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
  - 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
  - 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
  - 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
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: []