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-beta serine/threonine-protein kinase

Gene

AKT2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

AKT2 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.
One of the few specific substrates of AKT2 identified recently is PITX2. Phosphorylation of PITX2 impairs its association with the CCND1 mRNA-stabilizing complex thus shortening the half-life of CCND1. AKT2 seems also to be the principal isoform responsible of the regulation of glucose uptake. Phosphorylates C2CD5 on 'Ser-197' during insulin-stimulated adipocytes. AKT2 is also specifically involved in skeletal muscle differentiation, one of its substrates in this process being ANKRD2. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. Phosphorylates CLK2 on 'Thr-343'.

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Two specific sites, one in the kinase domain (Thr-309) and the other in the C-terminal regulatory region (Ser-474), need to be phosphorylated for its full activation. Aminofurazans are potent AKT2 inhibitors.2 Publications

Kineticsi

  1. KM=358.4 µM for ATP (for purified and in vitro activated AKT2)1 Publication
  2. KM=3.4 µM for peptide substrate (for purified and in vitro activated AKT2)1 Publication
  3. KM=564 µM for ATP (for recombinant myristoylated AKT2 expressed and immunoprecipitated from Rat-1 cells)1 Publication
  4. KM=2.3 µM for peptide substrate (for recombinant myristoylated AKT2 expressed and immunoprecipitated from Rat-1 cells)1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei181 – 1811ATPPROSITE-ProRule annotation
    Binding sitei181 – 1811Inhibitor
    Binding sitei200 – 2001Inhibitor
    Binding sitei232 – 2321Inhibitor; via amide nitrogen
    Binding sitei236 – 2361Inhibitor
    Active sitei275 – 2751Proton acceptorPROSITE-ProRule annotation
    Binding sitei279 – 2791Inhibitor; via carbonyl oxygen
    Binding sitei280 – 2801Manganese1 Publication
    Binding sitei293 – 2931Inhibitor
    Binding sitei293 – 2931Manganese1 Publication
    Binding sitei294 – 2941Inhibitor; via amide nitrogen

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi158 – 1669ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    • ATP binding Source: UniProtKB
    • kinase activity Source: Reactome
    • protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    • apoptotic process Source: UniProtKB-KW
    • carbohydrate transport Source: UniProtKB-KW
    • cellular protein modification process Source: ProtInc
    • cellular response to insulin stimulus Source: BHF-UCL
    • fat cell differentiation Source: UniProtKB
    • glucose metabolic process Source: UniProtKB-KW
    • glycogen biosynthetic process Source: UniProtKB-KW
    • insulin receptor signaling pathway Source: UniProtKB
    • intracellular protein transmembrane transport Source: UniProtKB
    • mammary gland epithelial cell differentiation Source: UniProtKB
    • membrane organization Source: Reactome
    • negative regulation of plasma membrane long-chain fatty acid transport Source: BHF-UCL
    • peripheral nervous system myelin maintenance Source: Ensembl
    • positive regulation of cell motility Source: BHF-UCL
    • positive regulation of fatty acid beta-oxidation Source: BHF-UCL
    • positive regulation of glucose import Source: BHF-UCL
    • positive regulation of glucose import in response to insulin stimulus Source: Ensembl
    • positive regulation of glucose metabolic process Source: BHF-UCL
    • positive regulation of glycogen biosynthetic process Source: BHF-UCL
    • positive regulation of protein phosphorylation Source: UniProtKB
    • positive regulation of protein targeting to membrane Source: UniProtKB
    • positive regulation of vesicle fusion Source: UniProtKB
    • protein localization to plasma membrane Source: Ensembl
    • regulation of cell cycle arrest Source: UniProtKB
    • regulation of cell migration Source: UniProtKB
    • regulation of translation Source: UniProtKB-KW
    • signal transduction Source: UniProtKB
    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, Sugar transport, Translation regulation, Transport

