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P31750

- AKT1_MOUSE

UniProt

P31750 - AKT1_MOUSE

Protein

RAC-alpha serine/threonine-protein kinase

Gene

Akt1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 160 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    Functioni

    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.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei53 – 531Inositol-(1,3,4,5)-tetrakisphosphateBy similarity
    Binding sitei86 – 861Inositol-(1,3,4,5)-tetrakisphosphateBy similarity
    Binding sitei161 – 1611Inhibitor; via amide nitrogenBy similarity
    Binding sitei179 – 1791ATP
    Binding sitei230 – 2301Inhibitor; via amide nitrogenBy similarity
    Binding sitei234 – 2341InhibitorBy similarity
    Active sitei274 – 2741Proton acceptorPROSITE-ProRule annotation
    Binding sitei292 – 2921InhibitorBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi156 – 1649ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. kinase activity Source: MGI
    3. nitric-oxide synthase regulator activity Source: Ensembl
    4. phosphatidylinositol-3,4,5-trisphosphate binding Source: Ensembl
    5. phosphatidylinositol-3,4-bisphosphate binding Source: Ensembl
    6. protein binding Source: UniProtKB
    7. protein kinase activity Source: UniProtKB
    8. protein kinase binding Source: UniProtKB
    9. protein serine/threonine/tyrosine kinase activity Source: MGI
    10. protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    1. activation-induced cell death of T cells Source: MGI
    2. aging Source: Ensembl
    3. anagen Source: MGI
    4. apoptotic mitochondrial changes Source: MGI
    5. cell projection organization Source: MGI
    6. cellular response to epidermal growth factor stimulus Source: UniProtKB
    7. cellular response to granulocyte macrophage colony-stimulating factor stimulus Source: MGI
    8. cellular response to growth factor stimulus Source: MGI
    9. cellular response to hypoxia Source: Ensembl
    10. cellular response to insulin stimulus Source: UniProtKB
    11. cellular response to mechanical stimulus Source: Ensembl
    12. cellular response to peptide Source: MGI
    13. cytoskeleton organization Source: UniProtKB
    14. endocrine pancreas development Source: Reactome
    15. execution phase of apoptosis Source: MGI
    16. germ cell development Source: MGI
    17. glucose homeostasis Source: MGI
    18. glucose metabolic process Source: MGI
    19. glucose transport Source: UniProtKB
    20. glycogen biosynthetic process Source: UniProtKB-KW
    21. glycogen cell differentiation involved in embryonic placenta development Source: MGI
    22. glycogen metabolic process Source: MGI
    23. hyaluronan metabolic process Source: Ensembl
    24. inflammatory response Source: MGI
    25. insulin-like growth factor receptor signaling pathway Source: UniProtKB
    26. insulin receptor signaling pathway Source: UniProtKB
    27. intracellular signal transduction Source: MGI
    28. labyrinthine layer blood vessel development Source: MGI
    29. maternal placenta development Source: MGI
    30. negative regulation of apoptotic process Source: UniProtKB
    31. negative regulation of autophagy Source: Ensembl
    32. negative regulation of cell size Source: MGI
    33. negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    34. negative regulation of fatty acid beta-oxidation Source: Ensembl
    35. negative regulation of JNK cascade Source: Ensembl
    36. negative regulation of plasma membrane long-chain fatty acid transport Source: Ensembl
    37. negative regulation of protein kinase activity Source: Ensembl
    38. negative regulation of proteolysis Source: Ensembl
    39. negative regulation of release of cytochrome c from mitochondria Source: UniProtKB
    40. osteoblast differentiation Source: MGI
    41. peptidyl-serine phosphorylation Source: MGI
    42. peripheral nervous system myelin maintenance Source: MGI
    43. positive regulation of apoptotic process Source: Ensembl
    44. positive regulation of blood vessel endothelial cell migration Source: Ensembl
    45. positive regulation of cell growth Source: Ensembl
    46. positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle Source: Ensembl
    47. positive regulation of endothelial cell proliferation Source: UniProtKB
    48. positive regulation of establishment of protein localization to plasma membrane Source: Ensembl
    49. positive regulation of fat cell differentiation Source: Ensembl
    50. positive regulation of glucose import Source: Ensembl
    51. positive regulation of glycogen biosynthetic process Source: Ensembl
    52. positive regulation of lipid biosynthetic process Source: Ensembl
    53. positive regulation of nitric oxide biosynthetic process Source: Ensembl
    54. positive regulation of nitric-oxide synthase activity Source: Ensembl
    55. positive regulation of peptidyl-serine phosphorylation Source: Ensembl
    56. positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: MGI
    57. positive regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
    58. positive regulation of sodium ion transport Source: MGI
    59. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    60. positive regulation of vasoconstriction Source: Ensembl
    61. protein catabolic process Source: MGI
    62. protein import into nucleus, translocation Source: Ensembl
    63. protein kinase B signaling Source: MGI
    64. protein phosphorylation Source: UniProtKB
    65. protein ubiquitination Source: MGI
    66. regulation of cell migration Source: UniProtKB
    67. regulation of neuron projection development Source: UniProtKB
    68. regulation of protein localization Source: MGI
    69. regulation of translation Source: UniProtKB-KW
    70. response to fluid shear stress Source: Ensembl
    71. response to food Source: MGI
    72. response to hormone Source: UniProtKB
    73. response to UV-A Source: Ensembl
    74. striated muscle cell differentiation Source: MGI
    75. translation Source: Ensembl

