| KDM4A Protein | |
|---|---|
| Protein Name | Lysine Specific Demethylase 4A (JMJD2A) |
| Gene | [KDM4A](/genes/kdm4a) |
| UniProt ID | O75173 |
| PDB Structure IDs | 2Q8M, 2OT7, 4LJP |
| Molecular Weight | 125,000 Da |
| Subcellular Localization | Nucleus, Chromatin |
| Protein Family | JMJD2 family (Jumonji C domain demethylase) |
Kdm4A Protein (Lysine Specific Demethylase 4A (Jmjd2A)) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
KDM4A is a jmjd2 family (jumonji c domain demethylase) that catalyzes the removal of methyl groups from histone lysine residues. This epigenetic enzyme plays critical roles in chromatin remodeling and gene expression regulation in the nervous system.
The KDM4A protein contains characteristic domains including the JmjN (Jumonji N-terminal) domain and the catalytic JmjC (Jumonji C-terminal) domain. These domains are conserved among 2-oxoglutarate-dependent dioxygenases and require iron (Fe²⁺) and 2-oxoglutarate as cofactors for demethylase activity.
In neurons, KDM4A regulates gene expression programs critical for:
The enzyme modulates chromatin accessibility by removing repressive or activating histone methylation marks, thereby controlling the transcription of genes essential for neuronal function and survival.
Dysregulation of KDM4A is associated with several neurological conditions:
Pathogenic variants or altered expression of KDM4A disrupt normal epigenetic patterns in neurons, leading to dysregulated gene expression that contributes to disease pathogenesis.
KDM4A is being investigated as a therapeutic target for:
Several small molecule inhibitors targeting the JmjC domain demethylases are in development, though achieving brain penetration remains a challenge.
The study of Kdm4A Protein (Lysine Specific Demethylase 4A (Jmjd2A)) 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.