Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
Symbol AKT1 contributors: mct - updated : 18-03-2019
HGNC name v-akt murine thymoma viral oncogene homolog 1
HGNC id 391
Corresponding disease
CWS6 Cowden syndrome 6
PROTS Proteus syndrome
Location 14q32.33      Physical location : 105.235.688 - 105.262.080
Synonym name
  • protein kinase B
  • rac protein kinase alpha
  • AKT1 kinase
  • RAC-alpha serine/threonine-protein kinase
  • proto-oncogene c-Akt
  • Synonym symbol(s) PKB, RAC, PRKBA, RAC-ALPHA, AKT, MGC99656, PKB-ALPHA, RAC-PK-alpha
    TYPE functioning gene
    STRUCTURE 26.39 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   HRE
    motif repetitive sequence
    text structure
  • transcriptional up-regulation of AKT1 by the Src/Stat3 pathway
  • major Stat3 response elements are located within exon 1 and intron 1 regions of the AKT1 gene, which is upstream of the AKT1 translation initiation site
  • two RUNX3-binding sites in AKT1 promoter and the binding of RUNX3 on AKT1 promoter significantly inhibits AKT1 expression
  • MAPPING cloned Y linked N status confirmed
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 3008 55 480 - 2010 20109457
  • variant 1, lacking exon 1, containing exon 2a (longer than 2b)
  • encoding the same product as variants 2 & 3
  • 15 splicing 2878 55 480 - 2010 20109457
  • variant 2, containing exon 2b (shorter than 2a)
  • encoding the same product as variants 1 & 3
  • 14 splicing 2794 55 480 - 2010 20109457
  • variant 3, lacking exon 2
  • encoding the same product as variants 1 & 2
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
     salivary gland   predominantly
    Endocrinepancreas   highly
    Lymphoid/Immunetonsils   highly
    Nervousnervecranial nerve  highly
    Reproductivefemale systembreastmammary gland moderately
     female systemovary  moderately
     male systemprostate  highly
    Skin/Tegumentskin   moderately
    cell lineage
    cell lines
    fluid/secretion lymph
    at STAGE
  • a cAMP-dependent, cGMP-dependent and protein kinase C domain
  • a SH2 and a pleckstrin homology (PH) N terminal domains
  • a short alpha helical linker
  • a PH domain, binding phosphoinositides
  • conjugated PhosphoP , ubiquitinated , sumoylated
    interspecies homolog to C.elegans f28h6.1
    homolog to rattus Akt1 (98.12 pc)
    homolog to murine Akt1 (98.33 pc)
  • protein kinase superfamily
  • AGC Ser/Thr protein kinase family
  • RAC subfamily
  • CATEGORY enzyme , protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
  • become enriched at cell membranes where it is activated by phosphorylation
  • localized in the cytoplasm
  • basic FUNCTION
  • a key regulator for cell growth, cell survival and metabolic insulin action
  • contributing to tumor-cell proliferation by phosphorylation and cytosolic retention of CDKN1B
  • apoptotic regulator activated in many cancers
  • regulating the methylation activity, through phosphorylation of EZH2
  • inhibits chromatin condensation during apoptosis by phosphorylating ACIN1 in the nucleus, revealing a specific mechanism by which nuclear AKT1 promotes cell survival
  • able to transform keratinocytes by specific mechanisms involving transcriptional and post-transcriptional processes
  • key regulator of lamellipodia formation and cell motility
  • involved in muscle differentiation through its involvement in PI3K signaling and is also involved in the regulation of MEF2A, MEF2B, MEF2C
  • with SLC9A1, has functions, including cell growth and survival, that might be regulated by increased H(+) efflux
  • AKT1 isoforms regulate intermediate filament expression and intermediate filament are may be involved in PI3K/Akt pathway
  • important mediator of cardiac myocyte growth and survival
  • primary Akt isoform activated by mutant KRAS in lung tumors
  • phosphorylates SP7 and its activation increases protein stability, osteogenic activity and transcriptional activity of SP7