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.1. 2681.
    ReactomeiREACT_115662. Downregulation of ERBB2:ERBB3 signaling.
    REACT_12442. AKT phosphorylates targets in the nucleus.
    REACT_12447. Negative regulation of the PI3K/AKT network.
    REACT_12564. AKT phosphorylates targets in the cytosol.
    REACT_13655. AKT-mediated inactivation of FOXO1A.
    REACT_1451. PDE3B signalling.
    REACT_147867. Translocation of GLUT4 to the plasma membrane.
    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_263991. VEGFR2 mediated vascular permeability.
    REACT_264178. deactivation of the beta-catenin transactivating complex.
    REACT_355377. TP53 Regulates Metabolic Genes.
    REACT_355468. Constitutive Signaling by AKT1 E17K in Cancer.
    REACT_549. Activation of BAD and translocation to mitochondria.
    REACT_6743. Inhibition of TSC complex formation by PKB.
    REACT_75829. PIP3 activates AKT signaling.
    REACT_790. Activation of PKB.
    SignaLinkiP31751.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    RAC-beta serine/threonine-protein kinase (EC:2.7.11.1)
    Alternative name(s):
    Protein kinase Akt-2
    Protein kinase B beta
    Short name:
    PKB beta
    RAC-PK-beta
    Gene namesi
    Name:AKT2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:392. AKT2.

    Subcellular locationi

    • Cytoplasm
    • Nucleus
    • Cell membrane; Peripheral membrane protein

    • Note: Localizes within both nucleus and cytoplasm of proliferative primary myoblasts and mostly within the nucleus of differentiated primary myoblasts. By virtue of the N-terminal PH domain, is recruited to sites of the plasma membrane containing increased PI(3,4,5)P3 or PI(3,4)P2, cell membrane targeting is also facilitared by interaction with CLIP3.

    GO - Cellular componenti

    • cell cortex Source: UniProtKB
    • cytosol Source: Reactome
    • nucleoplasm Source: Reactome
    • nucleus Source: UniProtKB
    • plasma membrane Source: UniProtKB
    • ruffle membrane Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Defects in AKT2 are a cause of susceptibility to breast cancer (BC). AKT2 promotes metastasis of tumor cells without affecting the latency of tumor development. With AKT3, plays also a pivotal role in the biology of glioblastoma.

    Diabetes mellitus, non-insulin-dependent (NIDDM)2 Publications

    The disease is caused by mutations affecting the gene represented in this entry.

    Disease descriptionA multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.

    See also OMIM:125853
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti274 – 2741R → H in NIDDM; associated with typical metabolic dyslipidemia with elevated fastin triglyceride, high VLDL triglyceride/cholesterol ratios, low HDL cholesterol levels and high small dense LDL levels; de novo lipogenesis and liver fat are also significantly elevated in this subject. 1 Publication
    VAR_067310
    Hypoinsulinemic hypoglycemia with hemihypertrophy (HIHGHH)1 Publication

    The disease is caused by mutations affecting the gene represented in this entry.

    Disease descriptionA disorder characterized by hypoglycemia, low insulin levels, low serum levels of ketone bodies and branched-chain amino acids, left-sided hemihypertrophy, neonatal macrosomia, reduced consciousness and hypoglycemic seizures.

    See also OMIM:240900
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti17 – 171E → K in HIHGHH; exhibits plasma membrane localization in serum-starved cells and produced inappropriate tonic nuclear exclusion of FOXO1 in preadipocytes. 1 Publication
    VAR_067309

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi309 – 3091T → A: Impairs interaction with TTC3; when associated with A-474. 2 Publications
    Mutagenesisi309 – 3091T → E: Constitutively active; when associated with D-474. 2 Publications
    Mutagenesisi474 – 4741S → A: Impairs interaction with TTC3; when associated with A-309. 2 Publications
    Mutagenesisi474 – 4741S → D: Constitutively active; when associated with E-309. 2 Publications

    Keywords - Diseasei

    Diabetes mellitus, Disease mutation, Proto-oncogene

    Organism-specific databases

    MIMi125853. phenotype.
    240900. phenotype.
    Orphaneti79085. Familial partial lipodystrophy due to AKT2 mutations.
    293964. Hypoinsulinemic hypoglycemia and body hemihypertrophy.
    PharmGKBiPA24685.

