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P31749

- AKT1_HUMAN

UniProt

P31749 - AKT1_HUMAN

Protein

RAC-alpha serine/threonine-protein kinase

Gene

AKT1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 183 (01 Oct 2014)
      Sequence version 2 (01 Feb 2005)
      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. Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity. Phosphorylation of BAD stimulates its pro-apoptotic activity. Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53.
    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.

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.3 Publications

    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. Inhibited by pyrrolopyrimidine inhibitors like aniline triazole and spiroindoline.6 Publications

    Kineticsi

    1. KM=52.8 µM for ATP (for purified and in vitro activated AKT1)1 Publication
    2. KM=0.5 µM for peptide substrate (for purified and in vitro activated AKT1)1 Publication
    3. KM=143.3 µM for ATP (for recombinant myristoylated AKT1 expressed and immunoprecipitated from Rat-1 cells)1 Publication
    4. KM=2.9 µM for peptide substrate (for recombinant myristoylated AKT1 expressed and immunoprecipitated from Rat-1 cells)1 Publication

    Sites

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

    Regions

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

    GO - Molecular functioni

    1. 14-3-3 protein binding Source: UniProtKB
    2. ATP binding Source: UniProtKB
    3. enzyme binding Source: BHF-UCL
    4. identical protein binding Source: IntAct
    5. kinase activity Source: MGI
    6. nitric-oxide synthase regulator activity Source: BHF-UCL
    7. phosphatidylinositol-3,4,5-trisphosphate binding Source: UniProtKB
    8. phosphatidylinositol-3,4-bisphosphate binding Source: UniProtKB
    9. protein binding Source: UniProtKB
    10. protein kinase activity Source: ProtInc
    11. protein serine/threonine/tyrosine kinase activity Source: MGI
    12. 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: Ensembl
    4. apoptotic mitochondrial changes Source: Ensembl
    5. apoptotic process Source: Reactome
    6. blood coagulation Source: Reactome
    7. cell differentiation Source: UniProtKB
    8. cell projection organization Source: Ensembl
    9. cell proliferation Source: UniProtKB
    10. cellular protein modification process Source: ProtInc
    11. cellular response to epidermal growth factor stimulus Source: Ensembl
    12. cellular response to hypoxia Source: Ensembl
    13. cellular response to insulin stimulus Source: BHF-UCL
    14. cellular response to mechanical stimulus Source: Ensembl
    15. endocrine pancreas development Source: Reactome
    16. epidermal growth factor receptor signaling pathway Source: Reactome
    17. execution phase of apoptosis Source: Ensembl
    18. Fc-epsilon receptor signaling pathway Source: Reactome
    19. fibroblast growth factor receptor signaling pathway Source: Reactome
    20. gene expression Source: Reactome
    21. germ cell development Source: Ensembl
    22. glucose homeostasis Source: Ensembl
    23. glucose metabolic process Source: UniProtKB-KW
    24. glucose transport Source: Ensembl
    25. glycogen biosynthetic process Source: UniProtKB-KW
    26. glycogen cell differentiation involved in embryonic placenta development Source: Ensembl
    27. G-protein coupled receptor signaling pathway Source: ProtInc
    28. hyaluronan metabolic process Source: Ensembl
    29. inflammatory response Source: Ensembl
    30. innate immune response Source: Reactome
    31. insulin-like growth factor receptor signaling pathway Source: UniProtKB
    32. insulin receptor signaling pathway Source: UniProtKB
    33. intracellular signal transduction Source: MGI
    34. intrinsic apoptotic signaling pathway Source: Reactome
    35. labyrinthine layer blood vessel development Source: Ensembl
    36. mammary gland epithelial cell differentiation Source: UniProtKB
    37. maternal placenta development Source: Ensembl
    38. membrane organization Source: Reactome
    39. mRNA metabolic process Source: Reactome
    40. negative regulation of apoptotic process Source: UniProtKB
    41. negative regulation of autophagy Source: BHF-UCL
    42. negative regulation of cell size Source: Ensembl
    43. negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    44. negative regulation of endopeptidase activity Source: BHF-UCL
    45. negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
    46. negative regulation of fatty acid beta-oxidation Source: BHF-UCL
    47. negative regulation of JNK cascade Source: Ensembl
    48. negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: BHF-UCL
    49. negative regulation of plasma membrane long-chain fatty acid transport Source: BHF-UCL
    50. negative regulation of protein kinase activity Source: BHF-UCL
    51. negative regulation of proteolysis Source: BHF-UCL
    52. negative regulation of release of cytochrome c from mitochondria Source: UniProtKB
    53. neurotrophin TRK receptor signaling pathway Source: Reactome
    54. nitric oxide biosynthetic process Source: ProtInc
    55. nitric oxide metabolic process Source: Reactome
    56. osteoblast differentiation Source: Ensembl
    57. peptidyl-serine phosphorylation Source: UniProtKB
    58. peripheral nervous system myelin maintenance Source: Ensembl
    59. phosphatidylinositol-mediated signaling Source: Reactome
    60. phosphorylation Source: UniProtKB
    61. platelet activation Source: Reactome
    62. positive regulation of apoptotic process Source: Ensembl
    63. positive regulation of blood vessel endothelial cell migration Source: DFLAT
    64. positive regulation of cell growth Source: UniProtKB
    65. positive regulation of cellular protein metabolic process Source: BHF-UCL
    66. positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle Source: BHF-UCL
    67. positive regulation of endothelial cell proliferation Source: UniProtKB
    68. positive regulation of establishment of protein localization to plasma membrane Source: BHF-UCL
    69. positive regulation of fat cell differentiation Source: BHF-UCL
    70. positive regulation of glucose import Source: BHF-UCL
    71. positive regulation of glucose metabolic process Source: BHF-UCL
    72. positive regulation of glycogen biosynthetic process Source: BHF-UCL
    73. positive regulation of lipid biosynthetic process Source: BHF-UCL
    74. positive regulation of nitric oxide biosynthetic process Source: BHF-UCL
    75. positive regulation of nitric-oxide synthase activity Source: BHF-UCL
    76. positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
    77. positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: Ensembl
    78. positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: Reactome
    79. positive regulation of protein phosphorylation Source: BHF-UCL
    80. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    81. positive regulation of sodium ion transport Source: Ensembl
    82. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    83. positive regulation of vasoconstriction Source: Ensembl
    84. protein autophosphorylation Source: UniProtKB
    85. protein catabolic process Source: Ensembl
    86. protein import into nucleus, translocation Source: UniProtKB
    87. protein kinase B signaling Source: Ensembl
    88. protein phosphorylation Source: UniProtKB
    89. protein ubiquitination Source: Ensembl
    90. regulation of cell cycle checkpoint Source: UniProtKB
    91. regulation of cell migration Source: UniProtKB
    92. regulation of glycogen biosynthetic process Source: BHF-UCL
    93. regulation of neuron projection development Source: UniProtKB
    94. regulation of nitric-oxide synthase activity Source: Reactome
    95. regulation of translation Source: UniProtKB-KW
    96. response to fluid shear stress Source: BHF-UCL
    97. response to food Source: Ensembl
    98. response to heat Source: ProtInc
    99. response to UV-A Source: BHF-UCL
    100. RNA metabolic process Source: Reactome
    101. signal transduction Source: UniProtKB
    102. small molecule metabolic process Source: Reactome
    103. striated muscle cell differentiation Source: Ensembl
    104. T cell costimulation Source: Reactome
    105. 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. 2681.
    ReactomeiREACT_111176. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
    REACT_115662. Downregulation of ERBB2:ERBB3 signaling.
    REACT_12442. AKT phosphorylates targets in the nucleus.
    REACT_12447. Negative regulation of the PI3K/AKT network.
    REACT_12477. eNOS activation.
    REACT_12564. AKT phosphorylates targets in the cytosol.
    REACT_13655. AKT-mediated inactivation of FOXO1A.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_147867. Translocation of GLUT4 to the plasma membrane.
    REACT_15523. Integrin alphaIIb beta3 signaling.
    REACT_1695. GPVI-mediated activation cascade.
    REACT_19290. G beta:gamma signalling through PI3Kgamma.
    REACT_19358. CD28 dependent PI3K/Akt signaling.
    REACT_19405. CTLA4 inhibitory signaling.
    REACT_200731. deactivation of the beta-catenin transactivating complex.
    REACT_24915. Butyrate Response Factor 1 (BRF1) destabilizes mRNA.
    REACT_25042. KSRP destabilizes mRNA.
    REACT_75829. PIP3 activates AKT signaling.
    SignaLinkiP31749.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    RAC-alpha serine/threonine-protein kinase (EC:2.7.11.1)
    Alternative name(s):
    Protein kinase B
    Short name:
    PKB
    Protein kinase B alpha
    Short name:
    PKB alpha
    Proto-oncogene c-Akt
    RAC-PK-alpha
    Gene namesi
    Name:AKT1
    Synonyms:PKB, RAC
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:391. AKT1.

    Subcellular locationi

    Cytoplasm. Nucleus. Cell membrane
    Note: Nucleus after activation by integrin-linked protein kinase 1 (ILK1). 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.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: UniProtKB
    3. microtubule cytoskeleton Source: HPA
    4. nucleoplasm Source: Reactome
    5. nucleus Source: UniProtKB
    6. plasma membrane Source: UniProtKB
    7. spindle Source: Ensembl

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.1 Publication
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
    Note: The gene represented in this entry may be involved in disease pathogenesis.
    Genetic variations in AKT1 may play a role in susceptibility to ovarian cancer.
    Proteus syndrome (PROTEUSS) [MIM:176920]: A highly variable, severe disorder of asymmetric and disproportionate overgrowth of body parts, connective tissue nevi, epidermal nevi, dysregulated adipose tissue, and vascular malformations. Many features of Proteus syndrome overlap with other overgrowth syndromes.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti17 – 171E → K in PROTEUSS and breast cancer; also detected in colorectal and ovarian cancer; somatic mutation; results in increased phosphorylation at T-308 and higher basal ubiquitination; the mutant protein is more efficiently recruited to the plasma membrane; alters phosphatidylinositiol phosphates lipid specificity of the AKT1 PH domain. 2 Publications
    Corresponds to variant rs121434592 [ dbSNP | Ensembl ].
    VAR_055422
    Cowden syndrome 6 (CWS6) [MIM:615109]: A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid.
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi8 – 81K → R: Substantial reduction of ubiquitination, phosphorylation at T-308 and S-473, AKT activation as well as IGF1-induced membrane recruitment. Decrease in ubiquitination and phosphorylation at T-308 as well as impaired association with the membrane; when associated with K-17. 1 Publication
    Mutagenesisi14 – 141K → A: Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. 3 Publications
    Mutagenesisi14 – 141K → Q: Substantial reduction of phosphorylation at T-308 and S-473, loss of AKT activation, and loss of binding to PIP3 as well as IGF1-induced membrane recruitment. 3 Publications
    Mutagenesisi14 – 141K → R: Substantial reduction of ubiquitination, phosphorylation at T-308 and S-473, AKT activation, loss of binding to PIP3 as well as IGF1-induced membrane recruitment. 3 Publications
    Mutagenesisi17 – 171E → K: No effect on membrane localization. Loss of membrane localization; when associated with Q-20. 1 Publication
    Mutagenesisi20 – 201K → Q: Substantial reduction of phosphorylation at T-308 and S-473, reduced AKT activation, and reduced binding to PIP3 as well as IGF1-induced membrane recruitment. Loss of membrane localization; when associated with K-17. 1 Publication
    Mutagenesisi20 – 201K → R: Slight increase of phosphorylation at T-308 and S-473. 1 Publication
    Mutagenesisi25 – 251R → A or C: Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. 1 Publication
    Mutagenesisi86 – 861R → A: Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. 1 Publication
    Mutagenesisi176 – 1761Y → F: Significant loss of interaction with TNK2. Loss of membrane localization. Significant reduction in phosphorylation on Ser-473. 1 Publication
    Mutagenesisi305 – 3051T → A: Reduces O-GlcNAc levels; Reduces O-GlcNAc levels even more; when associated with A-312. 1 Publication
    Mutagenesisi305 – 3051T → Y: Abolishes phosphorylation at Thr-308. 1 Publication
    Mutagenesisi308 – 3081T → D: 5-fold activation and 18-fold activation; when associated with D-473. 2 Publications
    Mutagenesisi312 – 3121T → A: Reduces O-GlcNAc levels; Reduces O-GlcNAc levels even more; when associated with A-305. 1 Publication
    Mutagenesisi312 – 3121T → Y: Abolishes phosphorylation at Thr-308. 1 Publication
    Mutagenesisi473 – 4731S → D: 7-fold activation and 25-fold activation; when associated with D-308. 2 Publications
    Mutagenesisi474 – 4741Y → F: 55% inhibition of activation. 1 Publication

