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## Question

# Gene Research for Functional Annotation

## ⚠️ CRITICAL: Gene/Protein Identification Context

**BEFORE YOU BEGIN RESEARCH:** You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

### Target Gene/Protein Identity (from UniProt):
- **UniProt Accession:** Q6DD88
- **Protein Description:** RecName: Full=Atlastin-3 {ECO:0000303|PubMed:14506257}; Short=AT3 {ECO:0000303|PubMed:18270207}; Short=ATL-3 {ECO:0000303|PubMed:27619977}; EC=3.6.5.- {ECO:0000269|PubMed:37102997};
- **Gene Information:** Name=ATL3 {ECO:0000312|HGNC:HGNC:24526};
- **Organism (full):** Homo sapiens (Human).
- **Protein Family:** Belongs to the TRAFAC class dynamin-like GTPase
- **Key Domains:** G_GB1_RHD3_dom. (IPR030386); Guanylate-bd/ATL_C. (IPR003191); Guanylate-bd_C_sf. (IPR036543); Guanylate-bd_N. (IPR015894); P-loop_NTPase. (IPR027417)

### MANDATORY VERIFICATION STEPS:

1. **Check if the gene symbol "ATL3" matches the protein description above**
2. **Verify the organism is correct:** Homo sapiens (Human).
3. **Check if protein family/domains align with what you find in literature**
4. **If you find literature for a DIFFERENT gene with the same or similar symbol, STOP**

### If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

**DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE.** Instead:
- State clearly: "The gene symbol 'ATL3' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

### Research Target:

Please provide a comprehensive research report on the gene **ATL3** (gene ID: ATL3, UniProt: Q6DD88) in human.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

## Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

# Gene Research for Functional Annotation

## ⚠️ CRITICAL: Gene/Protein Identification Context

**BEFORE YOU BEGIN RESEARCH:** You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

### Target Gene/Protein Identity (from UniProt):
- **UniProt Accession:** Q6DD88
- **Protein Description:** RecName: Full=Atlastin-3 {ECO:0000303|PubMed:14506257}; Short=AT3 {ECO:0000303|PubMed:18270207}; Short=ATL-3 {ECO:0000303|PubMed:27619977}; EC=3.6.5.- {ECO:0000269|PubMed:37102997};
- **Gene Information:** Name=ATL3 {ECO:0000312|HGNC:HGNC:24526};
- **Organism (full):** Homo sapiens (Human).
- **Protein Family:** Belongs to the TRAFAC class dynamin-like GTPase
- **Key Domains:** G_GB1_RHD3_dom. (IPR030386); Guanylate-bd/ATL_C. (IPR003191); Guanylate-bd_C_sf. (IPR036543); Guanylate-bd_N. (IPR015894); P-loop_NTPase. (IPR027417)

### MANDATORY VERIFICATION STEPS:

1. **Check if the gene symbol "ATL3" matches the protein description above**
2. **Verify the organism is correct:** Homo sapiens (Human).
3. **Check if protein family/domains align with what you find in literature**
4. **If you find literature for a DIFFERENT gene with the same or similar symbol, STOP**

### If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

**DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE.** Instead:
- State clearly: "The gene symbol 'ATL3' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

### Research Target:

Please provide a comprehensive research report on the gene **ATL3** (gene ID: ATL3, UniProt: Q6DD88) in human.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

## Research Report: Human **ATL3 / Atlastin-3** (UniProt: **Q6DD88**) — Functional Annotation

### 0) Target verification (gene/protein disambiguation)
The symbol **ATL3** in the retrieved scientific literature refers to **human atlastin GTPase 3 (atlastin-3)**, a member of the **atlastin family of ER-resident dynamin-like GTPases** that shape the tubular endoplasmic reticulum (ER) network via **homotypic ER membrane fusion**. Humans encode **three paralogs (ATL1–ATL3)** with differences in expression patterns and disease associations. (greco2024decipheringtherole pages 22-26, arias2025precisionmedicinefor pages 99-103, zlamalova2024atlastin1regulatesendosomal pages 1-2)

