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.
Substrate | Isoform | Organism | Site | Human Site | Sequence (+/-) | PMID | Substrate Function & Effect of Phosphorylation |
---|---|---|---|---|---|---|---|
14-3-3 z | Akt1 | human | S58 | S58 | VVGARRSsWRVVssI | 11956222 | A key regulatory protein in signal transduction, checkpoint control, apoptotic, and nutrient-sensing pathways; effect of phosphorylation is unknown |
acinus | Akt1 | human | S1180 | S1180 | GPRsRsRsRDRRRKE | 18559500, 16177823 | Induces chromatin condensation during apoptosis; phosphorylation inhibits this process |
Akt1 | rat | S1329 | S1331 | HSRSRSRsTPVRDRG | 16177823 | ||
ACLY | Akt1 | mouse | S455 | S455 | PAPSRtAsFsESRAD | 16007201 | Catalyzes the formation of acetyl-CoA and oxaloacetate (OAA) in the cytosol; phosphorylation enhances the catalytic activity of the enzyme |
ADRB2 | Akt1 | human | S346 | S346 | LLCLRRssLKAyGNG | 11809767 | A 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 |
Akt1 | Akt1 | human | S246, T72 | S246, T72 | LSRERVFsEDRARFY, TERPRPNtFIIRCLQ | 16549426 | Activated 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 |
Akt1 | mouse | S473 | S473 | RPHFPQFsYsAsGtA | 11570877, 10722653 | ||
AMPKA1 | Akt1 | rat | S485 | S485 | ATPQRSGsISNYRSC | 16340011 | Heterotrimeric complex that plays a key role in the regulation of energy homeostasis; phosphorylation regulates AMPK activity |
AMPKA2 | Akt1 | rat | S491 | S491 | STPQRSCsAAGLHRP | 16340011 | Heterotrimeric complex that plays a key role in the regulation of energy homeostasis; phosphorylation regulates AMPK activity |
APS | Akt1 | rat | S588 | S598 | SARSRSNsTEHLLEA | 16141217 | An adaptor protein recruited to the insulin receptor to signal insulin-stimulated glucose transport; phosphorylation promotes membrane localization |
AR | Akt1 | human | S213, S791 | S213, S791 | SGRAREAsGAPTsSK, CVRMRHLsQEFGWLQ | 11404460, 14555644, 17470458, 11156376 | Nuclear receptor; phosphorylation suppresses AR activation, expression of AR target genes, and AR-mediated apoptosis |
arfaptin 2 | Akt1 | human | S260 | S260 | GTRGRLEsAQATFQA | 15809304 | ADP ribosylation factor-interacting protein, implicated as a factor in Huntington's disease; phosphorylation promotes neuronal cell survival and neuroprotection |
ARHGAP22 | Akt1 | human | S16 | S16 | ARRARSKsLVMGEQS | 21969604 | A Rho GTPase activator that inhibits Rac1; phosphorylation allows 14-3-3 binding and regulation of cell motility |
AS160 | Akt1 | human | T642 | T642 | QFRRRAHtFsHPPss | 16880201, 11994271, 16935857 | Insulin stimulated Rab GTPase-activating protein, structurally and functionally similar to TBC1D1; phosphorylation results in increased Glut4 translocation |
ASK1 | Akt1, Akt2 | human | S83 | S83 | ATRGRGssVGGGSRR | 11154276, 15782121, 15911620, 14500571, 12697749 | MAPKKK, induces apoptosis via JNK pathway; phosphorylation inhibits activity and promotes survival |
ataxin-1 | Akt1 | human | S775 | S775 | ATRKRRWsAPESRKL | 17540008, 12757707 | 14-3-3 binds to and stabilizes ataxin-1, which forms polyglutamine aggregates and neurodegeneration; phosphorylation promotes 14-3-3 binding |
B-Raf | Akt1, Akt3 | human | S365, S429 | S365, S429 | GQRDRsssAPNVHIN, PQRERKsssSsEDRN | 10869359, 18451171 | Signaling intermediate in Erk1/2 pathway; phosphorylation causes inhibition |
BAD | Akt1 | human | S99 | S99 | PFRGRsRsAPPNLWA | 11020382, 10558990, 19667065 | Pro-apoptotic protein; phosphorylation inhibits function and promotes survival |
Akt1 | mouse | S112, S155 | S75, S118 | ETRsRHssyPAGtEE, GRELRRMsDEFEGSF | 9381178, 11723239, 10983986, 15123689, 10949026 | ||
Bcl-10 | Akt1 | human | S218, S231 | S218, S231 | EEGTCANsSEMFLPL, PLRSRtVsRQ_____ | 16280327 | A CARD (caspase recruitment domain) containing protein shown to induce apoptosis and activate NF-κB; phosphorylation induces nuclear translocation |
Bcl-xL | Akt1 | rat | S106 | S106 | LRYRRAFsDLTSQLH | 18951975 | Prevents apoptosis through binding to apoptotic proteins; phosphorylation promotes VDAC binding |
