H3-3A

Summary: Centromeric H3.3 occupancy does not yet resolve the narrower kinetochore localization assertion.

Reason: The target P84243 leaf is inside PTN008517672, a Unikonts duplication node bearing the GO:0000776 IBD assertion. All four retained experimental seed products resolve in the actual tree to centromeric histone H3 proteins (Candida and budding-yeast CSE4, Drosophila cid, and C. elegans hcp-3), and their current experimental kinetochore annotations were recovered. Human H3.3 is present in centromeric chromatin (PMID:21738837), but GO:0000776 denotes the spindle-microtubule attachment complex. The full FRET study distinguishes the C-terminal proximity of H3.1 from H3.3 to CENP-T while also finding the H3.3 N terminus in its distal neighborhood (PMID:25775162). That experiment therefore cannot be used as proof of total H3.3 exclusion. The available evidence leaves the exact complex-localization scope unresolved.

Summary: H3.3 occupies telomeric chromatin during S phase in the tested ES-cell context.

Reason: The original Results and imaging describe MYC-H3.3 at telomeres in undifferentiated mouse embryonic stem cells, with replication-linked loading and loss of enrichment upon differentiation. Retain the literal S-phase extension. The host and condition are explicit; the experiment does not establish ubiquitous telomeric enrichment or an H3-3A-specific endogenous locus.

Summary: The ancestral nucleosome-membership assertion is retained by H3.3.

Reason: The genuine PAINT family slice assigns GO:0000786 to PTN008967730 and the retrieved topology confirms P84243 descent. The retained IBD contains P84243 itself among experimentally grounded seeds; that is legitimate target grounding, not circular propagation. Nucleosome incorporation is independently supported by the H3.3 biochemical record (PMID:14718166).

Summary: H3.3 is incorporated into nucleosomes.

Reason: The abstract explicitly reports H3.3 deposition through a DNA-synthesis-independent nucleosome assembly pathway. Retain the core complex membership while keeping the genomic source of the shared H3.3 product unspecified.

Summary: Tagged human H3.3 occurs in purified mononucleosomes.

Reason: Mononucleosome preparation, FLAG immunopurification and protected-DNA sequencing directly support complex membership. H3.3/H2A.Z particle occupancy is distinct from sequence-specific DNA recognition.

Summary: The human H3.3 nucleosome was structurally resolved.

Reason: The primary abstract explicitly reports a human H3.3 nucleosome structure, and the linked primary PDB deposition 3AV2 identifies the recombinant human histone within the DNA-bound complex. This directly supports nucleosome membership.

Summary: H3.3-H4 is incorporated into reconstituted nucleosomes.

Reason: The abstract describes variant-selective tNASP-mediated H3.3-H4 deposition onto DNA. This explicitly supports the experimental nucleosome-membership assertion; no separate testis-specific physiological role is inferred.

Summary: H3.3 is a component of the nucleosome.

Reason: The current InterPro IPR000164 family mapping includes GO:0000786, and the native P84243 record contains that family. H3.3-containing H3-H4 units form part of the nucleosome core. This is conserved structural membership appropriate for the target.

Summary: Regulatory-region occupancy reflects DNA binding in nucleosomes.

Reason: FLAG-H3.3 nucleosome purification and sequencing map regulatory-region occupancy. These assays establish chromatin association, not recognition of a DNA sequence motif. The verified GO:0000978 ancestry requires sequence-specific DNA binding; nucleosomal DNA binding describes the demonstrated activity and is already represented elsewhere in this review.

Proposed replacements: nucleosomal DNA binding

Summary: Promoter enrichment does not establish sequence-specific promoter recognition.

Reason: Promoter-associated H3.3/H2A.Z particles were recovered by nucleosome immunopurification. The experiment supports nucleosomal DNA association without distinguishing a sequence-recognition mechanism. Replace the sequence-specific molecular function with the existing nucleosomal DNA-binding term; this proposes no additional annotation.

Proposed replacements: nucleosomal DNA binding

Summary: DNA binding is an intrinsic part of H3.3 nucleosome function.

Reason: InterPro IPR000164 (Histone H3/CENP-A) and IPR007125 (Core Histone H2A/H2B/H3 domain) both map to GO:0003677 and both occur in the native P84243 record. H3.3 contributes DNA-contacting histone structure in nucleosomes. This broad DNA-binding assertion is sound; it does not imply sequence-specific recognition.

Reason: dSfmbt binds mono- and dimethylated H3 peptides in quantitative assays. Retain this physical interaction with the fly protein; the shared histone-tail sequence does not establish a native human complex or H3-3A-specific function.

Reason: HP1α chromodomain binding to methylated H3 tail is measured directly, including competition with DNMT3A. This supports binding to a modified histone substrate, without establishing H3.3-selective recognition or a distinct H3-3A locus function.

