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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: P38879
• Protein Description: RecName: Full=Nascent polypeptide-associated complex subunit alpha; Short=NAC-alpha; AltName: Full=Alpha-NAC; AltName: Full=GAL4 DNA-binding enhancer protein 2;
• Gene Information: Name=EGD2; OrderedLocusNames=YHR193C;
• Organism (full): Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
• Protein Family: Belongs to the NAC-alpha family. .
• Key Domains: EGD2/NACA0like. (IPR016641); NAC-like_UBA. (IPR044034); NAC_A/B_dom_sf. (IPR038187); Nas_poly-pep-assoc_cplx_dom. (IPR002715); UBA-like_sf. (IPR009060)

MANDATORY VERIFICATION STEPS:

1. Check if the gene symbol "EGD2" matches the protein description above
2. Verify the organism is correct: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
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 'EGD2' 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 EGD2 (gene ID: EGD2, UniProt: P38879) in yeast.

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this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.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: P38879
• Protein Description: RecName: Full=Nascent polypeptide-associated complex subunit alpha; Short=NAC-alpha; AltName: Full=Alpha-NAC; AltName: Full=GAL4 DNA-binding enhancer protein 2;
• Gene Information: Name=EGD2; OrderedLocusNames=YHR193C;
• Organism (full): Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
• Protein Family: Belongs to the NAC-alpha family. .
• Key Domains: EGD2/NACA0like. (IPR016641); NAC-like_UBA. (IPR044034); NAC_A/B_dom_sf. (IPR038187); Nas_poly-pep-assoc_cplx_dom. (IPR002715); UBA-like_sf. (IPR009060)

MANDATORY VERIFICATION STEPS:

1. Check if the gene symbol "EGD2" matches the protein description above
2. Verify the organism is correct: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
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 'EGD2' 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 EGD2 (gene ID: EGD2, UniProt: P38879) in yeast.

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: Functional Annotation of EGD2 / YHR193C (UniProt P38879) in Saccharomyces cerevisiae (S288c)

Executive summary

EGD2 (YHR193C; UniProt P38879) encodes the sole Saccharomyces cerevisiae nascent polypeptide‑associated complex (NAC) α subunit (“NAC‑alpha”, Egd2). NAC is a ribosome‑associated cotranslational chaperone/adaptor that binds near the ribosomal exit tunnel and engages nascent chains very early during translation, influencing nascent-chain folding, aggregation avoidance, and targeting decisions, particularly interplay with SRP‑dependent ER targeting and auxiliary roles in mitochondrial protein biogenesis. (alamo2011definingthespecificity pages 1-2, pech2010dualbindingmode pages 1-2)

Recent yeast studies (2024) strengthen mechanistic understanding that NAC (including Egd2) can co-occupy the ribosomal tunnel exit together with the Zuo1/Hsp70 system in vivo (rather than being strictly mutually exclusive), and that EGD2 loss has only partial effects in some mitochondrial quality-control contexts (mitophagy), consistent with EGD2 acting as a supportive/auxiliary component within a broader cotranslational proteostasis network. (tian2024thenascentpolypeptideassociated pages 1-2, ziegelhoffer2024nacandzuotinhsp70 pages 1-2, ziegelhoffer2024nacandzuotinhsp70 media efe47529)

1) Key concepts and definitions (current understanding)

1.1. What is NAC?

The nascent chain‑associated complex (NAC) is an abundant, conserved cotranslational factor that binds ribosome‑nascent chain complexes close to the exit tunnel and can interact with very short nascent chains, consistent with an early role in nascent chain handling. (alamo2011definingthespecificity pages 1-2, pech2010dualbindingmode pages 1-2)

In budding yeast, NAC is generally an α/β heterodimer, though evidence supports that certain NAC subunits can also form homodimeric species under some conditions. (nyathi2015analysisofthe pages 7-9, alamo2011definingthespecificity pages 1-2)

