LC3 Protein

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LC3 Protein

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LC3 Protein

Introduction

Lc3 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

MAP1LC3A (Microtubule-Associated Protein 1 Light Chain 3 Alpha) [@johansen2009]

<div class="infobox infobox-protein"> [@mizushima2008]
<table>
<tr><th>Protein Name</th><td>LC3 (Microtubule-Associated Protein 1 Light Chain 3)</td></tr>
<tr><th>Gene</th><td>MAP1LC3A (also LC3)</td></tr>
<tr><th>UniProt ID</th><td>Q9YVQ1</td></tr>
<tr><th>PDB ID</th><td>2K6Q, 4Z0N</td></tr>
<tr><th>Molecular Weight</th><td>17 kDa (unlipidated), 14 kDa (lipidated)</td></tr>
<tr><th>Subcellular Localization</th><td>Cytoplasm, autophagosome membrane</td></tr>
<tr><th>Protein Family</th><td>ATG8 (LC3/GABARAP) family</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/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">2307 edges</a></td>
</tr>
</table>
</div>

Overview

This page provides comprehensive information about the institution/research center, its research programs, and contributions to neurodegenerative disease research.

Structure

...

LC3 Protein

Introduction

Lc3 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

MAP1LC3A (Microtubule-Associated Protein 1 Light Chain 3 Alpha) [@johansen2009]

<div class="infobox infobox-protein"> [@mizushima2008]
<table>
<tr><th>Protein Name</th><td>LC3 (Microtubule-Associated Protein 1 Light Chain 3)</td></tr>
<tr><th>Gene</th><td>MAP1LC3A (also LC3)</td></tr>
<tr><th>UniProt ID</th><td>Q9YVQ1</td></tr>
<tr><th>PDB ID</th><td>2K6Q, 4Z0N</td></tr>
<tr><th>Molecular Weight</th><td>17 kDa (unlipidated), 14 kDa (lipidated)</td></tr>
<tr><th>Subcellular Localization</th><td>Cytoplasm, autophagosome membrane</td></tr>
<tr><th>Protein Family</th><td>ATG8 (LC3/GABARAP) family</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/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">2307 edges</a></td>
</tr>
</table>
</div>

Overview

This page provides comprehensive information about the institution/research center, its research programs, and contributions to neurodegenerative disease research.

Structure

LC3 (MAP1LC3A) is a ubiquitin-like protein that undergoes post-translational processing:

Pro-LC3: Full-length protein synthesized in the cytoplasm
LC3-I: Cytosolic form after cleavage by ATG4
LC3-II: Lipidated form (conjugated to phosphatidylethanolamine) that associates with autophagosome membranes

The protein contains an LC3-interacting region (LIR) that allows binding to autophagy receptors containing LIR motifs.

Normal Function

LC3 is essential for autophagosome formation and function:

Autophagosome biogenesis: LC3-II is incorporated into the growing autophagosome membrane
Cargo recognition: LC3 binds to autophagy receptors (p62, NDP52, OPTN) that recognize ubiquitinated cargo
Selective autophagy: Facilitates selective degradation of damaged organelles, protein aggregates, and intracellular pathogens
Membrane fusion: Involved in autophagosome-lysosome fusion

LC3 exists in multiple isoforms (LC3A, LC3B, LC3C) with slightly different functions and tissue distributions.

Role in Disease

Alzheimer's Disease

LC3-positive autophagic vacuoles accumulate in AD brains
Impaired autophagic flux in [neurons](/entities/neurons)
Reduced clearance of [Aβ](/proteins/amyloid-beta) and [tau](/proteins/tau) aggregates
Dysregulated autophagy contributes to synaptic loss

Parkinson's Disease

LC3 is a key player in mitophagy
Impaired LC3-mediated clearance of damaged mitochondria
Lewy bodies contain LC3-positive autophagic structures
Mutations in autophagy receptors (p62, GABARAP) linked to PD

Amyotrophic Lateral Sclerosis (ALS)

Accumulation of LC3-positive aggregates in motor neurons
Impaired autophagy of damaged proteins
Dysregulated selective autophagy pathways

Therapeutic Targeting

| Approach | Description | Status |
|----------|-------------|--------|
| [Autophagy](/entities/autophagy) inducers | Enhance LC3 lipidation and autophagosome formation | Preclinical |
| [mTOR](/entities/mtor) inhibitors | Rapamycin increases LC3-II levels | Clinical trials |
| p62 stabilizers | Enhance selective autophagy | Discovery |

Key Publications

Klionsky DJ, et al. (2021). Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 17(1):1-382.

