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UniProtKB - P31751 (AKT2_HUMAN)

Protein

RAC-beta serine/threonine-protein kinase

Gene

AKT2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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'.

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

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Activity 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)DescriptionActionsGraphical viewLength
    Binding sitei181ATPPROSITE-ProRule annotation1
    Binding sitei181Inhibitor1
    Binding sitei200Inhibitor1
    Binding sitei232Inhibitor; via amide nitrogen1
    Binding sitei236Inhibitor1
    Active sitei275Proton acceptorPROSITE-ProRule annotation1
    Binding sitei279Inhibitor; via carbonyl oxygen1
    Metal bindingi280Manganese1 Publication1
    Metal bindingi293Manganese1 Publication1
    Binding sitei293Inhibitor1
    Binding sitei294Inhibitor; via amide nitrogen1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi158 – 166ATPPROSITE-ProRule annotation9

    GO - Molecular functioni

    • ATP binding Source: UniProtKB
    • metal ion binding Source: UniProtKB-KW
    • protein serine/threonine kinase activity Source: UniProtKB
    View the complete GO annotation on QuickGO ...

    GO - Biological processi

    View the complete GO annotation on QuickGO ...

    Keywordsi

    Molecular functionDevelopmental protein, Kinase, Serine/threonine-protein kinase, Transferase
    Biological processApoptosis, Carbohydrate metabolism, Glucose metabolism, Glycogen biosynthesis, Glycogen metabolism, Sugar transport, Translation regulation, Transport
    LigandATP-binding, Manganese, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.1 2681
    ReactomeiR-HSA-111447 Activation of BAD and translocation to mitochondria
    R-HSA-1257604 PIP3 activates AKT signaling
    R-HSA-1358803 Downregulation of ERBB2:ERBB3 signaling
    R-HSA-1445148 Translocation of SLC2A4 (GLUT4) to the plasma membrane
    R-HSA-165158 Activation of AKT2
    R-HSA-165160 PDE3B signalling
    R-HSA-165181 Inhibition of TSC complex formation by PKB
    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-211163 AKT-mediated inactivation of FOXO1A
    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-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-69202 Cyclin E associated events during G1/S transition
    R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry
    R-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs
    R-HSA-8941332 RUNX2 regulates genes involved in cell migration
    R-HSA-8948751 Regulation of PTEN stability and activity
    SABIO-RKiP31751
    SignaLinkiP31751
    SIGNORiP31751

    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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
    Proteomesi
    • UP000005640 Componenti: Chromosome 19

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000105221.16
    HGNCiHGNC:392 AKT2
    MIMi164731 gene
    neXtProtiNX_P31751

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Endosome, 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)DescriptionActionsGraphical viewLength
    Natural variantiVAR_067310274R → 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 PublicationCorresponds to variant dbSNP:rs121434593EnsemblClinVar.1
    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)DescriptionActionsGraphical viewLength
    Natural variantiVAR_06730917E → K in HIHGHH; exhibits plasma membrane localization in serum-starved cells and produced inappropriate tonic nuclear exclusion of FOXO1 in preadipocytes. 1 PublicationCorresponds to variant dbSNP:rs387906659EnsemblClinVar.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi309T → A: Impairs interaction with TTC3; when associated with A-474. 2 Publications1
    Mutagenesisi309T → E: Constitutively active; when associated with D-474. 2 Publications1
    Mutagenesisi474S → A: Impairs interaction with TTC3; when associated with A-309. 2 Publications1
    Mutagenesisi474S → D: Constitutively active; when associated with E-309. 2 Publications1

    Keywords - Diseasei

    Diabetes mellitus, Disease mutation, Proto-oncogene

    Organism-specific databases

    DisGeNETi208
    MalaCardsiAKT2
    MIMi125853 phenotype
    240900 phenotype
    OpenTargetsiENSG00000105221
    Orphaneti79085 AKT2-related familial partial lipodystrophy
    293964 Hypoinsulinemic hypoglycemia and body hemihypertrophy
    PharmGKBiPA24685

    Chemistry databases

    ChEMBLiCHEMBL2431
    DrugBankiDB08073 (2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE
    DB07859 4-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINE
    DB07947 ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE
    GuidetoPHARMACOLOGYi1480

    Polymorphism and mutation databases

    BioMutaiAKT2
    DMDMi1170703

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000856081 – 481RAC-beta serine/threonine-protein kinaseAdd BLAST481

