SWI2

Summary: SWI2 is an obligate component of the SWI/SNF complex and localizes to chromatin at promoters and regulatory regions. IBA evidence from comparative genomics is appropriate for this well-characterized complex member.

Reason: SWI2 functions as the catalytic subunit of the SWI/SNF complex and is recruited to chromatin regions to perform nucleosome remodeling. The chromatin localization is a core functional context for this protein and well-supported by experimental evidence and evolutionary conservation.

Summary: SWI2 functions exclusively in the nucleus where chromatin remodeling occurs. Multiple direct experimental observations confirm nuclear localization.

Reason: All chromatin remodeling functions of SWI2 occur in the nucleus. IBA annotation is well-supported by experimental evidence showing nuclear localization and multiple IDA annotations confirming this.

Summary: IEA annotation confirming nuclear localization via InterPro domain analysis. Redundant with IBA and IDA annotations but acceptable.

Reason: While this is computational inference, it is correct and consistent with IBA and IDA evidence. Keeping for completeness.

Summary: HDA annotation based on protein localization data during DNA replication stress. Direct experimental observation of nuclear localization.

Reason: Direct observation of SWI2 nuclear localization under DNA replication stress conditions. HDA provides independent experimental confirmation of nuclear localization.

Summary: Direct experimental demonstration of nuclear localization in early SWI2 work. Pioneer work establishing SWI2 function.

Reason: Direct experimental evidence of SWI2 nuclear localization from seminal work characterizing the SWI2/SNF2 protein and complex.

Summary: IDA annotation showing nuclear localization is subject to oxygen regulation. Important for understanding SWI2 localization dynamics.

Reason: Experimental confirmation that SWI2 nuclear localization is dynamically regulated by oxygen availability, providing insight into regulatory mechanisms.

Summary: NAS annotation (non-traceable author statement) based on ComplexPortal describing SWI2 as component of chromatin-associated SWI/SNF complex.

Reason: Appropriate use of NAS for complex component annotation based on well-documented database knowledge. Consistent with IBA and IDA chromatin localization evidence.

Summary: SWI2 is a core catalytic subunit of the SWI/SNF complex. Multiple IDA annotations confirm structural and biochemical association with complex.

Reason: SWI2 is an essential obligate component of the SWI/SNF complex. All IDA annotations correctly document this fundamental structural relationship. This is a core functional annotation. Falcon deep research notes that SWI2/Snf2 is the motor ATPase at the center of the ~12-subunit holo-complex (with Arp7, Arp9, Snf5, Swi1, Swi3, Snf6, etc.), and that a minimal Snf2-Arp7-Arp9 module retains partial in vitro remodeling activity.

Summary: Early experimental work isolating and characterizing the SWI/SNF complex and demonstrating SWI2 is a component.

Reason: Pioneer biochemical work establishing SWI2 as part of the multisubunit SWI/SNF chromatin remodeling complex.

Summary: Biochemical isolation and characterization of the SWI/SNF complex containing SWI2 and other subunits.

Reason: Experimental demonstration of SWI2 as core component of the SWI/SNF complex through protein purification and mass spectrometry.

Summary: SWI/SNF complex component annotation confirmed by biochemical isolation.

Reason: Experimental confirmation of SWI2 as SWI/SNF complex member through biochemical purification.

Summary: Genetic/functional evidence that SWI2 is part of SWI/SNF complex through interaction studies.

Reason: IMP annotation demonstrating functional interdependence of SWI2 with other SWI/SNF subunits (SNF5, SNF6) establishing complex membership.

Summary: Computational annotation via ARBA machine learning model. Core catalytic function of SWI2 protein confirmed by multiple IDA and IMP annotations.

Reason: SWI2 is the primary ATP-dependent helicase-like ATPase of the SWI/SNF complex. This is the central enzymatic function and primary molecular activity. IEA annotation is backed by strong IDA/IMP evidence.

Summary: IMP annotation from early work demonstrating ATP hydrolysis is required for SWI/SNF-mediated nucleosome remodeling and transcriptional activation.

Reason: Genetic and biochemical evidence that ATP hydrolysis by SWI2 is essential for chromatin remodeling activity. Core functional annotation.

