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Q9Y243

- AKT3_HUMAN

UniProt

Q9Y243 - AKT3_HUMAN

Protein

RAC-gamma serine/threonine-protein kinase

Gene

AKT3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 155 (01 Oct 2014)
      Sequence version 1 (01 Nov 1999)
      Previous versions | rss
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    Functioni

    AKT3 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. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis.2 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Enzyme regulationi

    Two specific sites, one in the kinase domain (Thr-305) and the other in the C-terminal regulatory region (Ser-472), need to be phosphorylated for its full activation By similarity. IGF-1 leads to the activation of AKT3, which may play a role in regulating cell survival.By similarity

    Kineticsi

    1. KM=87.9 µM for ATP (for purified and in vitro activated AKT3)1 Publication
    2. KM=12.4 µM for peptide substrate (for purified and in vitro activated AKT3)1 Publication
    3. KM=118.7 µM for ATP (for recombinant myristoylated AKT3 expressed and immunoprecipitated from Rat-1 cells)1 Publication
    4. KM=2.3 µM for peptide substrate (for recombinant myristoylated AKT3 expressed and immunoprecipitated from Rat-1 cells)1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei177 – 1771ATPPROSITE-ProRule annotation
    Active sitei271 – 2711Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi154 – 1629ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB
    2. protein binding Source: UniProtKB
    3. protein kinase activity Source: ProtInc
    4. protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    1. mitochondrial genome maintenance Source: UniProtKB
    2. protein phosphorylation Source: ProtInc
    3. signal transduction Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    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_147727. Constitutive PI3K/AKT Signaling in Cancer.
    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_75829. PIP3 activates AKT signaling.
    SignaLinkiQ9Y243.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    RAC-gamma serine/threonine-protein kinase (EC:2.7.11.1)
    Alternative name(s):
    Protein kinase Akt-3
    Protein kinase B gamma
    Short name:
    PKB gamma
    RAC-PK-gamma
    STK-2
    Gene namesi
    Name:AKT3
    Synonyms:PKBG
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:393. AKT3.

    Subcellular locationi

    Nucleus 1 Publication. Cytoplasm 1 Publication. Membrane 1 Publication; Peripheral membrane protein 1 Publication
    Note: Membrane-associated after cell stimulation leading to its translocation.

    GO - Cellular componenti

    1. cytoplasm Source: HPA
    2. Golgi apparatus Source: HPA
    3. nucleus Source: HPA
    4. plasma membrane Source: HPA

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    AKT3 is a key modulator of several tumors like melanoma, glioma and ovarian cancer. Active AKT3 increases progressively during melanoma tumor progression with highest levels present in advanced-stage metastatic melanomas. Promotes melanoma tumorigenesis by decreasing apoptosis. Plays a key role in the genesis of ovarian cancers through modulation of G2/M phase transition. With AKT2, plays a pivotal role in the biology of glioblastoma.
    Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH) [MIM:603387]: A syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti17 – 171E → K in MPPH and melanoma; results in activation of AKT. 3 Publications
    VAR_065830
    Natural varianti229 – 2291N → S in MPPH. 1 Publication
    VAR_069260
    Natural varianti465 – 4651R → W in MPPH; disease phenotype overlaps with megalencephaly-capillary malformation syndrome. 1 Publication
    VAR_069261

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi305 – 3051T → A: No activation after pervanadate treatment. 2 Publications
    Mutagenesisi305 – 3051T → D: 2-fold increase of phosphorylation steady state level, no activation after pervanadate treatment. 2 Publications
    Mutagenesisi447 – 4471T → A: No effect. 2 Publications
    Mutagenesisi447 – 4471T → D: No effect. 2 Publications
    Mutagenesisi472 – 4721S → A: 67% decrease of activity after pervanadate treatment. 1 Publication
    Mutagenesisi472 – 4721S → D: 1.4-fold increase of phosphorylation steady state level, 50% decrease of activity after pervanadate treatment. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi603387. phenotype.
    Orphaneti99802. Hemimegalencephaly.
    83473. Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus.
    PharmGKBiPA24686.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 479478RAC-gamma serine/threonine-protein kinasePRO_0000085611Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserine1 Publication
    Disulfide bondi59 ↔ 76By similarity
    Disulfide bondi293 ↔ 307By similarity
    Glycosylationi302 – 3021O-linked (GlcNAc)By similarity
    Modified residuei305 – 3051Phosphothreonine; by PDPK11 Publication
    Glycosylationi309 – 3091O-linked (GlcNAc)By similarity
    Modified residuei472 – 4721Phosphoserine; by PKC/PRKCZ1 Publication

