BRPF1 is a multivalent chromatin reader and scaffold that assembles and activates histone acetyltransferase complexes containing KAT6A/MOZ, KAT6B/MORF or KAT7/HBO1. It connects catalytic subunits with ING and MEAF6 cofactors and helps direct their activity toward nucleosomal histone H3, including H3K14 and H3K23. Its PZP module recognizes the unmodified H3 amino terminus and supports chromatin engagement, while its bromodomain recognizes acetylated histone ligands. BRPF1 acts principally in the nucleus, with partner-dependent localization observed in expression assays, and supports context-dependent transcriptional regulation. Monoallelic pathogenic variants cause an intellectual developmental disorder associated with deficient histone H3 acetylation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000123 histone acetyltransferase complex | IDA PMID:24065767 Exchange of associated factors directs a switch in HBO1 acet... | ACCEPT | Summary: BRPF1 is a scaffold subunit of alternative MOZ/MORF and HBO1 acetyltransferase assemblies. Reason: Native BRPF1 fractions and immunopurified complexes contain MOZ/MORF or HBO1 catalytic subunits with ING/MEAF6 factors. The generic complex term accommodates both alternative catalytic assemblies; replacing it solely with MOZ/MORF would drop the experimentally demonstrated HBO1 context. Complex membership does not confer intrinsic catalysis. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25281266 Structural insights into recognition of acetylated histone l... | MODIFY | Summary: BRPF1 recognizes H2AK5ac through its bromodomain. Reason: The original paper resolves the human BRPF1 bromodomain bound to the H2AK5ac peptide and tests binding-pocket mutants. The preserved canonical abstract directly states these structures and mutagenesis; selected Methods and Results in the authenticated fuller variant additionally establish the isolated-domain and peptide assay context. The exact histone H2AK5ac reader activity term captures the demonstrated modified ligand more precisely than the histone-wide parent. This is the recognition arm of a chromatin adaptor, supported by BRPF1 complex targeting in PMID:24065767. The source partner identifier is preserved; peptide recognition does not establish exclusive selectivity for this mark, distinguish every histone gene product, or demonstrate genome-wide targeting by full-length BRPF1. Proposed replacements: histone H2AK5ac reader activity |
| GO:0005515 protein binding | IPI PMID:25281266 Structural insights into recognition of acetylated histone l... | MODIFY | Summary: BRPF1 recognizes H4K12ac through its bromodomain. Reason: The original paper resolves the human BRPF1 bromodomain bound to the H4K12ac peptide and tests binding-pocket mutants. The preserved canonical abstract directly states these structures and mutagenesis; selected Methods and Results in the authenticated fuller variant additionally establish the isolated-domain and peptide assay context. The exact histone H4K12ac reader activity term captures the demonstrated modified ligand more precisely than the histone-wide parent. This is the recognition arm of a chromatin adaptor, supported by BRPF1 complex targeting in PMID:24065767. The source partner identifier is preserved; peptide recognition does not establish exclusive selectivity for this mark, distinguish every histone gene product, or demonstrate genome-wide targeting by full-length BRPF1. Proposed replacements: histone H4K12ac reader activity |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear activity is conserved and directly supported for human BRPF1. Reason: The PAINT inference through PTN001012887 is consistent with BRPF1-containing nuclear acetyltransferase complexes and direct localization studies. Human target evidence includes nuclear-fraction purification and a bromodomain-protein microscopy screen. No loss of this activity or contradictory localization is established; the target appearing among the descendant evidence is not circularity. The full ancestral tree was not re-audited. |
| GO:0005634 nucleus | IDA PMID:18794358 Molecular architecture of quartet MOZ/MORF histone acetyltra... | ACCEPT | Summary: BRPF1 enters the nucleus in association with its complex partners. Reason: Indexed primary Results and the Fig.2 caption show tagged BRPF1 relocalizing from cytoplasmic puncta to the nucleus upon partner coexpression, including MOZ in NIH3T3 cells and ING5 with EAF6 in HEK293 cells. These are overexpression localization assays, not measurements of the endogenous nuclear fraction. Independent nuclear BRPF1 purification and microscopy support the localization. |
