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PI3K / Akt Substrates Table

The PI3K / Akt Substrates Table provides a comprehensive list of demonstrated downstream targets of Akt phosphorylation, along with the relevant phosphorylation site, publication reference and effect of phosphorylation. This information was generated using PhosphoSitePlus®, CST's open scientific resource of protein modification information, available on the web at www.phosphosite.org.

SubstrateIsoformOrganismSiteHuman SiteSequence (+/-)PMIDSubstrate Function & Effect of Phosphorylation
14-3-3 zAkt1humanS58S58VVGARRSsWRVVssI11956222A key regulatory protein in signal transduction, checkpoint control, apoptotic, and nutrient-sensing pathways; effect of phosphorylation is unknown
acinusAkt1humanS1180S1180GPRsRsRsRDRRRKE18559500, 16177823Induces chromatin condensation during apoptosis; phosphorylation inhibits this process
 Akt1ratS1329S1331HSRSRSRsTPVRDRG16177823
ACLYAkt1mouseS455S455PAPSRtAsFsESRAD16007201Catalyzes the formation of acetyl-CoA and oxaloacetate (OAA) in the cytosol; phosphorylation enhances the catalytic activity of the enzyme
ADRB2Akt1humanS346S346LLCLRRssLKAyGNG11809767A receptor that binds epinephrine and norepinephrine, acting as a neuromodulator in the central nervous system and as a hormone in the vascular system; phosphorylation in response to insulin stimulation leads to sequestration of ADBR2
Akt1Akt1humanS246, T72S246, T72LSRERVFsEDRARFY, TERPRPNtFIIRCLQ16549426Activated by insulin and various growth and survival factors to function in a wortmannin-sensitive PI3 kinase-involved pathway controlling survival and apoptosis; autophosphorylation activates the kinase
 Akt1mouseS473S473RPHFPQFsYsAsGtA11570877, 10722653
AMPKA1Akt1ratS485S485ATPQRSGsISNYRSC16340011Heterotrimeric complex that plays a key role in the regulation of energy homeostasis; phosphorylation regulates AMPK activity
AMPKA2Akt1ratS491S491STPQRSCsAAGLHRP16340011Heterotrimeric complex that plays a key role in the regulation of energy homeostasis; phosphorylation regulates AMPK activity
APSAkt1ratS588S598SARSRSNsTEHLLEA16141217An adaptor protein recruited to the insulin receptor to signal insulin-stimulated glucose transport; phosphorylation promotes membrane localization
ARAkt1humanS213, S791S213, S791SGRAREAsGAPTsSK, CVRMRHLsQEFGWLQ11404460, 14555644, 17470458, 11156376Nuclear receptor; phosphorylation suppresses AR activation, expression of AR target genes, and AR-mediated apoptosis
arfaptin 2Akt1humanS260S260GTRGRLEsAQATFQA15809304ADP ribosylation factor-interacting protein, implicated as a factor in Huntington's disease; phosphorylation promotes neuronal cell survival and neuroprotection
ARHGAP22Akt1humanS16S16ARRARSKsLVMGEQS21969604A Rho GTPase activator that inhibits Rac1; phosphorylation allows 14-3-3 binding and regulation of cell motility
AS160Akt1humanT642T642QFRRRAHtFsHPPss16880201, 11994271, 16935857Insulin stimulated Rab GTPase-activating protein, structurally and functionally similar to TBC1D1; phosphorylation results in increased Glut4 translocation
ASK1Akt1, Akt2humanS83S83ATRGRGssVGGGSRR11154276, 15782121, 15911620, 14500571, 12697749MAPKKK, induces apoptosis via JNK pathway; phosphorylation inhibits activity and promotes survival
ataxin-1Akt1humanS775S775ATRKRRWsAPESRKL17540008, 1275770714-3-3 binds to and stabilizes ataxin-1, which forms polyglutamine aggregates and neurodegeneration; phosphorylation promotes 14-3-3 binding
B-RafAkt1, Akt3humanS365, S429S365, S429GQRDRsssAPNVHIN, PQRERKsssSsEDRN10869359, 18451171Signaling intermediate in Erk1/2 pathway; phosphorylation causes inhibition
BADAkt1humanS99S99PFRGRsRsAPPNLWA11020382, 10558990, 19667065Pro-apoptotic protein; phosphorylation inhibits function and promotes survival
Akt1mouseS112, S155S75, S118ETRsRHssyPAGtEE, GRELRRMsDEFEGSF9381178, 11723239, 10983986, 15123689, 10949026