1.2. Yeast NAC subunit composition and nomenclature

Saccharomyces cerevisiae encodes:
- One α subunit: Egd2 (EGD2 / YHR193C)
- Two β paralogs: Egd1 (β1) and Btt1 (β′/β3)
forming two main heterodimers Egd2/Egd1 (αβ1) and Egd2/Btt1 (αβ3). (ott2015functionaldissectionof pages 1-2, alamo2011definingthespecificity pages 1-2, tian2024thenascentpolypeptideassociated pages 1-2)

The β paralog Btt1 is much less abundant than Egd1 (reported as ~100‑fold lower in some studies; also described as ~20–100‑fold lower), making Egd2/Egd1 the predominant heterodimer under standard conditions. (ott2015functionaldissectionof pages 1-2, schilke2024functionalsimilaritiesand pages 1-3)

1.3. Where does Egd2 act?

Egd2 functions primarily as a cytosolic, ribosome‑associated factor at the 60S tunnel exit region, contacting ribosomal proteins in the vicinity (e.g., contacts to Rpl17/Rpl35 are discussed across mechanistic studies). (nyathi2015analysisofthe pages 7-9, pech2010dualbindingmode pages 1-2)

The ribosome tunnel exit is a “hub” for multiple biogenesis factors, including NAC and the Zuo1/Hsp70 (RAC–Ssb) system; recent evidence indicates co-occupancy in vivo (see section 2.2). (ziegelhoffer2024nacandzuotinhsp70 pages 1-2)

1.4. What is the “function” of Egd2 (not an enzyme reaction)

EGD2 does not encode an enzyme or transporter with substrate specificity. Instead, Egd2 is a protein biogenesis factor whose “primary function” is best described as:
- a component of a general cotranslational chaperone/adaptor complex that helps manage nascent chain fate (folding/aggregation avoidance and targeting factor access) at the ribosome exit. (alamo2011definingthespecificity pages 1-2, ott2015functionaldissectionof pages 1-2)

2) Recent developments and latest research (prioritizing 2023–2024)

2.1. 2024: NAC and Zuo1/Hsp70 can coexist at the ribosome tunnel exit in vivo

A major 2024 advance in yeast is in vivo cross-linking evidence showing that NAC and Zuotin/Hsp70 systems can coexist and physically cross-link at the ribosome tunnel exit, including when translation initiation is inhibited. This supports a model where NAC’s globular domain is modestly shifted relative to mutually exclusive configurations inferred from some cryo-EM models, while still allowing productive Hsp70 positioning for nascent chain interaction. (ziegelhoffer2024nacandzuotinhsp70 pages 1-2)

Quantitative context from this work: NAC associates with ribosomes at approximately ~1:1, while RAC association is lower at ~0.3–0.5:1. (ziegelhoffer2024nacandzuotinhsp70 pages 1-2)

Visual evidence: the study provides schematic/model figures depicting co-occupancy of NAC with Zuo1 and Ssb at the tunnel exit. (ziegelhoffer2024nacandzuotinhsp70 media efe47529, ziegelhoffer2024nacandzuotinhsp70 media 7869bf08)

2.2. 2024: NAC subunits and mitochondrial quality control (mitophagy)

A 2024 Scientific Reports study focusing on Egd1 (β subunit) in mitophagy reports that:
- Mitophagy is strongly reduced in egd1Δ cells.
- By contrast, loss of the sole α subunit Egd2 causes only a partial reduction in mitophagy, consistent with Egd2 being supportive but not the primary limiting subunit for this phenotype.
- Mechanistically, Atg32 phosphorylation is decreased in egd1Δ, and forced Atg32 hyperphosphorylation can almost completely restore mitophagy in egd1Δ. (tian2024thenascentpolypeptideassociated pages 1-2)

