P31749 (AKT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified November 13, 2013. Version 173. History...
Names and origin
|Protein names||Recommended name:|
RAC-alpha serine/threonine-protein kinase
Protein kinase B
Protein kinase B alpha
Short name=PKB alpha
|Organism||Homo sapiens (Human) [Reference proteome]|
|Taxonomic identifier||9606 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo|
|Sequence length||480 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI3P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI3K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development. Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3. Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation. Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation. Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity. Phosphorylation of BAD stimulates its pro-apoptotic activity. Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53. Ref.6 Ref.8 Ref.11 Ref.12 Ref.13 Ref.14 Ref.17 Ref.19 Ref.20 Ref.22 Ref.24 Ref.25 Ref.32 Ref.35 Ref.38 Ref.40 Ref.41 Ref.44 Ref.45 Ref.47 Ref.48 Ref.49 Ref.50 Ref.51 Ref.52 Ref.63
AKT1-specific substrates have been recently identified, including palladin (PALLD), which phosphorylation modulates cytoskeletal organization and cell motility; prohibitin (PHB), playing an important role in cell metabolism and proliferation; and CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization. These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation. Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation. Ref.6 Ref.8 Ref.11 Ref.12 Ref.13 Ref.14 Ref.17 Ref.19 Ref.20 Ref.22 Ref.24 Ref.25 Ref.32 Ref.35 Ref.38 Ref.40 Ref.41 Ref.44 Ref.45 Ref.47 Ref.48 Ref.49 Ref.50 Ref.51 Ref.52 Ref.63
Three specific sites, one in the kinase domain (Thr-308) and the two other ones in the C-terminal regulatory region (Ser-473 and Tyr-474), need to be phosphorylated for its full activation. Inhibited by pyrrolopyrimidine inhibitors like aniline triazole and spiroindoline. Ref.9 Ref.11 Ref.66 Ref.67 Ref.68 Ref.70
Interacts (via the C-terminus) with CCDC88A (via its C-terminus). Interacts with GRB10; the interaction leads to GRB10 phosphorylation thus promoting YWHAE-binding By similarity. Interacts with AGAP2 (isoform 2/PIKE-A); the interaction occurs in the presence of guanine nucleotides. Interacts with AKTIP. Interacts (via PH domain) with MTCP1, TCL1A AND TCL1B. Interacts with CDKN1B; the interaction phosphorylates CDKN1B promoting 14-3-3 binding and cell-cycle progression. Interacts with MAP3K5 and TRAF6. Interacts with BAD, PPP2R5B, STK3 and STK4. Interacts (via PH domain) with SIRT1. Interacts with SRPK2 in a phosphorylation-dependent manner. Interacts with RAF1. Interacts with TRIM13; the interaction ubiquitinates AKT1 leading to its proteasomal degradation. Interacts with TNK2 and CLK2. Interacts (via the C-terminus) with THEM4 (via its C-terminus). Interacts with and phosphorylated by PDPK1. Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Ref.23 Ref.24 Ref.26 Ref.29 Ref.30 Ref.32 Ref.35 Ref.39 Ref.40 Ref.44 Ref.46 Ref.47 Ref.49 Ref.51 Ref.52 Ref.54 Ref.55 Ref.61 Ref.62 Ref.64 Ref.65
Cytoplasm. Nucleus. Cell membrane. Note: Nucleus after activation by integrin-linked protein kinase 1 (ILK1). Nuclear translocation is enhanced by interaction with TCL1A. Phosphorylation on Tyr-176 by TNK2 results in its localization to the cell membrane where it is targeted for further phosphorylations on Thr-308 and Ser-473 leading to its activation and the activated form translocates to the nucleus. Ref.18 Ref.39 Ref.52 Ref.62
Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Expressed in all human cell types so far analyzed. The Tyr-176 phosphorylated form shows a significant increase in expression in breast cancers during the progressive stages i.e. normal to hyperplasia (ADH), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and lymph node metastatic (LNMM) stages. Ref.6 Ref.39 Ref.52
Binding of the PH domain to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) following phosphatidylinositol 3-kinase alpha (PIK3CA) activity results in its targeting to the plasma membrane. The PH domain mediates interaction with TNK2 and Tyr-176 is also essential for this interaction.
The AGC-kinase C-terminal mediates interaction with THEM4.
O-GlcNAcylation at Thr-305 and Thr-312 inhibits activating phosphorylation at Thr-308 via disrupting the interaction between AKT1 and PDPK1. O-GlcNAcylation at Ser-473 also probably interferes with phosphorylation at this site.
Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required for full activity. Activated TNK2 phosphorylates it on Tyr-176 resulting in its binding to the anionic plasma membrane phospholipid PA. This phosphorylated form localizes to the cell membrane, where it is targeted by PDPK1 and PDPK2 for further phosphorylations on Thr-308 and Ser-473 leading to its activation. Ser-473 phosphorylation by mTORC2 favors Thr-308 phosphorylation by PDPK1. Ser-473 phosphorylation is enhanced by interaction with AGAP2 isoform 2 (PIKE-A). Ser-473 phosphorylation is enhanced in focal cortical dysplasias with Taylor-type balloon cells. Ser-473 phosphorylation is enhanced by signaling through activated FLT3. Dephosphorylated at Thr-308 and Ser-473 by PP2A phosphatase. The phosphorylated form of PPP2R5B is required for bridging AKT1 with PP2A phosphatase. Ref.9 Ref.10 Ref.11 Ref.21 Ref.26 Ref.27 Ref.31 Ref.33 Ref.34 Ref.52 Ref.55 Ref.58 Ref.66 Ref.68
Ubiquitinated via 'Lys-48'-linked polyubiquitination by ZNRF1, leading to its degradation by the proteasome By similarity. Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. TRAF6-induced 'Lys-63'-linked AKT1 ubiquitination is critical for phosphorylation and activation. When ubiquitinated, it translocates to the plasma membrane, where it becomes phosphorylated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome. Also ubiquitinated by TRIM13 leading to its proteasomal degradation. Ref.9 Ref.10 Ref.11 Ref.21 Ref.26 Ref.27 Ref.31 Ref.33 Ref.34 Ref.52 Ref.55 Ref.58 Ref.66 Ref.68
Acetylated on Lys-14 and Lys-20 by the histone acetyltransferases EP300 and KAT2B. Acetylation results in reduced phosphorylation and inhibition of activity. Deacetylated at Lys-14 and Lys-20 by SIRT1. SIRT1-mediated deacetylation relieves the inhibition.
|Involvement in disease|
Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.
Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Genetic variations in AKT1 may play a role in susceptibility to ovarian cancer.
Proteus syndrome (PROTEUSS) [MIM:176920]: A highly variable, severe disorder of asymmetric and disproportionate overgrowth of body parts, connective tissue nevi, epidermal nevi, dysregulated adipose tissue, and vascular malformations. Many features of Proteus syndrome overlap with other overgrowth syndromes.
Cowden syndrome 6 (CWS6) [MIM:615109]: A form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid.
Contains 1 AGC-kinase C-terminal domain.
Contains 1 PH domain.
Contains 1 protein kinase domain.
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.
KM=52.8 µM for ATP (for purified and in vitro activated AKT1) Ref.37
KM=0.5 µM for peptide substrate (for purified and in vitro activated AKT1)
KM=143.3 µM for ATP (for recombinant myristoylated AKT1 expressed and immunoprecipitated from Rat-1 cells)
KM=2.9 µM for peptide substrate (for recombinant myristoylated AKT1 expressed and immunoprecipitated from Rat-1 cells)
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 480||480||RAC-alpha serine/threonine-protein kinase||PRO_0000085605|
|Domain||5 – 108||104||PH|
|Domain||150 – 408||259||Protein kinase|
|Domain||409 – 480||72||AGC-kinase C-terminal|
|Nucleotide binding||156 – 164||9||ATP By similarity|
|Region||14 – 19||6||Inositol-(1,3,4,5)-tetrakisphosphate binding|
|Region||23 – 25||3||Inositol-(1,3,4,5)-tetrakisphosphate binding|
|Region||228 – 230||3||Inhibitor binding|
|Active site||274||1||Proton acceptor By similarity|
|Binding site||161||1||Inhibitor; via amide nitrogen|
|Binding site||179||1||ATP By similarity|
|Binding site||230||1||Inhibitor; via amide nitrogen|
Amino acid modifications
|Modified residue||14||1||N6-acetyllysine Ref.61|
|Modified residue||20||1||N6-acetyllysine Ref.61|
|Modified residue||124||1||Phosphoserine Ref.42|
|Modified residue||126||1||Phosphoserine; alternate Ref.42|
|Modified residue||129||1||Phosphoserine; alternate Ref.36 Ref.42|
|Modified residue||176||1||Phosphotyrosine; by TNK2 Ref.52|
|Modified residue||308||1||Phosphothreonine; by PDPK1 Ref.10 Ref.11 Ref.33 Ref.52 Ref.66 Ref.68|
|Modified residue||450||1||Phosphothreonine; by MTOR By similarity|
|Modified residue||473||1||Phosphoserine; by MTOR; alternate Ref.9 Ref.10 Ref.26 Ref.27 Ref.31 Ref.33 Ref.34 Ref.52 Ref.58|
|Modified residue||474||1||Phosphotyrosine Ref.21|
|Glycosylation||126||1||O-linked (GlcNAc); alternate Ref.62|
|Glycosylation||129||1||O-linked (GlcNAc); alternate Ref.62|
|Glycosylation||305||1||O-linked (GlcNAc) Ref.62|
|Glycosylation||312||1||O-linked (GlcNAc) Ref.62|
|Glycosylation||473||1||O-linked (GlcNAc); alternate By similarity|
|Disulfide bond||60 ↔ 77||Ref.69|
|Disulfide bond||296 ↔ 310||By similarity|
|Natural variant||17||1||E → K in PROTEUSS and breast cancer; also detected in colorectal and ovarian cancer; somatic mutation; results in increased phosphorylation at T-308 and higher basal ubiquitination; the mutant protein is more efficiently recruited to the plasma membrane; alters phosphatidylinositiol phosphates lipid specificity of the AKT1 PH domain. Ref.46 Ref.71 Ref.72 Ref.73|
Corresponds to variant rs121434592 [ dbSNP | Ensembl ].
