Skip Header

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

RAC-alpha serine/threonine-protein kinase

Gene

AKT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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)DescriptionActionsGraphical viewLength
    Binding sitei53Inositol-(1,3,4,5)-tetrakisphosphate1
    Binding sitei86Inositol-(1,3,4,5)-tetrakisphosphate1
    Binding sitei161Inhibitor; via amide nitrogen1
    Binding sitei179ATPPROSITE-ProRule annotation1
    Binding sitei230Inhibitor; via amide nitrogen1
    Binding sitei234Inhibitor1
    Active sitei274Proton acceptorPROSITE-ProRule annotation1
    Binding sitei292Inhibitor1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi156 – 164ATPPROSITE-ProRule annotation9

    GO - Molecular functioni

    • 14-3-3 protein binding Source: UniProtKB
    • ATP binding Source: UniProtKB
    • enzyme binding Source: BHF-UCL
    • kinase activity Source: MGI
    • nitric-oxide synthase regulator activity Source: BHF-UCL
    • phosphatidylinositol-3,4,5-trisphosphate binding Source: UniProtKB
    • phosphatidylinositol-3,4-bisphosphate binding Source: UniProtKB
    • protein kinase activity Source: ProtInc
    • protein serine/threonine/tyrosine kinase activity Source: MGI
    • protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    • activation-induced cell death of T cells Source: MGI
    • aging Source: Ensembl
    • apoptotic mitochondrial changes Source: Ensembl
    • cell differentiation Source: UniProtKB
    • cell projection organization Source: Ensembl
    • cell proliferation Source: UniProtKB
    • cellular protein modification process Source: ProtInc
    • cellular response to DNA damage stimulus Source: Ensembl
    • cellular response to epidermal growth factor stimulus Source: Ensembl
    • cellular response to granulocyte macrophage colony-stimulating factor stimulus Source: Ensembl
    • cellular response to hypoxia Source: Ensembl
    • cellular response to insulin stimulus Source: BHF-UCL
    • cellular response to mechanical stimulus Source: Ensembl
    • cellular response to nerve growth factor stimulus Source: UniProtKB
    • cellular response to organic cyclic compound Source: Ensembl
    • cellular response to prostaglandin E stimulus Source: Ensembl
    • cellular response to vascular endothelial growth factor stimulus Source: Ensembl
    • chemical synaptic transmission, postsynaptic Source: ParkinsonsUK-UCL
    • endocrine pancreas development Source: Reactome
    • ERBB2 signaling pathway Source: Reactome
    • establishment of protein localization to mitochondrion Source: ParkinsonsUK-UCL
    • execution phase of apoptosis Source: Ensembl
    • germ cell development Source: Ensembl
    • glucose homeostasis Source: Ensembl
    • glucose metabolic process Source: UniProtKB-KW
    • glucose transport Source: Ensembl
    • glycogen biosynthetic process Source: UniProtKB-KW
    • glycogen cell differentiation involved in embryonic placenta development Source: Ensembl
    • G-protein coupled receptor signaling pathway Source: ProtInc
    • hyaluronan metabolic process Source: Ensembl
    • inflammatory response Source: Ensembl
    • insulin-like growth factor receptor signaling pathway Source: UniProtKB
    • insulin receptor signaling pathway Source: UniProtKB
    • interleukin-18-mediated signaling pathway Source: BHF-UCL
    • intracellular signal transduction Source: MGI
    • labyrinthine layer blood vessel development Source: Ensembl
    • lipopolysaccharide-mediated signaling pathway Source: Ensembl
    • maintenance of protein location in mitochondrion Source: ParkinsonsUK-UCL
    • mammary gland epithelial cell differentiation Source: UniProtKB
    • maternal placenta development Source: Ensembl
    • negative regulation of apoptotic process Source: UniProtKB
    • negative regulation of autophagy Source: BHF-UCL
    • negative regulation of cell size Source: Ensembl
    • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    • negative regulation of endopeptidase activity Source: BHF-UCL
    • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
    • negative regulation of fatty acid beta-oxidation Source: BHF-UCL
    • negative regulation of gene expression Source: Ensembl
    • negative regulation of JNK cascade Source: Ensembl
    • negative regulation of neuron death Source: ParkinsonsUK-UCL
    • negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: BHF-UCL
    • negative regulation of plasma membrane long-chain fatty acid transport Source: BHF-UCL
    • negative regulation of protein kinase activity Source: BHF-UCL
    • negative regulation of protein kinase activity by protein phosphorylation Source: ParkinsonsUK-UCL
    • negative regulation of proteolysis Source: BHF-UCL
    • negative regulation of release of cytochrome c from mitochondria Source: UniProtKB
    • nitric oxide biosynthetic process Source: ProtInc
    • osteoblast differentiation Source: Ensembl
    • peptidyl-serine phosphorylation Source: UniProtKB
    • peptidyl-threonine phosphorylation Source: UniProtKB
    • peripheral nervous system myelin maintenance Source: Ensembl
    • phosphatidylinositol-mediated signaling Source: Reactome
    • phosphorylation Source: UniProtKB
    • platelet activation Source: Reactome
    • positive regulation of apoptotic process Source: Ensembl
    • positive regulation of blood vessel endothelial cell migration Source: DFLAT
    • positive regulation of cell growth Source: UniProtKB
    • positive regulation of cellular protein metabolic process Source: BHF-UCL
    • positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle Source: BHF-UCL
    • positive regulation of endodeoxyribonuclease activity Source: UniProtKB
    • positive regulation of endothelial cell proliferation Source: UniProtKB
    • positive regulation of epidermal growth factor receptor signaling pathway Source: Reactome
    • positive regulation of establishment of protein localization to plasma membrane Source: BHF-UCL
    • positive regulation of fat cell differentiation Source: BHF-UCL
    • positive regulation of fibroblast migration Source: Ensembl
    • positive regulation of glucose import Source: BHF-UCL
    • positive regulation of glucose metabolic process Source: BHF-UCL
    • positive regulation of glycogen biosynthetic process Source: BHF-UCL
    • positive regulation of lipid biosynthetic process Source: BHF-UCL
    • positive regulation of nitric oxide biosynthetic process Source: BHF-UCL
    • positive regulation of nitric-oxide synthase activity Source: BHF-UCL
    • positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
    • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: Ensembl
    • positive regulation of protein localization to nucleus Source: UniProtKB
    • positive regulation of protein phosphorylation Source: BHF-UCL
    • positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    • positive regulation of smooth muscle cell proliferation Source: BHF-UCL
    • positive regulation of sodium ion transport Source: Ensembl
    • positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    • positive regulation of vasoconstriction Source: Ensembl
    • protein autophosphorylation Source: UniProtKB
    • protein catabolic process Source: Ensembl
    • protein import into nucleus, translocation Source: UniProtKB
    • protein kinase B signaling Source: Ensembl
    • protein phosphorylation Source: UniProtKB
    • protein ubiquitination Source: Ensembl
    • regulation of cell cycle checkpoint Source: UniProtKB
    • regulation of cell migration Source: UniProtKB
    • regulation of glycogen biosynthetic process Source: BHF-UCL
    • regulation of mRNA stability Source: Reactome
    • regulation of myelination Source: Ensembl
    • regulation of neuron projection development Source: UniProtKB
    • regulation of nitric-oxide synthase activity Source: Reactome
    • regulation of phosphatidylinositol 3-kinase signaling Source: Reactome
    • regulation of signal transduction by p53 class mediator Source: Reactome
    • regulation of translation Source: UniProtKB-KW
    • response to fluid shear stress Source: BHF-UCL
    • response to food Source: Ensembl
    • response to growth hormone Source: AgBase
    • response to heat Source: ProtInc
    • response to insulin-like growth factor stimulus Source: AgBase
    • response to oxidative stress Source: ParkinsonsUK-UCL
    • response to UV-A Source: BHF-UCL
    • signal transduction Source: UniProtKB
    • spinal cord development Source: Ensembl
    • striated muscle cell differentiation Source: Ensembl
    • T cell costimulation Source: Reactome
    • 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

