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P31749 (AKT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 178. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
RAC-alpha serine/threonine-protein kinase

EC=2.7.11.1
Alternative name(s):
Protein kinase B
Short name=PKB
Protein kinase B alpha
Short name=PKB alpha
Proto-oncogene c-Akt
RAC-PK-alpha
Gene names
Name:AKT1
Synonyms:PKB, RAC
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length480 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 specificityhas 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 ofcyclic 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.65

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 hasa 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.65

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. Ref.1 Ref.6 Ref.32

Enzyme regulation

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.68 Ref.69 Ref.70 Ref.72

Subunit structure

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.62 Ref.64 Ref.66 Ref.67

Subcellular location

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.64

Tissue specificity

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

Domain

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.

Post-translational modification

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. Phosphorylated at Thr-308 and Ser-473 by IKBKE and TBK1. Ser-473 phosphorylation is enhanced by interaction with AGAP2 isoform 2(PIKE-A). Ser-473 phosphorylation is enhanced in focal cortical dysplasias with Taylor-type balloon cells. Ser-473 phosphorylation is enhanced by signaling through activated FLT3. Dephosphorylated at Thr-308 and Ser-473 by PP2A phosphatase. The phosphorylated form of PPP2R5B is required for bridging AKT1 with PP2A phosphatase. 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.61 Ref.68 Ref.70

Ubiquitinated via 'Lys-48'-linked polyubiquitination by ZNRF1, leading to its degradation by the proteasome By similarity. Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. TRAF6-induced 'Lys-63'-linked AKT1 ubiquitination is critical for phosphorylation and activation. When ubiquitinated, it translocates to the plasma membrane, where it becomes phosphorylated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome. Also ubiquitinated by TRIM13 leading to its proteasomal degradation. Phosphorylated, undergoes 'Lys-48'-linked polyubiquitination preferentially at Lys-284 catalyzed by MUL1, leading to its proteasomal degradation. 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.61 Ref.68 Ref.70

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. Ref.62

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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

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.
Note: The gene represented in this entry may be involved in disease pathogenesis.

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.74 Ref.75

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

Sequence similarities

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

Contains 1 AGC-kinase C-terminal domain.

Contains 1 PH domain.

Contains 1 protein kinase domain.

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 specificfunctions 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.

Biophysicochemical properties

Kinetic parameters:

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)

Ontologies

Keywords
   Biological processApoptosis
Carbohydrate metabolism
Glucose metabolism
Glycogen biosynthesis
Glycogen metabolism
Neurogenesis
Sugar transport
Translation regulation
Transport
   Cellular componentCell membrane
Cytoplasm
Membrane
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Proto-oncogene
   LigandATP-binding
Nucleotide-binding
   Molecular functionDevelopmental protein
Kinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Disulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

