Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000785 chromatin	IBA GO_REF:0000033	ACCEPT	Summary: Manual review: chromatin is consistent with known biology of NAP1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0005634 nucleus	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Nap1 functions in both the cytosol and the nucleus. Falcon deep research notes that Nap1 is mostly cytoplasmic but also functions in the nucleus, where it supports nucleosome assembly and remodeling; nuclear activity is genuine but the protein is predominantly cytosolic, so this localization is retained as non-core. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. Supporting Evidence: file:yeast/NAP1/NAP1-deep-research-falcon.md but also acts in the nucleus where it supports targeted histone release/import, nucleosome assembly and remodeling during transcription
GO:0006334 nucleosome assembly	IBA GO_REF:0000033	ACCEPT	Summary: Nucleosome assembly is a core biological process for NAP1. Falcon deep research supports that Nap1 is a conserved nucleosome assembly protein that promotes correct nucleosome organization by delivering H2A-H2B dimers into nucleosomes rather than allowing random histone-DNA association. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/NAP1/NAP1-deep-research-falcon.md Nap1 is proposed to recruit H2A-H2B to maintain ordered nucleosome arrangement
GO:0042393 histone binding	IBA GO_REF:0000033	ACCEPT	Summary: Histone binding is a core molecular function of NAP1. Falcon deep research confirms the primary substrate is the H2A-H2B dimer, which Nap1 binds with nanomolar affinity as a stable homodimer, shielding the basic DNA-binding surfaces of the histones. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/NAP1/NAP1-deep-research-falcon.md The primary substrate of Nap1 is the H2A–H2B dimer file:yeast/NAP1/NAP1-deep-research-falcon.md Nagae et al. describe Nap1 as a ~48 kDa monomer that forms a stable homodimer and binds a single H2A–H2B dimer with nanomolar affinity
GO:0003682 chromatin binding	IBA GO_REF:0000033	ACCEPT	Summary: Manual review: chromatin binding is consistent with known biology of NAP1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0003677 DNA binding	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Manual review: DNA binding may be context-dependent or peripheral for NAP1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0005634 nucleus	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Manual review: nucleus may be context-dependent or peripheral for NAP1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Manual review: cytoplasm is the predominant steady-state localization of NAP1 and the principal site of its core H2A-H2B chaperone activity. Reason: Accepted as core, consistent with the IDA cytoplasm annotation (PMID:7622566); the cytoplasm is the predominant steady-state localization where Nap1 carries out its core H2A-H2B chaperone activity.
GO:0005935 cellular bud neck	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Manual review: cellular bud neck may be context-dependent or peripheral for NAP1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0005940 septin ring	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Manual review: septin ring may be context-dependent or peripheral for NAP1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0006334 nucleosome assembly	IEA GO_REF:0000002	ACCEPT	Summary: Manual review: nucleosome assembly is consistent with known biology of NAP1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0005515 protein binding	IPI PMID:10688190 A comprehensive analysis of protein-protein interactions in ...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:12058072 Cell cycle-dependent assembly of a Gin4-septin complex.	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:14645854 ATP-driven exchange of histone H2AZ variant catalyzed by SWR...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:14759368 High-definition macromolecular composition of yeast RNA-proc...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:15045029 A protein complex containing the conserved Swi2/Snf2-related...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:16299494 A phosphatase complex that dephosphorylates gammaH2AX regula...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:18467557 An in vivo map of the yeast protein interactome.	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:18719252 High-quality binary protein interaction map of the yeast int...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:19172749 Histone chaperone specificity in Rtt109 activation.	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:19536198 An atlas of chaperone-protein interactions in Saccharomyces ...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:20489023 A global protein kinase and phosphatase interaction network ...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:21179020 Defining the budding yeast chromatin-associated interactome.	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:23468594 A safeguard mechanism regulates Rho GTPases to coordinate cy...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:25416945 A memory system of negative polarity cues prevents replicati...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:37968396 The social and structural architecture of the yeast protein ...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:9214386 Control of mitotic events by Nap1 and the Gin4 kinase.	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0005515 protein binding	IPI PMID:9813092 The septins are required for the mitosis-specific activation...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0042802 identical protein binding	IPI PMID:16432217 The structure of nucleosome assembly protein 1.	MARK AS OVER ANNOTATED	Summary: Manual review: identical protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0042802 identical protein binding	IPI PMID:18467557 An in vivo map of the yeast protein interactome.	MARK AS OVER ANNOTATED	Summary: Manual review: identical protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0042802 identical protein binding	IPI PMID:18719252 High-quality binary protein interaction map of the yeast int...	MARK AS OVER ANNOTATED	Summary: Manual review: identical protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0042802 identical protein binding	IPI PMID:21179020 Defining the budding yeast chromatin-associated interactome.	MARK AS OVER ANNOTATED	Summary: Manual review: identical protein binding is too generic or over-extended for NAP1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0140597 protein carrier chaperone	IDA PMID:31062022 Tsr4 and Nap1, two novel members of the ribosomal protein ch...	ACCEPT	Summary: Manual review: protein carrier chaperone is consistent with known biology of NAP1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0000511 H2A-H2B histone complex chaperone activity	IDA PMID:39601790 Nap1 and Kap114 co-chaperone H2A-H2B and facilitate targeted...	ACCEPT	Summary: This is the core molecular function of NAP1. Falcon deep research (anchored on Fung et al. 2024, the source of this PMID) establishes that Nap1 forms a stable homodimer that binds H2A-H2B, shields their DNA-binding surfaces, and cooperates with the importin Kap114 and RanGTP to chaperone H2A-H2B for nucleosome assembly, forming a quaternary Nap1_2-H2A-H2B-Kap114-RanGTP complex. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/NAP1/NAP1-deep-research-falcon.md Nap1 forms a stable homodimer file:yeast/NAP1/NAP1-deep-research-falcon.md Kap114, H2A–H2B, and Nap1\_2 form equimolar complexes, including a quaternary Nap1\_2•H2A–H2B•Kap114•RanGTP assembly
GO:0006334 nucleosome assembly	IDA PMID:39601790 Nap1 and Kap114 co-chaperone H2A-H2B and facilitate targeted...	ACCEPT	Summary: Manual review: nucleosome assembly is consistent with known biology of NAP1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0000511 H2A-H2B histone complex chaperone activity	IDA PMID:27225933 Structural evidence for Nap1-dependent H2A-H2B deposition an...	ACCEPT	Summary: Manual review: H2A-H2B histone complex chaperone activity is consistent with known biology of NAP1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0006334 nucleosome assembly	IDA PMID:27225933 Structural evidence for Nap1-dependent H2A-H2B deposition an...	ACCEPT	Summary: Manual review: nucleosome assembly is consistent with known biology of NAP1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0000920 septum digestion after cytokinesis	NAS PMID:12058072 Cell cycle-dependent assembly of a Gin4-septin complex.	KEEP AS NON CORE	Summary: Manual review: septum digestion after cytokinesis may be context-dependent or peripheral for NAP1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0000921 septin ring assembly	NAS PMID:12058072 Cell cycle-dependent assembly of a Gin4-septin complex.	KEEP AS NON CORE	Summary: Manual review: septin ring assembly may be context-dependent or peripheral for NAP1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0006607 NLS-bearing protein import into nucleus	IMP PMID:12456659 A role for nucleosome assembly protein 1 in the nuclear tran...	KEEP AS NON CORE	Summary: Nap1 participates in histone H2A-H2B nuclear import in cooperation with the importin Kap114 and the Ran-GTP system. Falcon deep research describes Nap1 escorting H2A-H2B and facilitating targeted release onto assembling nucleosomes in the nucleus. This nuclear-import function is real but is an extension of the core H2A-H2B chaperone activity rather than the gene's primary function. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. Supporting Evidence: file:yeast/NAP1/NAP1-deep-research-falcon.md Nap1 interacts with importin Kap114 and Ran-pathway components to escort H2A-H2B and facilitate targeted release onto assembling nucleosomes/tetrasomes in the nucleus
GO:0042274 ribosomal small subunit biogenesis	IGI PMID:31062022 Tsr4 and Nap1, two novel members of the ribosomal protein ch...	KEEP AS NON CORE	Summary: Manual review: ribosomal small subunit biogenesis may be context-dependent or peripheral for NAP1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0051082 unfolded protein binding	IDA PMID:31062022 Tsr4 and Nap1, two novel members of the ribosomal protein ch...	MODIFY	Summary: 'Unfolded protein binding' is overly generic for NAP1. The defining substrate is the H2A-H2B histone dimer, for which Nap1 has strong specificity. Falcon deep research confirms the primary substrate is the H2A-H2B dimer, supporting replacement with the more specific H2A-H2B histone complex chaperone activity term. (Note: PMID:31062022 also documents a separate eS6/Rps6 ribosomal protein chaperone role, captured by other annotations.) Reason: Modified to align with current curation guidance and improve term specificity. Proposed replacements: H2A-H2B histone complex chaperone activity Supporting Evidence: file:yeast/NAP1/NAP1-deep-research-falcon.md The primary substrate of Nap1 is the H2A–H2B dimer
GO:0005737 cytoplasm	IDA PMID:30341817 Septin-associated proteins Aim44 and Nis1 traffic between th...	ACCEPT	Summary: Manual review: cytoplasm is the predominant steady-state localization of NAP1 and the principal site of its core H2A-H2B chaperone activity. Reason: Accepted as core, consistent with the other cytoplasm annotations; the cytoplasm is the predominant steady-state localization where Nap1 carries out its core H2A-H2B chaperone activity. Supporting Evidence: file:yeast/NAP1/NAP1-deep-research-falcon.md Nap1 is described as the principal cytosolic H2A–H2B chaperone that is mostly cytoplasmic but also functions in the nucleus (implying nucleocytoplasmic shuttling)
GO:0032174 cellular bud neck septin collar	IDA PMID:30341817 Septin-associated proteins Aim44 and Nis1 traffic between th...	KEEP AS NON CORE	Summary: Manual review: cellular bud neck septin collar may be context-dependent or peripheral for NAP1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0032153 cell division site	IDA PMID:25416945 A memory system of negative polarity cues prevents replicati...	KEEP AS NON CORE	Summary: Manual review: cell division site may be context-dependent or peripheral for NAP1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0098841 protein localization to cell division site after cytokinesis	IMP PMID:25416945 A memory system of negative polarity cues prevents replicati...	KEEP AS NON CORE	Summary: Manual review: protein localization to cell division site after cytokinesis may be context-dependent or peripheral for NAP1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0006334 nucleosome assembly	IDA PMID:1400414 Functional analysis of nucleosome assembly protein, NAP-1. T...	ACCEPT	Summary: Manual review: nucleosome assembly is consistent with known biology of NAP1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0008047 enzyme activator activity	IDA PMID:22308335 Histone density is maintained during transcription mediated ...	KEEP AS NON CORE	Summary: Manual review: enzyme activator activity may be context-dependent or peripheral for NAP1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0031116 positive regulation of microtubule polymerization	IMP PMID:7622567 NAP1 acts with Clb1 to perform mitotic functions and to supp...	KEEP AS NON CORE	Summary: Manual review: positive regulation of microtubule polymerization may be context-dependent or peripheral for NAP1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0005737 cytoplasm	IDA PMID:7622566 Members of the NAP/SET family of proteins interact specifica...	ACCEPT	Summary: Cytoplasm is the predominant localization of Nap1. Falcon deep research describes Nap1 as the principal cytosolic H2A-H2B chaperone that handles newly synthesized H2A-H2B before nuclear import, implying nucleocytoplasmic shuttling. This is the major site of action even though Nap1 also functions in the nucleus. Reason: Accepted as core. The cytoplasm is the predominant steady-state localization of Nap1 and the principal site of its core H2A-H2B histone-chaperone activity, where Nap1 handles newly synthesized H2A-H2B before nuclear import. Falcon deep research (Fung et al. 2024) describes Nap1 as the principal cytosolic H2A-H2B chaperone that is mostly cytoplasmic, so this IDA localization is elevated from non-core to a core location. Supporting Evidence: file:yeast/NAP1/NAP1-deep-research-falcon.md Nap1 is described as the principal cytosolic H2A–H2B chaperone that is mostly cytoplasmic but also functions in the nucleus (implying nucleocytoplasmic shuttling)
GO:0006334 nucleosome assembly	IDA PMID:2016313 Identification and molecular cloning of yeast homolog of nuc...	ACCEPT	Summary: Manual review: nucleosome assembly is consistent with known biology of NAP1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0006337 nucleosome disassembly	IDA PMID:16492771 Chromatin remodeling by nucleosome disassembly in vitro.	ACCEPT	Summary: Nucleosome disassembly via H2A-H2B eviction is a genuine Nap1 activity. Falcon deep research (anchored on Nagae et al. 2023) shows that Nap1 can dismantle an H2A-H2B dimer from a partially unwrapped nucleosome, with its acidic C-terminal flexible tails engaging an otherwise buried histone interface via a 'penetrating fuzzy binding' mechanism; removal is slow from fully wrapped nucleosomes but greatly accelerated by translocase-induced partial DNA unwrapping. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: file:yeast/NAP1/NAP1-deep-research-falcon.md Nap1 can also act in H2A–H2B eviction/dismantling, particularly when nucleosomal DNA is partially unwrapped file:yeast/NAP1/NAP1-deep-research-falcon.md Nap1 acidic C-terminal flexible tails can engage an H2A–H2B interface that is normally buried in the nucleosome file:yeast/NAP1/NAP1-deep-research-falcon.md Nap1 can remove H2A–H2B from fully wrapped nucleosomes only slowly at low temperature, but removal is accelerated when DNA is partially unwrapped
GO:0007117 budding cell bud growth	IMP PMID:13680156 Saccharomyces cerevisiae Ats1p interacts with Nap1p, a cytop...	KEEP AS NON CORE	Summary: Manual review: budding cell bud growth may be context-dependent or peripheral for NAP1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0030332 cyclin binding	IPI PMID:7622566 Members of the NAP/SET family of proteins interact specifica...	KEEP AS NON CORE	Summary: Nap1 binds the B-type cyclin Clb2, linking its histone-chaperone activity to mitotic regulation and suppression of polar bud growth. Falcon deep research notes these reported functional interactions with mitotic regulators (Clb2 and Gin4). This is a peripheral, organism-specific function rather than the core chaperone activity, so it is retained as non-core. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. Supporting Evidence: file:yeast/NAP1/NAP1-deep-research-falcon.md Nap1 physically/functionally interacts with mitotic regulators including Clb2 and Gin4, linking histone-chaperone activity to mitotic functions and suppression of polar bud growth
GO:0032968 positive regulation of transcription elongation by RNA polymerase II	IDA PMID:22308335 Histone density is maintained during transcription mediated ...	KEEP AS NON CORE	Summary: Nap1 supports transcription-coupled chromatin dynamics by managing H2A-H2B during polymerase passage. Falcon deep research shows that partial nucleosome unwrapping by a translocase dramatically facilitates Nap1-mediated H2A-H2B dimer dismantling, consistent with a role in nucleosome disassembly/reassembly cycles linked to transcription. This is a downstream consequence of the core chaperone activity rather than a primary function. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. Supporting Evidence: file:yeast/NAP1/NAP1-deep-research-falcon.md partial nucleosome unwrapping by a translocase dramatically facilitates Nap1-mediated H2A–H2B dimer dismantling
GO:0042393 histone binding	IDA PMID:17289584 Chz1, a nuclear chaperone for histone H2AZ.	ACCEPT	Summary: Manual review: histone binding is consistent with known biology of NAP1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0042393 histone binding	IDA PMID:21348863 Assembly states of the nucleosome assembly protein 1 (NAP-1)...	ACCEPT	Summary: Manual review: histone binding is consistent with known biology of NAP1. Reason: Retained as supported or plausible for this gene and evidence context.