    Polymorphism and mutation databases

    BioMutaiAKT2.
    DMDMi1170703.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 481481RAC-beta serine/threonine-protein kinasePRO_0000085608Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine1 Publication
    Modified residuei14 – 141N6-acetyllysineBy similarity
    Modified residuei20 – 201N6-acetyllysineBy similarity
    Modified residuei34 – 341Phosphoserine1 Publication
    Disulfide bondi60 ↔ 77By similarity
    Modified residuei126 – 1261Phosphoserine1 Publication
    Modified residuei128 – 1281Phosphoserine; alternateBy similarity
    Glycosylationi128 – 1281O-linked (GlcNAc); alternateBy similarity
    Modified residuei131 – 1311Phosphoserine; alternateBy similarity
    Glycosylationi131 – 1311O-linked (GlcNAc); alternateBy similarity
    Modified residuei178 – 1781PhosphotyrosineBy similarity
    Disulfide bondi297 ↔ 3111 Publication
    Glycosylationi306 – 3061O-linked (GlcNAc)By similarity
    Modified residuei309 – 3091Phosphothreonine; by PDPK14 Publications
    Glycosylationi313 – 3131O-linked (GlcNAc)By similarity
    Modified residuei447 – 4471Phosphoserine1 Publication
    Modified residuei449 – 4491PhosphothreonineBy similarity
    Modified residuei451 – 4511Phosphothreonine2 Publications
    Modified residuei474 – 4741Phosphoserine3 Publications
    Modified residuei475 – 4751PhosphotyrosineBy similarity
    Modified residuei478 – 4781Phosphoserine1 Publication

    Post-translational modificationi

    Phosphorylation on Thr-309 and Ser-474 is required for full activity.4 Publications
    Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. TRAF6-induced 'Lys-63'-linked AKT2 ubiquitination. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome.2 Publications
    O-GlcNAcylation at Thr-306 and Thr-313 inhibits activating phosphorylation at Thr-309 via disrupting the interaction between AKT and PDK1.By similarity

    Keywords - PTMi

    Acetylation, Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP31751.
    PaxDbiP31751.
    PRIDEiP31751.

    PTM databases

    PhosphoSiteiP31751.

    Expressioni

    Tissue specificityi

    Expressed in all cell types so far analyzed.

    Gene expression databases

    BgeeiP31751.
    CleanExiHS_AKT2.
    ExpressionAtlasiP31751. baseline and differential.
    GenevisibleiP31751. HS.

    Organism-specific databases

    HPAiCAB004204.

    Interactioni

    Subunit structurei

    Interacts with BTBD10 (By similarity). Interacts with KCTD20 (By similarity). Interacts (via PH domain) with MTCP1, TCL1A AND TCL1B. Interacts with CLK2, PBH2 and TRAF6. Interacts (when phosphorylated) with CLIP3, the interaction promotes cell membrane localization (PubMed:19139280).By similarity6 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    GSK3BP498412EBI-296058,EBI-373586
    HSP90AB1P082382EBI-296058,EBI-352572
    VIMP086706EBI-296058,EBI-353844

    Protein-protein interaction databases

    BioGridi106711. 45 interactions.
    DIPiDIP-32583N.
    IntActiP31751. 22 interactions.
    MINTiMINT-87790.
    STRINGi9606.ENSP00000375892.