    Keywords - Diseasei

    Disease mutation, Proto-oncogene

    Organism-specific databases

    MIMi114480. phenotype.
    114500. phenotype.
    176920. phenotype.
    615109. phenotype.
    Orphaneti201. Cowden syndrome.
    744. Proteus syndrome.
    PharmGKBiPA24684.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 480480RAC-alpha serine/threonine-protein kinasePRO_0000085605Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei14 – 141N6-acetyllysine1 Publication
    Modified residuei20 – 201N6-acetyllysine1 Publication
    Disulfide bondi60 ↔ 771 Publication
    Modified residuei124 – 1241Phosphoserine1 Publication
    Modified residuei126 – 1261Phosphoserine; alternate1 Publication
    Glycosylationi126 – 1261O-linked (GlcNAc); alternate1 Publication
    Modified residuei129 – 1291Phosphoserine; alternate2 Publications
    Glycosylationi129 – 1291O-linked (GlcNAc); alternate1 Publication
    Modified residuei176 – 1761Phosphotyrosine; by TNK21 Publication
    Cross-linki284 – 284Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Disulfide bondi296 ↔ 310By similarity
    Glycosylationi305 – 3051O-linked (GlcNAc)1 Publication
    Modified residuei308 – 3081Phosphothreonine; by IKKE, PDPK1 and TBK17 Publications
    Glycosylationi312 – 3121O-linked (GlcNAc)1 Publication
    Modified residuei450 – 4501Phosphothreonine; by MTORBy similarity
    Modified residuei473 – 4731Phosphoserine; by IKKE, MTOR and TBK1; alternate11 Publications
    Glycosylationi473 – 4731O-linked (GlcNAc); alternateBy similarity
    Modified residuei474 – 4741Phosphotyrosine1 Publication

    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.14 Publications
    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 cell 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 interaction with AGAP2 isoform 2 (PIKE-A). Ser-473 phosphorylation is enhanced in focal cortical dysplasias with Taylor-type balloon cells. 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.15 Publications
    Ubiquitinated via 'Lys-48'-linked polyubiquitination by ZNRF1, leading to its degradation by the proteasome 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. Phosphorylated, undergoes 'Lys-48'-linked polyubiquitination preferentially at Lys-284 catalyzed by MUL1, leading to its proteasomal degradation.By similarity4 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.1 Publication

    Keywords - PTMi

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

    Proteomic databases

    MaxQBiP31749.
    PaxDbiP31749.
    PRIDEiP31749.

    PTM databases

    PhosphoSiteiP31749.

    Miscellaneous databases

    PMAP-CutDBP31749.

    Expressioni

    Tissue specificityi

    Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Expressed in all human cell types so far analyzed. The Tyr-176 phosphorylated form shows a significant increase in expression in breast cancers during the progressive stages i.e. normal to hyperplasia (ADH), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and lymph node metastatic (LNMM) stages.3 Publications

    Gene expression databases

    ArrayExpressiP31749.
    BgeeiP31749.
    CleanExiHS_AKT1.
    GenevestigatoriP31749.

    Organism-specific databases

    HPAiCAB003765.
    HPA002891.

    Interactioni

    Subunit structurei

    Interacts (via the C-terminus) with CCDC88A (via its C-terminus). Interacts with GRB10; the interaction leads to GRB10 phosphorylation thus promoting YWHAE-binding 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 RAF1. Interacts with TRIM13; the interaction ubiquitinates AKT1 leading to its proteasomal degradation. Interacts with TNK2 and CLK2. Interacts (via the C-terminus) with THEM4 (via its C-terminus). Interacts with and phosphorylated by PDPK1.By similarity28 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself2EBI-296087,EBI-296087
    Arrb2P290672EBI-296087,EBI-1636616From a different organism.
    ASXL1Q8IXJ92EBI-296087,EBI-1646500
    BCL10O959994EBI-296087,EBI-958922
    CDC37Q165432EBI-296087,EBI-295634
    CREBBPQ927933EBI-296087,EBI-81215
    FAM110CQ1W6H92EBI-296087,EBI-3942563
    FAM129AQ9BZQ82EBI-296087,EBI-6916466
    GSK3BP498413EBI-296087,EBI-373586
    HSPA5P110212EBI-296087,EBI-354921
    LRRK2Q5S0076EBI-296087,EBI-5323863
    MAP3K5Q996832EBI-296087,EBI-476263
    MAPK14Q165392EBI-296087,EBI-73946
    MDM2Q009874EBI-296087,EBI-389668
    MTORP423452EBI-296087,EBI-359260
    NOS3P294742EBI-296087,EBI-1391623
    NR3C1P041505EBI-296087,EBI-493507
    PDPK1O155303EBI-296087,EBI-717097
    PEBP4Q96S962EBI-296087,EBI-8563667
    PLCG1P191749EBI-296087,EBI-79387
    PPLO604372EBI-296087,EBI-368321
    PPP1CAP621366EBI-296087,EBI-357253
    PPP2CAP677755EBI-296087,EBI-712311
    PPP2R1AP301532EBI-296087,EBI-302388
    PRKCZQ055132EBI-296087,EBI-295351
    RAF1P040492EBI-296087,EBI-365996
    RPS6KB1P234432EBI-296087,EBI-1775921
    SETDB1Q150479EBI-296087,EBI-79691
    SIRT1Q96EB65EBI-296087,EBI-1802965
    SMAD4Q134852EBI-296087,EBI-347263
    STK4Q1304313EBI-296087,EBI-367376
    TOPBP1Q925472EBI-296087,EBI-308302
    VIMP0867029EBI-296087,EBI-353844
    XP031653EBI-296087,EBI-7683985From a different organism.

    Protein-protein interaction databases

    BioGridi106710. 214 interactions.
    DIPiDIP-24269N.
    IntActiP31749. 93 interactions.
    MINTiMINT-203775.
    STRINGi9606.ENSP00000270202.

    Structurei

    Secondary structure

    1
    480
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi2 – 43
    Beta strandi6 – 1510
    Beta strandi17 – 193
    Beta strandi22 – 309
    Beta strandi33 – 408
    Helixi45 – 484
    Beta strandi52 – 565
    Beta strandi61 – 655
    Beta strandi67 – 693
    Beta strandi72 – 798
    Beta strandi82 – 898
    Helixi93 – 11523
    Helixi147 – 1493
    Beta strandi150 – 1589
    Beta strandi160 – 16910
    Turni170 – 1723
    Beta strandi175 – 1828
    Helixi183 – 1886
    Helixi192 – 20413
    Beta strandi213 – 2186
    Beta strandi220 – 2278
    Helixi235 – 2428
    Helixi247 – 26822
    Helixi277 – 2793
    Beta strandi280 – 2823
    Beta strandi284 – 2863
    Beta strandi288 – 2903
    Beta strandi309 – 3113
    Helixi313 – 3153
    Helixi318 – 3225
    Helixi330 – 34415
    Helixi354 – 36310
    Helixi374 – 38310
    Helixi388 – 3903
    Turni396 – 3983
    Helixi399 – 4035
    Helixi406 – 4083
    Helixi413 – 4175
    Beta strandi430 – 4334
    Helixi440 – 4434
    Beta strandi464 – 4663
    Beta strandi473 – 4753

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1H10X-ray1.40A1-123[»]
    1UNPX-ray1.65A1-121[»]
    1UNQX-ray0.98A1-123[»]
    1UNRX-ray1.25A1-123[»]
    2UVMX-ray1.94A1-123[»]
    2UZRX-ray1.94A1-123[»]
    2UZSX-ray2.46A1-123[»]
    3CQUX-ray2.20A144-480[»]
    3CQWX-ray2.00A144-480[»]
    3MV5X-ray2.47A144-480[»]
    3MVHX-ray2.01A144-480[»]
    3O96X-ray2.70A2-443[»]
    3OCBX-ray2.70A/B144-480[»]
    3OW4X-ray2.60A/B144-480[»]
    3QKKX-ray2.30A144-480[»]
    3QKLX-ray1.90A144-480[»]
    3QKMX-ray2.20A144-480[»]
    4EJNX-ray2.19A2-446[»]
    4EKKX-ray2.80A/B144-480[»]
    4EKLX-ray2.00A144-480[»]
    4GV1X-ray1.49A144-480[»]
    ProteinModelPortaliP31749.
    SMRiP31749. Positions 1-477.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP31749.

    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 binding
    Regioni23 – 253Inositol-(1,3,4,5)-tetrakisphosphate binding
    Regioni228 – 2303Inhibitor binding

    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.

    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.
    HOGENOMiHOG000233033.
    HOVERGENiHBG108317.
    InParanoidiP31749.
    KOiK04456.
    OMAiSRERVFP.
    PhylomeDBiP31749.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P31749-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MSDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVDQREA    50
    PLNNFSVAQC QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWT 100
    TAIQTVADGL KKQEEEEMDF 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 SGLLKKDPKQ RLGGGSEDAK 400
    EIMQHRFFAG IVWQHVYEKK LSPPFKPQVT SETDTRYFDE EFTAQMITIT 450
    PPDQDDSMEC VDSERRPHFP QFSYSASGTA 480
    Length:480
    Mass (Da):55,686
    Last modified:February 1, 2005 - v2
    Checksum:i6EAFF4F8AD436714
    GO
    Isoform 2 (identifier: P31749-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-62: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:418
    Mass (Da):48,347
    Checksum:i671C0EB4BDF8F45F
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti173 – 1742GR → A in CAA43372. (PubMed:1718748)Curated
    Sequence conflicti202 – 2021L → Q in CAA43372. (PubMed:1718748)Curated
    Sequence conflicti212 – 2121A → R in CAA43372. (PubMed:1718748)Curated
    Sequence conflicti246 – 2461S → A in CAA43372. (PubMed:1718748)Curated
    Sequence conflicti409 – 4091A → T in CAA43372. (PubMed:1718748)Curated
    Sequence conflicti476 – 4761A → P in CAA43372. (PubMed:1718748)Curated
    Sequence conflicti478 – 4781G → A in CAA43372. (PubMed:1718748)Curated
    Sequence conflicti478 – 4781G → S in AAA36539. (PubMed:1851997)Curated
    Sequence conflicti478 – 4781G → S in AAL55732. (PubMed:11508278)Curated
    Sequence conflicti478 – 4781G → S in BAG36922. (PubMed:14702039)Curated
    Sequence conflicti478 – 4781G → S in BAG70056. (PubMed:19054851)Curated
    Sequence conflicti478 – 4781G → S in BAG70181. (PubMed:19054851)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti17 – 171E → K in PROTEUSS and breast cancer; also detected in colorectal and ovarian cancer; somatic mutation; results in increased phosphorylation at T-308 and higher basal ubiquitination; the mutant protein is more efficiently recruited to the plasma membrane; alters phosphatidylinositiol phosphates lipid specificity of the AKT1 PH domain. 2 Publications
    Corresponds to variant rs121434592 [ dbSNP | Ensembl ].
    VAR_055422
    Natural varianti25 – 251R → C in CWD6. 1 Publication
    VAR_069791
    Natural varianti167 – 1671V → A.
    Corresponds to variant rs11555433 [ dbSNP | Ensembl ].
    VAR_051617
    Natural varianti435 – 4351T → P in CWD6. 1 Publication
    VAR_069792

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 6262Missing in isoform 2. 1 PublicationVSP_056180Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M63167 mRNA. Translation: AAA36539.1.
    AF283830
    , AF283819, AF283820, AF283821, AF283822, AF283823, AF283824, AF283825, AF283826, AF283827, AF283828, AF283829 Genomic DNA. Translation: AAL55732.1.
    AK299310 mRNA. Translation: BAH12997.1.
    AK314256 mRNA. Translation: BAG36922.1.
    AB451242 mRNA. Translation: BAG70056.1.
    AB451367 mRNA. Translation: BAG70181.1.
    AL583722 Genomic DNA. No translation available.
    AL590327 Genomic DNA. No translation available.
    BC000479 mRNA. Translation: AAH00479.1.
    BC084538 mRNA. Translation: AAH84538.1.
    X61037 mRNA. Translation: CAA43372.1.
    CCDSiCCDS9994.1.
    PIRiA39360.
    RefSeqiNP_001014431.1. NM_001014431.1.
    NP_001014432.1. NM_001014432.1.
    NP_005154.2. NM_005163.2.
    XP_005267458.1. XM_005267401.1.
    UniGeneiHs.525622.

