Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P31749

- AKT1_HUMAN

UniProt

P31749 - AKT1_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

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

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 kinase activity Source: ProtInc
  10. protein serine/threonine/tyrosine kinase activity Source: MGI
  11. 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 granulocyte macrophage colony-stimulating factor stimulus Source: Ensembl
  13. cellular response to hypoxia Source: Ensembl
  14. cellular response to insulin stimulus Source: BHF-UCL
  15. cellular response to mechanical stimulus Source: Ensembl
  16. endocrine pancreas development Source: Reactome
  17. epidermal growth factor receptor signaling pathway Source: Reactome
  18. execution phase of apoptosis Source: Ensembl
  19. Fc-epsilon receptor signaling pathway Source: Reactome
  20. fibroblast growth factor receptor signaling pathway Source: Reactome
  21. gene expression Source: Reactome
  22. germ cell development Source: Ensembl
  23. glucose homeostasis Source: Ensembl
  24. glucose metabolic process Source: UniProtKB-KW
  25. glucose transport Source: Ensembl
  26. glycogen biosynthetic process Source: UniProtKB-KW
  27. glycogen cell differentiation involved in embryonic placenta development Source: Ensembl
  28. G-protein coupled receptor signaling pathway Source: ProtInc
  29. hyaluronan metabolic process Source: Ensembl
  30. inflammatory response Source: Ensembl
  31. innate immune response Source: Reactome
  32. insulin-like growth factor receptor signaling pathway Source: UniProtKB
  33. insulin receptor signaling pathway Source: UniProtKB
  34. intracellular signal transduction Source: MGI
  35. intrinsic apoptotic signaling pathway Source: Reactome
  36. labyrinthine layer blood vessel development Source: Ensembl
  37. mammary gland epithelial cell differentiation Source: UniProtKB
  38. maternal placenta development Source: Ensembl
  39. membrane organization Source: Reactome
  40. mRNA metabolic process Source: Reactome
  41. negative regulation of apoptotic process Source: UniProtKB
  42. negative regulation of autophagy Source: BHF-UCL
  43. negative regulation of cell size Source: Ensembl
  44. negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  45. negative regulation of endopeptidase activity Source: BHF-UCL
  46. negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
  47. negative regulation of fatty acid beta-oxidation Source: BHF-UCL
  48. negative regulation of JNK cascade Source: Ensembl
  49. negative regulation of neuron death Source: ParkinsonsUK-UCL
  50. negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: BHF-UCL
  51. negative regulation of plasma membrane long-chain fatty acid transport Source: BHF-UCL
  52. negative regulation of protein kinase activity Source: BHF-UCL
  53. negative regulation of proteolysis Source: BHF-UCL
  54. negative regulation of release of cytochrome c from mitochondria Source: UniProtKB
  55. neurotrophin TRK receptor signaling pathway Source: Reactome
  56. nitric oxide biosynthetic process Source: ProtInc
  57. nitric oxide metabolic process Source: Reactome
  58. osteoblast differentiation Source: Ensembl
  59. peptidyl-serine phosphorylation Source: UniProtKB
  60. peripheral nervous system myelin maintenance Source: Ensembl
  61. phosphatidylinositol-mediated signaling Source: Reactome
  62. phosphorylation Source: UniProtKB
  63. platelet activation Source: Reactome
  64. positive regulation of apoptotic process Source: Ensembl
  65. positive regulation of blood vessel endothelial cell migration Source: DFLAT
  66. positive regulation of cell growth Source: UniProtKB
  67. positive regulation of cellular protein metabolic process Source: BHF-UCL
  68. positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle Source: BHF-UCL
  69. positive regulation of endothelial cell proliferation Source: UniProtKB
  70. positive regulation of establishment of protein localization to plasma membrane Source: BHF-UCL
  71. positive regulation of fat cell differentiation Source: BHF-UCL
  72. positive regulation of glucose import Source: BHF-UCL
  73. positive regulation of glucose metabolic process Source: BHF-UCL
  74. positive regulation of glycogen biosynthetic process Source: BHF-UCL
  75. positive regulation of lipid biosynthetic process Source: BHF-UCL
  76. positive regulation of nitric oxide biosynthetic process Source: BHF-UCL
  77. positive regulation of nitric-oxide synthase activity Source: BHF-UCL
  78. positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
  79. positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: Ensembl
  80. positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway Source: Reactome
  81. positive regulation of protein phosphorylation Source: BHF-UCL
  82. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  83. positive regulation of sodium ion transport Source: Ensembl
  84. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  85. positive regulation of vasoconstriction Source: Ensembl
  86. protein autophosphorylation Source: UniProtKB
  87. protein catabolic process Source: Ensembl
  88. protein import into nucleus, translocation Source: UniProtKB
  89. protein kinase B signaling Source: Ensembl
  90. protein phosphorylation Source: UniProtKB
  91. protein ubiquitination Source: Ensembl
  92. regulation of cell cycle checkpoint Source: UniProtKB
  93. regulation of cell migration Source: UniProtKB
  94. regulation of glycogen biosynthetic process Source: BHF-UCL
  95. regulation of neuron projection development Source: UniProtKB
  96. regulation of nitric-oxide synthase activity Source: Reactome
  97. regulation of translation Source: UniProtKB-KW
  98. response to fluid shear stress Source: BHF-UCL
  99. response to food Source: Ensembl
  100. response to heat Source: ProtInc
  101. response to UV-A Source: BHF-UCL
  102. RNA metabolic process Source: Reactome
  103. signal transduction Source: UniProtKB
  104. small molecule metabolic process Source: Reactome
  105. striated muscle cell differentiation Source: Ensembl
  106. T cell costimulation Source: Reactome
  107. translation Source: Ensembl
Complete GO annotation...

