation is implicated in the regulation
cell proliferation and cell growth. AKT plays a role as key
modulator of the AKT-mTOR signaling pathway controlling the tempo
of the process of newborn neurons integration during adult
neurogenesis, including correct neuron positioning, dendritic
development and synapse formation. Signals downstream of
phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of
various growth factors such as platelet-derived growth factor
(PDGF), epidermal growth factor (EGF), insulin and insulin-like
growth factor I (IGF-I). AKT mediates the antiapoptotic effects of
IGF-I. Essential for the SPATA13-mediated regulation of cell
migration and adhesion assembly and disassembly. May be involved
in the regulation of the placental development. Phosphorylates
STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its:
kinase activity, nuclear translocation, autophosphorylation and
ability to phosphorylate FOXO3. Phosphorylates STK3/MST2 at 'Thr-
117' and 'Thr-384' leading to inhibition of its: cleavage, kinase
activity, autophosphorylation at Thr-180, binding to RASSF1 and
nuclear translocation. Phosphorylates SRPK2 and enhances its
kinase activity towards SRSF2 and ACIN1 and promotes its nuclear
translocation. Phosphorylates RAF1 at 'Ser-259' and negatively
regulates its activity. Phosphorylation of BAD stimulates its pro-
apoptotic activity. Phosphorylates KAT6A at 'Thr-369' and this
phosphorylation inhibits the interaction of KAT6A with PML and
negatively regulates its acetylation activity towards p53/TP53.
-!- FUNCTION: AKT1-specific substrates have been recently identified,
including palladin (PALLD), which phosphorylation modulates
cytoskeletal organization and cell motility; prohibitin (PHB),
playing an important role in cell metabolism and proliferation;
and CDKN1A, for which phosphorylation at 'Thr-145' induces its
release from CDK2 and cytoplasmic relocalization. These recent
findings indicate that the AKT1 isoform has a more specific role
in cell motility and proliferation. Phosphorylates CLK2 thereby
controlling cell survival to ionizing radiation.
-!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
{ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:1718748,
ECO:0000269|PubMed:1851997}.
-!- ENZYME REGULATION: Three specific sites, one in the kinase domain
(Thr-308) and the two other ones in the C-terminal regulatory
region (Ser-473 and Tyr-474), need to be phosphorylated for its
full activation. Inhibited by pyrrolopyrimidine inhibitors like
aniline triazole and spiroindoline. {ECO:0000269|PubMed:18456494,
ECO:0000269|PubMed:20481595, ECO:0000269|PubMed:20810279,
ECO:0000269|PubMed:21392984, ECO:0000269|PubMed:9512493,
ECO:0000269|PubMed:9736715}.
-!- BIOPHYSICOCHEMICAL PROPERTIES:
Kinetic parameters:
KM=52.8 uM for ATP (for purified and in vitro activated AKT1)
{ECO:0000269|PubMed:16540465};
KM=0.5 uM for peptide substrate (for purified and in vitro
activated AKT1) {ECO:0000269|PubMed:16540465};
KM=143.3 uM for ATP (for recombinant myristoylated AKT1
expressed and immunoprecipitated from Rat-1 cells)
{ECO:0000269|PubMed:16540465};
KM=2.9 uM for peptide substrate (for recombinant myristoylated
AKT1 expressed and immunoprecipitated from Rat-1 cells)
{ECO:0000269|PubMed:16540465};
-!- SUBUNIT: Interacts with BTBD10 (By similarity). Interacts with
KCTD20 (By similarity). Interacts (via the C-terminus) with
CCDC88A (via its C-terminus). Interacts with GRB10; the
interaction leads to GRB10 phosphorylation thus promoting YWHAE-
binding (By similarity). Interacts with AGAP2 (isoform 2/PIKE-A);
the interaction occurs in the presence of guanine nucleotides.
Interacts with AKTIP. Interacts (via PH domain) with MTCP1, TCL1A
AND TCL1B. Interacts with CDKN1B; the interaction phosphorylates
CDKN1B promoting 14-3-3 binding and cell-cycle progression.
Interacts with MAP3K5 and TRAF6. Interacts with BAD, PPP2R5B, STK3
and STK4. Interacts (via PH domain) with SIRT1. Interacts with
SRPK2 in a phosphorylation-dependent manner. Interacts with RAF1.
Interacts with TRIM13; the interaction ubiquitinates AKT1 leading
to its proteasomal degradation. Interacts with TNK2 and CLK2.
Interacts (via the C-terminus) with THEM4 (via its C-terminus).
Interacts with and phosphorylated by PDPK1. Interacts with PA2G4
(By similarity). Interacts with KIF14; the interaction is detected
in the plasma membrane upon INS stimulation and promotes AKT1
phosphorylation (PubMed:24784001). Interacts with FAM83B;
activates the PI3K/AKT signaling cascade (PubMed:23676467).
Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529). Forms
a complex with WDFY2 and FOXO1 (By similarity). Interacts with
FAM168A (PubMed:23251525). {ECO:0000250|UniProtKB:P31750,
ECO:0000250|UniProtKB:P47196, ECO:0000269|PubMed:10576742,
ECO:0000269|PubMed:10716693, ECO:0000269|PubMed:10926925,
ECO:0000269|PubMed:10983986, ECO:0000269|PubMed:11154276,
ECO:0000269|PubMed:11598301, ECO:0000269|PubMed:11839817,
ECO:0000269|PubMed:12042314, ECO:0000269|PubMed:12176338,
ECO:0000269|PubMed:12244301, ECO:0000269|PubMed:12964941,
ECO:0000269|PubMed:14749367, ECO:0000269|PubMed:14761976,
ECO:0000269|PubMed:15118108, ECO:0000269|PubMed:16139227,
ECO:0000269|PubMed:16417524, ECO:0000269|PubMed:16792529,
ECO:0000269|PubMed:17726016, ECO:0000269|PubMed:17932490,
ECO:0000269|PubMed:19592491, ECO:0000269|PubMed:19713527,
ECO:0000269|PubMed:20086174, ECO:0000269|PubMed:20231902,
ECO:0000269|PubMed:20333297, ECO:0000269|PubMed:20682768,
ECO:0000269|PubMed:21329884, ECO:0000269|PubMed:21333377,
ECO:0000269|PubMed:21775285, ECO:0000269|PubMed:22629392,
ECO:0000269|PubMed:23251525, ECO:0000269|PubMed:23676467,
ECO:0000269|PubMed:24784001}.
