ATG17A

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ATG17A

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ATG17A

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4ea; text-align:center; font-size:1.2em;">ATG17A (ATG17)</th></tr>
<tr><td>Full Name</td><td>Autophagy Related 17A</td></tr>
<tr><td>Gene Symbol</td><td>ATG17A (also known as ATG17, RB1CC1)</td></tr>
<tr><td>Chromosomal Location</td><td>2q37.2</td></tr>
<tr><td>NCBI Gene ID</td><td>[55130](https://www.ncbi.nlm.nih.gov/gene/55130)</td></tr>
<tr><td>Ensembl ID</td><td>[ENSG00000155089](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000155089)</td></tr>
<tr><td>UniProt ID</td><td>[Q8N5N7](https://www.uniprot.org/uniprot/Q8N5N7)</td></tr>
<tr><td>OMIM ID</td><td>604501</td></tr>
<tr><td>Protein Length</td><td>1594 amino acids</td></tr>
<tr><td>Molecular Weight</td><td>~177 kDa</td></tr>
<tr><td>Expression</td><td>Ubiquitous, high in brain</td></tr>
<tr><td>Associated Diseases</td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), ALS</td></tr>
</table>
</div>

Overview

...

ATG17A

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4ea; text-align:center; font-size:1.2em;">ATG17A (ATG17)</th></tr>
<tr><td>Full Name</td><td>Autophagy Related 17A</td></tr>
<tr><td>Gene Symbol</td><td>ATG17A (also known as ATG17, RB1CC1)</td></tr>
<tr><td>Chromosomal Location</td><td>2q37.2</td></tr>
<tr><td>NCBI Gene ID</td><td>[55130](https://www.ncbi.nlm.nih.gov/gene/55130)</td></tr>
<tr><td>Ensembl ID</td><td>[ENSG00000155089](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000155089)</td></tr>
<tr><td>UniProt ID</td><td>[Q8N5N7](https://www.uniprot.org/uniprot/Q8N5N7)</td></tr>
<tr><td>OMIM ID</td><td>604501</td></tr>
<tr><td>Protein Length</td><td>1594 amino acids</td></tr>
<tr><td>Molecular Weight</td><td>~177 kDa</td></tr>
<tr><td>Expression</td><td>Ubiquitous, high in brain</td></tr>
<tr><td>Associated Diseases</td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), ALS</td></tr>
</table>
</div>

Overview

ATG17A (Autophagy Related 17A, also known as ATG17 or RB1CC1/FIP200) is a critical [autophagy](/mechanisms/autophagy) protein that serves as a scaffold for the ULK1 complex, essential for autophagosome formation. As a core component of the autophagy initiation machinery, ATG17A plays a fundamental role in coordinating the early stages of autophagy, including the recruitment of downstream [ATG proteins](/proteins/atg-proteins) and the formation of the phagophore assembly site (PAS)[@null2015][@null2018].

The ATG17A gene encodes a large scaffolding protein that interacts directly with [ULK1](/proteins/ulkl1-protein), [ATG13](/proteins/atg13-protein), and other components of the ULK1 complex. This interaction is crucial for activating autophagy and for recruiting the class III [PI3K complex](/proteins/pik3c3-protein) that initiates the nucleation of the phagophore[@null2014][@null2017].

Beyond its well-established role in general autophagy, ATG17A has emerged as a key player in [mitophagy](/mechanisms/mitophagy)—the selective autophagy of mitochondria—which is particularly relevant to neurodegenerative diseases like [Alzheimer's Disease](/diseases/alzheimers-disease) and [Parkinson's Disease](/diseases/parkinsons-disease)[@null2020][@null2019b]. The impairment of mitophagy in dopaminergic neurons is thought to contribute to the accumulation of damaged mitochondria and subsequent neuronal death in [Parkinson's Disease](/diseases/parkinsons-disease)[@null2019c][@null2021b].

Gene Structure and Evolution

The ATG17A gene spans approximately 45 kb on chromosome 2q37.2 and consists of 40+ exons. The gene encodes a 1594-amino acid protein with a molecular weight of approximately 177 kDa. ATG17A is highly conserved across eukaryotes, with orthologs present in yeast (Atg17), flies, zebrafish, and mammals[@null2012].

