MAPK1 Gene

MAPK1 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">MAPK1 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>MAPK1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Mitogen-Activated Protein Kinase 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>22q11.22</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>5594</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000100030</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>176948</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P28482</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Compound</td>
</tr>
<tr>
<td class="label">MEK inhibitors</td>
<td>Selumetinib, Trametinib</td>
</tr>
<tr>
<td class="label">ERK inhibitors</td>
<td>FR180204, Ulixertinib</td>
</tr>
<tr>
<td class="label">Neuroprotective</td>
<td>BDNF mimetics</td>
</tr>
<tr>
<td class="label">Activity-dependent</td>
<td>Synaptic stabilizers</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</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/autism" style="color:#ef9a9a">Autism</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="col

...

MAPK1 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">MAPK1 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>MAPK1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Mitogen-Activated Protein Kinase 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>22q11.22</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>5594</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000100030</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>176948</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P28482</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Compound</td>
</tr>
<tr>
<td class="label">MEK inhibitors</td>
<td>Selumetinib, Trametinib</td>
</tr>
<tr>
<td class="label">ERK inhibitors</td>
<td>FR180204, Ulixertinib</td>
</tr>
<tr>
<td class="label">Neuroprotective</td>
<td>BDNF mimetics</td>
</tr>
<tr>
<td class="label">Activity-dependent</td>
<td>Synaptic stabilizers</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</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/autism" style="color:#ef9a9a">Autism</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">422 edges</a></td>
</tr>
</table>

Introduction

Mapk1 Gene 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

The MAPK1 gene (Mitogen-Activated Protein Kinase 1) encodes ERK2 (Extracellular Signal-Regulated Kinase 2), a serine/threonine kinase central to cell signaling. MAPK1/ERK2 is involved in neuronal development, synaptic plasticity, learning, and memory. Dysregulated MAPK signaling contributes to neurodegeneration. [@ref2005]

Gene Information

Protein Information

MAPK1 encodes ERK2, a 360-amino acid protein kinase. It is closely related to MAPK3 (ERK1).

Normal Function

ERK/MAPK signaling regulates:

• Cell Growth and Proliferation: Key pathway for mitogenic signaling
• Neuronal Differentiation: Critical for neuronal development
• Synaptic Plasticity: Required for [LTP](/mechanisms/long-term-potentiation), learning, and memory
• Gene Transcription: Activates transcription factors (ELK-1, CREB)
• Protein Synthesis: Regulates translation machinery

Disease Associations

Alzheimer's Disease

• Synaptic Dysfunction: ERK2 activation impairs synaptic plasticity
• [Tau](/proteins/tau) Phosphorylation: Can phosphorylate [tau](/proteins/tau) at certain sites
• Memory Impairment: ERK inhibition impairs memory consolidation
• Amyloid Effects: [Aβ](/proteins/amyloid-beta) modulates ERK signaling

Parkinson's Disease

• ERK activation in dopaminergic [neurons](/entities/neurons)
• Contributes to neuronal death
• Links to LRRK2 pathway

Stroke and TBI

• Excitotoxicity activates ERK pathway
• Contributes to ischemic damage

Cancer

• MAPK pathway is oncogenic when overactivated

Expression Pattern

MAPK1 (ERK2) is ubiquitously expressed throughout the brain with particularly high levels in the [hippocampus](/brain-regions/hippocampus), cerebral [cortex](/brain-regions/cortex), and cerebellum. Within neurons, ERK2 localizes to both cytoplasmic and nuclear compartments, with activity-dependent nuclear translocation following synaptic activation. In the hippocampus, ERK2 is highly expressed in CA1 pyramidal neurons and dentate gyrus granule cells — regions critical for learning and memory. Expression is relatively constant across development but shows activity-dependent regulation in the adult brain. [NMDA](/entities/nmda-receptor) receptor activation, membrane depolarization, and neurotrophic factors (BDNF, NGF) all stimulate ERK2 activation and nuclear translocation. In AD brains, ERK2 activation patterns are altered, with both increased and decreased phosphorylation observed in different neuronal populations and disease stages.

