KAT6B — MORF Protein
Introduction
KAT6B (Lysine Acetyltransferase 6B), also known as MORF (MOZ-Related Factor), is a histone acetyltransferase closely related to KAT6A that plays critical roles in gene regulation and has been implicated in neurodegenerative processes. [@katbmorf2023]
Brain Atlas Resources
The [Allen Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=KAT6B) provides gene expression data for KAT6B:
- Human Brain Expression: Searchable expression data across brain regions
- Cell Type Specificity: Expression patterns in different neuronal populations
- [View Expression Data](https://human.brain-map.org/microarray/search/show?search_term=KAT6B)
<div class="infobox infobox-protein"> [@myst2022]
<div class="infobox-header">KAT6B</div> [@epigenetic2023]
<div class="infobox-row"><strong>Gene:</strong> [KAT6B](/genes/kat6b)</div> [@histone2022]
<div class="infobox-row"><strong>UniProt ID:</strong> [Q8WYB5](https://www.uniprot.org/uniprot/Q8WYB5)</div> [@katb2021]
<div class="infobox-row"><strong>PDB ID:</strong> [5C83](https://www.rcsb.org/structure/5C83)</div>
<div class="infobox-row"><strong>Molecular Weight:</strong> ~235 kDa (2071 amino acids)</div>
<div class="infobox-row"><strong>Subcellular Localization:</strong> Nucleus, nuclear speckles</div>
<div class="infobox-row"><strong>Protein Family:</strong> MYST family</div>
<div class="infobox-row"><strong>Associated Diseases:</strong> [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Neurodevelopmental disorders, Ohdo syndrome</div>
</div>
Overview
KAT6B (also known as MORF, MYST4, or QCR) is a transcriptional coactivator and histone acetyltransferase belonging to the MYST family, closely related to KAT6A/MOZ. [@morf2022] Encoded by the KAT6B gene, this 2071-amino acid protein shares significant homology with KAT6A and has overlapping as well as distinct functions in transcriptional regulation. KAT6B plays essential roles in development, cell cycle regulation, and neuronal function.
Structure
KAT6B has a complex multi-domain architecture similar to KAT6A:
Domain Organization
- N-terminal domain (residues 1-520): Transcriptional activation
- PHD-type zinc fingers (residues 520-820): Chromatin binding
- CHROMO domain (residues 820-970): Histone binding
- MYST HAT domain (residues 1420-1850): Histone acetyltransferase activity
- C-terminal region (residues 1850-2071): Regulatory
Structural Features
- Highly conserved HAT domain (78% identity with KAT6A)
- Multiple chromatin reader domains
- Nuclear localization signals
- Dimerization interfaces
Normal Function
Transcriptional Regulation
KAT6B functions as a transcriptional coactivator:
Core Functions
- Histone H3 and H4 acetylation [^7]
- Transcriptional activation of development and stress response genes
- Regulation of neuronal differentiation
- Complex formation with other transcriptional coactivators
Target Pathways
| Pathway | Function | Brain Relevance |
|---------|----------|-----------------|
| p53 pathway | Stress response | Neuronal survival |
| Nuclear receptors | Hormone signaling | Synaptic plasticity |
| Wnt signaling | Development | Neurogenesis |
Brain Function
- Expressed in neural progenitor cells
- Required for cortical development
- Role in synaptic plasticity and memory
- Expressed in [hippocampus](/brain-regions/hippocampus) and [cortex](/brain-regions/cortex)
Role in Neurodegeneration
Alzheimer's Disease
- Altered expression in AD brain [^8]
- Role in epigenetic dysregulation
- Interaction with [tau](/proteins/tau) pathology
- Potential therapeutic target
Parkinson's Disease
- Dysregulated in PD models [^9]
- Role in dopaminergic neuron survival
- Epigenetic modifications in neurodegeneration
Neurodevelopmental Disorders
- KAT6B mutations cause Ohdo syndrome [^10]
- Intellectual disability phenotypes
- Genitopatellar syndrome
- Important for early brain development
Therapeutic Targeting
Drug Development
- HAT domain-specific inhibitors
- Epigenetic therapy approaches
- Combination with [HDAC](/entities/hdac-enzymes) inhibitors
- Targeted degradation strategies
- Histone acetylation sensors
- ChIP-grade antibodies
- CRISPR epigenetic editors
See Also
- [KAT6B Gene](/genes/kat6b)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
External Links
- [UniProt: Q8WYB5](https://www.uniprot.org/uniprot/Q8WYB5)
- [PDB structures](https://www.rcsb.org/search?q=uniprot:Q8WYB5)
- [GeneCards: KAT6B](https://www.genecards.org/cgi-bin/carddisp.pl?gene=KAT6B)
References
[Unknown, KAT6B/MORF: Functions and mechanisms (2023) (2023)](https://doi.org/10.1016/j.tcb.2023.02.008)
[Unknown, MYST family histone acetyltransferases in the brain (2022) (2022)](https://doi.org/10.1016/j.neuroscience.2022.01.025)
[Unknown, Epigenetic therapy for neurodegenerative disease (2023) (2023)](https://doi.org/10.1038/s41582-023-00789-2)
[Unknown, Histone acetylation deficits in AD (2022) (2022)](https://doi.org/10.1002/alz.12678)
[Unknown, KAT6B and neurodevelopment (2021) (2021)](https://doi.org/10.1038/gim.2021.203)
[Unknown, MORF and MOZ in transcription (2022) (2022)](https://doi.org/10.1016/j.jmb.2022.167456)