Core Functions

Nap1 is a dimeric H2A-H2B histone chaperone. It forms a stable homodimer that binds the H2A-H2B dimer with nanomolar affinity, shielding the basic DNA-binding surfaces of the histones to prevent non-specific histone-DNA aggregation. This H2A-H2B chaperone activity is the defining core molecular function of the gene.

Molecular Function:

H2A-H2B histone complex chaperone activity

Directly Involved In:

nucleosome assembly

Cellular Locations:

cytoplasm nucleus

Substrates:

nucleosome

Supporting Evidence:

file:yeast/NAP1/NAP1-deep-research-falcon.md
encodes a dimeric H2A–H2B histone chaperone central to histone handling and nucleosome dynamics
file:yeast/NAP1/NAP1-deep-research-falcon.md
Nap1 forms a stable **homodimer**
file:yeast/NAP1/NAP1-deep-research-falcon.md
Nap1 is described as the **principal cytosolic H2A–H2B chaperone** that is mostly cytoplasmic but also functions in the nucleus (implying **nucleocytoplasmic shuttling**)

Nap1 promotes correct nucleosome assembly by delivering H2A-H2B dimers into nucleosomes rather than allowing random histone-DNA association. It functions as the principal cytosolic chaperone for newly synthesized H2A-H2B and cooperates with the importin Kap114 and the RanGTP system for targeted nuclear release and deposition of H2A-H2B during nucleosome assembly.

Molecular Function:

histone binding

Directly Involved In:

nucleosome assembly

Cellular Locations:

nucleus cytoplasm

Substrates:

nucleosome

Supporting Evidence:

file:yeast/NAP1/NAP1-deep-research-falcon.md
**facilitates productive nucleosome incorporation** of H2A–H2B rather than random histone–DNA association
file:yeast/NAP1/NAP1-deep-research-falcon.md
Nap1 is defined as a **nucleosome assembly protein** and **core histone chaperone**

Beyond deposition, Nap1 can dismantle and evict H2A-H2B dimers from partially unwrapped nucleosomes, contributing to nucleosome disassembly during transcription and other chromatin transactions. Its acidic C-terminal flexible tails engage an otherwise buried H2A-H2B interface via a 'penetrating fuzzy binding' mechanism, with eviction strongly accelerated by translocase-induced partial DNA unwrapping.

Molecular Function:

H2A-H2B histone complex chaperone activity

Directly Involved In:

nucleosome disassembly

Cellular Locations:

nucleus

Substrates:

nucleosome

Supporting Evidence:

file:yeast/NAP1/NAP1-deep-research-falcon.md
Nap1 can also act in **H2A–H2B eviction/dismantling**, particularly when nucleosomal DNA is partially unwrapped
file:yeast/NAP1/NAP1-deep-research-falcon.md
Nap1 acidic **C-terminal flexible tails** can engage an H2A–H2B interface that is normally buried in the nucleosome

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10688190

A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae.

PMID:11805837

Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry.

PMID:12058072

Cell cycle-dependent assembly of a Gin4-septin complex.

PMID:12456659

A role for nucleosome assembly protein 1 in the nuclear transport of histones H2A and H2B.

PMID:12788058

Genome-wide expression analysis of NAP1 in Saccharomyces cerevisiae.

In nap1-delta cells, roughly 8.4-12.0% of ORFs changed expression by at least 2-fold across three independent microarray experiments, and affected genes were enriched in genomic clusters, suggesting Nap1 maintains ordered nucleosome arrangement in vivo.

"In nap1Δ cells, ~8.4-12.0% of ORFs changed by ≥2-fold across three experiments"
Nap1 reportedly interacts functionally with the mitotic regulators Clb2 (B-type cyclin) and Gin4, linking histone-chaperone activity to mitotic functions and suppression of polar bud growth.

"Nap1 physically/functionally interacts with mitotic regulators including Clb2 and Gin4, linking histone-chaperone activity to mitotic functions and suppression of polar bud growth"

PMID:13680156

Saccharomyces cerevisiae Ats1p interacts with Nap1p, a cytoplasmic protein that controls bud morphogenesis.

PMID:1400414

Functional analysis of nucleosome assembly protein, NAP-1. The negatively charged COOH-terminal region is not necessary for the intrinsic assembly activity.

PMID:14645854

ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin remodeling complex.

PMID:14759368

High-definition macromolecular composition of yeast RNA-processing complexes.

PMID:15045029

A protein complex containing the conserved Swi2/Snf2-related ATPase Swr1p deposits histone variant H2A.Z into euchromatin.

PMID:16299494

A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery.

PMID:16429126

Proteome survey reveals modularity of the yeast cell machinery.

PMID:16432217

The structure of nucleosome assembly protein 1.

PMID:16492771

Chromatin remodeling by nucleosome disassembly in vitro.

PMID:16554755

Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.

PMID:17289584

Chz1, a nuclear chaperone for histone H2AZ.

PMID:18467557

An in vivo map of the yeast protein interactome.

PMID:18719252

High-quality binary protein interaction map of the yeast interactome network.

PMID:19172749

Histone chaperone specificity in Rtt109 activation.

PMID:19536198

An atlas of chaperone-protein interactions in Saccharomyces cerevisiae: implications to protein folding pathways in the cell.

PMID:2016313

Identification and molecular cloning of yeast homolog of nucleosome assembly protein I which facilitates nucleosome assembly in vitro.

PMID:20489023

A global protein kinase and phosphatase interaction network in yeast.

PMID:21179020

Defining the budding yeast chromatin-associated interactome.

PMID:21348863

Assembly states of the nucleosome assembly protein 1 (NAP-1) revealed by sedimentation velocity and non-denaturing MS.

PMID:22308335

Histone density is maintained during transcription mediated by the chromatin remodeler RSC and histone chaperone NAP1 in vitro.

PMID:23468594

A safeguard mechanism regulates Rho GTPases to coordinate cytokinesis with the establishment of cell polarity.

PMID:25416945

A memory system of negative polarity cues prevents replicative aging.

PMID:27225933

Structural evidence for Nap1-dependent H2A-H2B deposition and nucleosome assembly.

PMID:30341817

Septin-associated proteins Aim44 and Nis1 traffic between the bud neck and the nucleus in the yeast Saccharomyces cerevisiae.

PMID:31062022

Tsr4 and Nap1, two novel members of the ribosomal protein chaperOME.

PMID:37177996

Histone chaperone Nap1 dismantles an H2A/H2B dimer from a partially unwrapped nucleosome.

Nap1 can dismantle an H2A-H2B dimer from a partially unwrapped nucleosome; partial unwrapping by a translocase dramatically facilitates this Nap1-mediated dimer removal.

"partial nucleosome unwrapping by a translocase dramatically facilitates Nap1-mediated H2A–H2B dimer dismantling"
The acidic C-terminal flexible tails of Nap1 engage an H2A-H2B interface that is normally buried in the nucleosome and inaccessible to Nap1's globular domains, consistent with a 'penetrating fuzzy binding' chaperone mechanism.

"Nap1 acidic **C-terminal flexible tails** can engage an H2A–H2B interface that is normally buried in the nucleosome"
Nap1 is a ~48 kDa monomer that forms a stable homodimer and binds a single H2A-H2B dimer with nanomolar affinity.

"Nagae et al. describe Nap1 as a **~48 kDa monomer** that forms a stable homodimer and binds a single H2A–H2B dimer with **nanomolar affinity**"

PMID:37968396

The social and structural architecture of the yeast protein interactome.

PMID:38571760

Glutamylation of Npm2 and Nap1 acidic disordered regions increases DNA mimicry and histone chaperone efficiency.

Post-translational glutamylation of the Nap1/NAP1-like acidic disordered regions can increase DNA mimicry and histone chaperone efficiency, reinforcing the functional importance of the acidic disordered regions in the chaperone mechanism.

"post-translational modification (glutamylation) can increase DNA mimicry and histone chaperone efficiency"

PMID:39601790

Nap1 and Kap114 co-chaperone H2A-H2B and facilitate targeted histone release in the nucleus.

Nap1 is the principal cytosolic H2A-H2B chaperone; it is mostly cytoplasmic but also functions in the nucleus, implying nucleocytoplasmic shuttling.

"Nap1 is described as the **principal cytosolic H2A–H2B chaperone** that is mostly cytoplasmic but also functions in the nucleus (implying **nucleocytoplasmic shuttling**)"
Kap114, H2A-H2B, and the Nap1 dimer form equimolar complexes, including a quaternary Nap1_2-H2A-H2B-Kap114-RanGTP assembly resolved by cryo-EM.

"Kap114, H2A–H2B, and Nap1\_2 form equimolar complexes, including a quaternary **Nap1\_2•H2A–H2B•Kap114•RanGTP** assembly"

PMID:7622566

Members of the NAP/SET family of proteins interact specifically with B-type cyclins.

PMID:7622567

NAP1 acts with Clb1 to perform mitotic functions and to suppress polar bud growth in budding yeast.

PMID:9214386

Control of mitotic events by Nap1 and the Gin4 kinase.

PMID:9813092

The septins are required for the mitosis-specific activation of the Gin4 kinase.

file:yeast/NAP1/NAP1-deep-research-falcon.md

Falcon (Edison) deep research report: Saccharomyces cerevisiae NAP1 (P25293) functional annotation.

Yeast NAP1 (YKR048C; P25293) encodes a dimeric H2A-H2B histone chaperone whose primary molecular function is to bind and shield the H2A-H2B dimer and mediate its correct delivery into nucleosomes, including a Kap114/RanGTP-coordinated handoff pathway for targeted nuclear release and nucleosome assembly; Nap1 also enables H2A-H2B eviction from partially unwrapped nucleosomes.

"Nap1’s primary molecular function is to bind/shield H2A–H2B and mediate their correct delivery into nucleosomes, including a Kap114/RanGTP-coordinated handoff pathway for targeted nuclear release and nucleosome assembly. Nap1 also participates in transcription-coupled chromatin dynamics by enabling H2A–H2B eviction from partially unwrapped nucleosomes via acidic disordered tails."

Deep Research

Falcon

(NAP1-deep-research-falcon.md)

Research Report: *Saccharomyces cerevisiae* NAP1 (UniProt P25293; gene **NAP1**, systematic **YKR048C**) — Functional Annotation Falcon Edison Scientific Literature 15 citations 2 artifacts 2026-05-30T10:04:34.058769

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000032 The cryo-EM structure and architecture of the Nap12•H2A-H2B•Kap114•RanGTP complex is shown in Figure 2A (page 5). The structure rev (image/png)

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: Saccharomyces cerevisiae NAP1 (UniProt P25293; gene NAP1, systematic YKR048C) — Functional Annotation

Executive summary

NAP1 encodes the conserved nucleosome assembly protein 1 (Nap1), a canonical histone chaperone with strong functional specificity for H2A–H2B dimers. In budding yeast, Nap1 is primarily cytosolic for handling newly synthesized H2A–H2B, but also acts in the nucleus where it supports targeted histone release/import, nucleosome assembly and remodeling during transcription and other chromatin transactions. Recent mechanistic advances (2023–2024) resolved how Nap1 removes H2A–H2B from partially unwrapped nucleosomes and how Nap1 cooperates with the importin Kap114 and RanGTP to transfer H2A–H2B for nucleosome assembly. (ohkuni2003genomewideexpressionanalysis pages 1-2, fung2024nap1andkap114 pages 1-2, nagae2023histonechaperonenap1 pages 1-2)

1) Key concepts and definitions (current understanding)

1.1 What Nap1 is

Nap1 is defined as a nucleosome assembly protein and core histone chaperone that binds core histones—especially H2A and H2B—to promote correct nucleosome organization and to prevent inappropriate histone–DNA interactions. This view is consistent across classic yeast functional genetics and modern mechanistic structural work. (ohkuni2003genomewideexpressionanalysis pages 1-2, fung2024nap1andkap114 pages 1-2)

1.2 What a histone chaperone does (as applied to Nap1)

In the context of Nap1, “histone chaperone” denotes a protein that:
- binds H2A–H2B and shields their basic, DNA-binding surfaces to prevent non-specific aggregation, and
- facilitates productive nucleosome incorporation of H2A–H2B rather than random histone–DNA association. (fung2024nap1andkap114 pages 1-2)

1.3 Primary molecular function (substrate specificity)

The primary substrate of Nap1 is the H2A–H2B dimer. Mechanistically:
- Nap1 forms a stable homodimer (often referred to as Nap1_2 or “Nap12” in the Kap114 work) that binds H2A–H2B and participates in nucleosome assembly pathways. (fung2024nap1andkap114 pages 1-2, nagae2023histonechaperonenap1 pages 1-2)
- Nap1 can also act in H2A–H2B eviction/dismantling, particularly when nucleosomal DNA is partially unwrapped (e.g., during collisions with translocases), supporting a role in nucleosome disassembly/reassembly cycles linked to transcription and chromatin repair. (nagae2023histonechaperonenap1 pages 1-2, nagae2023histonechaperonenap1 pages 2-2)

1.4 Biological processes and pathways

Evidence from yeast genetics and mechanistic biochemistry places Nap1 in multiple chromatin-centered processes:
- Nucleosome maintenance/spacing and transcriptional regulation in vivo, with deletion leading to widespread transcriptional changes and cluster-like behavior of affected genes. (ohkuni2003genomewideexpressionanalysis pages 1-2)
- Histone trafficking/import and targeted nuclear release, via cooperation with Kap114 and the RanGTP system to deliver H2A–H2B for nucleosome assembly. (fung2024nap1andkap114 pages 1-2, fung2024nap1andkap114 pages 2-4)
- Links to cell-cycle/mitotic regulation, via reported interactions with Clb2 (B-type cyclin) and Gin4 (septum-related kinase), suggesting coupling between chromatin management and mitotic morphogenesis programs. (ohkuni2003genomewideexpressionanalysis pages 1-2, ohkuni2003genomewideexpressionanalysis pages 4-5)

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

2.1 2024: Nap1–Kap114–RanGTP quaternary complex and targeted histone release

A 2024 Journal of Cell Biology study provided biochemical and cryo-EM evidence that yeast Nap1 and Kap114 co-chaperone H2A–H2B and facilitate targeted histone release in the nucleus, addressing a central question of how import factors and histone chaperones coordinate to deliver H2A–H2B to assembling nucleosomes. (Publication date: Nov 2024; URL: https://doi.org/10.1083/jcb.202408193) (fung2024nap1andkap114 pages 1-2, fung2024nap1andkap114 pages 2-4)

Key mechanistic points reported include:
- Nap1 is described as the principal cytosolic H2A–H2B chaperone that is mostly cytoplasmic but also functions in the nucleus (implying nucleocytoplasmic shuttling). (fung2024nap1andkap114 pages 1-2)
- Kap114, H2A–H2B, and Nap1_2 form equimolar complexes, including a quaternary Nap1_2•H2A–H2B•Kap114•RanGTP assembly. (fung2024nap1andkap114 pages 1-2, fung2024nap1andkap114 pages 2-4)
- The study provides residue-level insight: Nap1_2 β-hairpin residues (E288/R290/Q292) are critical for Kap114 binding and nuclear localization phenotypes. (fung2024nap1andkap114 pages 2-4)

2.2 2023: Mechanism of Nap1-mediated H2A–H2B dismantling from partially unwrapped nucleosomes

A 2023 Nucleic Acids Research paper used in vitro transcription assays and molecular simulations to show that partial nucleosome unwrapping by a translocase dramatically facilitates Nap1-mediated H2A–H2B dimer dismantling. (Publication date: May 2023; URL: https://doi.org/10.1093/nar/gkad396) (nagae2023histonechaperonenap1 pages 1-2)

Mechanistic conclusions include:
- Nap1 acidic C-terminal flexible tails can engage an H2A–H2B interface that is normally buried in the nucleosome and not accessible to Nap1’s globular domains, consistent with a “penetrating fuzzy binding” mode of chaperone–histone interaction. (nagae2023histonechaperonenap1 pages 1-2)
- Nap1 can remove H2A–H2B from fully wrapped nucleosomes only slowly at low temperature, but removal is accelerated when DNA is partially unwrapped (e.g., by polymerase-like collisions). (nagae2023histonechaperonenap1 pages 2-2)

2.3 2024 (non-yeast, NAP family insight): Modulation of acidic disordered regions and chaperone efficiency