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei1N-acetylmethionineCombined sources1
    Modified residuei34PhosphoserineCombined sources1
    Disulfide bondi60 ↔ 77By similarity
    Modified residuei126PhosphoserineCombined sources1
    Glycosylationi128O-linked (GlcNAc) serineBy similarity1
    Glycosylationi131O-linked (GlcNAc) serineBy similarity1
    Disulfide bondi297 ↔ 3111 Publication
    Glycosylationi306O-linked (GlcNAc) threonineBy similarity1
    Modified residuei309Phosphothreonine; by PDPK14 Publications1
    Glycosylationi313O-linked (GlcNAc) threonineBy similarity1
    Modified residuei447PhosphoserineCombined sources1
    Modified residuei451PhosphothreonineCombined sources1
    Modified residuei474PhosphoserineCombined sources2 Publications1
    Modified residuei478PhosphoserineCombined sources1

    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

    EPDiP31751
    MaxQBiP31751
    PaxDbiP31751
    PeptideAtlasiP31751
    PRIDEiP31751
    ProteomicsDBi54801

    PTM databases

    iPTMnetiP31751
    PhosphoSitePlusiP31751

    Expressioni

    Tissue specificityi

    Expressed in all cell types so far analyzed.

    Gene expression databases

    BgeeiENSG00000105221 Expressed in 207 organ(s), highest expression level in right hemisphere of cerebellum
    CleanExiHS_AKT2
    ExpressionAtlasiP31751 baseline and differential
    GenevisibleiP31751 HS

    Organism-specific databases

    HPAiCAB004204
    HPA064521

    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). Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529).By similarity7 Publications

    Binary interactionsi

    Protein-protein interaction databases

    BioGridi106711, 67 interactors
    CORUMiP31751
    DIPiDIP-32583N
    ELMiP31751
    IntActiP31751, 33 interactors
    MINTiP31751
    STRINGi9606.ENSP00000375892

    Chemistry databases

    BindingDBiP31751

    Structurei

    Secondary structure

    1481
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    DisProtiDP00304
    ProteinModelPortaliP31751
    SMRiP31751
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP31751

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini5 – 108PHPROSITE-ProRule annotationAdd BLAST104
    Domaini152 – 409Protein kinasePROSITE-ProRule annotationAdd BLAST258
    Domaini410 – 481AGC-kinase C-terminalAdd BLAST72

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni230 – 232Inhibitor binding3
    Regioni277 – 279Inhibitor binding3
    Regioni292 – 293Inhibitor binding2

    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

    Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.Curated

    Phylogenomic databases

    eggNOGiKOG0598 Eukaryota
    ENOG410XNPH LUCA
    GeneTreeiENSGT00930000150811
    HOGENOMiHOG000233033
    HOVERGENiHBG108317
    InParanoidiP31751
    KOiK04456
    OrthoDBiEOG091G06FF
    PhylomeDBiP31751
    TreeFamiTF102004

    Family and domain databases

    CDDicd01241 PH_PKB, 1 hit
    cd05595 STKc_PKB_beta, 1 hit
    Gene3Di2.30.29.30, 1 hit
    InterProiView protein in InterPro
    IPR000961 AGC-kinase_C
    IPR034677 Akt2
    IPR011009 Kinase-like_dom_sf
    IPR011993 PH-like_dom_sf
    IPR001849 PH_domain
    IPR039026 PH_PKB
    IPR017892 Pkinase_C
    IPR000719 Prot_kinase_dom
    IPR017441 Protein_kinase_ATP_BS
    IPR039027 RAC_alpha/beta
    IPR008271 Ser/Thr_kinase_AS
    PANTHERiPTHR24356:SF176 PTHR24356:SF176, 1 hit
    PfamiView protein in Pfam
    PF00169 PH, 1 hit
    PF00069 Pkinase, 1 hit
    PF00433 Pkinase_C, 1 hit
    SMARTiView protein in SMART
    SM00233 PH, 1 hit
    SM00133 S_TK_X, 1 hit
    SM00220 S_TKc, 1 hit
    SUPFAMiSSF56112 SSF56112, 1 hit
    PROSITEiView protein in PROSITE
    PS51285 AGC_KINASE_CTER, 1 hit
    PS50003 PH_DOMAIN, 1 hit
    PS00107 PROTEIN_KINASE_ATP, 1 hit
    PS50011 PROTEIN_KINASE_DOM, 1 hit
    PS00108 PROTEIN_KINASE_ST, 1 hit

    Sequences (2+)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 2 described isoforms and 22 potential isoforms that are computationally mapped.Show allAlign All

    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

    Computationally mapped potential isoform sequencesi

    There are 22 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    		Gene namesLengthAnnotation
    M0R0P9M0R0P9_HUMAN
    Non-specific serine/threonine prote...
    AKT2
    		450Annotation score:
    C9JHS6C9JHS6_HUMAN
    RAC-beta serine/threonine-protein k...
    AKT2
    		184Annotation score:
    J3QLS6J3QLS6_HUMAN
    RAC-beta serine/threonine-protein k...
    AKT2
    		157Annotation score:
    M0QZK3M0QZK3_HUMAN
    RAC-beta serine/threonine-protein k...
    AKT2
    		151Annotation score:
    J3QKW1J3QKW1_HUMAN
    RAC-beta serine/threonine-protein k...
    AKT2
    		292Annotation score:
    J3QL45J3QL45_HUMAN
    RAC-beta serine/threonine-protein k...
    AKT2
    		106Annotation score:
    M0R283M0R283_HUMAN
    RAC-beta serine/threonine-protein k...
    AKT2
    		117Annotation score:
    M0R275M0R275_HUMAN
    RAC-beta serine/threonine-protein k...
    AKT2
    		129Annotation score:
    C9JIJ1C9JIJ1_HUMAN
    RAC-beta serine/threonine-protein k...
    AKT2
    		119Annotation score:
    A8MX96A8MX96_HUMAN
    RAC-beta serine/threonine-protein k...
    AKT2
    		133Annotation score:
    There are more potential isoformsShow all

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti478 – 481SIRE → FREEKDLLMSLFVSLILFSD FSSLKSHSFSSNFILLSFSS LKK in AAA36585 (PubMed:1801921).Curated4

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_06730917E → K in HIHGHH; exhibits plasma membrane localization in serum-starved cells and produced inappropriate tonic nuclear exclusion of FOXO1 in preadipocytes. 1 PublicationCorresponds to variant dbSNP:rs387906659EnsemblClinVar.1
    Natural variantiVAR_040356188I → V1 PublicationCorresponds to variant dbSNP:rs55859611Ensembl.1
    Natural variantiVAR_040357208R → K1 PublicationCorresponds to variant dbSNP:rs35817154Ensembl.1
    Natural variantiVAR_067310274R → 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 PublicationCorresponds to variant dbSNP:rs121434593EnsemblClinVar.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_056930278 – 320Missing in isoform 2. 1 PublicationAdd BLAST43

    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]
    CCDS82350.1 [P31751-2]
    PIRiA46288
    RefSeqiNP_001317440.1, NM_001330511.1 [P31751-2]
    NP_001617.1, NM_001626.5 [P31751-1]
    XP_011524916.1, XM_011526614.1 [P31751-1]
    XP_011524917.1, XM_011526615.1 [P31751-1]
    XP_011524918.1, XM_011526616.1 [P31751-1]
    XP_011524920.1, XM_011526618.1 [P31751-1]
    XP_011524921.1, XM_011526619.1 [P31751-1]
    XP_011524922.1, XM_011526620.1 [P31751-1]
    XP_016881959.1, XM_017026470.1 [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
    UCSCiuc002onf.3 human [P31751-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    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]
    CCDS82350.1 [P31751-2]
    PIRiA46288
    RefSeqiNP_001317440.1, NM_001330511.1 [P31751-2]
    NP_001617.1, NM_001626.5 [P31751-1]
    XP_011524916.1, XM_011526614.1 [P31751-1]
    XP_011524917.1, XM_011526615.1 [P31751-1]
    XP_011524918.1, XM_011526616.1 [P31751-1]
    XP_011524920.1, XM_011526618.1 [P31751-1]
    XP_011524921.1, XM_011526619.1 [P31751-1]
    XP_011524922.1, XM_011526620.1 [P31751-1]
    XP_016881959.1, XM_017026470.1 [P31751-1]
    UniGeneiHs.631535

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    		PDB 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
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi106711, 67 interactors
    CORUMiP31751
    DIPiDIP-32583N
    ELMiP31751
    IntActiP31751, 33 interactors
    MINTiP31751
    STRINGi9606.ENSP00000375892

    Chemistry databases

    BindingDBiP31751
    ChEMBLiCHEMBL2431
    DrugBankiDB08073 (2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE
    DB07859 4-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINE
    DB07947 ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE
    GuidetoPHARMACOLOGYi1480

