intranuclear quality control compartment

cellstructuremech:intranuclear_quality_control_compartment · Inclusion · Inclusion body · Proposed

A stress-induced membraneless nuclear inclusion characterized in budding yeast that concentrates misfolded and other conditionally recruited proteins near the nuclear envelope, distinct from the cytoplasmic juxtanuclear quality control compartment. [DOI:10.1038/ncomms7533]

Multi-panel characterization of yeast INQ. Panels d-e distinguish nuclear Cmr1/VHL colocalization from cytoplasmic VHL foci; panel f shows a subset of Cct6 foci overlapping Cmr1. Microscopy scale bars: 2 micrometers. Other panels show screening, deletion phenotypes and immunoblots, not a universal INQ composition. FLUORESCENCE · *Saccharomyces cerevisiae* (`NCBITaxon:4932`) · Irene Gallina, Camilla Colding, Peter Henriksen, Petra Beli, Kyosuke Nakamura, Judith Offman, David P. Mathiasen, Sonia Silva, Eva Hoffmann, Anja Groth, et al.; CC BY, via PubMed Central · CC_BY_4_0 · source: PMC PMC4389229.1 f3 · `DOI:10.1038/ncomms7533`

Synonyms: INQ

Part of: nucleus (GO:0005634)

UniProt location names: UniProt Consortium, CC BY 4.0. Reference label and route sources.

Components

Component	Type	Part of / acts on	Grounding	Genes	Essential	Role
heterogeneous INQ protein cargo	Other	part of	Reviewed label only (reviewed name; no accession asserted)		UNKNOWN	Sequestered protein material; includes misfolded reporters and stress-recruited endogenous proteins. Recruitment does not prove that every endogenous client is misfolded. `DOI:10.1038/ncomms7533` Figure 3 and Discussion distinguish diverse recruited endogenous proteins from a universal set of misfolded substrates. `DOI:10.1038/s41556-023-01128-6` Figure 1 and Results use nuclear-targeted misfolding reporters to distinguish INQ from cytoplasmic inclusions.
Btn2-type aggregase	Protein	part of	Reviewed label only (reviewed name; no accession asserted)	BTN2	CONDITIONAL	INQ-enriched aggregase supporting nuclear protein deposition in tested yeast assays. Nuclear-targeted Hsp42 can experimentally substitute, so native requirements are not universal essentiality. `DOI:10.15252/embj.201489524` Figures 6 and 7B-D support INQ enrichment, deletion phenotypes and engineered rescue. `https://www.ebi.ac.uk/interpro/api/entry/interpro/protein/uniprot/P53286/?page_size=200` Native integrated matches checked through next=null on 2026-10-05; domain-only result does not identify a whole-protein family.
Hsp104-type disaggregase	Protein	acts on	Reviewed label only (reviewed name; no accession asserted)	HSP104	UNKNOWN	Chaperone recruited to nuclear deposits; Hsp104 inhibition stabilizes reporter INQ during recovery in the tested assay. Recruitment is not an invariant stoichiometric coat. `DOI:10.15252/embj.201489524` Figure 2 and Results on recovery support direct localization and an inhibitor-sensitive dissolution phenotype; the supplementary figure itself was not inspected. `https://www.ebi.ac.uk/interpro/api/entry/interpro/protein/uniprot/P31539/?page_size=200` All integrated native matches inspected on 2026-10-05, next=null; family matches remain broader than the component.
WD repeat-containing DNA damage-binding protein	Protein	part of	`InterPro:IPR050853`	CMR1	DISPENSABLE	Conditionally recruited family member exemplified by Cmr1 in yeast INQ. Cmr1 is a stable resident marker in the genotoxic-stress assays, not proven misfolded cargo or an invariant assembly scaffold; Mrc1 foci still form without Cmr1. `DOI:10.1038/ncomms7533` Figure 3d-g and Results on Mrc1 localization support nuclear recruitment, protein stability and dispensability for the tested Mrc1 focus readout. `InterPro:IPR050853` Native integrated family identity, canonical label and Q12510 membership verified. The entry's unchecked LLM-generated description is not used as mechanistic evidence; INQ recruitment is asserted only for the cited yeast example.

Organism-specific protein examples

Named proteins in which each component's role was established, with the organism the evidence comes from. The component above is the taxon-agnostic family; these are the specific entries behind it.

Btn2-type aggregase

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P53286`	Protein BTN2	BTN2	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reviewed reference-sequence example; not a reassignment of the paper's experimental strain background. `UniProtKB:P53286` Native reviewed entry verifies accession, protein name, primary gene and reference taxon. `DOI:10.15252/embj.201489524` Figures 6 and 7B-D: nuclear deposition requires Btn2 in tested backgrounds; Btn2 is enriched at INQ and engineered Hsp42-NLS can substitute.

