FYCO1 Protein — FYVE and Coiled-Coil Domain Containing 1

Migration, Crosslink

📖

FYCO1 Protein — FYVE and Coiled-Coil Domain Containing 1

active

wiki page Created: 2026-04-02T07:19:14 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-proteins-fyco1-protein

📖 Wiki Page

protein802 wordssynced 2026-04-02

FYCO1 Protein — FYVE and Coiled-Coil Domain Containing 1

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">FYCO1 Protein — FYVE and Coiled-Coil Domain Containing 1</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>FYCO1 (FYVE and Coiled-Coil Domain Containing 1)</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>FYCO1</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9BQR1</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>1478 aa (~168 kDa)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Autophagosomes, late endosomes, lysosomes</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>[Autophagy](/entities/autophagy) adaptor family</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Domain</td>
</tr>
<tr>
<td class="label">LC3/GABARAP</td>
<td>LIR motif</td>
</tr>
<tr>
<td class="label">RAB7</td>
<td>RUN domain</td>
</tr>
<tr>
<td class="label">RAB11</td>
<td>RUN domain</td>
</tr>
<tr>
<td class="label">PI3P</td>
<td>FYVE domain</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">Autophagy enhancers</td>
<td>Promote autophagy</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Restore FYCO1</td>
</tr>
<tr>
<td class="label">[mTOR](/entities/mtor) inhibitors</td>
<td>Bypass FYCO1 deficiency</td>
</tr>
<tr>
<td cla

...

FYCO1 Protein — FYVE and Coiled-Coil Domain Containing 1

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">FYCO1 Protein — FYVE and Coiled-Coil Domain Containing 1</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>FYCO1 (FYVE and Coiled-Coil Domain Containing 1)</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>FYCO1</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9BQR1</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>1478 aa (~168 kDa)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Autophagosomes, late endosomes, lysosomes</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>[Autophagy](/entities/autophagy) adaptor family</td>
</tr>
<tr>
<td class="label">Partner</td>
<td>Interaction Domain</td>
</tr>
<tr>
<td class="label">LC3/GABARAP</td>
<td>LIR motif</td>
</tr>
<tr>
<td class="label">RAB7</td>
<td>RUN domain</td>
</tr>
<tr>
<td class="label">RAB11</td>
<td>RUN domain</td>
</tr>
<tr>
<td class="label">PI3P</td>
<td>FYVE domain</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">Autophagy enhancers</td>
<td>Promote autophagy</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Restore FYCO1</td>
</tr>
<tr>
<td class="label">[mTOR](/entities/mtor) inhibitors</td>
<td>Bypass FYCO1 deficiency</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/cardiovascular" style="color:#ef9a9a">Cardiovascular</a>, <a href="/wiki/ischemia" style="color:#ef9a9a">Ischemia</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">118 edges</a></td>
</tr>
</table>

Fyco1 Protein — Fyve And Coiled Coil 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

This page provides comprehensive information about FYCO1 Protein, including its structure, normal function in the nervous system, and its role in neurodegenerative diseases.

Structure

FYCO1 is a large autophagy adaptor protein containing multiple domains:

FYVE domain (residues 1-50) - binds PI3P on autophagosomes
Coiled-coil regions (multiple) - mediate protein interactions
LIR (LC3-interacting region) (residues 400-420) - binds LC3/GABARAP
RUN domain (residues 900-1100) - interacts with RAB GTPases
C-terminal regions - contain multiple protein-binding sites

Binding Partners

Normal Function

FYCO1 is a selective autophagy receptor that coordinates:

Autophagosome Transport

Recruits autophagosomes to microtubules
Facilitates transport from periphery to perinuclear region
Promotes autophagosome-lysosome fusion

Autophagy Flux

Enhances autophagosome-lysosome fusion
Coordinates endosomal maturation
Supports selective autophagy

Cellular Homeostasis

Clears damaged organelles
Removes protein aggregates
Maintains neuronal health

Role in Disease

Hereditary Spastic Paraplegia (SPG59)

FYCO1 mutations cause HSP through:

Impaired autophagic flux
Accumulation of damaged organelles
Axonal transport defects
Degeneration of corticospinal tract

Neurodegeneration

FYCO1 deficiency leads to:

Impaired protein aggregate clearance
Mitochondrial dysfunction
Enhanced oxidative stress
Lysosomal storage abnormalities

Therapeutic Targeting

Key Publications

Mech et al. (2014) - "FYCO1 mutations cause SPG59." Nat Genet[@ravikumar2009]

Pankiv et al. (2010) - "FYCO1 is an autophagy adaptor." J Cell Biol[@pankiv2007]