|Natural variant||25||1||R → C in CWD6. Ref.74||VAR_069791|
|Natural variant||167||1||V → A.|
Corresponds to variant rs11555433 [ dbSNP | Ensembl ].
|Natural variant||435||1||T → P in CWD6. Ref.74||VAR_069792|
|Mutagenesis||8||1||K → R: Substantial reduction of ubiquitination, phosphorylation at T-308 and S-473, AKT activation as well as IGF1-induced membrane recruitment. Decrease in ubiquitination and phosphorylation at T-308 as well as impaired association with the membrane; when associated with K-17. Ref.46|
|Mutagenesis||14||1||K → A: Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. Ref.46 Ref.61 Ref.64|
|Mutagenesis||14||1||K → Q: Substantial reduction of phosphorylation at T-308 and S-473, loss of AKT activation, and loss of binding to PIP3 as well as IGF1-induced membrane recruitment. Ref.46 Ref.61 Ref.64|
|Mutagenesis||14||1||K → R: Substantial reduction of ubiquitination, phosphorylation at T-308 and S-473, AKT activation, loss of binding to PIP3 as well as IGF1-induced membrane recruitment. Ref.46 Ref.61 Ref.64|
|Mutagenesis||17||1||E → K: No effect on membrane localization. Loss of membrane localization; when associated with Q-20. Ref.61|
|Mutagenesis||20||1||K → Q: Substantial reduction of phosphorylation at T-308 and S-473, reduced AKT activation, and reduced binding to PIP3 as well as IGF1-induced membrane recruitment. Loss of membrane localization; when associated with K-17. Ref.61|
|Mutagenesis||20||1||K → R: Slight increase of phosphorylation at T-308 and S-473. Ref.61|
|Mutagenesis||25||1||R → A or C: Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. Ref.64|
|Mutagenesis||86||1||R → A: Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. Ref.64|
|Mutagenesis||176||1||Y → F: Significant loss of interaction with TNK2. Loss of membrane localization. Significant reduction in phosphorylation on Ser-473. Ref.52|
|Mutagenesis||305||1||T → A: Reduces O-GlcNAc levels; Reduces O-GlcNAc levels even more; when associated with A-312. Ref.62|
|Mutagenesis||305||1||T → Y: Abolishes phosphorylation at Thr-308. Ref.62|
|Mutagenesis||308||1||T → D: 5-fold activation and 18-fold activation; when associated with D-473. Ref.10 Ref.24|
|Mutagenesis||312||1||T → A: Reduces O-GlcNAc levels; Reduces O-GlcNAc levels even more; when associated with A-305. Ref.62|
|Mutagenesis||312||1||T → Y: Abolishes phosphorylation at Thr-308. Ref.62|
|Mutagenesis||473||1||S → D: 7-fold activation and 25-fold activation; when associated with D-308. Ref.10 Ref.24|
|Mutagenesis||474||1||Y → F: 55% inhibition of activation. Ref.21|
|Sequence conflict||173 – 174||2||GR → A in CAA43372. Ref.6|
|Sequence conflict||202||1||L → Q in CAA43372. Ref.6|
|Sequence conflict||212||1||A → R in CAA43372. Ref.6|
|Sequence conflict||246||1||S → A in CAA43372. Ref.6|
|Sequence conflict||409||1||A → T in CAA43372. Ref.6|
|Sequence conflict||476||1||A → P in CAA43372. Ref.6|
|Sequence conflict||478||1||G → A in CAA43372. Ref.6|
|Sequence conflict||478||1||G → S in AAA36539. Ref.1|
|Sequence conflict||478||1||G → S in AAL55732. Ref.2|
|Sequence conflict||478||1||G → S in BAG36922. Ref.3|
|Sequence conflict||478||1||G → S in BAG70056. Ref.4|
|Sequence conflict||478||1||G → S in BAG70181. Ref.4|
Helix Strand Turn
|Helix||2 – 4||3|
|Beta strand||6 – 15||10|
|Beta strand||17 – 19||3|
|Beta strand||22 – 30||9|
|Beta strand||33 – 40||8|
|Helix||45 – 48||4|
|Beta strand||52 – 56||5|
|Beta strand||61 – 65||5|
|Beta strand||67 – 69||3|
|Beta strand||72 – 79||8|
|Beta strand||82 – 89||8|
|Helix||93 – 115||23|
|Helix||147 – 149||3|
|Beta strand||150 – 158||9|
|Beta strand||160 – 169||10|
|Turn||170 – 172||3|
|Beta strand||175 – 182||8|
|Helix||183 – 188||6|
|Helix||192 – 204||13|
|Beta strand||213 – 218||6|
|Beta strand||220 – 227||8|
|Helix||235 – 242||8|
|Helix||247 – 268||22|
|Helix||277 – 279||3|
|Beta strand||280 – 282||3|
|Beta strand||284 – 286||3|
|Beta strand||288 – 290||3|
|Beta strand||309 – 311||3|
|Helix||313 – 315||3|
|Helix||318 – 322||5|
|Helix||330 – 344||15|
|Helix||354 – 363||10|
|Helix||374 – 383||10|
|Helix||388 – 390||3|
|Turn||396 – 398||3|
|Helix||399 – 403||5|
|Helix||406 – 408||3|
|Helix||413 – 417||5|
|Beta strand||430 – 433||4|
|Helix||440 – 443||4|
|Beta strand||464 – 466||3|
|Beta strand||473 – 475||3|
|||"Molecular cloning and identification of a serine/threonine protein kinase of the second-messenger subfamily."|
Jones P.F., Jakubowicz T., Pitossi F.J., Maurer F., Hemmings B.A.