    Post-translational modificationi

    Phosphorylation on Thr-305 and Ser-472 is required for full activity.By similarity
    Ubiquitinated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome.3 Publications
    O-GlcNAcylation at Thr-302 and Thr-309 inhibits activating phosphorylation at Thr-305 via disrupting the interaction between AKT and PDK1.By similarity

    Keywords - PTMi

    Acetylation, Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ9Y243.
    PaxDbiQ9Y243.
    PRIDEiQ9Y243.

    PTM databases

    PhosphoSiteiQ9Y243.

    Expressioni

    Tissue specificityi

    In adult tissues, it is highly expressed in brain, lung and kidney, but weakly in heart, testis and liver. In fetal tissues, it is highly expressed in heart, liver and brain and not at all in kidney.

    Gene expression databases

    ArrayExpressiQ9Y243.
    BgeeiQ9Y243.
    CleanExiHS_AKT3.
    GenevestigatoriQ9Y243.

    Organism-specific databases

    HPAiCAB013090.
    HPA026441.

    Interactioni

    Subunit structurei

    Interacts (via PH domain) with TCL1A; this enhances AKT3 phosphorylation and activation. Interacts with TRAF6.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CASP3P425742EBI-296115,EBI-524064
    CDC37Q165432EBI-296115,EBI-295634

    Protein-protein interaction databases

    BioGridi115318. 9 interactions.
    DIPiDIP-32584N.
    IntActiQ9Y243. 7 interactions.
    MINTiMINT-222821.
    STRINGi9606.ENSP00000263826.

    Structurei

    Secondary structure

    1
    479
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi6 – 1510
    Beta strandi17 – 3014
    Beta strandi33 – 419
    Helixi44 – 463
    Beta strandi51 – 555
    Beta strandi60 – 645
    Beta strandi66 – 683
    Beta strandi71 – 755
    Turni80 – 823
    Beta strandi84 – 885
    Helixi92 – 11322

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2X18X-ray1.46A/B/C/D/E/F/G/H1-118[»]
    ProteinModelPortaliQ9Y243.
    SMRiQ9Y243. Positions 3-476.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini5 – 107103PHPROSITE-ProRule annotationAdd
    BLAST
    Domaini148 – 405258Protein kinasePROSITE-ProRule annotationAdd
    BLAST
    Domaini406 – 47974AGC-kinase C-terminalAdd
    BLAST

    Domaini

    Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI3K) 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.
    HOGENOMiHOG000233033.
    HOVERGENiHBG108317.
    InParanoidiQ9Y243.
    KOiK04456.
    OMAiMRHSFFA.
    OrthoDBiEOG7Q5HCW.
    PhylomeDBiQ9Y243.
    TreeFamiTF102004.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    InterProiIPR000961. AGC-kinase_C.
    IPR011009. Kinase-like_dom.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR017892. Pkinase_C.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00169. PH. 1 hit.
    PF00069. Pkinase. 1 hit.
    PF00433. Pkinase_C. 1 hit.
    [Graphical view]
    SMARTiSM00233. PH. 1 hit.
    SM00133. S_TK_X. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
    PS50003. PH_DOMAIN. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9Y243-1) [UniParc]FASTAAdd to Basket

    Also known as: PKB gamma

    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

    MSDVTIVKEG WVQKRGEYIK NWRPRYFLLK TDGSFIGYKE KPQDVDLPYP    50
    LNNFSVAKCQ LMKTERPKPN TFIIRCLQWT TVIERTFHVD TPEEREEWTE 100
    AIQAVADRLQ RQEEERMNCS PTSQIDNIGE EEMDASTTHH KRKTMNDFDY 150
    LKLLGKGTFG KVILVREKAS GKYYAMKILK KEVIIAKDEV AHTLTESRVL 200
    KNTRHPFLTS LKYSFQTKDR LCFVMEYVNG GELFFHLSRE RVFSEDRTRF 250
    YGAEIVSALD YLHSGKIVYR DLKLENLMLD KDGHIKITDF GLCKEGITDA 300
    ATMKTFCGTP EYLAPEVLED NDYGRAVDWW GLGVVMYEMM CGRLPFYNQD 350
    HEKLFELILM EDIKFPRTLS SDAKSLLSGL LIKDPNKRLG GGPDDAKEIM 400
    RHSFFSGVNW QDVYDKKLVP PFKPQVTSET DTRYFDEEFT AQTITITPPE 450
    KYDEDGMDCM DNERRPHFPQ FSYSASGRE 479
    Length:479
    Mass (Da):55,775
    Last modified:November 1, 1999 - v1
    Checksum:iF08BDDE6502E78FB
    GO
    Isoform 2 (identifier: Q9Y243-2) [UniParc]FASTAAdd to Basket

    Also known as: PKB gamma 1

    The sequence of this isoform differs from the canonical sequence as follows:
         452-479: YDEDGMDCMDNERRPHFPQFSYSASGRE → CQQSDCGMLGNWKK

    Show »
    Length:465
    Mass (Da):54,032
    Checksum:i592EF88B6937D1E0
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti279 – 2791L → R in AAI21155. (PubMed:15489334)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti17 – 171E → K in MPPH and melanoma; results in activation of AKT. 3 Publications
    VAR_065830
    Natural varianti171 – 1711G → R in a glioblastoma multiforme sample; somatic mutation. 1 Publication
    VAR_040358
    Natural varianti229 – 2291N → S in MPPH. 1 Publication
    VAR_069260
    Natural varianti465 – 4651R → W in MPPH; disease phenotype overlaps with megalencephaly-capillary malformation syndrome. 1 Publication
    VAR_069261

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei452 – 47928YDEDG…ASGRE → CQQSDCGMLGNWKK in isoform 2. 3 PublicationsVSP_004947Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF124141 mRNA. Translation: AAD29089.1.
    AF135794 mRNA. Translation: AAD24196.1.
    AF085234 mRNA. Translation: AAL40392.1.
    AJ245709 mRNA. Translation: CAB53537.1.
    AL117525 mRNA. Translation: CAB55977.1. Different termination.
    AY005799 mRNA. Translation: AAF91073.1.
    AL591721
    , AC096539, AL592151, AL662889 Genomic DNA. Translation: CAH71866.1.
    AL591721
    , AC096539, AL592151, AL662889 Genomic DNA. Translation: CAH71867.1.
    AL592151
    , AC096539, AL591721, AL662889 Genomic DNA. Translation: CAH72891.1.
    AL592151
    , AC096539, AL591721, AL662889 Genomic DNA. Translation: CAH72892.1.
    AL662889
    , AC096539, AL591721, AL592151 Genomic DNA. Translation: CAH73072.1.
    AL662889
    , AC096539, AL591721, AL592151 Genomic DNA. Translation: CAH73073.1.
    CH471148 Genomic DNA. Translation: EAW77093.1.
    CH471148 Genomic DNA. Translation: EAW77094.1.
    BC121154 mRNA. Translation: AAI21155.1.
    CCDSiCCDS31076.1. [Q9Y243-2]
    CCDS31077.1. [Q9Y243-1]
    PIRiA59380.
    T17287.
    RefSeqiNP_001193658.1. NM_001206729.1. [Q9Y243-2]
    NP_005456.1. NM_005465.4. [Q9Y243-1]
    NP_859029.1. NM_181690.2. [Q9Y243-2]
    XP_005273051.1. XM_005272994.2. [Q9Y243-1]
    XP_005273052.1. XM_005272995.2. [Q9Y243-1]
    XP_006711788.1. XM_006711725.1. [Q9Y243-2]
    XP_006725022.1. XM_006724959.1. [Q9Y243-1]
    XP_006725023.1. XM_006724960.1. [Q9Y243-1]
    XP_006725024.1. XM_006724961.1. [Q9Y243-2]
    UniGeneiHs.498292.