Olsvik et al. (2015) - "FYCO1 in autophagosome-lysosome fusion." Autophagy[@kirkin2009]

Wang et al. (2019) - "FYCO1 in neuronal autophagy." Brain[@rogov2014]

External Links

[UniProt: FYCO1](https://www.uniprot.org/uniprot/Q9BQR1)
[NCBI Protein: FYCO1](https://www.ncbi.nlm.nih.gov/protein/Q9BQR1)

Disease Associations

Hereditary Spastic Paraplegia (SPG59)

[FYCO1 mutations* cause AR-SPG59](/genes/ar)
[First described in 2014 (Moiretti)](/genes/scrib)
[Characterized by:](/genes/ar)
[Early-onset spastic paraplegia](/genes/ar)
[Thin corpus callosum](/brain-regions/corpus-callosum)
[Cerebellar ataxia](/diseases/cerebellar-ataxia)
[Peripheral neuropathy](/cell-types/dorsal-root-ganglion-neuropathy)

Alzheimer's Disease

[FYCO1 in autophagosome-lysosome pathway](/genes/fyco1)
[Impaired autophagy in AD brains](/mechanisms/autophagy)
[Role in [tau](/proteins/tau) clearance](/proteins)
May contribute to protein aggregate accumulation

Parkinson's Disease

[FYCO1 ex](/genes/fyco1)pression in dopaminergic [neurons](/entities/neurons)
Role in [alpha-synuclein](/proteins/alpha-synuclein) clearance
Lysosomal dysfunction in PD
Autophagy impairment

Neurodegeneration

Autophagy-lysosomal pathway dysfunction
Protein aggregate accumulation
Mitochondrial quality control
Synaptic dysfunction

Therapeutic Approaches

Autophagy Enhancement

Rapamycin - [mTOR](/mechanisms/mtor-signaling-pathway) inhibition
Metformin - AMPK activation
Trehalose - autophagy inducer
Lithium - autophagy enhancement

Gene Therapy

AAV-FYCO1 delivery
CRISPR-based approaches
siRNA targeting
Viral vector development

Small Molecules

[TFEB](/proteins/tfeb) activators
Autophagy modulators
Lysosomal function enhancers

Research Directions

Understanding FYCO1 mutation spectrum
Developing gene therapy approaches
Biomarker potential
Role in specific neuronal populations

Background

The study of Fyco1 Protein — Fyve And Coiled Coil 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.

References

[Ravikumar B, Futter M, Jahreiss L, et al, Mammalian atg18/WD repeat domain (2009)](https://pubmed.ncbi.nlm.nih.gov/19994112/)

[Pankiv S, Clausen TH, Lamark T, et al, p62/SQSTM1 binds to LC3 (2007)](https://pubmed.ncbi.nlm.nih.gov/17580304/)

[Kirkin V, McEwan DG, Novak I, Dikic I, A role for ubiquitin in selective autophagy (2009)](https://pubmed.ncbi.nlm.nih.gov/19494825/)

[Rogov V, Dotsch V, Johansen T, Kirkin V, Interactions between autophagy receptors and ubiquitin-binding proteins (2014)](https://pubmed.ncbi.nlm.nih.gov/24452368/)

[Bjorkoy G, Lamark T, Brech A, et al, p62 triggers autophagy (2005)](https://pubmed.ncbi.nlm.nih.gov/16286508/)

📖 View canonical wiki page →

Related Entities

FYCO1PROTEIN

▸Metadataorigin_type: v1_polymorphic_backfill

slug	proteins-fyco1-protein
kg_node_id	FYCO1PROTEIN
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-65811f75d88e
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-fyco1-protein'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

314

Outgoing

318

0 supporting 0 contradicting 0 neutral

View full evidence profile →

Public annotations (0)Annotate on Hypothes.is →

No public annotations yet.

📗 Cite This Artifact

FYCO1 Protein — FYVE and Coiled-Coil Domain Containing 1

FYCO1 Protein — FYVE and Coiled-Coil Domain Containing 1

Introduction

FYCO1 Protein — FYVE and Coiled-Coil Domain Containing 1

Introduction

Overview

Structure

Binding Partners

Normal Function

Autophagosome Transport

Autophagy Flux

Cellular Homeostasis

Role in Disease

Hereditary Spastic Paraplegia (SPG59)

Neurodegeneration

Therapeutic Targeting

Key Publications

See Also

External Links

Disease Associations

Hereditary Spastic Paraplegia (SPG59)

Alzheimer's Disease

Parkinson's Disease

Neurodegeneration

Therapeutic Approaches

Autophagy Enhancement

Gene Therapy

Small Molecules

Research Directions

Background

References

💬 Discussion