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FLASH GENE
Symbol AKT1 contributors: mct - updated : 18-03-2014
HGNC name v-akt murine thymoma viral oncogene homolog 1
HGNC id 391
Corresponding disease
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
    EC.number 2.7.1.37, 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 26.39 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    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
  • MAPPING cloned Y linked N status confirmed
    Physical map
    LOC390507 14 similar to proline-rich glycoprotein (sgp158) LOC388021 14 similar to expressed sequence AI839735 MGC13251 14q32.33 hypothetical protein MGC13251 FLJ22056 14q32.33 hypothetical protein FLJ22056 LOC388022 14 hypothetical gene supported by AK131040 ADSSL1 14q32.33 adenylosuccinate synthase like 1 SIVA 14q32.33 CD27-binding (Siva) protein AKT1 14q32.32 v-akt murine thymoma viral oncogene homolog 1 LOC390508 14 similar to MGC53446 protein MGC23270 14q32.33 hypothetical protein MGC23270 RPS2P4 14q32.33 ribosomal protein S2 pseudogene 4 KIAA0284 14q32.33 KIAA0284 LOC122618 14q32.33 hypothetical protein BC015003 C14orf78 14 chromosome 14 open reading frame 78 C14orf157 14q32.33 chromosome 14 open reading frame 157 C14orf79 14q32.33 chromosome 14 open reading frame 79 CDCA4 14q32.33 cell division cycle associated 4 GPR132 14q32.3 G protein-coupled receptor 132 JAG2 14q32 jagged 2 NUDT14 14q32.33 nudix (nucleoside diphosphate linked moiety X)-type motif 14 LOC390509 14 similar to chloride intracellular channel 6; chloride channel form A BRF1 14q32.33 BRF1 homolog, subunit of RNA polymerase III transcription initiation factor IIIB (S. cerevisiae) BTBD6 14q32 BTB (POZ) domain containing 6
    RNA
    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
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    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
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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
    HOMOLOGY
    interspecies homolog to C.elegans f28h6.1
    homolog to rattus Akt1 (98.12 pc)
    homolog to murine Akt1 (98.33 pc)
    Homologene
    FAMILY
  • protein kinase superfamily
  • AGC Ser/Thr protein kinase family
  • RAC subfamily
  • CATEGORY enzyme , protooncogene
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,nucleoplasm
    text
  • 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
  • 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
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS
    text transduction of antiapoptotic and proliferation signals in T cells, survival of lymphoid and other cell types
    PATHWAY
    metabolism
    signaling
  • 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
  • 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
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • 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)
  • 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
  • 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 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
  • PIK3CA activates AKT1, independently of PDPK1, and AKT2 by cooperating with PDPK1 in the insulin signal transduction pathway linked to SLC2A4 translocation
  • cell & other
    REGULATION
    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
    ASSOCIATED DISORDERS
    corresponding disease(s) PROTS
    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
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • both Akt1-/- and Igf2-/- mice exhibited decreased placental weight, fetal weight and viability