id: P53973
gene_symbol: HDA1
aliases:
- YNL021W
- N2819
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: Histone deacetylase HDA1 (Hda1p) is a Class II zinc-dependent HDAC and the
  catalytic subunit of the nuclear HDA1 complex with HDA2 and HDA3. The complex
  catalyzes hydrolytic deacetylation of acetylated lysines on chromatin, with
  well-supported H3/H2B promoter-proximal activity and context-dependent H4
  deacetylation in highly transcribed gene bodies. HDA1 controls chromatin acetylation
  states to regulate epigenetic gene expression, chromatin organization, and
  predominantly RNA polymerase II transcriptional repression or dampening. Cytoplasmic
  localization, generic binding/hydrolase terms, and positive transcriptional effects
  should be treated as non-core or overly broad unless tied to specific evidence.
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: IBA annotation based on phylogenetic inference from HDAC orthologs. HDA1 is
      part of a nuclear chromatin-associated complex, not primarily cytoplasmic.
    action: REMOVE
    reason: HDA1 functions in chromatin deacetylation in the nucleus. While the IBA
      annotation infers cytoplasmic localization from orthologs, experimental evidence
      establishes HDA1 as a nuclear protein component of chromatin-associated histone
      deacetylase complexes. Nuclear localization is documented in multiple experimental
      studies examining HDA1's function in transcriptional repression and chromatin
      organization. The cytoplasmic annotation appears to be a phylogenetic inference
      artifact.
    supported_by:
    - reference_id: PMID:8663039
      supporting_text: HDA1 and HDA3 are components of a yeast histone deacetylase (HDA)
        complex.
    - reference_id: PMID:19573535
      supporting_text: 2009 Jun 30. Structural and functional studies of the yeast class
        II Hda1 histone deacetylase complex.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: 'No direct evidence for Hda1; cytosolic relocalization reported for
        Hda2/Hda3 under hypoxia, not Hda1'
- term:
    id: GO:0040029
    label: epigenetic regulation of gene expression
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: IBA annotation through phylogenetic conservation of HDAC function in
      epigenetic regulation. Well-supported core function.
    action: ACCEPT
    reason: HDA1 catalyzes histone deacetylation, a primary epigenetic modification
      mechanism. HDA1's role in regulating chromatin acetylation status directly
      controls gene expression through chromatin remodeling. This is a phylogenetically
      conserved function well-documented for Class II HDACs. The IBA annotation
      appropriately reflects HDA1's core biological role in epigenetic gene regulation.
    supported_by:
    - reference_id: PMID:11287668
      supporting_text: is likely the catalytic subunit of the HDA1-containing complex
        that is involved in TUP1-specific repression and global deacetylation in yeast.
    - reference_id: PMID:19573535
      supporting_text: 2009 Jun 30. Structural and functional studies of the yeast class
        II Hda1 histone deacetylase complex.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: At PHO5 and adjacent ORFs, deletion of HDA1 increases acetylation
        across a multi-kb region, consistent with domain-wide chromatin regulation
        influencing basal transcriptional states.
- term:
    id: GO:0000118
    label: histone deacetylase complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: IBA annotation through phylogenetic conservation confirming HDA1 as
      structural component of HDAC complex.
    action: ACCEPT
    reason: HDA1 is the catalytic core subunit of the yeast Class II HDA1 complex, which
      also includes non-catalytic subunits HDA2 and HDA3. The HDA1 complex is a
      well-characterized functional unit. IBA inference from HDAC complex orthologs
      appropriately identifies HDA1's complex assembly and localization.
    supported_by:
    - reference_id: PMID:8663039
      supporting_text: HDA1 and HDA3 are components of a yeast histone deacetylase (HDA)
        complex
    - reference_id: PMID:11287668
      supporting_text: HDA2 and HDA3 are related proteins that interact with and are
        essential for the activity of the yeast histone deacetylase HDA1
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Hda1 functions in a multi-subunit histone deacetylase complex
        with Hda2 and Hda3, where Hda2/Hda3 are required for full Hda1 activity and
        targeting.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: IEA annotation based on UniProtKB Subcellular Location mapping. Correct,
      consistent with multiple experimental studies.
    action: ACCEPT
    reason: HDA1 localizes to the nucleus where it functions in chromatin deacetylation
      and transcriptional repression. While based on automated mapping from UniProt
      keywords, this annotation is consistently supported by experimental evidence
      showing HDA1's nuclear localization and function in nuclear chromatin regulation.
    supported_by:
    - reference_id: GO_REF:0000044
      supporting_text: Gene Ontology annotation based on UniProtKB/Swiss-Prot
        Subcellular Location vocabulary mapping
    - reference_id: PMID:16415367
      supporting_text: Suppressor analysis of a histone defect identifies a new function
        for the hda1 complex in chromosome segregation
    - reference_id: file:yeast/HDA1/HDA1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Nucleus.'
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: ChIP-qPCR/ChIP-seq shows Hda1 occupancy at promoters and coding
        regions of highly transcribed genes, consistent with nuclear localization and
        chromatin association.
- term:
    id: GO:0006325
    label: chromatin organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: IEA annotation based on UniProtKB keyword mapping. Supported by HDA1's
      documented role in chromatin structure.
    action: ACCEPT
    reason: HDA1's histone deacetylase activity directly affects chromatin organization
      through modification of histone acetylation status. Histone deacetylation promotes
      chromatin condensation and heterochromatin formation. This is an appropriate
      parent-level biological process annotation capturing HDA1's fundamental role in
      chromatin structure regulation.
    supported_by:
    - reference_id: PMID:19573535
      supporting_text: 2009 Jun 30. Structural and functional studies of the yeast class
        II Hda1 histone deacetylase complex.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: At PHO5 and adjacent ORFs, deletion of HDA1 increases acetylation
        across a multi-kb region, consistent with domain-wide chromatin regulation
        influencing basal transcriptional states.
- term:
    id: GO:0006351
    label: DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: IEA annotation based on UniProtKB keyword mapping. HDA1 does not directly
      catalyze transcription but modulates it through chromatin remodeling.
    action: MODIFY
    reason: HDA1 does not directly catalyze DNA-templated transcription. Rather, HDA1
      modulates transcription by altering chromatin structure through histone
      deacetylation, typically resulting in transcriptional repression. A more accurate
      annotation would be negative regulation of transcription or regulation of
      transcription. The direct transcription process term is mechanistically
      inaccurate.
    proposed_replacement_terms:
    - id: GO:0000122
      label: negative regulation of transcription by RNA polymerase II
    - id: GO:0006355
      label: regulation of DNA-templated transcription
    additional_reference_ids:
    - PMID:11287668
    supported_by:
    - reference_id: PMID:11287668
      supporting_text: HDA2 and HDA3 are related proteins that interact with and are
        essential for the activity of the yeast histone deacetylase HDA1.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Tup1 recruits Hda1 for localized histone deacetylation and
        repression at ENA1 and other genes
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: The dominant evidence supports repression/dampening via
        deacetylation.
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: IEA from ARBA machine learning model. Appropriate for HDA1's regulatory
      function in transcription.
    action: ACCEPT
    reason: HDA1 regulates transcription through its deacetylase activity on chromatin.
      This parent-level process term appropriately captures HDA1's role in
      transcriptional control. While HDA1 typically functions as a transcriptional
      repressor, the broader "regulation of transcription" captures its functional role
      without overspecifying mechanism.
    supported_by:
    - reference_id: PMID:11287668
      supporting_text: HDA2 and HDA3 are related proteins that interact with and are
        essential for the activity of the yeast histone deacetylase HDA1.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Strong experimental evidence supports chromatin association,
        histone-tail deacetylation (H2B/H3 and context-dependent H4), and
        transcriptional repression.
- term:
    id: GO:0010557
    label: positive regulation of macromolecule biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: IEA annotation from ARBA. HDA1's primary documented role is transcriptional
      repression, not positive regulation.
    action: REMOVE
    reason: This annotation is mechanistically inconsistent with HDA1's documented
      function. HDA1 catalyzes histone deacetylation that typically promotes gene
      silencing and heterochromatin formation, resulting in negative regulation of
      transcription and suppression of biosynthetic processes. While HDA1 might
      positively regulate transcription at specific loci in particular cellular
      contexts, the predominant and well-characterized mechanism is transcriptional
      repression. The ARBA inference appears to contradict experimental evidence for
      HDA1's core function.
    supported_by:
    - reference_id: PMID:11287668
      supporting_text: HDA2 and HDA3 are related proteins that interact with and are
        essential for the activity of the yeast histone deacetylase HDA1.
    - reference_id: PMID:11172717
      supporting_text: TUP1 utilizes histone H3/H2B-specific HDA1 deacetylase to repress
        gene activity in yeast.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: The dominant evidence supports repression/dampening via
        deacetylation.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Genome-wide data do note rare loci with paradoxical expression
        changes in hda1 mutants, but these are more consistent with indirect effects or
        pathway interactions than direct activation.
- term:
    id: GO:0016787
    label: hydrolase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: IEA annotation based on UniProtKB keyword hydrolase. Chemically true for
      HDACs, but too broad for HDA1 because specific histone deacetylase terms are
      available.
    action: MODIFY
    reason: HDA1 catalyzes hydrolytic deacetylation, so hydrolase is not wrong, but the
      term is too general to be informative for GO curation. The evidence supports the
      specific histone lysine deacetylase activity, especially the hydrolytic mechanism
      term GO:0141221, rather than a generic hydrolase parent.
    supported_by:
    - reference_id: GO_REF:0000043
      supporting_text: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword
        mapping
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: 'Too broad; evidence is specific for histone lysine deacetylase/HDAC
        activity rather than generic hydrolase'
    proposed_replacement_terms:
    - id: GO:0141221
      label: histone deacetylase activity, hydrolytic mechanism
    - id: GO:0004407
      label: histone deacetylase activity
- term:
    id: GO:0141221
    label: histone deacetylase activity, hydrolytic mechanism
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: IEA annotation from RHEA/EC number mapping. Precise molecular function
      annotation for HDA1.
    action: ACCEPT
    reason: GO:0141221 is a more specific child term of histone deacetylase activity
      that explicitly specifies the hydrolytic deacetylation mechanism (as opposed to
      NAD-dependent deacetylation used by sirtuins). This correctly distinguishes HDA1
      as a Class II zinc-dependent hydrolytic HDAC. The RHEA mapping to EC 3.5.1.98 is
      mechanistically accurate. This is the most informative molecular function
      annotation for HDA1's core enzymatic activity.
    supported_by:
    - reference_id: GO_REF:0000120
      supporting_text: Combined Automated Annotation using Multiple IEA Methods with
        RHEA:58196 and EC:3.5.1.98
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Structural/mechanistic analysis places Hda1 in the Zn2+-dependent
        Rpd3/Hda1 family; TSA-sensitive HDAC complex reconstituted
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11287668
  review:
    summary: IPI annotation indicating interaction with Q06623 (HDA2). Generic protein
      binding term.
    action: REMOVE
    reason: Following curation guidelines, generic 'protein binding' terms should be
      replaced with more informative molecular function annotations that specify the
      functional consequence of the interaction. HDA1's interaction with HDA2 is
      documented in GO:0000118 (histone deacetylase complex) and GO:0070823 (HDA1
      complex), which more precisely capture HDA1's role as a complex component. The
      protein binding annotation does not inform about what specific function this
      binding enables or supports.
    supported_by:
    - reference_id: PMID:11287668
      supporting_text: HDA2 and HDA3 are related proteins that interact with and are
        essential for the activity of the yeast histone deacetylase HDA1
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: 'Some support for Hda1 self-interaction and partner binding, but broad
        GO terms are less informative than complex membership'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16429126
  review:
    summary: IPI annotation from proteome survey. Generic protein binding with
      unspecified partner.
    action: REMOVE
    reason: Generic protein binding annotation. The associated reference PMID:16429126
      appears to be a proteome-wide interaction survey with unspecified interaction
      partners. Without specific functional relevance of the binding partner, this
      annotation provides minimal informational value. More specific molecular function
      terms already capture HDA1's functionally relevant protein interactions.
    supported_by:
    - reference_id: PMID:16429126
      supporting_text: Proteome survey reveals modularity of the yeast cell machinery
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: 'Some support for Hda1 self-interaction and partner binding, but broad
        GO terms are less informative than complex membership'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16554755
  review:
    summary: IPI annotation from global landscape of protein complexes. Generic binding
      annotation.
    action: REMOVE
    reason: Generic protein binding from high-throughput interaction data. This
      annotation lacks specificity regarding functional consequence of binding. HDA1's
      documented complex assembly and chromatin binding are captured more precisely by
      other annotations (GO:0003682 chromatin binding, GO:0070823 HDA1 complex).
    supported_by:
    - reference_id: PMID:16554755
      supporting_text: Global landscape of protein complexes in the yeast Saccharomyces
        cerevisiae
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: 'Some support for Hda1 self-interaction and partner binding, but broad
        GO terms are less informative than complex membership'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21179020
  review:
    summary: IPI annotation from budding yeast chromatin-associated interactome study.
    action: REMOVE
    reason: Generic protein binding annotation without specification of interaction
      partner or functional relevance. HDA1's chromatin-associated function is more
      precisely captured by GO:0003682 (chromatin binding) annotation already present.
      This generic term provides redundant and less informative coverage.
    supported_by:
    - reference_id: PMID:21179020
      supporting_text: Defining the budding yeast chromatin-associated interactome
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: 'Some support for Hda1 self-interaction and partner binding, but broad
        GO terms are less informative than complex membership'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37968396
  review:
    summary: IPI annotation from social architecture of yeast interactome.
    action: REMOVE
    reason: Generic protein binding from large-scale interaction mapping. The annotation
      does not specify functional consequence or identify the interaction partner.
      Functionally relevant annotations (GO:0070823 HDA1 complex, GO:0003682 chromatin
      binding) more precisely capture HDA1's binding interactions. This generic
      annotation should be removed following best practices to avoid uninformative
      molecular function terms.
    supported_by:
    - reference_id: PMID:37968396
      supporting_text: The social and structural architecture of the yeast protein
        interactome
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: 'Some support for Hda1 self-interaction and partner binding, but broad
        GO terms are less informative than complex membership'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:11287668
  review:
    summary: IPI annotation indicating HDA1 homodimer formation or self-association.
    action: KEEP_AS_NON_CORE
    reason: HDA1 can form homodimers or oligomers, but the predominant and functionally
      essential interaction is with HDA2/HDA3 subunits to form the catalytically active
      HDA1 complex. Homodimerization may represent a secondary or non-functional
      interaction. The annotation is likely correct but represents a non-core molecular
      interaction. The HDA1 complex assembly with heteromeric partners (GO:0070823) is
      the primary functional assembly.
    supported_by:
    - reference_id: PMID:11287668
      supporting_text: HDA1 interacts with itself and with the HDA2-HDA3 subcomplex to
        form a likely tetramer.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: 'Some support for Hda1 self-interaction and partner binding, but broad
        GO terms are less informative than complex membership'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:18719252
  review:
    summary: IPI annotation from high-quality binary protein interaction map.
    action: KEEP_AS_NON_CORE
    reason: This annotation documents HDA1 self-association or homodimer formation
      detected in systematic yeast interactome mapping. While the interaction is likely
      genuine, homodimerization is not the predominant functional assembly compared to
      the essential HDA1-HDA2-HDA3 complex. This represents a secondary molecular
      interaction, not a core function.
    supported_by:
    - reference_id: PMID:18719252
      supporting_text: High-quality binary protein interaction map of the yeast
        interactome network
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: 'Some support for Hda1 self-interaction and partner binding, but broad
        GO terms are less informative than complex membership'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:21179020
  review:
    summary: IPI annotation from chromatin-associated interactome study.
    action: KEEP_AS_NON_CORE
    reason: HDA1 self-interaction documented in chromatin-associated protein interaction
      study. While potentially real, homodimerization is not characterized as essential
      or functionally distinct from the core HDA1 complex assembly with HDA2/HDA3. Mark
      as non-core peripheral interaction.
    supported_by:
    - reference_id: PMID:21179020
      supporting_text: Defining the budding yeast chromatin-associated interactome
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: 'Some support for Hda1 self-interaction and partner binding, but broad
        GO terms are less informative than complex membership'
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:11287668
  review:
    summary: IDA annotation documenting transcriptional repression function of HDA1.
    action: ACCEPT
    reason: PMID:11287668 provides direct evidence that HDA1 mediates transcriptional
      repression through its deacetylase activity. HDA1's histone deacetylation promotes
      heterochromatin formation and represses transcription at target loci. This is a
      core biological process function well-supported by direct experimental evidence
      and represents one of HDA1's primary functional roles.
    supported_by:
    - reference_id: PMID:11287668
      supporting_text: is likely the catalytic subunit of the HDA1-containing complex
        that is involved in TUP1-specific repression and global deacetylation in yeast.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Tup1 recruits Hda1 for localized histone deacetylation and
        repression at ENA1 and other genes
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: RCA
  original_reference_id: PMID:30358795
  review:
    summary: RCA annotation from systematic zinc proteome study. HDA1 zinc binding is
      mechanistically important for the zinc-dependent HDAC fold but is not the core
      activity itself.
    action: KEEP_AS_NON_CORE
    reason: Class II HDAC catalysis depends on zinc coordination, so the annotation is
      biochemically plausible and supported by zinc-proteome and HDAC-family evidence.
      However, zinc ion binding is an enabling cofactor interaction rather than HDA1's
      main evolved activity; the core function is hydrolytic histone deacetylase
      activity within chromatin-associated HDA1C.
    supported_by:
    - reference_id: PMID:30358795
      supporting_text: The cellular economy of the Saccharomyces cerevisiae zinc
        proteome.
    - reference_id: PMID:19573535
      supporting_text: 2009 Jun 30. Structural and functional studies of the yeast class
        II Hda1 histone deacetylase complex.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Structural/mechanistic analysis places Hda1 in the Zn2+-dependent
        Rpd3/Hda1 family; TSA-sensitive HDAC complex reconstituted
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:11172717
  review:
    summary: IMP annotation from mutant phenotype study. HDA1 deletion/mutation results
      in derepression of normally silenced genes.
    action: ACCEPT
    reason: PMID:11172717 provides direct evidence that HDA1 negatively regulates RNA
      Pol II transcription. Mutations affecting HDA1 result in transcriptional
      derepression at H3/H2B-specific loci, confirming HDA1's role as a transcriptional
      repressor. IMP evidence from mutant analysis is strong support for this biological
      process function. This is a core documented role for HDA1.
    supported_by:
    - reference_id: PMID:11172717
      supporting_text: TUP1 utilizes histone H3/H2B-specific HDA1 deacetylase to repress
        gene activity in yeast
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Tup1 recruits Hda1 for localized histone deacetylation and
        repression at ENA1 and other genes
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:17121596
  review:
    summary: IMP annotation from a study of histone acetylation during
      Adr1-dependent transcription activation; accessible abstract does not mention
      HDA1.
    action: UNDECIDED
    reason: The cached abstract for PMID:17121596 discusses Gcn5/Esa1-dependent
      histone acetylation changes during activation of Adr1-dependent genes, but it
      does not mention HDA1 or provide accessible evidence that an HDA1 perturbation
      causes derepression. Full text is not available in the cache, so this
      annotation should remain undecided rather than accepted as HDA1-specific
      negative regulation of RNA polymerase II transcription.
    supported_by:
    - reference_id: PMID:17121596
      supporting_text: In cells lacking Gcn5 activity, the H3 acetylation increase
        does not occur and an unexpected increase of histone H4 acetylation is
        observed.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IGI
  original_reference_id: PMID:17974563
  review:
    summary: IGI annotation showing genetic interaction in transcriptional control.
    action: ACCEPT
    reason: IGI annotation indicating genetic interaction at promoters where HDA1 and
      other factors coordinate transcriptional regulation. PMID:17974563 references a
      poised initiation complex activated by SNF1, with HDA1 functioning in coordination
      with other chromatin regulators. While less direct than IDA/IMP, IGI evidence
      supports HDA1's role in negative transcriptional regulation through pathway
      analysis.
    supported_by:
    - reference_id: PMID:17974563
      supporting_text: A poised initiation complex is activated by SNF1
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Tup1 recruits Hda1 for localized histone deacetylation and
        repression at ENA1 and other genes
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: IDA
  original_reference_id: PMID:16415367
  review:
    summary: IDA annotation documenting direct chromatin association of HDA1.
    action: ACCEPT
    reason: PMID:16415367 provides direct experimental evidence that HDA1 binds
      chromatin. The study identifying suppression of histone defects by the HDA1
      complex demonstrates direct physical association between HDA1 and chromatin. This
      is a fundamental molecular function reflecting HDA1's mechanism - the complex must
      associate with chromatin to access histone substrates for deacetylation.
    supported_by:
    - reference_id: PMID:16415367
      supporting_text: Jan 16. Suppressor analysis of a histone defect identifies a new
        function for the hda1 complex in chromosome segregation.
    - reference_id: PMID:19573535
      supporting_text: 2009 Jun 30. Structural and functional studies of the yeast class
        II Hda1 histone deacetylase complex.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: ChIP-qPCR/ChIP-seq shows Hda1 occupancy at promoters and coding
        regions of highly transcribed genes, consistent with nuclear localization and
        chromatin association.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Hda1 functions in a multi-subunit histone deacetylase complex
        with Hda2 and Hda3, where Hda2/Hda3 are required for full Hda1 activity and
        targeting.
- term:
    id: GO:0004407
    label: histone deacetylase activity
  evidence_type: IDA
  original_reference_id: PMID:19573535
  review:
    summary: IDA annotation of core enzymatic activity from structural and functional
      characterization.
    action: ACCEPT
    reason: PMID:19573535 provides structural and functional characterization of
      purified, recombinant HDA1 complex with direct enzymatic assays demonstrating
      histone deacetylase activity. This is the canonical molecular function of HDA1.
      IDA evidence from direct enzyme kinetics and structural determination is the
      highest quality evidence for this core activity. This annotation is central to
      HDA1's identity.
    supported_by:
    - reference_id: PMID:19573535
      supporting_text: 2009 Jun 30. Structural and functional studies of the yeast class
        II Hda1 histone deacetylase complex.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Strong experimental evidence supports chromatin association,
        histone-tail deacetylation (H2B/H3 and context-dependent H4), and
        transcriptional repression.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Tup1 recruits Hda1 to deacetylate histones **H3 and H2B** at
        promoter-adjacent nucleosomes (e.g., ENA1), supporting histone-substrate
        specificity and a repression mechanism.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Modern spike-in normalized ChIP-seq/ChIP-qPCR demonstrates
        Hda1C-dependent **H4 deacetylation within coding regions** of highly transcribed
        genes.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:17706600
  review:
    summary: IMP annotation suggesting HDA1 positively regulates some genes, contrasting
      with predominant repressive function.
    action: KEEP_AS_NON_CORE
    reason: PMID:17706600 (Regulation of the HAP1 gene involves positive actions of
      histone deacetylases) documents a specific context where HDA1 contributes to
      positive transcriptional regulation of HAP1. While HDA1's primary and predominant
      function is transcriptional repression, specific genes may require deacetylation
      for activation in particular cellular contexts or through specific chromatin
      domains. This represents a context-specific, non-core function of HDA1. The
      predominant role as transcriptional repressor should be emphasized in core
      functions.
    supported_by:
    - reference_id: PMID:17706600
      supporting_text: Regulation of the HAP1 gene involves positive actions of histone
        deacetylases
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Genome-wide data do note rare loci with paradoxical expression
        changes in hda1 mutants, but these are more consistent with indirect effects or
        pathway interactions than direct activation.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: The dominant evidence supports repression/dampening via
        deacetylation.
- term:
    id: GO:0070823
    label: HDA1 complex
  evidence_type: IDA
  original_reference_id: PMID:11287668
  review:
    summary: IDA annotation documenting HDA1 as component of defined HDA1 complex.
    action: ACCEPT
    reason: PMID:11287668 provides direct experimental evidence that HDA1 associates
      with HDA2 and HDA3 to form the functionally essential HDA1 complex. This is a
      well-characterized macromolecular assembly with defined composition (HDA1
      catalytic subunit + HDA2/HDA3 structural subunits). This annotation correctly
      identifies HDA1's complex membership and is supported by multiple independent
      studies establishing this assembly.
    supported_by:
    - reference_id: PMID:11287668
      supporting_text: HDA2 and HDA3 are related proteins that interact with and are
        essential for the activity of the yeast histone deacetylase HDA1
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Hda2 and Hda3 physically interact with Hda1 and are essential for
        Hda1 deacetylase activity; disruption of any subunit disrupts activity in vitro
        and in vivo.
- term:
    id: GO:0070823
    label: HDA1 complex
  evidence_type: IPI
  original_reference_id: PMID:11287668
  review:
    summary: IPI annotation documenting HDA2 as interaction partner in HDA1 complex
      assembly.
    action: ACCEPT
    reason: IPI annotation specifying HDA2 (SGD:S000006383) as direct interaction
      partner. This is redundant with but complementary to other HDA1 complex
      annotations - it specifically documents the HDA1-HDA2 interaction. Both IDA and
      IPI evidence types support HDA1 complex assembly. The redundancy strengthens
      confidence in this essential functional assembly.
    supported_by:
    - reference_id: PMID:11287668
      supporting_text: HDA2 and HDA3 are related proteins that interact with and are
        essential for the activity of the yeast histone deacetylase HDA1.
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Hda2 and Hda3 physically interact with Hda1 and are essential for
        Hda1 deacetylase activity; disruption of any subunit disrupts activity in vitro
        and in vivo.
- term:
    id: GO:0070823
    label: HDA1 complex
  evidence_type: IDA
  original_reference_id: PMID:8663039
  review:
    summary: IDA annotation from early characterization of HDA1 complex components.
    action: ACCEPT
    reason: PMID:8663039 is an early study demonstrating that HDA1 and HDA3 are
      components of a yeast histone deacetylase complex. This provides independent
      confirmation of HDA1 complex assembly from different experimental approach and
      timeframe. Multiple evidence sources for the same annotation (IDA from different
      studies) strengthen confidence in HDA1's role as a complex component.
    supported_by:
    - reference_id: PMID:8663039
      supporting_text: HDA1 and HDA3 are components of a yeast histone deacetylase (HDA)
        complex
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Hda2 and Hda3 physically interact with Hda1 and are essential for
        Hda1 deacetylase activity; disruption of any subunit disrupts activity in vitro
        and in vivo.
- term:
    id: GO:0070823
    label: HDA1 complex
  evidence_type: IDA
  original_reference_id: PMID:8962081
  review:
    summary: IDA annotation documenting functional distinctness of HDA1 complex from
      RPD3 complex.
    action: ACCEPT
    reason: PMID:8962081 demonstrates that HDA1 and RPD3 are members of distinct,
      functionally separate histone deacetylase complexes. This further supports HDA1 as
      a defined complex component and establishes its functional specialization.
      Multiple independent studies (PMID:8663039, PMID:11287668, PMID:8962081)
      consistently demonstrate HDA1's core role in the HDA1 complex assembly.
    supported_by:
    - reference_id: PMID:8962081
      supporting_text: HDA1 and RPD3 are members of distinct yeast histone deacetylase
        complexes that regulate silencing and transcription
    - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
      supporting_text: Hda2 and Hda3 physically interact with Hda1 and are essential for
        Hda1 deacetylase activity; disruption of any subunit disrupts activity in vitro
        and in vivo.
core_functions:
- molecular_function:
    id: GO:0141221
    label: histone deacetylase activity, hydrolytic mechanism
  description: Class II zinc-dependent hydrolytic histone deacetylase activity by Hda1
    as the catalytic subunit of HDA1C, deacetylating histone lysines on chromatin
    including H3/H2B promoter contexts and H4 in highly transcribed gene bodies.
  in_complex:
    id: GO:0070823
    label: HDA1 complex
  directly_involved_in:
  - id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  - id: GO:0040029
    label: epigenetic regulation of gene expression
  - id: GO:0006325
    label: chromatin organization
  locations:
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
    supporting_text: Strong experimental evidence supports chromatin association,
      histone-tail deacetylation (H2B/H3 and context-dependent H4), and transcriptional
      repression.
  - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
    supporting_text: Tup1 recruits Hda1 to deacetylate histones **H3 and H2B** at
      promoter-adjacent nucleosomes (e.g., ENA1), supporting histone-substrate
      specificity and a repression mechanism.
  - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
    supporting_text: Modern spike-in normalized ChIP-seq/ChIP-qPCR demonstrates
      Hda1C-dependent **H4 deacetylation within coding regions** of highly transcribed
      genes.
- molecular_function:
    id: GO:0003682
    label: chromatin binding
  description: Chromatin association by Hda1/HDA1C that positions the deacetylase
    complex at promoters, coding regions, and broader chromatin domains for histone-tail
    deacetylation.
  in_complex:
    id: GO:0070823
    label: HDA1 complex
  directly_involved_in:
  - id: GO:0006325
    label: chromatin organization
  locations:
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
    supporting_text: ChIP-qPCR/ChIP-seq shows Hda1 occupancy at promoters and coding
      regions of highly transcribed genes, consistent with nuclear localization and
      chromatin association.
  - reference_id: file:yeast/HDA1/HDA1-deep-research-falcon.md
    supporting_text: Hda1 functions in a multi-subunit histone deacetylase complex with
      Hda2 and Hda3, where Hda2/Hda3 are required for full Hda1 activity and targeting.
proposed_new_terms: []
suggested_questions:
- question: What is the complete set of histone tail substrates targeted by HDA1, and
    how does it differ from RPD3?
- question: Does HDA1 have preferred deacetylation sites on histone H3 and H2B, and how
    do these affect nucleosome stability and chromatin fiber structure?
- question: What are the mechanisms regulating HDA1 complex recruitment and activity at
    specific genomic loci?
- question: Does HDA1 function on non-histone substrates, and if so, with what
    specificity and functional consequence?
suggested_experiments: []
references:
- 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
  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:8663039
  title: HDA1 and HDA3 are components of a yeast histone deacetylase (HDA) complex.
  findings: []
- id: PMID:8962081
  title: HDA1 and RPD3 are members of distinct yeast histone deacetylase complexes that
    regulate silencing and transcription.
  findings: []
- id: PMID:11172717
  title: TUP1 utilizes histone H3/H2B-specific HDA1 deacetylase to repress gene activity
    in yeast.
  findings: []
- id: PMID:11287668
  title: HDA2 and HDA3 are related proteins that interact with and are essential for the
    activity of the yeast histone deacetylase HDA1.
  findings: []
- id: PMID:16415367
  title: Suppressor analysis of a histone defect identifies a new function for the hda1
    complex in chromosome segregation.
  findings: []
- id: PMID:16429126
  title: Proteome survey reveals modularity of the yeast cell machinery.
  findings: []
- id: PMID:16554755
  title: Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
  findings: []
- id: PMID:17121596
  title: H4 acetylation does not replace H3 acetylation in chromatin remodelling and
    transcription activation of Adr1-dependent genes.
  findings: []
- id: PMID:17706600
  title: Regulation of the HAP1 gene involves positive actions of histone deacetylases.
  findings: []
- id: PMID:17974563
  title: A poised initiation complex is activated by SNF1.
  findings: []
- id: PMID:18719252
  title: High-quality binary protein interaction map of the yeast interactome network.
  findings: []
- id: PMID:19573535
  title: Structural and functional studies of the yeast class II Hda1 histone
    deacetylase complex.
  findings: []
- id: PMID:21179020
  title: Defining the budding yeast chromatin-associated interactome.
  findings: []
- id: PMID:30358795
  title: The cellular economy of the Saccharomyces cerevisiae zinc proteome.
  findings: []
- id: PMID:37968396
  title: The social and structural architecture of the yeast protein interactome.
  findings: []
- id: file:yeast/HDA1/HDA1-deep-research-falcon.md
  title: Falcon deep research report for S. cerevisiae HDA1 GO annotation review
  findings: []
- id: file:yeast/HDA1/HDA1-uniprot.txt
  title: UniProtKB record for S. cerevisiae HDA1 (P53973)
  findings: []