-!- INTERACTION:
Self; NbExp=2; IntAct=EBI-296087, EBI-296087;
Q9UKG1:APPL1; NbExp=2; IntAct=EBI-296087, EBI-741243;
P29067:Arrb2 (xeno); NbExp=2; IntAct=EBI-296087, EBI-1636616;
Q8IXJ9:ASXL1; NbExp=2; IntAct=EBI-296087, EBI-1646500;
O95999:BCL10; NbExp=5; IntAct=EBI-296087, EBI-958922;
Q16543:CDC37; NbExp=2; IntAct=EBI-296087, EBI-295634;
Q92793:CREBBP; NbExp=3; IntAct=EBI-296087, EBI-81215;
Q1W6H9:FAM110C; NbExp=2; IntAct=EBI-296087, EBI-3942563;
Q9BZQ8:FAM129A; NbExp=2; IntAct=EBI-296087, EBI-6916466;
P49841:GSK3B; NbExp=3; IntAct=EBI-296087, EBI-373586;
P11021:HSPA5; NbExp=2; IntAct=EBI-296087, EBI-354921;
Q5S007:LRRK2; NbExp=6; IntAct=EBI-296087, EBI-5323863;
Q99683:MAP3K5; NbExp=2; IntAct=EBI-296087, EBI-476263;
Q16539:MAPK14; NbExp=2; IntAct=EBI-296087, EBI-73946;
Q00987:MDM2; NbExp=4; IntAct=EBI-296087, EBI-389668;
P42345:MTOR; NbExp=2; IntAct=EBI-296087, EBI-359260;
P29474:NOS3; NbExp=2; IntAct=EBI-296087, EBI-1391623;
P04150:NR3C1; NbExp=5; IntAct=EBI-296087, EBI-493507;
Q15118-1:PDK1; NbExp=2; IntAct=EBI-12562306, EBI-12562315;
O15530:PDPK1; NbExp=3; IntAct=EBI-296087, EBI-717097;
Q96S96:PEBP4; NbExp=2; IntAct=EBI-296087, EBI-8563667;
P19174:PLCG1; NbExp=9; IntAct=EBI-296087, EBI-79387;
O60437:PPL; NbExp=2; IntAct=EBI-296087, EBI-368321;
P62136:PPP1CA; NbExp=4; IntAct=EBI-296087, EBI-357253;
P67775:PPP2CA; NbExp=4; IntAct=EBI-296087, EBI-712311;
P30153:PPP2R1A; NbExp=2; IntAct=EBI-296087, EBI-302388;
Q05513:PRKCZ; NbExp=2; IntAct=EBI-296087, EBI-295351;
P04049:RAF1; NbExp=2; IntAct=EBI-296087, EBI-365996;
P23443:RPS6KB1; NbExp=2; IntAct=EBI-296087, EBI-1775921;
Q15047:SETDB1; NbExp=9; IntAct=EBI-296087, EBI-79691;
Q96EB6:SIRT1; NbExp=5; IntAct=EBI-296087, EBI-1802965;
Q13485:SMAD4; NbExp=2; IntAct=EBI-296087, EBI-347263;
Q13043:STK4; NbExp=13; IntAct=EBI-296087, EBI-367376;
P56279:TCL1A; NbExp=3; IntAct=EBI-296087, EBI-749995;
Q9NYB0:TERF2IP; NbExp=2; IntAct=EBI-296087, EBI-750109;
Q92547:TOPBP1; NbExp=2; IntAct=EBI-296087, EBI-308302;
P08670:VIM; NbExp=29; IntAct=EBI-296087, EBI-353844;
P03165:X (xeno); NbExp=3; IntAct=EBI-296087, EBI-7683985;
-!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell membrane.
Note=Nucleus after activation by integrin-linked protein kinase 1
(ILK1). Nuclear translocation is enhanced by interaction with
TCL1A. Phosphorylation on Tyr-176 by TNK2 results in its
localization to the cell membrane where it is targeted for further
phosphorylations on Thr-308 and Ser-473 leading to its activation
and the activated form translocates to the nucleus. Colocalizes
with WDFY2 in intracellular vesicles (PubMed:16792529).
{ECO:0000269|PubMed:16792529}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=P31749-1; Sequence=Displayed;
Name=2;
IsoId=P31749-2; Sequence=VSP_056180;
Note=No experimental confirmation available.;
-!- TISSUE SPECIFICITY: Expressed in prostate cancer and levels
increase from the normal to the malignant state (at protein
level). Expressed in all human cell types so far analyzed. The
Tyr-176 phosphorylated form shows a significant increase in
expression in breast cancers during the progressive stages i.e.
normal to hyperplasia (ADH), ductal carcinoma in situ (DCIS),
invasive ductal carcinoma (IDC) and lymph node metastatic (LNMM)
stages. {ECO:0000269|PubMed:1718748, ECO:0000269|PubMed:17932490,
ECO:0000269|PubMed:20333297}.
-!- DOMAIN: Binding of the PH domain to phosphatidylinositol 3,4,5-
trisphosphate (PI(3,4,5)P3) following phosphatidylinositol 3-
kinase alpha (PIK3CA) activity results in its targeting to the
plasma membrane. The PH domain mediates interaction with TNK2 and
Tyr-176 is also essential for this interaction.
-!- DOMAIN: The AGC-kinase C-terminal mediates interaction with THEM4.
-!- PTM: O-GlcNAcylation at Thr-305 and Thr-312 inhibits activating
phosphorylation at Thr-308 via disrupting the interaction between
AKT1 and PDPK1. O-GlcNAcylation at Ser-473 also probably
interferes with phosphorylation at this site.
{ECO:0000269|PubMed:14761976, ECO:0000269|PubMed:15047712,
ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:16266983,
ECO:0000269|PubMed:17013611, ECO:0000269|PubMed:18456494,
ECO:0000269|PubMed:20333297, ECO:0000269|PubMed:20481595,
ECO:0000269|PubMed:20978158, ECO:0000269|PubMed:21464307,
ECO:0000269|PubMed:23799035, ECO:0000269|PubMed:8978681,
ECO:0000269|PubMed:9512493, ECO:0000269|PubMed:9736715}.
-!- PTM: Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required
for full activity. Activated TNK2 phosphorylates it on Tyr-176
resulting in its binding to the anionic plasma membrane
phospholipid PA. This phosphorylated form localizes to the cell
membrane, where it is targeted by PDPK1 and PDPK2 for further
phosphorylations on Thr-308 and Ser-473 leading to its activation.
Ser-473 phosphorylation by mTORC2 favors Thr-308 phosphorylation
by PDPK1. Phosphorylated at Thr-308 and Ser-473 by IKBKE and TBK1.
Ser-473 phosphorylation is enhanced by interaction with AGAP2
isoform 2 (PIKE-A). Ser-473 phosphorylation is enhanced in focal
cortical dysplasias with Taylor-type balloon cells. Ser-473
phosphorylation is enhanced by signaling through activated FLT3.
Dephosphorylated at Thr-308 and Ser-473 by PP2A phosphatase. The
phosphorylated form of PPP2R5B is required for bridging AKT1 with
PP2A phosphatase. Ser-473 is dephosphorylated by CPPED1, leading
to termination of signaling. {ECO:0000269|PubMed:12149249,
ECO:0000269|PubMed:14761976, ECO:0000269|PubMed:15047712,
ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:16266983,
ECO:0000269|PubMed:17013611, ECO:0000269|PubMed:18456494,
ECO:0000269|PubMed:20333297, ECO:0000269|PubMed:20481595,
ECO:0000269|PubMed:20978158, ECO:0000269|PubMed:21464307,
ECO:0000269|PubMed:23799035, ECO:0000269|PubMed:8978681,
ECO:0000269|PubMed:9512493, ECO:0000269|PubMed:9736715}.
-!- PTM: Ubiquitinated via 'Lys-48'-linked polyubiquitination by
ZNRF1, leading to its degradation by the proteasome (By
similarity). Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-
linked polyubiquitination. TRAF6-induced 'Lys-63'-linked AKT1
ubiquitination is critical for phosphorylation and activation.
When ubiquitinated, it translocates to the plasma membrane, where
it becomes phosphorylated. When fully phosphorylated and
translocated into the nucleus, undergoes 'Lys-48'-
polyubiquitination catalyzed by TTC3, leading to its degradation
by the proteasome. Also ubiquitinated by TRIM13 leading to its
proteasomal degradation. Phosphorylated, undergoes 'Lys-48'-linked
polyubiquitination preferentially at Lys-284 catalyzed by MUL1,
leading to its proteasomal degradation. {ECO:0000250,
ECO:0000269|PubMed:19713527, ECO:0000269|PubMed:20059950,
ECO:0000269|PubMed:21333377, ECO:0000269|PubMed:22410793}.