  • enhances the osteogenic function of Osterix (SP7) by increasing protein stability and transcriptional activity
  • molecular role for AKT1/FOXO and MAPK8/JUN in maintaining a differentiation blockade that can be targeted to inhibit leukemias with a range of genetic lesions
  • AKT1 and AKT2 are equally important for the regulation of insulin-stimulated metabolic pathways in human adipocytes
  • AKT1 and insulin-like growth factor 2 (IGF2) regulate placentation and fetal/postnatal development (r
  • SSPN-dependent AKT1 activation is required for UTRN expression and muscle regeneration
  • participates in the control of meiosis resumption and, at metaphase II stage, regulates polar body emission and spindle organization
  • major signaling hub integrating metabolic, survival, growth, and cell cycle regulatory signals
  • regulates LMNA transcription, having a function in the control of prelamin A stability and expression
  • facilitated the endocytic trafficking of EGFR to promote its degradation
  • plays essential roles in cell proliferation and tumorigenesis
  • sustained AKT1 activation is crucial for TGFB-induced myofibroblast (MF) formation and persistent differentiation
  • AKT1 and AKT3 are essential for the proliferation of reprogrammed cells
  • both AKT1 and AKT2 are involved in albumin endocytosis, and phosphorylation of DAB2 by AKT induces albumin endocytosis in proximal tubule epithelial cells
  • role of the FKBP51-AKT1 kinase-synapsin pathway in stress responsiveness
  • ERBB2 and AKT1 are important for cranial neural crest (CNC) migration, but other ERBB receptors and AKT1-independent signaling pathways are implicated
  • plays an important role in cell survival or tumor progression
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, antiapoptosis
    text transduction of antiapoptotic and proliferation signals in T cells, survival of lymphoid and other cell types
  • AKT1 signalling has emerged as one of the major pathways involved in myelination, implicated in the regulation of several steps during the development of myelinating Schwann cells and oligodendrocytes
  • PIK3CA/AKT1/MTOR signaling pathway, which was overactivated in aldosterone-producing adenomas (APAs), idiopathic hyperaldosteronism (IHA)compared with normal zona glomerulosa, may mediate aldosterone hypersecretion and participate in the development of primary aldosteronism (PA)
  • a component
  • PRKACA, AKT1 and RAPGEF3 were all shown to establish complexes with neuronal A-kinase anchoring protein150 (AKAP5)
  • AKT1/NF-kappaB/ACIN1 pathway functions as one of the important regulatory mechanisms required for modulating ionizing radiation sensitivity
  • AKT1-PAK1-AJUBA feedback loop integrates spatiotemporal signaling with actin remodeling at cell-cell contacts and stabilizes preassembled cadherin complexes
  • the RUNX3-mediated inhibition of AKT1 caused CTNNB1 protein degradation and then CCND1 downregulation
  • part of functional molecular complex formed by STYK1, AKT1 and GSK3B that may relay a STYK1-directed tumourigenic cascade
  • roles of AKT1 and SGK1 in the regulation of renal tubular transport
    small molecule
  • phosphorylating NUR77 within its DNA binding domain
  • inactivating components of the apoptotic machinery including BAD, CASP9 and the transcription factor FKHRL1
  • GSK3B (AKT1/GSK3B signaling required for axons elongation and branching)
  • interacting with thrombospondin to regulate angiogenesis (AKT-thrombospondin axis)
  • down-regulating the mesenchymal transition and enhanced cell migration induced by IGF-I or EGF stimulation
  • cross-regulating the ERK signaling pathway
  • direct target gene of STAT3 and contributes to STAT3 anti-apoptotic function
  • interacting with BCL2 (functions as an activator of the AKT1 signaling pathway in pancreatic cancer)
  • binds to PLEKHM3
  • AKT1 may induce anti-apoptotic signals at least in part through the regulation of the amount and activity of BCL2L2
  • association with PTK6 occuring through the SH3 domain of PTK6 and is enhanced through SH2 domain-mediated interactions following tyrosine phosphorylation of AKT1
  • interaction involving IQGAP1, MTOR and AKT1 (IQGAP1 is a scaffold that facilitates MTOR and AKT interaction)
  • interacting with RPS3 (selectively initiates anti-apoptotic defenses and represses programmed cell death by regulation of RPS3 and manipulation of nuclear RPS3)
  • interaction between AKT1 and CFLAR
  • binding of AKT1 (tail region) to VIM (head region) results in Vim Ser39 phosphorylation enhancing the ability of VIM to induce motility and invasion while protecting VIMfrom caspase-induced proteolysis
  • AKT1 and FOXM1 are downstream targets of NOTCH1 signaling
  • interacts with MEN1 (through interaction with AKT1, menin suppresses both AKT1-induced proliferation and antiapoptosis in nonendocrine and endocrine cells)
  • interaction with TBK1 (regulatory mechanism for AKT1 activation mediated by TBK1 and role of AKT1 in TLR-mediated immune responses)
  • TNFRSF4 primarily functions to augment AKT1 signaling in T cells by enhancing the amount of PIK3CD and AKT1 available to the TCR
  • AKT1 is a direct TBK1 substrate that connects TBK1 to prosurvival signaling
  • physiological function of IKBKE/TBK1 in AKT1 regulation and a possible mechanism of IKBKE/TBK1 in oncogenesis by activating AKT1
  • IKBKE is a critical regulator of AKT1
  • AKT1 induces senescence in cells via MTOR and TP53 in the absence of DNA damage
  • AKT1 was found to directly interact with MUL1 and to be ubiquitinated by MUL1
  • role for CYLD in tightly regulating the resolution of lung injury and preventing fibrosis by deubiquitinating AKT1
  • PROM1 has negative effect on the growth of cells through AKT1-dependent signalling pathway
  • SSPN regulates AKT1 signaling to control UTRN expression
  • DLX3 is a novel target of AKT1 and the activity of DLX3 could be modulated by a novel mechanism involving AKT1 during osteoblast differentiation
  • PHF20 is a novel substrate for AKT1 and its phosphorylation by AKT1 plays an important role in tumorigenesis via regulating of TP53 mediated signaling
  • HOX expression could be controlled by the function of AKT1 through epigenetic modification such as DNA methylation
  • AKT1 activity, mediated in part through MTOR, links RIPK1 to JNK activation and autocrine production of TNF
  • AKT1 phosphorylation and activation of PIKFYVE is likely to be a common feedback mechanism for terminating RTK signaling and reducing receptor abundance
  • ARHGEF3 negatively regulates cell survival and skeletal myoblast differentiation by inhibiting CRTC2 and subsequently the Ser/Thr kinase AKT1
  • AKT1 mediated TGFB1-induced ACTA2 synthesis through the contractile gene transcription factors myocardin and serum response factor (SRF)
  • PIK3CA activates AKT1, independently of PDPK1, and AKT2 by cooperating with PDPK1 in the insulin signal transduction pathway linked to SLC2A4 translocation
  • AKT1 and its downstream MTOR signaling mediates POMC-induced survival in retinal pigment epithelium cells
  • CARD11 is a novel target for AKT1 phosphorylation, suggesting that AKT1-mediated phosphorylation of CARD11 is an additional regulatory mechanism tuning the NFKB1 response downstream of antigen receptor and co-stimulatory signaling
  • FAM3A plays crucial roles in the regulation of glucose and lipid metabolism in the liver, where it activates the PIK3CA-AKT1 signaling pathway by way of a Ca(2+) /CALM1-dependent mechanism
  • AKT1 is an inter-mediator between the upstream regulator, ALCAM, and downstream effector, FOXO1, in liver cancer cells
  • AKT1 phosphorylation and regulation of TKT is a nodal point for amino acid control of purine synthesis
  • AKT1 augments STAT3 activity through activation of MTOR and upregulation of LIFR expression
  • both AKT1 and AKT2 are involved in albumin endocytosis, and phosphorylation of DAB2 by AKT induces albumin endocytosis in proximal tubule