| GO:0005634 nucleus | IDA PMID:24065767 Exchange of associated factors directs a switch in HBO1 acet... | ACCEPT | Summary: BRPF1-containing acetyltransferase assemblies occur in the nucleus. Reason: The actual Methods describe affinity purification of tagged BRPF1 from HeLa nuclear extracts; Results identify partner complexes and chromatin association. This directly supports nuclear localization. The genome-wide ChIP reagent also recognizes BRPF2, so that experiment is not treated as a BRPF1-exclusive map. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:25593309 Screen identifies bromodomain protein ZMYND8 in chromatin re... | ACCEPT | Summary: The bromodomain-protein screen directly reports nuclear BRPF1. Reason: The fuller fetched source Results explicitly include BRPF1 among proteins showing focal nuclear accumulation without relocalization after laser damage. This supports the nuclear annotation even though the title emphasizes ZMYND8. The canonical cache is abstract-only; the supplemental source body supplies the BRPF1-specific observation. No ZMYND8 DNA-repair mechanism is transferred to BRPF1. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:27939640 Mutations in the Chromatin Regulator Gene BRPF1 Cause Syndro... | ACCEPT | Summary: Nuclear BRPF1 localization is consistent with its chromatin-regulator function. Reason: The cited primary Methods specify EGFP-BRPF1 or mutant imaging in HEK293 cells with or without KAT6A, ING5 and MEAF6. The exact supplementary Fig.S4 localization results were not retrieved, so variant-specific distributions are not claimed. The nuclear assertion itself is independently supported by the 2008 localization Results, 2013 nuclear purification and 2015 microscopy screen. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: The UniProt nucleus mapping agrees with direct localization evidence. Reason: The electronic mapping retains the nuclear compartment in the immutable UniProt record. Nuclear complex purification and microscopy directly corroborate it; cytoplasmic signal in some tagged-expression conditions does not contradict nuclear localization. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Nucleoplasmic localization is compatible with the observed nuclear chromatin-associated pools. Reason: The source is an immunofluorescence curation record. Its individual image was not inspected, but primary BRPF1 nuclear-puncta microscopy and nuclear-complex/chromatin experiments independently support this broad compartment. The assignment does not imply nucleolar exclusivity or localization of every isoform. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3318486 | ACCEPT | Summary: BRPF1 acts in nuclear histone acetyltransferase complexes. Reason: The cached Reactome reaction explicitly describes BRPF1 in KAT6A/KAT6B-associated ING5 assemblies acting on nucleosomal H3. This supports the modeled nucleoplasmic compartment and is corroborated by primary nuclear localization and complex isolation. Its narrow historical H3K14 wording does not replace the broader H3K14/H3K23 evidence. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6805620 | ACCEPT | Summary: The modeled nucleoplasmic compartment is appropriate for BRPF1. Reason: The cached reaction describes KAT6A association with PML and TP53. The existing annotation asserts only the nucleoplasmic compartment of a complex constituent, supported independently by BRPF1 nuclear localization and nuclear-complex purification. It does not establish that BRPF1 itself catalyzes this reaction or directly contacts every reaction participant; the individual reaction experiment was not re-audited. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6805638 | ACCEPT | Summary: The modeled nucleoplasmic compartment is appropriate for BRPF1. Reason: The cached reaction describes TP53 acetylation by KAT6A. The existing annotation asserts only the nucleoplasmic compartment of a complex constituent, supported independently by BRPF1 nuclear localization and nuclear-complex purification. It does not establish that BRPF1 itself catalyzes this reaction or directly contacts every reaction participant; the individual reaction experiment was not re-audited. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6805640 | ACCEPT | Summary: The modeled nucleoplasmic compartment is appropriate for BRPF1. Reason: The cached reaction describes AKT phosphorylation of KAT6A. The existing annotation asserts only the nucleoplasmic compartment of a complex constituent, supported independently by BRPF1 nuclear localization and nuclear-complex purification. It does not establish that BRPF1 itself catalyzes this reaction or directly contacts every reaction participant; the individual reaction experiment was not re-audited. |
| GO:0005694 chromosome | EXP PMID:24065767 Exchange of associated factors directs a switch in HBO1 acet... | ACCEPT | Summary: BRPF1 associates with chromosomal chromatin. Reason: Purified BRPF1 complexes copurify histone H3 and require the PZP module for chromatin engagement and acetylation. ChIP analysis additionally places BRPF1/2-containing complexes near active promoters, but the antibody recognizes both paralogs. Together these observations support the chromosome annotation without claiming a paralog-exclusive genomic map. Supporting Evidence: |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: The UniProt chromosome mapping is supported by chromatin experiments. Reason: The electronic compartment mapping agrees with BRPF1 histone/chromatin binding and nuclear-complex experiments in the original primary study. It does not require a special role on condensed mitotic chromosomes. Supporting Evidence: |