    Keywords - Molecular functioni

    Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Apoptosis, Carbohydrate metabolism, Glucose metabolism, Glycogen biosynthesis, Glycogen metabolism, Neurogenesis, Sugar transport, Translation regulation, Transport

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.1. 3474.
    ReactomeiREACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_198695. Butyrate Response Factor 1 (BRF1) destabilizes mRNA.
    REACT_198696. KSRP destabilizes mRNA.
    REACT_199047. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
    REACT_199054. Translocation of GLUT4 to the plasma membrane.
    REACT_199061. Downregulation of ERBB2:ERBB3 signaling.
    REACT_214733. Negative regulation of the PI3K/AKT network.
    REACT_218211. AKT phosphorylates targets in the nucleus.
    REACT_219771. deactivation of the beta-catenin transactivating complex.
    REACT_220092. GPVI-mediated activation cascade.
    REACT_220918. AKT phosphorylates targets in the cytosol.
    REACT_221264. eNOS activation.
    REACT_221926. AKT-mediated inactivation of FOXO1A.
    REACT_223974. G beta:gamma signalling through PI3Kgamma.
    REACT_226151. CD28 dependent PI3K/Akt signaling.
    REACT_226341. PIP3 activates AKT signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    RAC-alpha serine/threonine-protein kinase (EC:2.7.11.1)
    Alternative name(s):
    AKT1 kinase
    Protein kinase B
    Short name:
    PKB
    Protein kinase B alpha
    Short name:
    PKB alpha
    Proto-oncogene c-Akt
    RAC-PK-alpha
    Thymoma viral proto-oncogene
    Gene namesi
    Name:Akt1
    Synonyms:Akt, Rac
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 12

    Organism-specific databases

    MGIiMGI:87986. Akt1.

    Subcellular locationi

    Cytoplasm. Nucleus. Cell membrane By similarity
    Note: Nucleus after activation by integrin-linked protein kinase 1 (ILK1) By similarity. Nuclear translocation is enhanced by interaction with TCL1A. Phosphorylation on Tyr-176 by TNK2 results in its localization to the cell membrane where it is targeted for further phosphorylations on Thr-308 and Ser-473 leading to its activation and the activated form translocates to the nucleus.By similarity

    GO - Cellular componenti

    1. cell-cell junction Source: MGI
    2. ciliary basal body Source: MGI
    3. cytoplasm Source: MGI
    4. cytosol Source: Reactome
    5. mitochondrion Source: MGI
    6. nucleoplasm Source: Reactome
    7. nucleus Source: UniProtKB
    8. plasma membrane Source: UniProtKB
    9. spindle 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

