P31749 (AKT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	480 AA.
Sequence status	Complete.
Protein existence	Evidence 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 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
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.66 Ref.67 Ref.68 Ref.70
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.61 Ref.62 Ref.64 Ref.65
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.62
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. 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. 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.72 Ref.73
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 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.
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 process	Apoptosis Carbohydrate metabolism Glucose metabolism Glycogen biosynthesis Glycogen metabolism Neurogenesis Sugar transport Translation regulation Transport
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Proto-oncogene
Ligand	ATP-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Traceable author statement PubMed 10570282. Source: ProtInc 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: Compara anagen Inferred from electronic annotation. Source: Compara apoptotic mitochondrial changes Inferred from electronic annotation. Source: Compara cell projection organization Inferred from electronic annotation. Source: Compara cell proliferation Traceable author statement Ref.60. Source: UniProtKB cellular response to epidermal growth factor stimulus Inferred from electronic annotation. Source: Compara cellular response to hypoxia Inferred from electronic annotation. Source: Compara endocrine pancreas development Traceable author statement. Source: Reactome epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome 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: Compara glucose homeostasis Inferred from electronic annotation. Source: Compara glucose metabolic process Inferred from electronic annotation. Source: UniProtKB-KW glucose transport Inferred from electronic annotation. Source: Compara glycogen biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW glycogen cell differentiation involved in embryonic placenta development Inferred from electronic annotation. Source: Compara inflammatory response Inferred from electronic annotation. Source: Compara 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 labyrinthine layer blood vessel development Inferred from electronic annotation. Source: Compara 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: Compara negative regulation of JNK cascade Inferred from electronic annotation. Source: Compara 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: Compara negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of fatty acid beta-oxidation Inferred from mutant phenotype PubMed 16814735. 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 nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome nitric oxide biosynthetic process Traceable author statement PubMed 10376602. Source: ProtInc osteoblast differentiation Inferred from electronic annotation. Source: Compara peptidyl-serine phosphorylation Inferred from direct assay Ref.32. Source: UniProtKB peripheral nervous system myelin maintenance Inferred from electronic annotation. Source: Compara phosphatidylinositol-mediated signaling Traceable author statement. Source: Reactome platelet activation Traceable author statement. Source: Reactome positive regulation of apoptotic process Inferred from electronic annotation. Source: Compara 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 cyclin-dependent protein serine/threonine kinase activity involved in G1/S Inferred from direct assay PubMed 18483258. Source: BHF-UCL 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 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: Compara 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: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of vasoconstriction Inferred from electronic annotation. Source: Compara protein autophosphorylation Traceable author statement PubMed 16280327. Source: UniProtKB protein catabolic process Inferred from electronic annotation. Source: Compara protein import into nucleus, translocation Inferred from mutant phenotype PubMed 16280327. Source: UniProtKB protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara protein ubiquitination Inferred from electronic annotation. Source: Compara regulation of cell cycle checkpoint Traceable author statement Ref.60. Source: UniProtKB regulation of neuron projection development Inferred from sequence or structural similarity. Source: UniProtKB 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: Compara response to heat Traceable author statement PubMed 10958679. Source: ProtInc small molecule metabolic process Traceable author statement. Source: Reactome striated muscle cell differentiation Inferred from electronic annotation. Source: Compara translation Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from direct assay PubMed 21045808. Source: UniProtKB lamellipodium Inferred from electronic annotation. Source: Compara microtubule cytoskeleton Inferred from direct assay. Source: HPA nucleoplasm Traceable author statement. Source: Reactome plasma membrane Inferred from direct assay PubMed 19203586Ref.52. Source: UniProtKB spindle Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from direct assay Ref.37. Source: UniProtKB enzyme binding Inferred from sequence or structural similarity. Source: BHF-UCL 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 serine/threonine kinase activity Inferred from direct assay Ref.19Ref.32Ref.37PubMed 19667065. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		3	EBI-296087,EBI-296087
Arrb2	P29067	2	EBI-296087,EBI-1636616	From a different organism.
ASXL1	Q8IXJ9	2	EBI-296087,EBI-1646500
BCL10	O95999	4	EBI-296087,EBI-958922
CDC37	Q16543	2	EBI-296087,EBI-295634
GSK3B	P49841	2	EBI-296087,EBI-373586
MAP3K5	Q99683	2	EBI-296087,EBI-476263
PPL	O60437	2	EBI-296087,EBI-368321
SETDB1	Q15047	9	EBI-296087,EBI-79691
SIRT1	Q96EB6	5	EBI-296087,EBI-1802965
VIM	P08670	29	EBI-296087,EBI-353844