    BioCyciZFISH:HS06908-MONOMER.
    BRENDAi2.7.11.1. 2681.
    ReactomeiR-HSA-111447. Activation of BAD and translocation to mitochondria.
    R-HSA-114604. GPVI-mediated activation cascade.
    R-HSA-1257604. PIP3 activates AKT signaling.
    R-HSA-1358803. Downregulation of ERBB2:ERBB3 signaling.
    R-HSA-1445148. Translocation of GLUT4 to the plasma membrane.
    R-HSA-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
    R-HSA-165159. mTOR signalling.
    R-HSA-198323. AKT phosphorylates targets in the cytosol.
    R-HSA-198693. AKT phosphorylates targets in the nucleus.
    R-HSA-199418. Negative regulation of the PI3K/AKT network.
    R-HSA-203615. eNOS activation.
    R-HSA-211163. AKT-mediated inactivation of FOXO1A.
    R-HSA-354192. Integrin alphaIIb beta3 signaling.
    R-HSA-3769402. Deactivation of the beta-catenin transactivating complex.
    R-HSA-389357. CD28 dependent PI3K/Akt signaling.
    R-HSA-389513. CTLA4 inhibitory signaling.
    R-HSA-392451. G beta:gamma signalling through PI3Kgamma.
    R-HSA-450385. Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
    R-HSA-450604. KSRP (KHSRP) binds and destabilizes mRNA.
    R-HSA-5218920. VEGFR2 mediated vascular permeability.
    R-HSA-5628897. TP53 Regulates Metabolic Genes.
    R-HSA-5674400. Constitutive Signaling by AKT1 E17K in Cancer.
    R-HSA-6804757. Regulation of TP53 Degradation.
    R-HSA-6804758. Regulation of TP53 Activity through Acetylation.
    R-HSA-6804759. Regulation of TP53 Activity through Association with Co-factors.
    R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
    R-HSA-69202. Cyclin E associated events during G1/S transition.
    R-HSA-8849469. PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1.
    R-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.
    SABIO-RKP31749.
    SignaLinkiP31749.
    SIGNORiP31749.

    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
    Proteomesi
    • UP000005640 Componenti: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:391. AKT1.

    Subcellular locationi

    GO - Cellular componenti

    • cell-cell junction Source: Ensembl
    • ciliary basal body Source: Ensembl
    • cytoplasm Source: UniProtKB
    • cytosol Source: UniProtKB
    • microtubule cytoskeleton Source: HPA
    • mitochondrion Source: Ensembl
    • nucleoplasm Source: Reactome
    • nucleus Source: UniProtKB
    • plasma membrane Source: UniProtKB
    • postsynapse Source: GOC
    • protein complex Source: Ensembl
    • spindle Source: Ensembl
    • vesicle Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Breast cancer (BC)1 Publication
    Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Disease descriptionA 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.
    See also OMIM:114480
    Colorectal cancer (CRC)
    The gene represented in this entry may be involved in disease pathogenesis.
    Disease descriptionA 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.
    See also OMIM:114500

    Genetic variations in AKT1 may play a role in susceptibility to ovarian cancer.

    Proteus syndrome (PROTEUSS)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA 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.
    See also OMIM:176920
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_05542217E → 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. 4 PublicationsCorresponds to variant rs121434592dbSNPEnsembl.1
    Cowden syndrome 6 (CWS6)
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA 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.
    See also OMIM:615109
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_06979125R → C in CWS6. 1 PublicationCorresponds to variant rs397514644dbSNPEnsembl.1
    Natural variantiVAR_069792435T → P in CWS6. 1 PublicationCorresponds to variant rs397514645dbSNPEnsembl.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi8K → 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 Publication1
    Mutagenesisi14K → A: Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. 3 Publications1
    Mutagenesisi14K → 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 Publications1
    Mutagenesisi14K → 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 Publications1
    Mutagenesisi17E → K: No effect on membrane localization. Loss of membrane localization; when associated with Q-20. 1 Publication1
    Mutagenesisi20K → 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 Publication1
    Mutagenesisi20K → R: Slight increase of phosphorylation at T-308 and S-473. 1 Publication1
    Mutagenesisi25R → A or C: Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. 1 Publication1
    Mutagenesisi86R → A: Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. 1 Publication1
    Mutagenesisi176Y → F: Significant loss of interaction with TNK2. Loss of membrane localization. Significant reduction in phosphorylation on Ser-473. 1 Publication1
    Mutagenesisi305T → A: Reduces O-GlcNAc levels; Reduces O-GlcNAc levels even more; when associated with A-312. 1 Publication1
    Mutagenesisi305T → Y: Abolishes phosphorylation at Thr-308. 1 Publication1
    Mutagenesisi308T → D: 5-fold activation and 18-fold activation; when associated with D-473. 2 Publications1
    Mutagenesisi312T → A: Reduces O-GlcNAc levels; Reduces O-GlcNAc levels even more; when associated with A-305. 1 Publication1
    Mutagenesisi312T → Y: Abolishes phosphorylation at Thr-308. 1 Publication1
    Mutagenesisi473S → D: 7-fold activation and 25-fold activation; when associated with D-308. 2 Publications1
    Mutagenesisi474Y → F: 55% inhibition of activation. 1 Publication1