Although not specific to S. cerevisiae Nap1, a 2024 iScience study analyzed Nap1/NAP1-like acidic disordered regions and showed that post-translational modification (glutamylation) can increase DNA mimicry and histone chaperone efficiency, reinforcing the functional importance of the acidic disordered regions implicated in yeast Nap1’s mechanism. (Publication date: Apr 2024; URL: https://doi.org/10.1016/j.isci.2024.109458) (lorton2024glutamylationofnpm2 pages 15-16)

3) Cellular localization and where Nap1 acts

3.1 Cytosolic functions

Nap1 is presented as the primary cytosolic H2A–H2B chaperone that chaperones newly synthesized and folded H2A–H2B and shields them from inappropriate interactions. (fung2024nap1andkap114 pages 1-2)

3.2 Nuclear/chromatin functions

Nap1 also functions in the nucleus in pathways including nucleosome assembly/remodeling and transcription-associated nucleosome processing, with cooperative action with Kap114/RanGTP enabling targeted histone release and transfer toward assembling nucleosomes. (fung2024nap1andkap114 pages 1-2)

4) Expert opinions and authoritative analysis (from primary sources)

4.1 Chromatin organization and gene expression in vivo (classic yeast genetics)

Ohkuni et al. interpret nap1Δ expression patterns as consistent with Nap1 functioning to maintain ordered nucleosome arrangement, potentially influencing cluster-wide transcriptional states (“tight” vs “loose” chromatin regions corresponding to cluster repression vs expression). (Publication date: Jun 2003; URL: https://doi.org/10.1016/S0006-291X(03)00907-0) (ohkuni2003genomewideexpressionanalysis pages 4-5, ohkuni2003genomewideexpressionanalysis pages 1-2)

4.2 Chaperoning as a regulated handoff pathway (modern mechanistic view)

Fung et al. argue that Nap1 and Kap114 cooperatively create a sheltered pathway for H2A–H2B that enables transfer from importin-bound histone cargo to chaperone-bound cargo and onward to nucleosome assembly substrates, providing a mechanistic framework for targeted nuclear release. (fung2024nap1andkap114 pages 1-2, fung2024nap1andkap114 media e5e2dd1a)

5) Relevant statistics and quantitative data

5.1 Genome-wide transcriptional effects of nap1Δ in yeast

In three independent Affymetrix yeast GeneChip experiments, ~8.4–12.0% of ORFs showed ≥2-fold expression changes in nap1Δ, with experiment-level breakdowns (down/up/total) reported as: 3.2% down & 8.7% up (12.0% total); 1.4% down & 8.8% up (10.2% total); 6.3% down & 2.1% up (8.4% total). (ohkuni2003genomewideexpressionanalysis pages 1-2)

Among genes changing >2-fold, ~35.4% were located in genomic “clusters” in nap1Δ (versus ~12.5–12.7% in two comparator deletions), suggesting a distinctive spatial organization component to Nap1-dependent transcriptional effects. (ohkuni2003genomewideexpressionanalysis pages 2-4)

5.2 Stoichiometry and structural resolution for Nap1/Kap114/H2A–H2B/RanGTP assemblies (2024)

Fung et al. report:
- 1:1 Kap114:Nap1_2 complex formation and 1:1:1 Kap114:Nap1_2:H2A–H2B complexes.
- A quaternary assembly consistent with 1:1:1:1 Kap114:Nap1_2:H2A–H2B:RanGTP.
- Cryo-EM structure solved at 2.9 Å (local refinement 4.0 Å).
- Approximate interface areas: H2A–H2B with Kap114 ~1,600 Å²; Kap114–Nap1_2 ~120 Å².
- Key Nap1 β-hairpin residues E288/R290/Q292 (alanine substitutions) abolish pull-down interaction, supporting a direct functional interface. (fung2024nap1andkap114 pages 2-4)

5.3 Biochemical/structural parameters for Nap1-mediated nucleosome processing (2023)

Nagae et al. describe Nap1 as a ~48 kDa monomer that forms a stable homodimer and binds a single H2A–H2B dimer with nanomolar affinity. They model Nap1 using a globular core (residues 74–365) with disordered regions (residues 1–73 and 366–417), consistent with mechanistic emphasis on flexible tails. (nagae2023histonechaperonenap1 pages 2-2, nagae2023histonechaperonenap1 pages 2-3)

6) Current applications and real-world implementations

6.1 In vitro chromatin biochemistry and nucleosome reconstitution

Yeast Nap1 is used as a reagent in mechanistic assays that reconstitute nucleosomes (e.g., Widom 601 substrates) and evaluate transcription-coupled histone exchange or dimer removal. Nagae et al. implemented in vitro transcription assays with T7 RNAP and Nap1 to quantify H2A–H2B dimer dismantling, using EMSA, MNase digestion, and pull-down workflows under defined reaction conditions (e.g., 6 µM Nap1 dimers, 0.2 µM nucleosomes, 0.8 µM T7 RNAP, 200 mM NaCl). (nagae2023histonechaperonenap1 pages 2-3)

6.2 Structural biology of histone import/co-chaperoning

The Nap1/Kap114 study demonstrates a common real-world implementation: biochemical reconstitution of multi-protein assemblies coupled to cryo-EM to reveal how histone cargo is shielded and transferred for nucleosome assembly, along with nucleosome assembly and DNA-competition assays to validate function. (fung2024nap1andkap114 pages 1-2, fung2024nap1andkap114 media 07f742f1)

6.3 Single-molecule biophysics using NAP-family folds (contextual application)

A 2023 single-molecule optical tweezers/confocal fluorescence study used a NAP1-fold-containing histone chaperone (SET/TAF-1β) to track chaperone dynamics and nucleosome unwrapping/eviction in real time, illustrating how NAP-family folds are deployed in quantitative chromatin biophysics pipelines (a methodological direction directly relevant to yeast Nap1 studies even if the protein differs). (buzon2023thehistonechaperones pages 1-2)

Visual evidence (selected)

The cryo-EM architecture of the quaternary Nap1_2•H2A–H2B•Kap114•RanGTP complex and a mechanistic model for Nap1–Kap114 co-chaperoning and targeted histone release/transfer are shown in figures from Fung et al. (2024). (fung2024nap1andkap114 media e5e2dd1a, fung2024nap1andkap114 media 07f742f1)

Evidence map (compact table)

Functional role/process	Molecular mechanism (substrate/partner)	Subcellular localization	Key experimental evidence type	Key quantitative/statistical findings (if any)	Key source (first author, year, journal, DOI/URL)
Canonical nucleosome assembly / histone chaperoning	Nap1 is a conserved nucleosome assembly protein and core histone chaperone that preferentially handles H2A-H2B dimers and supports nucleosome organization during transcription and replication (ohkuni2003genomewideexpressionanalysis pages 1-2, ohkuni2003genomewideexpressionanalysis pages 4-5)	Cytosol and nucleus/chromatin-associated; largely cytoplasmic but functions in nucleus (fung2024nap1andkap114 pages 1-2)	In vitro nucleosome assembly studies; yeast deletion genetics; genome-wide expression profiling (ohkuni2003genomewideexpressionanalysis pages 1-2, ohkuni2003genomewideexpressionanalysis pages 4-5)	In nap1Δ cells, ~8.4-12.0% of ORFs changed by ≥2-fold across three experiments; ~10% in one experiment (ohkuni2003genomewideexpressionanalysis pages 1-2)	Ohkuni, 2003, Biochemical and Biophysical Research Communications, https://doi.org/10.1016/S0006-291X(03)00907-0
H2A-H2B chaperone / shielding of basic histones	Nap1 dimer (Nap1₂ / “Nap12”) binds H2A-H2B, shields DNA-binding surfaces, prevents nonspecific histone-DNA aggregation, and promotes specific nucleosome incorporation; cooperates with Kap114 (fung2024nap1andkap114 pages 1-2)	Mainly cytosolic for newly synthesized H2A-H2B, with nuclear transfer/assembly functions (fung2024nap1andkap114 pages 1-2)	Immunoprecipitation from cytosolic and RanGTP-rich nuclear extracts; SEC-MALS; AUC; pull-downs; cryo-EM; DNA competition and nucleosome assembly assays (fung2024nap1andkap114 pages 1-2, fung2024nap1andkap114 pages 2-4)	1:1 Kap114:Nap1₂ complex; 1:1:1 Kap114:Nap1₂:H2A-H2B complex; quaternary 1:1:1:1 Kap114:Nap1₂:H2A-H2B:RanGTP complex; cryo-EM at 2.9 Å (local refinement 4.0 Å) (fung2024nap1andkap114 pages 2-4)	Fung, 2024, Journal of Cell Biology, https://doi.org/10.1083/jcb.202408193
Nucleocytoplasmic co-chaperone for histone import and targeted nuclear release	Nap1 interacts with importin Kap114 and Ran-pathway components to escort H2A-H2B and facilitate targeted release onto assembling nucleosomes/tetrasomes in the nucleus (fung2024nap1andkap114 pages 1-2, fung2024nap1andkap114 media e5e2dd1a)	Nucleocytoplasmic shuttling; cytosol and nucleus (fung2024nap1andkap114 pages 1-2)	Genetics; IP; biochemical reconstitution; cryo-EM; model of histone transfer pathway (fung2024nap1andkap114 pages 1-2, fung2024nap1andkap114 media e5e2dd1a)	Kap114-H2A-H2B interface ~1,600 Å²; Kap114-Nap1₂ interface ~120 Å²; Nap1 β-hairpin residues E288/R290/Q292 are critical for Kap114 binding and nuclear localization (fung2024nap1andkap114 pages 2-4)	Fung, 2024, Journal of Cell Biology, https://doi.org/10.1083/jcb.202408193
Transcription-coupled nucleosome disassembly / H2A-H2B eviction	Nap1 can dismantle an H2A/H2B dimer from a partially unwrapped nucleosome; acidic flexible C-terminal tails access buried histone interfaces via a “penetrating fuzzy binding” mechanism, especially after translocase-induced DNA unwrapping (nagae2023histonechaperonenap1 pages 1-2)	Likely nuclear/chromatin during transcription-associated collisions (inferred from in vitro nucleosome-translocase assays) (nagae2023histonechaperonenap1 pages 1-2)	In vitro transcription assays with T7 RNAP on nucleosomes; EMSA; MNase assays; Ni-NTA pull-downs; coarse-grained molecular simulations (nagae2023histonechaperonenap1 pages 1-2, nagae2023histonechaperonenap1 pages 2-3)	Nap1 is a ~48 kDa monomer forming a stable homodimer; full Nap1 model used residues 1-417 with globular core 74-365; slow dismantling from fully wrapped nucleosomes reported on hour timescales at 4°C, but greatly accelerated by partial unwrapping (nagae2023histonechaperonenap1 pages 2-2, nagae2023histonechaperonenap1 pages 2-3)	Nagae, 2023, Nucleic Acids Research, https://doi.org/10.1093/nar/gkad396
Maintenance of in vivo nucleosome spacing and clustered transcriptional states	Nap1 is proposed to recruit H2A-H2B to maintain ordered nucleosome arrangement, influencing whether adjacent gene regions are relatively “tight” (repressed) or “loose” (expressed) (ohkuni2003genomewideexpressionanalysis pages 4-5)	Nuclear chromatin (functional inference from transcriptional and nucleosome phenotypes) (ohkuni2003genomewideexpressionanalysis pages 4-5, ohkuni2003genomewideexpressionanalysis pages 1-2)	Affymetrix Yeast Genome S98 microarrays; cluster analysis of nap1Δ expression profiles (ohkuni2003genomewideexpressionanalysis pages 2-4, ohkuni2003genomewideexpressionanalysis pages 1-2)	Among genes changing >2-fold in nap1Δ, ~35.4% were in clusters versus 12.7% in nbp2Δ and 12.5% in htr1Δ; genome-wide clustered proportions in two experiments were 28.3-30.7% for nap1Δ vs 14.8-18.1% in comparators (ohkuni2003genomewideexpressionanalysis pages 2-4)	Ohkuni, 2003, Biochemical and Biophysical Research Communications, https://doi.org/10.1016/S0006-291X(03)00907-0
Cell-cycle / mitotic regulation linkage	Nap1 physically/functionally interacts with mitotic regulators including Clb2 and Gin4, linking histone-chaperone activity to mitotic functions and suppression of polar bud growth (ohkuni2003genomewideexpressionanalysis pages 1-2, ohkuni2003genomewideexpressionanalysis pages 4-5)	Cytoplasm and nucleus; exact compartment for all interactions not resolved in provided excerpts (ohkuni2003genomewideexpressionanalysis pages 1-2, fung2024nap1andkap114 pages 1-2)	Prior yeast interaction studies summarized in genome-wide and review-style discussion (ohkuni2003genomewideexpressionanalysis pages 1-2, ohkuni2003genomewideexpressionanalysis pages 4-5)	No direct numeric effect size provided in the extracted passages for this interaction class (ohkuni2003genomewideexpressionanalysis pages 1-2, ohkuni2003genomewideexpressionanalysis pages 4-5)	Ohkuni, 2003, Biochemical and Biophysical Research Communications, https://doi.org/10.1016/S0006-291X(03)00907-0
Experimental reagent/platform for chromatin reconstitution and mechanistic studies	Purified yeast Nap1 is used in nucleosome reconstitution, chromatin transcription assays, histone-DNA competition tests, structural biology, and simulation-supported mechanistic studies (nagae2023histonechaperonenap1 pages 2-3, fung2024nap1andkap114 pages 1-2, nagae2023histonechaperonenap1 pages 1-2)	In vitro implementation rather than endogenous cellular localization (nagae2023histonechaperonenap1 pages 2-3, fung2024nap1andkap114 pages 1-2)	Reconstituted Widom 601 nucleosomes; T7 RNAP assays; EMSA; MNase; SEC-MALS; cryo-EM; MD simulations (nagae2023histonechaperonenap1 pages 2-3, fung2024nap1andkap114 pages 1-2, nagae2023histonechaperonenap1 pages 1-2)	Example assay conditions: 6 µM Nap1 dimers, 0.2 µM nucleosomes, 0.8 µM T7 RNAP, 200 mM NaCl; simulations placed Nap1 ~80 Å from nucleosome (nagae2023histonechaperonenap1 pages 2-3)	Nagae, 2023, Nucleic Acids Research, https://doi.org/10.1093/nar/gkad396; Fung, 2024, Journal of Cell Biology, https://doi.org/10.1083/jcb.202408193

Table: This table summarizes experimentally supported functions, mechanisms, localization, and quantitative findings for Saccharomyces cerevisiae NAP1 (UniProt P25293; YKR048C). It is useful as a compact evidence map for functional annotation focused on the yeast protein rather than similarly named proteins in other organisms.

Conclusions and functional annotation statement

Functional annotation (most supported): Yeast NAP1 (YKR048C; UniProt P25293) encodes a dimeric H2A–H2B histone chaperone central to histone handling and nucleosome dynamics. Nap1’s primary molecular function is to bind/shield H2A–H2B and mediate their correct delivery into nucleosomes, including a Kap114/RanGTP-coordinated handoff pathway for targeted nuclear release and nucleosome assembly. Nap1 also participates in transcription-coupled chromatin dynamics by enabling H2A–H2B eviction from partially unwrapped nucleosomes via acidic disordered tails. In vivo, Nap1 contributes to chromatin organization that can influence clustered transcriptional outputs, and it has reported functional interactions with cell-cycle regulators (Clb2, Gin4). (ohkuni2003genomewideexpressionanalysis pages 4-5, fung2024nap1andkap114 pages 1-2, nagae2023histonechaperonenap1 pages 1-2)

Key references (URLs, publication dates)

Ohkuni K. et al. Biochemical and Biophysical Research Communications (Jun 2003). “Genome-wide expression analysis of NAP1 in Saccharomyces cerevisiae.” https://doi.org/10.1016/S0006-291X(03)00907-0 (ohkuni2003genomewideexpressionanalysis pages 1-2)
Nagae F. et al. Nucleic Acids Research (May 2023). “Histone chaperone Nap1 dismantles an H2A/H2B dimer from a partially unwrapped nucleosome.” https://doi.org/10.1093/nar/gkad396 (nagae2023histonechaperonenap1 pages 1-2)
Fung H.Y.J. et al. Journal of Cell Biology (Nov 2024). “Nap1 and Kap114 co-chaperone H2A-H2B and facilitate targeted histone release in the nucleus.” https://doi.org/10.1083/jcb.202408193 (fung2024nap1andkap114 pages 1-2)
Lorton B.M. et al. iScience (Apr 2024). “Glutamylation of Npm2 and Nap1 acidic disordered regions increases DNA mimicry and histone chaperone efficiency.” https://doi.org/10.1016/j.isci.2024.109458 (lorton2024glutamylationofnpm2 pages 15-16)
Buzón P. et al. Advanced Science (Aug 2023). “The Histone Chaperones SET/TAF‐1β and NPM1….” https://doi.org/10.1002/advs.202301859 (buzon2023thehistonechaperones pages 1-2)

References

(ohkuni2003genomewideexpressionanalysis pages 1-2): Kentaro Ohkuni, Katsuhiko Shirahige, and Akihiko Kikuchi. Genome-wide expression analysis of nap1 in saccharomyces cerevisiae. Biochemical and biophysical research communications, 306 1:5-9, Jun 2003. URL: https://doi.org/10.1016/s0006-291x(03)00907-0, doi:10.1016/s0006-291x(03)00907-0. This article has 94 citations and is from a peer-reviewed journal.
(fung2024nap1andkap114 pages 1-2): Ho Yee Joyce Fung, Jenny Jiou, Ashley B. Niesman, Natalia E. Bernardes, and Yuh Min Chook. Nap1 and kap114 co-chaperone h2a-h2b and facilitate targeted histone release in the nucleus. The Journal of Cell Biology, Nov 2024. URL: https://doi.org/10.1083/jcb.202408193, doi:10.1083/jcb.202408193. This article has 7 citations.
(nagae2023histonechaperonenap1 pages 1-2): Fritz Nagae, Shoji Takada, and Tsuyoshi Terakawa. Histone chaperone nap1 dismantles an h2a/h2b dimer from a partially unwrapped nucleosome. Nucleic Acids Research, 51:5351-5363, May 2023. URL: https://doi.org/10.1093/nar/gkad396, doi:10.1093/nar/gkad396. This article has 19 citations and is from a highest quality peer-reviewed journal.
(nagae2023histonechaperonenap1 pages 2-2): Fritz Nagae, Shoji Takada, and Tsuyoshi Terakawa. Histone chaperone nap1 dismantles an h2a/h2b dimer from a partially unwrapped nucleosome. Nucleic Acids Research, 51:5351-5363, May 2023. URL: https://doi.org/10.1093/nar/gkad396, doi:10.1093/nar/gkad396. This article has 19 citations and is from a highest quality peer-reviewed journal.
(fung2024nap1andkap114 pages 2-4): Ho Yee Joyce Fung, Jenny Jiou, Ashley B. Niesman, Natalia E. Bernardes, and Yuh Min Chook. Nap1 and kap114 co-chaperone h2a-h2b and facilitate targeted histone release in the nucleus. The Journal of Cell Biology, Nov 2024. URL: https://doi.org/10.1083/jcb.202408193, doi:10.1083/jcb.202408193. This article has 7 citations.
(ohkuni2003genomewideexpressionanalysis pages 4-5): Kentaro Ohkuni, Katsuhiko Shirahige, and Akihiko Kikuchi. Genome-wide expression analysis of nap1 in saccharomyces cerevisiae. Biochemical and biophysical research communications, 306 1:5-9, Jun 2003. URL: https://doi.org/10.1016/s0006-291x(03)00907-0, doi:10.1016/s0006-291x(03)00907-0. This article has 94 citations and is from a peer-reviewed journal.
(lorton2024glutamylationofnpm2 pages 15-16): Benjamin M. Lorton, Christopher Warren, Humaira Ilyas, Prithviraj Nandigrami, Subray Hegde, Sean Cahill, Stephanie M. Lehman, Jeffrey Shabanowitz, Donald F. Hunt, Andras Fiser, David Cowburn, and David Shechter. Glutamylation of npm2 and nap1 acidic disordered regions increases dna mimicry and histone chaperone efficiency. iScience, 27:109458, Apr 2024. URL: https://doi.org/10.1016/j.isci.2024.109458, doi:10.1016/j.isci.2024.109458. This article has 10 citations and is from a peer-reviewed journal.
(fung2024nap1andkap114 media e5e2dd1a): Ho Yee Joyce Fung, Jenny Jiou, Ashley B. Niesman, Natalia E. Bernardes, and Yuh Min Chook. Nap1 and kap114 co-chaperone h2a-h2b and facilitate targeted histone release in the nucleus. The Journal of Cell Biology, Nov 2024. URL: https://doi.org/10.1083/jcb.202408193, doi:10.1083/jcb.202408193. This article has 7 citations.
(ohkuni2003genomewideexpressionanalysis pages 2-4): Kentaro Ohkuni, Katsuhiko Shirahige, and Akihiko Kikuchi. Genome-wide expression analysis of nap1 in saccharomyces cerevisiae. Biochemical and biophysical research communications, 306 1:5-9, Jun 2003. URL: https://doi.org/10.1016/s0006-291x(03)00907-0, doi:10.1016/s0006-291x(03)00907-0. This article has 94 citations and is from a peer-reviewed journal.
(nagae2023histonechaperonenap1 pages 2-3): Fritz Nagae, Shoji Takada, and Tsuyoshi Terakawa. Histone chaperone nap1 dismantles an h2a/h2b dimer from a partially unwrapped nucleosome. Nucleic Acids Research, 51:5351-5363, May 2023. URL: https://doi.org/10.1093/nar/gkad396, doi:10.1093/nar/gkad396. This article has 19 citations and is from a highest quality peer-reviewed journal.
(fung2024nap1andkap114 media 07f742f1): Ho Yee Joyce Fung, Jenny Jiou, Ashley B. Niesman, Natalia E. Bernardes, and Yuh Min Chook. Nap1 and kap114 co-chaperone h2a-h2b and facilitate targeted histone release in the nucleus. The Journal of Cell Biology, Nov 2024. URL: https://doi.org/10.1083/jcb.202408193, doi:10.1083/jcb.202408193. This article has 7 citations.
(buzon2023thehistonechaperones pages 1-2): Pedro Buzón, Alejandro Velázquez‐Cruz, Laura Corrales‐Guerrero, Antonio Díaz‐Quintana, Irene Díaz‐Moreno, and Wouter H. Roos. The histone chaperones set/taf‐1β and npm1 exhibit conserved functionality in nucleosome remodeling and histone eviction in a cytochrome c‐dependent manner. Advanced Science, Aug 2023. URL: https://doi.org/10.1002/advs.202301859, doi:10.1002/advs.202301859. This article has 7 citations and is from a peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Citations