| GO:0005737 cytoplasm | EXP PMID:18794358 Molecular architecture of quartet MOZ/MORF histone acetyltra... | KEEP AS NON CORE | Summary: A cytoplasmic BRPF1 pool is observed in tagged-expression assays. Reason: Indexed 2008 primary Results describe mainly cytoplasmic HA-BRPF1 when expressed alone in NIH3T3 cells and GFP-BRPF1 puncta in HEK293 cells. Complex-partner coexpression shifts the distribution toward the nucleus. Retain the experimentally observed compartment as a conditional non-core localization, without inferring a separate cytoplasmic biochemical activity or an endogenous steady-state fraction. Supporting Evidence: |
| GO:0005737 cytoplasm | IDA PMID:27939640 Mutations in the Chromatin Regulator Gene BRPF1 Cause Syndro... | KEEP AS NON CORE | Summary: Conditional cytoplasmic localization is plausible and independently documented. Reason: The 2017 primary Methods include EGFP-BRPF1 imaging with and without complex partners, but the exact Fig.S4 localization data were not recovered. The broad cytoplasmic assertion is independently demonstrated in the 2008 tagged-expression experiments and agrees with the preserved UniProt record. Retain it with this explicit source-specific limit; no exact variant distribution is inferred from the unavailable panel. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The electronic cytoplasm mapping captures an observed conditional pool. Reason: UniProt records cytoplasmic BRPF1 as well as nuclear localization. The 2008 experiments independently demonstrate cytoplasmic tagged BRPF1 that redistributes after complex-partner expression. This supports retention as a non-core location, without assigning a separate cytoplasmic function. Supporting Evidence: |
| GO:0006338 chromatin remodeling | IBA GO_REF:0000033 | ACCEPT | Summary: BRPF1 participates in chromatin remodeling through histone recognition and assembly/activation of acetyltransferase complexes. Reason: GO:0006338 is defined as "A dynamic process of chromatin reorganization resulting in changes to chromatin structure." The ontology separately specifies that histone modifying activity (GO:0140993) is part_of this process; this is an MF-to-BP relation, not an is_a claim between two biological processes. Human BRPF1 supplies chromatin engagement and acetyltransferase-complex assembly/activation, rather than the acetyl-transfer chemistry: PZP deletion disrupts nucleosomal binding and acetylation in PMID:24065767. This supports participation through histone modification without asserting ATP-dependent nucleosome sliding. The full PAINT node placement was not reconstructed, and target inclusion among descendant evidence remains legitimate. |
| GO:0006338 chromatin remodeling | IMP PMID:27939640 Mutations in the Chromatin Regulator Gene BRPF1 Cause Syndro... | ACCEPT | Summary: BRPF1-dependent assembly and chromatin engagement support the histone-modification component of chromatin remodeling. Reason: The human variant study reports deficient H3K23 acetylation; independent BRPF1 PZP experiments show that disrupting substrate engagement abolishes chromatin acetylation while sparing activity on free histones (PMID:24065767). BRPF1 therefore contributes the scaffold and chromatin-targeting functions needed by the modifying complex, rather than being only a downstream phenotypic requirement. The current ontology places histone modifying activity (GO:0140993) part_of chromatin remodeling (GO:0006338), supporting the retained process assignment through that mechanism. The KAT subunit performs acetyl transfer; no BRPF1 ATPase, nucleosome-sliding assay or intrinsic acetyltransferase activity is inferred. |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:18794358 Molecular architecture of quartet MOZ/MORF histone acetyltra... | ACCEPT | Summary: BRPF1 regulates transcription through partner-dependent chromatin coactivation. Reason: The canonical abstract and indexed primary transcription Results support cooperation with MOZ in Runx-dependent reporter activation. This is a context-dependent contribution: Gal4-BRPF1 alone was inactive, and partner effects differed among promoters. Retain the broad transcription-regulation assertion without turning it into autonomous sequence-specific DNA binding. Supporting Evidence: |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: The Pol II transcription-regulation inference matches BRPF1 chromatin coactivation. Reason: The PAINT PTN001012887 assignment is consistent with human Runx-responsive reporter assays and BRPF1-containing HAT complexes near actively transcribed genes. This supports regulation of Pol II transcription through chromatin rather than a catalytic polymerase or sequence-specific transcription-factor role. The ancestral placement itself was not reanalyzed. |