    Genome annotation databases

    EnsembliENST00000263826; ENSP00000263826; ENSG00000117020. [Q9Y243-1]
    ENST00000336199; ENSP00000336943; ENSG00000117020. [Q9Y243-2]
    ENST00000366539; ENSP00000355497; ENSG00000117020. [Q9Y243-1]
    ENST00000366540; ENSP00000355498; ENSG00000117020. [Q9Y243-2]
    GeneIDi10000.
    KEGGihsa:10000.
    UCSCiuc001hzz.1. human. [Q9Y243-2]
    uc001iab.2. human. [Q9Y243-1]

    Polymorphism databases

    DMDMi12643943.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF124141 mRNA. Translation: AAD29089.1 .
    AF135794 mRNA. Translation: AAD24196.1 .
    AF085234 mRNA. Translation: AAL40392.1 .
    AJ245709 mRNA. Translation: CAB53537.1 .
    AL117525 mRNA. Translation: CAB55977.1 . Different termination.
    AY005799 mRNA. Translation: AAF91073.1 .
    AL591721
    , AC096539 , AL592151 , AL662889 Genomic DNA. Translation: CAH71866.1 .
    AL591721
    , AC096539 , AL592151 , AL662889 Genomic DNA. Translation: CAH71867.1 .
    AL592151
    , AC096539 , AL591721 , AL662889 Genomic DNA. Translation: CAH72891.1 .
    AL592151
    , AC096539 , AL591721 , AL662889 Genomic DNA. Translation: CAH72892.1 .
    AL662889
    , AC096539 , AL591721 , AL592151 Genomic DNA. Translation: CAH73072.1 .
    AL662889
    , AC096539 , AL591721 , AL592151 Genomic DNA. Translation: CAH73073.1 .
    CH471148 Genomic DNA. Translation: EAW77093.1 .
    CH471148 Genomic DNA. Translation: EAW77094.1 .
    BC121154 mRNA. Translation: AAI21155.1 .
    CCDSi CCDS31076.1. [Q9Y243-2 ]
    CCDS31077.1. [Q9Y243-1 ]
    PIRi A59380.
    T17287.
    RefSeqi NP_001193658.1. NM_001206729.1. [Q9Y243-2 ]
    NP_005456.1. NM_005465.4. [Q9Y243-1 ]
    NP_859029.1. NM_181690.2. [Q9Y243-2 ]
    XP_005273051.1. XM_005272994.2. [Q9Y243-1 ]
    XP_005273052.1. XM_005272995.2. [Q9Y243-1 ]
    XP_006711788.1. XM_006711725.1. [Q9Y243-2 ]
    XP_006725022.1. XM_006724959.1. [Q9Y243-1 ]
    XP_006725023.1. XM_006724960.1. [Q9Y243-1 ]
    XP_006725024.1. XM_006724961.1. [Q9Y243-2 ]
    UniGenei Hs.498292.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2X18 X-ray 1.46 A/B/C/D/E/F/G/H 1-118 [» ]
    ProteinModelPortali Q9Y243.
    SMRi Q9Y243. Positions 3-476.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 115318. 9 interactions.
    DIPi DIP-32584N.
    IntActi Q9Y243. 7 interactions.
    MINTi MINT-222821.
    STRINGi 9606.ENSP00000263826.

    Chemistry

    BindingDBi Q9Y243.
    ChEMBLi CHEMBL4816.
    GuidetoPHARMACOLOGYi 2286.

    PTM databases

    PhosphoSitei Q9Y243.

    Polymorphism databases

    DMDMi 12643943.

    Proteomic databases

    MaxQBi Q9Y243.
    PaxDbi Q9Y243.
    PRIDEi Q9Y243.