    Keywords - Diseasei

    Disease mutation, Proto-oncogene

    Organism-specific databases

    DisGeNETi207.
    MalaCardsiAKT1.
    MIMi114480. phenotype.
    114500. phenotype.
    176920. phenotype.
    615109. phenotype.
    OpenTargetsiENSG00000142208.
    Orphaneti201. Cowden syndrome.
    744. Proteus syndrome.
    PharmGKBiPA24684.

    Chemistry databases

    ChEMBLiCHEMBL4282.
    DrugBankiDB00171. Adenosine triphosphate.
    DB01169. Arsenic trioxide.
    GuidetoPHARMACOLOGYi1479.

    Polymorphism and mutation databases

    BioMutaiAKT1.
    DMDMi60391226.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000856051 – 480RAC-alpha serine/threonine-protein kinaseAdd BLAST480

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei14N6-acetyllysine1 Publication1
    Modified residuei20N6-acetyllysine1 Publication1
    Disulfide bondi60 ↔ 771 Publication
    Modified residuei124PhosphoserineCombined sources1
    Modified residuei126Phosphoserine; alternateCombined sources1
    Glycosylationi126O-linked (GlcNAc); alternate1 Publication1
    Modified residuei129Phosphoserine; alternateCombined sources1
    Glycosylationi129O-linked (GlcNAc); alternate1 Publication1
    Modified residuei176Phosphotyrosine; by TNK21 Publication1
    Cross-linki284Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
    Disulfide bondi296 ↔ 310By similarity
    Glycosylationi305O-linked (GlcNAc)1 Publication1
    Modified residuei308Phosphothreonine; by IKKE, PDPK1 and TBK17 Publications1
    Glycosylationi312O-linked (GlcNAc)1 Publication1
    Modified residuei448PhosphothreonineCombined sources1
    Modified residuei450PhosphothreonineCombined sources1
    Modified residuei473Phosphoserine; by IKKE, MTOR and TBK1; alternate11 Publications1
    Glycosylationi473O-linked (GlcNAc); alternateBy similarity1
    Modified residuei474Phosphotyrosine1 Publication1

    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

    EPDiP31749.
    MaxQBiP31749.
    PaxDbiP31749.
    PeptideAtlasiP31749.
    PRIDEiP31749.

    PTM databases

    iPTMnetiP31749.
    PhosphoSitePlusiP31749.

    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

    BgeeiENSG00000142208.
    CleanExiHS_AKT1.
    ExpressionAtlasiP31749. baseline and differential.
    GenevisibleiP31749. HS.

    Organism-specific databases

    HPAiCAB003765.
    HPA002891.

    Interactioni

    Subunit structurei

    Interacts with BTBD10 (By similarity). Interacts with KCTD20 (By similarity). 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. Interacts with PA2G4 (By similarity). Interacts with KIF14; the interaction is detected in the plasma membrane upon INS stimulation and promotes AKT1 phosphorylation (PubMed:24784001). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (PubMed:23676467). Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529). Forms a complex with WDFY2 and FOXO1 (By similarity). Interacts with FAM168A (PubMed:23251525).By similarity32 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself2EBI-296087,EBI-296087
    APPL1Q9UKG12EBI-296087,EBI-741243
    Arrb2P290672EBI-296087,EBI-1636616From a different organism.
    ASXL1Q8IXJ92EBI-296087,EBI-1646500
    BCL10O959995EBI-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
    PPP1CAP621364EBI-296087,EBI-357253
    PPP2CAP677754EBI-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
    TERF2IPQ9NYB02EBI-296087,EBI-750109
    TOPBP1Q925472EBI-296087,EBI-308302
    VIMP0867029EBI-296087,EBI-353844
    XP031653EBI-296087,EBI-7683985From a different organism.