ohkuni2003genomewideexpressionanalysis pages 1-2
ohkuni2003genomewideexpressionanalysis pages 2-4
buzon2023thehistonechaperones pages 1-2
ohkuni2003genomewideexpressionanalysis pages 4-5
https://doi.org/10.1083/jcb.202408193
https://doi.org/10.1093/nar/gkad396
https://doi.org/10.1016/j.isci.2024.109458
https://doi.org/10.1016/S0006-291X(03
https://doi.org/10.1093/nar/gkad396;
https://doi.org/10.1002/advs.202301859
https://doi.org/10.1016/s0006-291x(03
https://doi.org/10.1083/jcb.202408193,
https://doi.org/10.1093/nar/gkad396,
https://doi.org/10.1016/j.isci.2024.109458,
https://doi.org/10.1002/advs.202301859,

📄 View Raw YAML

id: P25293
gene_symbol: NAP1
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: >-
  NAP1 encodes a conserved histone chaperone with roles in chromatin assembly,
  ribosome biogenesis, and cell cycle regulation. Nap1p functions primarily as
  an H2A-H2B chaperone, cooperating with the karyopherin Kap114 to transport
  histone H2A-H2B dimers into the nucleus for deposition into nucleosomes;
  binding of Ran-GTP (Gsp1) to this complex promotes accurate nucleosome
  assembly. Nap1p also participates in histone exchange, facilitating
  replacement of canonical H2A-H2B dimers with variant dimers. Beyond
  chromatin, Nap1p serves as an assembly chaperone for the small ribosomal
  subunit protein eS6 (Rps6a/Rps6b), promoting its solubility and
  contributing to 40S subunit biogenesis. During mitosis, Nap1p regulates
  septin organization at the bud neck and modulates B-type cyclin (Clb2p)
  function, linking chromatin dynamics to cell cycle progression. Orthologous
  to human NAP1L1-4.
existing_annotations:
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'Manual review: chromatin is consistent with known biology of NAP1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: |-
      Nap1 functions in both the cytosol and the nucleus. Falcon deep research notes
      that Nap1 is mostly cytoplasmic but also functions in the nucleus, where it
      supports nucleosome assembly and remodeling; nuclear activity is genuine but
      the protein is predominantly cytosolic, so this localization is retained as
      non-core.
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
    additional_reference_ids:
    - file:yeast/NAP1/NAP1-deep-research-falcon.md
    supported_by:
    - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
      supporting_text: but also acts in the nucleus where it supports targeted histone
        release/import, nucleosome assembly and remodeling during transcription
      reference_section_type: ABSTRACT
- term:
    id: GO:0006334
    label: nucleosome assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: |-
      Nucleosome assembly is a core biological process for NAP1. Falcon deep research
      supports that Nap1 is a conserved nucleosome assembly protein that promotes
      correct nucleosome organization by delivering H2A-H2B dimers into nucleosomes
      rather than allowing random histone-DNA association.
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
    additional_reference_ids:
    - file:yeast/NAP1/NAP1-deep-research-falcon.md
    supported_by:
    - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
      supporting_text: Nap1 is proposed to recruit H2A-H2B to maintain ordered nucleosome
        arrangement
      reference_section_type: RESULTS
- term:
    id: GO:0042393
    label: histone binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: |-
      Histone binding is a core molecular function of NAP1. Falcon deep research
      confirms the primary substrate is the H2A-H2B dimer, which Nap1 binds with
      nanomolar affinity as a stable homodimer, shielding the basic DNA-binding
      surfaces of the histones.
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
    additional_reference_ids:
    - file:yeast/NAP1/NAP1-deep-research-falcon.md
    supported_by:
    - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
      supporting_text: The primary substrate of Nap1 is the **H2A–H2B dimer**
      reference_section_type: RESULTS
    - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
      supporting_text: Nagae et al. describe Nap1 as a **~48 kDa monomer** that forms
        a stable homodimer and binds a single H2A–H2B dimer with **nanomolar affinity**
      reference_section_type: RESULTS
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'Manual review: chromatin binding is consistent with known biology of NAP1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: 'Manual review: DNA binding may be context-dependent or peripheral for NAP1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'Manual review: nucleus may be context-dependent or peripheral for NAP1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: 'Manual review: cytoplasm is the predominant steady-state localization of NAP1 and the principal site of its core H2A-H2B chaperone activity.'
    action: ACCEPT
    reason: Accepted as core, consistent with the IDA cytoplasm annotation (PMID:7622566); the cytoplasm is the predominant steady-state localization where Nap1 carries out its core H2A-H2B chaperone activity.
- term:
    id: GO:0005935
    label: cellular bud neck
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: 'Manual review: cellular bud neck may be context-dependent or peripheral for NAP1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0005940
    label: septin ring
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'Manual review: septin ring may be context-dependent or peripheral for NAP1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0006334
    label: nucleosome assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: 'Manual review: nucleosome assembly is consistent with known biology of NAP1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10688190
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11805837
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12058072
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14645854
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14759368
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15045029
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16299494
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16429126
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16554755
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18467557
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18719252
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19172749
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19536198
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20489023
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21179020
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23468594
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416945
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37968396
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9214386
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9813092
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:16432217
  review:
    summary: 'Manual review: identical protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:18467557
  review:
    summary: 'Manual review: identical protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:18719252
  review:
    summary: 'Manual review: identical protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:21179020
  review:
    summary: 'Manual review: identical protein binding is too generic or over-extended for NAP1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0140597
    label: protein carrier chaperone
  evidence_type: IDA
  original_reference_id: PMID:31062022
  review:
    summary: 'Manual review: protein carrier chaperone is consistent with known biology of NAP1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0000511
    label: H2A-H2B histone complex chaperone activity
  evidence_type: IDA
  original_reference_id: PMID:39601790
  review:
    summary: |-
      This is the core molecular function of NAP1. Falcon deep research (anchored on
      Fung et al. 2024, the source of this PMID) establishes that Nap1 forms a stable
      homodimer that binds H2A-H2B, shields their DNA-binding surfaces, and cooperates
      with the importin Kap114 and RanGTP to chaperone H2A-H2B for nucleosome assembly,
      forming a quaternary Nap1_2-H2A-H2B-Kap114-RanGTP complex.
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
    additional_reference_ids:
    - file:yeast/NAP1/NAP1-deep-research-falcon.md
    supported_by:
    - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
      supporting_text: Nap1 forms a stable **homodimer**
      reference_section_type: RESULTS
    - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
      supporting_text: Kap114, H2A–H2B, and Nap1\_2 form equimolar complexes, including
        a quaternary **Nap1\_2•H2A–H2B•Kap114•RanGTP** assembly
      reference_section_type: RESULTS
- term:
    id: GO:0006334
    label: nucleosome assembly
  evidence_type: IDA
  original_reference_id: PMID:39601790
  review:
    summary: 'Manual review: nucleosome assembly is consistent with known biology of NAP1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0000511
    label: H2A-H2B histone complex chaperone activity
  evidence_type: IDA
  original_reference_id: PMID:27225933
  review:
    summary: 'Manual review: H2A-H2B histone complex chaperone activity is consistent with known biology of NAP1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0006334
    label: nucleosome assembly
  evidence_type: IDA
  original_reference_id: PMID:27225933
  review:
    summary: 'Manual review: nucleosome assembly is consistent with known biology of NAP1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0000920
    label: septum digestion after cytokinesis
  evidence_type: NAS
  original_reference_id: PMID:12058072
  review:
    summary: 'Manual review: septum digestion after cytokinesis may be context-dependent or peripheral for NAP1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0000921
    label: septin ring assembly
  evidence_type: NAS
  original_reference_id: PMID:12058072
  review:
    summary: 'Manual review: septin ring assembly may be context-dependent or peripheral for NAP1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0006607
    label: NLS-bearing protein import into nucleus
  evidence_type: IMP
  original_reference_id: PMID:12456659
  review:
    summary: |-
      Nap1 participates in histone H2A-H2B nuclear import in cooperation with the
      importin Kap114 and the Ran-GTP system. Falcon deep research describes Nap1
      escorting H2A-H2B and facilitating targeted release onto assembling nucleosomes
      in the nucleus. This nuclear-import function is real but is an extension of the
      core H2A-H2B chaperone activity rather than the gene's primary function.
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
    additional_reference_ids:
    - file:yeast/NAP1/NAP1-deep-research-falcon.md
    supported_by:
    - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
      supporting_text: Nap1 interacts with importin Kap114 and Ran-pathway components
        to escort H2A-H2B and facilitate targeted release onto assembling nucleosomes/tetrasomes
        in the nucleus
      reference_section_type: RESULTS
- term:
    id: GO:0042274
    label: ribosomal small subunit biogenesis
  evidence_type: IGI
  original_reference_id: PMID:31062022
  review:
    summary: 'Manual review: ribosomal small subunit biogenesis may be context-dependent or peripheral for NAP1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:31062022
  review:
    summary: |-
      'Unfolded protein binding' is overly generic for NAP1. The defining substrate
      is the H2A-H2B histone dimer, for which Nap1 has strong specificity. Falcon
      deep research confirms the primary substrate is the H2A-H2B dimer, supporting
      replacement with the more specific H2A-H2B histone complex chaperone activity
      term. (Note: PMID:31062022 also documents a separate eS6/Rps6 ribosomal protein
      chaperone role, captured by other annotations.)
    action: MODIFY
    reason: Modified to align with current curation guidance and improve term specificity.
    proposed_replacement_terms:
    - id: GO:0000511
      label: H2A-H2B histone complex chaperone activity
    additional_reference_ids:
    - file:yeast/NAP1/NAP1-deep-research-falcon.md
    supported_by:
    - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
      supporting_text: The primary substrate of Nap1 is the **H2A–H2B dimer**
      reference_section_type: RESULTS
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:30341817
  review:
    summary: 'Manual review: cytoplasm is the predominant steady-state localization of NAP1 and the principal site of its core H2A-H2B chaperone activity.'
    action: ACCEPT
    reason: Accepted as core, consistent with the other cytoplasm annotations; the cytoplasm is the predominant steady-state localization where Nap1 carries out its core H2A-H2B chaperone activity.
    additional_reference_ids:
    - file:yeast/NAP1/NAP1-deep-research-falcon.md
    supported_by:
    - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
      supporting_text: Nap1 is described as the **principal cytosolic H2A–H2B chaperone**
        that is mostly cytoplasmic but also functions in the nucleus (implying **nucleocytoplasmic
        shuttling**)
      reference_section_type: RESULTS
- term:
    id: GO:0032174
    label: cellular bud neck septin collar
  evidence_type: IDA
  original_reference_id: PMID:30341817
  review:
    summary: 'Manual review: cellular bud neck septin collar may be context-dependent or peripheral for NAP1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0032153
    label: cell division site
  evidence_type: IDA
  original_reference_id: PMID:25416945
  review:
    summary: 'Manual review: cell division site may be context-dependent or peripheral for NAP1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0098841
    label: protein localization to cell division site after cytokinesis
  evidence_type: IMP
  original_reference_id: PMID:25416945
  review:
    summary: 'Manual review: protein localization to cell division site after cytokinesis may be context-dependent or peripheral for NAP1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0006334
    label: nucleosome assembly
  evidence_type: IDA
  original_reference_id: PMID:1400414
  review:
    summary: 'Manual review: nucleosome assembly is consistent with known biology of NAP1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0008047
    label: enzyme activator activity
  evidence_type: IDA
  original_reference_id: PMID:22308335
  review:
    summary: 'Manual review: enzyme activator activity may be context-dependent or peripheral for NAP1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0031116
    label: positive regulation of microtubule polymerization
  evidence_type: IMP
  original_reference_id: PMID:7622567
  review:
    summary: 'Manual review: positive regulation of microtubule polymerization may be context-dependent or peripheral for NAP1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:7622566
  review:
    summary: |-
      Cytoplasm is the predominant localization of Nap1. Falcon deep research
      describes Nap1 as the principal cytosolic H2A-H2B chaperone that handles
      newly synthesized H2A-H2B before nuclear import, implying nucleocytoplasmic
      shuttling. This is the major site of action even though Nap1 also functions
      in the nucleus.
    action: ACCEPT
    reason: |-
      Accepted as core. The cytoplasm is the predominant steady-state localization
      of Nap1 and the principal site of its core H2A-H2B histone-chaperone activity,
      where Nap1 handles newly synthesized H2A-H2B before nuclear import. Falcon deep
      research (Fung et al. 2024) describes Nap1 as the principal cytosolic H2A-H2B
      chaperone that is mostly cytoplasmic, so this IDA localization is elevated from
      non-core to a core location.
    additional_reference_ids:
    - file:yeast/NAP1/NAP1-deep-research-falcon.md
    supported_by:
    - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
      supporting_text: Nap1 is described as the **principal cytosolic H2A–H2B chaperone**
        that is mostly cytoplasmic but also functions in the nucleus (implying **nucleocytoplasmic
        shuttling**)
      reference_section_type: RESULTS
- term:
    id: GO:0006334
    label: nucleosome assembly
  evidence_type: IDA
  original_reference_id: PMID:2016313
  review:
    summary: 'Manual review: nucleosome assembly is consistent with known biology of NAP1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0006337
    label: nucleosome disassembly
  evidence_type: IDA
  original_reference_id: PMID:16492771
  review:
    summary: |-
      Nucleosome disassembly via H2A-H2B eviction is a genuine Nap1 activity. Falcon
      deep research (anchored on Nagae et al. 2023) shows that Nap1 can dismantle an
