id: P11978
gene_symbol: SIR4
aliases:
  - ASD1
  - STE9
  - UTH2
  - YDR227W
  - YD9934.12
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: Silent information regulator 4 (SIR4) is a structural component of 
  the SIR2-SIR3-SIR4 silent chromatin complex. SIR4 is an 
  architectural/scaffolding protein that lacks enzymatic activity itself 
  (deacetylase function is provided by SIR2). It serves as a bridge between the 
  silent chromatin machinery and nuclear organization, mediating interactions 
  with telomeric proteins (RAP1, YKU80) and the nuclear periphery (MPS3). SIR4 
  functions at both telomeric and mating-type loci, maintaining heterochromatin 
  through protein-protein interactions and DNA binding rather than catalytic 
  mechanisms.
existing_annotations:
  - term:
      id: GO:0003677
      label: DNA binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: IEA annotation based on UniProtKB keyword mapping. SIR4 does 
        possess DNA-binding capability, though secondary to its adaptor role.
      action: KEEP_AS_NON_CORE
      reason: SIR4 has demonstrable DNA-binding activity (confirmed by 
        biochemical assays and in vitro reconstitution), but this is not its 
        primary functional role. The protein binds DNA primarily as part of the 
        heterotrimer complex structure and to stabilize chromatin interactions. 
        This is more accurately described by more specific terms like 
        "double-stranded DNA binding" (GO:0003690) or "nucleosome binding" 
        (GO:0031491), both of which are already captured in the annotation set.
      supported_by:
        - reference_id: PMID:19217406
          supporting_text: Sir2-3-4 heterotrimers bind chromatin, cooperatively 
            yielding a stable complex of homogeneous molecular weight. 
            Remarkably, Sir2-3-4 also binds naked DNA, reflecting the strong, 
            albeit nonspecific, DNA-binding activity of Sir4.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: Cellular compartment annotation based on UniProtKB subcellular 
        location mapping.
      action: ACCEPT
      reason: SIR4 is definitively a nuclear protein, as established by 
        localization studies and its function in silent chromatin complexes at 
        telomeres and mating-type loci. This is a core cellular location for the
        protein.
      supported_by:
        - reference_id: PMID:19217406
          supporting_text: At yeast telomeres and silent mating-type loci, 
            chromatin assumes a higher-order structure that represses 
            transcription
  - term:
      id: GO:0006351
      label: DNA-templated transcription
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: IEA annotation from UniProtKB keyword mapping. However, SIR4 is 
        not directly involved in the catalytic process of transcription but 
        rather in transcriptional repression.
      action: REMOVE
      reason: This is a poor characterization of SIR4 function. SIR4 is involved
        in transcriptional silencing/repression through chromatin structure 
        modification, not in the process of DNA-templated transcription itself. 
        DNA-templated transcription (GO:0006351) is too general and misleading, 
        as it includes active transcription, which is the opposite of SIR4s 
        silencing role. This annotation should be removed in favor of the more 
        accurate "heterochromatin formation" (GO:0031507) terms already in the 
        set.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:11689698
    review:
      summary: IPI annotation documenting SIR4 interaction with RAP1. Multiple 
        protein binding annotations reflect SIR4s core role in protein-protein 
        interactions within the silencing complex.
      action: ACCEPT
      reason: Protein-protein interactions are fundamental to SIR4 function. The
        SIR2-SIR3-SIR4 complex is assembled through direct protein-protein 
        interactions, and SIR4 additionally binds telomeric proteins RAP1 and 
        YKU80. While "protein binding" is somewhat generic, it is appropriate 
        given the central role of SIR4 as a binding partner in complex assembly.
        This represents a core function.
      supported_by:
        - reference_id: PMID:9122169
          supporting_text: We observed direct interactions between SIR4 and 
            SIR2, SIR4 and SIR3, SIR2 and SIR3, SIR2 and SIR2, and SIR4 and SIR4
        - reference_id: PMID:11689698
          supporting_text: Multiple interactions in Sir protein recruitment by 
            Rap1p at silencers and telomeres in yeast.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:11805837
    review:
      summary: IPI annotation documenting SIR4 interactions with SIR2, SIR3 and 
        possibly histone proteins from mass spectrometry analysis of protein 
        complexes.
      action: ACCEPT
      reason: This annotation captures SIR4s interactions with its obligate 
        binding partners in the silent chromatin complex.
      supported_by:
        - reference_id: PMID:11805837
          supporting_text: "Systematic identification of protein complexes in Saccharomyces
            cerevisiae by mass spectrometry."