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 480

480

RAC-alpha serine/threonine-protein kinase

PRO_0000085605

Regions

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

Sites

Active site

274

1

Proton acceptor By similarity

Binding site

53

1

Inositol-(1,3,4,5)-tetrakisphosphate

Binding site

86

1

Inositol-(1,3,4,5)-tetrakisphosphate

Binding site

161

1

Inhibitor; via amide nitrogen

Binding site

179

1

ATP By similarity

Binding site

230

1

Inhibitor; via amide nitrogen

Binding site

234

1

Inhibitor

Binding site

292

1

Inhibitor

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 variations

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 ].

VAR_055422

Natural variant

167

1

V → A.
Corresponds to variant rs11555433 [ dbSNP | Ensembl ].

VAR_051617

Experimental info

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

Secondary structure

1

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480

Helix Strand Turn

Details...

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 – 159

10

Beta strand

162 – 169

8

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 – 228

9

Helix

235 – 242

8

Helix

247 – 266

20

Turn

267 – 269

3

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 – 321

4

Helix

330 – 344

15

Helix

354 – 363

10

Helix

374 – 383

10

Turn

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

Sequences

	Sequence		Length	Mass (Da)
	P31749 [UniParc]. Last modified February 1, 2005. Version 2. Checksum: 6EAFF4F8AD436714	FASTA	480	55,686
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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]	"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.
[62]	"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.
[63]	"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. 0:0-0(2013) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[64]	"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.
[65]	"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.
[66]	"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.
[67]	"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.
[68]	"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. , 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.
[69]	"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.
[70]	"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.
[71]	"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. , 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.
[72]	"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.
[73]	"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. , 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M63167 mRNA. Translation: AAA36539.1.
AF283830 , 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.

IPI

IPI00012866.

PIR

A39360.

RefSeq

NP_001014431.1. NM_001014431.1.
NP_001014432.1. NM_001014432.1.
NP_005154.2. NM_005163.2.

UniGene

Hs.525622.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1H10	X-ray	1.40	A	1-123	[»]
1UNP	X-ray	1.65	A	1-121	[»]
1UNQ	X-ray	0.98	A	1-123	[»]
1UNR	X-ray	1.25	A	1-123	[»]
2UVM	X-ray	1.94	A	1-123	[»]
2UZR	X-ray	1.94	A	1-123	[»]
2UZS	X-ray	2.46	A	1-123	[»]
3CQU	X-ray	2.20	A	144-480	[»]
3CQW	X-ray	2.00	A	144-480	[»]
3MV5	X-ray	2.47	A	144-480	[»]
3MVH	X-ray	2.01	A	144-480	[»]
3O96	X-ray	2.70	A	2-443	[»]
3OCB	X-ray	2.70	A/B	144-480	[»]
3OW4	X-ray	2.60	A/B	144-480	[»]
3QKK	X-ray	2.30	A	144-480	[»]
3QKL	X-ray	1.90	A	144-480	[»]
3QKM	X-ray	2.20	A	144-480	[»]
4EJN	X-ray	2.19	A	2-446	[»]
4EKK	X-ray	2.80	A/B	144-480	[»]
4EKL	X-ray	2.00	A	144-480	[»]
4GV1	X-ray	1.49	A	144-480	[»]

ProteinModelPortal

P31749.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-24269N.

IntAct

P31749. 35 interactions.

MINT

MINT-203775.

STRING

9606.ENSP00000270202.

PTM databases

PhosphoSite

P31749.

Polymorphism databases

DMDM

60391226.

Proteomic databases

PaxDb

P31749.

PRIDE

P31749.