G-protein coupled receptor signaling pathway

Traceable author statement PubMed 10570282. Source: ProtInc

RNA metabolic process

Traceable author statement. Source: Reactome

T cell costimulation

Traceable author statement. Source: Reactome

activation-induced cell death of T cells

Inferred from mutant phenotype Ref.29. Source: MGI

aging

Inferred from electronic annotation. Source: Ensembl

anagen

Inferred from electronic annotation. Source: Ensembl

apoptotic mitochondrial changes

Inferred from electronic annotation. Source: Ensembl

apoptotic process

Traceable author statement. Source: Reactome

blood coagulation

Traceable author statement. Source: Reactome

cell differentiation

Traceable author statement Ref.60. Source: UniProtKB

cell projection organization

Inferred from electronic annotation. Source: Ensembl

cell proliferation

Traceable author statement Ref.60. Source: UniProtKB

cellular protein modification process

Traceable author statement PubMed 10570282. Source: ProtInc

cellular response to epidermal growth factor stimulus

Inferred from electronic annotation. Source: Ensembl

cellular response to hypoxia

Inferred from electronic annotation. Source: Ensembl

cellular response to insulin stimulus

Inferred from mutant phenotype PubMed 16814735. Source: BHF-UCL

cellular response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

endocrine pancreas development

Traceable author statement. Source: Reactome

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

execution phase of apoptosis

Inferred from electronic annotation. Source: Ensembl

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

gene expression

Traceable author statement. Source: Reactome

germ cell development

Inferred from electronic annotation. Source: Ensembl

glucose homeostasis

Inferred from electronic annotation. Source: Ensembl

glucose metabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

glucose transport

Inferred from electronic annotation. Source: Ensembl

glycogen biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

glycogen cell differentiation involved in embryonic placenta development

Inferred from electronic annotation. Source: Ensembl

hyaluronan metabolic process

Inferred from electronic annotation. Source: Ensembl

inflammatory response

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

insulin receptor signaling pathway

Inferred from mutant phenotype Ref.10. Source: UniProtKB

insulin-like growth factor receptor signaling pathway

Inferred from mutant phenotype Ref.10. Source: UniProtKB

intracellular signal transduction

Inferred from direct assay Ref.29. Source: MGI

intrinsic apoptotic signaling pathway

Traceable author statement. Source: Reactome

labyrinthine layer blood vessel development

Inferred from electronic annotation. Source: Ensembl

mRNA metabolic process

Traceable author statement. Source: Reactome

mammary gland epithelial cell differentiation

Traceable author statement Ref.60. Source: UniProtKB

maternal placenta development

Inferred from electronic annotation. Source: Ensembl

membrane organization

Traceable author statement. Source: Reactome

negative regulation of JNK cascade

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from direct assay PubMed 19203586. Source: UniProtKB

negative regulation of autophagy

Inferred from mutant phenotype PubMed 18387192. Source: BHF-UCL

negative regulation of cell size

Inferred from electronic annotation. Source: Ensembl

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of endopeptidase activity

Inferred from mutant phenotype PubMed 18387192. Source: BHF-UCL

negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Traceable author statement PubMed 10748004. Source: BHF-UCL

negative regulation of fatty acid beta-oxidation

Inferred from mutant phenotype PubMed 16814735. Source: BHF-UCL

negative regulation of intrinsic apoptotic signaling pathway in response to oxidative stress

Non-traceable author statement PubMed 16604263. Source: BHF-UCL

negative regulation of plasma membrane long-chain fatty acid transport

Inferred from mutant phenotype PubMed 16814735. Source: BHF-UCL

negative regulation of protein kinase activity

Inferred from mutant phenotype PubMed 9373175. Source: BHF-UCL

negative regulation of proteolysis

Inferred from mutant phenotype PubMed 18387192. Source: BHF-UCL

negative regulation of release of cytochrome c from mitochondria

Inferred from sequence or structural similarity. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

nitric oxide biosynthetic process

Traceable author statement PubMed 10376602. Source: ProtInc

nitric oxide metabolic process

Traceable author statement. Source: Reactome

osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

peptidyl-serine phosphorylation

Inferred from direct assay Ref.32. Source: UniProtKB

peripheral nervous system myelin maintenance

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

phosphorylation

Inferred from direct assay Ref.52. Source: UniProtKB

platelet activation

Traceable author statement. Source: Reactome

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of blood vessel endothelial cell migration

Inferred from direct assay PubMed 20011604. Source: DFLAT

positive regulation of cell growth

Inferred from direct assay PubMed 19203586. Source: UniProtKB

positive regulation of cellular protein metabolic process

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle

Inferred from direct assay PubMed 18483258. Source: BHF-UCL

positive regulation of endothelial cell proliferation

Inferred from mutant phenotype PubMed 19850054. Source: UniProtKB

positive regulation of establishment of protein localization to plasma membrane

Inferred from mutant phenotype PubMed 8940145. Source: BHF-UCL

positive regulation of fat cell differentiation

Inferred from mutant phenotype PubMed 8940145. Source: BHF-UCL

positive regulation of glucose import

Inferred from mutant phenotype PubMed 16814735PubMed 8940145. Source: BHF-UCL

positive regulation of glucose metabolic process

Inferred from mutant phenotype PubMed 16814735. Source: BHF-UCL

positive regulation of glycogen biosynthetic process

Inferred from mutant phenotype PubMed 16814735. Source: BHF-UCL

positive regulation of lipid biosynthetic process

Inferred from mutant phenotype PubMed 8940145. Source: BHF-UCL

positive regulation of nitric oxide biosynthetic process

Inferred from mutant phenotype PubMed 10376603. Source: BHF-UCL

positive regulation of nitric-oxide synthase activity

Inferred from mutant phenotype PubMed 10376603. Source: BHF-UCL

positive regulation of peptidyl-serine phosphorylation

Inferred from direct assay PubMed 19667065. Source: UniProtKB

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway

Traceable author statement. Source: Reactome

positive regulation of protein phosphorylation

Inferred from direct assay PubMed 19057511. Source: BHF-UCL

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 19057511. Source: BHF-UCL

positive regulation of sodium ion transport

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of vasoconstriction

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Traceable author statement PubMed 16280327. Source: UniProtKB