    Structurei

    Secondary structure

    1
    481
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi6 – 1510Combined sources
    Beta strandi17 – 204Combined sources
    Beta strandi22 – 309Combined sources
    Turni31 – 333Combined sources
    Beta strandi34 – 407Combined sources
    Beta strandi45 – 473Combined sources
    Beta strandi52 – 565Combined sources
    Beta strandi58 – 603Combined sources
    Beta strandi62 – 654Combined sources
    Beta strandi67 – 759Combined sources
    Beta strandi86 – 927Combined sources
    Helixi93 – 11018Combined sources
    Helixi149 – 1513Combined sources
    Beta strandi152 – 1609Combined sources
    Beta strandi162 – 17110Combined sources
    Turni172 – 1743Combined sources
    Beta strandi177 – 1848Combined sources
    Helixi185 – 1906Combined sources
    Helixi194 – 20512Combined sources
    Beta strandi215 – 2206Combined sources
    Beta strandi222 – 2309Combined sources
    Helixi237 – 2448Combined sources
    Helixi249 – 26820Combined sources
    Beta strandi280 – 2834Combined sources
    Beta strandi289 – 2913Combined sources
    Beta strandi298 – 3003Combined sources
    Beta strandi310 – 3123Combined sources
    Helixi314 – 3163Combined sources
    Helixi319 – 3224Combined sources
    Beta strandi323 – 3253Combined sources
    Helixi331 – 34515Combined sources
    Beta strandi351 – 3533Combined sources
    Helixi355 – 36410Combined sources
    Beta strandi371 – 3733Combined sources
    Helixi375 – 38410Combined sources
    Turni389 – 3913Combined sources
    Turni393 – 3953Combined sources
    Turni397 – 3993Combined sources
    Helixi400 – 4045Combined sources
    Helixi407 – 4093Combined sources
    Helixi414 – 4185Combined sources
    Beta strandi431 – 4344Combined sources
    Beta strandi437 – 4393Combined sources
    Helixi441 – 4444Combined sources
    Beta strandi474 – 4763Combined sources
    Turni477 – 4793Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1GZKX-ray2.30A146-460[»]
    1GZNX-ray2.50A146-480[»]
    1GZOX-ray2.75A146-460[»]
    1MRVX-ray2.80A143-481[»]
    1MRYX-ray2.80A143-481[»]
    1O6KX-ray1.70A146-481[»]
    1O6LX-ray1.60A146-467[»]
    1P6SNMR-A1-111[»]
    2JDOX-ray1.80A146-467[»]
    2JDRX-ray2.30A146-467[»]
    2UW9X-ray2.10A146-467[»]
    2X39X-ray1.93A146-467[»]
    2XH5X-ray2.72A146-479[»]
    3D0EX-ray2.00A/B146-480[»]
    3E87X-ray2.30A/B146-480[»]
    3E88X-ray2.50A/B146-480[»]
    3E8DX-ray2.70A/B146-480[»]
    DisProtiDP00304.
    ProteinModelPortaliP31751.
    SMRiP31751. Positions 1-480.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP31751.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini5 – 108104PHPROSITE-ProRule annotationAdd
    BLAST
    Domaini152 – 409258Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini410 – 48172AGC-kinase C-terminalAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni230 – 2323Inhibitor binding
    Regioni277 – 2793Inhibitor binding
    Regioni292 – 2932Inhibitor 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.

    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.
    GeneTreeiENSGT00770000120449.
    HOGENOMiHOG000233033.
    HOVERGENiHBG108317.
    InParanoidiP31751.
    KOiK04456.
    OrthoDBiEOG7Q5HCW.
    PhylomeDBiP31751.
    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. AlignAdd to basket

    Isoform 1 (identifier: P31751-1) [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
    MNEVSVIKEG WLHKRGEYIK TWRPRYFLLK SDGSFIGYKE RPEAPDQTLP
    60 70 80 90 100
    PLNNFSVAEC QLMKTERPRP NTFVIRCLQW TTVIERTFHV DSPDEREEWM
    110 120 130 140 150
    RAIQMVANSL KQRAPGEDPM DYKCGSPSDS STTEEMEVAV SKARAKVTMN
    160 170 180 190 200
    DFDYLKLLGK GTFGKVILVR EKATGRYYAM KILRKEVIIA KDEVAHTVTE
    210 220 230 240 250
    SRVLQNTRHP FLTALKYAFQ THDRLCFVME YANGGELFFH LSRERVFTEE
    260 270 280 290 300
    RARFYGAEIV SALEYLHSRD VVYRDIKLEN LMLDKDGHIK ITDFGLCKEG
    310 320 330 340 350
    ISDGATMKTF CGTPEYLAPE VLEDNDYGRA VDWWGLGVVM YEMMCGRLPF
    360 370 380 390 400
    YNQDHERLFE LILMEEIRFP RTLSPEAKSL LAGLLKKDPK QRLGGGPSDA
    410 420 430 440 450
    KEVMEHRFFL SINWQDVVQK KLLPPFKPQV TSEVDTRYFD DEFTAQSITI
    460 470 480
    TPPDRYDSLG LLELDQRTHF PQFSYSASIR E
    Length:481
    Mass (Da):55,769
    Last modified:November 1, 1995 - v2
    Checksum:iB18C87A7246BFB24
    GO
    Isoform 2 (identifier: P31751-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         278-320: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:438
    Mass (Da):51,083
    Checksum:iEEAF3B6E42F6A5C1
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti478 – 4814SIRE → FREEKDLLMSLFVSLILFSD FSSLKSHSFSSNFILLSFSS LKK in AAA36585 (PubMed:1801921).Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti17 – 171E → K in HIHGHH; exhibits plasma membrane localization in serum-starved cells and produced inappropriate tonic nuclear exclusion of FOXO1 in preadipocytes. 1 Publication
    VAR_067309
    Natural varianti188 – 1881I → V.1 Publication
    Corresponds to variant rs55859611 [ dbSNP | Ensembl ].
    VAR_040356
    Natural varianti208 – 2081R → K.1 Publication
    Corresponds to variant rs35817154 [ dbSNP | Ensembl ].
    VAR_040357
    Natural varianti274 – 2741R → H in NIDDM; associated with typical metabolic dyslipidemia with elevated fastin triglyceride, high VLDL triglyceride/cholesterol ratios, low HDL cholesterol levels and high small dense LDL levels; de novo lipogenesis and liver fat are also significantly elevated in this subject. 1 Publication
    VAR_067310

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei278 – 32043Missing in isoform 2. 1 PublicationVSP_056930Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M77198 mRNA. Translation: AAA36585.1.
    M95936 mRNA. Translation: AAA58364.1.
    AK314619 mRNA. Translation: BAG37185.1.
    AC118344 Genomic DNA. No translation available.
    BC032709 mRNA. Translation: AAH32709.1.
    BC120995 mRNA. Translation: AAI20996.1.
    BC120994 mRNA. Translation: AAI20995.1.
    AY708392 Genomic DNA. Translation: AAT97984.1.
    CCDSiCCDS12552.1. [P31751-1]
    PIRiA46288.
    RefSeqiNP_001617.1. NM_001626.5. [P31751-1]
    UniGeneiHs.631535.

    Genome annotation databases

    EnsembliENST00000311278; ENSP00000309428; ENSG00000105221. [P31751-2]
    ENST00000392038; ENSP00000375892; ENSG00000105221. [P31751-1]
    ENST00000424901; ENSP00000399532; ENSG00000105221. [P31751-2]
    GeneIDi208.
    KEGGihsa:208.
    UCSCiuc002one.3. human. [P31751-1]
    uc010egs.3. human.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology
    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M77198 mRNA. Translation: AAA36585.1.
    M95936 mRNA. Translation: AAA58364.1.
    AK314619 mRNA. Translation: BAG37185.1.
    AC118344 Genomic DNA. No translation available.
    BC032709 mRNA. Translation: AAH32709.1.
    BC120995 mRNA. Translation: AAI20996.1.
    BC120994 mRNA. Translation: AAI20995.1.
    AY708392 Genomic DNA. Translation: AAT97984.1.
    CCDSiCCDS12552.1. [P31751-1]
    PIRiA46288.
    RefSeqiNP_001617.1. NM_001626.5. [P31751-1]
    UniGeneiHs.631535.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1GZKX-ray2.30A146-460[»]
    1GZNX-ray2.50A146-480[»]
    1GZOX-ray2.75A146-460[»]
    1MRVX-ray2.80A143-481[»]
    1MRYX-ray2.80A143-481[»]
    1O6KX-ray1.70A146-481[»]
    1O6LX-ray1.60A146-467[»]
    1P6SNMR-A1-111[»]
    2JDOX-ray1.80A146-467[»]
    2JDRX-ray2.30A146-467[»]
    2UW9X-ray2.10A146-467[»]
    2X39X-ray1.93A146-467[»]
    2XH5X-ray2.72A146-479[»]
    3D0EX-ray2.00A/B146-480[»]
    3E87X-ray2.30A/B146-480[»]
    3E88X-ray2.50A/B146-480[»]
    3E8DX-ray2.70A/B146-480[»]
    DisProtiDP00304.
    ProteinModelPortaliP31751.
    SMRiP31751. Positions 1-480.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi106711. 45 interactions.
    DIPiDIP-32583N.
    IntActiP31751. 22 interactions.
    MINTiMINT-87790.
    STRINGi9606.ENSP00000375892.