Bcl-10Akt1humanS218, S231S218, S231EEGTCANsSEMFLPL, PLRSRtVsRQ_____16280327A CARD (caspase recruitment domain) containing protein shown to induce apoptosis and activate NF-κB; phosphorylation induces nuclear translocation
Bcl-xLAkt1ratS106S106LRYRRAFsDLTSQLH18951975Prevents apoptosis through binding to apoptotic proteins; phosphorylation promotes VDAC binding
Bex1Akt1ratS105S102KLRERQLsHSLRAVS16498402A neurotrophin and nerve growth factor signaling adaptor molecule involved in promoting cell cycle progression; phosphorylation prevents degradation by the proteasome
BimAkt1humanS87S87FIFMRRssLLSRSss16282323Pro-apoptotic protein; phosphorylation promotes 14-3-3 binding/inactivation and cell survival
BRCA1Akt1humanS694, T509S694, T509QTSKRHDsDTFPELK, LKRKRRPtsGLHPED20085797, 10542266Breast cancer susceptibility gene product, tumor suppressor; phosphorylation alters function, perhaps by preventing nuclear localization
BRF1Akt1humanS92, S203S92, S203RFRDRsFsEGGERLL, PRLQHsFsFAGFPSA17030608, 15538381A CCCH zinc-finger protein that binds to AU-rich elements (ARE) found in the 3'-untranslated regions of mRNAs and promotes de-adenylation and rapid degradation by the exosome; phosphorylation results in binding by 14-3-3 protein and inactivation of BRF1
CACNB2Akt1ratS625S630KQRSRHKsKDRYCDK15311280Voltage-dependent calcium channel; phosphorylation regulates channel trafficking to plasma membrane
CaRHSP1Akt1humanS52S52tRRtRtFsAtVRASQ15910284RNA binding protein; phosphorylation effect currently unknown
Casp9Akt1humanS196S196KLRRRFssLHFMVEV9812896Protease, initiates apoptosis; phosphorylation inhibits protease activity
CBPAkt1mouseT1872T1871LMRRRMAtMNTRNVP17166829Acetylates histone and non-histone proteins; phosphorylation increases activity
CBY1Akt1, Akt2humanS20S20TPPRKSAsLSNLHsL18573912An inhibitor of the Wnt signaling pathway; phosphorylation allows 14-3-3 binding and β-catenin sequestration in the cytoplasm
CCT2Akt1humanS260S260GsRVRVDstAkVAEI19332537Member of the protein chaperone complex; effect of phosphorylation currently unknown
CD34Akt2mouseS343S346yssGPGAsPETQGKA21499536A type I transmembrane glycophosphoprotein expressed by hematopoietic stem/progenitor cells, vascular endothelium and some fibroblasts as a negative regulator of cell adhesion; effect of phosphorylation currently unknown
Cdc25BAkt1mouseS351S353VQSKRRKsVtPLEEQ17554083Protein phosphatase responsible for cdc2 activation; phosphorylation promotes activation of M-phase promoting factor
CDK2Akt1humanT39T39LkKIRLDtETEGVPs18354084Cyclin-dependent kinase functioning in S-phase; phosphorylation increases cyclin A binding
CELF1Akt1humanS28S28GQVPRTWsEKDLREL18570922RNA-binding protein; phosphorylation enhances interaction with cyclin D1 mRNA
CENTB1Akt1humanS554S554SIRPRPGsLRSKPEP16256741GTPase-activating protein (GAP) for ARF proteins; phosphorylation prevents recycling of b1-integrin containing endosomes and cell migration
CENTG1Akt1humanS985S985THLSRVRsLDLDDWP19176382A GTPase activating protein for ARF1 and ARF5; phosphorylation enhances CENTG1 GTP binding and NF-κB activity
CFLARAkt1humanS273S273LLRDTFTsLGYEVQK19339247A regulator of apoptosis; phosphorylation targets CFLAR for degradation
Chk1Akt1humanS280S280AKRPRVtsGGVsEsP15107605, 12062056DNA damage effector that regulates G2/M transition during DNA damage; phosphorylation inhibits function by preventing phosphorylation by ATM/ATR
CK1-DAkt1ratS370S370MERERKVsMRLHRGA17594292Kinase and core component of circadian clock; phosphorylation inhibits kinase activity
CLK2Akt1humanS34, T127S34, T127HKRRRSRsWSSSSDR, RRRRRSRtFSRSSSQ20682768A dual specificity serine/threonine and tyrosine kinase; phosphorylation increases cell survival after ionizing radiation
CotAkt1humanS400S400EDQPRCQsLDSALLE12138205Oncogene; phosphorylation induces NF-κB-dependent transcription
CREBAkt1ratS133S133EILsRRPsYRkILND9829964bZIP transcription factor that activates target genes through cAMP response elements; activated by phosphorylation
CTNNB1Akt1, Akt2humanS552S552QDtQRRtsMGGtQQQ17287208Wnt signaling pathway protein; phosphorylation causes nuclear localization