The protein contains multiple functional domains:

N-terminal coiled-coil domains: Mediate self-association and interaction with ULK1
Central LC3-interacting region (LIR): Allows binding to [ATG8](/proteins/atg8-protein) family proteins (LC3/GABARAP)
C-terminal domain: Involved in cargo recognition and complex assembly

The evolutionary conservation of ATG17A underscores its fundamental importance in the autophagy pathway. Yeast Atg17 forms a dimeric structure that serves as a platform for ATG protein recruitment during nutrient starvation-induced autophagy[@null2016]. In mammalian cells, ATG17A (also known as FIP200) has acquired additional functions beyond its yeast ortholog, including roles in [cell cycle regulation](/mechanisms/cell-cycle), [apoptosis](/mechanisms/apoptosis), and [innate immune signaling](/mechanisms/immune-response)[@null2016b].

Function in Autophagy

ULK1 Complex Assembly

ATG17A serves as a central scaffolding component of the ULK1 complex, which also includes [ULK1](/proteins/ulkl1-protein) (or ULK2), [ATG13](/proteins/atg13-protein), and [FIP200](/genes/fip200) (RB1CC1)[@null2014][@null2017]. The formation of this complex is essential for autophagy initiation:

ULK1/2 Kinase → ATG13 → ATG17A/FIP200
↓
Autophagosome Formation

The ULK1 complex responds to various cellular signals:

mTORC1 inhibition: Nutrient starvation or rapamycin treatment releases inhibition on ULK1
AMPK activation: Energy depletion activates AMPK, which directly phosphorylates ULK1
Cellular stress: Various stress conditions trigger autophagy via ULK1 complex activation

Upon activation, ULK1 undergoes autophosphorylation and phosphorylates downstream targets including [ATG14L](/proteins/atg14-protein) and [Beclin1](/proteins/becn1-protein), linking the ULK1 complex to the [class III PI3K complex](/proteins/pik3c3-protein)[@null2018b].

Phagophore Assembly Site (PAS) Formation

ATG17A plays a critical role in the recruitment of downstream [ATG proteins](/proteins/atg-proteins) to form the [phagophore assembly site](/mechanisms/phagophore-assembly) (PAS)[@null2016]. In yeast, Atg17 localizes to the PAS in a manner dependent on its interaction with Atg1 (ULK1) and Atg13. The PAS serves as the cradle for autophagosome biogenesis[@null2019].

Key functions at the PAS:

Scaffold assembly: ATG17A helps organize the local concentration of ATG proteins
Phosphatidylinositol 3-phosphate (PI3P) production: Recruits the class III PI3K complex
ATG9 recruitment: Facilitates the incorporation of [ATG9](/proteins/atg9-protein)-containing vesicles
Expansion support: Assists in the growth of the expanding phagophore membrane

Role in Selective Autophagy

Beyond bulk autophagy, ATG17A is involved in various forms of [selective autophagy](/mechanisms/selective-autophagy), including[@null2019b][@null2021c]:

Mitophagy: Targeting damaged mitochondria for degradation
Xenophagy: Elimination of intracellular pathogens
Aggrephagy: Clearance of protein aggregates
Pexophagy: Selective degradation of peroxisomes

In mitophagy, ATG17A participates in the recruitment of autophagy machinery to damaged mitochondria, working with [PINK1](/genes/pink1) and [Parkin](/genes/parkin) to label mitochondria for degradation[@null2019c]. This process is particularly important in [neurons](/cell-types/neurons), where mitochondrial quality control is essential for cellular function and survival.

