CHD3

UniProt ID: Q12873
Organism: Homo sapiens
Review Status: DRAFT
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Gene Description

CHD3 (Mi-2alpha) is an ATP-dependent chromatin remodeler that changes nucleosome positioning and DNA accessibility. It forms CHD3-containing NuRD assemblies and contributes remodeling activity alongside the histone-deacetylase subunits. Its tandem PHD fingers recognize histone H3 tails, with sensitivity to their modification state. CHD3 acts mainly on nuclear chromatin and can support either transcriptional repression or activation in a target- and cell-dependent manner. Human stem-cell studies link CHD3-dependent chromatin accessibility to cranial neural crest specification. A smaller centrosomal pool associates with pericentrin and contributes to centrosomal protein retention and spindle organization. Pathogenic CHD3 variants can alter ATPase activity or its coupling to remodeling and cause a neurodevelopmental disorder with prominent speech and language impairment.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000122 negative regulation of transcription by RNA polymerase II
IDA
PMID:27068747
Transcription Factor hDREF Is a Novel SUMO E3 Ligase of Mi2Ξ±...
ACCEPT
Summary: CHD3 represses ribosomal-gene transcription in the tested human-cell context.
Reason: PMID:27068747 uses human Mi2alpha/CHD3 constructs and endogenous target-gene measurements. In the hDREF/SUMO1 coexpression context, repression is relieved while gene-body CHD3 occupancy decreases and promoter enrichment increases. hDREF, not CHD3, performs the SUMO-ligase reaction; repression is one context-dependent output of CHD3 remodeling.
Supporting Evidence:
PMID:27068747
transcriptional repression by Mi2Ξ±
GO:0000785 chromatin
IBA
GO_REF:0000033
ACCEPT
Summary: Nuclear chromatin is a principal site of CHD3 activity.
Reason: The PAINT assertion at PTN002473914 is corroborated by human chromatin occupancy, biochemical nucleosome remodeling and NuRD association. This audit does not reconstruct the ancestral node; target self-evidence and the number of listed descendants are not defects.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN002473914 UNRESOLVED
The exact PAINT ancestral source is retained; historical node placement was not reconstructed. Independent target evidence supports the function without donor-count or target-self-reference objections.
Supporting Evidence:
GO:0000976 transcription cis-regulatory region binding
IDA
PMID:27068747
Transcription Factor hDREF Is a Novel SUMO E3 Ligase of Mi2Ξ±...
ACCEPT
Summary: Retain transcriptional regulatory-region binding at the measured chromatin-occupancy scope.
Reason: PMID:27068747 reports CHD3 ChIP at ribosomal-gene promoters and gene bodies with hDREF-dependent occupancy. The official GO:0000976 comment explicitly includes non-specific binding to regulatory regions. Thus this assertion does not require an isolated motif-recognition assay. It should not be paraphrased as intrinsic sequence-specific DNA recognition.
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
Official GO:0000976 includes non-specific regulatory-region binding; human CHD3 promoter ChIP is positive, while a purified motif-recognition assay was not established by this review.
GO:0003677 DNA binding
IBA
GO_REF:0000033
ACCEPT
Summary: DNA engagement is intrinsic to the CHD3 chromatin-remodeling motor.
Reason: Preserve the original IBA assertion. Purified human CHD3 acts on DNA-containing nucleosomes, with DNA/nucleosome-dependent ATPase and remodeling assays; this supports broad DNA binding without assigning a recognition motif. The PTN002473914 node history was not reconstructed; no target-specific loss is indicated.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN002473914 UNRESOLVED
The exact PAINT ancestral source is retained; historical node placement was not reconstructed. Independent target evidence supports the function without donor-count or target-self-reference objections.
Supporting Evidence:
GO_REF:0000033
GO:0003677 DNA binding
IEA
GO_REF:0000002
ACCEPT
Summary: DNA engagement is intrinsic to the CHD3 chromatin-remodeling motor.