-!- PTM: Acetylated on Lys-14 and Lys-20 by the histone
acetyltransferases EP300 and KAT2B. Acetylation results in reduced
phosphorylation and inhibition of activity. Deacetylated at Lys-14
and Lys-20 by SIRT1. SIRT1-mediated deacetylation relieves the
inhibition. {ECO:0000269|PubMed:21775285}.
-!- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy
originating from breast epithelial tissue. Breast neoplasms can be
distinguished by their histologic pattern. Invasive ductal
carcinoma is by far the most common type. Breast cancer is
etiologically and genetically heterogeneous. Important genetic
factors have been indicated by familial occurrence and bilateral
involvement. Mutations at more than one locus can be involved in
different families or even in the same case.
{ECO:0000269|PubMed:17611497}. Note=Disease susceptibility is
associated with variations affecting the gene represented in this
entry.
-!- DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease
characterized by malignant lesions arising from the inner wall of
the large intestine (the colon) and the rectum. Genetic
alterations are often associated with progression from
premalignant lesion (adenoma) to invasive adenocarcinoma. Risk
factors for cancer of the colon and rectum include colon polyps,
long-standing ulcerative colitis, and genetic family history.
Note=The gene represented in this entry may be involved in disease
pathogenesis.
-!- DISEASE: Note=Genetic variations in AKT1 may play a role in
susceptibility to ovarian cancer.
-!- DISEASE: Proteus syndrome (PROTEUSS) [MIM:176920]: A highly
variable, severe disorder of asymmetric and disproportionate
overgrowth of body parts, connective tissue nevi, epidermal nevi,
dysregulated adipose tissue, and vascular malformations. Many
features of Proteus syndrome overlap with other overgrowth
syndromes. {ECO:0000269|PubMed:18954143,
ECO:0000269|PubMed:21793738}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: Cowden syndrome 6 (CWS6) [MIM:615109]: A form of Cowden
syndrome, a hamartomatous polyposis syndrome with age-related
penetrance. Cowden syndrome is characterized by hamartomatous
lesions affecting derivatives of ectodermal, mesodermal and
endodermal layers, macrocephaly, facial trichilemmomas (benign
tumors of the hair follicle infundibulum), acral keratoses,
papillomatous papules, and elevated risk for development of
several types of malignancy, particularly breast carcinoma in
women and thyroid carcinoma in both men and women. Colon cancer
and renal cell carcinoma have also been reported. Hamartomas can
be found in virtually every organ, but most commonly in the skin,
gastrointestinal tract, breast and thyroid.
{ECO:0000269|PubMed:23246288}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
protein kinase family. RAC subfamily. {ECO:0000305}.
-!- CAUTION: In light of strong homologies in the primary amino acid
sequence, the 3 AKT kinases were long surmised to play redundant
and overlapping roles. More recent studies has brought into
question the redundancy within AKT kinase isoforms and instead
pointed to isoform specific functions in different cellular events
and diseases. AKT1 is more specifically involved in cellular
survival pathways, by inhibiting apoptotic processes; whereas AKT2
is more specific for the insulin receptor signaling pathway.
Moreover, while AKT1 and AKT2 are often implicated in many aspects
of cellular transformation, the 2 isoforms act in a complementary
opposing manner. The role of AKT3 is less clear, though it appears
to be predominantly expressed in brain. {ECO:0000305}.
-!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
and Haematology;
URL="http://atlasgeneticsoncology.org/Genes/AKT1ID355ch14q32.html";
-----------------------------------------------------------------------
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-----------------------------------------------------------------------
EMBL; M63167; AAA36539.1; -; mRNA.
EMBL; AF283830; AAL55732.1; -; Genomic_DNA.
EMBL; AF283819; AAL55732.1; JOINED; Genomic_DNA.
EMBL; AF283820; AAL55732.1; JOINED; Genomic_DNA.
EMBL; AF283821; AAL55732.1; JOINED; Genomic_DNA.
EMBL; AF283822; AAL55732.1; JOINED; Genomic_DNA.
EMBL; AF283823; AAL55732.1; JOINED; Genomic_DNA.
EMBL; AF283824; AAL55732.1; JOINED; Genomic_DNA.
EMBL; AF283825; AAL55732.1; JOINED; Genomic_DNA.
EMBL; AF283826; AAL55732.1; JOINED; Genomic_DNA.
EMBL; AF283827; AAL55732.1; JOINED; Genomic_DNA.
EMBL; AF283828; AAL55732.1; JOINED; Genomic_DNA.
EMBL; AF283829; AAL55732.1; JOINED; Genomic_DNA.
EMBL; AK299310; BAH12997.1; -; mRNA.
EMBL; AK314256; BAG36922.1; -; mRNA.
EMBL; AB451242; BAG70056.1; -; mRNA.
EMBL; AB451367; BAG70181.1; -; mRNA.
EMBL; AL583722; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AL590327; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC000479; AAH00479.1; -; mRNA.
EMBL; BC084538; AAH84538.1; -; mRNA.
EMBL; X61037; CAA43372.1; -; mRNA.
CCDS; CCDS9994.1; -. [P31749-1]
PIR; A39360; A39360.
RefSeq; NP_001014431.1; NM_001014431.1. [P31749-1]
RefSeq; NP_001014432.1; NM_001014432.1. [P31749-1]
RefSeq; NP_005154.2; NM_005163.2. [P31749-1]
RefSeq; XP_005267458.1; XM_005267401.1. [P31749-1]
UniGene; Hs.525622; -.
PDB; 1H10; X-ray; 1.40 A; A=1-123.
PDB; 1UNP; X-ray; 1.65 A; A=1-121.
PDB; 1UNQ; X-ray; 0.98 A; A=1-123.
PDB; 1UNR; X-ray; 1.25 A; A=1-123.
PDB; 2UVM; X-ray; 1.94 A; A=1-123.
PDB; 2UZR; X-ray; 1.94 A; A=1-123.
PDB; 2UZS; X-ray; 2.46 A; A=1-123.
PDB; 3CQU; X-ray; 2.20 A; A=144-480.
PDB; 3CQW; X-ray; 2.00 A; A=144-480.
PDB; 3MV5; X-ray; 2.47 A; A=144-480.
PDB; 3MVH; X-ray; 2.01 A; A=144-480.
PDB; 3O96; X-ray; 2.70 A; A=2-443.
PDB; 3OCB; X-ray; 2.70 A; A/B=144-480.
PDB; 3OW4; X-ray; 2.60 A; A/B=144-480.
PDB; 3QKK; X-ray; 2.30 A; A=144-480.
PDB; 3QKL; X-ray; 1.90 A; A=144-480.
PDB; 3QKM; X-ray; 2.20 A; A=144-480.
PDB; 4EJN; X-ray; 2.19 A; A=2-446.
PDB; 4EKK; X-ray; 2.80 A; A/B=144-480.
PDB; 4EKL; X-ray; 2.00 A; A=144-480.
PDB; 4GV1; X-ray; 1.49 A; A=144-480.
PDB; 5KCV; X-ray; 2.70 A; A=2-446.
PDBsum; 1H10; -.
PDBsum; 1UNP; -.
PDBsum; 1UNQ; -.
PDBsum; 1UNR; -.
PDBsum; 2UVM; -.
PDBsum; 2UZR; -.
PDBsum; 2UZS; -.
PDBsum; 3CQU; -.
PDBsum; 3CQW; -.
PDBsum; 3MV5; -.
PDBsum; 3MVH; -.
PDBsum; 3O96; -.
PDBsum; 3OCB; -.
PDBsum; 3OW4; -.