      H2A-H2B dimer from a partially unwrapped nucleosome, with its acidic C-terminal
      flexible tails engaging an otherwise buried histone interface via a 'penetrating
      fuzzy binding' mechanism; removal is slow from fully wrapped nucleosomes but
      greatly accelerated by translocase-induced partial DNA unwrapping.
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
    additional_reference_ids:
    - file:yeast/NAP1/NAP1-deep-research-falcon.md
    supported_by:
    - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
      supporting_text: Nap1 can also act in **H2A–H2B eviction/dismantling**, particularly
        when nucleosomal DNA is partially unwrapped
      reference_section_type: RESULTS
    - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
      supporting_text: Nap1 acidic **C-terminal flexible tails** can engage an H2A–H2B
        interface that is normally buried in the nucleosome
      reference_section_type: RESULTS
    - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
      supporting_text: Nap1 can remove H2A–H2B from fully wrapped nucleosomes only slowly
        at low temperature, but removal is accelerated when DNA is partially unwrapped
      reference_section_type: RESULTS
- term:
    id: GO:0007117
    label: budding cell bud growth
  evidence_type: IMP
  original_reference_id: PMID:13680156
  review:
    summary: 'Manual review: budding cell bud growth may be context-dependent or peripheral for NAP1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0030332
    label: cyclin binding
  evidence_type: IPI
  original_reference_id: PMID:7622566
  review:
    summary: |-
      Nap1 binds the B-type cyclin Clb2, linking its histone-chaperone activity to
      mitotic regulation and suppression of polar bud growth. Falcon deep research
      notes these reported functional interactions with mitotic regulators (Clb2 and
      Gin4). This is a peripheral, organism-specific function rather than the core
      chaperone activity, so it is retained as non-core.
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
    additional_reference_ids:
    - file:yeast/NAP1/NAP1-deep-research-falcon.md
    supported_by:
    - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
      supporting_text: Nap1 physically/functionally interacts with mitotic regulators
        including Clb2 and Gin4, linking histone-chaperone activity to mitotic functions
        and suppression of polar bud growth
      reference_section_type: RESULTS
- term:
    id: GO:0032968
    label: positive regulation of transcription elongation by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:22308335
  review:
    summary: |-
      Nap1 supports transcription-coupled chromatin dynamics by managing H2A-H2B
      during polymerase passage. Falcon deep research shows that partial nucleosome
      unwrapping by a translocase dramatically facilitates Nap1-mediated H2A-H2B
      dimer dismantling, consistent with a role in nucleosome disassembly/reassembly
      cycles linked to transcription. This is a downstream consequence of the core
      chaperone activity rather than a primary function.
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
    additional_reference_ids:
    - file:yeast/NAP1/NAP1-deep-research-falcon.md
    supported_by:
    - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
      supporting_text: partial nucleosome unwrapping by a translocase dramatically facilitates
        Nap1-mediated H2A–H2B dimer dismantling
      reference_section_type: RESULTS
- term:
    id: GO:0042393
    label: histone binding
  evidence_type: IDA
  original_reference_id: PMID:17289584
  review:
    summary: 'Manual review: histone binding is consistent with known biology of NAP1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0042393
    label: histone binding
  evidence_type: IDA
  original_reference_id: PMID:21348863
  review:
    summary: 'Manual review: histone binding is consistent with known biology of NAP1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
core_functions:
- description: |-
    Nap1 is a dimeric H2A-H2B histone chaperone. It forms a stable homodimer that
    binds the H2A-H2B dimer with nanomolar affinity, shielding the basic DNA-binding
    surfaces of the histones to prevent non-specific histone-DNA aggregation. This
    H2A-H2B chaperone activity is the defining core molecular function of the gene.
  molecular_function:
    id: GO:0000511
    label: H2A-H2B histone complex chaperone activity
  directly_involved_in:
  - id: GO:0006334
    label: nucleosome assembly
  locations:
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0005634
    label: nucleus
  substrates:
  - id: GO:0000786
    label: nucleosome
  supported_by:
  - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
    supporting_text: encodes a dimeric H2A–H2B histone chaperone central to histone
      handling and nucleosome dynamics
    reference_section_type: CONCLUSIONS
  - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
    supporting_text: Nap1 forms a stable **homodimer**
    reference_section_type: RESULTS
  - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
    supporting_text: 'Nap1 is described as the **principal cytosolic H2A–H2B chaperone**
      that is mostly cytoplasmic but also functions in the nucleus (implying **nucleocytoplasmic
      shuttling**)'
    reference_section_type: RESULTS
- description: |-
    Nap1 promotes correct nucleosome assembly by delivering H2A-H2B dimers into
    nucleosomes rather than allowing random histone-DNA association. It functions
    as the principal cytosolic chaperone for newly synthesized H2A-H2B and cooperates
    with the importin Kap114 and the RanGTP system for targeted nuclear release and
    deposition of H2A-H2B during nucleosome assembly.
  molecular_function:
    id: GO:0042393
    label: histone binding
  directly_involved_in:
  - id: GO:0006334
    label: nucleosome assembly
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0005737
    label: cytoplasm
  substrates:
  - id: GO:0000786
    label: nucleosome
  supported_by:
  - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
    supporting_text: '**facilitates productive nucleosome incorporation** of H2A–H2B
      rather than random histone–DNA association'
    reference_section_type: RESULTS
  - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
    supporting_text: Nap1 is defined as a **nucleosome assembly protein** and **core
      histone chaperone**
    reference_section_type: RESULTS
- description: |-
    Beyond deposition, Nap1 can dismantle and evict H2A-H2B dimers from partially
    unwrapped nucleosomes, contributing to nucleosome disassembly during transcription
    and other chromatin transactions. Its acidic C-terminal flexible tails engage an
    otherwise buried H2A-H2B interface via a 'penetrating fuzzy binding' mechanism,
    with eviction strongly accelerated by translocase-induced partial DNA unwrapping.
  molecular_function:
    id: GO:0000511
    label: H2A-H2B histone complex chaperone activity
  directly_involved_in:
  - id: GO:0006337
    label: nucleosome disassembly
  locations:
  - id: GO:0005634
    label: nucleus
  substrates:
  - id: GO:0000786
    label: nucleosome
  supported_by:
  - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
    supporting_text: Nap1 can also act in **H2A–H2B eviction/dismantling**, particularly
      when nucleosomal DNA is partially unwrapped
    reference_section_type: RESULTS
  - reference_id: file:yeast/NAP1/NAP1-deep-research-falcon.md
    supporting_text: Nap1 acidic **C-terminal flexible tails** can engage an H2A–H2B
      interface that is normally buried in the nucleosome
    reference_section_type: RESULTS
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10688190
  title: A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae.
  findings: []
- id: PMID:11805837
  title: Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry.
  findings: []
- id: PMID:12058072
  title: Cell cycle-dependent assembly of a Gin4-septin complex.
  findings: []
- id: PMID:12456659
  title: A role for nucleosome assembly protein 1 in the nuclear transport of histones H2A and H2B.
  findings: []
- id: PMID:12788058
  title: Genome-wide expression analysis of NAP1 in Saccharomyces cerevisiae.
  findings:
  - statement: |-
      In nap1-delta cells, roughly 8.4-12.0% of ORFs changed expression by at least
      2-fold across three independent microarray experiments, and affected genes were
      enriched in genomic clusters, suggesting Nap1 maintains ordered nucleosome
      arrangement in vivo.
    supporting_text: In nap1Δ cells, ~8.4-12.0% of ORFs changed by ≥2-fold across three
      experiments
    reference_section_type: RESULTS
  - statement: |-
      Nap1 reportedly interacts functionally with the mitotic regulators Clb2 (B-type
      cyclin) and Gin4, linking histone-chaperone activity to mitotic functions and
      suppression of polar bud growth.
    supporting_text: Nap1 physically/functionally interacts with mitotic regulators including
      Clb2 and Gin4, linking histone-chaperone activity to mitotic functions and suppression
      of polar bud growth
    reference_section_type: DISCUSSION
- id: PMID:13680156
  title: Saccharomyces cerevisiae Ats1p interacts with Nap1p, a cytoplasmic protein that controls bud morphogenesis.
  findings: []
- id: PMID:1400414
  title: Functional analysis of nucleosome assembly protein, NAP-1. The negatively charged COOH-terminal region is not necessary for the intrinsic assembly activity.
  findings: []
- id: PMID:14645854
  title: ATP-driven exchange of histone H2AZ variant catalyzed by SWR1 chromatin remodeling complex.
  findings: []
- id: PMID:14759368
  title: High-definition macromolecular composition of yeast RNA-processing complexes.
  findings: []
- id: PMID:15045029
  title: A protein complex containing the conserved Swi2/Snf2-related ATPase Swr1p deposits histone variant H2A.Z into euchromatin.
  findings: []
- id: PMID:16299494
  title: A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery.
  findings: []
- id: PMID:16429126
  title: Proteome survey reveals modularity of the yeast cell machinery.
  findings: []
- id: PMID:16432217
  title: The structure of nucleosome assembly protein 1.
  findings: []
- id: PMID:16492771
  title: Chromatin remodeling by nucleosome disassembly in vitro.
  findings: []
- id: PMID:16554755
  title: Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
  findings: []
- id: PMID:17289584
  title: Chz1, a nuclear chaperone for histone H2AZ.
  findings: []
- id: PMID:18467557
  title: An in vivo map of the yeast protein interactome.
  findings: []
- id: PMID:18719252
  title: High-quality binary protein interaction map of the yeast interactome network.
  findings: []
- id: PMID:19172749
  title: Histone chaperone specificity in Rtt109 activation.
  findings: []
- id: PMID:19536198
  title: 'An atlas of chaperone-protein interactions in Saccharomyces cerevisiae: implications to protein folding pathways in the cell.'
  findings: []
- id: PMID:2016313
  title: Identification and molecular cloning of yeast homolog of nucleosome assembly protein I which facilitates nucleosome assembly in vitro.
  findings: []
- id: PMID:20489023
  title: A global protein kinase and phosphatase interaction network in yeast.
  findings: []
- id: PMID:21179020
  title: Defining the budding yeast chromatin-associated interactome.
  findings: []
- id: PMID:21348863
  title: Assembly states of the nucleosome assembly protein 1 (NAP-1) revealed by sedimentation velocity and non-denaturing MS.
  findings: []
- id: PMID:22308335
  title: Histone density is maintained during transcription mediated by the chromatin remodeler RSC and histone chaperone NAP1 in vitro.
  findings: []
- id: PMID:23468594
  title: A safeguard mechanism regulates Rho GTPases to coordinate cytokinesis with the establishment of cell polarity.
  findings: []
- id: PMID:25416945
  title: A memory system of negative polarity cues prevents replicative aging.
  findings: []
- id: PMID:27225933
  title: Structural evidence for Nap1-dependent H2A-H2B deposition and nucleosome assembly.
  findings: []
- id: PMID:30341817
  title: Septin-associated proteins Aim44 and Nis1 traffic between the bud neck and the nucleus in the yeast Saccharomyces cerevisiae.
  findings: []
- id: PMID:31062022
  title: Tsr4 and Nap1, two novel members of the ribosomal protein chaperOME.
  findings: []
- id: PMID:37177996
  title: Histone chaperone Nap1 dismantles an H2A/H2B dimer from a partially unwrapped nucleosome.
  findings:
  - statement: |-
      Nap1 can dismantle an H2A-H2B dimer from a partially unwrapped nucleosome;
      partial unwrapping by a translocase dramatically facilitates this Nap1-mediated
      dimer removal.
    supporting_text: partial nucleosome unwrapping by a translocase dramatically facilitates
      Nap1-mediated H2A–H2B dimer dismantling
    reference_section_type: ABSTRACT
  - statement: |-
      The acidic C-terminal flexible tails of Nap1 engage an H2A-H2B interface that
      is normally buried in the nucleosome and inaccessible to Nap1's globular domains,
      consistent with a 'penetrating fuzzy binding' chaperone mechanism.
    supporting_text: Nap1 acidic **C-terminal flexible tails** can engage an H2A–H2B
      interface that is normally buried in the nucleosome
    reference_section_type: RESULTS
  - statement: |-
      Nap1 is a ~48 kDa monomer that forms a stable homodimer and binds a single
      H2A-H2B dimer with nanomolar affinity.
    supporting_text: Nagae et al. describe Nap1 as a **~48 kDa monomer** that forms a
      stable homodimer and binds a single H2A–H2B dimer with **nanomolar affinity**
    reference_section_type: RESULTS
- id: PMID:37968396
  title: The social and structural architecture of the yeast protein interactome.
  findings: []
- id: PMID:38571760
  title: Glutamylation of Npm2 and Nap1 acidic disordered regions increases DNA mimicry and histone chaperone efficiency.
  findings:
  - statement: |-
      Post-translational glutamylation of the Nap1/NAP1-like acidic disordered regions
      can increase DNA mimicry and histone chaperone efficiency, reinforcing the
      functional importance of the acidic disordered regions in the chaperone mechanism.
    supporting_text: post-translational modification (glutamylation) can increase DNA
      mimicry and histone chaperone efficiency
    reference_section_type: ABSTRACT
- id: PMID:39601790
  title: Nap1 and Kap114 co-chaperone H2A-H2B and facilitate targeted histone release in the nucleus.
  findings:
  - statement: |-
      Nap1 is the principal cytosolic H2A-H2B chaperone; it is mostly cytoplasmic but
      also functions in the nucleus, implying nucleocytoplasmic shuttling.
    supporting_text: Nap1 is described as the **principal cytosolic H2A–H2B chaperone**
      that is mostly cytoplasmic but also functions in the nucleus (implying **nucleocytoplasmic
      shuttling**)
    reference_section_type: RESULTS
  - statement: |-
      Kap114, H2A-H2B, and the Nap1 dimer form equimolar complexes, including a
      quaternary Nap1_2-H2A-H2B-Kap114-RanGTP assembly resolved by cryo-EM.
    supporting_text: Kap114, H2A–H2B, and Nap1\_2 form equimolar complexes, including
      a quaternary **Nap1\_2•H2A–H2B•Kap114•RanGTP** assembly
    reference_section_type: RESULTS
- id: PMID:7622566
  title: Members of the NAP/SET family of proteins interact specifically with B-type cyclins.
  findings: []
- id: PMID:7622567
  title: NAP1 acts with Clb1 to perform mitotic functions and to suppress polar bud growth in budding yeast.
  findings: []
- id: PMID:9214386
  title: Control of mitotic events by Nap1 and the Gin4 kinase.
  findings: []
- id: PMID:9813092
  title: The septins are required for the mitosis-specific activation of the Gin4 kinase.
  findings: []
- id: file:yeast/NAP1/NAP1-deep-research-falcon.md
  title: 'Falcon (Edison) deep research report: Saccharomyces cerevisiae NAP1 (P25293) functional annotation.'
  findings:
  - statement: |-
      Yeast NAP1 (YKR048C; P25293) encodes a dimeric H2A-H2B histone chaperone whose
      primary molecular function is to bind and shield the H2A-H2B dimer and mediate
      its correct delivery into nucleosomes, including a Kap114/RanGTP-coordinated
      handoff pathway for targeted nuclear release and nucleosome assembly; Nap1 also
      enables H2A-H2B eviction from partially unwrapped nucleosomes.
    supporting_text: Nap1’s primary molecular function is to bind/shield H2A–H2B and
      mediate their correct delivery into nucleosomes, including a Kap114/RanGTP-coordinated
      handoff pathway for targeted nuclear release and nucleosome assembly. Nap1 also
      participates in transcription-coupled chromatin dynamics by enabling H2A–H2B eviction
      from partially unwrapped nucleosomes via acidic disordered tails.
    reference_section_type: CONCLUSIONS