Bex1 | Akt1 | rat | S105 | S102 | KLRERQLsHSLRAVS | 16498402 | A neurotrophin and nerve growth factor signaling adaptor molecule involved in promoting cell cycle progression; phosphorylation prevents degradation by the proteasome |
Bim | Akt1 | human | S87 | S87 | FIFMRRssLLSRSss | 16282323 | Pro-apoptotic protein; phosphorylation promotes 14-3-3 binding/inactivation and cell survival |
BRCA1 | Akt1 | human | S694, T509 | S694, T509 | QTSKRHDsDTFPELK, LKRKRRPtsGLHPED | 20085797, 10542266 | Breast cancer susceptibility gene product, tumor suppressor; phosphorylation alters function, perhaps by preventing nuclear localization |
BRF1 | Akt1 | human | S92, S203 | S92, S203 | RFRDRsFsEGGERLL, PRLQHsFsFAGFPSA | 17030608, 15538381 | A 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 |
CACNB2 | Akt1 | rat | S625 | S630 | KQRSRHKsKDRYCDK | 15311280 | Voltage-dependent calcium channel; phosphorylation regulates channel trafficking to plasma membrane |
CaRHSP1 | Akt1 | human | S52 | S52 | tRRtRtFsAtVRASQ | 15910284 | RNA binding protein; phosphorylation effect currently unknown |
Casp9 | Akt1 | human | S196 | S196 | KLRRRFssLHFMVEV | 9812896 | Protease, initiates apoptosis; phosphorylation inhibits protease activity |
CBP | Akt1 | mouse | T1872 | T1871 | LMRRRMAtMNTRNVP | 17166829 | Acetylates histone and non-histone proteins; phosphorylation increases activity |
CBY1 | Akt1, Akt2 | human | S20 | S20 | TPPRKSAsLSNLHsL | 18573912 | An inhibitor of the Wnt signaling pathway; phosphorylation allows 14-3-3 binding and β-catenin sequestration in the cytoplasm |
CCT2 | Akt1 | human | S260 | S260 | GsRVRVDstAkVAEI | 19332537 | Member of the protein chaperone complex; effect of phosphorylation currently unknown |
CD34 | Akt2 | mouse | S343 | S346 | yssGPGAsPETQGKA | 21499536 | A 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 |
Cdc25B | Akt1 | mouse | S351 | S353 | VQSKRRKsVtPLEEQ | 17554083 | Protein phosphatase responsible for cdc2 activation; phosphorylation promotes activation of M-phase promoting factor |
CDK2 | Akt1 | human | T39 | T39 | LkKIRLDtETEGVPs | 18354084 | Cyclin-dependent kinase functioning in S-phase; phosphorylation increases cyclin A binding |
CELF1 | Akt1 | human | S28 | S28 | GQVPRTWsEKDLREL | 18570922 | RNA-binding protein; phosphorylation enhances interaction with cyclin D1 mRNA |
CENTB1 | Akt1 | human | S554 | S554 | SIRPRPGsLRSKPEP | 16256741 | GTPase-activating protein (GAP) for ARF proteins; phosphorylation prevents recycling of b1-integrin containing endosomes and cell migration |
CENTG1 | Akt1 | human | S985 | S985 | THLSRVRsLDLDDWP | 19176382 | A GTPase activating protein for ARF1 and ARF5; phosphorylation enhances CENTG1 GTP binding and NF-κB activity |
CFLAR | Akt1 | human | S273 | S273 | LLRDTFTsLGYEVQK | 19339247 | A regulator of apoptosis; phosphorylation targets CFLAR for degradation |
Chk1 | Akt1 | human | S280 | S280 | AKRPRVtsGGVsEsP | 15107605, 12062056 | DNA damage effector that regulates G2/M transition during DNA damage; phosphorylation inhibits function by preventing phosphorylation by ATM/ATR |
CK1-D | Akt1 | rat | S370 | S370 | MERERKVsMRLHRGA | 17594292 | Kinase and core component of circadian clock; phosphorylation inhibits kinase activity |
CLK2 | Akt1 | human | S34, T127 | S34, T127 | HKRRRSRsWSSSSDR, RRRRRSRtFSRSSSQ | 20682768 | A dual specificity serine/threonine and tyrosine kinase; phosphorylation increases cell survival after ionizing radiation |
Cot | Akt1 | human | S400 | S400 | EDQPRCQsLDSALLE | 12138205 | Oncogene; phosphorylation induces NF-κB-dependent transcription |
CREB | Akt1 | rat | S133 | S133 | EILsRRPsYRkILND | 9829964 | bZIP transcription factor that activates target genes through cAMP response elements; activated by phosphorylation |
CTNNB1 | Akt1, Akt2 | human | S552 | S552 | QDtQRRtsMGGtQQQ | 17287208 | Wnt signaling pathway protein; phosphorylation causes nuclear localization |
CTNND2 | Akt1 | mouse | T454 | T457 | tGTFRtstAPssPGV | 17993462 | Transcriptional activator, plays a role in adhesion molecule regulation; phosphorylation promotes binding to p190RhoGEF, dendritic morphogenesis |
Cx43 | Akt1 | rat | S369 | S369 | RPssRAssRAssRPR | 18163231 | Gap junction protein; phosphorylation allows 14-3-3 binding |
Akt1, Akt3 | rat | S373 | S373 | RAssRAssRPRPDDL | 17008717, 18163231 | ||
DLC1 | Akt1 | rat | S330 | S766 | VTRTRSLsTCNKRVG | 16338927 | Tumor suppressor and insulin stimulated phosphoprotein, may play role in Glut4 translocation; phosphorylation may inhibit its GAP activity |
DNAJC5 | Akt1 | rat | S10 | S10 | DQRQRsLsTSGESLY | 16243840 | Exocytosis; phosphorylation regulates the kinetics of late stage exocytosis |
DNMT1 | Akt1 | human | S143 | S143 | RtPRRsksDGEAkPE | 21151116 | A maintenance methyltransferase, transferring proper methylation patterns to newly synthesized DNA during replication; phosphorylation increases DNMT1 stability and prevents methylation |
EDC3 | Akt1, Akt2 | human | S161 | S161 | sFRRRHNsWssSsRH | 20051463 | Involved 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-1 | Akt1 | human | T236 | T236 | RTRSRRLtFRKNISK | 11583630 | G protein-coupled receptor; phosphorylation activates signaling to promote cell migration |
eIF4B | Akt1 | mouse | S422 | S422 | RERsRtGsEssQtGA | 18836482 | Necessary for binding of mRNA to ribosomes; phosphorylation increases transcriptional activity |
ENaC-a | Akt1 | rat | S621 | S594 | RFRSRYWsPGRGARG | 21220922 | An amiloride sensitive epithelial sodium channel that mediates sodium reabsorption; phosphorylation increases ENaC specific activity |
eNOS | Akt1 | human | S615, S1177 | S615, S1177 | SYKIRFNsISCSDPL, TsRIRtQsFsLQERQ | 12511559, 12446767, 10376603, 18622039, 12171920 | Enzyme that catalyzes the production of nitric oxide (NO); phosphorylation results in enzyme activation, NO production, and cardiovascular homeostasis (vasodilation, vascular remodeling, angiogenesis) |
EphA2 | Akt1 | human | S897 | S897 | RVsIRLPstsGsEGV | 19573808 | Receptor 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-a | Akt1, Akt2 | human | S167 | S167 | GGRERLAsTNDKGSM | 11139588, 16113102, 11507039 | Nuclear receptor and transcription factor; phosphorylation activates the receptor and increases gene expression, causing mammary and uterine cell proliferation |
Akt1 | human | S305 | S305 | IkRSkkNsLALSLtA | 20101208 | ||
ER-b | Akt1 | mouse | S236 | D236 | VRRQRSAsEQVHCLN | 17166829 | Nuclear receptor and transcription factor; phosphorylation prevents cofactor binding and decreases activity |
EZH2 | Akt1 | human | S21 | S21 | CWRKRVKsEYMRLRQ | 16224021 | Methyltransferase; phosphorylation decreases histone H3 methylation of Lys27 and increases gene expression |
ezrin | Akt2 | human | T567 | T567 | QGRDKYKtLRQIRQG | 15531580 | Plasma membrane/cytoskeletal linker protein; phosphorylation promotes actin binding and cytoskeletal organization |
FANCA | Akt1 | human | S1149 | S1149 | CLRSRDPsLMVDFIL | 11855836 | ATPase involved in DNA repair; phosphorylation is negatively regulated by Akt |
FLEG1 | Akt1 | human | S486 | S486 | GLEtRRLsLPSsKAK | 17256767 | A chaperone protein involved in directing specific histones to the centromere; phosphorylation allows binding to 14-3-3 |
FLNC | Akt1, Akt2 | human | S2233 | S2233 | LGRERLGsFGsItRQ | 15461588 | Muscle-specific filamin functioning in muscle cells; phosphorylation effect currently unknown |
FOXA2 | Akt1 | human | T156 | T156 | KTYRRSYtHAKPPYS | 14500912 | Transcription factor involved in embryonic development and differentiation; phosphorylation results in nuclear exclusion and inhibition of FoxA2-dependent transcriptional activity |
FOXG1 | Akt1 | human | T279 | T279 | KLRRRSttsRAKLAF | 17435750 | Transcriptional repression factor involved in brain development; phosphorylation promotes nuclear export |
FOXO1A | Akt1 | human | S256, S319, T24 | S256, S319, T24 | sPrRrAAsMDNNSkF, TFRPRtssNAsTIsG, LPRPRSCtWPLPRPE | 15668399, 10358075, 11237865, 16076959, 11311120 | Transcription factor involved in cell cycle arrest, apoptosis, and glucose metabolism; phosphorylation causes export from the nucleus and inhibits activity |
FOXO3A | Akt1 | human | S253, T32 | S253, T32 | APRRRAVsMDNSNKY, QSRPRsCtWPLQRPE | 10910908, 10995739, 10102273, 11154281 | Transcription factor involved in cell cycle arrest and apoptosis; phosphorylation causes export from the nucleus and inhibits activity |
FOXO4 | Akt1 | human | S197, S262, T32 | S197, S262, T32 | APRRRAAsMDSSSKL, TFRPRSssNASSVST, QSRPRsCtWPLPRPE | 11313479, 11313479, 10217147, 16272144 | Transcription factor involved in cell cycle arrest, apoptosis, and insulin signaling; phosphorylation causes export from the nucleus and inhibits activity |
Gab2 | Akt1 | human | S159 | S159 | LLRERKSsAPSHsSQ | 11782427 | Docking/scaffolding protein, proto-oncogene, RTK signaling intermediate; phosphorylation inhibits activity |
GABRB2 | Akt1 | rat | S434 | S434 | SRLRRRAsQLKITIP | 12818177 | Receptor that mediates fast inhibitory synaptic transmission in the brain; phosphorylation increases the number of receptors on the cell surface |
GAPDH | Akt2 | human | T237 | T237 | GMAFRVPtANVSVVD | 21979951 | Catalyzes the phosphorylation of glyceraldehyde-3-phosphate during glycolysis; phosphorylation decreases nuclear translocation and GAPDH induced apoptosis |
GATA1 | Akt1 | human | S310 | S310 | QTRNRKAsGkGkkkR | 16107690 | Transcription factor; phosphorylation increases activity and promotes blood cell differentiation |
GATA2 | Akt1 | human | S401 | S401 | QTRNRKMsNKSKKSK | 15837948 | Transcription factor; phosphorylation inhibits activity to promote adipogenesis and reduce inflammation |
girdin | Akt1 | human | S1417 | S1417 | INRERQKsLtLTPTR | 16139227 | Actin binding protein; phosphorylation promotes cell migration |
GOLGA3 | Akt1 | mouse | S174, S385 | S174, S389 | VKRHRERsSQPAtKM, EVRsRRDsICsSVSM | 17888676 | Golgi auto-antigen; phosphorylation results in reduced apoptosis |
Grb10 | Akt1 | mouse | S455 | S428 | NAPMRsVsENsLVAM | 15722337 | An adaptor protein that interacts with many receptor tyrosine kinases as well as downstream signal molecules; phosphorylation allows binding to 14-3-3 |
GSK-3a | Akt1 | human | S21 | S21 | SGRARtssFAEPGGG | 11340086, 11563975, 11577096 | Serine/threonine protein kinase that phosphorylates and inactivates glycogen synthase; phosphorylation inhibits activity |
GSK-3b | Akt1 | human | S9 | S9 | SGRPRttsFAESCKP | 12900420, 15457186, 11563975, 11340086, 11577096, 8985174 | Serine/threonine protein kinase that phosphorylates and inactivates glycogen synthase; phosphorylation inhibits activity |
H2B | Akt1 | human | S37 | S37 | RKRsRkEsysIyVyk | 8985174 | Core component of the nucleosome; phosphorylation effect currently unknown |
H3 | Akt1 | mouse | S10 | S10 | tKQTARksTGGkAPR | 12529330 | Core component of the nucleosome; phosphorylation is correlated with chromosome condensation during mitosis and meiosis |
HMOX1 | Akt1 | human | S188 | S188 | LYRSRMNsLEMtPAV | 15581622 | Heme oxygenase involved in stress response; phosphorylation regulates binding affinity |
hnRNP A1 | Akt1 | human | S199 | S199 | sQrGrsGsGNFGGGr | 18562319 | Involved 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 E1 | Akt1, Akt2 | mouse | S43 | S43 | VKRIREEsGARINIS | 20154680 | Binds to single-stranded nucleic acid; phosphorylation results in disruption of BAT element binding and translational activation of Dab2 and ILEI mRNA |
HSP27 | Akt1 | human | S82 | S82 | RALsRQLssGVSEIR | 12740362 | Heat shock protein that confers cellular resistance to stress and adverse environmental change; phosphorylation alters tertiary structure, modulates actin polymerization, and reorganization |
HTRA2 | Akt1, Akt2 | human | S212 | S212 | RVRVRLLsGDTYEAV | 17311912 | Protease released during apoptosis; phosphorylation inhibits activity and attenuates its pro-apoptotic function |
Huntingtin | Akt1 | human | S421 | S421 | GGRsRsGsIVELIAG | 12062094, 14725621, 15843398, 16452687 | Huntington's disease; Akt phosphorylation blocks nuclear aggregation and provides neuroprotection |
IKK-a | Akt1, Akt2 | human | T23 | T23 | EMRERLGtGGFGNVC | 18515365, 12048203, 10485710, 19609947 | NF-κB signaling intermediate; phosphorylation activates NF-κB and immune/stress response |
IP3R1 | Akt1 | rat | S2682 | S2690 | FPRMRAMsLVSSDSE | 16332683 | Ca2+ release and signaling; phosphorylation induces resistance to apoptosis, possibly through caspase-3 inactivation |
IRAK1 | Akt1 | human | T100 | T100 | LRARDIItAWHPPAP | 11976320 | A serine/threonine-specific IL-1 receptor-associated kinase involved in Toll signaling; phosphorylation inhibits IRAK mediated NK-κB activation |
IRS1 | Akt1 | human | S629 | S629 | VPSGRKGsGDyMPMs | 17640984 | Insulin receptor signaling intermediate; phosphorylation inhibits function |
Akt1 | rat | S522 | S527 | RFRKRTHsAGTSPTI | 17579213 | ||
KHSRP | Akt1, Akt2 | human | S193 | S193 | GLPERSVsLTGAPES | 17177604 | Recruits degradation machinery, activates mRNA turnover, regulates splicing; phosphorylation inhibits RNA turnover by degradation |
Kv11.1 iso5 | Akt1 | human | T897 | T897 | SFRRRtDtDtEQPGE | 18791070 | Pore-forming subunit of voltage-gated potassium channels, essential for rhythmic excitability of cardiac muscle and endocrine cells; phosphorylation inhibits channels |
Lamin A/C | Akt1 | rat | S301, S404 | S301, S404 | RSRGRASsHSSQSQG | 18808171 | Component of nuclear lamina; phosphorylation regulates function of nuclear lamina |
LTB4R2 | Akt1 | human | T355 | T355 | GGRsREGtMELRTTP | 22044535 | A low-affinity leukotriene receptor involved in chemotaxis; phosphorylation regulates activation of chemotactic responses |
Mad1 | Akt1 | human | S145 | S145 | IERIRMDsIGSTVSS | 18451027, 19526459, | Component of spindle-assembly checkpoint; phosphorylation results in ubiquitination and degradation through 26S proteasome pathway |
MDM2 | Akt1 | human | S166, S186, S188 | S166, S186, S188 | SsRRRAIsEtEENsD, RQRKRHKsDsIsLsF, RKRHKsDsIsLsFDE | 11715018, 15169778, 11504915, 11850850, 11923280, 15527798, 11960368 | Ubiquitin ligase involved in p53 degradation; phosphorylation results in translocation to the nucleus and inhibition of p53 |
MDM4 | Akt1 | human | S367 | S367 | PDCRRtIsAPVVRPK | 18356162 | RING-finger domain protein involved in p53 degradation and apoptosis; phosphorylation stabilizes MDM4 and MDM2 |
METTL1 | Akt1 | human | S27 | S27 | yYRQrAHsNPMADHT | 15861136 | Catalyzes the formation of m7G46 in tRNA; phosphorylation results in inactivation |
MKK4 | Akt1 | human | S80 | S80 | IERLRtHsIEsSGKL | 15911620, 11707464 | Signaling intermediate of the JNK/SAPK pathway involved in stress/inflammation; phosphorylation inhibits activity |
MLK3 | Akt1 | human | S674 | S674 | PGRERGEsPTtPPTP | 12458207 | JNK-mediated neuronal cell death; phosphorylation inhibits activity |
MST1 | Akt1 | human | T120 | T120 | IIRLRNktLTEDEIA | 19940129 | Pro-apoptotic kinase; phosphorylation inhibits kinase activity and nuclear translocation resulting in inhibition of pro-apoptotic signaling |
MST2 | Akt1 | human | T117, T384 | T117, T384 | IIRLRNktLIEDEIA, GTMKRNAtsPQVQRP | 20231902, 20086174 | Upstream activator of the MAPK pathway that regulates apoptosis, morphogenesis, and cytoskeletal rearrangements; phosphorylation inhibits pro-apoptotic activity |
mTOR | Akt1 | human | T2446, S2448 | T2446, S2448 | RsRtRtDsysAGQsV | 15208671, 10910062, 10567225 | Protein synthesis and cell growth; phosphorylation increases activity |
MYO5A | Akt2 | mouse | S1650 | S1652 | GLRKRtssIADEGty | 17515613 | Actin-based motor protein with a role in cytoplasmic vesicle transport and anchorage; phosphorylation promotes insulin-mediated Glut4 vesicle translocation |
Myt1 | Akt1 | starfish | S75 | S83 | ESRPRAVsFRQSEPS | 11802161 | Wee1 family member and cell cycle regulator; phosphorylation downregulates Myt1 and initiates M-phase |
NDRG2 | Akt1 | human | S332, T348 | S332, T348 | LsRsRtAsLtsAAsV, GNRsRsRtLsQssEs | 15461589 | Insulin-stimulated phosphoprotein; phosphorylation promotes insulin signaling |
NFAT90 | Akt1 | human | S647 | S647 | rGrGRGGsIRGRGRG | 18097023, 20870937 | Translation inhibitory protein; phosphorylation required for nuclear export |
NHE1 | Akt1 | human | S648, S703, S796 | S648, S703, S796 | KTRQRLRsyNRHTLV, MsRARIGsDPLAyEP, QRIQRCLsDPGPHPE | 18757828, 20026127 | Sodium/hydrogen exchanger involved in pH regulation and signal transduction; phosphorylation inhibits activity |
NMDAR2C | Akt1 | mouse | S1084 | S1081 | GPRPRHAsLPSSVAE | 19477150 | Glutamate receptor channel subunit; phosphorylation promotes binding to 14-3-3ε and leads to increased surface expression of cerebellar NMDA receptors |
Akt1 | rat | S1083 | S1081 | GPRPRHAsLPSSVAE | 19477150 | ||
NuaK1 | Akt1 | human | S600 | S600 | PARQRIRsCVSAENF | 15060171, 12409306 | AMPK family member activated under glucose starvation that mediates cell survival; phosphorylation increases kinase activity |
Nur77 | Akt1 | human | S351 | S351 | GRRGRLPsKPKQPPD | 16434970, 11274386 | A nuclear receptor and transcription factor regulating T cell apoptosis; phosphorylation inhibits transcriptional activity |
p21 Cip1 | Akt1 | human | S146, T145 | S146, T145 | GRkRRQtsMTDFYHs, QGRkRRQtsMTDFYH | 17855660, 11231573, 11756412, 15173090, 11463845, 116982699 | Regulates cell cycle and cell survival; phosphorylation increases protein stability |
p27Kip1 | Akt1 | human | S10, T157, T198 | S10, T157, T198 | NVRVsNGsPsLErMD, GIRkrPAtDDSSTQN, PGLRRRQt_______ | 18710949, 12042314, 12244302 | A cyclin-dependent kinase inhibitor that enforces the G1 cell cycle restriction point; phosphorylation promotes 14-3-3 binding and cytoplasmic localization |
p300 | Akt1 | human | S1834 | S1834 | MLRRRMAsMQRTGVV | 16024795, 11116148 | Transcriptional co-activator; phosphorylation can either activate or suppress transcriptional activity depending on cell type and physiological stimuli |
p47phox | Akt1 | human | S304, S328 | S304, S328 | GAPPRRssIRNAHSI, QDAYRRNsVRFLQQR | 12734380 | A 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 |
PAK1 | Akt1 | mouse | S21 | S21 | APPMRNTsTMIGAGS | 14585966 | A 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 |
palladin | Akt1 | human | S1118 | S1118 | VRRPRsRsRDsGDEN | 20471940 | Actin-bundling protein; phosphorylation promotes F-actin bundling and inhibits cell migration |
PAR-4 | Akt1 | rat | S249 | N257 | SRHNRDTsAPANFAS | 16209943 | A 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 |
PDCD4 | Akt1 | human | S67, S457 | S67, S457 | kRRLRKNssRDsGRG, RGRKRFVsEGDGGRL | 16357133 | Tumor suppressor protein that is strongly induced during apoptosis; phosphorylation inhibits tumor suppressor function |
PDE3A | Akt1 | mouse | S290, S291, S292 | S290, S291, S292 | GWKRRRRsssVVAGE, WKRRRRsssVVAGEM, KRRRRsssVVAGEMS | 17124499 | Regulates levels of cAMP and cGMP, insulin-dependent oocyte maturation; phosphorylation increases activity |
PDE3B | Akt1 | mouse | S273 | S295 | VIRPRRRssCVsLGE | 10454575 | Regulates levels of cAMP and cGMP, activated by insulin to regulate lipolysis; phosphorylation increases activity |
PEA-15 | Akt1 | human | S116 | S116 | KDIIRQPsEEEIIKL | 12808093 | A 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 |
peripherin | Akt1 | mouse | S66 | S59 | SSSARLGsFRAPRAG | 17569669 | Neuronal intermediate filament protein; phosphorylation promotes motor nerve regeneration |
PFKFB2 | Akt1 | human | S466, S483 | S466, S483 | PVRMRRNsFtPLSSS, IRRPRNysVGSRPLK | 12853467 | Glycolytic enzyme, insulin-mediated glucose metabolism; phosphorylation increases activity |
PFKFB3 | Akt1 | human | S461 | S461 | NPLMRRNsVtPLAsP | 15896703 | Synthesis and degradation of fructose 2,6-bisphosphate; phosphorylation decreases sensitivity to inhibition |
PGC-1 a | Akt1, Akt2 | mouse | S570 | S571 | RMRSRsRsFsRHRSC | 17554339 | Regulates gluconeogenesis and fatty acid oxidation; phosphorylation inhibits function |
PIP5K | Akt1 | human | S307 | S307 | PARNRsAsItNLsLD | 15546921 | A protein/ lipid kinase involved in membrane trafficking; phosphorylated in response to insulin |
Akt1 | mouse | S105 | S105 | EELHRRSsVLENTLP | 20513353 | ||
PLB | Akt1 | rat | S16 | S16 | RSAIRRAstIEMPQQ | 18838385 | A major phosphoprotein calcium regulation component of the sarcoplasmic reticulum; phosphorylation causes release of inhibition and increases calcium uptake by the sarcoplasmic reticulum |
PLCG1 | Akt1 | human | S1248 | S1248 | HGRAREGsFEsRyQQ | 16525023 | Catalyzes PI 4,5 bisphosphate to IP3 and DAG, increases intracellular Ca2+ levels; phosphorylation increases activity and enhances EGF-stimulated cell motility |