PDBsum; 3QKK; -.
PDBsum; 3QKL; -.
PDBsum; 3QKM; -.
PDBsum; 4EJN; -.
PDBsum; 4EKK; -.
PDBsum; 4EKL; -.
PDBsum; 4GV1; -.
PDBsum; 5KCV; -.
ProteinModelPortal; P31749; -.
SMR; P31749; -.
BioGrid; 106710; 298.
DIP; DIP-24269N; -.
ELM; P31749; -.
IntAct; P31749; 149.
MINT; MINT-203775; -.
STRING; 9606.ENSP00000270202; -.
BindingDB; P31749; -.
ChEMBL; CHEMBL4282; -.
DrugBank; DB00171; Adenosine triphosphate.
DrugBank; DB01169; Arsenic trioxide.
GuidetoPHARMACOLOGY; 1479; -.
iPTMnet; P31749; -.
PhosphoSitePlus; P31749; -.
BioMuta; AKT1; -.
DMDM; 60391226; -.
EPD; P31749; -.
MaxQB; P31749; -.
PaxDb; P31749; -.
PeptideAtlas; P31749; -.
PRIDE; P31749; -.
DNASU; 207; -.
Ensembl; ENST00000349310; ENSP00000270202; ENSG00000142208. [P31749-1]
Ensembl; ENST00000402615; ENSP00000385326; ENSG00000142208. [P31749-1]
Ensembl; ENST00000407796; ENSP00000384293; ENSG00000142208. [P31749-1]
Ensembl; ENST00000554581; ENSP00000451828; ENSG00000142208. [P31749-1]
Ensembl; ENST00000554848; ENSP00000451166; ENSG00000142208. [P31749-1]
Ensembl; ENST00000555528; ENSP00000450688; ENSG00000142208. [P31749-1]
GeneID; 207; -.
KEGG; hsa:207; -.
UCSC; uc001ypk.4; human. [P31749-1]
CTD; 207; -.
DisGeNET; 207; -.
GeneCards; AKT1; -.
GeneReviews; AKT1; -.
HGNC; HGNC:391; AKT1.
HPA; CAB003765; -.
HPA; HPA002891; -.
MalaCards; AKT1; -.
MIM; 114480; phenotype.
MIM; 114500; phenotype.
MIM; 164730; gene.
MIM; 176920; phenotype.
MIM; 615109; phenotype.
neXtProt; NX_P31749; -.
OpenTargets; ENSG00000142208; -.
Orphanet; 201; Cowden syndrome.
Orphanet; 744; Proteus syndrome.
PharmGKB; PA24684; -.
eggNOG; KOG0598; Eukaryota.
eggNOG; ENOG410XNPH; LUCA.
GeneTree; ENSGT00890000139324; -.
HOGENOM; HOG000233033; -.
HOVERGEN; HBG108317; -.
InParanoid; P31749; -.
KO; K04456; -.
OMA; QHRFFAS; -.
OrthoDB; EOG091G06FF; -.
PhylomeDB; P31749; -.
TreeFam; TF102004; -.
BRENDA; 2.7.11.1; 2681.
Reactome; R-HSA-111447; Activation of BAD and translocation to mitochondria.
Reactome; R-HSA-114604; GPVI-mediated activation cascade.
Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
Reactome; R-HSA-1358803; Downregulation of ERBB2:ERBB3 signaling.
Reactome; R-HSA-1445148; Translocation of GLUT4 to the plasma membrane.
Reactome; R-HSA-1474151; Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
Reactome; R-HSA-165159; mTOR signalling.
Reactome; R-HSA-198323; AKT phosphorylates targets in the cytosol.
Reactome; R-HSA-198693; AKT phosphorylates targets in the nucleus.
Reactome; R-HSA-199418; Negative regulation of the PI3K/AKT network.
Reactome; R-HSA-203615; eNOS activation.
Reactome; R-HSA-211163; AKT-mediated inactivation of FOXO1A.
Reactome; R-HSA-354192; Integrin alphaIIb beta3 signaling.
Reactome; R-HSA-3769402; Deactivation of the beta-catenin transactivating complex.
Reactome; R-HSA-389357; CD28 dependent PI3K/Akt signaling.
Reactome; R-HSA-389513; CTLA4 inhibitory signaling.
Reactome; R-HSA-392451; G beta:gamma signalling through PI3Kgamma.
Reactome; R-HSA-450385; Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
Reactome; R-HSA-450604; KSRP (KHSRP) binds and destabilizes mRNA.
Reactome; R-HSA-5218920; VEGFR2 mediated vascular permeability.
Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer.
Reactome; R-HSA-6785807; Interleukin-4 and 13 signaling.
Reactome; R-HSA-6804757; Regulation of TP53 Degradation.
Reactome; R-HSA-6804758; Regulation of TP53 Activity through Acetylation.
Reactome; R-HSA-6804759; Regulation of TP53 Activity through Association with Co-factors.
Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
Reactome; R-HSA-69202; Cyclin E associated events during G1/S transition.
Reactome; R-HSA-8849469; PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1.
Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
SABIO-RK; P31749; -.
SignaLink; P31749; -.
SIGNOR; P31749; -.
ChiTaRS; AKT1; human.
EvolutionaryTrace; P31749; -.
GeneWiki; AKT1; -.
GenomeRNAi; 207; -.
PMAP-CutDB; P31749; -.
PRO; PR:P31749; -.
Proteomes; UP000005640; Chromosome 14.
Bgee; ENSG00000142208; -.
CleanEx; HS_AKT1; -.
ExpressionAtlas; P31749; baseline and differential.
Genevisible; P31749; HS.
GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
GO; GO:0036064; C:ciliary basal body; IEA:Ensembl.
GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO; GO:0005829; C:cytosol; IDA:UniProtKB.
GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
GO; GO:0098794; C:postsynapse; IEA:GOC.
GO; GO:0043234; C:protein complex; IDA:UniProtKB.
GO; GO:0005819; C:spindle; IEA:Ensembl.
GO; GO:0031982; C:vesicle; IDA:UniProtKB.
GO; GO:0071889; F:14-3-3 protein binding; IPI:UniProtKB.
GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
GO; GO:0019899; F:enzyme binding; ISS:BHF-UCL.
GO; GO:0032794; F:GTPase activating protein binding; IEA:Ensembl.
GO; GO:0042802; F:identical protein binding; IPI:IntAct.
GO; GO:0016301; F:kinase activity; IDA:MGI.
GO; GO:0030235; F:nitric-oxide synthase regulator activity; IMP:BHF-UCL.
GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB.
GO; GO:0043325; F:phosphatidylinositol-3,4-bisphosphate binding; IDA:UniProtKB.
GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
GO; GO:0005080; F:protein kinase C binding; IEA:Ensembl.
GO; GO:0051721; F:protein phosphatase 2A binding; IEA:Ensembl.
GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IDA:MGI.
GO; GO:0006924; P:activation-induced cell death of T cells; IMP:MGI.
GO; GO:0007568; P:aging; IEA:Ensembl.
GO; GO:0043276; P:anoikis; NAS:ParkinsonsUK-UCL.
GO; GO:0008637; P:apoptotic mitochondrial changes; IEA:Ensembl.
GO; GO:0030154; P:cell differentiation; TAS:UniProtKB.
GO; GO:0030030; P:cell projection organization; IEA:Ensembl.
GO; GO:0008283; P:cell proliferation; TAS:UniProtKB.
GO; GO:0006464; P:cellular protein modification process; TAS:ProtInc.
GO; GO:0071276; P:cellular response to cadmium ion; IMP:CAFA.