Importantly for Egd2’s functional annotation, this paper also notes:
- NAC is a peripheral component of cytoplasmic ribosomes interacting with nascent chains.
- Loss of Egd2 causes partial defects in mitochondrial protein import.
- Cells lacking both Egd1 and Egd2 produce polypeptides normally but have fewer ribosomes associated with the mitochondrial surface, linking NAC subunits (including Egd2) to ribosome positioning relevant for mitochondrial protein biogenesis. (tian2024thenascentpolypeptideassociated pages 1-2)

2.3. 2024: Proteotoxic aggregation models (polyQ/prions) implicate NAC as an aggregation organizer

A 2024 PLOS ONE yeast study reports that disruption of NAC reduces polyglutamine (polyQ) aggregation/toxicity: NAC disruption improved viability in cells expressing expanded polyQ, delayed and reduced aggregation, and altered aggregate morphology; it also changed de novo prion induction. (dublinryan2024disruptionofthe pages 1-2)

While this study is not uniquely about Egd2, it directly includes yeast NAC composition (Egd2 as α; Egd1/Btt1 as β) and reinforces that NAC is a key determinant of aggregate organization in vivo. (dublinryan2024disruptionofthe pages 1-2)

2.4. 2024: Comparative subunit-function analysis underscores abundance and paralog-specific roles

A 2024 Cell Stress and Chaperones paper emphasizes that NAC is extremely abundant (near ribosome stoichiometry), with Nacβ2 (Btt1) much less abundant than Nacβ1 (Egd1), and describes subunit-specific functional specialization (including links to CCR4–Not/Caf130 effects on Rpl4 mRNA in other contexts). It also notes “recent reports” linking β subunits to selective mitochondrial degradation and protein import (consistent with the mitophagy work above). (schilke2024functionalsimilaritiesand pages 1-3, schilke2024functionalsimilaritiesand pages 9-10)

3) Experimentally supported functions, pathways, and localization of Egd2

3.1. Ribosome binding and physical positioning at the exit tunnel

Mechanistic mapping of NAC in yeast indicates it is quantitatively associated with ribosomes and contacts ribosomal proteins at the tunnel exit; Egd2 (αNAC) is reported to contact Rpl17 near Rpl31, supporting the proposal of an adapter surface at Rpl31/Rpl17 for ribosome-associated factors. (pech2010dualbindingmode pages 1-2)

Further, the first ~23 amino acids of βNAC are sufficient to target an otherwise non-associated protein to ribosomes, consistent with a major ribosome-anchoring role for the β subunit, while α (Egd2) contributes additional tunnel-exit contacts and functional capacity. (pech2010dualbindingmode pages 1-2, ott2015functionaldissectionof pages 1-2)

3.2. Chaperone function and interaction with other cotranslational proteostasis systems (RAC–Ssb)

A functional dissection of yeast NAC shows that while deletion of NAC alone can be mild, combined perturbation with the Hsp70 system reveals essential overlap:
- nacΔssbΔ cells show aggravated defects including impaired growth on L‑canavanine or hygromycin B, increased aggregation of newly synthesized proteins, and reduced translational activity due to ribosome biogenesis defects.
- The abundant αβ-NAC (Egd2/Egd1) heterodimer (but not αβ′/Egd2/Btt1) can suppress these defects, and this rescue requires ribosome association and high expression.
- Deletion of the α‑NAC UBA domain enhances aggregation-preventing activity, suggesting a negative regulatory role for this domain in vivo. (ott2015functionaldissectionof pages 1-2, ott2015functionaldissectionof pages 2-4)

These observations support annotation of Egd2 as part of a ribosome-bound chaperone system acting in parallel/overlap with RAC–Ssb to preserve cotranslational proteostasis. (ott2015functionaldissectionof pages 1-2)

3.3. Modulating SRP-dependent ER targeting and preventing aggregation of secretory nascent chains

A key mechanistic role for NAC is to regulate access of biogenesis factors at the exit site, including SRP pathway components. Transcript-level RNC association analysis indicates overlap between NAC and SRP substrates and suggests NAC modulates SRP specificity and fidelity in vivo. (alamo2011definingthespecificity pages 1-2)