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi176 – 1761Y → F: Significant loss of interaction with TNK2. Loss of membrane localization. Significant reduction in phosphorylation on Ser-473. 1 Publication
    Mutagenesisi179 – 1791K → A: Lacks kinase activity. Overexpression inhibits insulin-stimulated translocation of SLC2A4/GLUT4 in a dominant negative manner. 1 Publication
    Mutagenesisi308 – 3081T → A: Does not affect ubiquitination by ZNRF1. 1 Publication
    Mutagenesisi473 – 4731S → A: Does not affect ubiquitination by ZNRF1. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 480480RAC-alpha serine/threonine-protein kinasePRO_0000085606Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei14 – 141N6-acetyllysineBy similarity
    Modified residuei20 – 201N6-acetyllysineBy similarity
    Disulfide bondi60 ↔ 77By similarity
    Modified residuei124 – 1241Phosphoserine
    Modified residuei126 – 1261Phosphoserine; alternate
    Glycosylationi126 – 1261O-linked (GlcNAc); alternateBy similarity
    Modified residuei129 – 1291Phosphoserine; alternate1 Publication
    Glycosylationi129 – 1291O-linked (GlcNAc); alternateBy similarity
    Modified residuei176 – 1761Phosphotyrosine; by TNK21 Publication
    Cross-linki284 – 284Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Disulfide bondi296 ↔ 310By similarity
    Glycosylationi305 – 3051O-linked (GlcNAc)By similarity
    Modified residuei308 – 3081Phosphothreonine; by IKKE, PDPK1 and TBK13 Publications
    Glycosylationi312 – 3121O-linked (GlcNAc)By similarity
    Modified residuei450 – 4501Phosphothreonine; by MTOR1 Publication
    Modified residuei473 – 4731Phosphoserine; by IKKE, MTOR and TBK1; alternate3 Publications
    Glycosylationi473 – 4731O-linked (GlcNAc); alternateBy similarity
    Modified residuei474 – 4741PhosphotyrosineBy similarity

    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.9 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

    MaxQBiP31750.
    PaxDbiP31750.
    PRIDEiP31750.

    PTM databases

    PhosphoSiteiP31750.

    Expressioni

    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

    ArrayExpressiP31750.
    BgeeiP31750.
    CleanExiMM_AKT1.
    GenevestigatoriP31750.

    Interactioni

    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.By similarity5 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ARRB2P321213EBI-298707,EBI-714559From a different organism.
    FAM110CQ1W6H93EBI-298707,EBI-3942563From a different organism.
    Hsp90aa1P079016EBI-298707,EBI-78930
    PREX1Q8TCU62EBI-298707,EBI-1046542From a different organism.
    Trib3Q8K4K25EBI-298707,EBI-448962
    UbcP629913EBI-298707,EBI-413074
    XP031652EBI-298707,EBI-7683985From a different organism.

    Protein-protein interaction databases

    BioGridi198056. 16 interactions.
    DIPiDIP-736N.
    IntActiP31750. 24 interactions.
    MINTiMINT-4049532.

    Structurei

    3D structure databases

    ProteinModelPortaliP31750.
    SMRiP31750. Positions 1-477.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini5 – 108104PHPROSITE-ProRule annotationAdd
    BLAST
    Domaini150 – 408259Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini409 – 48072AGC-kinase C-terminalAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni14 – 196Inositol-(1,3,4,5)-tetrakisphosphate bindingBy similarity
    Regioni23 – 253Inositol-(1,3,4,5)-tetrakisphosphate bindingBy similarity
    Regioni228 – 2303Inhibitor bindingBy similarity

