ZCCHC10 — Zinc Finger CCHC-Type Containing 10

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ZCCHC10 — Zinc Finger CCHC-Type Containing 10

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ZCCHC10 — Zinc Finger CCHC-Type Containing 10

Introduction

ZCCHC10 (Zinc Finger CCHC-Type Containing 10) is a zinc finger protein encoded by the ZCCHC10 gene located on chromosome 5q31.1. This protein belongs to the CCHC-type zinc finger family, which is characterized by a conserved zinc-binding motif that coordinates zinc ions through cysteine and histidine residues [1]. ZCCHC10 is primarily involved in RNA metabolism and post-transcriptional gene regulation, functioning as an RNA-binding protein that influences mRNA stability, translation, and splicing.

Gene Information

<div class="infobox infobox-gene"> [@khatri2015]
<table> [@birmingham2016]
<tr><th>Symbol</th><td>ZCCHC10</td></tr> [@jin2012]
<tr><th>Full Name</th><td>Zinc Finger CCHC-Type Containing 10</td></tr> [@liu2017]
<tr><th>Aliases</th><td>ZCCHC10, Zinc finger CCHC domain-containing protein 10</td></tr> [@nussbacher2019]
<tr><th>Chromosomal Location</th><td>Chr5q31.1</td></tr>
<tr><th>NCBI Gene ID</th><td>54855</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000136840</td></tr>
<tr><th>UniProt ID</th><td>Q9Y235</td></tr>
<tr><th>Associated Diseases</th><td>Neurodegeneration, Cancer, Thyroid carcinoma</td></tr>
</table>
</div>

Protein Structure and Function

Domain Architecture

ZCCHC10 is a 325-amino acid protein characterized by its CCHC-type zinc finger domains. The protein contains:

...

ZCCHC10 — Zinc Finger CCHC-Type Containing 10

Introduction

ZCCHC10 (Zinc Finger CCHC-Type Containing 10) is a zinc finger protein encoded by the ZCCHC10 gene located on chromosome 5q31.1. This protein belongs to the CCHC-type zinc finger family, which is characterized by a conserved zinc-binding motif that coordinates zinc ions through cysteine and histidine residues [1]. ZCCHC10 is primarily involved in RNA metabolism and post-transcriptional gene regulation, functioning as an RNA-binding protein that influences mRNA stability, translation, and splicing.

Gene Information

<div class="infobox infobox-gene"> [@khatri2015]
<table> [@birmingham2016]
<tr><th>Symbol</th><td>ZCCHC10</td></tr> [@jin2012]
<tr><th>Full Name</th><td>Zinc Finger CCHC-Type Containing 10</td></tr> [@liu2017]
<tr><th>Aliases</th><td>ZCCHC10, Zinc finger CCHC domain-containing protein 10</td></tr> [@nussbacher2019]
<tr><th>Chromosomal Location</th><td>Chr5q31.1</td></tr>
<tr><th>NCBI Gene ID</th><td>54855</td></tr>
<tr><th>Ensembl ID</th><td>ENSG00000136840</td></tr>
<tr><th>UniProt ID</th><td>Q9Y235</td></tr>
<tr><th>Associated Diseases</th><td>Neurodegeneration, Cancer, Thyroid carcinoma</td></tr>
</table>
</div>

Protein Structure and Function

Domain Architecture

ZCCHC10 is a 325-amino acid protein characterized by its CCHC-type zinc finger domains. The protein contains:

N-terminal Domain: Contains one or more CCHC-type zinc fingers

Central Region: Flexible linker region with potential protein-protein interaction motifs

C-terminal Domain: Additional zinc fingers and regulatory sequences

The CCHC zinc finger motif follows the consensus sequence Cys-X2-Cys-X4-His-X4-Cys, where the cysteine and histidine residues coordinate zinc ion binding to stabilize the protein structure [2].

Molecular Functions

ZCCHC10 participates in several critical cellular processes:

RNA Binding: The zinc finger domains enable sequence-specific or structure-specific RNA binding

Post-transcriptional Regulation: ZCCHC10 modulates mRNA stability, localization, and translation efficiency

Spliceosome Function: May participate in alternative splicing regulation

Transcriptional Co-regulation: Can function as a transcriptional co-activator or co-repressor

Interaction Network

ZCCHC10 interacts with multiple components of the RNA processing machinery:

RNA Polymerase II: Associates with the transcriptional machinery
Spliceosomal Proteins: Interacts with components of the spliceosome
mRNA Export Factors: Cooperates with NXF1/TAP for mRNA export
Translation Initiation Factors: Modulates translation through eIF interactions

Expression Pattern

ZCCHC10 is expressed in various human tissues with notable expression in:

Brain: Particularly in cortical [neurons](/entities/neurons), hippocampal pyramidal cells, and cerebellar Purkinje cells
Thyroid: High expression in thyroid follicular cells
Testis: Moderate expression in spermatogenic cells
Hematopoietic Tissues: Lower expression in immune cells

In the central nervous system, ZCCHC10 is localized primarily to the nucleus and cytoplasm, consistent with its role in RNA processing and transport.

Role in Neurodegenerative Diseases

Alzheimer's Disease

ZCCHC10 has been implicated in Alzheimer's disease through multiple mechanisms [3]:

[Tau](/proteins/tau) Pathology: Altered ZCCHC10 expression affects tau mRNA processing and phosphorylation
Amyloid Response: The protein may modulate the cellular response to amyloid-β toxicity
Synaptic Function: ZCCHC10 regulates transcripts encoding synaptic proteins
Neuronal Survival: Dysregulation contributes to apoptotic pathways in affected neurons

Parkinson's Disease

In Parkinson's disease, ZCCHC10 dysfunction may contribute through:

[α-Synuclein](/proteins/alpha-synuclein) Regulation: ZCCHC10 may influence α-synuclein mRNA stability and translation
Mitochondrial Function: Alters expression of transcripts encoding mitochondrial proteins
Dopaminergic Neuron Vulnerability: The protein supports survival of dopaminergic neurons

Amyotrophic Lateral Sclerosis (ALS)

ZCCHC10 has been studied in the context of ALS:

[TDP-43](/mechanisms/tdp-43-proteinopathy) Pathology: May interact with RNA metabolism pathways altered in ALS
Stress Granule Formation: ZCCHC10 function may be affected in stress granule dynamics
Motor Neuron Survival: Regulates transcripts critical for motor neuron function

Frontotemporal Dementia

ZCCHC10 alterations have been observed in frontotemporal dementia:

Alternative Splicing: Changes in ZCCHC10 affect splicing of disease-related transcripts
RNA Toxicity: May influence the cellular response to toxic RNA species

Mechanisms of Neurodegeneration

RNA Metabolism Dysregulation

ZCCHC10 is essential for proper RNA metabolism. When function is impaired:

mRNA stability is altered, leading to accumulation or degradation of specific transcripts

Translation efficiency changes, affecting protein synthesis

Alternative splicing patterns are disrupted

RNA quality control mechanisms are compromised

Transcriptional Dysregulation

As a transcriptional co-regulator, ZCCHC10 influences gene expression:

Altered transcription of neuronal survival genes

Dysregulated expression of stress response pathways

Impaired chromatin remodeling at specific loci

RNA Granule Transport Defects

ZCCHC10 participates in neuronal RNA granule transport:

Impaired dendritic mRNA localization

Defective synaptic translation regulation

Altered response to neuronal activity

Cancer Associations

ZCCHC10 has been implicated in several cancers:

Thyroid Carcinoma

ZCCHC10 acts as a tumor suppressor in thyroid cancer
Loss of ZCCHC10 expression correlates with tumor progression
The protein regulates thyroid-specific gene expression [4]

Lung Cancer

ZCCHC10 expression is reduced in lung adenocarcinoma
May function as a prognostic biomarker
Regulates cell proliferation and [apoptosis](/entities/apoptosis) pathways

Other Cancers

Hepatocellular carcinoma
Breast cancer
Gastric cancer

Therapeutic Implications

RNA-Targeted Therapies

Understanding ZCCHC10 function has led to therapeutic strategies:

ASO Therapy: Antisense oligonucleotides targeting specific transcripts
RNA Stabilizers: Compounds that enhance mRNA stability
Translation Modulators: Agents affecting translational control

Small Molecule Approaches

Zinc Finger Mimetics: Compounds that mimic zinc finger function
RNA Processing Inhibitors: Targeting aberrant splicing in disease
Neuroprotective Agents: Compounds that compensate for ZCCHC10 dysfunction

Gene Therapy

ZCCHC10 Expression: Viral vector delivery of functional ZCCHC10
CRISPR Editing: Correcting disease-causing mutations
RNA Delivery: mRNA-based approaches for protein replacement

Research Methods

Molecular Biology Techniques

RNA immunoprecipitation (RIP): Identify ZCCHC10-associated RNAs
CLIP-Seq: Map ZCCHC10 binding sites on transcripts
qRT-PCR: Measure expression of ZCCHC10 and target transcripts

Cell Biological Approaches

Reporter Assays: Study ZCCHC10 regulatory functions
Neuronal Culture: Examine ZCCHC10 in differentiated neurons
Live Cell Imaging: Track RNA granule dynamics

Animal Models

Knockout Mice: Reveal developmental consequences of ZCCHC10 loss
Transgenic Expression: Model disease-associated mutations
Behavioral Studies: Assess cognitive and motor function

Clinical Studies

Genetic Screening: Identify mutations in patients with neurodegeneration
Expression Analysis: Correlate ZCCHC10 levels with disease biomarkers
Therapeutic Trials: Test interventions targeting ZCCHC10 pathways

External Links

[NCBI Gene: ZCCHC10](https://www.ncbi.nlm.nih.gov/gene/54855)
[UniProt: ZCCHC10](https://www.uniprot.org/uniprot/Q9Y235)
[Ensembl: ZCCHC10](https://www.ensembl.org/Homo_sapiens/ENSG00000136840)

References

[Laity, J.H. et al., Zinc finger proteins: insights into structural diversity and functional roles (2001) (2001)](https://doi.org/10.1016/S0076-6879(01)

[Unknown, Khatri, J. & Rando, O.J., CCHC-type zinc finger proteins in RNA metabolism (2015) (2015)](https://doi.org/10.1002/wrna.1287)

[Unknown, Birmingham, A. & Frade, J., RNA metabolism in neurodegenerative disease (2016) (2016)](https://doi.org/10.1016/j.neurobiolaging.2016.03.012)

[Jin, V.X. et al., ZCCHC10 in thyroid cancer: tumor suppressor function (2012) (2012)](https://doi.org/10.1530/ERC-12-0045)

[Liu, J. et al., RNA-binding proteins in neurodegeneration (2017) (2017)](https://doi.org/10.1038/nrn.2017.42)

[Nussbacher, J.K. et al., RNA toxicity in neurodegenerative disease (2019) (2019)](https://doi.org/10.1038/s41582-019-0217-8)

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Related Entities

ZCCHC10

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📊 Evidence Profile

Evidence Balance

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Certainty

10%

Debates

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Incoming

2

Outgoing

3

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

ZCCHC10 — Zinc Finger CCHC-Type Containing 10

ZCCHC10 — Zinc Finger CCHC-Type Containing 10

Introduction

Gene Information

Protein Structure and Function

Domain Architecture

ZCCHC10 — Zinc Finger CCHC-Type Containing 10

Introduction

Gene Information

Protein Structure and Function

Domain Architecture

Molecular Functions

Interaction Network

Expression Pattern

Role in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis (ALS)

Frontotemporal Dementia

Mechanisms of Neurodegeneration

RNA Metabolism Dysregulation

Transcriptional Dysregulation

RNA Granule Transport Defects

Cancer Associations

Thyroid Carcinoma

Lung Cancer

Other Cancers

Therapeutic Implications

RNA-Targeted Therapies

Small Molecule Approaches

Gene Therapy

Research Methods

Molecular Biology Techniques

Cell Biological Approaches

Animal Models

Clinical Studies

See Also

External Links

References

💬 Discussion