Hsp104-type disaggregase

Accession	Protein	Gene	Organism	Entry
`UniProtKB:P31539`	Heat shock protein 104	HSP104	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reviewed reference-sequence example; not a reassignment of the paper's experimental strain background. `UniProtKB:P31539` Native reviewed entry verifies accession, protein name, primary gene and reference taxon. `DOI:10.15252/embj.201489524` Figure 2 follows Hsp104-marked nuclear deposits by fluorescence and immunogold microscopy; Results describe guanidinium inhibition of dissolution with Supplementary Figure S6.

WD repeat-containing DNA damage-binding protein

Accession	Protein	Gene	Organism	Entry
`UniProtKB:Q12510`	DNA damage-binding protein CMR1	CMR1	Saccharomyces cerevisiae S288C (`NCBITaxon:559292`)	REVIEWED
Role and evidence (2 references) Reviewed reference-sequence example; not a reassignment of the paper's experimental strain background. `UniProtKB:Q12510` Native reviewed entry verifies accession, protein name, primary gene and reference taxon. `DOI:10.1038/ncomms7533` Figure 3 localizes Cmr1 to INQ; Results on Mrc1 state that Cmr1 and Mrc1 focus formation is independent of each other's presence.

Canonical examples

NCBITaxon:4932 Saccharomyces cerevisiae — INQ characterized by nuclear-envelope markers, stress perturbations and fluorescent protein localization. Methods use RAD5 W303 derivatives by default, with S288C libraries and exceptions; unread supplemental strain tables preclude finer reassignment of each assay. [DOI:10.1038/ncomms7533]
NCBITaxon:559292 Saccharomyces cerevisiae S288C — Reference-sequence taxon for the reviewed Btn2 accession, not an assertion that every image or deletion assay used S288C. The other protein examples have their own accession evidence. [UniProtKB:P53286]

Functions

spatial sequestration of nuclear protein cargo — Concentrates selected misfolded and stress-recruited proteins in a nuclear deposit. INQ formation is not obligatory for degradation of every reporter and does not establish universal stress protection.
- DOI:10.15252/embj.201489524 Figures 1-3 establish nuclear deposition; Figure 6C finds similar reporter degradation during recovery when BTN2/HSP42-dependent deposition is impaired.
- DOI:10.1038/ncomms7533 Figure 3 and Discussion show stress-dependent recruitment beyond misfolded reporters.
conditional routing of nuclear quality-control cargo to the vacuole — Nuclear reporter deposits can undergo nuclear-vacuolar-junction- and Vps4-dependent vacuolar delivery alongside proteasomal clearance. This is a demonstrated route in the tested reporter conditions, not the fate of all INQ clients.
- DOI:10.1038/s41556-023-01128-6 Figures 5-8 combine contact-site and ESCRT perturbations, Keima acidification, protease inhibition and live imaging. Exact membrane-budding steps remain a model.

Mechanism graphs

Stress- and cargo-dependent INQ deposition (ASSEMBLY)

Bounded interventions distinguish nuclear deposition from stress-specific recruitment of a resident marker.

Subject	Predicate	Object	Evidence
Nuclear-targeted LuciTs misfolding at 37 C	induces	intranuclear quality control compartment	`DOI:10.1038/s41556-023-01128-6` Figure 1b-c and Results distinguish reporter-induced INQ formation from an obligatory consequence of proteasome inhibition.
BTN2 deletion	impairs	intranuclear quality control compartment	`DOI:10.15252/embj.201489524` Figure 6 separates soluble nuclear reporter from nuclear aggregate deposition.
Engineered nuclear-targeted Hsp42 in btn2 deletion cells	restores	intranuclear quality control compartment	`DOI:10.15252/embj.201489524` Figure 7C-D: localization-engineered rescue is not native Hsp42 recruitment.
Methyl methanesulfonate treatment	induces	Cmr1-positive INQ foci in genotoxic-stress assays	`DOI:10.1038/ncomms7533` Figure 3c and Results measure stress-induced Cmr1 foci.
BTN2 deletion	reduces	Cmr1-positive INQ foci in genotoxic-stress assays	`DOI:10.1038/ncomms7533` Figure 3c reports residual percentages, not universal absence of all INQ-like material.
HSP42 deletion	reduces	Cmr1-positive INQ foci in genotoxic-stress assays	`DOI:10.1038/ncomms7533` Figure 3c; Discussion distinguishes this dependence from MG132-induced VHL targeting, which requires BTN2 but not HSP42.

