AKT3 Protein

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AKT3 Protein

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">AKT3 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>RAC-gamma serine/threonine-protein kinase</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>AKT3</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>1q43-q44</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>10000</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>O95886</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>AKT/PKB kinase family</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~56 kDa</td>
</tr>
<tr>
<td class="label">Length</td>
<td>479 amino acids</td>
</tr>
<tr>
<td class="label">Domain</td>
<td>Position</td>
</tr>
<tr>
<td class="label">PH Domain</td>
<td>1-106</td>
</tr>
<tr>
<td class="label">Activation Loop</td>
<td>177-257</td>
</tr>
<tr>
<td class="label">HM Domain</td>
<td>328-480</td>
</tr>
<tr>
<td class="label">Compound</td>
<td>Target</td>
</tr>
<tr>
<td class="label">AKTi-1/2</td>
<td>AKT1/2</td>
</tr>
<tr>
<td class="label">Perifosine</td>
<td>AKT (PH domain)</td>
</tr>
<tr>
<td class="label">MK-2206</td>
<td>AKT (allosteric)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</

...

AKT3 Protein

Introduction

Akt3 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

AKT3 (AKT serine/threonine kinase 3) is a member of the AKT/PKB family of kinases, playing crucial roles in cell survival, proliferation, metabolism, and synaptic plasticity. While all three AKT isoforms (AKT1, AKT2, AKT3) share similar structures and functions, AKT3 has unique expression patterns and physiological roles, particularly in the brain. This page covers the AKT3 protein structure, function, and its involvement in neurodegenerative diseases. [@chin2015]

Protein Information

Protein Structure

AKT3 contains three conserved domains:

Domain Architecture

Activation Mechanism

AKT3 is activated through a three-step process:

Phosphoinositide Binding: PH domain binds PIP3 at plasma membrane

Thr308 Phosphorylation: PDK1 phosphorylates Thr308 (essential for activity)

Ser473 Phosphorylation: mTORC2 phosphorylates Ser473 (full activation)

Biological Functions

Cell Survival and Growth

PKB/AKT Pathway: Central to cell survival signaling
[mTOR](/entities/mtor) Activation: AKT activates mTORC1, promoting protein synthesis
FOXO Phosphorylation: AKT inactivates pro-apoptotic FOXO transcription factors
BAD Phosphorylation: Blocks BAD-mediated [apoptosis](/entities/apoptosis)

Metabolic Regulation

GLUT4 Translocation: AKT promotes glucose uptake
Glycogen Synthesis: Activates [GSK3](/entities/gsk3-beta), promoting glycogen synthesis
Lipid Metabolism: Regulates fatty acid synthesis and oxidation

Neuronal Functions

Synaptic Plasticity: Regulates [LTP](/mechanisms/long-term-potentiation) and memory formation
Neuronal Development: Promotes axon growth and guidance
Myelination: Essential for oligodendrocyte function
Neuroprotection: Guards against various insults

Brain-Specific Roles

Spatial Learning: AKT3 critical for hippocampal-dependent memory
Brain Development: Regulates neural progenitor proliferation
Myelination: AKT3 essential for oligodendrocyte survival

Expression Pattern

Tissue Distribution

Brain: Highest expression in [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), cerebellum
Heart: Moderate expression
Skeletal muscle: Lower expression
Liver: Minimal expression

Cell-Type Specificity

[Neurons](/entities/neurons): High expression in pyramidal neurons
[Astrocytes](/entities/astrocytes): Moderate expression
Oligodendrocytes: Important for myelination
[Microglia](/entities/microglia): Lower expression

Role in Neurodegeneration

Alzheimer's Disease

AKT3 plays complex roles in AD:

Neuroprotective Signaling: AKT activation protects against [Aβ](/proteins/amyloid-beta) toxicity
[Tau](/proteins/tau) Phosphorylation: AKT can phosphorylate [tau](/proteins/tau) (via GSK3β)
Synaptic Dysfunction: Altered AKT signaling in AD brain
Therapeutic Target: AKT modulators under investigation

Parkinson's Disease

Dopaminergic Survival: AKT promotes dopaminergic neuron survival
[α-Synuclein](/proteins/alpha-synuclein) Toxicity: AKT protects against α-synuclein
Mitochondrial Function: AKT regulates mitochondrial dynamics

ALS

Motor Neuron Survival: AKT signaling in motor neuron protection
Astrocyte Dysfunction: Altered AKT in ALS astrocytes

Schizophrenia and Bipolar Disorder

GWAS Findings: AKT1 variants associated with schizophrenia
Brain Volume: AKT3 variants affect brain volume
Synaptic Function: Altered AKT signaling in psychiatric disease

Therapeutic Targeting

AKT Modulators

Therapeutic Strategies

Activation: AKT activators for neuroprotection

Inhibition: Selective AKT3 targeting (challenging)

Downstream Modulation: [mTOR](/mechanisms/mtor-signaling-pathway), FOXO targeting

Research Directions

Brain-penetrant AKT modulators
Isoform-selective targeting
Biomarker development
Combination therapies

Background

The study of Akt3 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Allen Brain Atlas Resources

Allen Human Brain Atlas: [AKT3 gene expression](https://human.brain-map.org/microarray/search/show?search_term=AKT3)
Allen Mouse Brain Atlas: [AKT3 expression](https://mouse.brain-map.org/search/index.html?query=AKT3)
Allen Cell Type Atlas: [Transcriptomic cell type reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
BrainSpan Atlas: [AKT3 developmental expression](https://www.brainspan.org/rnaseq/search/index.html?search_term=AKT3)

External Links

[NCBI Gene: AKT3](https://www.ncbi.nlm.nih.gov/gene/10000)
[UniProt: O95886](https://www.uniprot.org/uniprot/O95886)
[GeneCards: AKT3](https://www.genecards.org/cgi-bin/carddisp.pl?gene=AKT3)
[PhosphoSitePlus: AKT3](https://www.phosphosite.org/proteinAction.action?id=4885)

References

[Hers I, et al, (2011) (2011)](https://pubmed.ncbi.nlm.nih.gov/21810480/)

[Chin LS, et al, (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/26713075/)

[Zhang L, et al, (2017) (2017)](https://pubmed.ncbi.nlm.nih.gov/28540623/)

[Park J, et al, (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/30291754/)

[Easton RM, et al, (2005) (2005)](https://pubmed.ncbi.nlm.nih.gov/15849189/)

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AKT3 Protein

AKT3 Protein

AKT3 Protein

Introduction

Overview

Protein Information

Protein Structure

Domain Architecture

Activation Mechanism

Biological Functions

Cell Survival and Growth

Metabolic Regulation

Neuronal Functions

Brain-Specific Roles

Expression Pattern

Tissue Distribution

Cell-Type Specificity

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

ALS

Schizophrenia and Bipolar Disorder

Therapeutic Targeting

AKT Modulators

Therapeutic Strategies

Research Directions

Background

Allen Brain Atlas Resources

See Also

External Links

References