PPP1CA | Akt1 | human | T320 | T320 | NPGGRPItPPRNSAK | 14633703 | A serine/threonine phosphatase involved in cell cycle regulation; phosphorylation inhibits activity |
PRAS40 | Akt1 | human | T246 | T246 | LPRPRLNtsDFQKLK | 12524439, 17277771, 18372248 | Binds to and inhibits mTOR; phosphorylation causes 14-3-3 binding/inhibition and results in increased protein synthesis |
PRPF19 | Akt1 | human | T193 | T193 | ERKKRGKtVPEELVK | 20629186 | A member of the splicesome that also functions in DNA double strand break repair; phosphorylation allows 14-3-3 binding |
PRPK | Akt1 | human | S250 | S250 | RLRGRKRsMVG____ | 17712528 | p53 binding protein and kinase; phosphorylation causes activation and results in p53 phosphorylation |
PTP1B | Akt1 | human | S50 | S50 | RNRyRDVsPFDHsRI | 11579209 | Protein tyrosine phosphatase that dephosphorylates the insulin receptor; phosphorylation inhibits activity |
QIK | Akt2 | mouse | S358 | S358 | DGRQRRPstIAEQTV | 17805301 | AMPK related protein; phosphorylation leads to kinase activation and promotes ubiquitination/degradation of TORC2 |
Rac1 | Akt1 | human | S71 | S71 | yDRLRPLsYPQTDVF | 10617634 | Rho-GTPase, actin cytoskeletal organization; phosphorylation inhibits GTP-binding activity |
Raf1 | Akt1 | mouse | S259 | S259 | SQRQRStsTPNVHMV | 12087097, 12087097 | Signaling intermediate in Erk1/2 pathway; phosphorylation inhibits activity |
Akt1 | rat | S259 | S259 | SQRQRSTsTPNVHMV | 11443134 | ||
RANBP3 | Akt1 | human | S126 | S126 | VKRERtssLtQFPPs | 18280241 | RAN binding protein 3 functions in nuclear transport; phosphorylation mediates Ran binding and regulates nuclear transport |
RARA | Akt1 | human | S96 | S96 | FVCQDKSsGYHYGVS | 16417524 | Nuclear receptor for retinoic acid that acts as a direct regulator of gene expression, phosphorylation of the DNA binding domain inhibits RARA activity |
RGC32 | Akt1 | human | S65 | S65 | ERMKRRSsAsVSDSS | 19162005 | A regulator of cell cycle-specific kinases in response to DNA damage; phosphorylation leads to activation and regulation of growth factors |
RNF11 | Akt1 | human | T135 | T135 | DWLMRSFtCPSCMEP | 16123141 | A member of a ubiquitin editing complex that modulates transient inflammatory signaling; phosphorylation allows 14-3-3 binding |
Ron | Akt1 | human | S1394 | S1394 | VRRPRPLsEPPRPT_ | 12919677, 14505491 | Receptor tyrosine kinase for macrophage stimulating protein (MSP), cell adhesion, proliferation and migration; phosphorylation causes 14-3-3 binding |
RPS3 | Akt1 | human | T70 | T70 | GrrIrELtAVVQkRF | 20605787 | A 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 |
S6 | Akt1 | mouse | S236 | S236 | AKRRRLssLRAstsK | 12151408 | S6 ribosomal protein; phosphorylation activates the protein and promotes protein synthesis |
Akt1, Akt2 | rat | S235, S236 | S235, S236 | IAKRRRLssLRAsts, AKRRRLssLRAstsK | 15358595 | ||
SFRS5 | Akt2 | rat | S86 | S86 | GRGRGRYsDRFSSRR | 15684423 | A member of the splicesome involved in constitutive and alternative splicing; phosphorylation activates alternative splicing exon inclusion |
SH3BP4 | Akt1 | mouse | S245 | S246 | FRSKRSysLsELsVL | 19122209 | Controls selective internalization of the transferrin receptor through endocytosis; phosphorylation promotes 14-3-3 binding at the plasma membrane |
SH3RF1 | Akt1, Akt2 | human | S304 | S304 | KNTKKRHsFtsLTMA | 17535800 | Scaffolding protein that binds to activated Rac and promotes apoptosis via JNK activation; phosphorylation reduces ability to bind Rac, promoting apoptosis |
SKI | Akt1 | human | T458 | T458 | QPRKRKLtVDTPGAP | 19875456 | Negative regulator of TGF-b signaling by binding to Smads; phosphorylation causes its destabilization and reduces SKI-mediated inhibition of expression of Smad7 |
SOX2 | Akt1 | mouse | T118 | T116 | kYRPRRktkTLMkKD | 20945330 | A transcription factor required for early embryogenesis and embryonic stem cell pluripotency; phosphorylation stabilizes SOX2, increasing transcriptional activity |
SRPK2 | Akt1 | human | T492 | T492 | PSHDRSRtVsAsstG | 19592491 | A protein kinase targeting the serine/arginine family of splicing factors; phosphorylation causes nuclear translocation and upregulation of targets regulating cell cycle progression and apoptosis |