Conditional INQ positioning and vacuolar disposal (FUNCTION)

Nuclear reporter deposition, spatial convergence and vacuolar clearance are separable readouts.

Subject	Predicate	Object	Evidence
intranuclear quality control compartment	undergoes	INQ/JUNQ convergence across the nuclear envelope	`DOI:10.1038/s41556-023-01128-6` Figure 3 and Results describe distinct compartments homing across the envelope.
intranuclear quality control compartment	can undergo	Vacuolar delivery and clearance of nuclear reporter cargo	`DOI:10.1038/s41556-023-01128-6` Figures 7-8: Keima, protease perturbation, reporter fragments and live imaging provide complementary evidence.
NVJ1 deletion	impairs	Vacuolar delivery and clearance of nuclear reporter cargo	`DOI:10.1038/s41556-023-01128-6` Figures 5f-h and 8a distinguish persistent inclusions and failed vacuolar interaction from initial formation.
VAC8 deletion	impairs	Vacuolar delivery and clearance of nuclear reporter cargo	`DOI:10.1038/s41556-023-01128-6` Figure 5g-h and Extended Data Figure 5c-e are described in Results; this is not a block of initial convergence.
CHM7 deletion	disrupts	INQ/JUNQ convergence across the nuclear envelope	`DOI:10.1038/s41556-023-01128-6` Figure 6b separates convergence from formation; activated Chm7OPEN is not an invariant native coat.
VPS4 deletion	impairs	Vacuolar delivery and clearance of nuclear reporter cargo	`DOI:10.1038/s41556-023-01128-6` Figures 6e-f and 8a support persistent inclusions and defective clearance; the exact budding mechanism is proposed.

Discussions

INTERPRETATION (RESOLVED): Keep INQ distinct from JUNQ, IPOD and nuclear stress granules. Early papers use different JUNQ/INQ interpretations; shared perinuclear proximity is not exact identity.
CURATION_TODO (OPEN): Resolve exact source-neutral grounding for Btn2-type, Hsp104-type and heterogeneous cargo classes. Domain-only and broader family hits cannot serve as exact identities for narrower component classes.
INTERPRETATION (RESOLVED): Separate directly localized proteins from regulators, reporters and partially colocalizing complexes. Genetic dependence, fluorescence overlap and biochemical interaction do not establish fixed composition or universal assembly requirements.
INTERPRETATION (RESOLVED): Do not equate INQ deposition with obligatory degradation or a universal genome-protection mechanism. Different substrates and perturbations give different turnover effects; deposition, refolding, degradation and adaptation are distinct claims.
CURATION_TODO (OPEN): Resolve native client inventories, material state, precise experimental strain mappings and prevalence. Reporter induction and one microbial species do not establish lineage prevalence, universal dimensions or fixed molecular composition.

Evidence

DOI:10.15252/embj.201489524 Miller et al. (2015), PMID 25672362, PMC4369314. Read all main Results and Discussion and initial Methods via public PMC. Supplementary strain tables and actual figure pixels were not inspected. Heat-induced INQ also forms without MG132; the older JUNQ redefinition is not adopted as exact synonymy.
DOI:10.1038/ncomms7533 Gallina et al. (2015), PMID 25817432, PMC4389229.1. Verified native metadata/JATS; read INQ characterization, Mrc1 Results, full Discussion and strain Methods. Figure 3 caption and actual image inspected. Supplements were not independently inspected.
DOI:10.1038/s41556-023-01128-6 Sontag et al. (2023), PMID 37081164, PMC12349969.1. Verified native metadata/JATS; read all main Results (S1-S8), Discussion, strain-table pointer and Data availability. Actual figures and supplemental strain tables were not inspected. TDM metadata does not establish a Creative Commons hosting licence.
GO:0016604 Native QuickGO verifies nuclear body as an active cellular-component class for a membraneless organelle in the nucleoplasm; broader parent only.
GO:0016234 Native QuickGO verifies inclusion body as a discrete intracellular aggregation; broader parent, not exact INQ identity.
GO:0005634 Native QuickGO verifies nucleus. Nuclear localization in the cited microscopy supports parthood for INQ, not for cytoplasmic JUNQ or post-extrusion cargo.

Curation history

2026-10-05T06:40:32Z codex · CREATED_RECORD — Scaffolded by scripts/new_record.py
2026-10-05T06:42:58Z codex · EXPANDED_RECORD — Added yeast-scoped INQ identity, conditional resident/machinery classes, two intervention graphs, source-boundary discussions and an inspected CC BY 4.0 primary figure.

Source: data/structures/inclusion/intranuclear_quality_control_compartment.yaml