    Genome annotation databases

    EnsembliENST00000349310; ENSP00000270202; ENSG00000142208.
    ENST00000402615; ENSP00000385326; ENSG00000142208.
    ENST00000407796; ENSP00000384293; ENSG00000142208.
    ENST00000544168; ENSP00000443897; ENSG00000142208.
    ENST00000554581; ENSP00000451828; ENSG00000142208.
    ENST00000554848; ENSP00000451166; ENSG00000142208.
    ENST00000555528; ENSP00000450688; ENSG00000142208.
    GeneIDi207.
    KEGGihsa:207.
    UCSCiuc001ypk.3. human.

    Polymorphism databases

    DMDMi60391226.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M63167 mRNA. Translation: AAA36539.1 .
    AF283830
    , AF283819 , AF283820 , AF283821 , AF283822 , AF283823 , AF283824 , AF283825 , AF283826 , AF283827 , AF283828 , AF283829 Genomic DNA. Translation: AAL55732.1 .
    AK299310 mRNA. Translation: BAH12997.1 .
    AK314256 mRNA. Translation: BAG36922.1 .
    AB451242 mRNA. Translation: BAG70056.1 .
    AB451367 mRNA. Translation: BAG70181.1 .
    AL583722 Genomic DNA. No translation available.
    AL590327 Genomic DNA. No translation available.
    BC000479 mRNA. Translation: AAH00479.1 .
    BC084538 mRNA. Translation: AAH84538.1 .
    X61037 mRNA. Translation: CAA43372.1 .
    CCDSi CCDS9994.1.
    PIRi A39360.
    RefSeqi NP_001014431.1. NM_001014431.1.
    NP_001014432.1. NM_001014432.1.
    NP_005154.2. NM_005163.2.
    XP_005267458.1. XM_005267401.1.
    UniGenei Hs.525622.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1H10 X-ray 1.40 A 1-123 [» ]
    1UNP X-ray 1.65 A 1-121 [» ]
    1UNQ X-ray 0.98 A 1-123 [» ]
    1UNR X-ray 1.25 A 1-123 [» ]
    2UVM X-ray 1.94 A 1-123 [» ]
    2UZR X-ray 1.94 A 1-123 [» ]
    2UZS X-ray 2.46 A 1-123 [» ]
    3CQU X-ray 2.20 A 144-480 [» ]
    3CQW X-ray 2.00 A 144-480 [» ]
    3MV5 X-ray 2.47 A 144-480 [» ]
    3MVH X-ray 2.01 A 144-480 [» ]
    3O96 X-ray 2.70 A 2-443 [» ]
    3OCB X-ray 2.70 A/B 144-480 [» ]
    3OW4 X-ray 2.60 A/B 144-480 [» ]
    3QKK X-ray 2.30 A 144-480 [» ]
    3QKL X-ray 1.90 A 144-480 [» ]
    3QKM X-ray 2.20 A 144-480 [» ]
    4EJN X-ray 2.19 A 2-446 [» ]
    4EKK X-ray 2.80 A/B 144-480 [» ]
    4EKL X-ray 2.00 A 144-480 [» ]
    4GV1 X-ray 1.49 A 144-480 [» ]
    ProteinModelPortali P31749.
    SMRi P31749. Positions 1-477.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 106710. 214 interactions.
    DIPi DIP-24269N.
    IntActi P31749. 93 interactions.
    MINTi MINT-203775.
    STRINGi 9606.ENSP00000270202.

    Chemistry

    BindingDBi P31749.
    ChEMBLi CHEMBL3038463.
    DrugBanki DB00171. Adenosine triphosphate.
    DB01169. Arsenic trioxide.
    GuidetoPHARMACOLOGYi 1479.

    PTM databases

    PhosphoSitei P31749.

    Polymorphism databases

    DMDMi 60391226.

    Proteomic databases

    MaxQBi P31749.
    PaxDbi P31749.
    PRIDEi P31749.

    Protocols and materials databases

    DNASUi 207.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000349310 ; ENSP00000270202 ; ENSG00000142208 .
    ENST00000402615 ; ENSP00000385326 ; ENSG00000142208 .
    ENST00000407796 ; ENSP00000384293 ; ENSG00000142208 .
    ENST00000544168 ; ENSP00000443897 ; ENSG00000142208 .
    ENST00000554581 ; ENSP00000451828 ; ENSG00000142208 .
    ENST00000554848 ; ENSP00000451166 ; ENSG00000142208 .
    ENST00000555528 ; ENSP00000450688 ; ENSG00000142208 .
    GeneIDi 207.
    KEGGi hsa:207.
    UCSCi uc001ypk.3. human.

    Organism-specific databases

    CTDi 207.
    GeneCardsi GC14M105235.
    GeneReviewsi AKT1.
    HGNCi HGNC:391. AKT1.
    HPAi CAB003765.
    HPA002891.
    MIMi 114480. phenotype.
    114500. phenotype.
    164730. gene.
    176920. phenotype.
    615109. phenotype.
    neXtProti NX_P31749.
    Orphaneti 201. Cowden syndrome.
    744. Proteus syndrome.
    PharmGKBi PA24684.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233033.
    HOVERGENi HBG108317.
    InParanoidi P31749.
    KOi K04456.
    OMAi SRERVFP.
    PhylomeDBi P31749.
    TreeFami TF102004.

    Enzyme and pathway databases

    BRENDAi 2.7.11.1. 2681.
    Reactomei REACT_111176. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
    REACT_115662. Downregulation of ERBB2:ERBB3 signaling.
    REACT_12442. AKT phosphorylates targets in the nucleus.
    REACT_12447. Negative regulation of the PI3K/AKT network.
    REACT_12477. eNOS activation.
    REACT_12564. AKT phosphorylates targets in the cytosol.
    REACT_13655. AKT-mediated inactivation of FOXO1A.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_147867. Translocation of GLUT4 to the plasma membrane.
    REACT_15523. Integrin alphaIIb beta3 signaling.
    REACT_1695. GPVI-mediated activation cascade.
    REACT_19290. G beta:gamma signalling through PI3Kgamma.
    REACT_19358. CD28 dependent PI3K/Akt signaling.
    REACT_19405. CTLA4 inhibitory signaling.
    REACT_200731. deactivation of the beta-catenin transactivating complex.
    REACT_24915. Butyrate Response Factor 1 (BRF1) destabilizes mRNA.
    REACT_25042. KSRP destabilizes mRNA.
    REACT_75829. PIP3 activates AKT signaling.
    SignaLinki P31749.

    Miscellaneous databases

    ChiTaRSi AKT1. human.
    EvolutionaryTracei P31749.
    GeneWikii AKT1.
    GenomeRNAii 207.
    NextBioi 828.
    PMAP-CutDB P31749.
    PROi P31749.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P31749.
    Bgeei P31749.
    CleanExi HS_AKT1.
    Genevestigatori P31749.