Reason: Structural and biochemical assays show DNMT3A ADD-domain recognition of H3 with unmethylated K4. The positive shared-tail interaction is retained; DNA methyltransferase activity belongs to DNMT3A, not this histone.

Reason: ATRX immunoprecipitation recovers MYC-H3.3 in mouse embryonic stem cells, with reduced recovery after H3 K4 mutation. Retain the demonstrated association with mouse ATRX; this is not a locus-specific human assay or purified pairwise binding experiment.

Reason: Flag affinity purification from HeLa cells recovers DAXX with H3.3 oligonucleosomes. This human association is distinct from the paper's endogenous mouse H3.3B tagging arm and does not identify the contributing human H3.3 locus.

Reason: Purified PELP1 binds dimethylated H3K4/H3K9 peptides, with supporting MCF7 extract assays. Retain the physical interaction, while recognizing that the shared tail is not H3.3-specific and does not confer demethylase activity on H3.

Reason: Purified DAXX binds recombinant human H3.3–H4 preferentially over H3.1–H4. This directly supports the chaperone–histone interaction; H3.3 is the bound histone, not the histone chaperone.

Reason: Recombinant human DAXX and H3.3–H4 interact in pull-down assays, with variant-specific core residues contributing to recognition. Retain binding without assigning DAXX's assembly or remodeling activities to H3.3.

Reason: TAF3 PHD binds H3K4me3 peptides, and adjacent T3 phosphorylation reduces affinity. This supports modification-dependent tail binding, not H3.3-selective recognition; the experiments do not distinguish H3-3A from H3-3B.

Reason: The DAXX–H3.3–H4 structure and biochemical complexes support H3.3–H4 association. Stabilizing substitutions used for crystallography are disclosed; the histone interaction remains supported without assigning DAXX's chaperone activity to H3.3.

Reason: The reported CAF1 p150 association is gained by H3.3 G90M (Fig. 4a), rather than demonstrated for unmodified wild-type H3.3. This source therefore overextends mutant evidence; it does not establish that all H3.3–CAF1 association is impossible.

Reason: Biochemical assays show ASF1 binding H3.3–H4, and ASF1B perturbation changes competition with DAXX. Retain the histone–chaperone interaction without asserting that ASF1B and DAXX occupy one common histone complex.

Reason: Structural and cellular assays support DAXX binding H3.3–H4 through the variant-recognition interface. Retain the incoming DAXX isoform identifier; the experiments do not establish that binding is unique to this isoform.

Reason: A purified human DAXX–H3.3–H4 complex resolves the H3.3–H4 heterodimer structurally. Retain the demonstrated histone association without promoting this generic binding annotation into a separate core activity.

Reason: Human DAXX–H3.3–H4 crystallography and coimmunoprecipitation support the DAXX interaction. Preserve the supplied DAXX isoform context without inferring isoform-exclusive binding or H3-3A-specific expression.

Reason: Curated anti-tag coimmunoprecipitation records identify H3.3–H4 in human cell lines. Retain this positive physical association without transferring the paper's mutant PRC2 effects or claiming locus-specific H3-3A evidence.

Reason: The human H3.3-SNAP coimmunoprecipitation arm detects DAXX association, which decreases after Cul4A/DDB1 depletion. Retain binding; the yeast ubiquitination experiments are a separate arm and do not establish ubiquitin-ligase activity of H3.3.

Reason: Mouse ZMYND11 domains bind H3.3K36me3 peptides in structural and affinity assays, with H3.3 S31 contributing specificity. Retain this defined interaction with the supplied mouse partner, without assigning the reader's regulatory activity to H3.3.

Reason: Retain established H3.3–DAXX binding, supported independently by human-cell association and purified binding. The specific AP-MS assignment in PMID:24981860 remains unverified; no H3-3A-specific origin is inferred.

Reason: The curated dataset records P84243–NASP isoform 2 in validated yeast two-hybrid assays. Retain the tested physical association; multiple assay-method records from this one study do not establish independent studies or isoform-exclusive binding.

Reason: Purified human H3.3–H4 complexes and their structures support H4 association. The reconstitution uses defined histone fragments and chaperones, without resolving the endogenous H3.3 gene of origin.

Reason: The structure resolves ASF1B and MCM2 around an H3.3–H4 dimer, using a linked MCM2–ASF1B construct. Retain the supported ASF1B contact while preserving this engineered context and avoiding a chaperone-activity assignment to H3.3.

Reason: AF10 PZP binds H3 peptides and nucleosomes containing unmodified K27. Retain the positive physical interaction; shared-tail recognition does not establish H3.3 selectivity or transfer AF10/DOT1L enzymatic functions to H3.

Reason: AF17 PZP binds H3 tail peptides and reconstituted nucleosomes, with K27 modification disrupting recognition. This supports the stated association without establishing a locus-specific H3-3A role or assigning AF17's regulatory functions to the histone.

Reason: HuRI records the P84243–DAXX pair in yeast two-hybrid formats. Retain the inspected physical association; three assay-method records belong to one study and do not independently establish its endogenous setting or gene of origin.

Reason: Recombinant human DNAJC9 binds H3.3–H4 directly, supported by pull-down, affinity and structural assays. Retain this histone–chaperone interaction; the chaperone and heat-shock functions are properties of DNAJC9 rather than H3.3.

Reason: BioPlex records HP1α with tagged P84243 in HEK293T affinity purification. Retain this complex association without treating the spoke-expanded record as direct pairwise binding or evidence identifying the endogenous H3.3 locus.

Reason: BioPlex records CAF1 p150 with tagged P84243 in HEK293T affinity purification. This positive complex association is retained independently of the separate G90M-specific experiment; it does not establish purified pairwise binding.

Reason: BioPlex records ASF1B with tagged P84243 in HEK293T affinity purification. Retain the observed complex association, while distinguishing spoke-expanded co-purification from a direct interaction measured with purified partners.

Reason: BioPlex records DAXX–P84243 association in HEK293T affinity purifications. Retain this assay-supported complex association; the dataset does not resolve H3-3A versus H3-3B origin or alone establish a distinct histone molecular function.

Summary: Extracellular H3.3 in chromatin exposed after cell death.

Reason: Reactome includes P84243 in extracellular chromatin bound by serum amyloid P. This supports a released-chromatin location, peripheral to its nuclear chromatin role; it does not establish conventional secretion or H3.3-specific control of amyloid formation.

Summary: Extracellular citrullinated H3.3 in the modeled chromatin activator of factor XII.

Reason: Reactome places citrullinated P84243 in decondensed chromatin among extracellular polyanionic activators bound by factor XII. Retain this non-core released-chromatin location; factor XII performs the proteolysis, and the mapping does not resolve the encoding H3.3 locus.

Summary: Extracellular citrullinated H3.3 in the modeled chromatin activator of factor XII.

Reason: Reactome places citrullinated P84243 in decondensed chromatin among extracellular polyanionic activators associated with factor XII autoactivation. Retain this non-core released-chromatin location; factor XII performs the proteolysis, and the mapping does not resolve the encoding H3.3 locus.

Summary: The sperm-specific nuclear proteomics assignment needs its target identification record.

Reason: The abstract establishes purified human sperm nuclei and histone detection, but the H3.3 identification and discriminating peptides were not accessible. General nuclear H3.3 localization does not independently verify this sperm context. Preserve CL:0000019 and the curator assertion while leaving the source-specific assignment unresolved.

Summary: The nuclear localization inherited from the histone family is correct for H3.3.

Reason: P84243 descends from the nuclear-localization gain at PTN008967730. P84243 itself is an experimentally grounded seed in the retained IBD, and the native UniProt record and human H3.3 immunofluorescence (PMID:34876591) independently support nuclear localization. The self-donor is expected and is not evidence of circularity.

Summary: Nuclear localization is consistent with the demonstrated nucleosomal role.

Reason: The primary abstract and deposited human H3.3 nucleosome structure establish the chromatin structural product. Retain the unequivocal nuclear location and defer to the experimental curator; the inaccessible full article prevents an independent account of any additional cellular localization assay. The crystal structure itself is not presented as an imaging experiment.

Summary: The UniProt nuclear-location mapping is appropriate.

Reason: The native P84243 UniProt record explicitly gives nucleus as its subcellular location. The SL-0191 to GO:0005634 mapping therefore agrees with the target record and with human H3.3 nuclear localization (PMID:34876591).

Summary: Wild-type and tested variant H3.3 proteins localize to the nucleus.

Reason: The Results report nuclear localization in HEK293T cells, and Methods specify human H3-3A and H3-3B cDNAs and immunofluorescence. This supports nuclear H3.3 localization, without converting mutant effects into separate normal functions.

Summary: HPA immunofluorescence supports nucleoplasmic localization.

Reason: The HPA H3-3A subcellular page reports supported nucleoplasmic localization, using antibodies CAB011481, HPA050968 and HPA064058 in human cell lines. The assay is indirect immunofluorescence with confocal microscopy. This agrees with the nuclear chromatin function of H3.3. The staining supports localization of the histone product, not exclusive attribution of the indistinguishable H3.3 protein to the H3-3A gene.

Summary: The ARBA nucleoplasm prediction matches a verified target rule condition and known localization.

