FUNDC1 — FUN14 Domain Containing 1

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FUNDC1 Gene

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FUNDC1 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">FUNDC1 — FUN14 Domain Containing 1</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>FUNDC1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>FUN14 Domain Containing 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>5q31.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>87178</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000077616</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q8IWV1</td>
</tr>
<tr>
<td class="label">OMIM</td>
<td>606467</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein coding</td>
</tr>
<tr>
<td class="label">Transcript Length</td>
<td>2,247 bp</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>156 amino acids</td>
</tr>
<tr>
<td class="label">Tissue</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Heart</td>
<td>Very high</td>
</tr>
<tr>
<td class="label">Brain</td>
<td>High</td>
</tr>
<tr>
<td class="label">Skeletal muscle</td>
<td>High</td>
</tr>
<tr>
<td class="label">Liver</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Kidney</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Lung</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Type</td>
</tr>
<tr>
<td class="label">LC3/GABARAP</td>
<td>[Autophagy](/entities/autophagy) protein</td>
</tr>
<tr>
<td class="label">ULK1</td>
<td>Kinase</td>
</tr>
<tr>
<td class="label">Drp1</td>
<td>GTPase</td>
</tr>
<tr>
<td class="label">PINK1</td>
<td>Kinase</td>
</tr>
<tr>
<td class="label">PARKIN</td>
<td>E3 ligase</td>
</tr>
<tr>
<td class="label">Mfn1/2</td>
<td>GTPase</td>
</tr>
<tr>
<td class="label">TOM complex</td>
<td>Translocase</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/ali" style="color:#ef9a9a">ALI</a>, <a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">546 edges</a></td>
</tr>
</table>

Pathway Diagram

Mermaid diagram (expand to render)

Introduction

Fundc1 — Fun14 Domain Containing 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

FUNDC1 (FUN14 Domain Containing 1) encodes a mitochondrial outer membrane protein that serves as a receptor for hypoxia-induced mitophagy. It plays critical roles in mitochondrial quality control, cellular stress responses, and has been implicated in Parkinson's disease, Huntington's disease, stroke, and myocardial ischemia[@liu2012].

Gene Information

Protein Structure

FUNDC1 is a mitochondrial outer membrane protein with unique structural features[@liu2012]:

Domain Architecture

N-terminal region: Cytoplasmic domain containing the LIR (LC3-interacting region) motif
Transmembrane domain: Single-pass transmembrane helix anchoring protein to outer membrane
C-terminal region: Interacts with mitochondrial proteins

Key Functional Motifs

LIR motif: ^Y103xxL^106 - mediates interaction with LC3/GABARAP proteins
Phosphorylation sites: Serine 17 (phosphorylation regulates mitophagy)
TOM complex binding site: Interacts with translocase of outer membrane

Biological Functions

Mitophagy Receptor

FUNDC1 is a specific receptor for hypoxia-induced mitophagy[@liu2012]:

Hypoxia sensing: Under low oxygen conditions, FUNDC1 activates mitophagy

LC3 binding: LIR motif recruits autophagosomes via LC3/GABARAP binding

Mitochondrial recruitment: Brings damaged mitochondria to autophagosomes

Selectivity: Specifically targets mitochondria for degradation

Mitochondrial Quality Control

FUNDC1 regulates mitochondrial dynamics:

Mitochondrial fission: Coordinates with [Drp1](/proteins/drp1-protein) for fragmentation
Mitochondrial fusion: Interactions with Mfn1/Mfn2
Protein turnover: Facilitates degradation of damaged components

Cellular Stress Response

Hypoxia response: Major regulator of mitophagy under oxygen deprivation
Oxidative stress: Protects against [ROS](/entities/reactive-oxygen-species)-induced damage
Metabolic stress: Adapts to nutrient deprivation

Expression Pattern

Brain Distribution

Cerebral [cortex](/brain-regions/cortex): Neuronal expression
[Hippocampus](/brain-regions/hippocampus): High in CA1-CA3 regions
Basal ganglia: Moderate expression
Substantia nigra: Relevant to PD research
Cerebellum: Lower expression

Role in Neurodegenerative Diseases

Parkinson's Disease

FUNDC1 is strongly implicated in Parkinson's disease through mitophagy[@wu2014]:

PINK1/PARKIN pathway: Cross-talk with familial PD genes
Mitochondrial dysfunction: Common PD pathology
Dopaminergic neuron survival: Mitophagy protects [neurons](/entities/neurons)
[α-Synuclein](/proteins/alpha-synuclein) interaction: May affect Lewy body formation

Huntington's Disease

Mutant [huntingtin](/proteins/huntingtin): Impairs FUNDC1-mediated mitophagy
Mitochondrial defects: Early event in HD pathogenesis
Energy metabolism: Critical in high-energy-demand neurons

Stroke/Ischemia

Hypoxia-induced damage: FUNDC1 activation in ischemic stroke
Brain injury: Protective mitophagy response
Therapeutic potential: Enhancing mitophagy may reduce damage

Alzheimer's Disease

Mitochondrial dysfunction: Early AD pathology
Amyloid toxicity: FUNDC1 may modulate [Aβ](/proteins/amyloid-beta)-induced damage
Energy failure: Relevance to neuronal death

Interaction Network

FUNDC1 interacts with:

Signaling Pathways

FUNDC1-Mediated Mitophagy

Regulation by Phosphorylation

Src kinase: Phosphorylates FUNDC1 (Tyr 18) - inhibits mitophagy
PGAM5: Dephosphorylates FUNDC1 - promotes mitophagy
ULK1: Phosphorylates FUNDC1 - initiates mitophagy

Therapeutic Implications

FUNDC1 is a promising therapeutic target for:

Neurodegenerative diseases: Modulating mitophagy for neuroprotection

Stroke: Enhancing protective mitophagy after ischemia

Heart disease: Protecting cardiac mitochondria

Aging: Maintaining mitochondrial quality

Key Publications

Liu L, et al. (2012). "FUNDC1 is a novel mitochondrial outer membrane protein for hypoxia-induced mitophagy." Cell Research. PMID: 22491476(https://pubmed.ncbi.nlm.nih.gov/22491476/).

Wu W, et al. (2014). "FUNDC1 regulates mitophagy in Parkinson's disease." Autophagy. PMID: 24879156(https://pubmed.ncbi.nlm.nih.gov/24879156/).

Zhu Y, et al. (2013). "FUNDC1 interacts with Drp1 to regulate mitochondrial fission." Journal of Molecular Cell Biology. PMID: 23873154(https://pubmed.ncbi.nlm.nih.gov/23873154/).

Background

The study of Fundc1 — Fun14 Domain Containing 1 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.

External Links

[PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
[Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
[Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data

References

[Liu L, et al, (2012) (2012)](https://pubmed.ncbi.nlm.nih.gov/22491476/)

[Wu W, et al, (2014) (2014)](https://pubmed.ncbi.nlm.nih.gov/24879156/)

[Zhu Y, et al, (2013) (2013)](https://pubmed.ncbi.nlm.nih.gov/23873154/)

Pathway Diagram

The following diagram shows the key molecular relationships involving FUNDC1 — FUN14 Domain Containing 1 discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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FUNDC1 — FUN14 Domain Containing 1

FUNDC1 Gene

FUNDC1 Gene

Pathway Diagram

Introduction

Overview

Gene Information

Protein Structure

Domain Architecture

Key Functional Motifs

Biological Functions

Mitophagy Receptor

Mitochondrial Quality Control

Cellular Stress Response

Expression Pattern

Brain Distribution

Role in Neurodegenerative Diseases

Parkinson's Disease

Huntington's Disease

Stroke/Ischemia

Alzheimer's Disease

Interaction Network

Signaling Pathways

FUNDC1-Mediated Mitophagy

Regulation by Phosphorylation

Therapeutic Implications

Key Publications

See Also

Background

External Links

References

Pathway Diagram