SSB | Akt1 | mouse | T301 | T302 | LLRNKKVtWKVLEGH | 18836485 | RNA 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 |
STXBP4 | Akt2 | mouse | S99 | S99 | RAKLRsEsPWEIAFI | 15753124 | Inhibits formation and translocation of intracellular vesicles; insulin-stimulated phosphorylation of STXBP4 releases inhibition |
SYTL1 | Akt1 | human | S241 | S241 | RMLSSSSsVSSLNSS | 15998322 | A secretory factor family member that is involved in granule exocytosis; phosphorylation regulates SYTL1 subnuclear localization |
TAL1 | Akt1 | human | T90 | T90 | EARHRVPttELCRPP | 15930267, 19406989 | Transcription factor; phosphorylation inhibits transcriptional repressor activity and regulates intracellular localization |
TBC1D1 | Akt1 | human | T596 | T596 | AFRRRANtLsHFPIE | 17995453 | Rab GTPase-activating protein involved in insulin-stimulated Glut4 trafficking; phosphorylation promotes glucose transport |
TERT | Akt1 | human | S227, S824 | S227, S824 | GARRRGGsASRSLPL, AVRIRGKsYVQCQGI | 10224060 | Telomerase reverse transcriptase, chromosome length maintenance; phosphorylation enhances telomerase activity |
THOC4 | Akt1 | human | S34, T219 | S34, T219 | RGRGRAGsQGGrGGG, GGGtrRGtRGGARGR | 18562279 | An 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 |
TOPBP1 | Akt1 | human | S1159 | S1159 | EERARLAsNLQWPSC | 19477925 | Induces a large increase in the kinase activity of ATR; phosphorylation prevents the enhanced association of ATR with TopBP1 after DNA damage |
TRF1 | Akt1 | human | T273 | T273 | SKRTRTItSQDKPSG | 19160102 | Controls telomere structure; phosphorylation decreases telomere length |
TSC2 | Akt1 | human | S939, S981, T1462 | S939, S981, T1462 | sFRARstsLNERPKs, AFRCRSIsVSEHVVR, GLRPRGytIsDSAPs | 15342917, 12150915, 16636147 | Tumor suppressor that inhibits mTOR; phosphorylation inhibits function and allows protein synthesis to occur |
Akt1 | rat | S1130, S1132 | S1130, S1132 | GARDRVRsMsGGHGL, RDRVRsMsGGHGLRV | 12172553 | ||
TTC3 | Akt1 | human | S378 | S378 | AYTPRsLsAPIFTTS | 20059950 | E3 ligase to Akt; phosphorylation promotes TTC3 function, such as ability to ubiquitinylate and destabilize Akt |
TWIST1 | Akt1 | human | S42, S123 | S42, S123 | GGRKRRSsRRSAGGG, RERQRTQsLNEAFAA | 20400976 | A regulatory basic helix-loop-helix anti-apoptotic transcription factor; phosphorylation activates TWIST1, causing inhibition of p53 and promotion of cell survival |
USP8 | Akt1 | mouse | T907 | T945 | TCRRRSRtFEAFMYL | 17210635 | Deubiquitinating enzyme that plays a role in growth factor receptor trafficking and degradation; phosphorylation increases protein stability |
VCP | Akt1 | human | S352, S746, S748 | S352, S746, S748 | AAtNRPNsIDPALRR, AMRFARRsVsDNDIR, RFARRsVsDNDIRky | 16551632, 16027165 | ATPase and molecular chaperone; phosphorylation may impair its pro-apoptotic effects and promote cell survival |
Vimentin | Akt1 | human | S39 | S39 | ttsTrtysLGsALRP | 20856200 | A cytoskeletal intermediate filament protein; phosphorylation induces cellular motility and invasion by protection from proteolysis |
Wee1 | Akt1 | human | S642 | S642 | KKMNRsVsLTIy___ | 15964826 | A 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 |
WNK1 | Akt1 | human | T60 | T60 | EYRRRRHtMDKDSRG | 14611643, 16081417 | Regulates ion channels; phosphorylation of WNK1 causes SGK1 activation and regulation of sodium ion transport |
XIAP | Akt1, Akt2 | human | S87 | S87 | VGRHRKVsPNCRFIN | 14645242, 17537996 | Inhibitor of apoptosis; phosphorylation prevents ubiquitination/degradation and causes increased cell survival |
YAP1 | Akt1 | human | S127 | S127 | PQHVRAHssPAsLQL | 12535517 | A transcriptional co-activator of PEBP2 and other transcription factors; phosphorylation suppresses p73-mediated apoptosis |
YB-1 | Akt1 | human | S102 | S102 | NPRKyLRsVGDGEtV | 22417301 | A transcription/translation factor involved in mRNA stability and expression; phosphorylation induces activation and translocation to the nucleus |
zyxin | Akt1 | human | S142 | S142 | PQPREKVssIDLEId | 17572661 | A 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