  • AKT1/CCDC88A signaling in cancer-associated fibroblasts contributes to tumor progression
  • TNFAIP8L2 inhibited the phosphorylation of AKT1, while promoting the phosphorylation of MAPK14, but had no effect on NFKBIA and ERK pathway
  • phosphorylation of PDE3B by AKT1 is not required for insulin to suppress adipocyte lipolysis
  • CD82 regulated BCL2L12 expression via STAT5A and AKT1 signaling and stimulated proliferation and engrafting of leukemia cells
  • ZNRF1 promotes Wallerian degeneration by degrading AKT1 to induce GSK3B activation
  • SMYD3-mediated methylation of AKT1 at lysine 14 is essential for AKT1 activation
  • TNFAIP8L2 suppressed breast cancer tumorigenesis, growth and metastasis possibly via regulation of the AKT1 and MAPK14 signaling pathways
  • ZP3 regulates AKT1 phosphorylation, lamin binding to the nuclear membrane via AIPL1, and organization of the actin cytoskeleton via DIAPH2
  • TRIM14 functions as an oncogene by upregulating the AKT1 signaling pathway in osteosarcoma cells
  • PDCD5 competitively inhibited interaction between histone deacetylase 3 (HDAC3) and AKT1
  • C terminus of AKT1, AKT2 and the N terminus of VRK2 facilitate the interaction of Akt and VRK2 in mammalian cells
  • EPS8L3 might likely promote proliferation by hyperactivating the AKT1 signaling pathway and subsequently inhibiting the FOXO1A transcriptional activity
  • DSC3 suppresses Colorectal cell growth through inhibition of AKT1 pathway and regulation of CDH1
  • SAV1 suppresses AKT1 activation by blocking Akt's movement to plasma membrane
  • TIGAR may promote glioblastoma growth and progression through oxidation resistance and AKT1 activation
  • SOX2 mediates the expression of HBEGF and FSCN1 by activating AKT1 and CTNNB1 signaling pathways
  • AKT1 and RNF167-mediated CASTOR1 degradation activates MTOR independent of arginine and promotes breast cancer progression
  • cell & other
    activated by growth factors via PI3K (phosphatidylinositol 3-kinase), binding to PH domain induced by insulin growth factor 1,
    and maybe others activated by phosphadidylinositol 3-kinase in the antiapoptotic PI3K pathway
    coactivated by TCL1
    phosphorylation by TGFB1
    PREX1 and CRTC2 (activation of AKT1 through CRTC2 and PREX1 regulates cancer cell migration, invasion and metastasis)
    Phosphorylated by a MRE11A-ATM-RNF168 signaling complex, implicated in a signaling cascade that directly promotes a PI3K-independent pathway of AKT1 phosphorylation
    CRTC2, that phosphorylates the hydrophobic motif site Ser473 on the Ser/Thr kinase AKT1 that is necessary for its activation
    PDK1 that phosphorylates AKT1 at Thr308 and AKT2 at Thr309
    Other its ubiquitination and activation is regulated by TRAF6
    AKT1 SUMOylation provides a novel regulatory mechanism for activating AKT1 function
    degradation of AKT1 by MUL1 suppresses cell proliferation and viability
  • CSNK2A1-dependent phosphorylation is a crucial event which, discriminating between AKT1 and AKT2, can account for different substrate specificities
    corresponding disease(s) PROTS , CWS6
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    amplified in gastric carcinoma
    tumoral     --over  
    in prostate, breast cancer
    constitutional somatic mutation      
    somatic activating mutation in Proteus syndrome
    constitutional germinal mutation     gain of function
    in Cowden and Cowden-like syndrome
    tumoral   amplification --over  
    in a defined subset of bone and soft tissue tumors, including benign tumors
    tumoral   amplification    
    amplification of AKT1 and/or AKT2 and high-level polysomy were found in lung carcinomas
    Susceptibility to schizophrenia and bipolar disorders
    Variant & Polymorphism SNP
    Candidate gene
    Therapy target
  • both Akt1-/- and Igf2-/- mice exhibited decreased placental weight, fetal weight and viability