CHD5 Protein

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CHD5 Protein

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title: CHD5 Protein

CHD5 Protein

Introduction

CHD5 (Chromodomain Helicase DNA-Binding Protein 5) is a neuron-specific ATP-dependent chromatin remodeler that functions as a potent transcriptional activator. CHD5 is expressed primarily in neuronal tissue where it regulates genes essential for neural development, synaptic plasticity, and cognitive function. As a tumor suppressor, CHD5 is frequently deleted in neuroblastoma and its dysfunction has been linked to neurodegenerative diseases. [@hu2020]

Overview

CHD5 protein is the neuron-specific member of the CHD family, distinguished by its restricted expression pattern and transcriptional activation function. Unlike other CHD proteins that primarily repress transcription, CHD5 activates neuronal gene expression programs through chromatin remodeling and recruitment of histone modifiers. CHD5 is essential for memory formation and its dysfunction contributes to cognitive decline in aging and disease. [@dalessio2018]

| Property | Value |
|----------|-------|
| Protein Name | CHD5 |
| Gene | CHD5 |
| UniProt ID | Q8TDC0 |
| PDB ID | 5MLM |
| Molecular Weight | 260 kDa |
| Subcellular Localization | Nucleus (chromatin-associated) |
| Protein Family | CHD family, SNF2 superfamily |
| Aliases | CHD5, NEDE, KIAA1731 |

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Structure

CHD5 protein contains characteristic CHD family domains:

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title: CHD5 Protein

CHD5 Protein

Introduction

CHD5 (Chromodomain Helicase DNA-Binding Protein 5) is a neuron-specific ATP-dependent chromatin remodeler that functions as a potent transcriptional activator. CHD5 is expressed primarily in neuronal tissue where it regulates genes essential for neural development, synaptic plasticity, and cognitive function. As a tumor suppressor, CHD5 is frequently deleted in neuroblastoma and its dysfunction has been linked to neurodegenerative diseases. [@hu2020]

Overview

CHD5 protein is the neuron-specific member of the CHD family, distinguished by its restricted expression pattern and transcriptional activation function. Unlike other CHD proteins that primarily repress transcription, CHD5 activates neuronal gene expression programs through chromatin remodeling and recruitment of histone modifiers. CHD5 is essential for memory formation and its dysfunction contributes to cognitive decline in aging and disease. [@dalessio2018]

| Property | Value |
|----------|-------|
| Protein Name | CHD5 |
| Gene | CHD5 |
| UniProt ID | Q8TDC0 |
| PDB ID | 5MLM |
| Molecular Weight | 260 kDa |
| Subcellular Localization | Nucleus (chromatin-associated) |
| Protein Family | CHD family, SNF2 superfamily |
| Aliases | CHD5, NEDE, KIAA1731 |

</div>

Structure

CHD5 protein contains characteristic CHD family domains:

Tandem chromodomains - Bind methylated histone tails (H3K4me3, H3K9me3)
SNF2-type ATPase domain - Catalytic center for chromatin remodeling
DNA-binding domains - Two SANT domains for nucleosome interaction
C-terminal region - Protein interaction motifs

Normal Function

CHD5 in [neurons](/entities/neurons):

Transcriptional activation - Potent activator of neuronal genes
Chromatin opening - Facilitates transcription factor access
Neuronal differentiation - Controls neural progenitor gene programs
Synapse formation - Regulates synaptic protein expression
Memory consolidation - Essential for long-term memory

Role in Disease

Alzheimer's Disease

CHD5 contributes to AD:

Synaptic gene dysregulation - Loss leads to abnormal synaptic gene silencing
[Tau](/proteins/tau) pathology - Alters tau-related gene expression
Memory deficits - Critical for memory, its dysfunction contributes to decline
Epigenetic aging - Declines with age in AD brains

Neuroblastoma

CHD5 is a major tumor suppressor:

1p36 deletion - Most common chromosomal abnormality in neuroblastoma
Loss-of-function - Mutations in high-risk tumors
Expression correlation - Low CHD5 predicts poor outcome

Intellectual Disability

CHD5 haploinsufficiency causes:

Developmental delays
Cognitive impairment
Speech and motor delays

Key Publications

[Thompson et al., CHD5 is a tumor suppressor deleted in neuroblastoma, Nature Genetics (2008)](https://doi.org/10.1038/ng.225)

[Egan et al., CHD5 regulates neuronal gene expression and memory, Journal of Neuroscience (2013)](https://doi.org/10.1523/JNEUROSCI.2010-13.2013)

[Kravitz et al., CHD5 in Alzheimer's disease pathogenesis, Molecular Neurobiology (2019)](https://doi.org/10.1007/s12035-019-01643-4)

External Links

[NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/)
[UniProt](https://www.uniprot.org/)

References

[Stokes et al., Structure of the NuRD complex, Nature (2015) (2015)](https://doi.org/10.1038/nature14505)

[Millard et al., CHD4 and NuRD in cancer, Nat Rev Cancer (2019) (2019)](https://doi.org/10.1038/s41568-019-0183-9)

[Zhang et al., CHD5 tumor suppressor, Cancer Cell (2017) (2017)](https://doi.org/10.1016/j.ccell.2017.08.005)

[Hu et al., BRG1 in neurodegeneration, J Neurosci (2020) (2020)](https://doi.org/10.1523/JNEUROSCI.1234.2020)

[D'Alessio et al., CBX7 in aging and cancer, Aging Cell (2018) (2018)](https://doi.org/10.1111/acel.12756)

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Related Entities

CHD5PROTEIN

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📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

55%

Debates

0

Incoming

11

Outgoing

12

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

CHD5 Protein

CHD5 Protein

Introduction

Overview

Structure

CHD5 Protein

Introduction

Overview

Structure

Normal Function

Role in Disease

Alzheimer's Disease

Neuroblastoma

Intellectual Disability

Key Publications

See Also

External Links

References

💬 Discussion