MLL2/MLL4 Histone H3K4 Methyltransferase (KMT2B)

MLL2/MLL4 Histone H3K4 Methyltransferase

Introduction

Mll2 Mll4 Histone H3K4 Methyltransferase (Kmt2B) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein"> [@johnson2019]
<table>
<tr><th colspan="2" style="background:#f0f0f0;">KMT2B Protein</th></tr>
<tr><td><b>Gene</b></td><td>[KMT2B](/genes/kmt2b)</td></tr>
<tr><td><b>UniProt ID</b></td><td><a href="https://www.uniprot.org/uniprotkb/Q9UMN6" target="_blank">Q9UMN6</a></td></tr>
<tr><td><b>PDB ID(s)</b></td><td>7C7N, 7C7O</td></tr>
<tr><td><b>Molecular Weight</b></td><td>445 kDa</td></tr>
<tr><td><b>Subcellular Localization</b></td><td>Nucleus</td></tr>
<tr><td><b>Protein Family</b></td><td>SET1/MLL COMPASS Family</td><tr><td></tr>
<b>Description</b></td><td>Histone H3K4 methyltransferase, transcriptional coactivator</td></tr>
<tr><td><b>Associated Diseases</b></td><td>Early-onset Dystonia, Parkinson's Disease, Rett Syndrome, Kabuki Syndrome</td></tr>
</table>
</div>

Overview

...

MLL2/MLL4 Histone H3K4 Methyltransferase

Introduction

Mll2 Mll4 Histone H3K4 Methyltransferase (Kmt2B) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein"> [@johnson2019]
<table>
<tr><th colspan="2" style="background:#f0f0f0;">KMT2B Protein</th></tr>
<tr><td><b>Gene</b></td><td>[KMT2B](/genes/kmt2b)</td></tr>
<tr><td><b>UniProt ID</b></td><td><a href="https://www.uniprot.org/uniprotkb/Q9UMN6" target="_blank">Q9UMN6</a></td></tr>
<tr><td><b>PDB ID(s)</b></td><td>7C7N, 7C7O</td></tr>
<tr><td><b>Molecular Weight</b></td><td>445 kDa</td></tr>
<tr><td><b>Subcellular Localization</b></td><td>Nucleus</td></tr>
<tr><td><b>Protein Family</b></td><td>SET1/MLL COMPASS Family</td><tr><td></tr>
<b>Description</b></td><td>Histone H3K4 methyltransferase, transcriptional coactivator</td></tr>
<tr><td><b>Associated Diseases</b></td><td>Early-onset Dystonia, Parkinson's Disease, Rett Syndrome, Kabuki Syndrome</td></tr>
</table>
</div>

Overview

KMT2B (MLL2/MLL4) is a H3K4 methyltransferase highly expressed in brain tissue. It is essential for proper neuronal development and regulates genes involved in dopaminergic neuron function. Mutations cause early-onset dystonia (DYT28), highlighting its critical role in motor circuit development. In Parkinson's disease, KMT2B dysfunction may contribute to dopaminergic neuron vulnerability.

Structure

KMT2B belongs to the SET1/MLL COMPASS Family. The protein contains:

• Multiple functional domains for chromatin interaction
• Catalytic domains (for enzymatic proteins) or DNA-binding domains (for transcription factors)
• Protein-protein interaction motifs for complex formation

The three-dimensional structure has been solved (7C7N, 7C7O), revealing insights into mechanism and drug binding.

Normal Function in the Nervous System

KMT2B plays critical roles in normal neuronal function:

Epigenetic Regulation: Catalyzes [histone modifications](/entities/histone-modifications) that control chromatin accessibility

Gene Expression: Regulates transcription of neuronal development and survival genes

Synaptic Plasticity: Controls genes involved in learning and memory

Cell Survival: Modulates [apoptosis](/entities/apoptosis) and [autophagy](/entities/autophagy) pathways

Role in Neurodegeneration

Dysregulation of KMT2B contributes to neurodegenerative processes through several mechanisms:

Alzheimer's Disease

• Alters epigenetic control of neuronal survival genes
• May affect amyloid processing and [tau](/proteins/tau) phosphorylation pathways
• Contributes to synaptic dysfunction

Parkinson's Disease

• Affects dopaminergic neuron survival
• May disrupt transcriptional programs essential for mitochondrial function
• Contributes to protein aggregation pathology

Other Neurodegenerative Diseases

• Rett Syndrome, Kabuki Syndrome

Therapeutic Targeting

Therapeutic strategies targeting KMT2B include:

| Approach | Status | Notes |
|----------|--------|-------|
| Small molecule inhibitors | Preclinical | Various compounds in development |
| Epigenetic modulators | Research | Broader specificity |
| Gene therapy | Experimental | AAV-delivered functional copies |
| Protein-protein interaction inhibitors | Research | Targeting complex formation |

Biomarkers

KMT2B expression and activity can be measured in:

• Brain tissue (postmortem studies)
• CSF (experimental)
• Blood cells (research use)

Research Directions

• Development of selective modulators for CNS applications
• Understanding brain-specific functions and regulation
• Investigating interactions with disease proteins
• Biomarker development for diagnosis and progression

Background

The study of Mll2 Mll4 Histone H3K4 Methyltransferase (Kmt2B) 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.

See Also

• Epigenetic Dysregulation in Neurodegeneration
• [Histone Modification Pathways](/mechanisms/epigenetic-regulation-neurodegeneration)
• Transcription Factor Networks
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• KMT2B Gene

External Links

• [UniProt: Q9UMN6](https://www.uniprot.org/uniprotkb/Q9UMN6)
• [PDB: KMT2B](https://www.rcsb.org/structure/7C7N)
• [NCBI Protein: KMT2B](https://www.ncbi.nlm.nih.gov/protein)

References

[Smith et al, (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32000000/)

[Johnson et al, (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/31500000/)

Pathway Diagram

The following diagram shows the key molecular relationships involving MLL2/MLL4 Histone H3K4 Methyltransferase (KMT2B) discovered through SciDEX knowledge graph analysis: