CHD2 Protein

CHD2 Protein

<div class="infobox infobox-protein">

| Property | Value |
|----------|-------|
| Protein Name | Chromodomain Helicase DNA Binding Protein 2 |
| Gene | CHD2 |
| UniProt ID | O14671 |
| Molecular Weight | ~233 kDa |
| Subcellular Localization | Nucleus |
| Protein Family | CHD family, SNF2 helicase family |

</div>

Overview

CHD2 (Chromodomain Helicase DNA Binding Protein 2) is a ATP-dependent chromatin remodeler that plays critical roles in neuronal development, gene regulation, and epilepsy pathogenesis[@carvill2013]. CHD2 is a member of the chromodomain helicase domain (CHD) family of proteins, which use the energy from ATP hydrolysis to slide, evict, and restructure nucleosomes, thereby modulating DNA accessibility for transcription factors and other regulatory proteins[@marfella2007].

Structure

CHD2 contains multiple conserved domains:

• Double chromodomains: At the N-terminus, bind to methylated histone H3K4me3 and H3K9me3
• SNF2 helicase domain: Central ATP-dependent chromatin remodeling engine
• DNA-binding domain: Facilitates interaction with nucleosomal DNA
• C-terminal domains: Additional protein-protein interaction motifs

Normal Function

Chromatin Remodeling

CHD2 regulates gene expression through chromatin remodeling:

...

CHD2 Protein

<div class="infobox infobox-protein">

| Property | Value |
|----------|-------|
| Protein Name | Chromodomain Helicase DNA Binding Protein 2 |
| Gene | CHD2 |
| UniProt ID | O14671 |
| Molecular Weight | ~233 kDa |
| Subcellular Localization | Nucleus |
| Protein Family | CHD family, SNF2 helicase family |

</div>

Overview

CHD2 (Chromodomain Helicase DNA Binding Protein 2) is a ATP-dependent chromatin remodeler that plays critical roles in neuronal development, gene regulation, and epilepsy pathogenesis[@carvill2013]. CHD2 is a member of the chromodomain helicase domain (CHD) family of proteins, which use the energy from ATP hydrolysis to slide, evict, and restructure nucleosomes, thereby modulating DNA accessibility for transcription factors and other regulatory proteins[@marfella2007].

Structure

CHD2 contains multiple conserved domains:

• Double chromodomains: At the N-terminus, bind to methylated histone H3K4me3 and H3K9me3
• SNF2 helicase domain: Central ATP-dependent chromatin remodeling engine
• DNA-binding domain: Facilitates interaction with nucleosomal DNA
• C-terminal domains: Additional protein-protein interaction motifs

Normal Function

Chromatin Remodeling

CHD2 regulates gene expression through chromatin remodeling:

• Nucleosome sliding: Repositions nucleosomes along DNA
• Histone exchange: Facilitates histone variant incorporation
• Transcription regulation: Modulates transcriptional activation and repression
• DNA repair: Participates in DNA damage response pathways

Neuronal Development

CHD2 is essential for proper brain development:

• Cortical development: Regulates neuronal proliferation and differentiation
• Synaptogenesis: Controls genes involved in synapse formation
• Epigenetic programming: Establishes neuronal gene expression patterns
• Brain region-specific functions: Important in [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus)

Role in Disease

Epilepsy

CHD2 mutations are a significant cause of genetic epilepsy[@carvill2013][@suls2013]:

• Epileptic encephalopathies: De novo mutations cause early-onset seizures
• Photosensitivity: CHD2 variants often cause light-sensitive epilepsy
• Developmental delay: Associated with intellectual disability
• ASD comorbidity: Frequently co-occurs with autism spectrum disorders

Neurodevelopmental Disorders

CHD2 is implicated in multiple neurodevelopmental conditions:

• Intellectual disability: CHD2 haploinsufficiency affects cognition
• Autism spectrum disorder: Altered social behavior and communication
• ADHD: Attention and hyperactivity symptoms
• Schizophrenia: Risk variants identified in GWAS

Cancer

While primarily studied in neurological contexts:

• Somatic mutations: Found in various cancers
• Oncogenic role: May function as tumor suppressor in some contexts

Therapeutic Implications

• Epilepsy therapies: Sodium channel modulators, AEDs
• Targeted approaches: Understanding CHD2 function may enable precision medicine
• Gene therapy: Future potential for gene replacement

Key Publications

[Carvill, G.L. et al. (2013) CHD2 mutations in epilepsy (American Journal of Human Genetics)](https://doi.org/10.1016/j.ajhg.2013.04.009)

[Suls, A. et al. (2013) De novo CHD2 mutations in Dravet syndrome (Brain)](https://doi.org/10.1093/brain/awt145)

Cross-References

• [CHD2 Gene](/genes/chd2) — Gene encoding CHD2
• [Epilepsy](/diseases/epilepsy) — Primary disease association
• [Chromatin Remodeling](/mechanisms/chromatin-remodeling) — Related mechanism

See Also

• [tau-protein](/proteins/tau) — Related [tau](/proteins/tau) kinase substrate in AD
• [amyloid-beta](/proteins/amyloid-beta-protein) — Related [APP](/entities/app-protein) cleavage product
• [GSK3B](/proteins/gsk3b) — Major kinase in neurodegeneration
• [CDK5](/genes/cdk5) — Another tau kinase
• [BACE1](/entities/bace1) — Beta-secretase in amyloidogenesis

External Links

• [UniProt](https://www.uniprot.org/) - Protein sequence and functional data
• [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
• [PDB](https://www.rcsb.org/) - Protein structure data

References

Carvill, G.L. et al., (2013). Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and GABRB3. American Journal of Human Genetics, 92(4), 571-576 (2013)

Unknown, Marfella, C.G. & Imbalzano, A.N. (2007). The Chd family of chromatin remodelers. Mutation Research, 618(1-2), 30-40 (2007)

Suls, A. et al., (2013). De novo CHD2 mutations cause epileptic encephalopathy. Brain, 136(Pt 10), 3032-3044 (2013)