Direct functional evidence in yeast indicates Egd2 can protect SRP-dependent nascent chains from aggregation:
- In an SRP mutant background (sec65‑1), deleting EGD2 increases detergent-insoluble aggregation after shift to 37°C, and pulse-labeling shows increased aggregation of newly synthesized proteins.
- Conversely, overexpression of Egd2 (or NAC) reduces aggregation of newly synthesized proteins and reduces ubiquitinated species in aggregates.
- Egd2 retains residual ribosome binding even without Egd1, and cross-linking data supports an Egd2 homodimeric species (a 52‑kDa cross-linked adduct). (nyathi2015analysisofthe pages 7-9)

Together these findings support that Egd2-containing NAC acts as an anti-aggregation factor particularly when SRP-dependent cotranslational targeting is compromised. (nyathi2015analysisofthe pages 7-9)

3.4. Mitochondrial protein biogenesis and mitophagy (auxiliary roles)

Evidence supports NAC involvement in mitochondrial protein targeting/import and associated quality control:
- RNC association analyses found mRNAs encoding mitochondrial proteins enriched with association to Btt1 and Egd2, and a synthetic growth defect between egd2Δ and mitochondrial targeting factor mft1Δ was reported, consistent with an auxiliary mitochondrial targeting role. (alamo2011definingthespecificity pages 17-18)
- In 2024 mitophagy work, loss of Egd2 caused partial defects in mitochondrial protein import and partial reduction in mitophagy, while combined loss of Egd1 and Egd2 reduced ribosome association with the mitochondrial surface. (tian2024thenascentpolypeptideassociated pages 1-2)

Thus, Egd2’s best-supported mitochondrial annotation is as a supportive NAC subunit contributing to efficient mitochondrial protein import and ribosome positioning, rather than a dedicated mitophagy factor. (tian2024thenascentpolypeptideassociated pages 1-2)

4) Current applications and real-world implementations

4.1. Yeast as a discovery platform for cotranslational proteostasis and targeting

Because yeast NAC is genetically tractable and its loss can be buffered unless combined with other perturbations, EGD2 and NAC mutants are used as sensitized backgrounds to reveal:
- mechanisms of cotranslational folding and nascent-chain aggregation,
- interplay between NAC, SRP, and ribosome-associated Hsp70 systems,
- determinants of organelle targeting and ribosome localization (ER/mitochondria). (nyathi2015analysisofthe pages 7-9, ott2015functionaldissectionof pages 1-2, tian2024thenascentpolypeptideassociated pages 1-2)

4.2. Proteotoxicity/aggregation model systems

The 2024 polyQ study suggests that modulating NAC can change aggregation kinetics/morphology and toxicity in yeast models of human misfolding proteins. Although this is not a clinical implementation, it is a real-world research application: NAC perturbation serves as a tool to explore mechanisms of aggregation and prion biology and to identify potentially “protective” cellular remodeling states. (dublinryan2024disruptionofthe pages 1-2)

5) Expert opinions and analysis (authoritative sources)

5.1. NAC as a general cotranslational chaperone and regulator of targeting-factor access

The combination of systematic RNC association and mechanistic ribosome-contact studies supports a consensus view that NAC is a general cotranslational chaperone and that it helps regulate access of other biogenesis factors at the exit tunnel, including SRP, rather than being solely an antagonist of SRP. (alamo2011definingthespecificity pages 1-2, pech2010dualbindingmode pages 1-2)

5.2. Functional modularity: EGD2 is important but often buffered

Multiple yeast studies highlight that loss of NAC alone is often mild, but strong phenotypes emerge when combined with defects in other cotranslational networks (e.g., Ssb/RAC or SRP pathway mutants). This is consistent with an expert interpretation of Egd2 as a robustness factor that provides redundancy and buffering capacity in proteostasis and targeting pathways. (ott2015functionaldissectionof pages 1-2, nyathi2015analysisofthe pages 7-9)