CTNND2Akt1mouseT454T457tGTFRtstAPssPGV17993462Transcriptional activator, plays a role in adhesion molecule regulation; phosphorylation promotes binding to p190RhoGEF, dendritic morphogenesis
Cx43Akt1ratS369S369RPssRAssRAssRPR18163231Gap junction protein; phosphorylation allows 14-3-3 binding
Akt1, Akt3ratS373S373RAssRAssRPRPDDL17008717, 18163231
DLC1Akt1ratS330S766VTRTRSLsTCNKRVG16338927Tumor suppressor and insulin stimulated phosphoprotein, may play role in Glut4 translocation; phosphorylation may inhibit its GAP activity
DNAJC5Akt1ratS10S10DQRQRsLsTSGESLY16243840Exocytosis; phosphorylation regulates the kinetics of late stage exocytosis
DNMT1Akt1humanS143S143RtPRRsksDGEAkPE21151116A maintenance methyltransferase, transferring proper methylation patterns to newly synthesized DNA during replication; phosphorylation increases DNMT1 stability and prevents methylation
EDC3Akt1, Akt2humanS161S161sFRRRHNsWssSsRH20051463Involved in removal of the mRNA 5' cap structure; phosphorylation induces 14-3-3 protein interaction and promotes ED3 mediated post-transcriptional regulation through mRNA
EDG-1Akt1humanT236T236RTRSRRLtFRKNISK11583630G protein-coupled receptor; phosphorylation activates signaling to promote cell migration
eIF4BAkt1mouseS422S422RERsRtGsEssQtGA18836482Necessary for binding of mRNA to ribosomes; phosphorylation increases transcriptional activity
ENaC-aAkt1ratS621S594RFRSRYWsPGRGARG21220922An amiloride sensitive epithelial sodium channel that mediates sodium reabsorption; phosphorylation increases ENaC specific activity
eNOSAkt1humanS615, S1177S615, S1177SYKIRFNsISCSDPL, TsRIRtQsFsLQERQ12511559, 12446767, 10376603, 18622039, 12171920Enzyme that catalyzes the production of nitric oxide (NO); phosphorylation results in enzyme activation, NO production, and cardiovascular homeostasis (vasodilation, vascular remodeling, angiogenesis)
EphA2Akt1humanS897S897RVsIRLPstsGsEGV19573808Receptor tyrosine kinase that binds to a GPI-anchored ephrin A ligand for regulation of cell adhesion, cell migration, axon guidance, and homeostasis; phosphorylation regulates EphA2 induced cell migration and invasion
ER-aAkt1, Akt2humanS167S167GGRERLAsTNDKGSM11139588, 16113102, 11507039Nuclear receptor and transcription factor; phosphorylation activates the receptor and increases gene expression, causing mammary and uterine cell proliferation
Akt1humanS305S305IkRSkkNsLALSLtA20101208
ER-bAkt1mouseS236D236VRRQRSAsEQVHCLN17166829Nuclear receptor and transcription factor; phosphorylation prevents cofactor binding and decreases activity
EZH2Akt1humanS21S21CWRKRVKsEYMRLRQ16224021Methyltransferase; phosphorylation decreases histone H3 methylation of Lys27 and increases gene expression
ezrinAkt2humanT567T567QGRDKYKtLRQIRQG15531580Plasma membrane/cytoskeletal linker protein; phosphorylation promotes actin binding and cytoskeletal organization
FANCAAkt1humanS1149S1149CLRSRDPsLMVDFIL11855836ATPase involved in DNA repair; phosphorylation is negatively regulated by Akt
FLEG1Akt1humanS486S486GLEtRRLsLPSsKAK17256767A chaperone protein involved in directing specific histones to the centromere; phosphorylation allows binding to 14-3-3
FLNCAkt1, Akt2humanS2233S2233LGRERLGsFGsItRQ15461588Muscle-specific filamin functioning in muscle cells; phosphorylation effect currently unknown
FOXA2Akt1humanT156T156KTYRRSYtHAKPPYS14500912Transcription factor involved in embryonic development and differentiation; phosphorylation results in nuclear exclusion and inhibition of FoxA2-dependent transcriptional activity
FOXG1Akt1humanT279T279KLRRRSttsRAKLAF17435750Transcriptional repression factor involved in brain development; phosphorylation promotes nuclear export
FOXO1AAkt1humanS256, S319, T24S256, S319, T24sPrRrAAsMDNNSkF, TFRPRtssNAsTIsG, LPRPRSCtWPLPRPE15668399, 10358075, 11237865, 16076959, 11311120Transcription factor involved in cell cycle arrest, apoptosis, and glucose metabolism; phosphorylation causes export from the nucleus and inhibits activity