    Domaini

    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

    Contains 1 AGC-kinase C-terminal domain.Curated
    Contains 1 PH domain.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00740000114960.
    HOGENOMiHOG000233033.
    HOVERGENiHBG108317.
    InParanoidiQ6GSA6.
    KOiK04456.
    OMAiSRERVFP.
    OrthoDBiEOG7Q5HCW.
    TreeFamiTF102004.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    InterProiIPR000961. AGC-kinase_C.
    IPR011009. Kinase-like_dom.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR017892. Pkinase_C.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00169. PH. 1 hit.
    PF00069. Pkinase. 1 hit.
    PF00433. Pkinase_C. 1 hit.
    [Graphical view]
    SMARTiSM00233. PH. 1 hit.
    SM00133. S_TK_X. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
    PS50003. PH_DOMAIN. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P31750-1 [UniParc]FASTAAdd to Basket

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    MNDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVDQRES    50
    PLNNFSVAQC QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWA 100
    TAIQTVADGL KRQEEETMDF RSGSPSDNSG AEEMEVSLAK PKHRVTMNEF 150
    EYLKLLGKGT FGKVILVKEK ATGRYYAMKI LKKEVIVAKD EVAHTLTENR 200
    VLQNSRHPFL TALKYSFQTH DRLCFVMEYA NGGELFFHLS RERVFSEDRA 250
    RFYGAEIVSA LDYLHSEKNV VYRDLKLENL MLDKDGHIKI TDFGLCKEGI 300
    KDGATMKTFC GTPEYLAPEV LEDNDYGRAV DWWGLGVVMY EMMCGRLPFY 350
    NQDHEKLFEL ILMEEIRFPR TLGPEAKSLL SGLLKKDPTQ RLGGGSEDAK 400
    EIMQHRFFAN IVWQDVYEKK LSPPFKPQVT SETDTRYFDE EFTAQMITIT 450
    PPDQDDSMEC VDSERRPHFP QFSYSASGTA 480
    Length:480
    Mass (Da):55,707
    Last modified:July 27, 2011 - v2
    Checksum:i98DF28E5EFE03730
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti367 – 3671R → A in AAA18254. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    CCDSiCCDS26194.1.
    PIRiS33364.
    RefSeqiNP_001159366.1. NM_001165894.1.
    NP_033782.1. NM_009652.3.
    XP_006515478.1. XM_006515415.1.
    XP_006515479.1. XM_006515416.1.
    UniGeneiMm.6645.

    Genome annotation databases

    EnsembliENSMUST00000001780; ENSMUSP00000001780; ENSMUSG00000001729.
    GeneIDi11651.
    KEGGimmu:11651.
    UCSCiuc007pex.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS26194.1.
    PIRi S33364.
    RefSeqi NP_001159366.1. NM_001165894.1.
    NP_033782.1. NM_009652.3.
    XP_006515478.1. XM_006515415.1.
    XP_006515479.1. XM_006515416.1.
    UniGenei Mm.6645.

    3D structure databases

    ProteinModelPortali P31750.
    SMRi P31750. Positions 1-477.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 198056. 16 interactions.
    DIPi DIP-736N.
    IntActi P31750. 24 interactions.
    MINTi MINT-4049532.

    Chemistry

    BindingDBi P31750.
    ChEMBLi CHEMBL5859.

    PTM databases

    PhosphoSitei P31750.

    Proteomic databases

    MaxQBi P31750.
    PaxDbi P31750.
    PRIDEi P31750.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000001780 ; ENSMUSP00000001780 ; ENSMUSG00000001729 .
    GeneIDi 11651.
    KEGGi mmu:11651.
    UCSCi uc007pex.2. mouse.

    Organism-specific databases

    CTDi 207.
    MGIi MGI:87986. Akt1.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00740000114960.
    HOGENOMi HOG000233033.
    HOVERGENi HBG108317.
    InParanoidi Q6GSA6.
    KOi K04456.
    OMAi SRERVFP.
    OrthoDBi EOG7Q5HCW.
    TreeFami TF102004.