    Protocols and materials databases

    DNASUi 10000.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000263826 ; ENSP00000263826 ; ENSG00000117020 . [Q9Y243-1 ]
    ENST00000336199 ; ENSP00000336943 ; ENSG00000117020 . [Q9Y243-2 ]
    ENST00000366539 ; ENSP00000355497 ; ENSG00000117020 . [Q9Y243-1 ]
    ENST00000366540 ; ENSP00000355498 ; ENSG00000117020 . [Q9Y243-2 ]
    GeneIDi 10000.
    KEGGi hsa:10000.
    UCSCi uc001hzz.1. human. [Q9Y243-2 ]
    uc001iab.2. human. [Q9Y243-1 ]

    Organism-specific databases

    CTDi 10000.
    GeneCardsi GC01M243653.
    HGNCi HGNC:393. AKT3.
    HPAi CAB013090.
    HPA026441.
    MIMi 603387. phenotype.
    611223. gene.
    neXtProti NX_Q9Y243.
    Orphaneti 99802. Hemimegalencephaly.
    83473. Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalus.
    PharmGKBi PA24686.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233033.
    HOVERGENi HBG108317.
    InParanoidi Q9Y243.
    KOi K04456.
    OMAi MRHSFFA.
    OrthoDBi EOG7Q5HCW.
    PhylomeDBi Q9Y243.
    TreeFami TF102004.

    Enzyme and pathway databases

    BRENDAi 2.7.11.1. 2681.
    Reactomei REACT_115662. Downregulation of ERBB2:ERBB3 signaling.
    REACT_12442. AKT phosphorylates targets in the nucleus.
    REACT_12447. Negative regulation of the PI3K/AKT network.
    REACT_12564. AKT phosphorylates targets in the cytosol.
    REACT_13655. AKT-mediated inactivation of FOXO1A.
    REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    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_75829. PIP3 activates AKT signaling.
    SignaLinki Q9Y243.

    Miscellaneous databases

    ChiTaRSi AKT3. human.
    GeneWikii AKT3.
    GenomeRNAii 10000.
    NextBioi 37765.
    PROi Q9Y243.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9Y243.
    Bgeei Q9Y243.
    CleanExi HS_AKT3.
    Genevestigatori Q9Y243.