| GO:0010698 acetyltransferase activator activity | IDA PMID:27939640 Mutations in the Chromatin Regulator Gene BRPF1 Cause Syndro... | ACCEPT | Summary: BRPF1 assembles and stimulates partner lysine acetyltransferases. Reason: BRPF1 physically assembles KAT6/MOZ-MORF complexes and increases acetyltransferase activity on histone substrates. The 2008 abstract explicitly reports reconstituted-complex stimulation; the 2017 abstract directly describes BRPF1 interaction/activation motifs and deficient H3K23 acetylation with variants. This supports acetyltransferase activator activity beyond a generic structural-adaptor description. Catalytic acetyl transfer belongs to the associated KAT subunit; no intrinsic BRPF1 HAT claim is made. |
| GO:0043995 histone H4K5 acetyltransferase activity | IDA PMID:16387653 ING tumor suppressor proteins are critical regulators of chr... | UNDECIDED | Summary: The precise H4K5 contribution of BRPF1 remains unresolved. Reason: The source already qualifies this as contributes_to, so it does not assign intrinsic BRPF1 catalysis. The original 2006 paper is available only as an abstract here and its exact BRPF1-containing complex/site assay has not been inspected. Later primary Results show BRPF1 complexes acetylating free H3 and H4 but predominantly H3 in chromatin, with H4K5/8/12 chromatin preference assigned to JADE-HBO1. This substrate/scaffold distinction does not categorically refute free-histone contribution. Preserve the machine qualifier and source; leave the particular H4 site unresolved pending the original experiment. |
| GO:0043996 histone H4K8 acetyltransferase activity | IDA PMID:16387653 ING tumor suppressor proteins are critical regulators of chr... | UNDECIDED | Summary: The precise H4K8 contribution of BRPF1 remains unresolved. Reason: The source already qualifies this as contributes_to, so it does not assign intrinsic BRPF1 catalysis. The original 2006 paper is available only as an abstract here and its exact BRPF1-containing complex/site assay has not been inspected. Later primary Results show BRPF1 complexes acetylating free H3 and H4 but predominantly H3 in chromatin, with H4K5/8/12 chromatin preference assigned to JADE-HBO1. This substrate/scaffold distinction does not categorically refute free-histone contribution. Preserve the machine qualifier and source; leave the particular H4 site unresolved pending the original experiment. |
| GO:0043997 histone H4K12 acetyltransferase activity | IDA PMID:16387653 ING tumor suppressor proteins are critical regulators of chr... | UNDECIDED | Summary: The precise H4K12 contribution of BRPF1 remains unresolved. Reason: The source already qualifies this as contributes_to, so it does not assign intrinsic BRPF1 catalysis. The original 2006 paper is available only as an abstract here and its exact BRPF1-containing complex/site assay has not been inspected. Later primary Results show BRPF1 complexes acetylating free H3 and H4 but predominantly H3 in chromatin, with H4K5/8/12 chromatin preference assigned to JADE-HBO1. This substrate/scaffold distinction does not categorically refute free-histone contribution. Preserve the machine qualifier and source; leave the particular H4 site unresolved pending the original experiment. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:18794358 Molecular architecture of quartet MOZ/MORF histone acetyltra... | ACCEPT | Summary: BRPF1 promotes transcription in cooperation with MOZ and Runx factors. Reason: The original abstract and indexed primary Results report Runx-responsive reporter coactivation in HEK293 cells with BRPF1 and MOZ. This positive regulatory role depends on promoter and partner context; it does not imply that isolated BRPF1 activates all promoters. The erratum swaps BR2/BR14 labels in Fig.6E, so uncorrected deletion mapping is not used. Supporting Evidence: PMID:18794358 BRPF1 enhances the transcriptional potential of MOZ |
| GO:0050793 regulation of developmental process | NAS PMID:16387653 ING tumor suppressor proteins are critical regulators of chr... | KEEP AS NON CORE | Summary: Developmental regulation is a supported biological context for BRPF1 chromatin control. Reason: The original 2006 non-traceable statement was not located beyond its abstract. The later human study nevertheless links monoallelic BRPF1 variants to developmental abnormalities and functionally shows disruption of the chromatin-acetylation machinery. Retain this broad existing developmental context as non-core, without asserting a separate instructive patterning activity or treating the phenotype as a new molecular function. |