Molecular Mechanisms

ERK2 (MAPK1) is a member of the MAP kinase family, a core component of signaling cascades that transduce extracellular signals to intracellular responses. The canonical MAPK/ERK pathway proceeds as follows:

Receptor activation: Growth factors, neurotransmitters, or stress signals activate cell surface receptors (RTKs, GPCRs)

Ras activation: Adaptor proteins (Shc, Grb2) recruit Ras-GTP

RAF activation: Ras-GTP activates RAF (MAP3K)

MEK activation: RAF phosphorylates and activates MEK1/2 (MAP2K)

ERK activation: MEK1/2 phosphorylates ERK1/2 (MAPK) on threonine and tyrosine residues

Nuclear translocation: Active ERK translocates to nucleus

Gene transcription: ERK phosphorylates transcription factors (ELK-1, CREB, c-Fos)

Key neuronal substrates of ERK2 include:

• Synaptic proteins: Synapsin, PSD-95, AMPA receptor subunits
• Transcription factors: ELK-1, CREB, c-Fos
• Cytoskeletal proteins: MAP2, Tau
• Other kinases: MSK1, RSK

Therapeutic Approaches

Animal Models

• Mapk1 knockout mice: Embryonic lethal, neural tube defects
• Conditional knockout: Show impaired [LTP](/entities/long-term-potentiation) and memory deficits
• ERK2 overexpression: Enhanced memory but also increased seizure susceptibility
• MEK inhibitors (PD98059, U0126): Block LTP and memory formation

Background

The study of Mapk1 Gene 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.

Brain Atlas Resources

Allen Brain Atlas Links

The Allen Brain Atlas provides comprehensive gene expression data across brain regions and cell types.

• [Allen Human Brain Atlas](https://human.brain-map.org/) — Gene expression data across the adult human brain
• [Allen Mouse Brain Atlas](https://mouse.brain-map.org/) — Gene expression in mouse brain
• [Allen Cell Type Atlas](https://celltype.brain-map.org/) — Single-cell transcriptomics data
• [BrainSpan Atlas of the Developing Human Brain](https://brainspan.org/) — Developmental expression data
• [Allen Brain Map Portal](https://portal.brain-map.org/) — Access to all Allen Institute brain data

Gene-Specific Expression Data

Search for expression data on the Allen Brain Atlas:

• [Human Brain Atlas search for this gene](https://human.brain-map.org/microarray/search/show?search_term=MAPK1)

Key Publications

External Links

• [NCBI Gene: MAPK1](https://www.ncbi.nlm.nih.gov/gene/5594)
• [UniProt: ERK2](https://www.uniprot.org/uniprot/P28482)
• [GeneCards: MAPK1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=MAPK1)

Brain Atlas Resources

Allen Brain Atlas Links

The Allen Brain Atlas provides comprehensive gene expression data across brain regions and cell types.

• [Allen Human Brain Atlas](https://human.brain-map.org/) — Gene expression data across the adult human brain
• [Allen Mouse Brain Atlas](https://mouse.brain-map.org/) — Gene expression in mouse brain
• [Allen Cell Type Atlas](https://celltype.brain-map.org/) — Single-cell transcriptomics data
• [BrainSpan Atlas of the Developing Human Brain](https://brainspan.org/) — Developmental expression data
• [Allen Brain Map Portal](https://portal.brain-map.org/) — Access to all Allen Institute brain data

Gene-Specific Expression Data

Search for expression data on the Allen Brain Atlas:

• [Human Brain Atlas search for this gene](https://human.brain-map.org/microarray/search/show?search_term=MAPK1)

References

[^5

Pathway Diagram

Pathway Diagram

The following diagram shows the key molecular relationships involving MAPK1 Gene discovered through SciDEX knowledge graph analysis: