SET1

Summary: SET1 catalyzes histone H3 lysine 4 methylation as the core enzymatic function of the COMPASS complex. IBA annotation based on phylogenetic inference across SET1/MLL family. Extensive direct biochemical evidence establishes this as the primary function.

Reason: Core SET1 function. IBA evidence is appropriate for this well-conserved family function. Deep research confirms SET1 is the sole H3K4 methyltransferase in yeast [evidence from PMID:11742990, 11751634, 11752412, 11805083].

Summary: SET1 is the catalytic core component of the COMPASS (Complex of Proteins Associated with Set1) complex. SET1 is part of an eight-subunit complex essential for H3K4 methylation. IBA annotation reflects phylogenetic conservation of this complex organization.

Reason: Core structural annotation. SET1 functions exclusively as component of COMPASS complex. IBA evidence appropriate for this conserved complex membership. Deep research establishes COMPASS as multi-subunit assembly with SET1 at catalytic core [PMID:11742990, 11687631]. Falcon deep research details the eight-subunit composition and a WRAD-like catalytic core (Swd1/Swd3/Bre2/Sdc1).

Summary: SET1 localizes to the nucleus where COMPASS complex catalyzes H3K4 methylation on chromatin. IEA from UniProt subcellular location annotation.

Reason: Correct localization but not informative about SET1 function. Localization without functional consequence should be marked non-core. SET1 functions exclusively in nucleus.

Summary: SET1 associates with chromatin/chromosomes as component of COMPASS complex catalyzing H3K4 methylation.

Reason: While true, this is vague and less informative than specific process or function annotations. Chromosome association is implied by core methyltransferase function.

Summary: H3K4 methylation by SET1/COMPASS contributes to chromatin organization and regulation of chromatin structure.

Reason: SET1 directly contributes to chromatin organization through H3K4 methylation, which affects nucleosome positioning, histone-DNA interactions, and chromatin state. IEA from keyword annotation is appropriate.

Summary: SET1 catalyzes methyl group transfer from SAM to histone H3 lysine 4, a methyltransferase activity.

Reason: True but overly broad. GO:0042800 (H3K4 methyltransferase activity) is more specific and informative. This parent term is less useful when specific substrate-level annotation available.

Summary: SET1 catalyzes transferase activity (methyl group transfer to histone substrate).

Reason: Extremely broad parent term. SET1 is a methyltransferase, which is a type of transferase. Parent term is less informative when more specific molecular function available.

Summary: SET1 catalyzes methylation of histone H3 lysine 4.

Reason: General process annotation. While accurate, more specific methyltransferase activity annotations (GO:0008168, GO:0042800) are more informative. Parent term less useful.

Summary: SET1 is the H3K4-specific methyltransferase, catalyzing mono-, di-, and trimethylation of histone H3 lysine 4. IEA from InterPro domain annotation.

Reason: Core molecular function annotation. IEA from InterPro recognition of SET domain is appropriate. Extensive literature confirms this is SET1 primary function. Duplicate of annotation 1 with different evidence source.

Summary: SET1-mediated H3K4 methylation marks and promotes active transcription, functioning in positive regulation of Pol II transcription.

Reason: SET1 function extends beyond catalytic activity to transcriptional regulation. H3K4me3 marks active promoters and is required for efficient transcription initiation. Deep research [PMID:27325136] confirms SET1 involvement in transcription regulation. However, SET1 also has roles in transcriptional repression, making this annotation incomplete.

Summary: SET1 is component of Set1C/COMPASS complex. IEA from InterPro domain recognition.

Reason: Core structural annotation. Duplicate of annotation 2 with different evidence. InterPro detection of SET domain-containing protein appropriately infers COMPASS complex membership.

Summary: SET1 catalyzes trimethylation of histone H3 lysine 4 (H3K4me3). IEA from RHEA and EC number annotation.

Reason: SET1 catalyzes all methylation states (me1, me2, me3) of H3K4. This annotation for trimethylation specifically is appropriate. Deep research confirms SET1 capacity for complete trimethylation [PMID:12845608, 22158900].

Summary: SET1 protein-protein interactions with COMPASS complex subunits (Bre2/Ash2, Swd1, Swd2, Swd3) and other proteins documented through co-immunoprecipitation and mass spectrometry. Multiple IPI annotations reflect experimentally validated interactions.

Reason: While interactions are real and well-documented (IPI evidence is appropriate), generic "protein binding" is not informative for SET1 function. These interactions are with known COMPASS subunits (Bre2, Swd1, Swd2, Swd3, Bre5, Chd1, Swd7) forming the complex. Specific complex membership (GO:0048188) is more informative than generic binding. COMPASS complex membership captures the functional significance.

Summary: SET1 interactions documented via mass spectrometry-based proteome survey.

Reason: Generic binding annotation. Specific COMPASS complex membership is more informative.

Summary: SET1 protein interactions identified in proteome survey.

Reason: Generic binding annotation. Specific complex membership captures functional relationships.

Summary: SET1 protein interactions from global landscape of yeast protein complexes study.

Reason: Generic binding annotation. Duplicate interactions captured more informatively by COMPASS complex membership.

Summary: SET1 interactions in context of histone crosstalk between H2B ubiquitination and H3 methylation via COMPASS.

Reason: Generic binding annotation despite interesting functional context. COMPASS complex membership is more specific and functional. Falcon deep research underscores that this trans-histone crosstalk is a defining regulatory principle: H2B monoubiquitination at K123 (installed by Rad6/Bre1) is required for normal levels of H3K4 di- and tri-methylation by COMPASS, with ubiquitin contacting the Set1 n-SET helix, Swd1, and Bre2. The mechanistic crosstalk is better captured by process/complex annotations than by generic protein binding.

Summary: SET1 protein interactions from cotranslational assembly studies of SET1C complex.

Reason: Generic binding annotation. Complex assembly dynamics captured by COMPASS membership annotation.

Summary: SET1 interactions from budding yeast chromatin-associated interactome study.

Reason: Generic binding annotation. COMPASS complex membership more informative.

Summary: SET1 interactions from recent social and structural architecture of yeast protein interactome study.

Reason: Generic binding annotation. Specific complex membership is more informative for understanding SET1 function.

Summary: SET1 interaction with Mec3 checkpoint protein documented. SET1 involvement in DNA repair and checkpoint functions.

Reason: While this Mec3 interaction is functionally distinct (DNA repair vs. COMPASS), generic "protein binding" is still not informative. The functional relationship (DNA repair, checkpoint) would be better captured by process annotations.

Summary: SET1 localizes to the nucleus as established by ComplexPortal NAS (Non-Annotated Sequence) curation.

Reason: Correct but not informative about function. Localization without functional consequence. SET1 functions in nucleus through H3K4 methylation which is already annotated.

Summary: SET1 has documented roles in subtelomeric heterochromatin formation and silencing of genes near chromosome ends.

Reason: SET1 contributes to subtelomeric heterochromatin formation through H3K4me3-dependent mechanisms. Deep research confirms role in telomeric gene silencing [PMID:11805083]. NAS evidence from ComplexPortal is appropriate. This is documented functional role.

Summary: SET1 contains an RNA recognition motif (RRM) at its N-terminus and binds RNA. IDA evidence from direct biochemical studies of SET1 RNA binding.

Reason: SET1 does bind RNA through its RRM domain (demonstrated PMID:29071121), but the functional role of this interaction is unclear. Deep research indicates RRM functions primarily in protein stability rather than direct catalytic relevance to H3K4 methylation. RNA binding is less central than methyltransferase activity. Falcon deep research notes that Set1 contains RNA-recognition motifs and binds mRNA co-/post-transcriptionally, with RNA binding contributing particularly to H3K4me3 deposition, so this remains a modulatory rather than core function.

Summary: SET1 is demonstrated to be component of Set1C/COMPASS complex through direct biochemical analysis and RNA binding studies.

Reason: Core structural annotation. IDA evidence from direct protein interaction studies appropriate. Duplicate annotation with different evidence from IBA (phylogenetic) and IEA (InterPro). This IDA evidence from direct studies is strong.

Summary: SET1 regulates transcription by RNA Pol II through H3K4 methylation. IMP evidence from set1 mutant studies showing defects in transcription regulation.

Reason: SET1 is essential for normal transcription regulation through H3K4 methylation. Deep research confirms H3K4me3 marks active promoters and affects transcription initiation and elongation [PMID:27325136]. IMP evidence appropriate.

Summary: SET1 genetic interaction with other transcription regulation genes. IGI evidence from genetic interaction studies.

Reason: Genetic interactions with transcription factors and regulators confirm SET1 role in transcription regulation. IMP and IGI both support this annotation from same reference.

Summary: SET1 contributes to cellular stress response through H3K4 methylation-dependent gene expression changes. IMP evidence from mutant analysis.

Reason: SET1 regulates genes involved in stress response. Deep research shows SET1 effects on stress-responsive gene expression. IMP evidence from set1 deletion/mutation studies.

Summary: Genetic interaction showing SET1 involvement in stress response pathways.

Reason: Genetic interaction data support stress response role. Duplicate from same reference with complementary evidence type.

Summary: SET1 contains zinc-binding motifs characteristic of SET domain proteins. RCA (Rule-based Computational Annotation) inferred from protein structure.

Reason: SET1 SET domain contains zinc-coordinating residues (part of catalytic pocket), but zinc binding is not the primary function - it is structural support for methyltransferase activity. RCA from structural features is appropriate, but zinc binding is a cofactor interaction rather than independent function. Less informative than methyltransferase activity annotation.

Summary: SET1 is required for proper methylation of histone H3 and formation of subtelomeric heterochromatin. Multiple IMP annotations confirm this functional role.

Reason: SET1 is essential for subtelomeric heterochromatin formation and silencing through H3K4 methylation-dependent mechanisms. IMP evidence from set1 mutant studies. Core functional role well-documented [PMID:11752412, 11805083, 9398665].

Summary: SET1 methylation activity required for telomeric silencing and subtelomeric heterochromatin.

Reason: Duplicate annotation with different reference but same functional role. IMP evidence appropriate.

Summary: SET1, a yeast member of the trithorax family, functions in transcriptional silencing and subtelomeric heterochromatin.

Reason: Foundational characterization of SET1 in heterochromatin. IMP evidence from early functional studies.

Summary: SET1 involvement in heterochromatin formation and telomere functions.

Reason: Additional IMP evidence. Multiple independent studies converge on SET1 role in subtelomeric heterochromatin formation.

Summary: Direct experimental evidence for SET1 RNA binding capacity. IDA from PMID:28483910 RNA Binding by Histone Methyltransferases Set1 and Set2.

Reason: While RNA binding is demonstrated (IDA evidence appropriate), the functional role in H3K4 methylation is unclear. RRM domain appears to function in protein stability/regulation rather than direct catalytic function. Less central than methyltransferase activity.

Summary: SET1 contributes to meiotic DNA double-strand break (DSB) formation. IMP evidence from genetic analysis of set1 in meiosis.

Reason: SET1 has specialized functions in meiotic recombination beyond transcription. Deep research shows SET1 targeting meiotic DSB sites and requirement for proper DSB formation [PMID:32290544]. Both catalytic and non-catalytic SET1 functions contribute to meiosis.

Summary: SET1 is involved in telomere maintenance through H3K4 methylation-dependent and independent mechanisms.

Reason: SET1 contributes to telomere length maintenance. Deep research documents SET1 roles in both H3K4me3-dependent telomeric silencing and H3K4me3-independent telomere length regulation [PMID:27911222]. IMP evidence from set1 mutant studies. Falcon deep research highlights primary 2023 evidence (Jezek et al., PMID:36416860) that set1 deletion shortens telomeres and that telomere length maintenance requires the Set1 catalytic core but is not strictly explained by H3K4 methylation status alone, implying a partially H3K4-substrate-independent catalytic role.

Summary: SET1 genetic interaction suggesting localization/function at telomeric regions. IGI evidence from genetic interaction studies.

Reason: Localization annotation without clear functional context. SET1 association with telomeric regions is implied by telomere maintenance and subtelomeric heterochromatin annotations. More specific process annotations are more informative.

Summary: Genetic interaction indicating SET1 involvement in subtelomeric heterochromatin formation.

Reason: Genetic interaction evidence supports subtelomeric heterochromatin function. IGI complements IMP evidence from other references.

Summary: SET1 involvement in repression of middle sporulation genes through H3K4 methylation maintenance.

Reason: SET1 has documented roles in repressing genes that should not be expressed. H3K4 methylation can mark both active and repressed genes depending on context. Deep research confirms SET1 contributes to negative regulation of specific gene sets [PMID:29066473].

Summary: SET1 catalyzes protein (histone) methylation as core enzymatic function. IMP evidence from catalytic studies.

Reason: Correct but overly broad. GO:0042800 (H3K4 methyltransferase activity) is more specific. Parent term less informative when specific substrate-level annotation available.

Summary: SET1 contributes to rDNA heterochromatin formation through H3K4 methylation-dependent mechanisms.

Reason: SET1 has specialized roles in rDNA locus silencing beyond general H3K4 methylation. IMP evidence from studies of SET domain catalytic function in rDNA silencing. Deep research confirms rDNA heterochromatin is SET1-dependent [PMID:23469257].

Summary: SET1-mediated H3K4 methylation can function in negative regulation of transcription at specific loci. IMP evidence from mutant analysis.

Reason: SET1 has dual roles in both positive and negative regulation depending on genomic context and partnering proteins. Deep research confirms Jhd2 demethylase opposition to Set1 in dynamic control [PMID:27325136]. Multiple regulatory roles appropriate.

Summary: SET1-mediated H3K4 methylation promotes positive regulation of Pol II transcription.

Reason: Primary transcriptional role of SET1. Both GO:0000122 (negative) and GO:0045944 (positive) from same reference indicate context-dependent function. IMP evidence appropriate for both.

Summary: SET1-mediated H3K4 methylation regulates chromatin organization state through coordinated interactions with chromatin modifiers.

Reason: SET1 is central to chromatin organization regulation through H3K4 methylation effects on nucleosome positioning, chromatin accessibility, and establishment of distinct chromatin domains. IMP evidence appropriate.

Summary: SET1 contributes to synaptonemal complex assembly during meiosis. IMP evidence from meiotic genetics.

Reason: SET1 specialized meiotic function. Synaptonemal complex assembly is essential for proper meiotic recombination. SET1 H3K4 methylation promotes this process [PMID:24797370].

Summary: SET1 is required for synaptonemal complex assembly during meiosis.

Reason: SET1 essential for meiotic recombination through synaptonemal complex assembly. IMP evidence from meiotic mutant studies. Both positive regulation (GO:1905088) and assembly (GO:0007130) appropriately annotated.

Summary: SET1 contributes to regulation of meiotic DSB formation through Spp1-mediated recruitment to meiotic recombination hotspots.

Reason: SET1 has documented roles in regulating meiotic DSB formation through Spp1 complex component. Deep research shows SET1 recruits H3K4me3 to chromosome axis sites, promoting DSB formation [PMID:23246437]. Specialized meiotic function distinct from transcriptional role.

Summary: SET1 H3K4 methyltransferase activity demonstrated by functional analysis. IMP evidence from studies of SET1 catalytic function.

Reason: Core molecular function. IMP evidence from direct biochemical characterization of SET1 catalytic activity [PMID:11751634]. Multiple IMP annotations with different references converge on primary function.

Summary: SET1 H3K4 methyltransferase activity confirmed through structural analysis studies.

Reason: Duplicate with different structural biology reference. Multiple independent studies support H3K4 methyltransferase function. IMP evidence appropriate.

Summary: SET1 is involved in maintenance of ergosterol homeostasis and resistance to Brefeldin A. IMP evidence from genetic and functional studies.

Reason: This appears to be a pleiotropic effect rather than core function. SET1 H3K4 methylation regulates genes involved in sterol metabolism, but sterol homeostasis is not a primary functional role. The annotation is not incorrect, but represents a downstream consequence of transcriptional regulation rather than direct SET1 function. Keep annotation but mark as non-central to SET1 biology.

Summary: SET1 is required for telomere maintenance. IMP evidence from foundational studies.

Reason: SET1 contributes to telomere length maintenance and integrity. Supported by multiple references [PMID:11742990, 9398665, 27911222]. IMP evidence from set1 mutant studies showing shortened telomeres.

Summary: SET1 involvement in telomere maintenance from early functional characterization.

Reason: Duplicate from foundational SET1 paper. Multiple references converge on telomere maintenance role.

Summary: Direct experimental evidence for SET1 RNA binding from structural characterization of RNA recognition motifs.

Reason: RNA binding demonstrated through structural studies and RRM characterization. IDA evidence appropriate. However, functional role unclear - appears to affect protein stability rather than catalytic activity. Less central than methyltransferase function.

Summary: IMP evidence for RNA binding role in SET1 function and regulation.

Reason: Both IDA and IMP from same reference. Functional role of RNA binding remains unclear despite experimental evidence.

Summary: SET1 catalyzes protein-lysine methylation as a core enzymatic activity. IMP evidence from functional studies.

Reason: SET1 is a protein-lysine N-methyltransferase (histone lysine methyltransferase). While less specific than GO:0042800 (H3K4 methyltransferase), this is appropriate parent term. Genetic interactions demonstrate methyltransferase activity role.

Summary: Genetic interaction evidence for SET1 protein-lysine methyltransferase activity.

Reason: IGI complements IMP evidence. Genetic interactions support methyltransferase function.

Summary: SET1 is required for proper ascospore formation during sporulation. IMP evidence from set1 mutant analysis.

Reason: SET1 has documented role in sporulation and ascospore formation. IMP evidence from set1 deletion strains showing defective sporulation [PMID:17150765].

Summary: SET1 is required for maintenance of silent mating-type cassette heterochromatin. IMP evidence from early SET1 characterization.

Reason: SET1 contributes to silencing at the silent mating loci (HML and HMR). H3K4 methylation marks these silent heterochromatic regions [PMID:9398665]. IMP evidence from set1 mutant derepression phenotype.

Summary: SET1 H3K4 methyltransferase activity demonstrated through direct biochemical and cellular experiments.

Reason: Core function with multiple evidence types. IDA from foundational COMPASS discovery paper [PMID:11742990]. Extensive biochemical characterization of SET1 catalytic activity.

Summary: SET1 H3K4 methyltransferase activity confirmed through functional genetic analysis.

Reason: IMP evidence from set1 deletion showing loss of H3K4 methylation. Multiple evidence types from same paper converge on catalytic function.

Summary: SET1-catalyzed H3K4 methylation demonstrated through trithorax-group complex characterization.

Reason: IMP evidence from trithorax complex purification and functional analysis [PMID:11752412].

Summary: Direct evidence for SET1 histone H3K4 methyltransferase activity from COMPASS characterization.

Reason: IDA evidence from biochemical analysis of COMPASS complex activity [PMID:11805083].

Summary: IMP evidence for H3K4 methyltransferase function from mutational analysis.

Reason: Multiple evidence types (IDA and IMP) from same reference support catalytic function.

Summary: SET1 is a methyltransferase specific for lysine 4 of histone H3 and required for efficient gene expression.

Reason: IMP evidence from studies of SET1 catalytic requirement for gene expression [PMID:12845608]. Converging evidence from multiple studies.

Summary: SET1 protein-protein interactions with COMPASS subunits documented through direct interaction studies.

Reason: Core structural annotation. IPI evidence from COMPASS co-immunoprecipitation studies [PMID:11687631]. Specific complex membership is more informative than generic protein binding. Multiple IPI annotations with different partners all converge on COMPASS complex membership.

Summary: SET1 interactions with COMPASS complex components demonstrated through multiple approaches.

Reason: Multiple independent IPI studies confirm COMPASS complex membership. Duplicate annotations appropriate for different reference sources.

Summary: IPI evidence for SET1 as component of trithorax-like COMPASS complex.

Reason: Convergent IPI evidence from trithorax complex co-purification studies.