### 1) Key concepts and definitions (current understanding)

#### 1.1 Atlastins and ER network formation
Atlastins are **large dynamin-like membrane GTPases** localized to the ER that catalyze **homotypic fusion of ER tubules** and thereby generate/maintain the polygonal ER network and **three-way junctions**. (zlamalova2024atlastin1regulatesendosomal pages 1-2, pletan2023theatlastiner pages 2-6)

ATL3 specifically is discussed as an ER reshaping factor enriched in **tubular ER/three-way junction regions**, consistent with a role in network branching and dynamics. (arias2025precisionmedicinefor pages 99-103)

#### 1.2 Biochemical activity (enzyme reaction and substrate specificity)
ATL3 is a **GTPase**: it binds and hydrolyzes **GTP** (substrate), and atlastin-family **GTPase activity is required** for their ER membrane fusion function. In a direct ATL3 functional context, **GTPase-defective ATL3 mutants fail to rescue ATL3-dependent phenotypes**, supporting that ATL3’s enzymatic cycle is required in cells. (pletan2023theatlastiner pages 2-6, pletan2023theatlastiner pages 6-9)

#### 1.3 ER-phagy (reticulophagy) and receptor logic
**ER-phagy** is selective autophagy of ER subdomains. Multiple reviews classify **ATL3 as an ER-phagy receptor (or receptor-like factor)** that preferentially targets **tubular ER** for degradation and connects ER membranes to ATG8-family proteins via interaction motifs. (hubner2020erphagyandhuman pages 1-2, hubner2020erphagyandhuman pages 2-4, hill2023er‐phagyinneurodegeneration pages 2-2)

A key ATL3-specific concept is its selective binding to the **ATG8-family subfamily GABARAP** through **GABARAP-interaction motifs (GIMs)**, reported as **two GIMs** in the N-terminal cytosolic region, with selectivity for **GABARAP rather than LC3** in cited work. (hill2023er‐phagyinneurodegeneration pages 5-5)

### 2) Recent developments and latest research (prioritize 2023–2024)

#### 2.1 2024: Single-molecule mechanism of atlastin-mediated ER fusion (family-mechanistic framework)
A major 2024 advance used **single-molecule FRET (smFRET)** and molecular dynamics to dissect nucleotide-dependent conformational transitions in human atlastin cytosolic domains (performed on **ATL1** as an atlastin-family model). The study supports a refined mechanism:

* **GTP binding** promotes formation of a **“loose crossover dimer”** (Form 2-like). (shi2024dissectingthemechanism pages 1-2, shi2024dissectingthemechanism pages 3-4, shi2024dissectingthemechanism pages 4-5)
* The **GTP hydrolysis transition state** drives tightening into a **“tight crossover dimer”** (Form 3-like), consistent with force generation for membrane fusion. (shi2024dissectingthemechanism pages 4-5, shi2024dissectingthemechanism pages 8-9)
* **Pi release** favors dimer disassembly and increased flexibility; **GDP dissociation** resets the monomeric conformational preferences for a new cycle. (shi2024dissectingthemechanism pages 1-2, shi2024dissectingthemechanism pages 8-9, shi2024dissectingthemechanism pages 9-10)
* A **membrane-embedded α-helical element** between the cytosolic helical bundle and transmembrane region **self-associates** and is **required** for atlastin function, providing a coupling element between cytosolic rearrangements and the bilayer. (shi2024dissectingthemechanism pages 1-2, shi2024dissectingthemechanism pages 8-9)

Quantitatively, crossover dimer smFRET populations were reported around **~0.28 (loose)** and **~0.66 (tight)** under specific nucleotide conditions, and monomeric state centers were also mapped (e.g., ~0.18, ~0.41, ~0.63, ~0.83). (shi2024dissectingthemechanism pages 4-5, shi2024dissectingthemechanism pages 8-9)