    Chemistry

    BindingDBiP31751.
    ChEMBLiCHEMBL2111353.
    GuidetoPHARMACOLOGYi1480.

    PTM databases

    PhosphoSiteiP31751.

    Polymorphism and mutation databases

    BioMutaiAKT2.
    DMDMi1170703.

    Proteomic databases

    MaxQBiP31751.
    PaxDbiP31751.
    PRIDEiP31751.

    Protocols and materials databases

    DNASUi208.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000311278; ENSP00000309428; ENSG00000105221. [P31751-2]
    ENST00000392038; ENSP00000375892; ENSG00000105221. [P31751-1]
    ENST00000424901; ENSP00000399532; ENSG00000105221. [P31751-2]
    GeneIDi208.
    KEGGihsa:208.
    UCSCiuc002one.3. human. [P31751-1]
    uc010egs.3. human.

    Organism-specific databases

    CTDi208.
    GeneCardsiGC19M040736.
    HGNCiHGNC:392. AKT2.
    HPAiCAB004204.
    MIMi125853. phenotype.
    164731. gene.
    240900. phenotype.
    neXtProtiNX_P31751.
    Orphaneti79085. Familial partial lipodystrophy due to AKT2 mutations.
    293964. Hypoinsulinemic hypoglycemia and body hemihypertrophy.
    PharmGKBiPA24685.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00770000120449.
    HOGENOMiHOG000233033.
    HOVERGENiHBG108317.
    InParanoidiP31751.
    KOiK04456.
    OrthoDBiEOG7Q5HCW.
    PhylomeDBiP31751.
    TreeFamiTF102004.

    Enzyme and pathway databases

    BRENDAi2.7.11.1. 2681.
    ReactomeiREACT_115662. Downregulation of ERBB2:ERBB3 signaling.
    REACT_12442. AKT phosphorylates targets in the nucleus.
    REACT_12447. Negative regulation of the PI3K/AKT network.
    REACT_12564. AKT phosphorylates targets in the cytosol.
    REACT_13655. AKT-mediated inactivation of FOXO1A.
    REACT_1451. PDE3B signalling.
    REACT_147867. Translocation of GLUT4 to the plasma membrane.
    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_263991. VEGFR2 mediated vascular permeability.
    REACT_264178. deactivation of the beta-catenin transactivating complex.
    REACT_355377. TP53 Regulates Metabolic Genes.
    REACT_355468. Constitutive Signaling by AKT1 E17K in Cancer.
    REACT_549. Activation of BAD and translocation to mitochondria.
    REACT_6743. Inhibition of TSC complex formation by PKB.
    REACT_75829. PIP3 activates AKT signaling.
    REACT_790. Activation of PKB.
    SignaLinkiP31751.

    Miscellaneous databases

    ChiTaRSiAKT2. human.
    EvolutionaryTraceiP31751.
    GeneWikiiAKT2.
    GenomeRNAii208.
    NextBioi836.
    PROiP31751.
    SOURCEiSearch...

    Gene expression databases

    BgeeiP31751.
    CleanExiHS_AKT2.
    ExpressionAtlasiP31751. baseline and differential.
    GenevisibleiP31751. HS.