Proc. Natl. Acad. Sci. U.S.A. 88:4171-4175(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY.
|||"Isolation and characterization of the human AKT1 gene, identification of 13 single nucleotide polymorphisms (SNPs), and their lack of association with Type II diabetes."|
Matsubara A., Wasson J.C., Donelan S.S., Welling C.M., Glaser B., Permutt M.A.
Diabetologia 44:910-913(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|||"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. Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Adrenal gland.
|||"Human protein factory for converting the transcriptome into an in vitro-expressed proteome."|
Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. Nomura N.
Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
|||"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].
Tissue: Muscle and Ovary.
|||"Molecular cloning and characterisation of a novel putative protein-serine kinase related to the cAMP-dependent and protein kinase C families."|
Coffer P.J., Woodgett J.R.
Eur. J. Biochem. 201:475-481(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 63-480, FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY.
Coffer P.J., Woodgett J.R.
Eur. J. Biochem. 205:1217-1218(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
|||"CREB is a regulatory target for the protein kinase Akt/PKB."|
Du K., Montminy M.
J. Biol. Chem. 273:32377-32379(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CREB1.
|||"Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase."|
Delcommenne M., Tan C., Gray V., Rue L., Woodgett J.R., Dedhar S.
Proc. Natl. Acad. Sci. U.S.A. 95:11211-11216(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, PHOSPHORYLATION AT SER-473.
|||"Mechanism of activation of protein kinase B by insulin and IGF-1."|
Alessi D.R., Andjelkovic M., Caudwell F.B., Cron P., Morrice N., Cohen P., Hemmings B.A.
EMBO J. 15:6541-6551(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF THR-308 AND SER-473, PHOSPHORYLATION AT THR-308 AND SER-473.
|||"Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro: comparison with protein kinase B alpha."|
Walker K.S., Deak M., Paterson A., Hudson K., Cohen P., Alessi D.R.
Biochem. J. 331:299-308(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-308 BY PDPK1.
|||"Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B."|
Rena G., Guo S., Cichy S.C., Unterman T.G., Cohen P.
J. Biol. Chem. 274:17179-17183(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF FOXO1.
|||"Phosphorylation and regulation of Raf by Akt (protein kinase B)."|
Zimmermann S., Moelling K.
Science 286:1741-1744(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF RAF1, INTERACTION WITH RAF1.
|||"Inhibition of Akt and its anti-apoptotic activities by tumor necrosis factor-induced protein kinase C-related kinase 2 (PRK2) cleavage."|
Koh H., Lee K.H., Kim D., Kim S., Kim J.W., Chung J.
J. Biol. Chem. 275:34451-34458(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF BAD, INTERACTION WITH BAD AND PKN2.
|||"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.
|||"Tcl1 enhances Akt kinase activity and mediates its nuclear translocation."|
Pekarsky Y., Koval A., Hallas C., Bichi R., Tresini M., Malstrom S., Russo G., Tsichlis P., Croce C.M.
Proc. Natl. Acad. Sci. U.S.A. 97:3028-3033(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TCL1A.
|||"Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1."|
Kim A.H., Khursigara G., Sun X., Franke T.F., Chao M.V.
Mol. Cell. Biol. 21:893-901(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF MAP3K5, INTERACTION WITH MAP3K5.
|||"Carboxyl-terminal modulator protein (CTMP), a negative regulator of PKB/Akt and v-Akt at the plasma membrane."|
Maira S.-M., Galetic I., Brazil D.P., Kaech S., Ingley E., Thelen M., Hemmings B.A.
Science 294:374-380(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH THEM4, SUBCELLULAR LOCATION.
|||"A method to identify serine kinase substrates. Akt phosphorylates a novel adipocyte protein with a Rab GTPase-activating protein (GAP) domain."|
Kane S., Sano H., Liu S.C.H., Asara J.M., Lane W.S., Garner C.C., Lienhard G.E.
J. Biol. Chem. 277:22115-22118(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TBC1D4.
|||"Akt-dependent phosphorylation of p27Kip1 promotes binding to 14-3-3 and cytoplasmic localization."|
Fujita N., Sato S., Katayama K., Tsuruo T.
J. Biol. Chem. 277:28706-28713(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDKN1B, FUNCTION.
|||"Direct identification of tyrosine 474 as a regulatory phosphorylation site for the Akt protein kinase."|
Conus N.M., Hannan K.M., Cristiano B.E., Hemmings B.A., Pearson R.B.
J. Biol. Chem. 277:38021-38028(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-474, MUTAGENESIS OF TYR-474.
|||"Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway."|
Manning B.D., Tee A.R., Logsdon M.N., Blenis J., Cantley L.C.
Mol. Cell 10:151-162(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TSC2.
|||"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.
|||"PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization."|
Shin I., Yakes F.M., Rojo F., Shin N.-Y., Bakin A.V., Baselga J., Arteaga C.L.
Nat. Med. 8:1145-1152(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDKN1B, FUNCTION, MUTAGENESIS OF THR-308 AND SER-473.
|||"Identification of Tyr900 in the kinase domain of c-Kit as a Src-dependent phosphorylation site mediating interaction with c-Crk."|
Lennartsson J., Wernstedt C., Engstrom U., Hellman U., Ronnstrand L.
Exp. Cell Res. 288:110-118(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PARTICIPATION IN KIT SIGNALING.
|||"PIKE (phosphatidylinositol 3-kinase enhancer)-A GTPase stimulates Akt activity and mediates cellular invasion."|
Ahn J.-Y., Rong R., Kroll T.G., Van Meir E.G., Snyder S.H., Ye K.
J. Biol. Chem. 279:16441-16451(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AGAP2, PHOSPHORYLATION AT SER-473.
|||"LGI1, a putative tumor metastasis suppressor gene, controls in vitro invasiveness and expression of matrix metalloproteinases in glioma cells through the ERK1/2 pathway."|
Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.
J. Biol. Chem. 279:23151-23157(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-473.
Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.
J. Biol. Chem. 282:2752-2752(2007)
|||"Regulation of apoptosis by the Ft1 protein, a new modulator of protein kinase B/Akt."|
Remy I., Michnick S.W.
Mol. Cell. Biol. 24:1493-1504(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AKTIP.
|||"PIKE-A is amplified in human cancers and prevents apoptosis by up-regulating Akt."|
Ahn J.-Y., Hu Y., Kroll T.G., Allard P., Ye K.
Proc. Natl. Acad. Sci. U.S.A. 101:6993-6998(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AGAP2.
|||"Constitutive activation of Akt by Flt3 internal tandem duplications is necessary for increased survival, proliferation, and myeloid transformation."|
Brandts C.H., Sargin B., Rode M., Biermann C., Lindtner B., Schwable J., Buerger H., Muller-Tidow C., Choudhary C., McMahon M., Berdel W.E., Serve H.
Cancer Res. 65:9643-9650(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-473 IN RESPONSE TO FLT3 SIGNALING.
|||"Akt/PKB regulates actin organization and cell motility via Girdin/APE."|
Enomoto A., Murakami H., Asai N., Morone N., Watanabe T., Kawai K., Murakumo Y., Usukura J., Kaibuchi K., Takahashi M.
Dev. Cell 9:389-402(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH CCDC88A.
|||"Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex."|
Sarbassov D.D., Guertin D.A., Ali S.M., Sabatini D.M.
Science 307:1098-1101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-308, PHOSPHORYLATION AT SER-473 BY MTOR.
|||"Activation of Akt independent of PTEN and CTMP tumor-suppressor gene mutations in epilepsy-associated Taylor-type focal cortical dysplasias."|
Schick V., Majores M., Engels G., Spitoni S., Koch A., Elger C.E., Simon M., Knobbe C., Bluemcke I., Becker A.J.
Acta Neuropathol. 112:715-725(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-473.
|||"Akt phosphorylates and suppresses the transactivation of retinoic acid receptor alpha."|
Srinivas H., Xia D., Moore N.L., Uray I.P., Kim H., Ma L., Weigel N.L., Brown P.H., Kurie J.M.
Biochem. J. 395:653-662(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RARA.
|||"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."|
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
|||"Kinetic mechanism of AKT/PKB enzyme family."|
Zhang X., Zhang S., Yamane H., Wahl R., Ali A., Lofgren J.A., Kendall R.L.
J. Biol. Chem. 281:13949-13956(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
|||"Only Akt1 is required for proliferation, while Akt2 promotes cell cycle exit through p21 binding."|
Heron-Milhavet L., Franckhauser C., Rana V., Berthenet C., Fisher D., Hemmings B.A., Fernandez A., Lamb N.J.
Mol. Cell. Biol. 26:8267-8280(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CDKN1A.
|||"The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1."|
Cinar B., Fang P.K., Lutchman M., Di Vizio D., Adam R.M., Pavlova N., Rubin M.A., Yelick P.C., Freeman M.R.
EMBO J. 26:4523-4534(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH STK4/MST1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
|||"Akt phosphorylates MstI and prevents its proteolytic activation, blocking FOXO3 phosphorylation and nuclear translocation."|
Jang S.W., Yang S.J., Srinivasan S., Ye K.
J. Biol. Chem. 282:30836-30844(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH STK4/MST1.
|||"Characterization of Akt overexpression in MiaPaCa-2 cells: prohibitin is an Akt substrate both in vitro and in cells."|
Han E.K., Mcgonigal T., Butler C., Giranda V.L., Luo Y.
Anticancer Res. 28:957-963(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PROHIBITIN.
|||"A quantitative atlas of mitotic phosphorylation."|
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-124; SER-126 AND SER-129, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
|||"The E3 ligase TTC3 facilitates ubiquitination and degradation of phosphorylated Akt."|
Suizu F., Hiramuki Y., Okumura F., Matsuda M., Okumura A.J., Hirata N., Narita M., Kohno T., Yokota J., Bohgaki M., Obuse C., Hatakeyama S., Obata T., Noguchi M.
Dev. Cell 17:800-810(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY TTC3.
|||"Interaction of Akt-phosphorylated SRPK2 with 14-3-3 mediates cell cycle and cell death in neurons."|
Jang S.W., Liu X., Fu H., Rees H., Yepes M., Levey A., Ye K.
J. Biol. Chem. 284:24512-24525(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF SRPK2, INTERACTION WITH SRPK2.
|||"The Rho-family GEF Asef2 activates Rac to modulate adhesion and actin dynamics and thereby regulate cell migration."|
Bristow J.M., Sellers M.H., Majumdar D., Anderson B., Hu L., Webb D.J.
J. Cell Sci. 122:4535-4546(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"The E3 ligase TRAF6 regulates Akt ubiquitination and activation."|
Yang W.-L., Wang J., Chan C.-H., Lee S.-W., Campos A.D., Lamothe B., Hur L., Grabiner B.C., Lin X., Darnay B.G., Lin H.-K.
Science 325:1134-1138(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH TRAF6, MUTAGENESIS OF LYS-8 AND LYS-14, CHARACTERIZATION OF VARIANT BREAST CANCER LYS-17.
|||"Proapoptotic kinase MST2 coordinates signaling crosstalk between RASSF1A, Raf-1, and Akt."|
Romano D., Matallanas D., Weitsman G., Preisinger C., Ng T., Kolch W.
Cancer Res. 70:1195-1203(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH STK3/MST2.
|||"Phosphoinositide 3-kinase/Akt inhibits MST1-mediated pro-apoptotic signaling through phosphorylation of threonine 120."|
Yuan Z., Kim D., Shu S., Wu J., Guo J., Xiao L., Kaneko S., Coppola D., Cheng J.Q.
J. Biol. Chem. 285:3815-3824(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"Phosphorylation of CLK2 at serine 34 and threonine 127 by AKT controls cell survival after ionizing radiation."|
Nam S.Y., Seo H.H., Park H.S., An S., Kim J.Y., Yang K.H., Kim C.S., Jeong M., Jin Y.W.
J. Biol. Chem. 285:31157-31163(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CLK2.
|||"The actin-bundling protein palladin is an Akt1-specific substrate that regulates breast cancer cell migration."|
Chin Y.R., Toker A.
Mol. Cell 38:333-344(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PALLD.
|||"Regulation of proapoptotic mammalian ste20-like kinase MST2 by the IGF1-Akt pathway."|
Kim D., Shu S., Coppola M.D., Kaneko S., Yuan Z.Q., Cheng J.Q.
PLoS ONE 5:E9616-E9616(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH STK3/MST2.
|||"Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation."|
Mahajan K., Coppola D., Challa S., Fang B., Chen Y.A., Zhu W., Lopez A.S., Koomen J., Engelman R.W., Rivera C., Muraoka-Cook R.S., Cheng J.Q., Schoenbrunn E., Sebti S.M., Earp H.S., Mahajan N.P.
PLoS ONE 5:E9646-E9646(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-176; THR-308 AND SER-473, MUTAGENESIS OF TYR-176, INTERACTION WITH TNK2, TISSUE SPECIFICITY.
|||"Initial characterization of the human central proteome."|
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
|||"Ret finger protein 2 enhances ionizing radiation-induced apoptosis via degradation of AKT and MDM2."|
Joo H.M., Kim J.Y., Jeong J.B., Seong K.M., Nam S.Y., Yang K.H., Kim C.S., Kim H.S., Jeong M., An S., Jin Y.W.
Eur. J. Cell Biol. 90:420-431(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TRIM13, UBIQUITINATION.
|||"Clk2 and B56-beta mediate insulin-regulated assembly of the PP2A phosphatase holoenzyme complex on Akt."|
Rodgers J.T., Vogel R.O., Puigserver P.
Mol. Cell 41:471-479(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PPP2R5B, DEPHOSPHORYLATION.
|||"Signal transduction via the stem cell factor receptor/c-Kit."|
Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON ROLE IN KIT SIGNALING.
|||"The protein kinase B/Akt signalling pathway in human malignancy."|
Nicholson K.M., Anderson N.G.
Cell. Signal. 14:381-395(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
|||"A novel human dynactin-associated protein, dynAP, promotes activation of Akt, and ergosterol-related compounds induce dynAP-dependent apoptosis of human cancer cells."|
Kunoh T., Noda T., Koseki K., Sekigawa M., Takagi M., Shin-ya K., Goshima N., Iemura S., Natsume T., Wada S., Mukai Y., Ohta S., Sasaki R., Mizukami T.
Mol. Cancer Ther. 9:2934-2942(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-473.
|||"Akt signalling in health and disease."|
Hers I., Vincent E.E., Tavare J.M.
Cell. Signal. 23:1515-1527(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
|||"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.
|||"The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy."|
Sundaresan N.R., Pillai V.B., Wolfgeher D., Samant S., Vasudevan P., Parekh V., Raghuraman H., Cunningham J.M., Gupta M., Gupta M.P.
Sci. Signal. 4:RA46-RA46(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SIRT1, ACETYLATION AT LYS-14 AND LYS-20, DEACETYLATION AT LYS-14 AND LYS-20, MUTAGENESIS OF LYS-14; GLU-17 AND LYS-20.
|||"Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates Akt signaling."|
Wang S., Huang X., Sun D., Xin X., Pan Q., Peng S., Liang Z., Luo C., Yang Y., Jiang H., Huang M., Chai W., Ding J., Geng M.
PLoS ONE 7:E37427-E37427(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT SER-126; SER-129; THR-305 AND THR-312, SUBCELLULAR LOCATION, INTERACTION WITH PDPK1, MUTAGENESIS OF THR-305 AND THR-312.
|||"MOZ increases p53 acetylation and premature senescence through its complex formation with PML."|
Rokudai S., Laptenko O., Arnal S.M., Taya Y., Kitabayashi I., Prives C.
Proc. Natl. Acad. Sci. U.S.A. 110:3895-3900(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"High-resolution structure of the pleckstrin homology domain of protein kinase b/akt bound to phosphatidylinositol (3,4,5)-trisphosphate."|
Thomas C.C., Deak M., Alessi D.R., van Aalten D.M.
Curr. Biol. 12:1256-1262(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 1-123, INTERACTION WITH PTDINS(3,4,5)P3 AND PTDINS(3,4)P2, MUTAGENESIS OF LYS-14; ARG-25 AND ARG-86.
|||"Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin homology domain of protein kinase B induces a conformational change."|
Milburn C.C., Deak M., Kelly S.M., Price N.C., Alessi D.R., Van Aalten D.M.
Biochem. J. 375:531-538(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (0.98 ANGSTROMS) OF 1-121, INTERACTION WITH PTDINS(1,3,4,5)P4.
|||"Synthesis and structure based optimization of novel Akt inhibitors."|
Lippa B., Pan G., Corbett M., Li C., Kauffman G.S., Pandit J., Robinson S., Wei L., Kozina E., Marr E.S., Borzillo G., Knauth E., Barbacci-Tobin E.G., Vincent P., Troutman M., Baker D., Rajamohan F., Kakar S., Clark T., Morris J.
Bioorg. Med. Chem. Lett. 18:3359-3363(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 144-480, PHOSPHORYLATION AT THR-308, ENZYME REGULATION.
|||"Discovery of pyrrolopyrimidine inhibitors of Akt."|
Blake J.F., Kallan N.C., Xiao D., Xu R., Bencsik J.R., Skelton N.J., Spencer K.L., Mitchell I.S., Woessner R.D., Gloor S.L., Risom T., Gross S.D., Martinson M., Morales T.H., Vigers G.P., Brandhuber B.J.
Bioorg. Med. Chem. Lett. 20:5607-5612(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 144-480, ENZYME REGULATION.
|||"Design of selective, ATP-competitive inhibitors of Akt."|
Freeman-Cook K.D., Autry C., Borzillo G., Gordon D., Barbacci-Tobin E., Bernardo V., Briere D., Clark T., Corbett M., Jakubczak J., Kakar S., Knauth E., Lippa B., Luzzio M.J., Mansour M., Martinelli G., Marx M., Nelson K. Morris J.
J. Med. Chem. 53:4615-4622(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.01 ANGSTROMS) OF 144-480, PHOSPHORYLATION AT THR-308, ENZYME REGULATION.
|||"Crystal structure of human AKT1 with an allosteric inhibitor reveals a new mode of kinase inhibition."|
Wu W.I., Voegtli W.C., Sturgis H.L., Dizon F.P., Vigers G.P., Brandhuber B.J.