Although these experiments are on ATL1, they represent the **current high-resolution mechanistic model for atlastin-family fusion**, which is widely used to interpret paralogs including ATL3. (shi2024dissectingthemechanism pages 1-2, shi2024dissectingthemechanism pages 9-10)

**Source details:** Shi et al., *Nature Communications* (published Mar 2024). DOI/URL: https://doi.org/10.1038/s41467-024-46919-z (shi2024dissectingthemechanism pages 1-2)

#### 2.2 2023: ATL3 as a host factor in non-enveloped virus entry (SV40)
A 2023 primary study demonstrated that **ATL3 and ATL2 are required** for formation of SV40-induced ER “escape” foci (ER-foci), but with **distinct roles**: **ATL3 relocalizes to ER-foci** and uses its **GTPase-dependent fusion activity** to promote **multi-tubular ER junctions** within these sites. (pletan2023theatlastiner pages 1-2)

ATL3 showed strong spatial association with ER-foci markers: approximately **75% of Bap31+ foci colocalized with ATL3 foci**. (pletan2023theatlastiner pages 6-9)

Mechanistically, ATL3 was found to engage components of an ER membrane penetration complex, including interactions with ER morphogenic proteins **Lunapark (LNP)** and **reticulon RTN4B**, and in infected extracts was detected in complexes containing viral structural protein VP1. (pletan2023theatlastiner pages 1-2, pletan2023theatlastiner pages 6-9)

Functionally, siRNA knockdown of ATL3 reduced infection and could be rescued by siRNA-resistant ATL3, but **not** by a **GTPase-defective ATL3 (K47A)**, demonstrating the requirement for ATL3’s enzymatic activity in this ER remodeling pathway. (pletan2023theatlastiner pages 2-6, pletan2023theatlastiner pages 6-9)

**Source details:** Pletan et al., *Journal of Virology* (published Aug 2023). DOI/URL: https://doi.org/10.1128/jvi.00756-23 (pletan2023theatlastiner pages 2-6)

#### 2.3 2023: Coronavirus subversion of ER-phagy via ATL3
A 2023 *Cell Reports* study reported that a SARS-CoV-2 protein (**ORF8**) forms condensates with **p62** and can **hijack ATL3 (and FAM134B)** into ORF8/p62 liquid droplets. This sequestration is reported to **inhibit ER-phagy**, promote ER stress, and facilitate viral replication/replication-organelle (DMV) formation. (tan2023coronavirussubvertserphagy pages 1-4)

**Source details:** Tan et al., *Cell Reports* (published Apr 2023). DOI/URL: https://doi.org/10.1016/j.celrep.2023.112286 (tan2023coronavirussubvertserphagy pages 1-4)

### 3) Current applications and real-world implementations

#### 3.1 Cell biology: manipulating ER morphology and junction architecture
ATL3 is operationally used in cell biology as an ER-shaping GTPase whose perturbation (knockdown, mutant expression) informs how **ER three-way junction formation** and **tubular ER remodeling** are controlled by the GTPase cycle and membrane-coupling helices. The SV40 ER-foci work provides an example where ATL3-dependent remodeling creates multi-tubular junctions functioning as a membrane penetration platform. (pletan2023theatlastiner pages 1-2, pletan2023theatlastiner pages 6-9)

#### 3.2 Autophagy research: tubular ER quality control (ER-phagy)
ATL3 is widely cited as a **tubular ER-phagy receptor** (or ER-phagy factor) and is used to study how ER tubules are selected for autophagic turnover under nutrient stress and other conditions, including selective engagement of **GABARAP** via GIMs. (hill2023er‐phagyinneurodegeneration pages 5-5, hubner2020erphagyandhuman pages 1-2, hubner2020erphagyandhuman pages 2-4)

#### 3.3 Infection biology: host factor dependencies
Both SV40 and SARS-CoV-2 studies position ATL3 as a host factor impacting infection: (i) **constructing ER penetration sites** (SV40) via GTPase-dependent remodeling, and (ii) being **targeted by viral proteins** to suppress ER-phagy (SARS-CoV-2 ORF8). (pletan2023theatlastiner pages 1-2, tan2023coronavirussubvertserphagy pages 1-4)

#### 3.4 Clinical genetics: rare neuropathy diagnostics
ATL3 is implemented as a candidate gene in genetic testing and mechanistic follow-up for inherited neuropathies. Open Targets lists ATL3 associations with **hereditary sensory neuropathy type 1F (HSAN1F)** and **axonal Charcot–Marie–Tooth disease type 2N**, supporting its clinical relevance in rare disease genetics. (OpenTargets Search: -ATL3)

### 4) Expert opinions and analysis (authoritative synthesis)

#### 4.1 ATL3 functional partitioning: fusion vs turnover
A 2023 review focused on ER-phagy in neurodegeneration summarizes the view that while atlastins are ER fusogens, **ATL3 may be relatively more involved in ER turnover**, citing evidence that ATL3 promotes **tubular ER degradation upon starvation** and binds GABARAP via **two GIMs** (selective vs LC3). (hill2023er‐phagyinneurodegeneration pages 5-5)

This “functional partitioning” model provides a coherent reconciliation of ATL3’s dual roles: a constitutive ER-shaping GTPase that can also act as an adaptor/receptor in ER-phagy pathways, potentially tuned by motif composition and paralog-specific activities. (hill2023er‐phagyinneurodegeneration pages 5-5, hubner2020erphagyandhuman pages 2-4)

#### 4.2 Paralog complexity
Evidence comparing paralogs indicates isoform-specific expression and phenotypic associations (e.g., ATL1 primarily CNS-enriched; ATL2/ATL3 more peripheral), with distinct disease spectra and potentially distinct mechanistic vulnerabilities within the shared atlastin fusion cycle. (greco2024decipheringtherole pages 22-26, arias2025precisionmedicinefor pages 99-103)

### 5) Relevant statistics and data (recent studies)

#### 5.1 Quantitative cell biology (SV40 ER-foci)
During SV40 infection, **~75% of Bap31+ ER foci colocalize with ATL3**, supporting strong ATL3 recruitment to penetration sites; rescue experiments and other quantifications were reported as mean ± SD across **three independent experiments** with standard significance thresholds (e.g., **P ≤ 0.01; ***P ≤ 0.001). (pletan2023theatlastiner pages 6-9)

#### 5.2 Quantitative ER–mitochondria contacts in an ATL3-variant study
In patient fibroblasts carrying a heterozygous **ATL3 p.Gln170Glu** variant (GTPase/globular domain), ER–mitochondria contacts measured by proximity ligation assay (IP3R–VDAC) were markedly reduced: **21.5 ± 2.5** and **24.8 ± 3.1 dots/cell** in two variant carriers versus **118.2 ± 7.7** (father) and **103.5 ± 6.0** (control). (arias2025precisionmedicinefor pages 107-112)

#### 5.3 Quantitative mechanistic biophysics (atlastin fusion cycle)
smFRET analysis of atlastin-family conformational states provides quantitative markers for mechanistic modeling: loose vs tight crossover dimer populations at approximately **~0.28** and **~0.66** FRET under defined nucleotide conditions, and multiple monomeric conformational states with nucleotide-dependent occupancy. (shi2024dissectingthemechanism pages 4-5, shi2024dissectingthemechanism pages 8-9)

### 6) Summary table (evidence map)
The following table consolidates ATL3’s functional annotation, mechanisms, disease links, and key recent sources.