Reason: ARBA00026290 (modified 2026-07-18) emits GO:0005654. Its condition set 29 requires FunFam 1.10.20.10:FF:000044 and 1.10.20.10:FF:000078 together with Hominidae. Both FunFam matches occur in the native P84243 record and the target is human, so this conjunction is satisfied. HPA independently supports the predicted nucleoplasmic location; no claim that the computational record is an additional experiment is made.

Summary: Nucleoplasmic H3.3 in the curated PRC2 recruits DNA methyltransferases event.

Reason: Reactome explicitly models P84243 as a chromatin constituent during PRC2-mediated recruitment of DNA methyltransferases in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated Polycomb Repressive Complex 2 (PRC2) Is recruited to chromatin event.

Reason: Reactome explicitly models P84243 as a chromatin constituent at PRC2 recruitment sites in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated PRC2 trimethylates histone H3 at lysine-27 event.

Reason: Reactome explicitly models P84243 as a histone substrate in PRC2-associated chromatin during H3K27 methylation in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated DNMT1,3A,3B:PRC2 methylates cytosine and histone H3 event.

Reason: Reactome explicitly models P84243 as a chromatin constituent and histone substrate in the DNMT:PRC2 reaction in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated KDM6B demethylates H3K27me3 on p16INK4A promoter event.

Reason: Reactome explicitly models P84243 as an H3K27-methylated nucleosome constituent at the CDKN2A locus, acted on by KDM6B in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated PRC1.4 complex binds H3K27Me3 nucleosomes on CDKN2A promoter event.

Reason: Reactome explicitly models P84243 as an H3K27-methylated nucleosome constituent bound by PRC1.4 at CDKN2A in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated p-MAPKAPK3 phosphorylates BMI1 event.

Reason: Reactome explicitly models P84243 as a CDKN2A chromatin constituent during MAPKAPK3 phosphorylation of BMI1 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated PRC2-EZH2 trimethylates nucleosomes associated with CDKN2A promoter event.

Reason: Reactome explicitly models P84243 as a CDKN2A-associated histone substrate for PRC2-EZH2 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated EHMT1:EHMT2 methylates IL8 promoter event.

Reason: Reactome explicitly models P84243 as an IL8-promoter nucleosome constituent modified by EHMT1:EHMT2 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated EHMT1:EHMT2 methylates IL6 promoter event.

Reason: Reactome explicitly models P84243 as an IL6-promoter nucleosome constituent modified by EHMT1:EHMT2 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated MBD2 binds methylcytosine in chromatin event.

Reason: Reactome explicitly models P84243 as a histone constituent of methylated chromatin bound by MBD2 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated eNoSC deacetylates histone H3 event.

Reason: Reactome explicitly models P84243 as an acetylated histone substrate for the SIRT1 component of eNoSC in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated eNoSC dimethylates histone H3 at lysine-9 event.

Reason: Reactome explicitly models P84243 as a histone substrate for the SUV39H1 component of eNoSC in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated Formation of energy-dependent Nucleolar Silencing Complex (eNoSC) event.

Reason: Reactome explicitly models P84243 as an H3K9-methylated chromatin constituent that recruits the eNoSC silencing complex in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated B-WICH:histone acetyltransferase acetylates histone H3 at lysine-9 event.

Reason: Reactome explicitly models P84243 as a nucleosomal histone substrate for B-WICH-associated acetyltransferases in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated AGO1,2:small RNA complexes interact with chromatin event.

Reason: Reactome explicitly models P84243 as a chromatin constituent in the modeled association of AGO:small-RNA complexes with chromatin in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated PKN1:AR complex binds promoters of KLK2 and KLK3 genes event.

Reason: Reactome explicitly models P84243 as a methylated nucleosome constituent at KLK2/KLK3 promoters bound by PKN1:AR in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated PKN1 phosphorylates histone 3 of nucleosomes associate with KLK2 and KLK3 promoters event.

Reason: Reactome explicitly models P84243 as a nucleosomal histone substrate for PKN1 at KLK2/KLK3 promoters in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated Demethylase KDM4C binds KLK2 and KLK3 promoters event.

Reason: Reactome explicitly models P84243 as a modified nucleosome constituent at KLK2/KLK3 promoters during KDM4C recruitment in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated KDM4C demethylates Me3K-10-H3 associated with KLK2 and KLK3 promoters event.

Reason: Reactome explicitly models P84243 as a methylated histone substrate for KDM4C at KLK2/KLK3 promoters in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated KDM1A demethylates dimethylated H3K9 (Me2K-10-H3) at KLK2 and KLK3 promoters event.

Reason: Reactome explicitly models P84243 as a modeled methylated histone substrate for KDM1A at KLK2/KLK3 promoters in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated Demethylase KDM1A binds KLK2 and KLK3 promoters event.