PLoS ONE 5:E12913-E12913(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 2-443, DISULFIDE BOND.
|||"Discovery and SAR of spirochromane Akt inhibitors."|
Kallan N.C., Spencer K.L., Blake J.F., Xu R., Heizer J., Bencsik J.R., Mitchell I.S., Gloor S.L., Martinson M., Risom T., Gross S.D., Morales T.H., Wu W.I., Vigers G.P., Brandhuber B.J., Skelton N.J.
Bioorg. Med. Chem. Lett. 21:2410-2414(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 144-480, ENZYME REGULATION.
|||"A transforming mutation in the pleckstrin homology domain of AKT1 in cancer."|
Carpten J.D., Faber A.L., Horn C., Donoho G.P., Briggs S.L., Robbins C.M., Hostetter G., Boguslawski S., Moses T.Y., Savage S., Uhlik M., Lin A., Du J., Qian Y.-W., Zeckner D.J., Tucker-Kellogg G., Touchman J., Patel K. Thomas J.E.
Nature 448:439-444(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BREAST CANCER LYS-17, CHARACTERIZATION OF VARIANT BREAST CANCER LYS-17.
|||"Molecular mechanism of an oncogenic mutation that alters membrane targeting: Glu17Lys modifies the PIP lipid specificity of the AKT1 PH domain."|
Landgraf K.E., Pilling C., Falke J.J.
Biochemistry 47:12260-12269(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT PROTEUSS LYS-17.
|||"A mosaic activating mutation in AKT1 associated with the Proteus syndrome."|
Lindhurst M.J., Sapp J.C., Teer J.K., Johnston J.J., Finn E.M., Peters K., Turner J., Cannons J.L., Bick D., Blakemore L., Blumhorst C., Brockmann K., Calder P., Cherman N., Deardorff M.A., Everman D.B., Golas G., Greenstein R.M. Biesecker L.G.
N. Engl. J. Med. 365:611-619(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PROTEUSS LYS-17.
|||"Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes."|
Orloff M.S., He X., Peterson C., Chen F., Chen J.L., Mester J.L., Eng C.
Am. J. Hum. Genet. 92:76-80(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CWD6 CYS-25 AND PRO-435.
|+||Additional computationally mapped references.|
|M63167 mRNA. Translation: AAA36539.1.|
AF283830 AF283829 Genomic DNA. Translation: AAL55732.1.
AK314256 mRNA. Translation: BAG36922.1.
AB451242 mRNA. Translation: BAG70056.1.
AB451367 mRNA. Translation: BAG70181.1.
BC000479 mRNA. Translation: AAH00479.1.
BC084538 mRNA. Translation: AAH84538.1.
X61037 mRNA. Translation: CAA43372.1.
|RefSeq||NP_001014431.1. NM_001014431.1. |
3D structure databases
|SMR||P31749. Positions 1-477. |
Protein-protein interaction databases
|IntAct||P31749. 70 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENST00000349310; ENSP00000270202; ENSG00000142208. |
ENST00000402615; ENSP00000385326; ENSG00000142208.
ENST00000407796; ENSP00000384293; ENSG00000142208.
ENST00000554581; ENSP00000451828; ENSG00000142208.
ENST00000554848; ENSP00000451166; ENSG00000142208.
ENST00000555528; ENSP00000450688; ENSG00000142208.
|UCSC||uc001ypk.3. human. |
|HGNC||HGNC:391. AKT1. |
|MIM||114480. phenotype. |
|Orphanet||201. Cowden syndrome. |
744. Proteus syndrome.
Enzyme and pathway databases
|BRENDA||22.214.171.124. 2681. |
|Reactome||REACT_111045. Developmental Biology. |
REACT_111102. Signal Transduction.
REACT_11123. Membrane Trafficking.
REACT_21257. Metabolism of RNA.
REACT_6900. Immune System.
REACT_71. Gene Expression.
Gene expression databases
Family and domain databases
|Gene3D||126.96.36.199. 1 hit. |
|InterPro||IPR000961. AGC-kinase_C. |
|Pfam||PF00169. PH. 1 hit. |
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
|SMART||SM00233. PH. 1 hit. |
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
|SUPFAM||SSF56112. SSF56112. 1 hit. |
|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.
|ChiTaRS||AKT1. human. |
|DrugBank||DB00171. Adenosine triphosphate. |
DB01169. Arsenic trioxide.
|Accession||Primary (citable) accession number: P31749|
Secondary accession number(s): B2RAM5, Q9BWB6
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
|Disclaimer||Any 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.|
|Human and mouse protein kinases|
Human and mouse protein kinases: classification and index
|Human chromosome 14|
Human chromosome 14: entries, gene names and cross-references to MIM
|Human entries with polymorphisms or disease mutations|
List of human entries with polymorphisms or disease mutations
|Human polymorphisms and disease mutations|
Index of human polymorphisms and disease mutations
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
Index of Protein Data Bank (PDB) cross-references
Index of protein domains and families