| Category | Key points | Key recent sources (with year, journal, DOI URL) |
|---|---|---|
| Identity/domains | ATL3 in this report corresponds to human atlastin GTPase 3, an ER-resident dynamin-like large GTPase/atlastin-family protein. Reported architecture includes an N-terminal GTPase domain, a stalk/3-helix bundle, and a C-terminal transmembrane region with membrane-associated helical elements; ATL3 is preferentially associated with ER three-way junctions/tubular ER and differs from ATL1/ATL2 by broader non-CNS expression and distinct disease associations (greco2024decipheringtherole pages 22-26, arias2025precisionmedicinefor pages 99-103, zlamalova2024atlastin1regulatesendosomal pages 1-2). | Arias 2025, unknown journal, n/a; Greco 2024, unknown journal, n/a; Zlamalova et al. 2024, *Neurobiology of Disease*, https://doi.org/10.1016/j.nbd.2024.106556 |
| Biochemical activity | ATL3 is a membrane-fusion GTPase that uses GTP as substrate; atlastin-family GTPase activity is required for homotypic ER membrane fusion and generation of ER three-way junctions. In ATL3-specific experiments, GTPase-defective ATL3 mutants fail to rescue functional phenotypes, supporting that ATL3’s enzymatic GTPase activity is required for its ER-remodeling function (pletan2023theatlastiner pages 2-6, pletan2023theatlastiner pages 1-2). | Pletan et al. 2023, *Journal of Virology*, https://doi.org/10.1128/jvi.00756-23 |
| Mechanism of ER fusion | Recent single-molecule work on human atlastin mechanism (performed on ATL1 cytosolic domain, used here as family-mechanistic context) supports a cycle in which GTP binding promotes a loose crossover dimer, GTP hydrolysis tightens the 3HB interface to drive fusion, and Pi/GDP release resets the protein. A membrane-embedded helix between the 3HB and transmembrane region self-associates and is required for fusion; small sequence differences between paralogs can tune this cycle and are relevant to ATL3 interpretation (shi2024dissectingthemechanism pages 1-2, shi2024dissectingthemechanism pages 3-4, shi2024dissectingthemechanism pages 4-5, shi2024dissectingthemechanism pages 8-9, shi2024dissectingthemechanism pages 9-10). | Shi et al. 2024, *Nature Communications*, https://doi.org/10.1038/s41467-024-46919-z |
| ER-phagy role | ATL3 is described as a tubular-ER ER-phagy/reticulophagy receptor or receptor-like factor. Reviews and cited primary work indicate ATL3 promotes degradation of tubular ER during starvation, preferentially targets ER tubules, and contains two GIM motifs in its N-terminal cytosolic region that mediate selective binding to GABARAP rather than LC3, linking tubular ER to the autophagy machinery (hill2023er‐phagyinneurodegeneration pages 5-5, hubner2020erphagyandhuman pages 1-2, hubner2020erphagyandhuman pages 2-4, hill2023er‐phagyinneurodegeneration pages 2-2, yang2026erphagyreceptorsstructural pages 2-4). | Hill et al. 2023, *Journal of Neuroscience Research*, https://doi.org/10.1002/jnr.25225; Hübner & Dikic 2020, *Cell Death & Differentiation*, https://doi.org/10.1038/s41418-019-0444-0; Yang & Sheng 2026, *Acta Pharmacologica Sinica*, https://doi.org/10.1038/s41401-025-01724-2 |
| Viral infection role | ATL3 has emerging infection-related functions in ER remodeling. During SV40 entry, ATL3 relocalizes to ER foci, forms complexes with LNP/RTN4B and virus-containing penetration machinery, and uses GTPase-dependent fusion activity to help build multi-tubular ER junctions needed for membrane penetration. In coronavirus studies, ATL3 is also reported as an ER-phagy receptor hijacked into ORF8/p62 condensates, suppressing ER-phagy and favoring viral replication/DMV formation (pletan2023theatlastiner pages 2-6, pletan2023theatlastiner pages 1-2, tan2023coronavirussubvertserphagy pages 1-4, pletan2023theatlastiner pages 6-9). | Pletan et al. 2023, *Journal of Virology*, https://doi.org/10.1128/jvi.00756-23; Tan et al. 2023, *Cell Reports*, https://doi.org/10.1016/j.celrep.2023.112286 |
| Disease associations | ATL3 is linked to inherited neuropathies, especially hereditary sensory and autonomic neuropathy type 1F and Charcot-Marie-Tooth disease axonal type 2N in target-disease databases. Human genetic/functional studies also support ATL3 variants causing sensory neuropathy and expanding phenotypes to motor axonopathy; disease-associated variants affect the GTPase/globular domain or later steps of the fusion cycle, with downstream effects on ER architecture, ER-mitochondria contacts, Golgi morphology, and autophagic flux (OpenTargets Search: -ATL3, arias2025precisionmedicinefor pages 93-99, arias2025precisionmedicinefor pages 112-116, arias2025precisionmedicinefor pages 116-120, arias2025precisionmedicinefor pages 107-112). | Open Targets, ATL3 associations, context pqac-00000000; Arias 2025, unknown journal, n/a |
| Quantitative data | Recent quantitative findings include: in ATL1 family-mechanistic smFRET experiments, crossover dimer states were centered around ~0.28 and ~0.66 FRET, with monomeric states around ~0.18, ~0.41, ~0.63, and ~0.83 depending on nucleotide state; in SV40 studies, ~75% of Bap31+ ER foci colocalized with ATL3 foci, and ATL3 rescue experiments were analyzed over 3 independent experiments with **P ≤ 0.01 or ***P ≤ 0.001; in ATL3 p.Gln170Glu patient fibroblasts, ER-mitochondria contact sites were reduced to 21.5 ± 2.5 and 24.8 ± 3.1 dots/cell versus 118.2 ± 7.7 and 103.5 ± 6.0 in controls/father (shi2024dissectingthemechanism pages 4-5, shi2024dissectingthemechanism pages 8-9, pletan2023theatlastiner pages 6-9, arias2025precisionmedicinefor pages 107-112). | Shi et al. 2024, *Nature Communications*, https://doi.org/10.1038/s41467-024-46919-z; Pletan et al. 2023, *Journal of Virology*, https://doi.org/10.1128/jvi.00756-23; Arias 2025, unknown journal, n/a |