Reason: Reactome explicitly models P84243 as a modeled modified nucleosome constituent during KDM1A recruitment to KLK2/KLK3 promoters in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated KDM1A demethylates monomethylated H3K9 (MeK-10-H3) at KLK2 and KLK3 promoters event.

Reason: Reactome explicitly models P84243 as a monomethylated histone substrate for KDM1A at KLK2/KLK3 promoters in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated RUNX1:CBFB, SIN3A(SIN3B), PRMT6 and HDAC1 bind the ITGA2B promoter event.

Reason: Reactome explicitly models P84243 as an H3K4me2 nucleosome constituent in the ITGA2B repression complex in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated RUNX1 and GATA1 bind the promoter of the ITGA2B gene event.

Reason: Reactome explicitly models P84243 as an H3K4me2 nucleosome constituent during RUNX1/GATA1 recruitment at ITGA2B in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated Core MLL complex methylates H3K4Me2-Nucleosome at the ITGA2B gene promoter event.

Reason: Reactome explicitly models P84243 as an H3K4me2 nucleosome substrate for the MLL complex at ITGA2B in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated PRMT6 arginine methylates H3K4me2-Nucleosome at the ITGA2B gene promoter event.

Reason: Reactome explicitly models P84243 as an ITGA2B nucleosome constituent modified by PRMT6 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated RUNX1:CBFB, SIN3A(SIN3B), PRMT6 and HDAC1 bind the GP1BA promoter event.

Reason: Reactome explicitly models P84243 as an H3K4me2 nucleosome constituent in the GP1BA repression complex in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated PRMT6 arginine methylates H3K4me2-Nucleosome at the GP1BA gene promoter event.

Reason: Reactome explicitly models P84243 as a GP1BA nucleosome constituent modified by PRMT6 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated RUNX1 and GATA1 bind the promoter of the GP1BA gene event.

Reason: Reactome explicitly models P84243 as an H3K4me2 nucleosome constituent during RUNX1/GATA1 recruitment at GP1BA in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated Core MLL complex methylates H3K4Me2-Nucleosome at the GP1BA gene promoter event.

Reason: Reactome explicitly models P84243 as an H3K4me2 nucleosome substrate for the MLL complex at GP1BA in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated RUNX1 and GATA1 bind the promoter of the THBS1 gene event.

Reason: Reactome explicitly models P84243 as a modeled H3K4me2 nucleosome constituent during RUNX1/GATA1 recruitment at THBS1 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated RUNX1:CBFB, SIN3A(SIN3B), PRMT6 and HDAC1 bind the THBS1 gene promoter event.

Reason: Reactome explicitly models P84243 as a modeled H3K4me2 nucleosome constituent in the THBS1 repression complex in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated Core MLL complex methylates H3K4Me2-Nucleosome at the THBS1 gene promoter event.

Reason: Reactome explicitly models P84243 as a modeled histone substrate for the MLL complex at THBS1 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated PRMT6 arginine methylates H3K4me2-Nucleosome at the THBS1 gene promoter event.

Reason: Reactome explicitly models P84243 as a THBS1 nucleosome constituent modified by PRMT6 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated RUNX1 and GATA1 bind the promoter of the MIR27A gene event.

Reason: Reactome explicitly models P84243 as an H3K4me2 nucleosome constituent during RUNX1/GATA1 recruitment at MIR27A in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated Core MLL complex methylates H3K4Me2-Nucleosome at the MIR27A gene promoter event.

Reason: Reactome explicitly models P84243 as an H3K4me2 nucleosome substrate for the MLL complex at MIR27A in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated PRMT6 arginine methylates H3K4me2-Nucleosome at the MIR27A gene promoter event.

Reason: Reactome explicitly models P84243 as a MIR27A nucleosome constituent modified by PRMT6 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated RUNX1:CBFB, SIN3A(SIN3B), PRMT6 and HDAC1 bind the MIR27A gene promoter event.

Reason: Reactome explicitly models P84243 as an H3K4me2 nucleosome constituent in the MIR27A repression complex in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated FOXA1 and GATA3 bind to CCND1 promoter event.

Reason: Reactome explicitly models P84243 as an H3K4-methylated nucleosome constituent at the CCND1 regulatory complex in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated Binding of AP1 transcriptional activator complexes to CCND1 promoter event.

Reason: Reactome explicitly models P84243 as a CCND1 nucleosome constituent during recruitment of transcriptional activators in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated KDM4B demethylates H3K9me3 on estrogen-responsive target enhancers event.