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. cell-cell junction Source: Ensembl
  2. ciliary basal body Source: Ensembl
  3. cytoplasm Source: UniProtKB
  4. cytosol Source: UniProtKB
  5. microtubule cytoskeleton Source: HPA
  6. mitochondrion Source: Ensembl
  7. nucleoplasm Source: Reactome
  8. nucleus Source: UniProtKB
  9. plasma membrane Source: UniProtKB
  10. spindle Source: Ensembl
Complete GO annotation...

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

BgeeiP31749.
CleanExiHS_AKT1.
ExpressionAtlasiP31749. baseline and differential.
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. 216 interactions.
DIPiDIP-24269N.
IntActiP31749. 94 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.
GeneTreeiENSGT00760000118793.
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.
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

        10         20         30         40         50
MSDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVDQREA
60 70 80 90 100
PLNNFSVAQC QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWT
110 120 130 140 150
TAIQTVADGL KKQEEEEMDF RSGSPSDNSG AEEMEVSLAK PKHRVTMNEF
160 170 180 190 200
EYLKLLGKGT FGKVILVKEK ATGRYYAMKI LKKEVIVAKD EVAHTLTENR
210 220 230 240 250
VLQNSRHPFL TALKYSFQTH DRLCFVMEYA NGGELFFHLS RERVFSEDRA
260 270 280 290 300
RFYGAEIVSA LDYLHSEKNV VYRDLKLENL MLDKDGHIKI TDFGLCKEGI
310 320 330 340 350
KDGATMKTFC GTPEYLAPEV LEDNDYGRAV DWWGLGVVMY EMMCGRLPFY
360 370 380 390 400
NQDHEKLFEL ILMEEIRFPR TLGPEAKSLL SGLLKKDPKQ RLGGGSEDAK
410 420 430 440 450
EIMQHRFFAG IVWQHVYEKK LSPPFKPQVT SETDTRYFDE EFTAQMITIT
460 470 480
PPDQDDSMEC VDSERRPHFP QFSYSASGTA
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. [P31749-1]
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. [P31749-1]
ENST00000402615; ENSP00000385326; ENSG00000142208. [P31749-1]
ENST00000407796; ENSP00000384293; ENSG00000142208. [P31749-1]
ENST00000544168; ENSP00000443897; ENSG00000142208. [P31749-2]
ENST00000554581; ENSP00000451828; ENSG00000142208. [P31749-1]
ENST00000554848; ENSP00000451166; ENSG00000142208. [P31749-1]
ENST00000555528; ENSP00000450688; ENSG00000142208. [P31749-1]
GeneIDi207.
KEGGihsa:207.
UCSCiuc001ypk.3. human. [P31749-1]

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. [P31749-1 ]
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. 216 interactions.
DIPi DIP-24269N.
IntActi P31749. 94 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 . [P31749-1 ]
ENST00000402615 ; ENSP00000385326 ; ENSG00000142208 . [P31749-1 ]
ENST00000407796 ; ENSP00000384293 ; ENSG00000142208 . [P31749-1 ]
ENST00000544168 ; ENSP00000443897 ; ENSG00000142208 . [P31749-2 ]
ENST00000554581 ; ENSP00000451828 ; ENSG00000142208 . [P31749-1 ]
ENST00000554848 ; ENSP00000451166 ; ENSG00000142208 . [P31749-1 ]
ENST00000555528 ; ENSP00000450688 ; ENSG00000142208 . [P31749-1 ]
GeneIDi 207.
KEGGi hsa:207.
UCSCi uc001ypk.3. human. [P31749-1 ]

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.
GeneTreei ENSGT00760000118793.
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 35479782.
PMAP-CutDB P31749.
PROi P31749.
SOURCEi Search...

Gene expression databases

Bgeei P31749.
CleanExi HS_AKT1.
ExpressionAtlasi P31749. baseline and differential.
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.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 184 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