Summary of AKT1
The AKT1 gene codes for AKT serine/threonine kinase 1 (AKT1).
AKT1 is an enzyme involved in many cellular processes, including [R, R, R]:
- Cell growth and division (cell proliferation)
- Cell specialization
- Cell survival
- Blood vessel formation
AKT1 dysregulation may promote [R]:
- Cancer
- Heart disease
- Schizophrenia
The Function of AKT1
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.
Protein names
Recommended name:
RAC-alpha serine/threonine-protein kinaseShort name:
PKBAlternative name(s):
Protein kinase BProtein kinase B alpha
PKB alpha
Proto-oncogene c-Akt
RAC-PK-alpha
- RS3730358 (AKT1) ??
- RS3803304 (AKT1) ??
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Top Gene-Substance Interactions
AKT1 Interacts with These Diseases
Disease | Score |
Fixes
Substances That Increase AKT1
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Substances That Decrease AKT1
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Advanced Summary
At least one mutation in the AKT1 gene has been found to cause Proteus syndrome, a rare condition characterized by overgrowth of the bones, skin, and other tissues. This mutation changes a single protein building block (amino acid) in AKT1 kinase. Specifically, it replaces the amino acid glutamic acid with the amino acid lysine at protein position 17 (written as Glu17Lys or E17K). The mutation is not inherited from a parent; in people with Proteus syndrome, the mutation arises randomly in one cell during the early stages of development before birth. As cells continue to grow and divide, some cells will have the mutation and other cells will not. This mixture of cells with and without a genetic mutation is known as mosaicism. The Glu17Lys mutation leads to the production of an overactive AKT1 kinase that is turned on when it should not be. The abnormally active protein disrupts a cell's ability to regulate its own growth, allowing the cell to grow and divide abnormally. Increased cell proliferation in various tissues and organs leads to the overgrowth characteristic of Proteus syndrome. Studies suggest that the AKT1 gene mutation is more common in groups of cells that experience overgrowth than in the parts of the body that grow normally. cancers The Glu17Lys mutation in the AKT1 gene (described above) has also been found in a small percentage of breast, ovarian, and colorectal cancers. In these cases the mutation is somatic, which means it is acquired during a person's lifetime and is present only in tumor cells. The mutation abnormally activates AKT1 kinase, allowing cells to grow and divide without control or order. This disordered cell proliferation leads to the development of cancerous tumors. Although the Glu17Lys mutation has been reported in only a few types of cancer, increased activity (expression) of the AKT1 gene is found in many types of cancer. other disorders Several common variations (polymorphisms) in the AKT1 gene have been found more often in people with schizophrenia than in those without the disease. These polymorphisms alter single DNA building blocks (nucleotides) in the AKT1 gene. It is unknown whether the genetic changes have an effect on the structure or function of AKT1 kinase, and if so, how they are related to the development of schizophrenia. AKT1 gene polymorphisms appear to be one of many genetic and environmental factors that contribute to the development of this complex psychiatric disorder.
The AKT1 gene provides instructions for making a protein called AKT1 kinase. This protein is found in various cell types throughout the body, where it plays a critical role in many signaling pathways. For example, AKT1 kinase helps regulate cell growth and division (proliferation), the process by which cells mature to carry out specific functions (differentiation), and cell survival. AKT1 kinase also helps control apoptosis, which is the self-destruction of cells when they become damaged or are no longer needed. Signaling involving AKT1 kinase appears to be essential for the normal development and function of the nervous system. Studies have suggested a role for AKT1 kinase in cell-to-cell communication among nerve cells (neurons), neuronal survival, and the formation of memories. The AKT1 gene belongs to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous.
Conditions with Increased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
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.
Gene Pathways:
- Immune System
- Non-small cell lung cancer
- Hemostasis
- Small cell lung cancer
- Apoptosis
- Insulin signaling pathway
- Regulation of Beta-Cell Development
- Chagas disease (American trypanosomiasis)
- Tuberculosis
- Toxoplasmosis
- Pathways in cancer
- Membrane Trafficking
- Toll-like receptor signaling pathway
- Gene Expression
- T cell receptor signaling pathway
- Disease
- Neurotrophin signaling pathway
- Progesterone-mediated oocyte maturation
- Chemokine signaling pathway
- Metabolism of RNA
- Osteoclast differentiation
- Translocation of Glut4 to the Plasma Membrane
- mTOR signaling pathway
- Measles
- VEGF signaling pathway
- Melanoma
- Fc epsilon RI signaling pathway
- Apoptosis
- Colorectal cancer
- Prostate cancer
- Endometrial cancer
- Adipocytokine signaling pathway
- Carbohydrate digestion and absorption
- Glioma
- Jak-STAT signaling pathway
- MAPK signaling pathway
- Signal Transduction
- Tight junction
- B cell receptor signaling pathway
- Acute myeloid leukemia
- Metabolism
- Chronic myeloid leukemia
- Pancreatic cancer
- Renal cell carcinoma
- Hepatitis C
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.
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.