Protocols and materials databases

DNASU

207.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000349310; ENSP00000270202; ENSG00000142208.
ENST00000402615; ENSP00000385326; ENSG00000142208.
ENST00000407796; ENSP00000384293; ENSG00000142208.
ENST00000554581; ENSP00000451828; ENSG00000142208.
ENST00000554848; ENSP00000451166; ENSG00000142208.
ENST00000555528; ENSP00000450688; ENSG00000142208.

GeneID

207.

KEGG

hsa:207.

UCSC

uc001ypk.3. human.

Organism-specific databases

CTD

207.

GeneCards

GC14M105235.

HGNC

HGNC:391. AKT1.

HPA

CAB003765.
HPA002891.

MIM

114480. phenotype.
114500. phenotype.
164730. gene.
176920. phenotype.

neXtProt

NX_P31749.

Orphanet

744. Proteus syndrome.

PharmGKB

PA24684.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233033.

HOVERGEN

HBG108317.

InParanoid

P31749.

KO

K04456.

OMA

REEWTKA.

OrthoDB

EOG40GCQP.

PhylomeDB

P31749.

Enzyme and pathway databases

BRENDA

2.7.11.1. 2681.

Pathway_Interaction_DB

a6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.
amb2_neutrophils_pathway. amb2 Integrin signaling.
angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
aurora_a_pathway. Aurora A signaling.
bcr_5pathway. BCR signaling pathway.
ceramidepathway. Ceramide signaling pathway.
pi3kciaktpathway. Class I PI3K signaling events mediated by Akt.
ar_pathway. Coregulation of Androgen receptor activity.
endothelinpathway. Endothelins.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
fgf_pathway. FGF signaling pathway.
hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.
foxopathway. FoxO family signaling.
hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins.
hif1_tfpathway. HIF-1-alpha transcription factor network.
ifngpathway. IFN-gamma pathway.
igf1_pathway. IGF1 pathway.
il2_pi3kpathway. IL2 signaling events mediated by PI3K.
il4_2pathway. IL4-mediated signaling events.
il6_7pathway. IL6-mediated signaling events.
insulin_pathway. Insulin Pathway.
insulin_glucose_pathway. Insulin-mediated glucose transport.
avb3_integrin_pathway. Integrins in angiogenesis.
lysophospholipid_pathway. LPA receptor mediated events.
mtor_4pathway. mTOR signaling pathway.
p75ntrpathway. p75(NTR)-mediated signaling.
pdgfrbpathway. PDGFR-beta signaling pathway.
er_nongenomic_pathway. Plasma membrane estrogen receptor signaling.
reelinpathway. Reelin signaling pathway.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
telomerasepathway. Regulation of Telomerase.
retinoic_acid_pathway. Retinoic acid receptors-mediated signaling.
s1p_s1p3_pathway. S1P3 pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
ptp1bpathway. Signaling events mediated by PTP1B.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
hedgehog_2pathway. Signaling events mediated by the Hedgehog family.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.
txa2pathway. Thromboxane A2 receptor signaling.
pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.
vegfr1_pathway. VEGFR1 specific signals.
lymphangiogenesis_pathway. VEGFR3 signaling in lymphatic endothelium.

Reactome

REACT_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.

Gene expression databases

ArrayExpress

P31749.

Bgee

P31749.

CleanEx

HS_AKT1.

Genevestigator

P31749.

GermOnline

ENSG00000142208. Homo sapiens.

Family and domain databases

Gene3D

2.30.29.30. 1 hit.

InterPro

IPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR011993. PH_like_dom.
IPR017892. Pkinase_C.
IPR001849. Pleckstrin_homology.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]

SMART

SM00233. PH. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 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.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P31749.

ChEMBL

CHEMBL4282.

ChiTaRS

AKT1. human.

DrugBank

DB00171. Adenosine triphosphate.
DB01169. Arsenic trioxide.

EvolutionaryTrace

P31749.

GenomeRNAi

207.

NextBio

828.

PMAP-CutDB

P31749.

SOURCE

Search...

Entry information

Entry name

AKT1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 167 of the entry and version 2 of the sequence. [Complete history]

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.