Reason: Reactome explicitly models P84243 as an H3K9-methylated nucleosome substrate for KDM4B at estrogen-responsive targets in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated ESR1:ESTG and KDM4B bind H3K9me3 target gene enhancers event.

Reason: Reactome explicitly models P84243 as an H3K9-methylated nucleosome constituent during ESR1/KDM4B recruitment in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated EP300 is recruited to MYC and BCL2 genes event.

Reason: Reactome explicitly models P84243 as an H3 constituent of HIST1H2AC-containing nucleosomes during EP300 recruitment at MYC/BCL2 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated Overexpressed HIST1H2AC and ESR1:ESTG bind MYC and BCL2 genes event.

Reason: Reactome explicitly models P84243 as an H3K9me2 nucleosome constituent in the modeled HIST1H2AC/ESR1 response at MYC/BCL2 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated KDM1A is recruited to MYC and BCL2 genes event.

Reason: Reactome explicitly models P84243 as an H3K9me2 nucleosome constituent during KDM1A recruitment at MYC/BCL2 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated KDM1A demethylates H3 on MYC and BCL genes in response to estrogen event.

Reason: Reactome explicitly models P84243 as an H3K9me2 histone substrate for KDM1A at MYC/BCL2 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated NR5A2, ZNF217 and NCOA3 bind GREB1 promoter event.

Reason: Reactome explicitly models P84243 as a nucleosome constituent at the estrogen-responsive GREB1 regulatory complex in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated Histone H3.3 deposition at telomere event.

Reason: Reactome explicitly models P84243 as the H3.3 histone deposited at telomeres by ATRX:DAXX in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated The GSDME gene promoter is hypermethylated event.

Reason: Reactome explicitly models P84243 as a chromatin constituent within the modeled DNMT:PRC2 catalyst complex at GSDME in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated ORC1 binds to H4K20me2 event.

Reason: Reactome explicitly models P84243 as an H3 nucleosome constituent accompanying the H4K20me2 mark recognized by ORC1 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated PRC2 (EZH2) core complex binds CDH1 gene promoter event.

Reason: Reactome explicitly models P84243 as a nucleosome constituent during PRC2 recruitment to CDH1 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated PRC2 (EZH2) core complex methylates nucleosomes at CDH1 gene promoter event.

Reason: Reactome explicitly models P84243 as a histone substrate in CDH1 nucleosomes modified by PRC2 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated SETDB1 in ATF7IP:SETDB1:SUMO2-6K-TRIM28:KRAB-ZFP:retroelement trimethylates lysine-9 of histone H3 in nucleosomes event.

Reason: Reactome explicitly models P84243 as a retroelement nucleosome substrate for SETDB1 recruited through TRIM28/ATF7IP in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated KRAB-ZFP binds retroelement DNA in chromatin event.

Reason: Reactome explicitly models P84243 as a retroelement chromatin constituent during KRAB-ZFP binding in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated ATF7IP:SETDB1 binds SUMO2-6K-TRIM28:KRAB-ZFP:retroelement chromatin event.

Reason: Reactome explicitly models P84243 as a retroelement chromatin constituent during recruitment of ATF7IP:SETDB1 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated Unliganded PPARG:RXRA heterodimer recruits corepressors to target gene loci event.

Reason: Reactome explicitly models P84243 as a nucleosome constituent at PPARG:RXRA-regulated adipogenic loci during corepressor recruitment in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated Corepressors are released from liganded PPARG:RXRA heterodimer event.

Reason: Reactome explicitly models P84243 as a nucleosome constituent at PPARG:RXRA-regulated adipogenic loci during corepressor release in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated RXRA binds ligands event.

Reason: Reactome explicitly models P84243 as a nucleosome constituent accompanying the PPARG:RXRA target-gene complex during RXRA ligand binding in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated Coactivators are recruited to liganded PPARG:RXRA heterodimer event.

Reason: Reactome explicitly models P84243 as a nucleosome constituent at ligand-activated PPARG:RXRA target loci during coactivator recruitment in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated CBX5 (HP-1alpha) binds TRIM28 (KAP1) in SUMO2-6K-TRIM28:KRAB-ZFP:retroelement chromatin event.

Reason: Reactome explicitly models P84243 as a retroelement chromatin constituent during CBX5 recruitment to TRIM28 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated SETDB1 in me3-K16-ATF7IP:SETDB1:MORC2:HUSH complex:L1 RNA trimethylates lysine-9 of histone H3 (H3K9me3) event.

Reason: Reactome explicitly models P84243 as a nucleosomal histone substrate for RNA-tethered SETDB1:HUSH in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated MPHOSPH8 (MPP8) in HUSH complex binds histone H3 trimethyl-lysine 9 (H3K9me3) in L1HS,L1PA2,3 heterochromatin event.

Reason: Reactome explicitly models P84243 as an H3K9-methylated nucleosome constituent recognized by the MPHOSPH8 component of HUSH in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated SETDB1 in me3-K16-ATF7IP:SETDB1:MORC2:HUSH complex:L1HS,L1PA2,3 heterochromatin trimethylates lysine-9 of histone H3 in adjacent nucleosome event.

Reason: Reactome explicitly models P84243 as an adjacent nucleosome substrate for HUSH-associated SETDB1 during heterochromatin spreading in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated CD274 gene binding to Nucleosome event.

Reason: Reactome explicitly models P84243 as a core histone constituent in the modeled assembly of CD274-associated nucleosomes in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated PRC2(EZH2) core binding to CD274 gene promoter event.

Reason: Reactome explicitly models P84243 as a CD274-promoter nucleosome constituent during PRC2 binding in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated Trimethylation of CD274 gene chromatin by MLL1/3 complex event.

Reason: Reactome explicitly models P84243 as a CD274-associated histone substrate for the modeled MLL1/MLL3 complex in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated Trimethylation of CD274 gene promoter by EZH2 event.

Reason: Reactome explicitly models P84243 as a CD274-promoter histone substrate for EZH2 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated BRD4 binding to CD274 gene chromatin event.

Reason: Reactome explicitly models P84243 as a CD274 chromatin constituent during BRD4 association with acetylated histones in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated MLL1,MLL3 complex binding to CD274 gene chromatin event.

Reason: Reactome explicitly models P84243 as a CD274 chromatin constituent during MLL1/MLL3 recruitment in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated HP1 alpha binds Histone H3K9(me)3 event.

Reason: Reactome explicitly models P84243 as a methylated H3 ligand in the HP1/CBX5 binding event in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated ZNF827 and NR2C2,NR2F2 recruit NuRD to telomeric chromatin event.

Reason: Reactome explicitly models P84243 as an H3 constituent of H4-acetylated telomeric chromatin during NuRD recruitment in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated NuRD deacetylates telomeric nucleosomes event.

Reason: Reactome explicitly models P84243 as an H3 constituent of telomeric nucleosomes whose H4 residues are deacetylated by NuRD in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated CHD1 and CHD2 bind H3K4me3 nucleosomes event.

Reason: Reactome explicitly models P84243 as an H3K4me3 nucleosome constituent recognized by CHD1/CHD2 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated CHD1:H3K4me3 interacts with post-initiation transcription complexes event.

Reason: Reactome explicitly models P84243 as an H3K4me3 chromatin constituent accompanying CHD1-associated transcription complexes in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated CHD6-9-dependent ATP hydrolysis event.

Reason: Reactome explicitly models P84243 as a nucleosome constituent in the chromatin substrate remodeled by CHD6-9 in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated NuRD deacetylates nucleosomes event.

Reason: Reactome explicitly models P84243 as a candidate acetylated H3 constituent of the generic NuRD chromatin substrate in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated NuRD binds TCF19 at FBP1 gene event.

Reason: Reactome explicitly models P84243 as an H3K4me3 nucleosome constituent at FBP1 during TCF19-dependent NuRD recruitment in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated NuRD binds TCF19 at G6PC gene event.

Reason: Reactome explicitly models P84243 as an H3K4me3 nucleosome constituent at G6PC during TCF19-dependent NuRD recruitment in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated NuRD binds TCF19 at PCK1 gene event.

Reason: Reactome explicitly models P84243 as an H3K4me3 nucleosome constituent at PCK1 during TCF19-dependent NuRD recruitment in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: Nucleoplasmic H3.3 in the curated JMJD1C demethylates H3K9 mono- and di-methylation event.

Reason: Reactome explicitly models P84243 as a methylated H3 substrate for JMJD1C in nucleoplasm. This supports its core nuclear chromatin location, without assigning the modifying or regulatory proteins' activities to H3.3 or resolving its encoding locus.

Summary: H3.3 is a chromosomal histone.

Reason: Chromosome association is consistent with H3.3 nucleosome incorporation and is retained as a well-established structural location. This paper directly documents nuclear WT and mutant H3.3; a separate chromosome-resolved assay was not independently identified in the inspected main text. The broad location is accepted without claiming that such an assay was read.

Summary: Chromosomal localization is supported.

Reason: UniProt lists chromosome; this supports chromatin association without specifying centromeres or kinetochores.

Summary: H3.3 is a structural participant in nucleosome assembly.

Reason: The tNASP assay deposits H3.3-H4 onto DNA and compares H3 variants. H3.3 supplies the assembled histone structure; tNASP performs the chaperone activity. The abstract explicitly reports this biochemical result, supporting the curator annotation without attributing chaperone catalysis to H3.3.