    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]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Molecular cloning of a second form of rac protein kinase."
      Jones P.F., Jakubowicz T., Hemmings B.A.
      Cell Regul. 2:1001-1009(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Epithelium.
    2. "AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas."
      Cheng J.Q., Godwin A.K., Bellacosa A., Taguchi T., Franke T.F., Hamilton T.C., Tsichlis P.N., Testa J.R.
      Proc. Natl. Acad. Sci. U.S.A. 89:9267-9271(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    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] (ISOFORM 1).
      Tissue: Placenta.
    4. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "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] (ISOFORMS 1 AND 2).
      Tissue: Lymph.
    6. NIEHS SNPs program
      Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 237-277.
    7. "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: CHARACTERIZATION, PHOSPHORYLATION AT THR-309 BY PDPK1.
    8. "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.
    9. Cited for: MUTAGENESIS OF THR-309 AND SER-474, PHOSPHORYLATION AT THR-309 AND SER-474.
    10. Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
    11. "Akt2 is implicated in skeletal muscle differentiation and specifically binds Prohibitin2/REA."
      Heron-Milhavet L., Mamaeva D., Rochat A., Lamb N.J., Fernandez A.
      J. Cell. Physiol. 214:158-165(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PBH2.
    12. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    13. Cited for: UBIQUITINATION BY TTC3, PHOSPHORYLATION AT THR-309 AND SER-474, MUTAGENESIS OF THR-309 AND SER-474.
    14. "ClipR-59 interacts with Akt and regulates Akt cellular compartmentalization."
      Ding J., Du K.
      Mol. Cell. Biol. 29:1459-1471(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CLIP3, SUBCELLULAR LOCATION.
    15. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-447; THR-451; SER-474 AND SER-478, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    16. Cited for: UBIQUITINATION, INTERACTION WITH TRAF6.
    17. Cited for: INVOLVEMENT IN CANCER.
    18. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    19. Cited for: REVIEW ON FUNCTION.
    20. "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.
    21. "Ankrd2/ARPP is a novel Akt2 specific substrate and regulates myogenic differentiation upon cellular exposure to H(2)O(2)."
      Cenni V., Bavelloni A., Beretti F., Tagliavini F., Manzoli L., Lattanzi G., Maraldi N.M., Cocco L., Marmiroli S.
      Mol. Biol. Cell 22:2946-2956(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN MUSCLE DIFFERENTIATION, INTERACTION WITH ANKRD2.
    22. "Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
      Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
      Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    23. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
      Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
      J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-34 AND THR-451, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    24. "Molecular mechanism for the regulation of protein kinase B/Akt by hydrophobic motif phosphorylation."
      Yang J., Cron P., Thompson V., Good V.M., Hess D., Hemmings B.A., Barford D.
      Mol. Cell 9:1227-1240(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 146-480.
    25. "Crystal structure of an activated Akt/protein kinase B ternary complex with GSK3-peptide and AMP-PNP."
      Yang J., Cron P., Good V.M., Thompson V., Hemmings B.A., Barford D.
      Nat. Struct. Biol. 9:940-944(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 146-467 IN COMPLEX WITH PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER AND MANGANESE, PHOSPHORYLATION AT THR-309.
    26. "Crystal structure of an inactive Akt2 kinase domain."
      Huang X., Begley M., Morgenstern K.A., Gu Y., Rose P., Zhao H., Zhu X.
      Structure 11:21-30(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 143-481, ATP-BINDING, SUBSTRATE-BINDING, DISULFIDE BOND.
    27. "Solution structure and backbone dynamics of the pleckstrin homology domain of the human protein kinase B (PKB/Akt). Interaction with inositol phosphates."
      Auguin D., Barthe P., Auge-Senegas M.T., Stern M.H., Noguchi M., Roumestand C.
      J. Biomol. NMR 28:137-155(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 1-111.
    28. Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 146-467, INHIBITOR-BINDING.
    29. "Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase."
      Heerding D.A., Rhodes N., Leber J.D., Clark T.J., Keenan R.M., Lafrance L.V., Li M., Safonov I.G., Takata D.T., Venslavsky J.W., Yamashita D.S., Choudhry A.E., Copeland R.A., Lai Z., Schaber M.D., Tummino P.J., Strum S.L., Wood E.R.
      , Duckett D.R., Eberwein D., Knick V.B., Lansing T.J., McConnell R.T., Zhang S., Minthorn E.A., Concha N.O., Warren G.L., Kumar R.
      J. Med. Chem. 51:5663-5679(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 146-480, ENZYME REGULATION.
    30. Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 146-480, ENZYME REGULATION.
    31. Cited for: VARIANT NIDDM HIS-274.
    32. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-188 AND LYS-208.
    33. Cited for: ASSOCIATION OF VARIANT NIDDM HIS-274 WITH TYPICAL METABOLIC DYSLIPIDEMIA.
    34. Cited for: VARIANT HIHGHH LYS-17.

    Entry informationi

    Entry nameiAKT2_HUMAN
    AccessioniPrimary (citable) accession number: P31751
    Secondary accession number(s): B2RBD8
    , Q05BV0, Q0VAN0, Q0VAN1, Q68GC0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1993
    Last sequence update: November 1, 1995
    Last modified: June 24, 2015
    This is version 169 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 19
      Human chromosome 19: 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

    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 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.