    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. "Molecular cloning and identification of a serine/threonine protein kinase of the second-messenger subfamily."
      Jones P.F., Jakubowicz T., Pitossi F.J., Maurer F., Hemmings B.A.
      Proc. Natl. Acad. Sci. U.S.A. 88:4171-4175(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY.
    2. "Isolation and characterization of the human AKT1 gene, identification of 13 single nucleotide polymorphisms (SNPs), and their lack of association with Type II diabetes."
      Matsubara A., Wasson J.C., Donelan S.S., Welling C.M., Glaser B., Permutt M.A.
      Diabetologia 44:910-913(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
      Tissue: Adrenal gland.
    4. "Human protein factory for converting the transcriptome into an in vitro-expressed proteome."
      Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.
      , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N.
      Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    5. "The DNA sequence and analysis of human chromosome 14."
      Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H.
      , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
      Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "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] (ISOFORM 1).
      Tissue: Muscle and Ovary.
    7. "Molecular cloning and characterisation of a novel putative protein-serine kinase related to the cAMP-dependent and protein kinase C families."
      Coffer P.J., Woodgett J.R.
      Eur. J. Biochem. 201:475-481(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 63-480 (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY.
      Tissue: Foreskin.
    8. Erratum
      Coffer P.J., Woodgett J.R.
      Eur. J. Biochem. 205:1217-1218(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: SEQUENCE REVISION.
    9. "CREB is a regulatory target for the protein kinase Akt/PKB."
      Du K., Montminy M.
      J. Biol. Chem. 273:32377-32379(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF CREB1.
    10. "Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase."
      Delcommenne M., Tan C., Gray V., Rue L., Woodgett J.R., Dedhar S.
      Proc. Natl. Acad. Sci. U.S.A. 95:11211-11216(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION, PHOSPHORYLATION AT SER-473.
    11. "Mechanism of activation of protein kinase B by insulin and IGF-1."
      Alessi D.R., Andjelkovic M., Caudwell F.B., Cron P., Morrice N., Cohen P., Hemmings B.A.
      EMBO J. 15:6541-6551(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF THR-308 AND SER-473, PHOSPHORYLATION AT THR-308 AND SER-473.
    12. "Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro: comparison with protein kinase B alpha."
      Walker K.S., Deak M., Paterson A., Hudson K., Cohen P., Alessi D.R.
      Biochem. J. 331:299-308(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-308 BY PDPK1.
    13. "Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B."
      Rena G., Guo S., Cichy S.C., Unterman T.G., Cohen P.
      J. Biol. Chem. 274:17179-17183(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF FOXO1.
    14. "Phosphorylation and regulation of Raf by Akt (protein kinase B)."
      Zimmermann S., Moelling K.
      Science 286:1741-1744(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF RAF1, INTERACTION WITH RAF1.
    15. "Inhibition of Akt and its anti-apoptotic activities by tumor necrosis factor-induced protein kinase C-related kinase 2 (PRK2) cleavage."
      Koh H., Lee K.H., Kim D., Kim S., Kim J.W., Chung J.
      J. Biol. Chem. 275:34451-34458(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF BAD, INTERACTION WITH BAD AND PKN2.
    16. "The protooncogene TCL1 is an Akt kinase coactivator."
      Laine J., Kuenstle G., Obata T., Sha M., Noguchi M.
      Mol. Cell 6:395-407(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MTCP1; TCL1A AND TCL1B.
    17. Cited for: INTERACTION WITH TCL1A.
    18. "Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1."
      Kim A.H., Khursigara G., Sun X., Franke T.F., Chao M.V.
      Mol. Cell. Biol. 21:893-901(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF MAP3K5, INTERACTION WITH MAP3K5.
    19. "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, SUBCELLULAR LOCATION.
    20. "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.
    21. "Akt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3 and cytoplasmic localization."
      Fujita N., Sato S., Katayama K., Tsuruo T.
      J. Biol. Chem. 277:28706-28713(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CDKN1B, FUNCTION.
    22. "Direct identification of tyrosine 474 as a regulatory phosphorylation site for the Akt protein kinase."
      Conus N.M., Hannan K.M., Cristiano B.E., Hemmings B.A., Pearson R.B.
      J. Biol. Chem. 277:38021-38028(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-474, MUTAGENESIS OF TYR-474.
    23. "Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway."
      Manning B.D., Tee A.R., Logsdon M.N., Blenis J., Cantley L.C.
      Mol. Cell 10:151-162(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF TSC2.
    24. "Identification of Akt association and oligomerization domains of the Akt kinase coactivator TCL1."
      Kuenstle G., Laine J., Pierron G., Kagami S., Nakajima H., Hoh F., Roumestand C., Stern M.H., Noguchi M.
      Mol. Cell. Biol. 22:1513-1525(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TCL1A.
    25. "PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization."
      Shin I., Yakes F.M., Rojo F., Shin N.-Y., Bakin A.V., Baselga J., Arteaga C.L.
      Nat. Med. 8:1145-1152(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CDKN1B, FUNCTION, MUTAGENESIS OF THR-308 AND SER-473.
    26. "Identification of Tyr900 in the kinase domain of c-Kit as a Src-dependent phosphorylation site mediating interaction with c-Crk."
      Lennartsson J., Wernstedt C., Engstrom U., Hellman U., Ronnstrand L.
      Exp. Cell Res. 288:110-118(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PARTICIPATION IN KIT SIGNALING.
    27. "PIKE (phosphatidylinositol 3-kinase enhancer)-A GTPase stimulates Akt activity and mediates cellular invasion."
      Ahn J.-Y., Rong R., Kroll T.G., Van Meir E.G., Snyder S.H., Ye K.
      J. Biol. Chem. 279:16441-16451(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AGAP2, PHOSPHORYLATION AT SER-473.
    28. "LGI1, a putative tumor metastasis suppressor gene, controls in vitro invasiveness and expression of matrix metalloproteinases in glioma cells through the ERK1/2 pathway."
      Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.
      J. Biol. Chem. 279:23151-23157(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-473.
    29. Erratum
      Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.
      J. Biol. Chem. 282:2752-2752(2007)
    30. "Regulation of apoptosis by the Ft1 protein, a new modulator of protein kinase B/Akt."
      Remy I., Michnick S.W.
      Mol. Cell. Biol. 24:1493-1504(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AKTIP.
    31. "PIKE-A is amplified in human cancers and prevents apoptosis by up-regulating Akt."
      Ahn J.-Y., Hu Y., Kroll T.G., Allard P., Ye K.
      Proc. Natl. Acad. Sci. U.S.A. 101:6993-6998(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AGAP2.
    32. "Constitutive activation of Akt by Flt3 internal tandem duplications is necessary for increased survival, proliferation, and myeloid transformation."
      Brandts C.H., Sargin B., Rode M., Biermann C., Lindtner B., Schwable J., Buerger H., Muller-Tidow C., Choudhary C., McMahon M., Berdel W.E., Serve H.
      Cancer Res. 65:9643-9650(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-473 IN RESPONSE TO FLT3 SIGNALING.
    33. Cited for: FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH CCDC88A.
    34. "Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex."
      Sarbassov D.D., Guertin D.A., Ali S.M., Sabatini D.M.
      Science 307:1098-1101(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-308, PHOSPHORYLATION AT SER-473 BY MTOR.
    35. "Activation of Akt independent of PTEN and CTMP tumor-suppressor gene mutations in epilepsy-associated Taylor-type focal cortical dysplasias."
      Schick V., Majores M., Engels G., Spitoni S., Koch A., Elger C.E., Simon M., Knobbe C., Bluemcke I., Becker A.J.
      Acta Neuropathol. 112:715-725(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-473.
    36. "Akt phosphorylates and suppresses the transactivation of retinoic acid receptor alpha."
      Srinivas H., Xia D., Moore N.L., Uray I.P., Kim H., Ma L., Weigel N.L., Brown P.H., Kurie J.M.
      Biochem. J. 395:653-662(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH RARA.
    37. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    38. Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
    39. "Only Akt1 is required for proliferation, while Akt2 promotes cell cycle exit through p21 binding."
      Heron-Milhavet L., Franckhauser C., Rana V., Berthenet C., Fisher D., Hemmings B.A., Fernandez A., Lamb N.J.
      Mol. Cell. Biol. 26:8267-8280(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF CDKN1A.