    GO - Molecular functioni

    • 14-3-3 protein binding Source: UniProtKB
    • enzyme binding Source: BHF-UCL

    Protein-protein interaction databases

    BioGridi106710. 285 interactors.
    DIPiDIP-24269N.
    IntActiP31749. 146 interactors.
    MINTiMINT-203775.
    STRINGi9606.ENSP00000270202.

    Chemistry databases

    BindingDBiP31749.

    Structurei

    Secondary structure

    1480
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi2 – 4Combined sources3
    Beta strandi6 – 15Combined sources10
    Beta strandi17 – 19Combined sources3
    Beta strandi22 – 30Combined sources9
    Beta strandi33 – 40Combined sources8
    Helixi45 – 48Combined sources4
    Beta strandi52 – 56Combined sources5
    Beta strandi61 – 65Combined sources5
    Beta strandi67 – 69Combined sources3
    Beta strandi72 – 79Combined sources8
    Beta strandi82 – 89Combined sources8
    Helixi93 – 115Combined sources23
    Helixi147 – 149Combined sources3
    Beta strandi150 – 158Combined sources9
    Beta strandi160 – 169Combined sources10
    Turni170 – 172Combined sources3
    Beta strandi175 – 182Combined sources8
    Helixi183 – 188Combined sources6
    Helixi192 – 204Combined sources13
    Beta strandi213 – 218Combined sources6
    Beta strandi220 – 227Combined sources8
    Helixi235 – 242Combined sources8
    Helixi247 – 268Combined sources22
    Helixi277 – 279Combined sources3
    Beta strandi280 – 282Combined sources3
    Beta strandi284 – 286Combined sources3
    Beta strandi288 – 290Combined sources3
    Beta strandi309 – 311Combined sources3
    Helixi313 – 315Combined sources3
    Helixi318 – 322Combined sources5
    Helixi330 – 344Combined sources15
    Helixi354 – 363Combined sources10
    Helixi374 – 383Combined sources10
    Helixi388 – 390Combined sources3
    Turni396 – 398Combined sources3
    Helixi399 – 403Combined sources5
    Helixi406 – 408Combined sources3
    Helixi413 – 417Combined sources5
    Beta strandi430 – 433Combined sources4
    Helixi440 – 443Combined sources4
    Beta strandi464 – 466Combined sources3
    Beta strandi473 – 475Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB 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[»]
    5KCVX-ray2.70A2-446[»]
    ProteinModelPortaliP31749.
    SMRiP31749.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP31749.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini5 – 108PHPROSITE-ProRule annotationAdd BLAST104
    Domaini150 – 408Protein kinasePROSITE-ProRule annotationAdd BLAST259
    Domaini409 – 480AGC-kinase C-terminalAdd BLAST72

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni14 – 19Inositol-(1,3,4,5)-tetrakisphosphate binding6
    Regioni23 – 25Inositol-(1,3,4,5)-tetrakisphosphate binding3
    Regioni228 – 230Inhibitor binding3

    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

    eggNOGiKOG0598. Eukaryota.
    ENOG410XNPH. LUCA.
    GeneTreeiENSGT00860000133668.
    HOGENOMiHOG000233033.
    HOVERGENiHBG108317.
    InParanoidiP31749.
    KOiK04456.
    OMAiQDDSMES.
    OrthoDBiEOG091G06FF.
    PhylomeDBiP31749.
    TreeFamiTF102004.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    InterProiIPR000961. AGC-kinase_C.
    IPR011009. Kinase-like_dom.
    IPR011993. PH_dom-like.
    IPR001849. PH_domain.
    IPR017892. Pkinase_C.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    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]
    SUPFAMiSSF50729. SSF50729. 1 hit.
    SSF56112. 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. AlignAdd to basket