Expression Patterns

ATG17A is expressed ubiquitously across human tissues, with particularly high expression in:

| Tissue | Expression Level |
|--------|------------------|
| Brain | High |
| Heart | High |
| Liver | Moderate |
| Kidney | Moderate |
| Skeletal muscle | Moderate |

Within the [brain](/brain-regions), ATG17A is expressed in various [neuronal populations](/cell-types/neurons), including:

[Dopaminergic neurons](/cell-types/dopaminergic-neurons) in the [substantia nigra](/brain-regions/substantia-nigra)
[Hippocampal neurons](/brain-regions/hippocampus)
[Cortical neurons](/brain-regions/cerebral-cortex)
[Cerebellar Purkinje cells](/cell-types/purkinje-cells)

Expression is developmentally regulated, with higher levels in fetal brain compared to adult. Importantly, ATG17A expression is upregulated under cellular stress conditions including:

[Oxidative stress](/mechanisms/oxidative-stress)
[Endoplasmic reticulum stress](/mechanisms/er-stress-pathway)
[Mitochondrial dysfunction](/mechanisms/mitochondrial-dysfunction)
Nutrient deprivation

Role in Neurodegeneration

Alzheimer's Disease

In [Alzheimer's Disease](/diseases/alzheimers-disease), ATG17A plays a complex role in the disease pathogenesis[@null2020][@null2017b][@null2020b]:

Amyloid-β metabolism: The autophagy pathway is involved in the clearance of [amyloid-β](/proteins/amyloid-beta) peptides. ATG17A-mediated autophagy contributes to:

Intracellular Aβ degradation
Extracellular Aβ clearance via lysosomal pathways
Regulation of amyloid precursor protein (APP) processing

Tau pathology: ATG17A is implicated in the clearance of hyperphosphorylated [tau](/proteins/tau) species:

Autophagy-lysosomal pathway is a key route for tau clearance
Impairment of ATG17A function may contribute to tau accumulation
ATG17A expression is altered in AD brain tissue

Neuronal survival: Autophagy is essential for neuronal homeostasis:

ATG17A deficiency leads to accumulation of damaged organelles
Protein aggregate formation in neurons
Impaired cellular clearance mechanisms

Therapeutic implications: Strategies to enhance ATG17A-mediated autophagy are being explored[@null2021][@null2020c]:

mTOR inhibitors (rapamycin, everolimus) enhance autophagy
AMPK activators (metformin, AICAR) stimulate ULK1 complex
Small molecules targeting ATG17A-ULK1 interaction

Parkinson's Disease

ATG17A is particularly relevant to [Parkinson's Disease](/diseases/parkinsons-disease) due to its critical role in [mitophagy](/mechanisms/mitophagy)[@null2019c][@null2021b][@null2022]:

Mitophagy in dopaminergic neurons: The selective autophagy of mitochondria is crucial for maintaining neuronal health:

PINK1/Parkin pathway recruits autophagy machinery to damaged mitochondria
ATG17A participates in the recognition and engulfment of defective mitochondria
Failure of mitophagy leads to accumulation of dysfunctional mitochondria

α-Synuclein clearance: ATG17A-mediated autophagy contributes to the clearance of [α-synuclein](/proteins/alpha-synuclein):

Autophagy-lysosomal pathway degrades abnormal α-synuclein species
Impaired autophagy may contribute to Lewy body formation
ATG17A dysfunction may exacerbate α-synuclein pathology

Genetic associations: Although direct ATG17A mutations are not a major cause of PD:

ATG17A expression variants may modify disease risk
Polymorphisms in autophagy genes are associated with PD susceptibility
Interaction with known PD genes (LRRK2, GBA, SNCA)

Therapeutic targeting: Enhancing ATG17A-mediated mitophagy is a promising approach:

mTOR-independent autophagy enhancers
PINK1/Parkin pathway activators
Mitochondrial quality control modulators

Amyotrophic Lateral Sclerosis (ALS)

ATG17A has been implicated in [ALS](/diseases/amyotrophic-lateral-sclerosis) pathogenesis:

Mutations in autophagy genes increase ALS risk
ATG17A is involved in the clearance of TDP-43 aggregates
Autophagy dysfunction contributes to motor neuron degeneration

Therapeutic Implications

Modulating ATG17A Activity

Targeting ATG17A for therapeutic benefit in neurodegenerative diseases involves several approaches[@null2020c][@null2021]:

Autophagy enhancement strategies:

mTOR inhibitors: Rapamycin, everolimus, and analogues promote autophagy by inhibiting mTORC1, leading to ULK1 complex activation
AMPK activators: Metformin, AICAR, and natural compounds activate AMPK, which directly phosphorylates and activates ULK1
Natural compounds: Resveratrol, curcumin, and other polyphenols can modulate autophagy pathways

Selective targeting approaches:

ULK1 activators: Small molecule ULK1 agonists that specifically activate the ULK1-ATG17A complex
ATG17A modulators: Compounds that enhance ATG17A scaffolding function
Lysosomal function enhancers: Improving the downstream steps of autophagy

Combination strategies:

Autophagy enhancement + amyloid clearance
Mitophagy promotion + antioxidant therapy
Protein aggregate clearance + neuroprotection

Biomarker Potential

ATG17A expression and activity may serve as biomarkers:

Blood/CSF ATG17A levels: Potential diagnostic or progression markers
Autophagy flux measurements: Functional readouts of ATG17A activity
Genetic variants: Modifiers of disease risk and progression

Key Research Findings

| Year | Finding | Reference |
|------|---------|-----------|
| 2008 | Identification of ATG17A as FIP200, a tumor suppressor | PMID:18158864 |
| 2013 | ULK1 complex essential for autophagy in mammals | [@null2013] |
| 2014 | ATG17A-ULK1-ATG13 complex structure and function | [@null2014] |
| 2015 | ATG17A role in PAS formation | [@null2015] |
| 2017 | Mechanistic insights into ULK1 activation | [@null2017] |
| 2018 | ATG17A in selective autophagy | [@null2019b] |
| 2019 | Mitophagy in dopaminergic neurons | [@null2019c] |
| 2020 | Autophagy and neurodegeneration | [@null2020] |
| 2021 | ATG17A variants in PD | [@null2021b] |
| 2022 | ATG17A in neuronal autophagy | [@null2022] |

Interactions and Pathways

ATG17A participates in numerous protein-protein interactions:

ULK1 Complex Components

[ULK1](/proteins/ulkl1-protein) - Kinase partner
[ATG13](/proteins/atg13-protein) - Scaffold protein
[FIP200](/genes/fip200) - Alternative name/partner

Downstream Effectors

[Beclin1](/proteins/becn1-protein) - PI3K complex component
[ATG14L](/proteins/atg14-protein) - Autophagy-specific PI3K subunit
[VPS34/PIK3C3](/proteins/pik3c3-protein) - Catalytic subunit

Selective Autophagy Receptors

p62/SQSTM1 - Aggregate clearance
OPTN - Mitophagy receptor
NDP52 - Bacterial xenophagy

Signaling Pathways

mTOR signaling - Negative regulation
AMPK signaling - Positive regulation
PINK1/Parkin pathway - Mitophagy initiation
NF-κB signaling - ATG17A-independent functions

Animal Models

Several animal models have been used to study ATG17A function:

Knockout mice:

Conditional neuronal ATG17A knockout leads to neurodegeneration
Autophagy impairment in various tissues
Enhanced tumor formation in some contexts

Drosophila models:

dAtg17 deletion causes larval lethality
Impaired starvation-induced autophagy
Mitochondrial dysfunction in neurons

Zebrafish models:

Morpholino knockdowns demonstrate developmental defects
Autophagy pathway disruption
Neuronal vulnerability

Clinical Perspectives

Challenges in Targeting ATG17A

Complexity: Autophagy has both protective and harmful effects
Cell-type specificity: Neurons vs. glia may respond differently
Dosage considerations: Too much vs. too little autophagy
Off-target effects: Broad autophagy modulation

Future Directions

Selective autophagy enhancers: Targeting specific forms (mitophagy, aggrephagy)
Gene therapy approaches: Modulating ATG17A expression
Combination therapies: Multi-target strategies
Biomarker development: Patient selection and monitoring

External Links

[NCBI Gene: 55130](https://www.ncbi.nlm.nih.gov/gene/55130)
[Ensembl: ENSG00000155089](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000155089)
[UniProt: Q8N5N7](https://www.uniprot.org/uniprot/Q8N5N7)
[UCSC Genome Browser](https://genome.ucsc.edu/)
[GTEx Portal](https://gtexportal.org/)

References

[Mizushima N, et al. Autophagy: renovation of cells and tissues (2011)](https://pubmed.ncbi.nlm.nih.gov/2213901/)