Summary: Direct demonstration of ATP-dependent chromatin remodeling activity by isolated SWI/SNF complex containing SWI2.

Reason: Biochemical characterization showing SWI2-containing SWI/SNF complex exhibits ATP-dependent nucleosome remodeling activity.

Summary: Direct biochemical assays demonstrating DNA-stimulated ATPase activity of SWI2 and its requirement for nucleosome remodeling.

Reason: Critical experimental work establishing SWI2 as an ATP-dependent helicase-like enzyme with DNA-stimulated ATPase activity required for chromatin remodeling.

Summary: Genetic evidence that SWI2 ATP hydrolysis activity is functionally essential for chromatin remodeling in vivo.

Reason: Functional analysis showing ATP hydrolysis is required for SWI2-mediated chromatin remodeling during transcriptional activation.

Summary: SWI2 bromodomain directly binds acetylated histones. Multiple IDA annotations show histone reader activity on specific histone modifications.

Reason: SWI2 contains a bromodomain that recognizes acetylated lysine residues on histone H3 and H4. This is a core molecular function enabling recruitment to acetylated chromatin regions. Falcon deep research adds that the SWI2/Snf2 bromodomain acts as an acetylation sensor whose competitive interactions (with acetylated histone tails versus acetylated Snf2 lysines) tune Swi/Snf occupancy dynamics on stress-responsive genes.

Summary: Functional evidence that SWI2 histone-binding capability is required for normal SWI/SNF function in vivo.

Reason: Genetic studies demonstrate that SWI2 bromodomain-mediated histone binding is functionally important for chromatin remodeling in vivo.

Summary: ARBA machine learning annotation predicting H4 reader activity. Supported by experimental data on SWI2 bromodomain specificity.

Reason: SWI2 bromodomain recognizes acetylated histone H4. IEA is backed by experimental IDA evidence for H4-specific binding.

Summary: Direct biochemical characterization of SWI2 bromodomain binding selectivity for acetylated histone H4 peptides.

Reason: Experimental demonstration that SWI2 bromodomain specifically recognizes acetylated histone H4 residues, establishing histone H4 reader activity as a core function.

Summary: Biochemical demonstration of SWI2 bromodomain binding to acetylated histone H3K14. Specific histone reader function.

Reason: Direct experimental evidence of SWI2 bromodomain recognizing acetylated lysine 14 on histone H3, demonstrating specificity of histone reader activity.

Summary: IBA annotation reflecting DNA binding activity of SNF2 family proteins across eukaryotes. SWI2 binds DNA through its helicase-like domain and AT-hook motifs.

Reason: SWI2 contains DNA-binding domains (AT-hooks and helicase-like domain) and functions as an ATP-dependent DNA translocase. DNA binding is a prerequisite for nucleosome remodeling activity.

Summary: InterPro-based IEA annotation for DNA binding based on AT-hook motif domain detection.

Reason: While correct and subsumed by more specific nucleosomal DNA binding annotations, it is consistent with IBA evidence and appropriate to keep.

Summary: Direct biochemical demonstration that SWI2 specifically binds nucleosomal DNA with high affinity.

Reason: More specific and informative than generic DNA binding. SWI2 directly binds nucleosomal DNA as a critical step in chromatin remodeling. This is a core functional annotation more specific than GO:0003677.

Summary: Specific demonstration that SWI2 binds ribosomal DNA sequences. Shows SWI2 involvement in rDNA transcriptional regulation.

Reason: SWI2 is recruited to rDNA loci and participates in regulation of RNA polymerase I transcription. Specific and supported by experimental evidence.

Summary: IBA annotation for chromatin binding capability. SWI2 must bind chromatin to perform all its remodeling functions. Phylogenetic inference is appropriate.

Reason: SWI2 must bind chromatin/nucleosomes to perform its catalytic functions. Chromatin binding is a core property of this chromatin remodeling enzyme.

Summary: InterPro-based annotation inferring histone binding from SnAC domain (histone-binding domain). SWI2 contacts histone core through multiple domains.

Reason: While correct, this is a general annotation subsumed by more specific histone reader activity annotations (H3, H4 acetyl-lysine binding). Keep for completeness but note more specific annotations exist.

Summary: IEA annotation based on InterPro helicase ATP-binding domain motifs. SWI2 contains conserved ATP-binding motifs (Walker A and Walker B boxes).

Reason: ATP binding is a prerequisite for enzymatic function but less informative than ATP hydrolysis activity. Correct but subsumed by more specific ATP hydrolysis and ATP-dependent chromatin remodeler activity annotations.

Summary: UniProtKB keyword-based IEA annotation for nucleotide binding. SWI2 contains nucleotide-binding domains in its helicase region.

Reason: Very general annotation subsumed by ATP binding and ATP hydrolysis annotations. Keep for completeness but less informative.

Summary: RHEA-based annotation for ATP hydrolysis activity. SWI2 catalyzes ATP hydrolysis as its primary enzymatic reaction. Core function.

Reason: SWI2 is an ATP-dependent helicase-like enzyme that catalyzes ATP hydrolysis coupled to DNA translocation and nucleosome remodeling. This is a core enzymatic function. Falcon deep research adds mechanistic detail on the SnAC and AT-hook domains that couple and tune this ATP hydrolysis output.

Summary: UniProtKB keyword-based annotation that SWI2 has hydrolase activity (ATP hydrolysis). Parent term to ATP hydrolysis activity.

Reason: Correct but very general parent term. ATP hydrolysis activity is the specific hydrolase function. Keep for completeness but ATP hydrolysis is more informative.

Summary: IBA annotation reflecting the ability of SNF2 family proteins to reposition nucleosomes within nucleosome arrays, affecting internucleosomal spacing.

Reason: SWI2-mediated nucleosome sliding and repositioning affects the spacing between adjacent nucleosomes in arrays. This is a specialized nucleosome remodeling activity. IBA is appropriate for this well-conserved function.

Summary: IPI annotation documenting SWI2 protein-protein interactions through proteomics. Multiple IPI annotations represent interactions with SWI/SNF subunits and other proteins.

Reason: While SWI2 protein interactions are real and documented, generic "protein binding" term is uninformative. The specific complex membership (SWI/SNF) and individual protein interactions are more useful. Keep as non-core since 16 IPI annotations document these interactions.

Summary: IPI annotation from proteomic analysis identifying SWI2 interactions. Part of larger set of interaction annotations.

Reason: Documented protein interactions but subsumed by SWI/SNF complex membership and more specific interaction terms (e.g., transcription factor binding).

Summary: IPI annotation documenting SWI2 interactions in proteome survey.

Reason: Generic protein binding annotation subsumed by more specific annotations.

Summary: IPI annotation from global protein complex mapping study.

Reason: Subsumed by complex membership and specific interaction annotations.

Summary: IPI annotation from study of SWI/SNF assembly and H2A-H2B displacement.

Reason: Subsumed by SWI/SNF complex membership.

Summary: IPI annotation documenting SWI2 interaction with Hmt1 methyltransferase.

Reason: Specific functional interaction but generic protein binding term is uninformative.

Summary: IPI annotation from cryo-EM structure study of SNF2-nucleosome complex.

Reason: Documented but subsumed by nucleosome binding and complex membership annotations.

Summary: IPI annotation from cryo-EM structure of SWI/SNF complex bound to nucleosome.

Reason: Subsumed by nucleosome binding and complex membership.

Summary: IPI annotation from recent protein interactome mapping.

Reason: Generic binding term subsumed by specific interaction terms.

Summary: IPI annotation documenting SNF11 interaction with SWI2.

Reason: Subsumed by SWI/SNF complex membership.

Summary: IPI annotation from GAL4 binding and SWI/SNF remodeling study.

Reason: Subsumed by transcription factor binding annotation.

Summary: IPI annotation from isolation of SWI/SNF complex.

Reason: Subsumed by SWI/SNF complex membership.

Summary: IPI annotation documenting SWI2 interaction with TFG/TAF30.

Reason: Subsumed by SWI/SNF complex membership.

Summary: IPI annotation documenting SWI2 interaction with actin-related proteins ARP7 and ARP9.

Reason: Subsumed by SWI/SNF complex membership.

Summary: Direct demonstration of SWI2 binding to transcription factors (Gal4). This is a core mechanism for SWI/SNF recruitment to target genes.

Reason: SWI2 and other SWI/SNF subunits are recruited to promoters through direct physical interactions with transcription factor activation domains. This is the primary recruitment mechanism for SWI/SNF. Falcon deep research adds that a discrete ~70 aa N-terminal activator-binding domain (ABD, aa 238-307) of Swi2 directly binds the transcriptional activation domains of Ino2, Gal4, Gcn4, Rap1, Aro80 and Swi5, although this ABD is dispensable in vivo due to redundancy with other SWI/SNF subunits that also contact activators.

Summary: Direct biochemical demonstration that SWI2-containing complexes catalyze chromatin remodeling and nucleosome sliding.

Reason: Chromatin remodeling is the primary biological process function of SWI2. Multiple lines of evidence (IDA, IMP) confirm this is a core function. Falcon deep research frames the core mechanism as ATP-dependent DNA translocation on nucleosomal substrates to reposition or destabilize nucleosomes.

Summary: Experimental demonstration of SWI/SNF chromatin remodeling catalyzed by SWI2.

Reason: Core functional annotation with strong experimental support.

Summary: Genetic evidence that SWI2 is required for chromatin remodeling.

Reason: Functional genetic studies establish SWI2 requirement for in vivo chromatin remodeling.

Summary: Genetic and biochemical evidence that SNF2 and SNF5 are required for transcriptional activation through chromatin alteration.

Reason: Pioneer work establishing SWI2-SNF5 requirement for chromatin remodeling-mediated transcriptional activation.

Summary: Genetic interaction studies demonstrating functional interdependence of SWI2 with SNF5 and SNF6 in chromatin remodeling.

Reason: IGI evidence shows SWI2 functions together with other SWI/SNF subunits in chromatin remodeling.

Summary: IBA annotation reflecting the well-conserved function of SNF2 family proteins in transcriptional activation. Core biological role.

Reason: SWI2 is essential for transcriptional activation of multiple gene classes. This is a primary biological function supported by extensive evidence. IBA is appropriate for this highly conserved role.

Summary: ARBA machine learning annotation for transcriptional activation. Supported by multiple IMP annotations.

Reason: Computational prediction backed by strong functional evidence. SWI2 is a positive regulator of RNAP II transcription.

Summary: Genetic evidence that SWI2 is required for Gcn4-mediated transcriptional activation in response to amino acid starvation.

Reason: Functional studies demonstrate SWI2 requirement for transcriptional activation of stress-response genes.

Summary: Pioneer work establishing SWI2 function in transcriptional activation. Genetic characterization of swi2 mutants.

Reason: Foundational work establishing SWI2 as a global activator of RNAP II transcription.

Summary: Genetic and molecular evidence of SWI2-dependent nucleosome movement at the INO1 promoter during gene induction.

Reason: Detailed mechanistic study showing SWI2-mediated nucleosome repositioning enables transcription factor binding and transcriptional activation.

Summary: Genetic interaction studies revealing interdependence of SWI2 with other SWI/SNF components in transcriptional activation.

Reason: IGI evidence demonstrating functional dependence on SWI/SNF complex assembly for transcriptional activation.

Summary: SWI2 involvement in cell cycle control of transcription, particularly HO gene expression.

Reason: SWI2 is required for periodic transcriptional activation of HO locus during cell cycle.

Summary: Functional evidence that SWI2 ATP hydrolysis is required for transcriptional activation.

Reason: Core functional studies showing ATP-dependent SWI2 activity is essential for gene activation.

Summary: SWI2 is directly involved in regulating RNAP II transcription through chromatin remodeling at gene promoters. The general (rather than purely positive) regulation term is appropriate because SWI/SNF acts in both directions.

Reason: Experimental work on mutant SWI/SNF complexes demonstrates direct requirement in transcriptional regulation. Falcon deep research surfaced a 2024 study (Morse et al.) showing that, in addition to its canonical activating role, SWI/SNF can REPRESS gene-proximal promoters by remodeling nucleosomes downstream of an active (distal) transcription start site, mediating transcriptional interference. This bidirectional role makes the general GO:0006357 term (regulation, not just positive regulation) an appropriate and well-supported annotation for SWI2.

Summary: UniProtKB keyword-based annotation that SWI2 is involved in transcription.

Reason: While correct and supported by strong evidence, more specific annotations (positive regulation of RNAP II transcription) are more informative. Keep but mark as non-core.

Summary: InterPro-based annotation for transcriptional regulation. Subsumed by more specific positive regulation annotation.

Reason: General transcriptional regulation term but more specific annotations (positive regulation of RNAP II transcription) are more informative.

Summary: ARBA machine learning annotation for transcription initiation-coupled chromatin remodeling. Specific and appropriate function.

Reason: SWI2 is specifically recruited to promoters during transcription initiation and catalyzes nucleosome remodeling coupled to this process. Specific and well-supported.

Summary: Functional evidence that SWI2 bromodomain-mediated histone binding is required for transcription initiation-coupled chromatin remodeling.

Reason: Detailed functional studies show SWI2 recruitment to acetylated nucleosomes at promoters and catalysis of initiation-coupled chromatin remodeling.

Summary: Genetic evidence that SWI2 is required for DNA replication through its role in chromatin remodeling at replication origins.

Reason: SWI2 participates in DNA replication by remodeling chromatin at replication origins to allow replication machinery access. Secondary but documented function.

Summary: ARBA annotation for SWI2 involvement in double-strand break repair. Supported by experimental IMP evidence.

Reason: SWI2 is required for efficient double-strand break repair through chromatin remodeling at damage sites. IEA backed by experimental evidence.

Summary: Genetic and functional evidence that SWI2 and the SWI/SNF complex are required for double-strand break repair.

Reason: Detailed experimental work showing SWI2 function in DSB repair through chromatin remodeling. Secondary but important function.

Summary: SWI2 is required for transcriptional activation of amino acid biosynthesis genes in response to amino acid starvation.

Reason: SWI2 mediates stress response through transcriptional activation of amino acid synthesis genes. Documented specific regulatory function. Falcon deep research adds that the Snf2 AT-hook auto-regulatory domain is specifically required in vivo for SWI/SNF-dependent rescue of cells under amino-acid starvation, linking high ATPase/remodeling efficiency to this stress program.

Summary: SWI2 is required for HO endonuclease gene expression, which initiates mating type switching.

Reason: Seminal work showing SWI2 is essential for HO locus activation and mating type switching. Key historical function identifying the gene.

Summary: SWI2 is required for DNA strand invasion during homologous recombination in heterochromatin regions.

Reason: SWI2 facilitates strand invasion by remodeling heterochromatin and making DNA accessible to recombination machinery.

Summary: IBA annotation suggesting SWI2 involvement in heterochromatin formation. However, literature emphasizes SWI2 role in euchromatin and transcriptional activation.

Reason: While SWI2 can access heterochromatin for DNA repair and specific gene regulation, its primary role is in euchromatin and transcriptional activation. The annotation may reflect SWI2 interaction with heterochromatin rather than heterochromatin formation per se. Mark as over-annotated for core SWI2 functions.

Proposed replacements: DNA strand invasion

Summary: SWI2 is required for FLO11 expression, which mediates cell surface adhesion and biofilm formation.

Reason: SWI2 positively regulates FLO11 transcription, which is essential for biofilm formation. Specific and documented regulatory function.

Summary: SWI2 is required for FLO11-mediated invasive growth in response to glucose limitation. Part of nutrient sensing and metabolic stress response.

Reason: SWI2 mediates transcriptional activation of FLO11 in response to glucose limitation, enabling invasive growth. Specific developmental/metabolic function.

Summary: SWI2 is involved in autophagy pathway for clearance of protein aggregates. Role in stress response and protein quality control.

Reason: SWI2 involvement in aggrephagy appears to be secondary to its primary transcriptional regulatory role. Likely related to transcriptional activation of autophagy genes rather than direct participation. Keep for completeness but mark as non-core.