    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)DescriptionActionsGraphical viewLength
    Sequence conflicti173 – 174GR → A in CAA43372 (PubMed:1718748).Curated2
    Sequence conflicti202L → Q in CAA43372 (PubMed:1718748).Curated1
    Sequence conflicti212A → R in CAA43372 (PubMed:1718748).Curated1
    Sequence conflicti246S → A in CAA43372 (PubMed:1718748).Curated1
    Sequence conflicti409A → T in CAA43372 (PubMed:1718748).Curated1
    Sequence conflicti476A → P in CAA43372 (PubMed:1718748).Curated1
    Sequence conflicti478G → A in CAA43372 (PubMed:1718748).Curated1
    Sequence conflicti478G → S in AAA36539 (PubMed:1851997).Curated1
    Sequence conflicti478G → S in AAL55732 (PubMed:11508278).Curated1
    Sequence conflicti478G → S in BAG36922 (PubMed:14702039).Curated1
    Sequence conflicti478G → S in BAG70056 (PubMed:19054851).Curated1
    Sequence conflicti478G → S in BAG70181 (PubMed:19054851).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_05542217E → 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. 4 PublicationsCorresponds to variant rs121434592dbSNPEnsembl.1
    Natural variantiVAR_06979125R → C in CWS6. 1 PublicationCorresponds to variant rs397514644dbSNPEnsembl.1
    Natural variantiVAR_051617167V → A.Corresponds to variant rs11555433dbSNPEnsembl.1
    Natural variantiVAR_069792435T → P in CWS6. 1 PublicationCorresponds to variant rs397514645dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0561801 – 62Missing in isoform 2. 1 PublicationAdd BLAST62

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    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. [P31749-1]
    NP_001014432.1. NM_001014432.1. [P31749-1]
    NP_005154.2. NM_005163.2. [P31749-1]
    XP_005267458.1. XM_005267401.1. [P31749-1]
    UniGeneiHs.525622.

    Genome annotation databases

    EnsembliENST00000349310; ENSP00000270202; ENSG00000142208. [P31749-1]
    ENST00000402615; ENSP00000385326; ENSG00000142208. [P31749-1]
    ENST00000407796; ENSP00000384293; ENSG00000142208. [P31749-1]
    ENST00000554581; ENSP00000451828; ENSG00000142208. [P31749-1]
    ENST00000554848; ENSP00000451166; ENSG00000142208. [P31749-1]
    ENST00000555528; ENSP00000450688; ENSG00000142208. [P31749-1]
    GeneIDi207.
    KEGGihsa:207.
    UCSCiuc001ypk.4. human. [P31749-1]

    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:
    EMBLi
    GenBanki
    DDBJi
    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. [P31749-1]
    NP_001014432.1. NM_001014432.1. [P31749-1]
    NP_005154.2. NM_005163.2. [P31749-1]
    XP_005267458.1. XM_005267401.1. [P31749-1]
    UniGeneiHs.525622.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB 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[»]
    5KCVX-ray2.70A2-446[»]
    ProteinModelPortaliP31749.
    SMRiP31749.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi106710. 285 interactors.
    DIPiDIP-24269N.
    IntActiP31749. 146 interactors.
    MINTiMINT-203775.
    STRINGi9606.ENSP00000270202.

    Chemistry databases

    BindingDBiP31749.
    ChEMBLiCHEMBL4282.
    DrugBankiDB00171. Adenosine triphosphate.
    DB01169. Arsenic trioxide.
    GuidetoPHARMACOLOGYi1479.

    PTM databases

    iPTMnetiP31749.
    PhosphoSitePlusiP31749.

    Polymorphism and mutation databases

    BioMutaiAKT1.
    DMDMi60391226.

    Proteomic databases

    EPDiP31749.
    MaxQBiP31749.
    PaxDbiP31749.
    PeptideAtlasiP31749.
    PRIDEiP31749.

    Protocols and materials databases

    DNASUi207.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000349310; ENSP00000270202; ENSG00000142208. [P31749-1]
    ENST00000402615; ENSP00000385326; ENSG00000142208. [P31749-1]
    ENST00000407796; ENSP00000384293; ENSG00000142208. [P31749-1]
    ENST00000554581; ENSP00000451828; ENSG00000142208. [P31749-1]
    ENST00000554848; ENSP00000451166; ENSG00000142208. [P31749-1]
    ENST00000555528; ENSP00000450688; ENSG00000142208. [P31749-1]
    GeneIDi207.
    KEGGihsa:207.
    UCSCiuc001ypk.4. human. [P31749-1]