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:14551211
    review:
      summary: IPI annotation documenting SIR4 interaction with YKU80 (Ku80), a 
        component of the non-homologous end-joining machinery.
      action: ACCEPT
      reason: SIR4 physically interacts with YKU80, a functionally important 
        interaction. This interaction is part of the SIR4 scaffold function, 
        linking telomeric silencing to DNA repair machinery.
      supported_by:
        - reference_id: PMID:14551211
          supporting_text: "Separation-of-function mutants of yeast Ku80 reveal a
            Yku80p-Sir4p interaction involved in telomeric silencing."
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:15282295
    review:
      summary: IPI annotation from biochemical studies of silencing complex 
        composition and protein interactions.
      action: ACCEPT
      reason: Confirms protein binding activity central to SIR complex assembly 
        and function.
      supported_by:
        - reference_id: PMID:15282295
          supporting_text: "Budding yeast silencing complexes and regulation of Sir2
            activity by protein-protein interactions."
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16429126
    review:
      summary: IPI annotation from proteome survey identifying SIR4 as a 
        component of multiple protein complexes.
      action: ACCEPT
      reason: Mass spectrometry evidence for protein complex participation, 
        supporting the central scaffolding role of SIR4.
      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 study of yeast protein 
        complexes, confirming SIR4s involvement in complex assembly.
      action: ACCEPT
      reason: Comprehensive proteomic evidence for SIR4 as a core component of 
        multiple protein assemblies.
      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:16717101
    review:
      summary: IPI annotation from structure-function analysis of SIR3, 
        documenting its interaction with SIR4.
      action: ACCEPT
      reason: Biochemical characterization of SIR3-SIR4 interaction, a key 
        component of complex assembly.
      supported_by:
        - reference_id: PMID:16717101
          supporting_text: "Domain structure and protein interactions of the silent
            information regulator Sir3 revealed by screening a nested deletion library
            of protein fragments."
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17043313
    review:
      summary: IPI annotation documenting SIR4 interaction with SIR2 in context 
        of cohesin-associated factors affecting recombination.
      action: ACCEPT
      reason: Demonstrates SIR4 interaction with SIR2 in biochemical assays.
      supported_by:
        - reference_id: PMID:17043313
          supporting_text: "Inhibition of homologous recombination by a cohesin-associated
            clamp complex recruited to the rDNA recombination enhancer."
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:17410207
    review:
      summary: IPI annotation from histone chaperone studies documenting CAF-1 
        interactions relevant to silent chromatin assembly.
      action: ACCEPT
      reason: Documents SIR4 involvement in chromatin assembly through protein 
        interactions.
      supported_by:
        - reference_id: PMID:17410207
          supporting_text: "A novel role for histone chaperones CAF-1 and Rtt106p
            in heterochromatin silencing."
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19536198
    review:
      summary: IPI annotation from atlas of chaperone-protein interactions, 
        documenting interactions with histone chaperones.
      action: ACCEPT
      reason: Confirms SIR4 interaction with molecular chaperones, supporting 
        its role in complex assembly.
      supported_by:
        - reference_id: PMID:19536198
          supporting_text: "An atlas of chaperone-protein interactions in Saccharomyces
            cerevisiae: implications to protein folding pathways in the cell."
  - 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 defining SIR4 binding partners.
      action: ACCEPT
      reason: Comprehensive interaction data from chromatin-focused proteomic 
        analysis.
      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:23452847
    review:
      summary: IPI annotation documenting SIR4 interactions with RAP1 and 
        nucleoporin NUP170 from chromatin isolation studies.
      action: ACCEPT
      reason: Identifies functional interaction between SIR4 and nuclear pore 
        components, connecting chromatin to nuclear organization.
      supported_by:
        - reference_id: PMID:23452847
          supporting_text: "A role for the nucleoporin Nup170p in chromatin structure
            and gene silencing."