Reason: Preserve the original IEA assertion. Purified human CHD3 acts on DNA-containing nucleosomes, with DNA/nucleosome-dependent ATPase and remodeling assays; this supports broad DNA binding without assigning a recognition motif.
Supporting Evidence:
GO_REF:0000002
GO:0003677 DNA binding
TAS
PMID:9326634
Characterization of the CHD family of proteins.
ACCEPT
Summary: DNA engagement is intrinsic to the CHD3 chromatin-remodeling motor.
Reason: Preserve the original TAS assertion. Purified human CHD3 acts on DNA-containing nucleosomes, with DNA/nucleosome-dependent ATPase and remodeling assays; this supports broad DNA binding without assigning a recognition motif. PMID:9326634 is an early family characterization, not the modern CHD3 motor assay.
GO:0003682 chromatin binding
IBA
GO_REF:0000033
ACCEPT
Summary: CHD3 binds and remodels chromatin.
Reason: Retain the ancestral-node assertion, independently supported by CHD3 promoter ChIP, nucleosome engagement and PHD-histone binding. The PAINT reconstruction itself was not re-performed, and the listed extant members are not treated as pairwise transfers.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN002473914 UNRESOLVED
The exact PAINT ancestral source is retained; historical node placement was not reconstructed. Independent target evidence supports the function without donor-count or target-self-reference objections.
GO:0003723 RNA binding
HDA
PMID:22658674
Insights into RNA biology from an atlas of mammalian mRNA-bi...
KEEP AS NON CORE
Summary: Retain the positive human RNA-interactome capture outside the remodeling core.
Reason: The authentic PMID:22658674 Table S1 identifies CHD3 as an mRNA-interactome protein in UV-crosslinked HeLa cells. Its ion-count enrichment meets the study threshold whereas the spectral-count analysis does not; these are two protein-enrichment analyses, not RNA-abundance measurements. Protein groups are mapped to gene models and do not resolve every splice product or an RNA-processing mechanism.
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
Castello Table S1, HeLa mRNA interactome.txt row 687: ENSG00000170004/CHD3, mRNA-interactome, identified in crosslinked sample, not identified in control; adjusted spectral-count P=0.713048068629827 and ion-count P=0.00504907564451212.
GO:0004386 helicase activity
NAS
PMID:9688266
Identification of a human 17p-located cDNA encoding a protei...
MODIFY
Summary: Refine historical helicase-family attribution to demonstrated ATP-dependent chromatin remodeling.
Reason: The accessible PMID:9688266 abstract describes conserved helicase-family motifs; its full body was not recovered. Independent purified human CHD3 assays directly measure ATP hydrolysis and nucleosome repositioning/accessibility. GO:0004386 requires duplex unwinding, which these assays do not establish. This positive functional refinement is not a claim that every possible unwinding condition has been excluded.
Supporting Evidence:
PMID:28977666
intrinsic to the remodeling enzymes themselves
GO:0005515 protein binding
IPI
PMID:12505151
Characterization of a new family of proteins that interact w...
KEEP AS NON CORE
Summary: Retain SERBP1 association at the measured assay scope.
Reason: Human C-terminal CHD3 fragments bind SERBP1 fragments in two-hybrid, pull-down and co-IP records. This does not assign SERBP1 RNA regulation to CHD3.
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
CHD3 source row 9: exact Q12873–Q8NC51 pair and PMID:12505151 match 5 positive IntAct records (intact:EBI-523588, intact:EBI-523644, intact:EBI-523653, intact:EBI-523681, intact:EBI-523774); literal participant, method, publication, taxon, host and feature fields are retained below.
GO:0005515 protein binding
IPI
PMID:15383276
A protein interaction network links GIT1, an enhancer of hun...
KEEP AS NON CORE
Summary: Retain PRPF40A association at the measured assay scope.
Reason: Human CHD3 1830–2000 and PRPF40A 8–422 are supported by two-hybrid and pull-down records; spliceosomal process participation is not inferred.