Molecular Function:
- Protein Serine/Threonine Kinase Activity
- Protein Serine/Threonine/Tyrosine Kinase Activity
- Atp Binding
- Phosphatidylinositol-3,4,5-Trisphosphate Binding
- Enzyme Binding
- Nitric-Oxide Synthase Regulator Activity
- Identical Protein Binding
- Phosphatidylinositol-3,4-Bisphosphate Binding
- 14-3-3 Protein Binding
Biological Processes:
- Activation-Induced Cell Death Of T Cells
- Aging
- Apoptotic Mitochondrial Changes
- Cell Differentiation
- Cell Projection Organization
- Cell Proliferation
- Cellular Protein Modification Process
- Cellular Response To Dna Damage Stimulus
- Cellular Response To Epidermal Growth Factor Stimulus
- Cellular Response To Granulocyte Macrophage Colony-Stimulating Factor Stimulus
- Cellular Response To Hypoxia
- Cellular Response To Insulin Stimulus
- Cellular Response To Mechanical Stimulus
- Cellular Response To Nerve Growth Factor Stimulus
- Cellular Response To Organic Cyclic Compound
- Cellular Response To Prostaglandin E Stimulus
- Cellular Response To Vascular Endothelial Growth Factor Stimulus
- Chemical Synaptic Transmission, Postsynaptic
- Endocrine Pancreas Development
- Erbb2 Signaling Pathway
- Establishment Of Protein Localization To Mitochondrion
- Execution Phase Of Apoptosis
- Germ Cell Development
- Glucose Homeostasis
- Glucose Metabolic Process
- Glucose Transport
- Glycogen Biosynthetic Process
- Glycogen Cell Differentiation Involved In Embryonic Placenta Development
- G-Protein Coupled Receptor Signaling Pathway
- Hyaluronan Metabolic Process
- Inflammatory Response
- Insulin-Like Growth Factor Receptor Signaling Pathway
- Insulin Receptor Signaling Pathway
- Interleukin-18-Mediated Signaling Pathway
- Intracellular Signal Transduction
- Labyrinthine Layer Blood Vessel Development
- Lipopolysaccharide-Mediated Signaling Pathway
- Maintenance Of Protein Location In Mitochondrion
- Mammary Gland Epithelial Cell Differentiation
- Maternal Placenta Development
- Negative Regulation Of Apoptotic Process
- Negative Regulation Of Autophagy
- Negative Regulation Of Cell Size
- Negative Regulation Of Cysteine-Type Endopeptidase Activity Involved In Apoptotic Process
- Negative Regulation Of Endopeptidase Activity
- Negative Regulation Of Extrinsic Apoptotic Signaling Pathway In Absence Of Ligand
- Negative Regulation Of Fatty Acid Beta-Oxidation
- Negative Regulation Of Gene Expression
- Negative Regulation Of Jnk Cascade
- Negative Regulation Of Neuron Death
- Negative Regulation Of Oxidative Stress-Induced Intrinsic Apoptotic Signaling Pathway
- Negative Regulation Of Plasma Membrane Long-Chain Fatty Acid Transport
- Negative Regulation Of Protein Kinase Activity
- Negative Regulation Of Protein Kinase Activity By Protein Phosphorylation
- Negative Regulation Of Proteolysis
- Negative Regulation Of Release Of Cytochrome C From Mitochondria
- Nitric Oxide Biosynthetic Process
- Osteoblast Differentiation
- Peptidyl-Serine Phosphorylation
- Peptidyl-Threonine Phosphorylation
- Peripheral Nervous System Myelin Maintenance
- Phosphatidylinositol-Mediated Signaling
- Phosphorylation
- Platelet Activation
- Positive Regulation Of Apoptotic Process
- Positive Regulation Of Blood Vessel Endothelial Cell Migration
- Positive Regulation Of Cell Growth
- Positive Regulation Of Cellular Protein Metabolic Process
- Positive Regulation Of Cyclin-Dependent Protein Serine/Threonine Kinase Activity Involved In G1/S Transition Of Mitotic Cell Cycle
- Positive Regulation Of Endodeoxyribonuclease Activity
- Positive Regulation Of Endothelial Cell Proliferation
- Positive Regulation Of Epidermal Growth Factor Receptor Signaling Pathway
- Positive Regulation Of Establishment Of Protein Localization To Plasma Membrane
- Positive Regulation Of Fat Cell Differentiation
- Positive Regulation Of Fibroblast Migration
- Positive Regulation Of Glucose Import
- Positive Regulation Of Glucose Metabolic Process
- Positive Regulation Of Glycogen Biosynthetic Process
- Positive Regulation Of Lipid Biosynthetic Process
- Positive Regulation Of Nitric Oxide Biosynthetic Process
- Positive Regulation Of Nitric-Oxide Synthase Activity
- Positive Regulation Of Peptidyl-Serine Phosphorylation
- Positive Regulation Of Proteasomal Ubiquitin-Dependent Protein Catabolic Process
- Positive Regulation Of Protein Localization To Nucleus
- Positive Regulation Of Protein Phosphorylation
- Positive Regulation Of Sequence-Specific Dna Binding Transcription Factor Activity
- Positive Regulation Of Smooth Muscle Cell Proliferation
- Positive Regulation Of Sodium Ion Transport
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
- Positive Regulation Of Vasoconstriction
- Protein Autophosphorylation
- Protein Catabolic Process
- Protein Import Into Nucleus, Translocation
- Protein Kinase B Signaling
- Protein Phosphorylation
- Protein Ubiquitination
- Regulation Of Cell Cycle Checkpoint
- Regulation Of Cell Migration
- Regulation Of Glycogen Biosynthetic Process
- Regulation Of Mrna Stability
- Regulation Of Myelination
- Regulation Of Neuron Projection Development
- Regulation Of Nitric-Oxide Synthase Activity
- Regulation Of Phosphatidylinositol 3-Kinase Signaling
- Regulation Of Signal Transduction By P53 Class Mediator
- Regulation Of Translation
- Response To Fluid Shear Stress
- Response To Food
- Response To Growth Hormone
- Response To Heat
- Response To Insulin-Like Growth Factor Stimulus
- Response To Oxidative Stress
- Response To Uv-A
- Signal Transduction
- Spinal Cord Development
- Striated Muscle Cell Differentiation
- T Cell Costimulation
- Translation
Drug Bank:
- Adenosine Triphosphate
- Arsenic Trioxide