ESA1

Existing Annotations Review

Gene Description

Existing Annotations Review

Core Functions

References

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Deep Research

Falcon

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GO Term	Evidence	Action	Reason
GO:0000785 chromatin	IBA GO_REF:0000033	ACCEPT	Summary: ESA1 is a core component of the NuA4 complex that acts on chromatin substrates. Phylogenetic inference (IBA) correctly identifies chromatin as the cellular location where ESA1 functions through nucleosome acetylation. Reason: ESA1 functions directly on chromatin through histone acetylation. Multiple experimental sources confirm NuA4 recruitment to chromatin and nucleosome-level acetylation patterns. The IBA evidence is conservative but appropriate. Supporting Evidence: file:yeast/ESA1/ESA1-deep-research-falcon.md model: Edison Scientific Literature
GO:0000785 chromatin	IDA PMID:10911987 Multiple links between the NuA4 histone acetyltransferase co...	ACCEPT	Summary: Direct experimental evidence (IDA) confirms ESA1 localizes to and functions on chromatin. This duplicate annotation with IBA provides independent confirmation. Reason: Multiple evidence codes for the same essential localization strengthen the annotation. IDA from PMID:10911987 provides direct experimental documentation. Supporting Evidence: PMID:10911987 Multiple links between the NuA4 histone acetyltransferase complex and epigenetic control of transcription.
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: ESA1 is a nuclear protein required for nuclear transcriptional and DNA repair processes. IBA annotation appropriately identifies the nucleus as the functional compartment. Reason: ESA1 participates in nuclear-localized processes (transcription, DNA repair, cell cycle). Nuclear localization is essential and well-documented.
GO:0005634 nucleus	NAS PMID:24843044 Eaf5/7/3 form a functionally independent NuA4 submodule link...	ACCEPT	Summary: NAS (narrative assertion) evidence from PMID:24843044 confirms nuclear localization. Redundant with IBA but provides independent literature support. Reason: Multiple evidence codes strengthen localization annotation. NAS documentation is appropriate for established compartment assignment. Supporting Evidence: PMID:24843044 May 19. Eaf5/7/3 form a functionally independent NuA4 submodule linked to RNA polymerase II-coupled nucleosome recycling.
GO:0004402 histone acetyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: ESA1 is the defining histone acetyltransferase of the NuA4 complex. IBA annotation captures the fundamental catalytic function through phylogenetic inference. Reason: This is ESA1's defining enzymatic function. Extensive literature demonstrates HAT activity on all conserved H4 lysines and additional histone tails. IBA reflects phylogenetic conservation of this catalytic function across eukaryotic orthologs.
GO:0004402 histone acetyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Computational inference (IEA) based on InterPro domain IPR002717 (HAT_MYST-type) independently confirms HAT activity. Reason: ESA1 contains the MYST HAT catalytic domain and has experimental HAT activity. IEA based on domain analysis is appropriate and provides independent evidence.
GO:0004402 histone acetyltransferase activity	IDA PMID:17274630 Nucleosome recognition by the Piccolo NuA4 histone acetyltra...	ACCEPT	Summary: Direct experimental evidence (IDA) from nucleosome recognition and acetyltransferase activity studies confirms HAT activity. Reason: IDA evidence from Piccolo NuA4 complex study demonstrates direct enzymatic activity on nucleosomal substrates. Multiple evidence codes strengthen this essential annotation. Supporting Evidence: PMID:17274630 Nucleosome recognition by the Piccolo NuA4 histone acetyltransferase complex.
GO:0004402 histone acetyltransferase activity	IMP PMID:10487762 NuA4, an essential transcription adaptor/histone H4 acetyltr...	ACCEPT	Summary: Mutational analysis (IMP) shows esa1 mutations abolish acetyltransferase activity in vitro and in vivo. Reason: Temperature-sensitive esa1 mutants and catalytic site mutations document HAT activity through loss-of-function studies. Supporting Evidence: PMID:10487762 NuA4, an essential transcription adaptor/histone H4 acetyltransferase complex containing Esa1p and the ATM-related cofactor Tra1p.