FOXO3AAkt1humanS253, T32S253, T32APRRRAVsMDNSNKY, QSRPRsCtWPLQRPE10910908, 10995739, 10102273, 11154281Transcription factor involved in cell cycle arrest and apoptosis; phosphorylation causes export from the nucleus and inhibits activity
FOXO4Akt1humanS197, S262, T32S197, S262, T32APRRRAAsMDSSSKL, TFRPRSssNASSVST, QSRPRsCtWPLPRPE11313479, 11313479, 10217147, 16272144Transcription factor involved in cell cycle arrest, apoptosis, and insulin signaling; phosphorylation causes export from the nucleus and inhibits activity
Gab2Akt1humanS159S159LLRERKSsAPSHsSQ11782427Docking/scaffolding protein, proto-oncogene, RTK signaling intermediate; phosphorylation inhibits activity
GABRB2Akt1ratS434S434SRLRRRAsQLKITIP12818177Receptor that mediates fast inhibitory synaptic transmission in the brain; phosphorylation increases the number of receptors on the cell surface
GAPDHAkt2humanT237T237GMAFRVPtANVSVVD21979951Catalyzes the phosphorylation of glyceraldehyde-3-phosphate during glycolysis; phosphorylation decreases nuclear translocation and GAPDH induced apoptosis
GATA1Akt1humanS310S310QTRNRKAsGkGkkkR16107690Transcription factor; phosphorylation increases activity and promotes blood cell differentiation
GATA2Akt1humanS401S401QTRNRKMsNKSKKSK15837948Transcription factor; phosphorylation inhibits activity to promote adipogenesis and reduce inflammation
girdinAkt1humanS1417S1417INRERQKsLtLTPTR16139227Actin binding protein; phosphorylation promotes cell migration
GOLGA3Akt1mouseS174, S385S174, S389VKRHRERsSQPAtKM, EVRsRRDsICsSVSM17888676Golgi auto-antigen; phosphorylation results in reduced apoptosis
Grb10Akt1mouseS455S428NAPMRsVsENsLVAM15722337An adaptor protein that interacts with many receptor tyrosine kinases as well as downstream signal molecules; phosphorylation allows binding to 14-3-3
GSK-3aAkt1humanS21S21SGRARtssFAEPGGG11340086, 11563975, 11577096Serine/threonine protein kinase that phosphorylates and inactivates glycogen synthase; phosphorylation inhibits activity
GSK-3bAkt1humanS9S9SGRPRttsFAESCKP12900420, 15457186, 11563975, 11340086, 11577096, 8985174Serine/threonine protein kinase that phosphorylates and inactivates glycogen synthase; phosphorylation inhibits activity
H2BAkt1humanS37S37RKRsRkEsysIyVyk8985174Core component of the nucleosome; phosphorylation effect currently unknown
H3Akt1mouseS10S10tKQTARksTGGkAPR12529330Core component of the nucleosome; phosphorylation is correlated with chromosome condensation during mitosis and meiosis
HMOX1Akt1humanS188S188LYRSRMNsLEMtPAV15581622Heme oxygenase involved in stress response; phosphorylation regulates binding affinity
hnRNP A1Akt1humanS199S199sQrGrsGsGNFGGGr18562319Involved in pre-mRNA packaging into hnRNP particles and transport of poly(A) mRNA from cytoplasm to nucleus; phosphorylation regulates role in cyclin D1 and c-Myc IRES activity
hnRNP E1Akt1, Akt2mouseS43S43VKRIREEsGARINIS20154680Binds to single-stranded nucleic acid; phosphorylation results in disruption of BAT element binding and translational activation of Dab2 and ILEI mRNA
HSP27Akt1humanS82S82RALsRQLssGVSEIR12740362Heat shock protein that confers cellular resistance to stress and adverse environmental change; phosphorylation alters tertiary structure, modulates actin polymerization, and reorganization
HTRA2Akt1, Akt2humanS212S212RVRVRLLsGDTYEAV17311912Protease released during apoptosis; phosphorylation inhibits activity and attenuates its pro-apoptotic function
HuntingtinAkt1humanS421S421GGRsRsGsIVELIAG12062094, 14725621, 15843398, 16452687Huntington's disease; Akt phosphorylation blocks nuclear aggregation and provides neuroprotection
IKK-aAkt1, Akt2humanT23T23EMRERLGtGGFGNVC18515365, 12048203, 10485710, 19609947NF-κB signaling intermediate; phosphorylation activates NF-κB and immune/stress response
IP3R1Akt1ratS2682S2690FPRMRAMsLVSSDSE16332683Ca2+ release and signaling; phosphorylation induces resistance to apoptosis, possibly through caspase-3 inactivation