5.3. Updated view (2024): simultaneous tunnel-exit occupancy is plausible in vivo

In vivo cross-linking evidence from 2024 supports a revised, more flexible model of the tunnel exit where NAC can coexist with Zuo1/Hsp70 systems, implying that factor competition and coordination is dynamic and context-dependent. (ziegelhoffer2024nacandzuotinhsp70 pages 1-2)

6) Statistics and quantitative data (recent studies and key mechanistic measurements)

• Relative abundance of NAC β paralogs: Btt1/Nacβ2 is reported as ~100× less concentrated than Egd1/Nacβ1 in yeast (also reported as ~20–100× lower), explaining why Egd2/Egd1 is predominant. (ott2015functionaldissectionof pages 1-2, schilke2024functionalsimilaritiesand pages 1-3)
• Ribosome stoichiometry: NAC associates with ribosomes at approximately ~1:1, while RAC associates at ~0.3–0.5:1 (yeast in vivo cross-linking study, 2024). (ziegelhoffer2024nacandzuotinhsp70 pages 1-2)
• Cross-link readouts: an Egd2 homodimer-like DSS cross-linked species at ~52 kDa was observed and increased with Egd2 overexpression. (nyathi2015analysisofthe pages 7-9)
• Gene category responses upon NAC perturbation (systems-level): induction of categories including protein folding genes (6%) and ribosome biogenesis genes (37%) was reported in a dataset analyzing responses to NAC perturbation. (alamo2011definingthespecificity pages 17-18)
• Mitophagy phenotype stratification (2024): Atg32-dependent mitophagy is strongly reduced in egd1Δ, while egd2Δ shows partial/slight reduction; Atg32 phosphorylation decreases in egd1Δ and forced hyperphosphorylation rescues mitophagy. (tian2024thenascentpolypeptideassociated pages 1-2)

Evidence map table (for rapid functional annotation)

The following table consolidates the core functional-annotation facts, partners, localization, phenotypes, and quantitative notes.

Table: This table summarizes the experimentally supported identity, localization, molecular functions, interaction network, and key phenotypes of yeast EGD2/NAC-alpha. It is designed as a compact evidence map for functional annotation, with quantitative notes and citations to the provided source contexts.

Visual evidence (ribosome tunnel-exit positioning and co-occupancy models)

Ziegelhoffer et al. (2024) provides models and schematic summaries of NAC positioning and co-occupancy with the Zuo1/Hsp70 system at the ribosome tunnel exit. (ziegelhoffer2024nacandzuotinhsp70 media efe47529, ziegelhoffer2024nacandzuotinhsp70 media 7869bf08)

Key references (with URLs and publication dates)

2024 (prioritized)
- Ziegelhoffer T. et al. Nucleic Acids Research (Jan 2024). “NAC and Zuotin/Hsp70 chaperone systems coexist at the ribosome tunnel exit in vivo.” https://doi.org/10.1093/nar/gkae005 (ziegelhoffer2024nacandzuotinhsp70 pages 1-2)
- Tian Y., Okamoto K. Scientific Reports (Jan 2024). “The nascent polypeptide-associated complex subunit Egd1 is required for efficient selective mitochondrial degradation in budding yeast.” https://doi.org/10.1038/s41598-023-50245-7 (tian2024thenascentpolypeptideassociated pages 1-2)
- Dublin-Ryan L.B. et al. PLOS ONE (Aug 2024). “Disruption of the nascent polypeptide-associated complex leads to reduced polyglutamine aggregation and toxicity.” https://doi.org/10.1371/journal.pone.0303008 (dublinryan2024disruptionofthe pages 1-2)
- Schilke B.A. et al. Cell Stress and Chaperones (Dec 2024). “Functional similarities and differences among subunits of the nascent polypeptide-associated complex (NAC) of Saccharomyces cerevisiae.” https://doi.org/10.1016/j.cstres.2024.10.004 (schilke2024functionalsimilaritiesand pages 1-3)

Foundational mechanistic references
- Nyathi Y., Pool M.R. J Cell Biol (Jul 2015). “Analysis of the interplay of protein biogenesis factors at the ribosome exit site reveals new role for NAC.” https://doi.org/10.1083/jcb.201410086 (nyathi2015analysisofthe pages 7-9)
- Ott A.-K. et al. PLOS ONE (Nov 2015). “Functional dissection of the nascent polypeptide-associated complex in Saccharomyces cerevisiae.” https://doi.org/10.1371/journal.pone.0143457 (ott2015functionaldissectionof pages 1-2)
- del Alamo M. et al. PLoS Biology (Jul 2011). “Defining the specificity of cotranslationally acting chaperones by systematic analysis of mRNAs associated with ribosome-nascent chain complexes.” https://doi.org/10.1371/journal.pbio.1001100 (alamo2011definingthespecificity pages 1-2)
- Pech M. et al. J Biol Chem (Jun 2010). “Dual binding mode of the nascent polypeptide-associated complex reveals a novel universal adapter site on the ribosome.” https://doi.org/10.1074/jbc.M109.092536 (pech2010dualbindingmode pages 1-2)

Notes on scope and evidence limitations

• The available evidence strongly supports Egd2’s ribosome/tunnel-exit association, roles in cotranslational chaperoning, and SRP/mitochondrial pathway interplay, but does not provide a single, universally agreed “substrate list” for Egd2 alone because NAC interacts broadly with nascent chains and different subunits show distinct preferences in RNC association assays. (alamo2011definingthespecificity pages 17-18, alamo2011definingthespecificity pages 1-2)
• Several quantitative outcomes in newer yeast studies are described as “partial/slight” rather than giving fold-changes in the accessible excerpts (e.g., Egd2’s magnitude of mitophagy reduction), and deeper numeric extraction would require targeted reading of full result tables/figures beyond the snippets. (tian2024thenascentpolypeptideassociated pages 1-2)

References

1. (alamo2011definingthespecificity pages 1-2): Marta del Alamo, Daniel J. Hogan, Sebastian Pechmann, Veronique Albanese, Patrick O. Brown, and Judith Frydman. Defining the specificity of cotranslationally acting chaperones by systematic analysis of mrnas associated with ribosome-nascent chain complexes. PLoS Biology, 9:e1001100, Jul 2011. URL: https://doi.org/10.1371/journal.pbio.1001100, doi:10.1371/journal.pbio.1001100. This article has 201 citations and is from a highest quality peer-reviewed journal.

2. (pech2010dualbindingmode pages 1-2): Markus Pech, Thomas Spreter, Roland Beckmann, and Birgitta Beatrix. Dual binding mode of the nascent polypeptide-associated complex reveals a novel universal adapter site on the ribosome. Journal of Biological Chemistry, 285:19679-19687, Jun 2010. URL: https://doi.org/10.1074/jbc.m109.092536, doi:10.1074/jbc.m109.092536. This article has 79 citations and is from a domain leading peer-reviewed journal.

3. (tian2024thenascentpolypeptideassociated pages 1-2): Yuan Tian and Koji Okamoto. The nascent polypeptide-associated complex subunit egd1 is required for efficient selective mitochondrial degradation in budding yeast. Scientific Reports, Jan 2024. URL: https://doi.org/10.1038/s41598-023-50245-7, doi:10.1038/s41598-023-50245-7. This article has 1 citations and is from a peer-reviewed journal.