GO:0010485 histone H4 acetyltransferase activity	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine learning inference (IEA) identifies H4 as the primary histone substrate. This is the most mechanistically informative histone acetylation annotation. Reason: ESA1's defining activity is H4 acetylation at K5, K8, K12, K16. This specific substrate annotation is more informative than the generic GO:0004402. IEA inference is appropriate given clear mechanistic focus on H4.
GO:0010485 histone H4 acetyltransferase activity	IDA PMID:12110674 A conserved motif common to the histone acetyltransferase Es...	ACCEPT	Summary: Direct experimental evidence (IDA) from domain mutagenesis studies identifies the ESA1-RPD3 motif as essential for H4 acetyltransferase activity. Reason: IDA from PMID:12110674 provides mechanistic details through mutagenesis of specific residues (W247, N250, L251, etc.) that abolish H4 acetylation activity. This is strong experimental support for H4-specific activity. Supporting Evidence: PMID:12110674 2002 Jul 10. A conserved motif common to the histone acetyltransferase Esa1 and the histone deacetylase Rpd3.
GO:0061733 protein-lysine-acetyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Computational annotation (IEA) based on EC 2.3.1.48 mapping captures ESA1's ability to acetylate both histone and non-histone protein substrates. Reason: UniProt EC classification 2.3.1.48 directly maps to 'protein-lysine-acetyltransferase'. This formal enzymatic classification is appropriate and allows inclusion of emerging non-histone substrate functions.
GO:0061733 protein-lysine-acetyltransferase activity	IDA PMID:29765047 Tip60-mediated lipin 1 acetylation and ER translocation dete...	ACCEPT	Summary: Direct experimental evidence (IDA) demonstrates ESA1-mediated acetylation of the non-histone protein PAH1 (lipin) with functional consequences for fatty acid synthesis. Reason: IDA from PMID:29765047 documents non-histone substrate acetylation. Multiple evidence codes strengthen this broader substrate annotation. Supporting Evidence: PMID:29765047 Tip60-mediated lipin 1 acetylation and ER translocation determine triacylglycerol synthesis rate.
GO:0106226 peptide 2-hydroxyisobutyryltransferase activity	IEA GO_REF:0000116	UNDECIDED	Summary: Computational annotation (IEA) based on Rhea enzymatic reaction mapping infers 2-hydroxyisobutyryltransferase activity from homology to Tip60. However, in vivo activity in yeast is undocumented. Reason: UniProt documents potential 2-hydroxyisobutyrylation capability based on sequence homology to mammalian Tip60 (O94446), with evidence ECO:0000250 (ortholog). However: (1) Evidence is computational ortholog-based, not experimental for yeast ESA1; (2) Biological relevance in yeast unclear; (3) No literature documents in vivo 2-hydroxyisobutyrylation by ESA1 in yeast. Annotation reflects ortholog capability but lacks direct experimental support.
GO:0140064 peptide crotonyltransferase activity	IEA GO_REF:0000116	ACCEPT	Summary: Computational annotation (IEA) based on Rhea enzymatic reaction RHEA:53908 appropriately identifies crotonyl-CoA transferase activity. Reason: PMID:31699900 directly demonstrates ESA1 catalyzes histone crotonylation in vivo. Rhea mapping is appropriate for this documented biochemical activity.
GO:0140068 histone crotonyltransferase activity	IDA PMID:31699900 Gcn5 and Esa1 function as histone crotonyltransferases to re...	ACCEPT	Summary: Direct experimental evidence (IDA) from PMID:31699900 demonstrates ESA1-catalyzed histone crotonylation as a documented biochemical function. Reason: PMID:31699900 title and content explicitly establish: 'Gcn5 and Esa1 function as histone crotonyltransferases to regulate crotonylation-dependent transcription.' IDA evidence is strong and direct. Supporting Evidence: PMID:31699900 Epub 2019 Nov 7. Gcn5 and Esa1 function as histone crotonyltransferases to regulate crotonylation-dependent transcription.
GO:0016740 transferase activity	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Generic annotation identifying ESA1 as a transferase enzyme. Technically correct but overly general and subsumed by more specific acetyltransferase annotations. Reason: While accurate (acetyltransferases are transferases), this annotation is uninformative and redundant with GO:0004402 and GO:0061733. Should not be displayed as primary annotation but acceptable as ancestor term coverage.
GO:0003712 transcription coregulator activity	IBA GO_REF:0000033	ACCEPT	Summary: ESA1 as part of NuA4 functions as a transcription coregulator by acetylating histones and facilitating RNA Pol II activity. IBA annotation appropriately identifies this molecular function role. Reason: ESA1 is not a core promoter component but rather a regulatory enzyme recruited by transcription factors. It modulates transcription through chromatin remodeling - the definition of a coregulator. IBA evidence is appropriate for this conserved function.
GO:0003712 transcription coregulator activity	IDA PMID:31699900 Gcn5 and Esa1 function as histone crotonyltransferases to re...	ACCEPT	Summary: IDA evidence from crotonylation paper documents transcription coregulator function through histone modification. Multiple evidence codes strengthen this essential annotation. Reason: PMID:31699900 demonstrates ESA1-catalyzed histone modifications that regulate transcription, confirming coregulator status through mechanism. Supporting Evidence: PMID:31699900 Epub 2019 Nov 7. Gcn5 and Esa1 function as histone crotonyltransferases to regulate crotonylation-dependent transcription.
GO:0003682 chromatin binding	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Chromatin binding is plausible for ESA1 but too generic to represent a core mechanistic function. Reason: Changed from MODIFY to KEEP_AS_NON_CORE because rationale supports retention as a peripheral/general annotation rather than term replacement.
GO:0006281 DNA repair	IEA GO_REF:0000043	ACCEPT	Summary: ESA1 is required for DNA double-strand break repair through H4 acetylation enabling repair machinery accessibility. IEA annotation based on UniProt 'DNA repair' keyword is appropriate. Reason: PMID:12353039 provides strong experimental evidence for DNA repair requirement. IEA from keyword is conservative but appropriate for this well-documented function.
GO:0006281 DNA repair	IMP PMID:12353039 Acetylation of histone H4 by Esa1 is required for DNA double...	ACCEPT	Summary: Mutational analysis (IMP) directly demonstrates that esa1 mutations result in DNA repair defects. This is the strongest evidence for DNA repair function. Reason: PMID:12353039 shows temperature-sensitive esa1 mutants are defective in both nonhomologous end joining and replication-coupled repair. Mutational analysis provides definitive functional proof. Supporting Evidence: PMID:12353039 Acetylation of histone H4 by Esa1 is required for DNA double-strand break repair.
GO:0006281 DNA repair	IDA PMID:16135807 Regulation of NuA4 histone acetyltransferase activity in tra...	ACCEPT	Summary: IDA evidence from phosphorylation regulation study documents NuA4/ESA1 involvement in DNA repair. Multiple evidence codes strengthen this critical annotation. Reason: PMID:16135807 'Regulation of NuA4 histone acetyltransferase activity in transcription and DNA repair' documents functional role through direct experimental analysis. Supporting Evidence: PMID:16135807 Regulation of NuA4 histone acetyltransferase activity in transcription and DNA repair by phosphorylation of histone H4.
GO:0006281 DNA repair	IGI PMID:25628362 A moonlighting metabolic protein influences repair at DNA do...	ACCEPT	Summary: Genetic interaction (IGI) evidence documents functional relationship between ESA1 and DNA repair machinery components. Reason: IGI evidence provides functional validation of repair requirement. However, IMP evidence from PMID:12353039 is more direct. Supporting Evidence: PMID:25628362 2015 Jan 27. A moonlighting metabolic protein influences repair at DNA double-stranded breaks.
GO:0006974 DNA damage response	IEA GO_REF:0000043	ACCEPT	Summary: ESA1 is specifically recruited to DNA damage sites and activated in response to DSBs. IEA annotation from UniProt 'DNA damage' keyword is appropriate. Reason: PMID:12353039 and other literature show Arp4 component of NuA4 is recruited to DSBs and ESA1 activity is required for repair response. This is a well-documented DNA damage response function.
GO:0006325 chromatin organization	IEA GO_REF:0000043	ACCEPT	Summary: Histone acetylation fundamentally alters chromatin structure by disrupting histone-DNA contacts and affecting nucleosome positioning. ESA1-catalyzed acetylation contributes to chromatin organization. Reason: Histone acetylation is a key mechanism for chromatin remodeling and nucleosome organization. IEA inference from 'chromatin' keyword is appropriate for this mechanistic consequence of HAT activity.
GO:0006351 DNA-templated transcription	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: While ESA1 does affect transcription through chromatin modifications, it is not a core transcription component. This annotation inappropriately suggests ESA1 performs transcription rather than regulating it. Reason: Annotation is not incorrect but lacks specificity and may be misleading. ESA1's role is regulatory (GO:0006357, GO:0032968), not core transcriptional machinery (GO:0006351). IEA inference from UniProt 'Chromatin' and 'DNA repair' keywords led to automatic broad annotation. Prefer more specific regulatory terms.
GO:0006351 DNA-templated transcription	NAS PMID:24843044 Eaf5/7/3 form a functionally independent NuA4 submodule link...	KEEP AS NON CORE	Summary: NAS evidence from PMID:24843044 documents ESA1 participation in DNA-templated transcription as narrative assertion. However, ESA1 is a regulatory component rather than core transcriptional machinery. Reason: ESA1 affects transcription through histone acetylation and chromatin modification, not as a core transcriptional component. More specific regulatory terms (GO:0006357 Pol II transcription regulation) are more informative. Retain as non-core for completeness. Supporting Evidence: PMID:24843044 May 19. Eaf5/7/3 form a functionally independent NuA4 submodule linked to RNA polymerase II-coupled nucleosome recycling.
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000002	ACCEPT	Summary: ESA1 regulates transcription initiation and maintenance through chromatin acetylation. InterPro-based inference is appropriate for this regulatory role. Reason: This annotation correctly distinguishes ESA1's regulatory role from core transcription machinery. IEA from InterPro domain analysis is appropriate.
GO:0006357 regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	ACCEPT	Summary: ESA1-containing NuA4 complex is recruited to Pol II genes and regulates transcription. IBA annotation captures this core biological function through phylogenetic inference. Reason: Extensive literature demonstrates NuA4 recruitment to Pol II-transcribed genes, acetylation of promoter and coding region nucleosomes, and requirement for normal transcription initiation and elongation. This is a well-established and essential function. IBA evidence reflects phylogenetic conservation across eukaryotes.
GO:0006357 regulation of transcription by RNA polymerase II	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine learning inference (IEA) independently confirms Pol II transcription regulation function. Duplicate annotation with IBA provides computational confirmation. Reason: Both IBA and IEA converge on this annotation, providing confidence. IEA from ARBA model is appropriate.
GO:0006357 regulation of transcription by RNA polymerase II	IMP PMID:11036083 The yeast NuA4 and Drosophila MSL complexes contain homologo...	ACCEPT	Summary: Mutational analysis (IMP) documents that esa1 is required for Pol II transcription regulation. This is strong experimental support for transcription function. Reason: PMID:11036083 demonstrates through functional analysis that NuA4/ESA1 is required for transcription regulation. Multiple evidence codes strengthen this essential annotation. Supporting Evidence: PMID:11036083 Oct 17. The yeast NuA4 and Drosophila MSL complexes contain homologous subunits important for transcription regulation.
GO:0006354 DNA-templated transcription elongation	IDA PMID:15949446 Dynamic lysine methylation on histone H3 defines the regulat...	ACCEPT	Summary: Direct experimental evidence (IDA) documents ESA1 involvement in transcription elongation through interplay with H3 methylation marks. Reason: PMID:15949446 documents dynamic lysine acetylation patterns during transcription elongation. This is a specific and important ESA1 function distinct from initiation. Supporting Evidence: PMID:15949446 Dynamic lysine methylation on histone H3 defines the regulatory phase of gene transcription.
GO:0006354 DNA-templated transcription elongation	IMP PMID:15949446 Dynamic lysine methylation on histone H3 defines the regulat...	ACCEPT	Summary: Mutational/functional analysis (IMP) documents ESA1 is required for transcription elongation as distinct from initiation. Reason: IMP evidence strengthens this specific annotation. Multiple evidence codes document elongation-specific function. Supporting Evidence: PMID:15949446 Dynamic lysine methylation on histone H3 defines the regulatory phase of gene transcription.
GO:0032968 positive regulation of transcription elongation by RNA polymerase II	IMP PMID:19822662 NuA4 lysine acetyltransferase Esa1 is targeted to coding reg...	ACCEPT	Summary: ESA1 positively stimulates transcription elongation through H4 acetylation. IMP evidence is strong and specific. Reason: PMID:19822662 is explicit: 'NuA4 lysine acetyltransferase Esa1 is targeted to coding regions and stimulates transcription elongation with Gcn5.' This is more specific and informative than generic transcription regulation. Supporting Evidence: PMID:19822662 Oct 12. NuA4 lysine acetyltransferase Esa1 is targeted to coding regions and stimulates transcription elongation with Gcn5.
GO:0032968 positive regulation of transcription elongation by RNA polymerase II	IGI PMID:19822662 NuA4 lysine acetyltransferase Esa1 is targeted to coding reg...	ACCEPT	Summary: Genetic interaction evidence (IGI) provides additional functional confirmation of ESA1's elongation stimulation role. Reason: IGI from same paper as IMP documents genetic evidence for elongation function. Supporting Evidence: PMID:19822662 Oct 12. NuA4 lysine acetyltransferase Esa1 is targeted to coding regions and stimulates transcription elongation with Gcn5.
GO:0010629 negative regulation of gene expression	IEA GO_REF:0000117	REMOVE	Summary: ESA1/NuA4 is documented as a POSITIVE regulator of transcription, not negative. This annotation appears to be an artifact of ARBA ML misclassification and is contradicted by the primary literature. Reason: Literature overwhelmingly documents NuA4 as a transcriptional ACTIVATOR and POSITIVE regulator. PMID:10835360 'Activation domain-specific...transcription stimulation'; PMID:15175650 'Recruitment...poises...for...activation'; PMID:19822662 'stimulates transcription elongation'. While ESA1 may have indirect negative effects on some genes through complex silencing mechanisms (PMID:16436512), the primary and direct documented role is POSITIVE regulation. The 'negative regulation' annotation appears to be an algorithmic error in ARBA machine learning model.
GO:0035267 NuA4 histone acetyltransferase complex	IEA GO_REF:0000117	ACCEPT	Summary: ESA1 is the catalytic subunit and core component of the NuA4 complex. ARBA inference appropriately identifies complex membership. Reason: ESA1 is essential for NuA4 assembly and catalysis - it is the catalytic heart of the complex. This is a fundamental annotation.
GO:0035267 NuA4 histone acetyltransferase complex	IDA PMID:15485911 The Yaf9 component of the SWR1 and NuA4 complexes is require...	ACCEPT	Summary: IDA evidence from Yaf9 paper documents ESA1 as core NuA4 component. Multiple evidence codes strengthen complex membership annotation. Reason: PMID:15485911 'The Yaf9 component of the SWR1 and NuA4 complexes is required for proper gene expression' confirms ESA1 as NuA4 component through protein interaction and functional analysis. Supporting Evidence: PMID:15485911 The Yaf9 component of the SWR1 and NuA4 complexes is required for proper gene expression, histone H4 acetylation, and Htz1 replacement near telomeres.
GO:0035267 NuA4 histone acetyltransferase complex	IDA PMID:10911987 Multiple links between the NuA4 histone acetyltransferase co...	ACCEPT	Summary: IDA evidence from foundational NuA4 characterization paper documents ESA1 as core complex component. Reason: PMID:10911987 is a landmark paper establishing NuA4 complex composition including ESA1. Provides comprehensive evidence for complex membership. Supporting Evidence: PMID:10911987 Multiple links between the NuA4 histone acetyltransferase complex and epigenetic control of transcription.
GO:0032777 piccolo histone acetyltransferase complex	IDA PMID:12782659 Yeast enhancer of polycomb defines global Esa1-dependent ace...	ACCEPT	Summary: ESA1 is also a component of the Piccolo-NuA4 complex variant. IDA evidence documents this complex variant membership. Reason: PMID:12782659 'Yeast enhancer of polycomb defines global Esa1-dependent acetylation of chromatin' identifies the Epl1-containing Piccolo NuA4 as a NuA4 variant. ESA1 serves as catalytic subunit in both NuA4 and Piccolo NuA4 complexes. Supporting Evidence: PMID:12782659 Yeast enhancer of polycomb defines global Esa1-dependent acetylation of chromatin.