    Enzyme and pathway databases

    BRENDAi 2.7.11.1. 3474.
    Reactomei REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_198695. Butyrate Response Factor 1 (BRF1) destabilizes mRNA.
    REACT_198696. KSRP destabilizes mRNA.
    REACT_199047. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
    REACT_199054. Translocation of GLUT4 to the plasma membrane.
    REACT_199061. Downregulation of ERBB2:ERBB3 signaling.
    REACT_214733. Negative regulation of the PI3K/AKT network.
    REACT_218211. AKT phosphorylates targets in the nucleus.
    REACT_219771. deactivation of the beta-catenin transactivating complex.
    REACT_220092. GPVI-mediated activation cascade.
    REACT_220918. AKT phosphorylates targets in the cytosol.
    REACT_221264. eNOS activation.
    REACT_221926. AKT-mediated inactivation of FOXO1A.
    REACT_223974. G beta:gamma signalling through PI3Kgamma.
    REACT_226151. CD28 dependent PI3K/Akt signaling.
    REACT_226341. PIP3 activates AKT signaling.

    Miscellaneous databases

    ChiTaRSi AKT1. mouse.
    NextBioi 279257.
    PROi P31750.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P31750.
    Bgeei P31750.
    CleanExi MM_AKT1.
    Genevestigatori P31750.