4. (ziegelhoffer2024nacandzuotinhsp70 pages 1-2): Thomas Ziegelhoffer, Amit K Verma, Wojciech Delewski, Brenda A Schilke, Paige M Hill, Marcin Pitek, Jaroslaw Marszalek, and Elizabeth A Craig. Nac and zuotin/hsp70 chaperone systems coexist at the ribosome tunnel exit in vivo. Nucleic Acids Research, 52:3346-3357, Jan 2024. URL: https://doi.org/10.1093/nar/gkae005, doi:10.1093/nar/gkae005. This article has 4 citations and is from a highest quality peer-reviewed journal.

5. (ziegelhoffer2024nacandzuotinhsp70 media efe47529): Thomas Ziegelhoffer, Amit K Verma, Wojciech Delewski, Brenda A Schilke, Paige M Hill, Marcin Pitek, Jaroslaw Marszalek, and Elizabeth A Craig. Nac and zuotin/hsp70 chaperone systems coexist at the ribosome tunnel exit in vivo. Nucleic Acids Research, 52:3346-3357, Jan 2024. URL: https://doi.org/10.1093/nar/gkae005, doi:10.1093/nar/gkae005. This article has 4 citations and is from a highest quality peer-reviewed journal.

6. (nyathi2015analysisofthe pages 7-9): Yvonne Nyathi and Martin R. Pool. Analysis of the interplay of protein biogenesis factors at the ribosome exit site reveals new role for nac. The Journal of Cell Biology, 210:287-301, Jul 2015. URL: https://doi.org/10.1083/jcb.201410086, doi:10.1083/jcb.201410086. This article has 52 citations.

7. (ott2015functionaldissectionof pages 1-2): Ann-Kathrin Ott, Lisa Locher, Miriam Koch, and Elke Deuerling. Functional dissection of the nascent polypeptide-associated complex in saccharomyces cerevisiae. PLoS ONE, 10:e0143457, Nov 2015. URL: https://doi.org/10.1371/journal.pone.0143457, doi:10.1371/journal.pone.0143457. This article has 41 citations and is from a peer-reviewed journal.

8. (schilke2024functionalsimilaritiesand pages 1-3): Brenda A. Schilke, Thomas Ziegelhoffer, Przemyslaw Domanski, Jaroslaw Marszalek, Bartlomiej Tomiczek, and Elizabeth A. Craig. Functional similarities and differences among subunits of the nascent polypeptide-associated complex (nac) of saccharomyces cerevisiae. Cell Stress and Chaperones, 29:721-734, Dec 2024. URL: https://doi.org/10.1016/j.cstres.2024.10.004, doi:10.1016/j.cstres.2024.10.004. This article has 1 citations and is from a peer-reviewed journal.

9. (ziegelhoffer2024nacandzuotinhsp70 media 7869bf08): Thomas Ziegelhoffer, Amit K Verma, Wojciech Delewski, Brenda A Schilke, Paige M Hill, Marcin Pitek, Jaroslaw Marszalek, and Elizabeth A Craig. Nac and zuotin/hsp70 chaperone systems coexist at the ribosome tunnel exit in vivo. Nucleic Acids Research, 52:3346-3357, Jan 2024. URL: https://doi.org/10.1093/nar/gkae005, doi:10.1093/nar/gkae005. This article has 4 citations and is from a highest quality peer-reviewed journal.

10. (dublinryan2024disruptionofthe pages 1-2): Leeran B. Dublin-Ryan, Ankan K. Bhadra, and Heather L. True. Disruption of the nascent polypeptide-associated complex leads to reduced polyglutamine aggregation and toxicity. PLOS ONE, 19:e0303008, Aug 2024. URL: https://doi.org/10.1371/journal.pone.0303008, doi:10.1371/journal.pone.0303008. This article has 0 citations and is from a peer-reviewed journal.

11. (schilke2024functionalsimilaritiesand pages 9-10): Brenda A. Schilke, Thomas Ziegelhoffer, Przemyslaw Domanski, Jaroslaw Marszalek, Bartlomiej Tomiczek, and Elizabeth A. Craig. Functional similarities and differences among subunits of the nascent polypeptide-associated complex (nac) of saccharomyces cerevisiae. Cell Stress and Chaperones, 29:721-734, Dec 2024. URL: https://doi.org/10.1016/j.cstres.2024.10.004, doi:10.1016/j.cstres.2024.10.004. This article has 1 citations and is from a peer-reviewed journal.