GO; GO:0006974; P:cellular response to DNA damage stimulus; IEA:Ensembl.
GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IEA:Ensembl.
GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; IEA:Ensembl.
GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
GO; GO:0032869; P:cellular response to insulin stimulus; IMP:BHF-UCL.
GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IMP:UniProtKB.
GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
GO; GO:0071380; P:cellular response to prostaglandin E stimulus; IEA:Ensembl.
GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:CAFA.
GO; GO:0071356; P:cellular response to tumor necrosis factor; IMP:UniProtKB.
GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IEA:Ensembl.
GO; GO:0099565; P:chemical synaptic transmission, postsynaptic; NAS:ParkinsonsUK-UCL.
GO; GO:0031018; P:endocrine pancreas development; TAS:Reactome.
GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:UniProtKB.
GO; GO:0072655; P:establishment of protein localization to mitochondrion; IMP:ParkinsonsUK-UCL.
GO; GO:0097194; P:execution phase of apoptosis; IEA:Ensembl.
GO; GO:0007186; P:G-protein coupled receptor signaling pathway; TAS:ProtInc.
GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:Reactome.
GO; GO:0007281; P:germ cell development; IEA:Ensembl.
GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
GO; GO:0006006; P:glucose metabolic process; IEA:UniProtKB-KW.
GO; GO:0015758; P:glucose transport; IEA:Ensembl.
GO; GO:0005978; P:glycogen biosynthetic process; IEA:UniProtKB-KW.
GO; GO:0060709; P:glycogen cell differentiation involved in embryonic placenta development; IEA:Ensembl.
GO; GO:0030212; P:hyaluronan metabolic process; IEA:Ensembl.
GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IMP:CAFA.
GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
GO; GO:0008286; P:insulin receptor signaling pathway; IMP:UniProtKB.
GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IMP:UniProtKB.
GO; GO:0035655; P:interleukin-18-mediated signaling pathway; IDA:BHF-UCL.
GO; GO:0035556; P:intracellular signal transduction; IDA:MGI.
GO; GO:0060716; P:labyrinthine layer blood vessel development; IEA:Ensembl.
GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl.
GO; GO:0072656; P:maintenance of protein location in mitochondrion; IMP:ParkinsonsUK-UCL.
GO; GO:0060644; P:mammary gland epithelial cell differentiation; TAS:UniProtKB.
GO; GO:0001893; P:maternal placenta development; IEA:Ensembl.
GO; GO:0061024; P:membrane organization; TAS:Reactome.
GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
GO; GO:0010507; P:negative regulation of autophagy; IMP:BHF-UCL.
GO; GO:0045792; P:negative regulation of cell size; IEA:Ensembl.
GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
GO; GO:0010951; P:negative regulation of endopeptidase activity; IMP:BHF-UCL.
GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; TAS:BHF-UCL.
GO; GO:0031999; P:negative regulation of fatty acid beta-oxidation; IMP:BHF-UCL.
GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
GO; GO:0046329; P:negative regulation of JNK cascade; IEA:Ensembl.
GO; GO:0016242; P:negative regulation of macroautophagy; NAS:ParkinsonsUK-UCL.
GO; GO:1901215; P:negative regulation of neuron death; NAS:ParkinsonsUK-UCL.
GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; NAS:BHF-UCL.
GO; GO:0010748; P:negative regulation of plasma membrane long-chain fatty acid transport; IMP:BHF-UCL.
GO; GO:0006469; P:negative regulation of protein kinase activity; IMP:BHF-UCL.
GO; GO:0100002; P:negative regulation of protein kinase activity by protein phosphorylation; TAS:ParkinsonsUK-UCL.
GO; GO:0045861; P:negative regulation of proteolysis; IMP:BHF-UCL.
GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISS:UniProtKB.
GO; GO:0038061; P:NIK/NF-kappaB signaling; IMP:CAFA.
GO; GO:0006809; P:nitric oxide biosynthetic process; TAS:ProtInc.
GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB.
GO; GO:0032287; P:peripheral nervous system myelin maintenance; IEA:Ensembl.
GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IMP:CAFA.
GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
GO; GO:0016310; P:phosphorylation; IDA:UniProtKB.
GO; GO:0030168; P:platelet activation; TAS:Reactome.
GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:DFLAT.
GO; GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB.
GO; GO:0008284; P:positive regulation of cell proliferation; IMP:UniProtKB.
GO; GO:0032270; P:positive regulation of cellular protein metabolic process; ISS:BHF-UCL.
GO; GO:0031659; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle; IDA:BHF-UCL.
GO; GO:0032079; P:positive regulation of endodeoxyribonuclease activity; IDA:UniProtKB.
GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:UniProtKB.
GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; TAS:Reactome.
GO; GO:0090004; P:positive regulation of establishment of protein localization to plasma membrane; IMP:BHF-UCL.
GO; GO:0045600; P:positive regulation of fat cell differentiation; IMP:BHF-UCL.
GO; GO:0010763; P:positive regulation of fibroblast migration; IEA:Ensembl.
GO; GO:0046326; P:positive regulation of glucose import; IMP:BHF-UCL.
GO; GO:0010907; P:positive regulation of glucose metabolic process; IMP:BHF-UCL.
GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; IMP:BHF-UCL.
GO; GO:1903721; P:positive regulation of I-kappaB phosphorylation; IMP:CAFA.
GO; GO:0046889; P:positive regulation of lipid biosynthetic process; IMP:BHF-UCL.
GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; IMP:UniProtKB.
GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IMP:BHF-UCL.
GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; IMP:BHF-UCL.
GO; GO:0046622; P:positive regulation of organ growth; IEA:Ensembl.
GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB.
GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:Ensembl.
GO; GO:1900182; P:positive regulation of protein localization to nucleus; IMP:UniProtKB.
GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:BHF-UCL.
GO; GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IDA:BHF-UCL.
GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:BHF-UCL.
GO; GO:0010765; P:positive regulation of sodium ion transport; IEA:Ensembl.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:CAFA.
GO; GO:0045907; P:positive regulation of vasoconstriction; IEA:Ensembl.
GO; GO:0046777; P:protein autophosphorylation; TAS:UniProtKB.
GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
GO; GO:0000060; P:protein import into nucleus, translocation; IMP:UniProtKB.
GO; GO:0043491; P:protein kinase B signaling; IEA:Ensembl.
GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
GO; GO:0016567; P:protein ubiquitination; IEA:Ensembl.
GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
GO; GO:1901976; P:regulation of cell cycle checkpoint; TAS:UniProtKB.
GO; GO:0030334; P:regulation of cell migration; IMP:UniProtKB.
GO; GO:0005979; P:regulation of glycogen biosynthetic process; IMP:BHF-UCL.
GO; GO:0043488; P:regulation of mRNA stability; TAS:Reactome.
GO; GO:0031641; P:regulation of myelination; IEA:Ensembl.
GO; GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB.
GO; GO:0050999; P:regulation of nitric-oxide synthase activity; TAS:Reactome.
GO; GO:0014066; P:regulation of phosphatidylinositol 3-kinase signaling; TAS:Reactome.
GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
GO; GO:0034405; P:response to fluid shear stress; IMP:BHF-UCL.
GO; GO:0032094; P:response to food; IEA:Ensembl.
GO; GO:0060416; P:response to growth hormone; ISS:AgBase.
GO; GO:0009408; P:response to heat; TAS:ProtInc.
GO; GO:1990418; P:response to insulin-like growth factor stimulus; ISS:AgBase.
GO; GO:0006979; P:response to oxidative stress; ISS:ParkinsonsUK-UCL.
GO; GO:0070141; P:response to UV-A; IDA:BHF-UCL.
GO; GO:0007165; P:signal transduction; TAS:UniProtKB.
GO; GO:0021510; P:spinal cord development; IEA:Ensembl.
GO; GO:0051146; P:striated muscle cell differentiation; IEA:Ensembl.
GO; GO:0031295; P:T cell costimulation; TAS:Reactome.
GO; GO:0031929; P:TOR signaling; NAS:ParkinsonsUK-UCL.
GO; GO:0006412; P:translation; IEA:Ensembl.
CDD; cd05594; STKc_PKB_alpha; 1.
Gene3D; 2.30.29.30; -; 1.
InterPro; IPR000961; AGC-kinase_C.
InterPro; IPR034676; Akt1.
InterPro; IPR011009; Kinase-like_dom.
InterPro; IPR011993; PH_dom-like.
InterPro; IPR001849; PH_domain.
InterPro; IPR017892; Pkinase_C.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR008271; Ser/Thr_kinase_AS.
Pfam; PF00169; PH; 1.
Pfam; PF00069; Pkinase; 1.
Pfam; PF00433; Pkinase_C; 1.
SMART; SM00233; PH; 1.
SMART; SM00133; S_TK_X; 1.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF50729; SSF50729; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS51285; AGC_KINASE_CTER; 1.
PROSITE; PS50003; PH_DOMAIN; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
1: Evidence at protein level;
3D-structure; Acetylation; Alternative splicing; Apoptosis;
ATP-binding; Carbohydrate metabolism; Cell membrane;
Complete proteome; Cytoplasm; Developmental protein; Disease mutation;
Disulfide bond; Glucose metabolism; Glycogen biosynthesis;
Glycogen metabolism; Glycoprotein; Isopeptide bond; Kinase; Membrane;
Neurogenesis; Nucleotide-binding; Nucleus; Phosphoprotein;
Polymorphism; Proto-oncogene; Reference proteome;
Serine/threonine-protein kinase; Sugar transport; Transferase;
Translation regulation; Transport; Ubl conjugation.
CHAIN 1 480 RAC-alpha serine/threonine-protein
kinase.
/FTId=PRO_0000085605.
DOMAIN 5 108 PH. {ECO:0000255|PROSITE-
ProRule:PRU00145}.
DOMAIN 150 408 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
DOMAIN 409 480 AGC-kinase C-terminal.
NP_BIND 156 164 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
REGION 14 19 Inositol-(1,3,4,5)-tetrakisphosphate
binding.
REGION 23 25 Inositol-(1,3,4,5)-tetrakisphosphate
binding.
REGION 228 230 Inhibitor binding.
ACT_SITE 274 274 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10027}.
BINDING 53 53 Inositol-(1,3,4,5)-tetrakisphosphate.
BINDING 86 86 Inositol-(1,3,4,5)-tetrakisphosphate.
BINDING 161 161 Inhibitor; via amide nitrogen.
BINDING 179 179 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
BINDING 230 230 Inhibitor; via amide nitrogen.
BINDING 234 234 Inhibitor.
BINDING 292 292 Inhibitor.
MOD_RES 14 14 N6-acetyllysine.
{ECO:0000269|PubMed:21775285}.
MOD_RES 20 20 N6-acetyllysine.
{ECO:0000269|PubMed:21775285}.
MOD_RES 124 124 Phosphoserine.
{ECO:0000244|PubMed:18669648}.
MOD_RES 126 126 Phosphoserine; alternate.
{ECO:0000244|PubMed:18669648}.
MOD_RES 129 129 Phosphoserine; alternate.
{ECO:0000244|PubMed:17081983,
ECO:0000244|PubMed:18669648,
ECO:0000244|PubMed:23186163}.
MOD_RES 176 176 Phosphotyrosine; by TNK2.
{ECO:0000269|PubMed:20333297}.
MOD_RES 308 308 Phosphothreonine; by IKKE, PDPK1 and
TBK1. {ECO:0000269|PubMed:15718470,
ECO:0000269|PubMed:18456494,
ECO:0000269|PubMed:20333297,
ECO:0000269|PubMed:20481595,
ECO:0000269|PubMed:21464307,
ECO:0000269|PubMed:8978681,
ECO:0000269|PubMed:9512493}.
MOD_RES 448 448 Phosphothreonine.
{ECO:0000244|PubMed:24275569}.
MOD_RES 450 450 Phosphothreonine.
{ECO:0000244|PubMed:24275569}.
MOD_RES 473 473 Phosphoserine; by IKKE, MTOR and TBK1;
alternate. {ECO:0000269|PubMed:14761976,
ECO:0000269|PubMed:15047712,
ECO:0000269|PubMed:15718470,
ECO:0000269|PubMed:16266983,
ECO:0000269|PubMed:17013611,
ECO:0000269|PubMed:20333297,
ECO:0000269|PubMed:20978158,
ECO:0000269|PubMed:21464307,
ECO:0000269|PubMed:23799035,
ECO:0000269|PubMed:8978681,
ECO:0000269|PubMed:9736715}.
MOD_RES 474 474 Phosphotyrosine.
{ECO:0000269|PubMed:12149249}.
CARBOHYD 126 126 O-linked (GlcNAc) serine; alternate.
{ECO:0000269|PubMed:22629392}.
CARBOHYD 129 129 O-linked (GlcNAc) serine; alternate.
{ECO:0000269|PubMed:22629392}.
CARBOHYD 305 305 O-linked (GlcNAc) threonine.
{ECO:0000269|PubMed:22629392}.
CARBOHYD 312 312 O-linked (GlcNAc) threonine.
{ECO:0000269|PubMed:22629392}.
CARBOHYD 473 473 O-linked (GlcNAc) serine; alternate.
{ECO:0000250}.
DISULFID 60 77 {ECO:0000269|PubMed:20886116}.
DISULFID 296 310 {ECO:0000250}.
CROSSLNK 284 284 Glycyl lysine isopeptide (Lys-Gly)
(interchain with G-Cter in ubiquitin).
{ECO:0000269|PubMed:22410793}.
VAR_SEQ 1 62 Missing (in isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_056180.
VARIANT 17 17 E -> K (in PROTEUSS and breast cancer;
also detected in colorectal and ovarian
cancer; somatic mutation; results in
increased phosphorylation at T-308 and
higher basal ubiquitination; the mutant
protein is more efficiently recruited to
the plasma membrane; alters
phosphatidylinositiol phosphates lipid
specificity of the AKT1 PH domain;
dbSNP:rs121434592).
{ECO:0000269|PubMed:17611497,
ECO:0000269|PubMed:18954143,
ECO:0000269|PubMed:19713527,
ECO:0000269|PubMed:21793738}.
/FTId=VAR_055422.
VARIANT 25 25 R -> C (in CWS6; dbSNP:rs397514644).
{ECO:0000269|PubMed:23246288}.
/FTId=VAR_069791.
VARIANT 167 167 V -> A (in dbSNP:rs11555433).
/FTId=VAR_051617.
VARIANT 435 435 T -> P (in CWS6; dbSNP:rs397514645).
{ECO:0000269|PubMed:23246288}.
/FTId=VAR_069792.
MUTAGEN 8 8 K->R: Substantial reduction of
ubiquitination, phosphorylation at T-308
and S-473, AKT activation as well as
IGF1-induced membrane recruitment.
Decrease in ubiquitination and
phosphorylation at T-308 as well as
impaired association with the membrane;
when associated with K-17.
{ECO:0000269|PubMed:19713527}.
MUTAGEN 14 14 K->A: Impairs interaction with
PtdIns(3,4,5)P3 and PtdIns(3,4)P2.