Summary: Histone H3.3 supports chromosome alignment during mitosis through chromosome structure.

Reason: The P84243 leaf genuinely descends from the Eukaryota IBD node PTN008517671. Its GO:0007080 seeds include ordinary fission-yeast histones hht1 (SPAC1834.04) and hht3 (SPBC1105.11c), as well as Drosophila cid; this is not solely a centromeric-H3 donor set. Independent combined H3f3a/H3f3b depletion in mouse embryonic fibroblasts caused chromosome misalignment in mitosis (PMID:28177753). Retain the inferred role as a contextual consequence of the structural chromatin function, without claiming a distinct H3-3A-specific alignment apparatus.

Reason: Combined H3F3A/H3F3B RNAi and H3.5 rescue were assessed by doubling time and BrdU labeling. These accessible endpoints establish proliferation dependence, not positive regulation of individual-cell size. This is an overextension of the demonstrated phenotype; the full article was not read.

Summary: The ancestral chromatin-structural function is retained by H3.3.

Reason: The genuine PTHR11426 slice places the GO:0030527 gain at PTN008967730, and the retrieved target topology confirms descent of P84243 from that node. The source IBD includes experimentally annotated P84243 itself alongside other histones. This self-donor is legitimate experimental grounding for an inherited histone function, not circular propagation.

Summary: H3.3 supplies structural histone material to chromatin.

Reason: Purified H3.3 deposition complexes and DNA-synthesis-independent assembly support its direct structural role. HIRA supplies chaperone activity; H3.3 contributes the histone structure. The accessible abstract explicitly distinguishes these roles, although the full article was unavailable.

Summary: H3.3 is a structural constituent of chromatin.

Reason: The InterPro IPR000164 mapping to GO:0030527 is present and appropriate for this target. H3.3 is incorporated into nucleosomes as a histone structural subunit, rather than merely regulating an unrelated chromatin protein.

Summary: H3.3 binds DNA within nucleosome particles.

Reason: Purification of tagged human H3.3 mononucleosomes and sequencing of their protected DNA directly support nucleosomal DNA association. The construct is identified as human H3.3, without establishing its genomic donor locus.

Summary: The source-specific telomere-organization assertion remains unresolved.

Reason: The article tests yeast Dot1/H4-dependent telomeric silencing and also biochemical activity on human core histones. Those human assays prevent a simple wrong-organism dismissal, but the inspected evidence does not establish a human H3.3-specific telomere-organizing contribution. Preserve the TAS assertion pending clarification; this is not evidence against H3.3 participation in telomeric chromatin.

Summary: Defined nucleosome membership provides greater specificity.

Reason: H3.3-H4 deposition intermediates support complex membership. Accepted nucleosome membership and H4 heterodimerization are more specific, without implying permanent HIRA-complex membership.

Summary: H3.3 heterodimerizes with histone H4.

Reason: The verified InterPro IPR009072 histone-fold mapping is GO:0046982. P84243 carries this fold, and experimental H3.3-containing complexes contain H3.3-H4 dimers (PMID:14718166). This is a defined structural interaction central to nucleosome assembly, rather than an unspecified protein-binding claim.

Summary: The inherited kinetochore-assembly assertion requires a more specific H3.3 mechanistic justification.

Reason: P84243 genuinely descends from PTN008517671, where the retained IBD assigns GO:0051382. The experimentally grounded seeds in that retained assertion are centromeric H3 proteins, including human CENP-A; a current CENPA IDA annotation traces to PMID:11682612. This is a question about the breadth of the ancestral gain, not a bad-source allegation or an outside-clade transfer. Human H3.3 is deposited at centromeric chromatin as a placeholder before CENP-A loading (PMID:21738837), while mouse H3.3 depletion increased, rather than reduced, centromeric CENP-A binding (PMID:26159997). Neither observation by itself establishes which assembly step H3.3 performs in building the microtubule-attachment complex. Leave unresolved rather than equating centromeric occupancy or necessity with assembly activity.

Summary: The exosome proteomics identification requires the target-level record.

Reason: The accessible abstract reports B-cell exosome mass spectrometry. It does not identify the H3.3 entry or its discriminating peptides, and the target supplementary identification has not yet been verified. Preserve the unextended experimental assertion without inferring an active secretion function.

Summary: The distinct exosome assertion retains an unresolved pituitary-cell extension.

Reason: The literal CL:0000639 extension denotes a basophil cell of the pars distalis, whereas the abstract explicitly describes B-cell exosomes. Target detection and this context mapping require clarification. Keep this row distinct from the unextended assertion and preserve the incoming extension; neither missing full text nor the mismatch establishes that the physical observation is false.