12. (ott2015functionaldissectionof pages 2-4): Ann-Kathrin Ott, Lisa Locher, Miriam Koch, and Elke Deuerling. Functional dissection of the nascent polypeptide-associated complex in saccharomyces cerevisiae. PLoS ONE, 10:e0143457, Nov 2015. URL: https://doi.org/10.1371/journal.pone.0143457, doi:10.1371/journal.pone.0143457. This article has 41 citations and is from a peer-reviewed journal.

13. (alamo2011definingthespecificity pages 17-18): Marta del Alamo, Daniel J. Hogan, Sebastian Pechmann, Veronique Albanese, Patrick O. Brown, and Judith Frydman. Defining the specificity of cotranslationally acting chaperones by systematic analysis of mrnas associated with ribosome-nascent chain complexes. PLoS Biology, 9:e1001100, Jul 2011. URL: https://doi.org/10.1371/journal.pbio.1001100, doi:10.1371/journal.pbio.1001100. This article has 201 citations and is from a highest quality peer-reviewed journal.

14. (hayashi2011egd1(β‐nac)mrna pages 1-2): Sachiko Hayashi, Tomoko Andoh, and Tokio Tani. Egd1 (β‐nac) mrna is localized in a novel cytoplasmic structure in saccharomyces cerevisiae. Genes to Cells, 16:316-329, Mar 2011. URL: https://doi.org/10.1111/j.1365-2443.2011.01489.x, doi:10.1111/j.1365-2443.2011.01489.x. This article has 6 citations and is from a peer-reviewed journal.

15. (deeng2012functionalandstructural pages 17-20): Julian Johannes Deeng. Functional and structural studies on the ribosome associated factors trigger factor and nac. Dissertation, Jan 2012. URL: https://doi.org/10.5282/edoc.17955, doi:10.5282/edoc.17955. This article has 0 citations.

Citations

1. tian2024thenascentpolypeptideassociated pages 1-2
2. dublinryan2024disruptionofthe pages 1-2
3. pech2010dualbindingmode pages 1-2
4. ott2015functionaldissectionof pages 1-2
5. alamo2011definingthespecificity pages 1-2
6. nyathi2015analysisofthe pages 7-9
7. alamo2011definingthespecificity pages 17-18
8. schilke2024functionalsimilaritiesand pages 1-3
9. schilke2024functionalsimilaritiesand pages 9-10
10. ott2015functionaldissectionof pages 2-4
11. deeng2012functionalandstructural pages 17-20
12. https://doi.org/10.1093/nar/gkae005
13. https://doi.org/10.1038/s41598-023-50245-7
14. https://doi.org/10.1371/journal.pone.0303008
15. https://doi.org/10.1016/j.cstres.2024.10.004
16. https://doi.org/10.1083/jcb.201410086
17. https://doi.org/10.1371/journal.pone.0143457
18. https://doi.org/10.1371/journal.pbio.1001100
19. https://doi.org/10.1074/jbc.M109.092536
20. https://doi.org/10.1371/journal.pbio.1001100,
21. https://doi.org/10.1074/jbc.m109.092536,
22. https://doi.org/10.1038/s41598-023-50245-7,
23. https://doi.org/10.1093/nar/gkae005,
24. https://doi.org/10.1083/jcb.201410086,
25. https://doi.org/10.1371/journal.pone.0143457,
26. https://doi.org/10.1016/j.cstres.2024.10.004,
27. https://doi.org/10.1371/journal.pone.0303008,
28. https://doi.org/10.1111/j.1365-2443.2011.01489.x,
29. https://doi.org/10.5282/edoc.17955,