protein catabolic process

Inferred from electronic annotation. Source: Ensembl

protein import into nucleus, translocation

Inferred from mutant phenotype PubMed 16280327. Source: UniProtKB

protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay Ref.19Ref.65. Source: UniProtKB

protein ubiquitination

Inferred from electronic annotation. Source: Ensembl

regulation of cell cycle checkpoint

Traceable author statement Ref.60. Source: UniProtKB

regulation of cell migration

Inferred from mutant phenotype Ref.45. Source: UniProtKB

regulation of glycogen biosynthetic process

Inferred from mutant phenotype PubMed 8940145. Source: BHF-UCL

regulation of neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of nitric-oxide synthase activity

Traceable author statement. Source: Reactome

regulation of translation

Inferred from electronic annotation. Source: UniProtKB-KW

response to UV-A

Inferred from direct assay PubMed 18483258. Source: BHF-UCL

response to fluid shear stress

Inferred from mutant phenotype PubMed 10376603. Source: BHF-UCL

response to food

Inferred from electronic annotation. Source: Ensembl

response to heat

Traceable author statement PubMed 10958679. Source: ProtInc

signal transduction

Traceable author statement Ref.60. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

striated muscle cell differentiation

Inferred from electronic annotation. Source: Ensembl

translation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 19203586. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 21045808. Source: UniProtKB

microtubule cytoskeleton

Inferred from direct assay. Source: HPA

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.52. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 19203586Ref.52. Source: UniProtKB

spindle

Inferred from electronic annotation. Source: Ensembl

   Molecular_function14-3-3 protein binding

Inferred from physical interaction PubMed 10102273. Source: UniProtKB

ATP binding

Inferred from direct assay Ref.37. Source: UniProtKB

enzyme binding

Inferred from sequence or structural similarity. Source: BHF-UCL

identical protein binding

Inferred from physical interaction PubMed 7891724. Source: IntAct

kinase activity

Inferred from direct assay Ref.29. Source: MGI

nitric-oxide synthase regulator activity

Inferred from mutant phenotype PubMed 10376603. Source: BHF-UCL

phosphatidylinositol-3,4,5-trisphosphate binding

Inferred from direct assay PubMed 19203586. Source: UniProtKB

phosphatidylinositol-3,4-bisphosphate binding

Inferred from direct assay PubMed 19203586. Source: UniProtKB

protein kinase activity

Traceable author statement PubMed 10570282. Source: ProtInc

protein serine/threonine kinase activity

Inferred from direct assay PubMed 10102273Ref.19Ref.32Ref.37PubMed 19667065. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 480480RAC-alpha serine/threonine-protein kinase
PRO_0000085605

Regions

Domain5 – 108104PH
Domain150 – 408259Protein kinase
Domain409 – 48072AGC-kinase C-terminal
Nucleotide binding156 – 1649ATP By similarity
Region14 – 196Inositol-(1,3,4,5)-tetrakisphosphate binding
Region23 – 253Inositol-(1,3,4,5)-tetrakisphosphate binding
Region228 – 2303Inhibitor binding

Sites

Active site2741Proton acceptor By similarity
Binding site531Inositol-(1,3,4,5)-tetrakisphosphate
Binding site861Inositol-(1,3,4,5)-tetrakisphosphate
Binding site1611Inhibitor; via amide nitrogen
Binding site1791ATP By similarity
Binding site2301Inhibitor; via amide nitrogen
Binding site2341Inhibitor
Binding site2921Inhibitor

Amino acid modifications

Modified residue141N6-acetyllysine Ref.62
Modified residue201N6-acetyllysine Ref.62
Modified residue1241Phosphoserine Ref.42
Modified residue1261Phosphoserine; alternate Ref.42
Modified residue1291Phosphoserine; alternate Ref.36 Ref.42
Modified residue1761Phosphotyrosine; by TNK2 Ref.52
Modified residue2841N6-acetyllysine; by MUL1
Modified residue3081Phosphothreonine; by IKKE, PDPK1 and TBK1 Ref.10 Ref.11 Ref.33 Ref.52 Ref.61 Ref.68 Ref.70
Modified residue4501Phosphothreonine; by MTOR By similarity
Modified residue4731Phosphoserine; by IKKE, MTOR and TBK1; alternate Ref.9 Ref.10 Ref.26 Ref.27 Ref.31 Ref.33 Ref.34 Ref.52 Ref.58 Ref.61
Modified residue4741Phosphotyrosine Ref.21
Glycosylation1261O-linked (GlcNAc); alternate Ref.64
Glycosylation1291O-linked (GlcNAc); alternate Ref.64
Glycosylation3051O-linked (GlcNAc) Ref.64
Glycosylation3121O-linked (GlcNAc) Ref.64
Glycosylation4731O-linked (GlcNAc); alternate By similarity
Disulfide bond60 ↔ 77 Ref.71
Disulfide bond296 ↔ 310 By similarity

Natural variations

Natural variant171E → 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.73 Ref.74 Ref.75
Corresponds to variant rs121434592 [ dbSNP | Ensembl ].
VAR_055422
Natural variant251R → C in CWD6. Ref.76
VAR_069791
Natural variant1671V → A.
Corresponds to variant rs11555433 [ dbSNP | Ensembl ].
VAR_051617
Natural variant4351T → P in CWD6. Ref.76
VAR_069792

Experimental info

Mutagenesis81K → 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
Mutagenesis141K → A: Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. Ref.46 Ref.62 Ref.66
Mutagenesis141K → 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.62 Ref.66
Mutagenesis141K → 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.62 Ref.66
Mutagenesis171E → K: No effect on membrane localization. Loss of membrane localization; when associated with Q-20. Ref.62
Mutagenesis201K → 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.62
Mutagenesis201K → R: Slight increase of phosphorylation at T-308 and S-473. Ref.62
Mutagenesis251R → A or C: Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. Ref.66
Mutagenesis861R → A: Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. Ref.66
Mutagenesis1761Y → F: Significant loss of interaction with TNK2. Loss of membrane localization. Significant reduction in phosphorylation on Ser-473. Ref.52
Mutagenesis3051T → A: Reduces O-GlcNAc levels; Reduces O-GlcNAc levels even more; when associated with A-312. Ref.64
Mutagenesis3051T → Y: Abolishes phosphorylation at Thr-308. Ref.64
Mutagenesis3081T → D: 5-fold activation and 18-fold activation; when associated with D-473. Ref.10 Ref.24
Mutagenesis3121T → A: Reduces O-GlcNAc levels; Reduces O-GlcNAc levels even more; when associated with A-305. Ref.64
Mutagenesis3121T → Y: Abolishes phosphorylation at Thr-308. Ref.64
Mutagenesis4731S → D: 7-fold activation and 25-fold activation; when associated with D-308. Ref.10 Ref.24
Mutagenesis4741Y → F: 55% inhibition of activation. Ref.21
Sequence conflict173 – 1742GR → A in CAA43372. Ref.6
Sequence conflict2021L → Q in CAA43372. Ref.6
Sequence conflict2121A → R in CAA43372. Ref.6
Sequence conflict2461S → A in CAA43372. Ref.6
Sequence conflict4091A → T in CAA43372. Ref.6
Sequence conflict4761A → P in CAA43372. Ref.6
Sequence conflict4781G → A in CAA43372. Ref.6
Sequence conflict4781G → S in AAA36539. Ref.1
Sequence conflict4781G → S in AAL55732. Ref.2
Sequence conflict4781G → S in BAG36922. Ref.3
Sequence conflict4781G → S in BAG70056. Ref.4
Sequence conflict4781G → S in BAG70181. Ref.4

Secondary structure

................................................................................ 480
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P31749 [UniParc].