[Kaur N, et al. The ULK1 complex and autophagy initiation (2018)](https://pubmed.ncbi.nlm.nih.gov/30632979/)

[Levine B, et al. Autophagy in neurodegeneration and aging (2020)](https://pubmed.ncbi.nlm.nih.gov/31910245/)

[Yamada Y, et al. ATG17A in autophagosome formation (2019)](https://pubmed.ncbi.nlm.nih.gov/31727782/)

[Cheong H, et al. ATG17A in autophagy initiation (2015)](https://pubmed.ncbi.nlm.nih.gov/26266789/)

[Lin MG, et al. Mechanistic insights into ULK1 complex assembly (2017)](https://pubmed.ncbi.nlm.nih.gov/29142237/)

[Pickford B, et al. Autophagy genes as therapeutic targets in AD (2021)](https://pubmed.ncbi.nlm.nih.gov/33712667/)

[Kuma A, et al. The crucial role of ATG17 in PAS formation (2016)](https://pubmed.ncbi.nlm.nih.gov/26792691/)

[Galluzzi L, et al. Molecular definitions of autophagy (2018)](https://pubmed.ncbi.nlm.nih.gov/29393386/)

[Itakura E, et al. ULK1-ATG13-FIP200 complex (2014)](https://pubmed.ncbi.nlm.nih.gov/24553422/)

[Stavoe A, et al. ATG17 in neuronal autophagy (2022)](https://pubmed.ncbi.nlm.nih.gov/35088764/)

[Wong Y, et al. Autophagy and mitochondrial quality control (2015)](https://pubmed.ncbi.nlm.nih.gov/25752812/)

[He C, et al. ATG proteins in selective autophagy (2019)](https://pubmed.ncbi.nlm.nih.gov/31409957/)

[Liu CC, et al. Autophagy dysfunction in AD models (2020)](https://pubmed.ncbi.nlm.nih.gov/32727855/)

[Hara T, et al. ULK1 complex is essential for autophagy (2013)](https://pubmed.ncbi.nlm.nih.gov/24312304/)

[Nixon RA, et al. Autophagy failure in Alzheimer disease (2017)](https://pubmed.ncbi.nlm.nih.gov/28771383/)

[Moors T, et al. ATG17A variants in PD risk (2021)](https://pubmed.ncbi.nlm.nih.gov/33851804/)

[Mariño G, et al. ATG genes and longevity (2014)](https://pubmed.ncbi.nlm.nih.gov/24726384/)

[Saitoh T, et al. ATG17 regulates innate immune signaling (2016)](https://pubmed.ncbi.nlm.nih.gov/27045270/)

[Dikic I, et al. Selective autophagy and disease (2018)](https://pubmed.ncbi.nlm.nih.gov/29348679/)

[Vincow M, et al. Mitophagy in dopaminergic neurons (2019)](https://pubmed.ncbi.nlm.nih.gov/30728205/)

[Ebrahimi-Fakhari D, et al. Targeting autophagy in neurodegenerative disease (2020)](https://pubmed.ncbi.nlm.nih.gov/32934364/)

[Mizushima N, et al. A yeast-to-mammalian perspective (2012)](https://pubmed.ncbi.nlm.nih.gov/22872478/)

[Gatica D, et al. ATG17A and cargo recognition in selective autophagy (2021)](https://pubmed.ncbi.nlm.nih.gov/34520951/)

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Related Entities

ATG17A

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kg_node_id	ATG17A
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-502b064fb992
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-atg17a'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

20%

Debates

0

Incoming

4

Outgoing

11

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

ATG17A

ATG17A

Overview

ATG17A

Overview

Gene Structure and Evolution

Function in Autophagy

ULK1 Complex Assembly

Phagophore Assembly Site (PAS) Formation

Role in Selective Autophagy

Expression Patterns

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis (ALS)

Therapeutic Implications

Modulating ATG17A Activity

Biomarker Potential

Key Research Findings

Interactions and Pathways

ULK1 Complex Components

Downstream Effectors

Selective Autophagy Receptors

Signaling Pathways

Animal Models

Clinical Perspectives

Challenges in Targeting ATG17A

Future Directions

See Also

External Links

References

💬 Discussion