    Family and domain databases

    Gene3Di 2.30.29.30. 1 hit.
    InterProi IPR000961. AGC-kinase_C.
    IPR011009. Kinase-like_dom.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR017892. Pkinase_C.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00169. PH. 1 hit.
    PF00069. Pkinase. 1 hit.
    PF00433. Pkinase_C. 1 hit.
    [Graphical view ]
    SMARTi SM00233. PH. 1 hit.
    SM00133. S_TK_X. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS51285. AGC_KINASE_CTER. 1 hit.
    PS50003. PH_DOMAIN. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Structure, expression and chromosomal mapping of c-akt: relationship to v-akt and its implications."
      Bellacosa A., Franke T.F., Gonzalez-Portal M.E., Datta K., Taguchi T., Gardner J., Cheng J.Q., Testa J.R., Tsichlis P.N.
      Oncogene 8:745-754(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
      Strain: AKR/J.
      Tissue: Thymus.
    2. "Protein kinase B alpha/Akt1 regulates placental development and fetal growth."
      Yang Z.Z., Tschopp O., Hemmings-Mieszczak M., Feng J., Brodbeck D., Perentes E., Hemmings B.A.
      J. Biol. Chem. 278:32124-32131(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, PHOSPHORYLATION AT SER-473, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
      Strain: 129/SvJ.
    3. "Complete nucleotide coding sequence for murine rac (related to A and C kinases) protein kinase."
      Bousquets X., Powell C.T.
      Submitted (JUN-1992) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: NOD.
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: 129/SvJ.
    6. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6.
      Tissue: Brain.
    8. "Physiological role of Akt in insulin-stimulated translocation of GLUT4 in transfected rat adipose cells."
      Cong L.N., Chen H., Li Y., Zhou L., McGibbon M.A., Taylor S.I., Quon M.J.
      Mol. Endocrinol. 11:1881-1890(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF LYS-179.
    9. "Insulin-induced phosphorylation and activation of cyclic nucleotide phosphodiesterase 3B by the serine-threonine kinase Akt."
      Kitamura T., Kitamura Y., Kuroda S., Hino Y., Ando M., Kotani K., Konishi H., Matsuzaki H., Kikkawa U., Ogawa W., Kasuga M.
      Mol. Cell. Biol. 19:6286-6296(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF PDE3B.
    10. "Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways."
      Mizuki M., Fenski R., Halfter H., Matsumura I., Schmidt R., Muller C., Gruning W., Kratz-Albers K., Serve S., Steur C., Buchner T., Kienast J., Kanakura Y., Berdel W.E., Serve H.
      Blood 96:3907-3914(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
    11. Cited for: SUBCELLULAR LOCATION.
    12. "Reperfusion-activated Akt kinase prevents apoptosis in transgenic mouse hearts overexpressing insulin-like growth factor-1."
      Yamashita K., Kajstura J., Discher D.J., Wasserlauf B.J., Bishopric N.H., Anversa P., Webster K.A.
      Circ. Res. 88:609-614(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    13. "Phosphorylation of PTP1B at Ser(50) by Akt impairs its ability to dephosphorylate the insulin receptor."
      Ravichandran L.V., Chen H., Li Y., Quon M.J.
      Mol. Endocrinol. 15:1768-1780(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF PTPN1.
    14. "Carboxyl-terminal modulator protein (CTMP), a negative regulator of PKB/Akt and v-Akt at the plasma membrane."
      Maira S.-M., Galetic I., Brazil D.P., Kaech S., Ingley E., Thelen M., Hemmings B.A.
      Science 294:374-380(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH THEM4.
    15. "A method to identify serine kinase substrates. Akt phosphorylates a novel adipocyte protein with a Rab GTPase-activating protein (GAP) domain."
      Kane S., Sano H., Liu S.C.H., Asara J.M., Lane W.S., Garner C.C., Lienhard G.E.
      J. Biol. Chem. 277:22115-22118(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF TBC1D4.
    16. Cited for: INTERACTION WITH CCDC88A, PHOSPHORYLATION AT THR-308 AND SER-473.
    17. "Phosphorylation of grb10 regulates its interaction with 14-3-3."
      Urschel S., Bassermann F., Bai R.Y., Munch S., Peschel C., Duyster J.
      J. Biol. Chem. 280:16987-16993(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GRB10.
    18. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    19. "O-GlcNAc modulation at Akt1 Ser473 correlates with apoptosis of murine pancreatic beta cells."
      Kang E.S., Han D., Park J., Kwak T.K., Oh M.A., Lee S.A., Choi S., Park Z.Y., Kim Y., Lee J.W.
      Exp. Cell Res. 314:2238-2248(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION AT SER-473.
    20. "Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance."
      Yang X., Ongusaha P.P., Miles P.D., Havstad J.C., Zhang F., So W.V., Kudlow J.E., Michell R.H., Olefsky J.M., Field S.J., Evans R.M.
      Nature 451:964-969(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, GLYCOSYLATION AT SER-473, PHOSPHORYLATION AT THR-308.
    21. "DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212."
      Kim J.Y., Duan X., Liu C.Y., Jang M.H., Guo J.U., Pow-anpongkul N., Kang E., Song H., Ming G.L.
      Neuron 63:761-773(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    22. "Cdc2-like kinase 2 is an insulin-regulated suppressor of hepatic gluconeogenesis."
      Rodgers J.T., Haas W., Gygi S.P., Puigserver P.
      Cell Metab. 11:23-34(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CLK2.
    23. "mTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt polypeptide."
      Oh W.J., Wu C.C., Kim S.J., Facchinetti V., Julien L.A., Finlan M., Roux P.P., Su B., Jacinto E.
      EMBO J. 29:3939-3951(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-450.
    24. Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-176; THR-308 AND SER-473, MUTAGENESIS OF TYR-176, INTERACTION WITH TNK2.
    25. Cited for: PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
    26. "ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B-dependent CRMP2 phosphorylation."
      Wakatsuki S., Saitoh F., Araki T.
      Nat. Cell Biol. 13:1415-1423(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, UBIQUITINATION BY ZNRF1, MUTAGENESIS OF THR-308 AND SER-473.
    27. "The protein kinase B/Akt signalling pathway in human malignancy."
      Nicholson K.M., Anderson N.G.
      Cell. Signal. 14:381-395(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.
    28. Cited for: REVIEW ON FUNCTION.
    29. "Akt1 and Akt2: differentiating the aktion."
      Heron-Milhavet L., Khouya N., Fernandez A., Lamb N.J.
      Histol. Histopathol. 26:651-662(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.

    Entry informationi

    Entry nameiAKT1_MOUSE
    AccessioniPrimary (citable) accession number: P31750
    Secondary accession number(s): Q62274, Q6GSA6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1993
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 160 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Caution

    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

    Documents

    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

    External Data

    Dasty 3