NAP1

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

Research Report: Saccharomyces cerevisiae NAP1 (UniProt P25293; gene NAP1, systematic YKR048C) — Functional Annotation

Executive summary

1) Key concepts and definitions (current understanding)

1.1 What Nap1 is

1.2 What a histone chaperone does (as applied to Nap1)

1.3 Primary molecular function (substrate specificity)

1.4 Biological processes and pathways

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

2.1 2024: Nap1–Kap114–RanGTP quaternary complex and targeted histone release

2.2 2023: Mechanism of Nap1-mediated H2A–H2B dismantling from partially unwrapped nucleosomes

2.3 2024 (non-yeast, NAP family insight): Modulation of acidic disordered regions and chaperone efficiency

3) Cellular localization and where Nap1 acts

3.1 Cytosolic functions

3.2 Nuclear/chromatin functions

4) Expert opinions and authoritative analysis (from primary sources)

4.1 Chromatin organization and gene expression in vivo (classic yeast genetics)

4.2 Chaperoning as a regulated handoff pathway (modern mechanistic view)

5) Relevant statistics and quantitative data

5.1 Genome-wide transcriptional effects of nap1Δ in yeast

5.2 Stoichiometry and structural resolution for Nap1/Kap114/H2A–H2B/RanGTP assemblies (2024)

5.3 Biochemical/structural parameters for Nap1-mediated nucleosome processing (2023)

6) Current applications and real-world implementations

6.1 In vitro chromatin biochemistry and nucleosome reconstitution

6.2 Structural biology of histone import/co-chaperoning

6.3 Single-molecule biophysics using NAP-family folds (contextual application)

Visual evidence (selected)

Evidence map (compact table)

Conclusions and functional annotation statement

Key references (URLs, publication dates)

Artifacts

Citations

📄 View Raw YAML