| GO:0070776 MOZ/MORF histone acetyltransferase complex | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic MOZ/MORF-complex membership agrees with direct human evidence. Reason: The IBA descends from PTN002674161 and is independently supported by human BRPF1 complex purification and reconstitution. BRPF1 bridges a MOZ/KAT6A or MORF/KAT6B catalytic subunit to ING5 and MEAF6. The target appearing among descendant evidence is expected, not circular. The full PAINT tree was not reconstructed; no target-specific loss is evident. |
| GO:0070776 MOZ/MORF histone acetyltransferase complex | IDA PMID:16387653 ING tumor suppressor proteins are critical regulators of chr... | ACCEPT | Summary: BRPF1 membership in the MOZ/MORF complex is independently corroborated. Reason: The 2006 abstract describes distinct ING5-HBO1 and ING5-MOZ/MORF assemblies but its BRPF1-specific panels were unavailable. The 2008 reconstitution abstract and 2013 actual BRPF1 purification Results independently verify MOZ/MORF-complex membership, so retain this clearly correct assignment while preserving the original source and its access limit. |
| GO:0070776 MOZ/MORF histone acetyltransferase complex | IDA PMID:18794358 Molecular architecture of quartet MOZ/MORF histone acetyltra... | ACCEPT | Summary: Reconstitution establishes BRPF1 as a bridging MOZ/MORF-complex subunit. Reason: The original abstract reports reconstituted MOZ/MORF complexes in which BRPF1 bridges the catalytic subunit with ING5 and EAF6/MEAF6. Indexed primary interaction Results and the 2013 purification study corroborate this architecture. MOZ and MORF designate related alternative catalytic assemblies, not mandatory coexistence in every complex. Supporting Evidence: PMID:18794358 assembling and activating MOZ/MORF acetyltransferase complexes |
| GO:0070776 MOZ/MORF histone acetyltransferase complex | IDA PMID:27939640 Mutations in the Chromatin Regulator Gene BRPF1 Cause Syndro... | ACCEPT | Summary: Human variant and complex-assembly data support MOZ/MORF-complex membership. Reason: Indexed primary 2017 complex-assembly Results describe co-immunoprecipitation of BRPF1, KAT6A, ING5 and MEAF6 and different assembly defects among BRPF1 variants. This directly corroborates the complex assignment. Figure images and the full supplementary panels were not inspected; 2008 reconstitution and 2013 BRPF1 purification provide independent support. |
| GO:0070776 MOZ/MORF histone acetyltransferase complex | IEA GO_REF:0000117 | ACCEPT | Summary: The electronic MOZ/MORF-complex annotation agrees with direct biochemical evidence. Reason: The ARBA00084417 electronic assignment agrees with direct human BRPF1 complex reconstitution and purification. Retain the complex membership; the detailed rule conditions were not independently audited. This does not transfer intrinsic KAT6 catalysis to the BRPF1 scaffold. |
| GO:0140566 histone reader activity | IBA GO_REF:0000033 | ACCEPT | Summary: BRPF1 is a multivalent histone reader that couples histone recognition to acetyltransferase complexes. Reason: The PTN001012887 inference is directly corroborated in human BRPF1: bromodomain structures and binding assays recognize acetylated H2A/H4 peptides, while PZP assays recognize the H3 N terminus with unmethylated Lys4 and enable chromatin engagement by the complex. H3K4me3 targeting of the assembled complex is mediated by ING5 and is not attributed to intrinsic BRPF1 PZP specificity. No full PAINT-tree reconstruction is claimed. |
| GO:1903706 regulation of hemopoiesis | NAS PMID:16387653 ING tumor suppressor proteins are critical regulators of chr... | UNDECIDED | Summary: The BRPF1-specific basis of the original hemopoiesis statement is unresolved. Reason: The 2006 abstract does not expose the BRPF1-specific evidence underlying this NAS annotation. Later discussion links BRPF1-dependent H3K23 acetylation to mouse hematopoietic stem-cell biology, but the relevant primary donor experiments and the original asserted mechanism were not inspected. This is not evidence that the annotation is false, and KAT6A developmental phenotypes are not transferred automatically to BRPF1. Leave the existing human process assertion unresolved. |
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Download this section (compressed HTML)Q: Do the original PMID:16387653 H4K5/H4K8/H4K12 assays demonstrate contribution by a BRPF1-containing complex on free histones, or do they reflect a distinct HBO1-JADE complex?
Q: Which human BRPF1 isoforms and endogenous partner combinations account for the nuclear and cytoplasmic pools observed in tagged-expression experiments?
Q: Which direct BRPF1-dependent transcriptional or chromatin steps support the original regulation-of-hemopoiesis annotation, distinct from KAT6A phenotypes?
Q: How should PZP-dependent recognition of the H3 N terminus with unmethylated Lys4 be represented within the existing broad histone-reader assertion, separately from bromodomain recognition of H2AK5ac and H4K12ac? The PZP evidence does not establish a requirement for H3K14 acetylation.
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