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FLASH GENE
Symbol AKT2 contributors: mct/npt/pgu - updated : 24-08-2015
HGNC name v-akt murine thymoma viral oncogene homolog 2
HGNC id 392
Corresponding disease
NIDDM6 diabetes mellitus, non insulin-dependent, 6
Location 19q13.12      Physical location : 40.736.224 - 40.791.265
Synonym name
  • rac protein kinase beta
  • RAC-beta serine/threonine-protein kinase
  • protein kinase Akt-2
  • Synonym symbol(s) PKB-BETA, PRKBB, RAC-BETA, PKBB, RAC-PK-beta
    EC.number 2.7.1.37/ 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 55.20 kb     14 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    FLJ38944 19q13.2 hypothetical protein FLJ38944 MGC20452 LOC390930 19 similar to Charot-Leyden crystal protein; Charcot-Leyden crystal protein; eosinophil lysophospholipase; lysolecithin acylhydrolase; galactin-10 PP13 19q13.1 placental protein 13 LOC390931 19 similar to placental protein 13-like protein LOC148003 19q13.2 similar to placental protein 13; galectin-13 LOC390932 19 similar to Eosinophil lysophospholipase (Charcot-Leyden crystal protein homolog) (Lysolecithin acylhydrolase) (CLC) (Galectin-10) PPL13 19q13.2 placental protein 13-like protein CLC 19q13.1 Charot-Leyden crystal protein LOC342900 19q13.2 hypothetical LOC342900 DYRK1B 19q12-q13.11 dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1B FBL 19q13.1 fibrillarin FCGBP 19q13.1 Fc fragment of IgG binding protein LOC388540 19 hypothetical gene supported by BX640962; NM_018457 PSMC4 19q13.11-q13.13 proteasome (prosome, macropain) 26S subunit, ATPase, 4 MGC43537 19q13.2 hypothetical protein MGC43537 LOC390933 19 similar to hypothetical protein FLJ36874 LOC163131 19q13.2 similar to BC331191_1 LOC284323 19q13.2 hypothetical protein LOC284323 MAP3K10 19q13.2 mitogen-activated protein kinase kinase kinase 10 FLJ30373 19q13.2 hypothetical protein FLJ30373 FLJ13265 19q13.2 hypothetical protein FLJ13265 AKT2 19q13.2 v-akt murine thymoma viral oncogene homolog 2 FLJ36888 19q13.2 hypothetical protein FLJ36888 PLD3 19q13.2 phospholipase D3 FLJ32818 PRX 19q13.13-13.2 periaxin SEI1 19q13.1-q13.2 periaxin RBT1 19q13.1-q13.2 periaxin BLVRB 19q13.13-q13.2 biliverdin reductase B (flavin reductase (NADPH)) SPTBN4 19q13.13 spectrin, beta, non-erythrocytic 4 LOC92799 19q13.2 hypothetical protein BC007653 LTBP4 19q13.1-q13.2 latent transforming growth factor beta binding protein 4 NUMBL 19q13-q13.2 numb homolog (Drosophila)-like ADCK4 19q13.2 aarF domain containing kinase 4 ITPKC 19q13.1 inositol 1,4,5-trisphosphate 3-kinase C FLJ41131 19q13.2 FLJ41131 protein SNRPA 19q13.2 small nuclear ribonucleoprotein polypeptide A MIA 19q13.32-q13.33 melanoma inhibitory activity RAB4B 19q13.2 RAB4B, member RAS oncogene family EGLN2 19q13.2 egl nine homolog 2 (C. elegans) CYP2T2P 19q13.2 cytochrome P450, family 2, subfamily T, polypeptide 2 pseudogene CYP2F1P 19q13.2 cytochrome P450, family 2, subfamily F, polypeptide 1 pseudogene CYP2A6 19q13.2 cytochrome P450, family 2, subfamily A, polypeptide 6 CYP2A7 19q13.2 cytochrome P450, family 2, subfamily A, polypeptide 7 CYP2G1 19q13.2 cytochrome P450, family 2, subfamily G, polypeptide 1 pseudogene
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 5317 55.8 481 - 1992 1409633
    13 - 5187 - 419 - -
    14 - 5280 - 419 - -
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinesmall intestine  highly
    Lymphoid/Immunespleen   highly
     thymus   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a SH2 and a pleckstrin homology (PH) N terminal domains
  • a short alpha helical linker
  • a C terminal kinase domain
  • HOMOLOGY
    interspecies homolog to V-akt murine thymoma viral oncogene 2
    homolog to C.elegans F28H6.1
    Homologene
    FAMILY
  • protein kinase superfamily
  • AGC Ser/Thr protein kinase family
  • RAC subfamily
  • CATEGORY enzyme , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text
  • mitochondrial localization of AKT2 raises the possibility that this isoform may be involved in both glucose-based energy metabolism and suppression of apoptosis
  • basic FUNCTION
  • AKT is a key regulator for cell growth, cell survival
  • playing a central role in insulin sensitivity
  • enhances palladin expression by maintaining protein stability and upregulating transcription
  • AKT2 is indispensable for the regulation of preadipocyte and adipocyte number, whereas AKT1 and AKT2 are equally important for the regulation of insulin-stimulated metabolic pathways in human adipocytes
  • protective effects of AKT2 on the aortic wall, that may serve as a therapeutic target in the prevention of Aortic aneurysm and dissection (AAD)
  • ASAH1 and AKT2 cooperate to induce malignant transformation
  • is essential to maintain podocyte viability and function during chronic kidney disease
  • is potentially important for neutrophil recruitment and neutrophil-platelet interactions under thromboinflammatory conditions such as sickle cell disease (SCD)
  • specific function for AKT2 in mediating survival of PTEN-deficient tumors
  • serine/threonine protein kinase AKT2 is critically involved in insulin-dependent RAC1 activation
  • both AKT1 and AKT2 are involved in albumin endocytosis, and phosphorylation of DAB2 by AKT induces albumin endocytosis in proximal tubule epithelial cells
  • macrophage AKT2 regulates migration, the inflammatory response and cholesterol metabolism
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS
    text
  • maintenance of normal glucose homeostasis, survival of lymphoid and other cell types
  • PATHWAY
    metabolism
    signaling
    PI3K/AKT/MTOR signaling pathway is involved in regulation of SPHK1, with AKT2 playing a key role in PDGF-induced SPHK1 expression in coronary artery smooth muscle cells
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • phosphorylating and inactivating components of the apoptotic machinery including BAD, CASP9 and the transcription factor FKHRL1 (phosphatidyl inositol)
  • down regulating hyperproliferation and antiapoptotic activities induced by IGF1R hyperstimulation
  • preferential interaction between WDFY2 and AKT2 that promotes the maintenance of AKT2 protein levels
  • MAPKAP1/CRTC2-AKT2 signaling axis is a key regulator of FOXO1 transcriptional activity in B cells
  • SNAI1 enhances the binding of AKT2 to the E-cadherin (CDH1) promoter and AKT2 interference prevents SNAI1 repression of CDH1 gene
  • is a negative regulator of NFATC1 activation through its ability to inhibit calcium mobilization from the ER
  • regulates RAC1 activity in the insulin-dependent signaling pathway leading to SLC2A4 translocation to the plasma membrane in skeletal muscle cells
  • PIK3CA activates AKT1, independently of PDPK1, and AKT2 by cooperating with PDPK1 in the insulin signal transduction pathway linked to SLC2A4 translocation
  • binding of CDKN1A to AKT2 in the nucleus is an essential component in determining the specific role of AKT2 in the cell cycle arrest that precedes myogenic differentiation
  • enhanced AKT2 or AKT3 activation also promotes reprogramming and coordinates with LIF to activate STAT3
  • both AKT1 and AKT2 are involved in albumin endocytosis, and phosphorylation of DAB2 by AKT induces albumin endocytosis in proximal tubule
  • APPL1 binds to AKT2, a key molecule in the insulin signaling pathway, thereby enhancing insulin-induced AKT2 activation and downstream signaling leading to insulin action and secretion
  • TMOD3 is a novel AKT2 effector regulating insulin-stimulated SLC2A4 exocytosis through cortical actin remodeling
  • cell & other
    REGULATION
    activated by growth factors via PI3K binding to PH domain, induced by insulin growth factor 1, and maybe others activated by phosphatidylinositol 3- kinase in the antiapoptotic PI3K pathway
    coactivated by TCL1
    Phosphorylated by PDK1 that phosphorylates AKT1 at Thr308 and AKT2 at Thr309
    Other
  • CSNK2A1-dependent phosphorylation is a crucial event which, discriminating between AKT1 and AKT2, can account for different substrate specificities
  • ASSOCIATED DISORDERS
    corresponding disease(s) NIDDM6
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in ovarian carcinoma
    tumoral   amplification    
    in ovarian and pancreatic carcinomas
    tumoral somatic mutation      
    in the kinase domain occuring in a small fraction of common cancers
    tumoral       gain of function
    associated with the survival of melanoma cells
    tumoral   amplification    
    amplification of AKT1 and/or AKT2 and high-level polysomy were found in lung carcinomas
    tumoral fusion      
    recurrent BCAM-AKT2 fusion gene leads to a constitutively activated AKT2 fusion kinase in high-grade serous ovarian carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerbrainglioma/neuroblstoma
    targeting AKT2 and AKT3 may hold promise for the treatment of patients with gliomas
    cardiovascularatheromacardiac
    argeting AKT2 in macrophages might be beneficial for treating atherosclerosis.
    ANIMAL & CELL MODELS
  • Akt2-deficient mice showed abnormal elastic fibers and reduced medial thickness in the aortic wall