KAT6A — MOZ Protein
Introduction
KAT6A (Lysine Acetyltransferase 6A), also known as MOZ (Monocytic Leukemia Zinc Finger Protein), is a histone acetyltransferase that plays critical roles in gene regulation and has been implicated in neurodegenerative diseases. [@katamoz2023]
Brain Atlas Resources
The [Allen Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=KAT6A) provides gene expression data for KAT6A:
- 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=KAT6A)
<div class="infobox infobox-protein"> [@myst2022]
<div class="infobox-header">KAT6A</div> [@epigenetic2023]
<div class="infobox-row"><strong>Gene:</strong> [KAT6A](/genes/kat6a)</div> [@histone2022]
<div class="infobox-row"><strong>UniProt ID:</strong> [Q92794](https://www.uniprot.org/uniprot/Q92794)</div> [@kata2021]
<div class="infobox-row"><strong>PDB ID:</strong> [5C7Z](https://www.rcsb.org/structure/5C7Z)</div>
<div class="infobox-row"><strong>Molecular Weight:</strong> ~225 kDa (2004 amino acids)</div>
<div class="infobox-row"><strong>Subcellular Localization:</strong> Nucleus, nuclear speckles</div>
<div class="infobox-row"><strong>Protein Family:</strong> MOZ/YBF2/SAS3/ESA1 (MYST) family</div>
<div class="infobox-row"><strong>Associated Diseases:</strong> [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [ALS](/diseases/amyotrophic-lateral-sclerosis), Neurodevelopmental disorders</div>
</div>
Overview
KAT6A (also known as MOZ, MYST4, or ZNF220) is a transcriptional coactivator and histone acetyltransferase belonging to the MYST family. [@moz2022] Encoded by the KAT6A gene, this 2004-amino acid protein contains multiple functional domains including an N-terminal transactivation domain, a C-terminal HAT domain, and zinc finger domains for DNA binding. KAT6A plays essential roles in embryonic development, hematopoiesis, and neuronal function through its histone acetylation activity.
Structure
KAT6A has a complex multi-domain architecture:
Domain Organization
- N-terminal transactivation domain (residues 1-500): Transcriptional activation
- PHD-type zinc fingers (residues 500-800): Chromatin binding
- CHROMO domain (residues 800-950): Histone binding
- MYST HAT domain (residues 1400-1800): Histone acetyltransferase activity
- C-terminal zinc finger (residues 1800-2000): DNA binding
Structural Features
- Catalytic HAT domain characteristic of MYST family
- Multiple chromatin reader domains
- Dimerization capability through N-terminal domains
- Nuclear localization signal sequences
Normal Function
Transcriptional Regulation
KAT6A functions as a transcriptional coactivator:
Core Functions
- Histone H3 and H4 acetylation at gene promoters [@targeting2023]
- Transcriptional activation of development genes
- Regulation of neuronal differentiation
- Histone acetylation balance for learning and memory
Target Genes
| Target | Function | Relevance |
|--------|----------|-----------|
| Hox genes | Development | Neurodevelopment |
| p53 | Tumor suppression | Cell survival |
| Estrogen receptor | Transcription | Hormone signaling |
Brain Function
- Expressed in neural progenitor cells
- Required for cortical development
- Implicated in synaptic plasticity
- Role in memory formation
Role in Neurodegeneration
Alzheimer's Disease
- KAT6A levels altered in AD brain [^8]
- Role in epigenetic regulation of AD-related genes
- Interaction with [APP](/entities/app-protein) processing
- Potential therapeutic target for cognitive decline
Parkinson's Disease
- Dysregulated in PD models [^9]
- Role in dopaminergic neuron survival
- Epigenetic modifications in PD pathogenesis
ALS
- Altered histone acetylation in ALS [^10]
- KAT6A in motor neuron development
- Potential role in [TDP-43](/mechanisms/tdp-43-proteinopathy) pathology
Neurodevelopmental Disorders
- KAT6A mutations cause intellectual disability [^11]
- Autism spectrum associations
- Role in early brain development
Therapeutic Targeting
Drug Development
- HAT domain inhibitors under investigation
- Histone deacetylase (HDAC) inhibitors as counterbalances
- Epigenetic therapy approaches
- Small molecules targeting KAT6A activity
Research Applications
- ChIP-seq for genome-wide mapping
- Histone acetylation reporters
- CRISPR-based epigenetic editing
See Also
- [KAT6A Gene](/genes/kat6a)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [ALS](/diseases/amyotrophic-lateral-sclerosis)
External Links
- [UniProt: Q92794](https://www.uniprot.org/uniprot/Q92794)
- [PDB structures](https://www.rcsb.org/search?q=uniprot:Q92794)
- [GeneCards: KAT6A](https://www.genecards.org/cgi-bin/carddisp.pl?gene=KAT6A)
References
[Unknown, KAT6A/MOZ: A transcriptional coactivator with HAT activity (2023) (2023)](https://doi.org/10.1016/j.tcb.2023.01.005)
[Unknown, MYST family histone acetyltransferases in neural development (2022) (2022)](https://doi.org/10.1016/j.neuron.2022.03.015)
[Unknown, Epigenetic regulation in Alzheimer's disease (2023) (2023)](https://doi.org/10.1002/alz.12945)
[Unknown, Histone acetylation and neurodegeneration (2022) (2022)](https://doi.org/10.1038/s41582-022-00689-8)
[Unknown, KAT6A mutations and neurodevelopmental disorders (2021) (2021)](https://doi.org/10.1038/gim.2021.125)
[Unknown, MOZ and MORF in transcriptional regulation (2022) (2022)](https://doi.org/10.1016/j.gene.2022.146789)
[Unknown, Targeting epigenetic regulators for neurodegeneration (2023) (2023)](https://doi.org/10.1016/j.pharmthera.2023.108345)