    PTM databases

    iPTMnetiP31751
    PhosphoSitePlusiP31751

    Polymorphism and mutation databases

    BioMutaiAKT2
    DMDMi1170703

    Proteomic databases

    EPDiP31751
    MaxQBiP31751
    PaxDbiP31751
    PeptideAtlasiP31751
    PRIDEiP31751
    ProteomicsDBi54801

    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
    UCSCiuc002onf.3 human [P31751-1]

    Organism-specific databases

    CTDi208
    DisGeNETi208
    EuPathDBiHostDB:ENSG00000105221.16
    GeneCardsiAKT2
    HGNCiHGNC:392 AKT2
    HPAiCAB004204
    HPA064521
    MalaCardsiAKT2
    MIMi125853 phenotype
    164731 gene
    240900 phenotype
    neXtProtiNX_P31751
    OpenTargetsiENSG00000105221
    Orphaneti79085 AKT2-related familial partial lipodystrophy
    293964 Hypoinsulinemic hypoglycemia and body hemihypertrophy
    PharmGKBiPA24685
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0598 Eukaryota
    ENOG410XNPH LUCA
    GeneTreeiENSGT00930000150811
    HOGENOMiHOG000233033
    HOVERGENiHBG108317
    InParanoidiP31751
    KOiK04456
    OrthoDBiEOG091G06FF
    PhylomeDBiP31751
    TreeFamiTF102004

    Enzyme and pathway databases

    BRENDAi2.7.11.1 2681
    ReactomeiR-HSA-111447 Activation of BAD and translocation to mitochondria
    R-HSA-1257604 PIP3 activates AKT signaling
    R-HSA-1358803 Downregulation of ERBB2:ERBB3 signaling
    R-HSA-1445148 Translocation of SLC2A4 (GLUT4) to the plasma membrane
    R-HSA-165158 Activation of AKT2
    R-HSA-165160 PDE3B signalling
    R-HSA-165181 Inhibition of TSC complex formation by PKB
    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-211163 AKT-mediated inactivation of FOXO1A
    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-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-69202 Cyclin E associated events during G1/S transition
    R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry
    R-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs
    R-HSA-8941332 RUNX2 regulates genes involved in cell migration
    R-HSA-8948751 Regulation of PTEN stability and activity
    SABIO-RKiP31751
    SignaLinkiP31751
    SIGNORiP31751

    Miscellaneous databases

    ChiTaRSiAKT2 human
    EvolutionaryTraceiP31751
    GeneWikiiAKT2
    GenomeRNAii208
    PROiPR:P31751
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000105221 Expressed in 207 organ(s), highest expression level in right hemisphere of cerebellum
    CleanExiHS_AKT2
    ExpressionAtlasiP31751 baseline and differential
    GenevisibleiP31751 HS

    Family and domain databases

    CDDicd01241 PH_PKB, 1 hit
    cd05595 STKc_PKB_beta, 1 hit
    Gene3Di2.30.29.30, 1 hit
    InterProiView protein in InterPro
    IPR000961 AGC-kinase_C
    IPR034677 Akt2
    IPR011009 Kinase-like_dom_sf
    IPR011993 PH-like_dom_sf
    IPR001849 PH_domain
    IPR039026 PH_PKB
    IPR017892 Pkinase_C
    IPR000719 Prot_kinase_dom
    IPR017441 Protein_kinase_ATP_BS
    IPR039027 RAC_alpha/beta
    IPR008271 Ser/Thr_kinase_AS
    PANTHERiPTHR24356:SF176 PTHR24356:SF176, 1 hit
    PfamiView protein in Pfam
    PF00169 PH, 1 hit
    PF00069 Pkinase, 1 hit
    PF00433 Pkinase_C, 1 hit
    SMARTiView protein in SMART
    SM00233 PH, 1 hit
    SM00133 S_TK_X, 1 hit
    SM00220 S_TKc, 1 hit
    SUPFAMiSSF56112 SSF56112, 1 hit
    PROSITEiView protein in PROSITE
    PS51285 AGC_KINASE_CTER, 1 hit
    PS50003 PH_DOMAIN, 1 hit
    PS00107 PROTEIN_KINASE_ATP, 1 hit
    PS50011 PROTEIN_KINASE_DOM, 1 hit
    PS00108 PROTEIN_KINASE_ST, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiAKT2_HUMAN
    AccessioniPrimary (citable) accession number: P31751
    Secondary accession number(s): B2RBD8
    , Q05BV0, Q0VAN0, Q0VAN1, Q68GC0
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
    Last sequence update: November 1, 1995
    Last modified: November 7, 2018
    This is version 205 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    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. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
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