Johansen T, et al. (2009). p62/SQSTM1 is a target gene for transcription factor NRF2. Molecular Cell. 34(2):149-159.

Mizushima N, et al. (2008). LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes. Journal of Cell Biology. 151(3):673-680.

LC3 in Neurodegenerative Diseases

Alzheimer's Disease

LC3-mediated autophagy in AD:

Impaired autophagic flux in AD neurons
LC3 accumulation in amyloid plaques and neurofibrillary tangles
Defective clearance of [Aβ](/proteins/amyloid-beta) through autophagy
LC3-II levels elevated in AD brain tissue

Parkinson's Disease

LC3 and PD pathogenesis:

Critical for mitophagy of damaged mitochondria
Impaired clearance of [α-synuclein](/proteins/alpha-synuclein) aggregates via autophagy
PINK1/PARK2-dependent mitophagy requires LC3
LC3-positive aggregates in PD substantia nigra

ALS

Autophagy defects in ALS:

Dysregulated autophagy including LC3 pathway
Impaired clearance of mutant SOD1 aggregates
Mutations in autophagy genes increase ALS risk
LC3 lipidation altered in ALS models

Huntington's Disease

Mutant [huntingtin](/proteins/huntingtin-protein) impairs autophagosome formation
LC3-mediated clearance defective in HD
Therapeutic potential of autophagy enhancement

Biomarkers

LC3 as a biomarker:

LC3-II/LC3-I ratio indicates autophagy activity
CSF LC3 levels in neurodegenerative diseases
Peripheral blood monocyte LC3 in PD
Monitoring autophagic flux in patient samples

Background

The study of Lc3 Protein 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

[UniProt: Q9YVQ1](https://www.uniprot.org/uniprot/Q9YVQ1)
[RCSB PDB: 2K6Q](https://www.rcsb.org/structure/2K6Q)
[NCBI Gene: MAP1LC3A](https://www.ncbi.nlm.nih.gov/gene/399521)

Last updated: 2026-03-04

Brain Atlas Resources

Allen Human Brain Atlas: [LC3 expression search](https://human.brain-map.org/microarray/search/show?search_term=MAP1LC3A)
Allen Cell Type Atlas: [Transcriptomic cell type reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
Allen Mouse Brain Atlas: [LC3 search](https://mouse.brain-map.org/search/index.html?query=MAP1LC3A)

[LC3 - Allen Brain Atlas](https://human.brain-map.org/microarray/search/show?search_term=MAP1LC3A)

References

[Klionsky DJ, et al, (2021) (2021)](https://doi.org/10.1080/15548627.2020.1797280)

[Johansen T, et al, (2009) (2009)](https://doi.org/10.1016/j.molcel.2009.03.013)

[Mizushima N, et al, (2008) (2008)](https://doi.org/10.1083/jcb.151.3.673)

Pathway Diagram

The following diagram shows key molecular relationships for LC3 Protein based on knowledge graph edges:

Mermaid diagram (expand to render)

Pathway Diagram

The following diagram shows the key molecular relationships involving LC3 Protein discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

LC3

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kg_node_id	LC3
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-fedfaddc1b3a
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-lc3'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

35

Outgoing

126

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

LC3 Protein

LC3 Protein

Introduction

Overview

Structure

LC3 Protein

Introduction

Overview

Structure

Normal Function

Role in Disease

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis (ALS)

Therapeutic Targeting

Key Publications

LC3 in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

ALS

Huntington's Disease

Biomarkers

Background

See Also

External Links

Brain Atlas Resources

References

Pathway Diagram

Pathway Diagram

💬 Discussion