IRAK1Akt1humanT100T100LRARDIItAWHPPAP11976320A serine/threonine-specific IL-1 receptor-associated kinase involved in Toll signaling; phosphorylation inhibits IRAK mediated NK-κB activation
IRS1Akt1humanS629S629VPSGRKGsGDyMPMs17640984Insulin receptor signaling intermediate; phosphorylation inhibits function
Akt1ratS522S527RFRKRTHsAGTSPTI17579213
KHSRPAkt1, Akt2humanS193S193GLPERSVsLTGAPES17177604Recruits degradation machinery, activates mRNA turnover, regulates splicing; phosphorylation inhibits RNA turnover by degradation
Kv11.1 iso5Akt1humanT897T897SFRRRtDtDtEQPGE18791070Pore-forming subunit of voltage-gated potassium channels, essential for rhythmic excitability of cardiac muscle and endocrine cells; phosphorylation inhibits channels
Lamin A/CAkt1ratS301, S404S301, S404RSRGRASsHSSQSQG18808171Component of nuclear lamina; phosphorylation regulates function of nuclear lamina
LTB4R2Akt1humanT355T355GGRsREGtMELRTTP22044535A low-affinity leukotriene receptor involved in chemotaxis; phosphorylation regulates activation of chemotactic responses
Mad1Akt1humanS145S145IERIRMDsIGSTVSS18451027, 19526459,Component of spindle-assembly checkpoint; phosphorylation results in ubiquitination and degradation through 26S proteasome pathway
MDM2Akt1humanS166, S186, S188S166, S186, S188SsRRRAIsEtEENsD, RQRKRHKsDsIsLsF, RKRHKsDsIsLsFDE11715018, 15169778, 11504915, 11850850, 11923280, 15527798, 11960368Ubiquitin ligase involved in p53 degradation; phosphorylation results in translocation to the nucleus and inhibition of p53
MDM4Akt1humanS367S367PDCRRtIsAPVVRPK18356162RING-finger domain protein involved in p53 degradation and apoptosis; phosphorylation stabilizes MDM4 and MDM2
METTL1Akt1humanS27S27yYRQrAHsNPMADHT15861136Catalyzes the formation of m7G46 in tRNA; phosphorylation results in inactivation
MKK4Akt1humanS80S80IERLRtHsIEsSGKL15911620, 11707464Signaling intermediate of the JNK/SAPK pathway involved in stress/inflammation; phosphorylation inhibits activity
MLK3Akt1humanS674S674PGRERGEsPTtPPTP12458207JNK-mediated neuronal cell death; phosphorylation inhibits activity
MST1Akt1humanT120T120IIRLRNktLTEDEIA19940129Pro-apoptotic kinase; phosphorylation inhibits kinase activity and nuclear translocation resulting in inhibition of pro-apoptotic signaling
MST2Akt1humanT117, T384T117, T384IIRLRNktLIEDEIA, GTMKRNAtsPQVQRP20231902, 20086174Upstream activator of the MAPK pathway that regulates apoptosis, morphogenesis, and cytoskeletal rearrangements; phosphorylation inhibits pro-apoptotic activity
mTORAkt1humanT2446, S2448T2446, S2448RsRtRtDsysAGQsV15208671, 10910062, 10567225Protein synthesis and cell growth; phosphorylation increases activity
MYO5AAkt2mouseS1650S1652GLRKRtssIADEGty17515613Actin-based motor protein with a role in cytoplasmic vesicle transport and anchorage; phosphorylation promotes insulin-mediated Glut4 vesicle translocation
Myt1Akt1starfishS75S83ESRPRAVsFRQSEPS11802161Wee1 family member and cell cycle regulator; phosphorylation downregulates Myt1 and initiates M-phase
NDRG2Akt1humanS332, T348S332, T348LsRsRtAsLtsAAsV, GNRsRsRtLsQssEs15461589Insulin-stimulated phosphoprotein; phosphorylation promotes insulin signaling
NFAT90Akt1humanS647S647rGrGRGGsIRGRGRG18097023, 20870937Translation inhibitory protein; phosphorylation required for nuclear export
NHE1Akt1humanS648, S703, S796S648, S703, S796KTRQRLRsyNRHTLV, MsRARIGsDPLAyEP, QRIQRCLsDPGPHPE18757828, 20026127Sodium/hydrogen exchanger involved in pH regulation and signal transduction; phosphorylation inhibits activity
NMDAR2CAkt1mouseS1084S1081GPRPRHAsLPSSVAE19477150Glutamate receptor channel subunit; phosphorylation promotes binding to 14-3-3ε and leads to increased surface expression of cerebellar NMDA receptors
Akt1ratS1083S1081GPRPRHAsLPSSVAE19477150
NuaK1Akt1humanS600S600PARQRIRsCVSAENF15060171, 12409306AMPK family member activated under glucose starvation that mediates cell survival; phosphorylation increases kinase activity
Nur77Akt1humanS351S351GRRGRLPsKPKQPPD16434970, 11274386A nuclear receptor and transcription factor regulating T cell apoptosis; phosphorylation inhibits transcriptional activity
p21 Cip1Akt1humanS146, T145S146, T145GRkRRQtsMTDFYHs, QGRkRRQtsMTDFYH17855660, 11231573, 11756412, 15173090, 11463845, 116982699Regulates cell cycle and cell survival; phosphorylation increases protein stability
p27Kip1Akt1humanS10, T157, T198S10, T157, T198NVRVsNGsPsLErMD, GIRkrPAtDDSSTQN, PGLRRRQt_______18710949, 12042314, 12244302A cyclin-dependent kinase inhibitor that enforces the G1 cell cycle restriction point; phosphorylation promotes 14-3-3 binding and cytoplasmic localization
p300Akt1humanS1834S1834MLRRRMAsMQRTGVV16024795, 11116148Transcriptional co-activator; phosphorylation can either activate or suppress transcriptional activity depending on cell type and physiological stimuli
p47phoxAkt1humanS304, S328S304, S328GAPPRRssIRNAHSI, QDAYRRNsVRFLQQR12734380A component of the phagocytic NADPH oxidase multiprotein enzyme that catalyzes the reduction of oxygen to superoxide in response to pathogenic invasion; phosphorylation regulates p47hox respiratory burst activity
PAK1Akt1mouseS21S21APPMRNTsTMIGAGS14585966A p21-activated kinase engaged in cytoskeletal reorganization, MAPK signaling, apoptotic signaling, control of phagocyte NADPH oxidase, and growth factor-induced neurite outgrowth; phosphorylation at Ser21 regulates binding with the adaptor protein Nck
palladinAkt1humanS1118S1118VRRPRsRsRDsGDEN20471940Actin-bundling protein; phosphorylation promotes F-actin bundling and inhibits cell migration
PAR-4Akt1ratS249N257SRHNRDTsAPANFAS16209943A pro-apoptotic factor that activates the Fas-FADD-caspase-8 pathway as well as inhibits the NF-κB pro-survival pathway; phosphorylation prevents nuclear translocation, promoting cell survival
PDCD4Akt1humanS67, S457S67, S457kRRLRKNssRDsGRG, RGRKRFVsEGDGGRL16357133Tumor suppressor protein that is strongly induced during apoptosis; phosphorylation inhibits tumor suppressor function
PDE3AAkt1mouseS290, S291, S292S290, S291, S292GWKRRRRsssVVAGE, WKRRRRsssVVAGEM, KRRRRsssVVAGEMS17124499Regulates levels of cAMP and cGMP, insulin-dependent oocyte maturation; phosphorylation increases activity
PDE3BAkt1mouseS273S295VIRPRRRssCVsLGE10454575Regulates levels of cAMP and cGMP, activated by insulin to regulate lipolysis; phosphorylation increases activity
PEA-15Akt1humanS116S116KDIIRQPsEEEIIKL12808093A phosphoprotein shown to coordinate cell growth, death, and glucose utilization; phosphorylation mediates binding to FADD or Erk and further regulates the Erk and apoptosis signaling pathways
peripherinAkt1mouseS66S59SSSARLGsFRAPRAG17569669Neuronal intermediate filament protein; phosphorylation promotes motor nerve regeneration
PFKFB2Akt1humanS466, S483S466, S483PVRMRRNsFtPLSSS, IRRPRNysVGSRPLK12853467Glycolytic enzyme, insulin-mediated glucose metabolism; phosphorylation increases activity
PFKFB3Akt1humanS461S461NPLMRRNsVtPLAsP15896703Synthesis and degradation of fructose 2,6-bisphosphate; phosphorylation decreases sensitivity to inhibition
PGC-1 aAkt1, Akt2mouseS570S571RMRSRsRsFsRHRSC17554339Regulates gluconeogenesis and fatty acid oxidation; phosphorylation inhibits function
PIP5KAkt1humanS307S307PARNRsAsItNLsLD15546921A protein/ lipid kinase involved in membrane trafficking; phosphorylated in response to insulin
Akt1mouseS105S105EELHRRSsVLENTLP20513353
PLBAkt1ratS16S16RSAIRRAstIEMPQQ18838385A major phosphoprotein calcium regulation component of the sarcoplasmic reticulum; phosphorylation causes release of inhibition and increases calcium uptake by the sarcoplasmic reticulum
PLCG1Akt1humanS1248S1248HGRAREGsFEsRyQQ16525023Catalyzes PI 4,5 bisphosphate to IP3 and DAG, increases intracellular Ca2+ levels; phosphorylation increases activity and enhances EGF-stimulated cell motility
PPP1CAAkt1humanT320T320NPGGRPItPPRNSAK14633703A serine/threonine phosphatase involved in cell cycle regulation; phosphorylation inhibits activity
PRAS40Akt1humanT246T246LPRPRLNtsDFQKLK12524439, 17277771, 18372248Binds to and inhibits mTOR; phosphorylation causes 14-3-3 binding/inhibition and results in increased protein synthesis
PRPF19Akt1humanT193T193ERKKRGKtVPEELVK20629186A member of the splicesome that also functions in DNA double strand break repair; phosphorylation allows 14-3-3 binding
PRPKAkt1humanS250S250RLRGRKRsMVG____17712528p53 binding protein and kinase; phosphorylation causes activation and results in p53 phosphorylation
PTP1BAkt1humanS50S50RNRyRDVsPFDHsRI11579209Protein tyrosine phosphatase that dephosphorylates the insulin receptor; phosphorylation inhibits activity
QIKAkt2mouseS358S358DGRQRRPstIAEQTV17805301AMPK related protein; phosphorylation leads to kinase activation and promotes ubiquitination/degradation of TORC2
Rac1Akt1humanS71S71yDRLRPLsYPQTDVF10617634Rho-GTPase, actin cytoskeletal organization; phosphorylation inhibits GTP-binding activity
Raf1Akt1mouseS259S259SQRQRStsTPNVHMV12087097, 12087097Signaling intermediate in Erk1/2 pathway; phosphorylation inhibits activity
Akt1ratS259S259SQRQRSTsTPNVHMV11443134
RANBP3Akt1humanS126S126VKRERtssLtQFPPs18280241RAN binding protein 3 functions in nuclear transport; phosphorylation mediates Ran binding and regulates nuclear transport
RARAAkt1humanS96S96FVCQDKSsGYHYGVS16417524Nuclear receptor for retinoic acid that acts as a direct regulator of gene expression, phosphorylation of the DNA binding domain inhibits RARA activity
RGC32Akt1humanS65S65ERMKRRSsAsVSDSS19162005A regulator of cell cycle-specific kinases in response to DNA damage; phosphorylation leads to activation and regulation of growth factors
RNF11Akt1humanT135T135DWLMRSFtCPSCMEP16123141A member of a ubiquitin editing complex that modulates transient inflammatory signaling; phosphorylation allows 14-3-3 binding
RonAkt1humanS1394S1394VRRPRPLsEPPRPT_12919677, 14505491Receptor tyrosine kinase for macrophage stimulating protein (MSP), cell adhesion, proliferation and migration; phosphorylation causes 14-3-3 binding
RPS3Akt1humanT70T70GrrIrELtAVVQkRF20605787A member of the 40S ribosomal subunit that also induces neuronal apoptosis and acts as an endonuclease; phosphorylation inhibits proapoptotic function, increases nuclear import/accumulation, and increases DNA repair
S6Akt1mouseS236S236AKRRRLssLRAstsK12151408S6 ribosomal protein; phosphorylation activates the protein and promotes protein synthesis
Akt1, Akt2ratS235, S236S235, S236IAKRRRLssLRAsts, AKRRRLssLRAstsK15358595
SFRS5Akt2ratS86S86GRGRGRYsDRFSSRR15684423A member of the splicesome involved in constitutive and alternative splicing; phosphorylation activates alternative splicing exon inclusion
SH3BP4Akt1mouseS245S246FRSKRSysLsELsVL19122209Controls selective internalization of the transferrin receptor through endocytosis; phosphorylation promotes 14-3-3 binding at the plasma membrane
SH3RF1Akt1, Akt2humanS304S304KNTKKRHsFtsLTMA17535800Scaffolding protein that binds to activated Rac and promotes apoptosis via JNK activation; phosphorylation reduces ability to bind Rac, promoting apoptosis
SKIAkt1humanT458T458QPRKRKLtVDTPGAP19875456Negative regulator of TGF-b signaling by binding to Smads; phosphorylation causes its destabilization and reduces SKI-mediated inhibition of expression of Smad7
SOX2Akt1mouseT118T116kYRPRRktkTLMkKD20945330A transcription factor required for early embryogenesis and embryonic stem cell pluripotency; phosphorylation stabilizes SOX2, increasing transcriptional activity
SRPK2Akt1humanT492T492PSHDRSRtVsAsstG19592491A protein kinase targeting the serine/arginine family of splicing factors; phosphorylation causes nuclear translocation and upregulation of targets regulating cell cycle progression and apoptosis
SSBAkt1mouseT301T302LLRNKKVtWKVLEGH18836485RNA binding protein, plays a role in processing of RNA polymerase III transcripts; phosphorylation promotes export to cytoplasm where it binds polysomes and regulates expression of a specific set of mRNAs
STXBP4Akt2mouseS99S99RAKLRsEsPWEIAFI15753124Inhibits formation and translocation of intracellular vesicles; insulin-stimulated phosphorylation of STXBP4 releases inhibition
SYTL1Akt1humanS241S241RMLSSSSsVSSLNSS15998322A secretory factor family member that is involved in granule exocytosis; phosphorylation regulates SYTL1 subnuclear localization
TAL1Akt1humanT90T90EARHRVPttELCRPP15930267, 19406989Transcription factor; phosphorylation inhibits transcriptional repressor activity and regulates intracellular localization
TBC1D1Akt1humanT596T596AFRRRANtLsHFPIE17995453Rab GTPase-activating protein involved in insulin-stimulated Glut4 trafficking; phosphorylation promotes glucose transport
TERTAkt1humanS227, S824S227, S824GARRRGGsASRSLPL, AVRIRGKsYVQCQGI10224060Telomerase reverse transcriptase, chromosome length maintenance; phosphorylation enhances telomerase activity
THOC4Akt1humanS34, T219S34, T219RGRGRAGsQGGrGGG, GGGtrRGtRGGARGR18562279An RNA binding and export protein that also acts as a chaperone for dimerization of transcription factors; phosphorylation regulates THOC4 subnuclear localization and activates mRNA export and cell proliferation
TOPBP1Akt1humanS1159S1159EERARLAsNLQWPSC19477925Induces a large increase in the kinase activity of ATR; phosphorylation prevents the enhanced association of ATR with TopBP1 after DNA damage
TRF1Akt1humanT273T273SKRTRTItSQDKPSG19160102Controls telomere structure; phosphorylation decreases telomere length
TSC2Akt1humanS939, S981, T1462S939, S981, T1462sFRARstsLNERPKs, AFRCRSIsVSEHVVR, GLRPRGytIsDSAPs15342917, 12150915, 16636147Tumor suppressor that inhibits mTOR; phosphorylation inhibits function and allows protein synthesis to occur
Akt1ratS1130, S1132S1130, S1132GARDRVRsMsGGHGL, RDRVRsMsGGHGLRV12172553
TTC3Akt1humanS378S378AYTPRsLsAPIFTTS20059950E3 ligase to Akt; phosphorylation promotes TTC3 function, such as ability to ubiquitinylate and destabilize Akt
TWIST1Akt1humanS42, S123S42, S123GGRKRRSsRRSAGGG, RERQRTQsLNEAFAA20400976A regulatory basic helix-loop-helix anti-apoptotic transcription factor; phosphorylation activates TWIST1, causing inhibition of p53 and promotion of cell survival
USP8Akt1mouseT907T945TCRRRSRtFEAFMYL17210635Deubiquitinating enzyme that plays a role in growth factor receptor trafficking and degradation; phosphorylation increases protein stability
VCPAkt1humanS352, S746, S748S352, S746, S748AAtNRPNsIDPALRR, AMRFARRsVsDNDIR, RFARRsVsDNDIRky16551632, 16027165ATPase and molecular chaperone; phosphorylation may impair its pro-apoptotic effects and promote cell survival
VimentinAkt1humanS39S39ttsTrtysLGsALRP20856200A cytoskeletal intermediate filament protein; phosphorylation induces cellular motility and invasion by protection from proteolysis
Wee1Akt1humanS642S642KKMNRsVsLTIy___15964826A protein kinase that inhibits cell cycle progression by phosphorylation inhibition of cdc2 kinase; phosphorylation promotes a change in Wee1 localization from nuclear to cytoplasmic and is associated with G2/M arrest
WNK1Akt1humanT60T60EYRRRRHtMDKDSRG14611643, 16081417Regulates ion channels; phosphorylation of WNK1 causes SGK1 activation and regulation of sodium ion transport
XIAPAkt1, Akt2humanS87S87VGRHRKVsPNCRFIN14645242, 17537996Inhibitor of apoptosis; phosphorylation prevents ubiquitination/degradation and causes increased cell survival
YAP1Akt1humanS127S127PQHVRAHssPAsLQL12535517A transcriptional co-activator of PEBP2 and other transcription factors; phosphorylation suppresses p73-mediated apoptosis
YB-1Akt1humanS102S102NPRKyLRsVGDGEtV22417301A transcription/translation factor involved in mRNA stability and expression; phosphorylation induces activation and translocation to the nucleus
zyxinAkt1humanS142S142PQPREKVssIDLEId17572661A focal adhesion molecule that moves between the cytoplasm and nucleus; phosphorylation promotes an association with acinus and anti-apoptotic activity

created October 2008

revised June 2015