    Organism-specific databases

    CTDi207.
    DisGeNETi207.
    GeneCardsiAKT1.
    GeneReviewsiAKT1.
    HGNCiHGNC:391. AKT1.
    HPAiCAB003765.
    HPA002891.
    MalaCardsiAKT1.
    MIMi114480. phenotype.
    114500. phenotype.
    164730. gene.
    176920. phenotype.
    615109. phenotype.
    neXtProtiNX_P31749.
    OpenTargetsiENSG00000142208.
    Orphaneti201. Cowden syndrome.
    744. Proteus syndrome.
    PharmGKBiPA24684.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0598. Eukaryota.
    ENOG410XNPH. LUCA.
    GeneTreeiENSGT00860000133668.
    HOGENOMiHOG000233033.
    HOVERGENiHBG108317.
    InParanoidiP31749.
    KOiK04456.
    OMAiQDDSMES.
    OrthoDBiEOG091G06FF.
    PhylomeDBiP31749.
    TreeFamiTF102004.

    Enzyme and pathway databases

    BioCyciZFISH:HS06908-MONOMER.
    BRENDAi2.7.11.1. 2681.
    ReactomeiR-HSA-111447. Activation of BAD and translocation to mitochondria.
    R-HSA-114604. GPVI-mediated activation cascade.
    R-HSA-1257604. PIP3 activates AKT signaling.
    R-HSA-1358803. Downregulation of ERBB2:ERBB3 signaling.
    R-HSA-1445148. Translocation of GLUT4 to the plasma membrane.
    R-HSA-1474151. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
    R-HSA-165159. mTOR signalling.
    R-HSA-198323. AKT phosphorylates targets in the cytosol.
    R-HSA-198693. AKT phosphorylates targets in the nucleus.
    R-HSA-199418. Negative regulation of the PI3K/AKT network.
    R-HSA-203615. eNOS activation.
    R-HSA-211163. AKT-mediated inactivation of FOXO1A.
    R-HSA-354192. Integrin alphaIIb beta3 signaling.
    R-HSA-3769402. Deactivation of the beta-catenin transactivating complex.
    R-HSA-389357. CD28 dependent PI3K/Akt signaling.
    R-HSA-389513. CTLA4 inhibitory signaling.
    R-HSA-392451. G beta:gamma signalling through PI3Kgamma.
    R-HSA-450385. Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA.
    R-HSA-450604. KSRP (KHSRP) binds and destabilizes mRNA.
    R-HSA-5218920. VEGFR2 mediated vascular permeability.
    R-HSA-5628897. TP53 Regulates Metabolic Genes.
    R-HSA-5674400. Constitutive Signaling by AKT1 E17K in Cancer.
    R-HSA-6804757. Regulation of TP53 Degradation.
    R-HSA-6804758. Regulation of TP53 Activity through Acetylation.
    R-HSA-6804759. Regulation of TP53 Activity through Association with Co-factors.
    R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
    R-HSA-69202. Cyclin E associated events during G1/S transition.
    R-HSA-8849469. PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1.
    R-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.
    SABIO-RKP31749.
    SignaLinkiP31749.
    SIGNORiP31749.

    Miscellaneous databases

    ChiTaRSiAKT1. human.
    EvolutionaryTraceiP31749.
    GeneWikiiAKT1.
    GenomeRNAii207.
    PMAP-CutDBP31749.
    PROiP31749.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000142208.
    CleanExiHS_AKT1.
    ExpressionAtlasiP31749. baseline and differential.
    GenevisibleiP31749. HS.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    InterProiIPR000961. AGC-kinase_C.
    IPR011009. Kinase-like_dom.
    IPR011993. PH_dom-like.
    IPR001849. PH_domain.
    IPR017892. Pkinase_C.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    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]
    SUPFAMiSSF50729. SSF50729. 1 hit.
    SSF56112. 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]
    ProtoNetiSearch...

    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: November 30, 2016
    This is version 208 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

    Caution

    In light of strong homologies in the primary amino acid sequence, the 3 AKT kinases were long surmised to play redundant and overlapping roles. More recent studies has brought into question the redundancy within AKT kinase isoforms and instead pointed to isoform specific functions in different cellular events and diseases. AKT1 is more specifically involved in cellular survival pathways, by inhibiting apoptotic processes; whereas AKT2 is more specific for the insulin receptor signaling pathway. Moreover, while AKT1 and AKT2 are often implicated in many aspects of cellular transformation, the 2 isoforms act in a complementary opposing manner. The role of AKT3 is less clear, though it appears to be predominantly expressed in brain.Curated

    Keywords - Technical termi

    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

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.