{ECO:0000269|PubMed:12176338,
ECO:0000269|PubMed:19713527,
ECO:0000269|PubMed:21775285}.
MUTAGEN 14 14 K->Q: Substantial reduction of
phosphorylation at T-308 and S-473, loss
of AKT activation, and loss of binding to
PIP3 as well as IGF1-induced membrane
recruitment.
{ECO:0000269|PubMed:12176338,
ECO:0000269|PubMed:19713527,
ECO:0000269|PubMed:21775285}.
MUTAGEN 14 14 K->R: Substantial reduction of
ubiquitination, phosphorylation at T-308
and S-473, AKT activation, loss of
binding to PIP3 as well as IGF1-induced
membrane recruitment.
{ECO:0000269|PubMed:12176338,
ECO:0000269|PubMed:19713527,
ECO:0000269|PubMed:21775285}.
MUTAGEN 17 17 E->K: No effect on membrane localization.
Loss of membrane localization; when
associated with Q-20.
{ECO:0000269|PubMed:21775285}.
MUTAGEN 20 20 K->Q: Substantial reduction of
phosphorylation at T-308 and S-473,
reduced AKT activation, and reduced
binding to PIP3 as well as IGF1-induced
membrane recruitment. Loss of membrane
localization; when associated with K-17.
{ECO:0000269|PubMed:21775285}.
MUTAGEN 20 20 K->R: Slight increase of phosphorylation
at T-308 and S-473.
{ECO:0000269|PubMed:21775285}.
MUTAGEN 25 25 R->A,C: Impairs interaction with
PtdIns(3,4,5)P3 and PtdIns(3,4)P2.
{ECO:0000269|PubMed:12176338}.
MUTAGEN 86 86 R->A: Impairs interaction with
PtdIns(3,4,5)P3 and PtdIns(3,4)P2.
{ECO:0000269|PubMed:12176338}.
MUTAGEN 176 176 Y->F: Significant loss of interaction
with TNK2. Loss of membrane localization.
Significant reduction in phosphorylation
on Ser-473.
{ECO:0000269|PubMed:20333297}.
MUTAGEN 305 305 T->A: Reduces O-GlcNAc levels; Reduces O-
GlcNAc levels even more; when associated
with A-312.
{ECO:0000269|PubMed:22629392}.
MUTAGEN 305 305 T->Y: Abolishes phosphorylation at Thr-
308. {ECO:0000269|PubMed:22629392}.
MUTAGEN 308 308 T->D: 5-fold activation and 18-fold
activation; when associated with D-473.
{ECO:0000269|PubMed:12244301,
ECO:0000269|PubMed:8978681}.
MUTAGEN 312 312 T->A: Reduces O-GlcNAc levels; Reduces O-
GlcNAc levels even more; when associated
with A-305.
{ECO:0000269|PubMed:22629392}.
MUTAGEN 312 312 T->Y: Abolishes phosphorylation at Thr-
308. {ECO:0000269|PubMed:22629392}.
MUTAGEN 473 473 S->D: 7-fold activation and 25-fold
activation; when associated with D-308.
{ECO:0000269|PubMed:12244301,
ECO:0000269|PubMed:8978681}.
MUTAGEN 474 474 Y->F: 55% inhibition of activation.
{ECO:0000269|PubMed:12149249}.
CONFLICT 173 174 GR -> A (in Ref. 7; CAA43372).
{ECO:0000305}.
CONFLICT 202 202 L -> Q (in Ref. 7; CAA43372).
{ECO:0000305}.
CONFLICT 212 212 A -> R (in Ref. 7; CAA43372).
{ECO:0000305}.
CONFLICT 246 246 S -> A (in Ref. 7; CAA43372).
{ECO:0000305}.
CONFLICT 409 409 A -> T (in Ref. 7; CAA43372).
{ECO:0000305}.
CONFLICT 476 476 A -> P (in Ref. 7; CAA43372).
{ECO:0000305}.
CONFLICT 478 478 G -> A (in Ref. 7; CAA43372).
{ECO:0000305}.
CONFLICT 478 478 G -> S (in Ref. 1; AAA36539, 2; AAL55732,
3; BAG36922 and 4; BAG70056/BAG70181).
{ECO:0000305}.
HELIX 2 4 {ECO:0000244|PDB:1UNQ}.
STRAND 6 15 {ECO:0000244|PDB:1UNQ}.
STRAND 17 19 {ECO:0000244|PDB:1UNQ}.
STRAND 22 30 {ECO:0000244|PDB:1UNQ}.
STRAND 33 40 {ECO:0000244|PDB:1UNQ}.
HELIX 45 48 {ECO:0000244|PDB:1UNQ}.
STRAND 52 56 {ECO:0000244|PDB:1UNQ}.
STRAND 61 65 {ECO:0000244|PDB:1UNQ}.
STRAND 67 69 {ECO:0000244|PDB:1UNQ}.
STRAND 72 79 {ECO:0000244|PDB:1UNQ}.
STRAND 82 89 {ECO:0000244|PDB:1UNQ}.
HELIX 93 115 {ECO:0000244|PDB:1UNQ}.
HELIX 147 149 {ECO:0000244|PDB:4GV1}.
STRAND 150 158 {ECO:0000244|PDB:4GV1}.
STRAND 160 169 {ECO:0000244|PDB:4GV1}.
TURN 170 172 {ECO:0000244|PDB:4GV1}.
STRAND 175 182 {ECO:0000244|PDB:4GV1}.
HELIX 183 188 {ECO:0000244|PDB:4GV1}.
HELIX 192 204 {ECO:0000244|PDB:4GV1}.
STRAND 213 218 {ECO:0000244|PDB:4GV1}.
STRAND 220 227 {ECO:0000244|PDB:4GV1}.
HELIX 235 242 {ECO:0000244|PDB:4GV1}.
HELIX 247 268 {ECO:0000244|PDB:4GV1}.
HELIX 277 279 {ECO:0000244|PDB:4GV1}.
STRAND 280 282 {ECO:0000244|PDB:4GV1}.
STRAND 284 286 {ECO:0000244|PDB:4EJN}.
STRAND 288 290 {ECO:0000244|PDB:4GV1}.
STRAND 309 311 {ECO:0000244|PDB:3MVH}.
HELIX 313 315 {ECO:0000244|PDB:4GV1}.
HELIX 318 322 {ECO:0000244|PDB:4GV1}.
HELIX 330 344 {ECO:0000244|PDB:4GV1}.
HELIX 354 363 {ECO:0000244|PDB:4GV1}.
HELIX 374 383 {ECO:0000244|PDB:4GV1}.
HELIX 388 390 {ECO:0000244|PDB:4GV1}.
TURN 396 398 {ECO:0000244|PDB:4GV1}.
HELIX 399 403 {ECO:0000244|PDB:4GV1}.
HELIX 406 408 {ECO:0000244|PDB:4GV1}.
HELIX 413 417 {ECO:0000244|PDB:4GV1}.
STRAND 430 433 {ECO:0000244|PDB:3MVH}.
HELIX 440 443 {ECO:0000244|PDB:4GV1}.
STRAND 464 466 {ECO:0000244|PDB:4GV1}.
STRAND 473 475 {ECO:0000244|PDB:4GV1}.
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


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Catalog number Product name Quantity
EIAAB31334 Bos taurus,Bovine,PKN,PKN1,PRK1,PRKCL1,Protein kinase C-like 1,Protein kinase C-like PKN,Protein kinase PKN-alpha,Protein-kinase C-related kinase 1,Serine_threonine-protein kinase N1,Serine-threonine
18-785-210338 p70 S6 Kinase (Phospho-Ser411) - EC 2.7.11.1; Ribosomal protein S6 kinase I; S6K; S6K1; 70 kDa ribosomal protein S6 kinase 1; p70 S6 kinase alpha; p70(S6K)-alpha; p70-S6K; P70S6K; p70-alpha Polyclonal 0.05 mg
18-785-210339 p70 S6 Kinase (Phospho-Ser424) - EC 2.7.11.1; Ribosomal protein S6 kinase I; S6K; S6K1; 70 kDa ribosomal protein S6 kinase 1; p70 S6 kinase alpha; p70(S6K)-alpha; p70-S6K; P70S6K; p70-alpha Polyclonal 0.05 mg
18-785-210339 p70 S6 Kinase (Phospho-Ser424) - EC 2.7.11.1; Ribosomal protein S6 kinase I; S6K; S6K1; 70 kDa ribosomal protein S6 kinase 1; p70 S6 kinase alpha; p70(S6K)-alpha; p70-S6K; P70S6K; p70-alpha Polyclonal 0.1 mg
18-785-210337 p70 S6 Kinase (Phospho-Thr421) - EC 2.7.11.1; Ribosomal protein S6 kinase I; S6K; S6K1; 70 kDa ribosomal protein S6 kinase 1; p70 S6 kinase alpha; p70(S6K)-alpha; p70-S6K; P70S6K; p70-alpha Polyclonal 0.05 mg
18-785-210338 p70 S6 Kinase (Phospho-Ser411) - EC 2.7.11.1; Ribosomal protein S6 kinase I; S6K; S6K1; 70 kDa ribosomal protein S6 kinase 1; p70 S6 kinase alpha; p70(S6K)-alpha; p70-S6K; P70S6K; p70-alpha Polyclonal 0.1 mg
18-785-210337 p70 S6 Kinase (Phospho-Thr421) - EC 2.7.11.1; Ribosomal protein S6 kinase I; S6K; S6K1; 70 kDa ribosomal protein S6 kinase 1; p70 S6 kinase alpha; p70(S6K)-alpha; p70-S6K; P70S6K; p70-alpha Polyclonal 0.1 mg
EIAAB25359 CDC42-binding protein kinase alpha,CDC42BPA,DMPK-like alpha,Homo sapiens,Human,KIAA0451,MRCK alpha,Myotonic dystrophy kinase-related CDC42-binding kinase alpha,Myotonic dystrophy protein kinase-like a
EIAAB31333 Homo sapiens,Human,PAK1,PAK-1,PKN,PKN1,PRK1,PRKCL1,Protease-activated kinase 1,Protein kinase C-like 1,Protein kinase C-like PKN,Protein kinase PKN-alpha,Protein-kinase C-related kinase 1,Serine_threo
EIAAB25358 CDC42-binding protein kinase alpha,Cdc42bpa,MRCK alpha,Myotonic dystrophy kinase-related CDC42-binding kinase alpha,Myotonic dystrophy protein kinase-like alpha,Pk428,Rat,Rattus norvegicus,Serine_thre
EIAAB31332 Mouse,Mus musculus,Pkn,Pkn1,Prk1,Prkcl1,Protein kinase C-like 1,Protein kinase C-like PKN,Protein-kinase C-related kinase 1,Serine_threonine-protein kinase N1,Serine-threonine protein kinase N
18-662-20052 Calcium_calmodulin-dependent protein kinase type II alpha chain - EC 2.7.11.17; CaM-kinase II alpha chain; CaM kinase II alpha subunit; CaMK-II subunit alpha Polyclonal 0.1 ml
17-662-20008 Calcium_calmodulin-dependent protein kinase type II alpha chain - EC 2.7.11.17; CaM-kinase II alpha chain; CaM kinase II alpha subunit; CaMK-II subunit alpha Serum 0.1 ml
EIAAB31006 Homo sapiens,Human,Phosphatidylinositol 4-kinase alpha,PI4KA,PI4K-alpha,PI4-kinase alpha,PIK4,PIK4CA,PtdIns-4-kinase alpha
18-785-210341 p70 S6 Kinase (Ab-421) - EC 2.7.11.1; Ribosomal protein S6 kinase I; S6K; S6K1; 70 kDa ribosomal protein S6 kinase 1; p70 S6 kinase alpha; p70(S6K)-alpha; p70-S6K; P70S6K; p70-alpha Polyclonal 0.1 mg
18-785-210342 p70 S6 Kinase (Ab-411) - EC 2.7.11.1; Ribosomal protein S6 kinase I; S6K; S6K1; 70 kDa ribosomal protein S6 kinase 1; p70 S6 kinase alpha; p70(S6K)-alpha; p70-S6K; P70S6K; p70-alpha Polyclonal 0.05 mg
18-785-210342 p70 S6 Kinase (Ab-411) - EC 2.7.11.1; Ribosomal protein S6 kinase I; S6K; S6K1; 70 kDa ribosomal protein S6 kinase 1; p70 S6 kinase alpha; p70(S6K)-alpha; p70-S6K; P70S6K; p70-alpha Polyclonal 0.1 mg
18-785-210341 p70 S6 Kinase (Ab-421) - EC 2.7.11.1; Ribosomal protein S6 kinase I; S6K; S6K1; 70 kDa ribosomal protein S6 kinase 1; p70 S6 kinase alpha; p70(S6K)-alpha; p70-S6K; P70S6K; p70-alpha Polyclonal 0.05 mg
18-785-210340 p70 S6 Kinase (Ab-389) - EC 2.7.11.1; Ribosomal protein S6 kinase I; S6K; S6K1; 70 kDa ribosomal protein S6 kinase 1; p70 S6 kinase alpha; p70(S6K)-alpha; p70-S6K; P70S6K; p70-alpha Polyclonal 0.1 mg
18-785-210340 p70 S6 Kinase (Ab-389) - EC 2.7.11.1; Ribosomal protein S6 kinase I; S6K; S6K1; 70 kDa ribosomal protein S6 kinase 1; p70 S6 kinase alpha; p70(S6K)-alpha; p70-S6K; P70S6K; p70-alpha Polyclonal 0.05 mg
18-785-210343 p70 S6 Kinase (Ab-424) - EC 2.7.11.1; Ribosomal protein S6 kinase I; S6K; S6K1; 70 kDa ribosomal protein S6 kinase 1; p70 S6 kinase alpha; p70(S6K)-alpha; p70-S6K; P70S6K; p70-alpha Polyclonal 0.05 mg
18-785-210343 p70 S6 Kinase (Ab-424) - EC 2.7.11.1; Ribosomal protein S6 kinase I; S6K; S6K1; 70 kDa ribosomal protein S6 kinase 1; p70 S6 kinase alpha; p70(S6K)-alpha; p70-S6K; P70S6K; p70-alpha Polyclonal 0.1 mg
EIAAB24858 c-Jun N-terminal kinase 2,Jnk2,MAP kinase 9,MAPK 9,Mapk9,Mitogen-activated protein kinase 9,p54-alpha,Prkm9,Rat,Rattus norvegicus,SAPK-alpha,Stress-activated protein kinase JNK2
EIAAB31007 Bos taurus,Bovine,Phosphatidylinositol 4-kinase alpha,PI4KA,PI4K-alpha,PI4-kinase alpha,PIK4CA,PtdIns-4-kinase alpha
EIAAB11059 80 kDa diacylglycerol kinase,DAG kinase alpha,DAGK,DAGK1,DGKA,DGK-alpha,Diacylglycerol kinase alpha,Diglyceride kinase alpha,Homo sapiens,Human


 

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