    40. "The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1."
      Cinar B., Fang P.K., Lutchman M., Di Vizio D., Adam R.M., Pavlova N., Rubin M.A., Yelick P.C., Freeman M.R.
      EMBO J. 26:4523-4534(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH STK4/MST1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    41. "Akt phosphorylates MstI and prevents its proteolytic activation, blocking FOXO3 phosphorylation and nuclear translocation."
      Jang S.W., Yang S.J., Srinivasan S., Ye K.
      J. Biol. Chem. 282:30836-30844(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH STK4/MST1.
    42. "Characterization of Akt overexpression in MiaPaCa-2 cells: prohibitin is an Akt substrate both in vitro and in cells."
      Han E.K., Mcgonigal T., Butler C., Giranda V.L., Luo Y.
      Anticancer Res. 28:957-963(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF PROHIBITIN.
    43. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124; SER-126 AND SER-129, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    44. Cited for: UBIQUITINATION BY TTC3.
    45. "Interaction of Akt-phosphorylated SRPK2 with 14-3-3 mediates cell cycle and cell death in neurons."
      Jang S.W., Liu X., Fu H., Rees H., Yepes M., Levey A., Ye K.
      J. Biol. Chem. 284:24512-24525(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF SRPK2, INTERACTION WITH SRPK2.
    46. "The Rho-family GEF Asef2 activates Rac to modulate adhesion and actin dynamics and thereby regulate cell migration."
      Bristow J.M., Sellers M.H., Majumdar D., Anderson B., Hu L., Webb D.J.
      J. Cell Sci. 122:4535-4546(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    47. Cited for: UBIQUITINATION, INTERACTION WITH TRAF6, MUTAGENESIS OF LYS-8 AND LYS-14, CHARACTERIZATION OF VARIANT BREAST CANCER LYS-17.
    48. "Proapoptotic kinase MST2 coordinates signaling crosstalk between RASSF1A, Raf-1, and Akt."
      Romano D., Matallanas D., Weitsman G., Preisinger C., Ng T., Kolch W.
      Cancer Res. 70:1195-1203(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH STK3/MST2.
    49. "Phosphoinositide 3-kinase/Akt inhibits MST1-mediated pro-apoptotic signaling through phosphorylation of threonine 120."
      Yuan Z., Kim D., Shu S., Wu J., Guo J., Xiao L., Kaneko S., Coppola D., Cheng J.Q.
      J. Biol. Chem. 285:3815-3824(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    50. "Phosphorylation of CLK2 at serine 34 and threonine 127 by AKT controls cell survival after ionizing radiation."
      Nam S.Y., Seo H.H., Park H.S., An S., Kim J.Y., Yang K.H., Kim C.S., Jeong M., Jin Y.W.
      J. Biol. Chem. 285:31157-31163(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH CLK2.
    51. "The actin-bundling protein palladin is an Akt1-specific substrate that regulates breast cancer cell migration."
      Chin Y.R., Toker A.
      Mol. Cell 38:333-344(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF PALLD.
    52. "Regulation of proapoptotic mammalian ste20-like kinase MST2 by the IGF1-Akt pathway."
      Kim D., Shu S., Coppola M.D., Kaneko S., Yuan Z.Q., Cheng J.Q.
      PLoS ONE 5:E9616-E9616(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH STK3/MST2.
    53. Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-176; THR-308 AND SER-473, MUTAGENESIS OF TYR-176, INTERACTION WITH TNK2, TISSUE SPECIFICITY.
    54. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    55. "Ret finger protein 2 enhances ionizing radiation-induced apoptosis via degradation of AKT and MDM2."
      Joo H.M., Kim J.Y., Jeong J.B., Seong K.M., Nam S.Y., Yang K.H., Kim C.S., Kim H.S., Jeong M., An S., Jin Y.W.
      Eur. J. Cell Biol. 90:420-431(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TRIM13, UBIQUITINATION.
    56. "Clk2 and B56-beta mediate insulin-regulated assembly of the PP2A phosphatase holoenzyme complex on Akt."
      Rodgers J.T., Vogel R.O., Puigserver P.
      Mol. Cell 41:471-479(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PPP2R5B, DEPHOSPHORYLATION.
    57. "Signal transduction via the stem cell factor receptor/c-Kit."
      Ronnstrand L.
      Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON ROLE IN KIT SIGNALING.
    58. "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.
    59. "A novel human dynactin-associated protein, dynAP, promotes activation of Akt, and ergosterol-related compounds induce dynAP-dependent apoptosis of human cancer cells."
      Kunoh T., Noda T., Koseki K., Sekigawa M., Takagi M., Shin-ya K., Goshima N., Iemura S., Natsume T., Wada S., Mukai Y., Ohta S., Sasaki R., Mizukami T.
      Mol. Cancer Ther. 9:2934-2942(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-473.
    60. Cited for: REVIEW ON FUNCTION.
    61. "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.
    62. "IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation."
      Xie X., Zhang D., Zhao B., Lu M.K., You M., Condorelli G., Wang C.Y., Guan K.L.
      Proc. Natl. Acad. Sci. U.S.A. 108:6474-6479(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-308 AND SER-473.
    63. "The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy."
      Sundaresan N.R., Pillai V.B., Wolfgeher D., Samant S., Vasudevan P., Parekh V., Raghuraman H., Cunningham J.M., Gupta M., Gupta M.P.
      Sci. Signal. 4:RA46-RA46(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SIRT1, ACETYLATION AT LYS-14 AND LYS-20, DEACETYLATION AT LYS-14 AND LYS-20, MUTAGENESIS OF LYS-14; GLU-17 AND LYS-20.
    64. Cited for: UBIQUITINATION AT LYS-284.
    65. "Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates Akt signaling."
      Wang S., Huang X., Sun D., Xin X., Pan Q., Peng S., Liang Z., Luo C., Yang Y., Jiang H., Huang M., Chai W., Ding J., Geng M.
      PLoS ONE 7:E37427-E37427(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION AT SER-126; SER-129; THR-305 AND THR-312, SUBCELLULAR LOCATION, INTERACTION WITH PDPK1, MUTAGENESIS OF THR-305 AND THR-312.
    66. "CSTP1, a novel protein phosphatase, blocks cell cycle, promotes cell apoptosis, and suppresses tumor growth of bladder cancer by directly dephosphorylating Akt at Ser473 site."
      Zhuo D.X., Zhang X.W., Jin B., Zhang Z., Xie B.S., Wu C.L., Gong K., Mao Z.B.
      PLoS ONE 8:E65679-E65679(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-473, DEPHOSPHORYLATION BY CPPED1.
    67. "MOZ increases p53 acetylation and premature senescence through its complex formation with PML."
      Rokudai S., Laptenko O., Arnal S.M., Taya Y., Kitabayashi I., Prives C.
      Proc. Natl. Acad. Sci. U.S.A. 110:3895-3900(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    68. "High-resolution structure of the pleckstrin homology domain of protein kinase b/akt bound to phosphatidylinositol (3,4,5)-trisphosphate."
      Thomas C.C., Deak M., Alessi D.R., van Aalten D.M.
      Curr. Biol. 12:1256-1262(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 1-123, INTERACTION WITH PTDINS(3,4,5)P3 AND PTDINS(3,4)P2, MUTAGENESIS OF LYS-14; ARG-25 AND ARG-86.
    69. "Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin homology domain of protein kinase B induces a conformational change."
      Milburn C.C., Deak M., Kelly S.M., Price N.C., Alessi D.R., Van Aalten D.M.
      Biochem. J. 375:531-538(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (0.98 ANGSTROMS) OF 1-121, INTERACTION WITH PTDINS(1,3,4,5)P4.
    70. Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 144-480, PHOSPHORYLATION AT THR-308, ENZYME REGULATION.
    71. Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 144-480, ENZYME REGULATION.
    72. Cited for: X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 144-480, PHOSPHORYLATION AT THR-308, ENZYME REGULATION.
    73. "Crystal structure of human AKT1 with an allosteric inhibitor reveals a new mode of kinase inhibition."
      Wu W.I., Voegtli W.C., Sturgis H.L., Dizon F.P., Vigers G.P., Brandhuber B.J.
      PLoS ONE 5:E12913-E12913(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 2-443, DISULFIDE BOND.
    74. Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 144-480, ENZYME REGULATION.
    75. Cited for: VARIANT BREAST CANCER LYS-17, CHARACTERIZATION OF VARIANT BREAST CANCER LYS-17.
    76. "Molecular mechanism of an oncogenic mutation that alters membrane targeting: Glu17Lys modifies the PIP lipid specificity of the AKT1 PH domain."
      Landgraf K.E., Pilling C., Falke J.J.
      Biochemistry 47:12260-12269(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANT PROTEUSS LYS-17.
    77. Cited for: VARIANT PROTEUSS LYS-17.
    78. "Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes."
      Orloff M.S., He X., Peterson C., Chen F., Chen J.L., Mester J.L., Eng C.
      Am. J. Hum. Genet. 92:76-80(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CWD6 CYS-25 AND PRO-435.

    Entry informationi

    Entry nameiAKT1_HUMAN
    AccessioniPrimary (citable) accession number: P31749
    Secondary accession number(s): B2RAM5, B7Z5R1, Q9BWB6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1993
    Last sequence update: February 1, 2005
    Last modified: October 1, 2014
    This is version 183 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 14
      Human chromosome 14: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3