    Family and domain databases

    Gene3Di 2.30.29.30. 1 hit.
    InterProi IPR000961. AGC-kinase_C.
    IPR011009. Kinase-like_dom.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR017892. Pkinase_C.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00169. PH. 1 hit.
    PF00069. Pkinase. 1 hit.
    PF00433. Pkinase_C. 1 hit.
    [Graphical view ]
    SMARTi SM00233. PH. 1 hit.
    SM00133. S_TK_X. 1 hit.
    SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS51285. AGC_KINASE_CTER. 1 hit.
    PS50003. PH_DOMAIN. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A human protein kinase B gamma with regulatory phosphorylation sites in the activation loop and in the C-terminal hydrophobic domain."
      Brodbeck D., Cron P., Hemmings B.A.
      J. Biol. Chem. 274:9133-9136(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS.
    2. "Identification of a human Akt3 (protein kinase B gamma) which contains the regulatory serine phosphorylation site."
      Nakatani K., Sakaue H., Thompson D.A., Weigel R.J., Roth R.A.
      Biochem. Biophys. Res. Commun. 257:906-910(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "Molecular cloning, expression and characterization of the human serine/threonine kinase Akt-3."
      Masure S., Haefner B., Wesselink J.-J., Hoefnagel E., Mortier E., Verhasselt P., Tuytelaars A., Gordon R., Richardson A.
      Eur. J. Biochem. 265:353-360(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Brain.
    4. "Cloning of a novel human cDNA, STK-2, which encodes a rat serine-threonine protein kinase (STK) homolog."
      Li X., Yu L., Huang H., Zhang M., Zhao Y., Zhao S.
      Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Testis.
    6. "Two splice variants of PKB gamma have different regulatory capacity depending on the presence or absence of the regulatory phosphorylation site Ser-472 in the C-terminal hydrophobic domain."
      Brodbeck D., Hill M.M., Hemmings B.A.
      J. Biol. Chem. 276:29550-29558(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), MUTAGENESIS OF THR-305 AND THR-447.
    7. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    10. "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-305 BY PDPK1.
    11. "Characterization of PDK2 activity against protein kinase B gamma."
      Hodgkinson C.P., Sale E.M., Sale G.J.
      Biochemistry 41:10351-10359(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-472.
    12. "Differential regulation of Akt kinase isoforms by the members of the TCL1 oncogene family."
      Laine J., Kuenstle G., Obata T., Noguchi M.
      J. Biol. Chem. 277:3743-3751(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TCL1A.
    13. "Identification of Akt association and oligomerization domains of the Akt kinase coactivator TCL1."
      Kuenstle G., Laine J., Pierron G., Kagami S., Nakajima H., Hoh F., Roumestand C., Stern M.H., Noguchi M.
      Mol. Cell. Biol. 22:1513-1525(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TCL1A.
    14. Cited for: INVOLVEMENT IN TUMORS.
    15. "A specific role for AKT3 in the genesis of ovarian cancer through modulation of G(2)-M phase transition."
      Cristiano B.E., Chan J.C., Hannan K.M., Lundie N.A., Marmy-Conus N.J., Campbell I.G., Phillips W.A., Robbie M., Hannan R.D., Pearson R.B.
      Cancer Res. 66:11718-11725(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN CANCER.
    16. Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
    17. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic kidney.
    18. "VEGF stimulation of mitochondrial biogenesis: requirement of AKT3 kinase."
      Wright G.L., Maroulakou I.G., Eldridge J., Liby T.L., Sridharan V., Tsichlis P.N., Muise-Helmericks R.C.
      FASEB J. 22:3264-3275(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    19. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
    20. Cited for: UBIQUITINATION BY TTC3.
    21. Cited for: INTERACTION WITH TRAF6.
    22. "The Akt isoforms are present at distinct subcellular locations."
      Santi S.A., Lee H.
      Am. J. Physiol. 298:C580-C591(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    23. Cited for: INVOLVEMENT IN TUMORS.
    24. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    25. "Expression of matrix metalloproteinase-13 is controlled by IL-13 via PI3K/Akt3 and PKC-delta in normal human dermal fibroblasts."
      Moriya C., Jinnin M., Yamane K., Maruo K., Muchemwa F.C., Igata T., Makino T., Fukushima S., Ihn H.
      J. Invest. Dermatol. 131:655-661(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    26. Cited for: REVIEW ON FUNCTION.
    27. "The crystal structure of the PH domain of human Akt3 protein kinase."
      Vollmar M., Wang J., Zhang Y., Elkins J.M., Burgess-Brown N., Chaikuad A., Pike A.C.W., Von Delft F., Bountra C., Arrowsmith C.H., Weigelt J., Edwards A., Knapp S.
      Submitted (DEC-2009) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (1.46 ANGSTROMS) OF 1-118.
    28. "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: VARIANT [LARGE SCALE ANALYSIS] ARG-171.
    29. Cited for: VARIANT MELANOMA LYS-17, CHARACTERIZATION OF VARIANT MELANOMA LYS-17.
    30. Cited for: VARIANTS MPPH SER-229 AND TRP-465.
    31. "De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly."
      Lee J.H., Huynh M., Silhavy J.L., Kim S., Dixon-Salazar T., Heiberg A., Scott E., Bafna V., Hill K.J., Collazo A., Funari V., Russ C., Gabriel S.B., Mathern G.W., Gleeson J.G.
      Nat. Genet. 44:941-945(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT MPPH LYS-17.
    32. Cited for: VARIANT MPPH LYS-17.

    Entry informationi

    Entry nameiAKT3_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y243
    Secondary accession number(s): Q0VAA6
    , Q5VTI1, Q5VTI2, Q96QV3, Q9UFP5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: November 1, 1999
    Last modified: October 1, 2014
    This is version 155 of the entry and version 1 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 1
      Human chromosome 1: 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