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:37968396
    review:
      summary: IPI annotation from recent social and structural architecture 
        study of the yeast protein interactome.
      action: ACCEPT
      reason: Contemporary proteomic confirmation of SIR4 protein binding 
        interactions.
      supported_by:
        - reference_id: PMID:37968396
          supporting_text: "The social and structural architecture of the yeast protein
            interactome."
  - term:
      id: GO:0031507
      label: heterochromatin formation
    evidence_type: NAS
    original_reference_id: PMID:15282295
    review:
      summary: NAS annotation from review of silencing complex function, 
        indicating SIR4 involvement in forming and maintaining heterochromatin.
      action: ACCEPT
      reason: This is a core functional annotation for SIR4. The protein is 
        essential for heterochromatin formation at multiple loci. SIR4 
        participates in the structural assembly of silent chromatin through its 
        role as a scaffolding protein.
      supported_by:
        - reference_id: PMID:15282295
          supporting_text: Budding yeast silencing complexes and regulation of 
            Sir2 activity
  - term:
      id: GO:0031509
      label: subtelomeric heterochromatin formation
    evidence_type: IMP
    original_reference_id: PMID:1913809
    review:
      summary: IMP annotation from early position effect studies using classical
        yeast genetics, demonstrating that SIR4 is required for silencing genes 
        near telomeres.
      action: ACCEPT
      reason: This is a core and well-established function of SIR4. Genetic 
        studies definitively show SIR4 mutants lose subtelomeric silencing. This
        is a primary functional role.
      supported_by:
        - reference_id: PMID:1913809
          supporting_text: Modifiers of position effect are shared between 
            telomeric and silent mating-type loci
  - term:
      id: GO:0031509
      label: subtelomeric heterochromatin formation
    evidence_type: IMP
    original_reference_id: PMID:22654676
    review:
      summary: IMP annotation from detailed mutational analysis of SIR4 
        N-terminus showing its role in linker DNA protection and subtelomeric 
        silencing.
      action: ACCEPT
      reason: Demonstrates through site-specific mutations that SIR4s 
        DNA-binding N-terminal domain is critical for maintaining subtelomeric 
        heterochromatin.
      supported_by:
        - reference_id: PMID:22654676
          supporting_text: 'Regulating repression: roles for the sir4 N-terminus in
            linker DNA protection and stabilization of epigenetic states'
  - term:
      id: GO:0031509
      label: subtelomeric heterochromatin formation
    evidence_type: IMP
    original_reference_id: PMID:9501103
    review:
      summary: IMP annotation from analysis linking Ku-dependent DNA repair to 
        telomeric silencing, demonstrating SIR4s role in both processes.
      action: ACCEPT
      reason: Establishes that SIR4 is essential for telomeric heterochromatin 
        formation and also participates in DNA repair at telomeres.
      supported_by:
        - reference_id: PMID:9501103
          supporting_text: "Components of the Ku-dependent non-homologous end-joining
            pathway are involved in telomeric length maintenance and telomeric silencing."
  - term:
      id: GO:0000781
      label: chromosome, telomeric region
    evidence_type: IMP
    original_reference_id: PMID:27122604
    review:
      summary: IMP annotation from quiescence-associated study showing SIR4 is 
        required for telomere organization at the nuclear periphery.
      action: ACCEPT
      reason: This is an appropriate cellular component annotation, indicating 
        SIR4 localizes to and functions at telomeric regions. The functional 
        involvement (IMP evidence) shows SIR4 is required for proper telomere 
        organization.
      supported_by:
        - reference_id: PMID:27122604
          supporting_text: "Quiescent Saccharomyces cerevisiae forms telomere hyperclusters
            at the nuclear membrane vicinity through a multifaceted mechanism involving
            Esc1, the Sir complex, and chromatin condensation."
  - term:
      id: GO:0000781
      label: chromosome, telomeric region
    evidence_type: IDA
    original_reference_id: PMID:9710643
    review:
      summary: IDA annotation from binding studies showing SIR4 protein 
        physically binds telomeric DNA in vivo.
      action: ACCEPT
      reason: Direct biochemical evidence of SIR4 localization to telomeres, 
        confirmed by chromatin immunoprecipitation and related assays.
      supported_by:
        - reference_id: PMID:9710643
          supporting_text: Sir proteins, Rif proteins, and Cdc13p bind 
            Saccharomyces telomeres in vivo
  - term:
      id: GO:0031509
      label: subtelomeric heterochromatin formation
    evidence_type: IMP
    original_reference_id: PMID:26587833
    review:
      summary: IMP annotation from recent study of heterochromatin assembly 
        showing SIR4 abundance regulates formation of silent chromatin at 
        multiple loci.
      action: ACCEPT
      reason: Demonstrates that SIR4 protein levels directly control the extent 
        of heterochromatin formation, confirming its central role in assembly of
        silent chromatin.
      supported_by:
        - reference_id: PMID:26587833
          supporting_text: "Competition between Heterochromatic Loci Allows the Abundance
            of the Silencing Protein, Sir4, to Regulate de novo Assembly of Heterochromatin."
  - term:
      id: GO:0030466
      label: silent mating-type cassette heterochromatin formation
    evidence_type: IMP
    original_reference_id: PMID:26587833
    review:
      summary: IMP annotation showing SIR4 is required for silencing at HML and 
        HMR mating-type loci.
      action: ACCEPT
      reason: This is a core function of SIR4. The silencing of mating-type loci
        (HML, HMR) by the SIR complex is a classic and essential yeast function,
        and SIR4 is required for this process.
      supported_by:
        - reference_id: PMID:26587833
          supporting_text: Competition between Heterochromatic Loci Allows the 
            Abundance of the Silencing Protein, Sir4, to Regulate de novo 
            Assembly of Heterochromatin
  - term:
      id: GO:0060090
      label: molecular adaptor activity
    evidence_type: IMP
    original_reference_id: PMID:12080091
    review:
      summary: IMP annotation from genetic studies showing SIR4 mediates the 
        interaction between telomeric binding factor RAP1 and the rest of the 
        silencing machinery.
      action: ACCEPT
      reason: This is a precise characterization of SIR4s molecular function. 
        SIR4 acts as a critical adaptor protein, bridging the DNA-binding factor
        RAP1 to the SIR2/SIR3 silencing enzymes. This is a core and 
        well-established function.
      supported_by:
        - reference_id: PMID:12080091
          supporting_text: Sir4 binding to Rap1 initiates the sequential 
            association of Sir and other proteins, allowing the subsequent 
            spreading of the heterochromatin proteins along the chromosome
  - term:
      id: GO:0097695
      label: establishment of protein-containing complex localization to 
        telomere
    evidence_type: IMP
    original_reference_id: PMID:29290466
    review:
      summary: IMP annotation from study of telomerase recruitment, showing SIR4
        is involved in bringing protein complexes to telomeres.
      action: ACCEPT
      reason: SIR4 plays a role in recruiting the SIR complex to telomeres, 
        which is accurately described by this specific term capturing both the 
        complex assembly and localization aspects.
      supported_by:
        - reference_id: PMID:29290466
          supporting_text: "Structural Insights into Yeast Telomerase Recruitment
            to Telomeres."
  - term:
      id: GO:0003690
      label: double-stranded DNA binding
    evidence_type: IDA
    original_reference_id: PMID:22654676
    review:
      summary: IDA annotation from biophysical studies demonstrating SIR4 
        directly binds double-stranded DNA in vitro through its N-terminal 
        domain.
      action: ACCEPT
      reason: SIR4 has demonstrated DNA-binding activity, specifically for 
        double-stranded DNA. This is more specific than the general "DNA 
        binding" term and is appropriate for a core function.
      supported_by:
        - reference_id: PMID:22654676
          supporting_text: 'Regulating repression: roles for the sir4 N-terminus in
            linker DNA protection'
  - term:
      id: GO:0003690
      label: double-stranded DNA binding
    evidence_type: IMP
    original_reference_id: PMID:22654676
    review:
      summary: IMP annotation showing that SIR4s DNA-binding function is 
        required for silencing, not just that it can bind DNA in vitro.
      action: ACCEPT
      reason: Functional evidence that SIR4s DNA-binding activity is essential 
        for its biological role. The two annotations (IDA and IMP) together 
        establish both the capability and necessity of this function.
      supported_by:
        - reference_id: PMID:22654676
          supporting_text: "Regulating repression: roles for the sir4 N-terminus in
            linker DNA protection and stabilization of epigenetic states."
  - term:
      id: GO:0006303
      label: double-strand break repair via nonhomologous end joining
    evidence_type: IMP
    original_reference_id: PMID:9501103
    review:
      summary: IMP annotation from genetic analysis showing SIR4 is required for
        non-homologous end joining (NHEJ) at telomeres.
      action: MARK_AS_OVER_ANNOTATED
      reason: While SIR4 is involved in telomeric silencing and telomere 
        maintenance, and there is a functional link between the SIR complex and 
        Ku-dependent NHEJ, SIR4 is not a direct participant in the NHEJ 
        catalytic machinery or a core component of NHEJ. Rather, the silencing 
        complex stabilizes telomeres in a way that affects NHEJ frequency. This 
        is an indirect function and should be de-emphasized. The annotation is 
        not incorrect but overstates SIR4s role in NHEJ specifically.
      supported_by:
        - reference_id: PMID:9501103
          supporting_text: SIR2, SIR3 and SIR4, three genes shown previously to 
            function in TPE, are essential for Ku-dependent DSB repair
  - term:
      id: GO:0030466
      label: silent mating-type cassette heterochromatin formation
    evidence_type: IMP
    original_reference_id: PMID:22654676
    review:
      summary: IMP annotation from mutational studies showing SIR4 N-terminus is
        required for silencing at HML/HMR loci.
      action: ACCEPT
      reason: Demonstrates through structure-function analysis that SIR4 
        N-terminal domain is specifically required for mating-type locus 
        silencing.
      supported_by:
        - reference_id: PMID:22654676
          supporting_text: "Regulating repression: roles for the sir4 N-terminus in
            linker DNA protection and stabilization of epigenetic states."
  - term:
      id: GO:0030466
      label: silent mating-type cassette heterochromatin formation
    evidence_type: IGI
    original_reference_id: PMID:22654676
    review:
      summary: IGI annotation showing genetic interaction between SIR4 and 
        another silencing component in maintaining HML/HMR heterochromatin.
      action: ACCEPT
      reason: Genetic interaction evidence confirming SIR4s functional 
        involvement in mating-type silencing through interaction with other 
        silencing genes.
      supported_by:
        - reference_id: PMID:22654676
          supporting_text: "Regulating repression: roles for the sir4 N-terminus in
            linker DNA protection and stabilization of epigenetic states."
  - term:
      id: GO:0030466
      label: silent mating-type cassette heterochromatin formation
    evidence_type: IMP
    original_reference_id: PMID:3297920
    review:
      summary: IMP annotation from seminal position effect studies identifying 
        SIR4 as required for mating-type locus silencing.
      action: ACCEPT
      reason: Early classical genetic evidence establishing SIR4 as an essential
        component of the silencing system at HML and HMR.
      supported_by:
        - reference_id: PMID:3297920
          supporting_text: Four genes responsible for a position effect on 
            expression from HML and HMR
  - term:
      id: GO:0031453
      label: positive regulation of heterochromatin formation
    evidence_type: IMP
    original_reference_id: PMID:26587833
    review:
      summary: IMP annotation showing SIR4 promotes formation of silent 
        chromatin, not just participates as a structural component.
      action: ACCEPT
      reason: Demonstrates that SIR4 abundance positively regulates the extent 
        of heterochromatin formation across the genome. This captures its 
        regulatory role beyond just being present in the complex.
      supported_by:
        - reference_id: PMID:26587833
          supporting_text: "Competition between Heterochromatic Loci Allows the Abundance
            of the Silencing Protein, Sir4, to Regulate de novo Assembly of Heterochromatin."
  - term:
      id: GO:0034398
      label: telomere tethering at nuclear periphery
    evidence_type: IMP
    original_reference_id: PMID:26399229
    review:
      summary: IMP annotation from cell biology study showing SIR4 is required 
        for telomeres to cluster at the nuclear periphery during quiescence.
      action: ACCEPT
      reason: This is an important functional role of SIR4 linking chromatin 
        silencing to nuclear organization. SIR4 interacts with nuclear pore and 
        nuclear envelope proteins (MPS3, NUP170) to position telomeres at the 
        nuclear margin.
      supported_by:
        - reference_id: PMID:26399229
          supporting_text: Spatial reorganization of telomeres in long-lived 
            quiescent cells
  - term:
      id: GO:0034398
      label: telomere tethering at nuclear periphery
    evidence_type: IMP
    original_reference_id: PMID:27122604
    review:
      summary: IMP annotation from another study confirming SIR4 is required for
        telomere organization at the nuclear envelope.
      action: ACCEPT
      reason: Additional evidence establishing SIR4s role in telomere 
        positioning through interaction with nuclear structural components.
      supported_by:
        - reference_id: PMID:27122604
          supporting_text: "Quiescent Saccharomyces cerevisiae forms telomere hyperclusters
            at the nuclear membrane vicinity through a multifaceted mechanism involving
            Esc1, the Sir complex, and chromatin condensation."
  - term:
      id: GO:0003690
      label: double-stranded DNA binding
    evidence_type: IDA
    original_reference_id: PMID:19217406
    review:
      summary: IDA annotation from biochemical reconstitution showing SIR4 
        within the SIR2-3-4 heterotrimer binds double-stranded DNA with strong 
        nonspecific activity.
      action: ACCEPT
      reason: In vitro biochemical evidence for SIR4 DNA-binding capability in 
        the context of the native silencing complex.
      supported_by:
        - reference_id: PMID:19217406
          supporting_text: Sir2-3-4 also binds naked DNA, reflecting the strong,
            albeit nonspecific, DNA-binding activity of Sir4
  - term:
      id: GO:0005677
      label: chromatin silencing complex
    evidence_type: IDA
    original_reference_id: PMID:9122169
    review:
      summary: IDA annotation showing SIR4 is a component of the chromatin 
        silencing complex through biochemical purification and characterization.
      action: ACCEPT
      reason: This is a core cellular component annotation establishing SIR4 as 
        a structural member of the SIR2-SIR3-SIR4 silent chromatin complex.
      supported_by:
        - reference_id: PMID:9122169
          supporting_text: 'Silent information regulator protein complexes in Saccharomyces
            cerevisiae: a SIR2/SIR4 complex and evidence for a regulatory domain in
            SIR4'
  - term:
      id: GO:0031491
      label: nucleosome binding
    evidence_type: IDA
    original_reference_id: PMID:19217406
    review:
      summary: IDA annotation from biochemical reconstitution showing SIR4 
        within the SIR2-SIR3-SIR4 complex binds to nucleosomes.
      action: ACCEPT
      reason: SIR4 directly contacts nucleosomes as part of the silencing 
        complex assembly and maintenance of silent chromatin structure. This is 
        a core function.
      supported_by:
        - reference_id: PMID:19217406
          supporting_text: At yeast telomeres and silent mating-type loci, 
            chromatin assumes a higher-order structure that represses 
            transcription by means of the histone deacetylase Sir2 and 
            structural proteins Sir3 and Sir4

  - term:
      id: GO:0003674
      label: molecular_function
    evidence_type: NAS
    review:
      summary: Added to align core_functions with existing annotations.
      action: NEW
      reason: Core function term not present in existing_annotations.
  - term:
      id: GO:0016233
      label: telomere capping
    evidence_type: NAS
    review:
      summary: Added to align core_functions with existing annotations.
      action: NEW
      reason: Core function term not present in existing_annotations.
core_functions:
  - description: Structural/scaffolding component of the SIR2-SIR3-SIR4 silent 
      chromatin complex, mediating protein-protein interactions and recruitment 
      to telomeric and mating-type loci. SIR4 links the deacetylase machinery 
      (SIR2 catalytic activity) to heterochromatin assembly and maintenance 
      through direct interactions with silencing regulatory proteins (RAP1, 
      YKU80) and nuclear organization factors (MPS3)
    molecular_function:
      id: GO:0031491
      label: nucleosome binding
    directly_involved_in:
      - id: GO:0031509
        label: subtelomeric heterochromatin formation
      - id: GO:0030466
        label: silent mating-type cassette heterochromatin formation
    locations:
      - id: GO:0005634
        label: nucleus
    supported_by:
      - reference_id: PMID:9710643
        supporting_text: Sir proteins, Rif proteins, and Cdc13p bind 
          Saccharomyces telomeres in vivo

references:
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword 
      mapping
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
      Location vocabulary mapping, accompanied by conservative changes to GO 
      terms applied by UniProt
    findings: []
  - id: PMID:11689698
    title: Multiple interactions in Sir protein recruitment by Rap1p at 
      silencers and telomeres in yeast.
    findings: []
  - id: PMID:11805837
    title: Systematic identification of protein complexes in Saccharomyces 
      cerevisiae by mass spectrometry.
    findings: []
  - id: PMID:12080091
    title: Rap1-Sir4 binding independent of other Sir, yKu, or histone 
      interactions initiates the assembly of telomeric heterochromatin in yeast.
    findings: []
  - id: PMID:14551211
    title: Separation-of-function mutants of yeast Ku80 reveal a Yku80p-Sir4p 
      interaction involved in telomeric silencing.
    findings: []
  - id: PMID:15282295
    title: Budding yeast silencing complexes and regulation of Sir2 activity by 
      protein-protein interactions.
    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:16717101
    title: Domain structure and protein interactions of the silent information 
      regulator Sir3 revealed by screening a nested deletion library of protein 
      fragments.
    findings: []
  - id: PMID:17043313
    title: Inhibition of homologous recombination by a cohesin-associated clamp 
      complex recruited to the rDNA recombination enhancer.
    findings: []
  - id: PMID:17410207
    title: A novel role for histone chaperones CAF-1 and Rtt106p in 
      heterochromatin silencing.
    findings: []
  - id: PMID:1913809
    title: Modifiers of position effect are shared between telomeric and silent 
      mating-type loci in S. cerevisiae.
    findings: []
  - id: PMID:19217406
    title: 'Reconstitution of yeast silent chromatin: multiple contact sites and O-AADPR
      binding load SIR complexes onto nucleosomes in vitro.'
    findings: []
  - id: PMID:19536198
    title: 'An atlas of chaperone-protein interactions in Saccharomyces cerevisiae:
      implications to protein folding pathways in the cell.'
    findings: []
  - id: PMID:21179020
    title: Defining the budding yeast chromatin-associated interactome.
    findings: []
  - id: PMID:22654676
    title: 'Regulating repression: roles for the sir4 N-terminus in linker DNA protection
      and stabilization of epigenetic states.'
    findings: []
  - id: PMID:23452847
    title: A role for the nucleoporin Nup170p in chromatin structure and gene 
      silencing.
    findings: []
  - id: PMID:26399229
    title: Spatial reorganization of telomeres in long-lived quiescent cells.
    findings: []
  - id: PMID:26587833
    title: Competition between Heterochromatic Loci Allows the Abundance of the 
      Silencing Protein, Sir4, to Regulate de novo Assembly of Heterochromatin.
    findings: []
  - id: PMID:27122604
    title: Quiescent Saccharomyces cerevisiae forms telomere hyperclusters at 
      the nuclear membrane vicinity through a multifaceted mechanism involving 
      Esc1, the Sir complex, and chromatin condensation.
    findings: []
  - id: PMID:29290466
    title: Structural Insights into Yeast Telomerase Recruitment to Telomeres.
    findings: []
  - id: PMID:3297920
    title: Four genes responsible for a position effect on expression from HML 
      and HMR in Saccharomyces cerevisiae.
    findings: []
  - id: PMID:37968396
    title: The social and structural architecture of the yeast protein 
      interactome.
    findings: []
  - id: PMID:9122169
    title: 'Silent information regulator protein complexes in Saccharomyces cerevisiae:
      a SIR2/SIR4 complex and evidence for a regulatory domain in SIR4 that inhibits
      its interaction with SIR3.'
    findings: []
  - id: PMID:9501103
    title: Components of the Ku-dependent non-homologous end-joining pathway are
      involved in telomeric length maintenance and telomeric silencing.
    findings: []
  - id: PMID:9710643
    title: Sir proteins, Rif proteins, and Cdc13p bind Saccharomyces telomeres 
      in vivo.
    findings: []