*Table: This table summarizes the current functional annotation of human ATL3, including identity, biochemical activity, ER fusion mechanism, ER-phagy, infection-related roles, disease links, and selected quantitative findings. It is useful as a compact evidence map with direct source and context-ID support.*

### 7) Limitations of this report (evidence boundaries)
* Several mechanistic details of the GTPase cycle are derived from 2024 single-molecule experiments performed on **ATL1** (family model), and are used here as the best available high-resolution mechanistic framework for atlastins, rather than as direct ATL3-only measurements. (shi2024dissectingthemechanism pages 1-2, shi2024dissectingthemechanism pages 9-10)
* Some newer ER-phagy receptor mechanistic reviews were retrieved (including 2026), but the most direct primary quantitative data extracted here are from 2023–2024 infection studies and a quantitative patient-fibroblast phenotype study. (tan2023coronavirussubvertserphagy pages 1-4, pletan2023theatlastiner pages 6-9, arias2025precisionmedicinefor pages 107-112)

### References (URLs and publication months/years)
* Shi L. et al. **Mar 2024**. *Nature Communications*. “Dissecting the mechanism of atlastin-mediated homotypic membrane fusion at the single-molecule level.” https://doi.org/10.1038/s41467-024-46919-z (shi2024dissectingthemechanism pages 1-2)
* Pletan M. et al. **Aug 2023**. *Journal of Virology*. “The atlastin ER morphogenic proteins promote formation of a membrane penetration site during non-enveloped virus entry.” https://doi.org/10.1128/jvi.00756-23 (pletan2023theatlastiner pages 2-6)
* Tan X. et al. **Apr 2023**. *Cell Reports*. “Coronavirus subverts ER-phagy by hijacking FAM134B and ATL3 into p62 condensates to facilitate viral replication.” https://doi.org/10.1016/j.celrep.2023.112286 (tan2023coronavirussubvertserphagy pages 1-4)
* Hill M.A. et al. **Jun 2023**. *Journal of Neuroscience Research*. “ER-phagy in neurodegeneration.” https://doi.org/10.1002/jnr.25225 (hill2023er‐phagyinneurodegeneration pages 5-5)
* Hübner C.A., Dikic I. **Oct 2020**. *Cell Death & Differentiation*. “ER-phagy and human diseases.” https://doi.org/10.1038/s41418-019-0444-0 (hubner2020erphagyandhuman pages 1-2)
* Open Targets Platform (disease-target associations for ATL3; accessed via tool context). (OpenTargets Search: -ATL3)


References

1. (greco2024decipheringtherole pages 22-26): F Greco. Deciphering the role of bmp signalling pathway in hereditary spastic paraplegia: identification of a novel therapeutic approach in zebrafish knockout models for …. Unknown journal, 2024.

2. (arias2025precisionmedicinefor pages 99-103): B Estévez Arias. Precision medicine for rare neuromuscular diseases: clinical, genetic and pathophysiological studies. Unknown journal, 2025.

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8. (hill2023er‐phagyinneurodegeneration pages 2-2): Melissa A. Hill, Alex M. Sykes, and George D. Mellick. Er‐phagy in neurodegeneration. Journal of Neuroscience Research, 101:1611-1623, Jun 2023. URL: https://doi.org/10.1002/jnr.25225, doi:10.1002/jnr.25225. This article has 23 citations and is from a peer-reviewed journal.

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15. (pletan2023theatlastiner pages 1-2): Madison Pletan, Xiaofang Liu, Grace Cha, Yu-Jie Chen, Jeffrey Knupp, and Billy Tsai. The atlastin er morphogenic proteins promote formation of a membrane penetration site during non-enveloped virus entry. Journal of Virology, Aug 2023. URL: https://doi.org/10.1128/jvi.00756-23, doi:10.1128/jvi.00756-23. This article has 5 citations and is from a domain leading peer-reviewed journal.

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## Artifacts

- [Edison artifact artifact-00](ATL3-deep-research-falcon_artifacts/artifact-00.md)

## Citations

1. arias2025precisionmedicinefor pages 99-103
2. shi2024dissectingthemechanism pages 1-2
3. pletan2023theatlastiner pages 1-2
4. pletan2023theatlastiner pages 6-9
5. pletan2023theatlastiner pages 2-6
6. tan2023coronavirussubvertserphagy pages 1-4
7. arias2025precisionmedicinefor pages 107-112
8. hubner2020erphagyandhuman pages 1-2
9. greco2024decipheringtherole pages 22-26
10. hubner2020erphagyandhuman pages 2-4
11. shi2024dissectingthemechanism pages 3-4
12. shi2024dissectingthemechanism pages 4-5
13. shi2024dissectingthemechanism pages 8-9
14. shi2024dissectingthemechanism pages 9-10
15. yang2026erphagyreceptorsstructural pages 2-4
16. arias2025precisionmedicinefor pages 93-99
17. arias2025precisionmedicinefor pages 112-116
18. arias2025precisionmedicinefor pages 116-120
19. https://doi.org/10.1038/s41467-024-46919-z
20. https://doi.org/10.1128/jvi.00756-23
21. https://doi.org/10.1016/j.celrep.2023.112286
22. https://doi.org/10.1016/j.nbd.2024.106556
23. https://doi.org/10.1002/jnr.25225;
24. https://doi.org/10.1038/s41418-019-0444-0;
25. https://doi.org/10.1038/s41401-025-01724-2
26. https://doi.org/10.1128/jvi.00756-23;
27. https://doi.org/10.1038/s41467-024-46919-z;
28. https://doi.org/10.1002/jnr.25225
29. https://doi.org/10.1038/s41418-019-0444-0
30. https://doi.org/10.1016/j.nbd.2024.106556,
31. https://doi.org/10.1128/jvi.00756-23,
32. https://doi.org/10.1038/s41418-019-0444-0,
33. https://doi.org/10.1002/jnr.25225,
34. https://doi.org/10.1038/s41467-024-46919-z,
35. https://doi.org/10.1016/j.celrep.2023.112286,
36. https://doi.org/10.1038/s41401-025-01724-2,