Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

RAC-alpha serine/threonine-protein kinase



Mus musculus (Mouse)
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli


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 PI3P-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 (PI3K) 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 (By similarity). Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity (By similarity). Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53 (By similarity).By similarity
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.10 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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.


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei53Inositol-(1,3,4,5)-tetrakisphosphateBy similarity1
Binding sitei86Inositol-(1,3,4,5)-tetrakisphosphateBy similarity1
Binding sitei161Inhibitor; via amide nitrogenBy similarity1
Binding sitei179ATP1
Binding sitei230Inhibitor; via amide nitrogenBy similarity1
Binding sitei234InhibitorBy similarity1
Active sitei274Proton acceptorPROSITE-ProRule annotation1
Binding sitei292InhibitorBy similarity1


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi156 – 164ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi


Molecular functionDevelopmental protein, Kinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Carbohydrate metabolism, Glucose metabolism, Glycogen biosynthesis, Glycogen metabolism, Neurogenesis, Sugar transport, Translation regulation, Transport
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 3474.
ReactomeiR-MMU-114604. GPVI-mediated activation cascade.
R-MMU-1257604. PIP3 activates AKT signaling.
R-MMU-1358803. Downregulation of ERBB2:ERBB3 signaling.
R-MMU-1445148. Translocation of GLUT4 to the plasma membrane.
R-MMU-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
R-MMU-165159. mTOR signalling.
R-MMU-165160. PDE3B signalling.
R-MMU-198323. AKT phosphorylates targets in the cytosol.
R-MMU-198693. AKT phosphorylates targets in the nucleus.
R-MMU-199418. Negative regulation of the PI3K/AKT network.
R-MMU-203615. eNOS activation.
R-MMU-211163. AKT-mediated inactivation of FOXO1A.
R-MMU-354192. Integrin alphaIIb beta3 signaling.
R-MMU-3769402. Deactivation of the beta-catenin transactivating complex.
R-MMU-389357. CD28 dependent PI3K/Akt signaling.
R-MMU-389513. CTLA4 inhibitory signaling.
R-MMU-392451. G beta:gamma signalling through PI3Kgamma.
R-MMU-450385. Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
R-MMU-450604. KSRP (KHSRP) binds and destabilizes mRNA.
R-MMU-5218920. VEGFR2 mediated vascular permeability.
R-MMU-5628897. TP53 Regulates Metabolic Genes.
R-MMU-6804757. Regulation of TP53 Degradation.
R-MMU-6804758. Regulation of TP53 Activity through Acetylation.
R-MMU-6804759. Regulation of TP53 Activity through Association with Co-factors.
R-MMU-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-MMU-69202. Cyclin E associated events during G1/S transition.
R-MMU-8849469. PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1.
R-MMU-8876198. RAB GEFs exchange GTP for GDP on RABs.

Names & Taxonomyi

Protein namesi
Recommended name:
RAC-alpha serine/threonine-protein kinase (EC:
Alternative name(s):
AKT1 kinase
Protein kinase B
Short name:
Protein kinase B alpha
Short name:
PKB alpha
Proto-oncogene c-Akt
Thymoma viral proto-oncogene
Gene namesi
Synonyms:Akt, Rac
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:87986. Akt1.

Subcellular locationi

GO - Cellular componenti

  • cell-cell junction Source: MGI
  • ciliary basal body Source: MGI
  • cytoplasm Source: UniProtKB
  • cytosol Source: MGI
  • microtubule cytoskeleton Source: MGI
  • mitochondrion Source: MGI
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • protein complex Source: MGI
  • spindle Source: MGI
  • vesicle Source: MGI

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Show fetal growth impairment and reduced vascularization in the placenta; majority of pups died within 10 days.1 Publication


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi176Y → F: Significant loss of interaction with TNK2. Loss of membrane localization. Significant reduction in phosphorylation on Ser-473. 1 Publication1
Mutagenesisi179K → A: Lacks kinase activity. Overexpression inhibits insulin-stimulated translocation of SLC2A4/GLUT4 in a dominant negative manner. 1 Publication1
Mutagenesisi308T → A: Does not affect ubiquitination by ZNRF1. 1 Publication1
Mutagenesisi473S → A: Does not affect ubiquitination by ZNRF1. 1 Publication1

Chemistry databases


PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000856061 – 480RAC-alpha serine/threonine-protein kinaseAdd BLAST480

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei14N6-acetyllysineBy similarity1
Modified residuei20N6-acetyllysineBy similarity1
Disulfide bondi60 ↔ 77By similarity
Modified residuei124PhosphoserineBy similarity1
Modified residuei126Phosphoserine; alternateBy similarity1
Glycosylationi126O-linked (GlcNAc) serine; alternateBy similarity1
Modified residuei129Phosphoserine; alternateCombined sources1
Glycosylationi129O-linked (GlcNAc) serine; alternateBy similarity1
Modified residuei176Phosphotyrosine; by TNK21 Publication1
Cross-linki284Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Disulfide bondi296 ↔ 310By similarity
Glycosylationi305O-linked (GlcNAc) threonineBy similarity1
Modified residuei308Phosphothreonine; by IKKE, PDPK1 and TBK13 Publications1
Glycosylationi312O-linked (GlcNAc) threonineBy similarity1
Modified residuei448PhosphothreonineBy similarity1
Modified residuei450Phosphothreonine; by MTOR1 Publication1
Modified residuei473Phosphoserine; by IKKE, MTOR and TBK1; alternate3 Publications1
Glycosylationi473O-linked (GlcNAc) serine; alternateBy similarity1
Modified residuei474PhosphotyrosineBy similarity1

Post-translational modificationi

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 (By similarity).By similarity
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 plasma 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 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 (By similarity).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. Ubiquitinated via 'Lys-48'-linked polyubiquitination by ZNRF1, leading to its degradation by the proteasome. Phosphorylated, undergoes 'Lys-48'-linked polyubiquitination preferentially at Lys-284 catalyzed by MUL1, leading to its proteasomal degradation.8 Publications
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 (By similarity).By similarity

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases


PTM databases



Tissue specificityi

Widely expressed. Low levels found in liver with slightly higher levels present in thymus and testis.1 Publication

Developmental stagei

Expressed in trophoblast and vessel endothelial cells of the placenta and in the brain at 14.5 dpc (at protein level).1 Publication

Gene expression databases

ExpressionAtlasiP31750. baseline and differential.
GenevisibleiP31750. MM.


Subunit structurei

Interacts with and phosphorylated by PDPK1 (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 TRIM13; the interaction ubiquitinates AKT1 leading to its proteasomal degradation. Interacts with RAF1 (By similarity). Interacts (via the C-terminus) with CCDC88A (via its C-terminus) and THEM4 (via its C-terminus). Interacts with GRB10; the interaction leads to GRB10 phosphorylation thus promoting YWHAE-binding. Interacts with KCTD20 (PubMed:24156551). Interacts with BTBD10 (PubMed:18160256). Interacts with PA2G4 (By similarity). Interacts with KIF14; the interaction is detected in the plasma membrane upon INS stimulation and promotes AKT1 phosphorylation (By similarity). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (By similarity). Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529, PubMed:20189988). Forms a complex with WDFY2 and FOXO1 (PubMed:18388859). Interacts with FAM168A (By similarity).By similarity10 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198056. 32 interactors.
IntActiP31750. 24 interactors.

Chemistry databases



3D structure databases


Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini5 – 108PHPROSITE-ProRule annotationAdd BLAST104
Domaini150 – 408Protein kinasePROSITE-ProRule annotationAdd BLAST259
Domaini409 – 480AGC-kinase C-terminalAdd BLAST72


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni14 – 19Inositol-(1,3,4,5)-tetrakisphosphate bindingBy similarity6
Regioni23 – 25Inositol-(1,3,4,5)-tetrakisphosphate bindingBy similarity3
Regioni228 – 230Inhibitor bindingBy similarity3


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.
The AGC-kinase C-terminal mediates interaction with THEM4.By similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0598. Eukaryota.

Family and domain databases

CDDicd05594. STKc_PKB_alpha. 1 hit.
Gene3Di2.30.29.30. 1 hit.
InterProiView protein in InterPro
IPR000961. AGC-kinase_C.
IPR034676. Akt1.
IPR011009. Kinase-like_dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
SMARTiView protein in SMART
SM00233. PH. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
SUPFAMiSSF50729. SSF50729. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS51285. AGC_KINASE_CTER. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.


Sequence statusi: Complete.

P31750-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
60 70 80 90 100
110 120 130 140 150
160 170 180 190 200
210 220 230 240 250
260 270 280 290 300
310 320 330 340 350
360 370 380 390 400
410 420 430 440 450
460 470 480
Mass (Da):55,707
Last modified:July 27, 2011 - v2

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti367R → A in AAA18254 (Ref. 3) Curated1

Sequence databases

Select the link destinations:
Links Updated
X65687 mRNA. Translation: CAA46620.1.
AF534134 Genomic DNA. Translation: AAN04036.1.
M94335 mRNA. Translation: AAA18254.1.
AK154936 mRNA. Translation: BAE32937.1.
CH466549 Genomic DNA. Translation: EDL18586.1.
BC066018 mRNA. Translation: AAH66018.1.
RefSeqiNP_001159366.1. NM_001165894.1.
NP_001318036.1. NM_001331107.1.
NP_033782.1. NM_009652.3.
XP_006515478.1. XM_006515415.1.

Genome annotation databases

EnsembliENSMUST00000001780; ENSMUSP00000001780; ENSMUSG00000001729.
UCSCiuc007pex.2. mouse.

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiAKT1_MOUSE
AccessioniPrimary (citable) accession number: P31750
Secondary accession number(s): Q62274, Q6GSA6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 27, 2011
Last modified: June 7, 2017
This is version 191 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program



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.Curated

Keywords - Technical termi

Complete proteome, Reference proteome


  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families