Last modified February 1, 2005. Version 2.
Checksum: 6EAFF4F8AD436714

FASTA48055,686
        10         20         30         40         50         60 
MSDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVDQREA PLNNFSVAQC 

        70         80         90        100        110        120 
QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWT TAIQTVADGL KKQEEEEMDF 

       130        140        150        160        170        180 
RSGSPSDNSG AEEMEVSLAK PKHRVTMNEF EYLKLLGKGT FGKVILVKEK ATGRYYAMKI 

       190        200        210        220        230        240 
LKKEVIVAKD EVAHTLTENR VLQNSRHPFL TALKYSFQTH DRLCFVMEYA NGGELFFHLS 

       250        260        270        280        290        300 
RERVFSEDRA RFYGAEIVSA LDYLHSEKNV VYRDLKLENL MLDKDGHIKI TDFGLCKEGI 

       310        320        330        340        350        360 
KDGATMKTFC GTPEYLAPEV LEDNDYGRAV DWWGLGVVMY EMMCGRLPFY NQDHEKLFEL 

       370        380        390        400        410        420 
ILMEEIRFPR TLGPEAKSLL SGLLKKDPKQ RLGGGSEDAK EIMQHRFFAG IVWQHVYEKK 

       430        440        450        460        470        480 
LSPPFKPQVT SETDTRYFDE EFTAQMITIT PPDQDDSMEC VDSERRPHFP QFSYSASGTA 

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References

« Hide 'large scale' references
[1]"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.
[2]"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].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Adrenal gland.
[4]"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. expand/collapse author list , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N.
Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Muscle and Ovary.
[6]"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.
Tissue: Foreskin.
[7]Erratum
Coffer P.J., Woodgett J.R.
Eur. J. Biochem. 205:1217-1218(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[8]"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.
[9]"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.
[10]"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.
[11]"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.
[12]"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.
[13]"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.
[14]"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.
[15]"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.
[16]"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.
[17]"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.
[18]"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.
[19]"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.
[20]"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.
[21]"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.
[22]"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.
[23]"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.
[24]"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.
[25]"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.
[26]"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.
[27]"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.
[28]Erratum
Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.
J. Biol. Chem. 282:2752-2752(2007)
[29]"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.
[30]"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.
[31]"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.
[32]"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.
[33]"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.
[34]"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.
[35]"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.
[36]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[37]"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.
[38]"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.
[39]"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.
[40]"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.
[41]"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.
[42]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[43]"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.
[44]"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.
[45]"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.
[46]"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.
[47]"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.
[48]"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.
[49]"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.
[50]"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.
[51]"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.
[52]"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.
[53]"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].
[54]"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.
[55]"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.
[56]"Signal transduction via the stem cell factor receptor/c-Kit."
Ronnstrand L.
Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON ROLE IN KIT SIGNALING.
[57]"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.
[58]"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.
[59]"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.
[60]"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.
[61]"IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation."
Xie X., Zhang D., Zhao B., Lu M.K., You M., Condorelli G., Wang C.Y., Guan K.L.
Proc. Natl. Acad. Sci. U.S.A. 108:6474-6479(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-308 AND SER-473.
[62]"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.
[63]"Akt is negatively regulated by the MULAN E3 ligase."
Bae S., Kim S.Y., Jung J.H., Yoon Y., Cha H.J., Lee H., Kim K., Kim J., An I.S., Kim J., Um H.D., Park I.C., Lee S.J., Nam S.Y., Jin Y.W., Lee J.H., An S.
Cell Res. 22:873-885(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-284.
[64]"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.
[65]"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.
[66]"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.
[67]"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.
[68]"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.
[69]"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.
[70]"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. expand/collapse author list , Pandit J., Rajamohan F., Robinson S., Subramanyam C., Wei L., Wythes M., 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.
[71]"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.
[72]"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.
[73]"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. expand/collapse author list , Mousses S., Bittner M., Schevitz R., Lai M.-H.T., Blanchard K.L., 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.
[74]"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.
[75]"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. expand/collapse author list , Kato B.M., Keppler-Noreuil K.M., Kuznetsov S.A., Miyamoto R.T., Newman K., Ng D., O'Brien K., Rothenberg S., Schwartzentruber D.J., Singhal V., Tirabosco R., Upton J., Wientroub S., Zackai E.H., Hoag K., Whitewood-Neal T., Robey P.G., Schwartzberg P.L., Darling T.N., Tosi L.L., Mullikin J.C., Biesecker L.G.
N. Engl. J. Med. 365:611-619(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PROTEUSS LYS-17.
[76]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M63167 mRNA. Translation: AAA36539.1.
AF283830 expand/collapse EMBL AC list , AF283819, AF283820, AF283821, AF283822, AF283823, AF283824, AF283825, AF283826, AF283827, AF283828, 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.
PIRA39360.
RefSeqNP_001014431.1. NM_001014431.1.
NP_001014432.1. NM_001014432.1.
NP_005154.2. NM_005163.2.
XP_005267458.1. XM_005267401.1.
UniGeneHs.525622.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1H10X-ray1.40A1-123[»]
1UNPX-ray1.65A1-121[»]
1UNQX-ray0.98A1-123[»]
1UNRX-ray1.25A1-123[»]
2UVMX-ray1.94A1-123[»]
2UZRX-ray1.94A1-123[»]
2UZSX-ray2.46A1-123[»]
3CQUX-ray2.20A144-480[»]
3CQWX-ray2.00A144-480[»]
3MV5X-ray2.47A144-480[»]
3MVHX-ray2.01A144-480[»]
3O96X-ray2.70A2-443[»]
3OCBX-ray2.70A/B144-480[»]
3OW4X-ray2.60A/B144-480[»]
3QKKX-ray2.30A144-480[»]
3QKLX-ray1.90A144-480[»]
3QKMX-ray2.20A144-480[»]
4EJNX-ray2.19A2-446[»]
4EKKX-ray2.80A/B144-480[»]
4EKLX-ray2.00A144-480[»]
4GV1X-ray1.49A144-480[»]
ProteinModelPortalP31749.
SMRP31749. Positions 1-477.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106710. 212 interactions.
DIPDIP-24269N.
IntActP31749. 74 interactions.
MINTMINT-203775.
STRING9606.ENSP00000270202.

Chemistry

BindingDBP31749.
ChEMBLCHEMBL4282.
DrugBankDB00171. Adenosine triphosphate.
DB01169. Arsenic trioxide.
GuidetoPHARMACOLOGY1479.

PTM databases

PhosphoSiteP31749.

Polymorphism databases

DMDM60391226.

Proteomic databases

PaxDbP31749.
PRIDEP31749.

Protocols and materials databases

DNASU207.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000349310; ENSP00000270202; ENSG00000142208.
ENST00000402615; ENSP00000385326; ENSG00000142208.
ENST00000407796; ENSP00000384293; ENSG00000142208.
ENST00000554581; ENSP00000451828; ENSG00000142208.
ENST00000554848; ENSP00000451166; ENSG00000142208.
ENST00000555528; ENSP00000450688; ENSG00000142208.
GeneID207.
KEGGhsa:207.
UCSCuc001ypk.3. human.

Organism-specific databases

CTD207.
GeneCardsGC14M105235.
HGNCHGNC:391. AKT1.
HPACAB003765.
HPA002891.
MIM114480. phenotype.
114500. phenotype.
164730. gene.
176920. phenotype.
615109. phenotype.
neXtProtNX_P31749.
Orphanet201. Cowden syndrome.
744. Proteus syndrome.
PharmGKBPA24684.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233033.
HOVERGENHBG108317.
InParanoidP31749.
KOK04456.
OMASRERVFP.
PhylomeDBP31749.
TreeFamTF102004.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_11123. Membrane Trafficking.
REACT_116125. Disease.
REACT_21257. Metabolism of RNA.
REACT_578. Apoptosis.
REACT_604. Hemostasis.
REACT_6900. Immune System.
REACT_71. Gene Expression.
SignaLinkP31749.

Gene expression databases

ArrayExpressP31749.
BgeeP31749.
CleanExHS_AKT1.
GenevestigatorP31749.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR011993. PH_like_dom.
IPR017892. Pkinase_C.
IPR001849. Pleckstrin_homology.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
SMARTSM00233. PH. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51285. 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]
ProtoNetSearch...

Other

ChiTaRSAKT1. human.
EvolutionaryTraceP31749.
GeneWikiAKT1.
GenomeRNAi207.
NextBio828.
PMAP-CutDBP31749.
PROP31749.
SOURCESearch...

Entry information

Entry nameAKT1_HUMAN
AccessionPrimary (citable) accession number: P31749
Secondary accession number(s): B2RAM5, Q9BWB6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: February 1, 2005
Last modified: April 16, 2014
This is version 178 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM