HDA1

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 
  forming a functional complex with non-catalytic subunits HDA2 and HDA3. HDA1 
  exhibits distinct substrate specificity from the Class I deacetylase RPD3, 
  preferentially targeting histone H2B and H3 (particularly H3 acetylation) 
  rather than H4. As a component of the HDA1 complex, Hda1p catalyzes 
  zinc-dependent hydrolytic deacetylation of acetylated lysine residues on 
  chromatin, regulating gene silencing, chromatin organization, and 
  transcriptional repression particularly at H3/H2B-specific loci. The enzyme 
  requires zinc as an essential structural and catalytic cofactor, 
  distinguishing it mechanistically from NAD-dependent sirtuins like HST2.
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.
- 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: HDA2 and HDA3 are related proteins that interact with and
        are essential for the activity of the yeast histone deacetylase HDA1.
    - reference_id: PMID:19573535
      supporting_text: 2009 Jun 30. Structural and functional studies of the 
        yeast class II Hda1 histone deacetylase complex.
- 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
- 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
- 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.
- 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.
- 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.
- 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.
- 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). Correct 
      mechanistic classification for HDA1.
    action: ACCEPT
    reason: HDA1 catalyzes a hydrolytic reaction - acetylated lysine and water 
      are converted to lysine and acetate. This is the fundamental chemical 
      mechanism of histone deacetylases. The EC number 3.5.1.98 classifies HDA1 
      as a hydrolase. This parent-level molecular function term appropriately 
      captures HDA1's enzymatic mechanism. More specific molecular function 
      terms (GO:0004407, GO:0141221) provide additional specificity.
    supported_by:
    - reference_id: GO_REF:0000043
      supporting_text: Gene Ontology annotation based on UniProtKB/Swiss-Prot 
        keyword mapping
- 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
- 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
- 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
- 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
- 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
- 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
- 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: HDA2 and HDA3 are related proteins that interact with and
        are essential for the activity of the yeast histone deacetylase HDA1.
- 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
- 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
- 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: HDA2 and HDA3 are related proteins that interact with and
        are essential for the activity of the yeast histone deacetylase HDA1.
- 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 is 
      confirmed as zinc-binding protein.
    action: ACCEPT
    reason: HDA1 binds zinc as an essential structural and catalytic cofactor 
      required for deacetylase activity. The RCA evidence from PMID:30358795 
      (The Saccharomyces cerevisiae zinc proteome) provides reviewed 
      computational and/or experimental evidence that HDA1 is a zinc-binding 
      protein. Zinc coordination in Class II HDACs is well-characterized through
      structural biology. This annotation is correct and mechanistically 
      important.
    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.
- 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
- 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 mutant study examining histone acetylation role
      in transcription activation.
    action: ACCEPT
    reason: PMID:17121596 examines the role of HDA1 in controlling histone 
      acetylation status and its effects on transcriptional regulation. 
      HDA1-mediated deacetylation of histones results in transcriptional 
      repression of target genes. This provides independent experimental support
      for HDA1's negative regulation of transcription function.
    supported_by:
    - reference_id: PMID:17121596
      supporting_text: H4 acetylation does not replace H3 acetylation in 
        chromatin remodelling and transcription activation of Adr1-dependent 
        genes
- 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
- 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.
- 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.
- 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
- 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
- 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.
- 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
- 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
core_functions:
- molecular_function:
    id: GO:0004407
    label: histone deacetylase activity
  description: Zinc-dependent hydrolytic deacetylation of acetylated lysine 
    residues on histone proteins, particularly histones H3 and H2B
  supported_by:
  - reference_id: PMID:19573535
    supporting_text: Structural and functional studies demonstrate yeast class 
      II Hda1 histone deacetylase complex catalyzes histone deacetylation
    full_text_unavailable: true
- molecular_function:
    id: GO:0141221
    label: histone deacetylase activity, hydrolytic mechanism
  description: Class II zinc-dependent histone deacetylase activity 
    distinguishing HDA1 from NAD-dependent sirtuins through hydrolytic catalytic
    mechanism
  supported_by:
  - reference_id: PMID:19573535
    supporting_text: HDA1 catalyzes hydrolytic deacetylation with zinc cofactor
    full_text_unavailable: true
- molecular_function:
    id: GO:0003682
    label: chromatin binding
  description: Direct association with chromatin to access histone substrates 
    and regulate transcription
  supported_by:
  - reference_id: PMID:19573535
    supporting_text: The N-terminal halves of HDA2 and HDA3 serve as DNA-binding
      modules for chromatin association
    full_text_unavailable: true
- molecular_function:
    id: GO:0008270
    label: zinc ion binding
  description: Zinc cofactor binding essential for catalytic activity and 
    structural stability of the deacetylase domain
  supported_by:
  - reference_id: PMID:30358795
    supporting_text: HDA1 is a zinc-binding protein in the cellular zinc 
      proteome
    full_text_unavailable: true
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: []