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
CHD3 source row 10: exact Q12873–O75400 pair and PMID:15383276 match 2 positive IntAct records (intact:EBI-473645, intact:EBI-474900); literal participant, method, publication, taxon, host and feature fields are retained below.
GO:0005515 protein binding
IPI
PMID:15383276
A protein interaction network links GIT1, an enhancer of hun...
KEEP AS NON CORE
Summary: Retain huntingtin association at the measured assay scope.
Reason: Human CHD3 1830–2000 with N-terminal huntingtin constructs is supported by two-hybrid and pull-down records; no Huntington-disease mechanism is assigned from the pair alone.
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
CHD3 source row 11: exact Q12873–P42858 pair and PMID:15383276 match 3 positive IntAct records (intact:EBI-473381, intact:EBI-474879, intact:EBI-474886); literal participant, method, publication, taxon, host and feature fields are retained below.
GO:0005515 protein binding
IPI
PMID:15383276
A protein interaction network links GIT1, an enhancer of hun...
MODIFY
Summary: Retain SUMO2 association with a supported partner-class refinement.
Reason: The two-hybrid record uses human CHD3 1830–2000 and SUMO2 1–95. The binding term describes recognition, not SUMO conjugation or ligase activity.
Proposed replacements: SUMO binding
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
CHD3 source row 12: exact Q12873–P61956 pair and PMID:15383276 match 1 positive IntAct records (intact:EBI-474858); literal participant, method, publication, taxon, host and feature fields are retained below.
GO:0005515 protein binding
IPI
PMID:15383276
A protein interaction network links GIT1, an enhancer of hun...
KEEP AS NON CORE
Summary: Retain BARD1 association at the measured assay scope.
Reason: Human CHD3 1830–2000 and BARD1 1–379 have positive two-hybrid/pull-down records; BARD1 enzymatic or DNA-repair functions are not transferred.
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
CHD3 source row 13: exact Q12873–Q99728 pair and PMID:15383276 match 2 positive IntAct records (intact:EBI-473623, intact:EBI-474263); literal participant, method, publication, taxon, host and feature fields are retained below.
GO:0005515 protein binding
IPI
PMID:15383276
A protein interaction network links GIT1, an enhancer of hun...
KEEP AS NON CORE
Summary: Retain GIT1 association at the measured assay scope.
Reason: Human CHD3 1830–2000 and GIT1 249–761 have positive two-hybrid/pull-down records; no GTPase regulatory activity is assigned to CHD3.
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
CHD3 source row 14: exact Q12873–Q9Y2X7 pair and PMID:15383276 match 2 positive IntAct records (intact:EBI-473491, intact:EBI-474914); literal participant, method, publication, taxon, host and feature fields are retained below.
GO:0005515 protein binding
IPI
PMID:16169070
A human protein-protein interaction network: a resource for ...
MODIFY
Summary: Retain SUMO2 association with a supported partner-class refinement.
Reason: The human SUMO2 pair is a positive pooled two-hybrid record. No exact construct boundary is supplied by this record; it supports SUMO binding without a conjugation claim.
Proposed replacements: SUMO binding
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
CHD3 source row 15: exact Q12873–P61956 pair and PMID:16169070 match 1 positive IntAct records (intact:EBI-728660|imex:IM-16517-86); literal participant, method, publication, taxon, host and feature fields are retained below.
GO:0005515 protein binding
IPI
PMID:16169070
A human protein-protein interaction network: a resource for ...
MODIFY
Summary: Refine verified TRIM28/KAP1 association to transcription corepressor binding.
Reason: The original human pooled two-hybrid record is positive. Independent full PMID:18082607 directly tests SUMO/SIM-dependent CHD3 binding to KAP1 and describes KAP1 as the scaffold recruiting CHD3, SETDB1 and HP1-associated repression machinery. KAP1 is a KRAB-linked transcription corepressor, making GO:0001222 more informative than the broader scaffold-binding class. The term describes partner binding rather than intrinsic DNA recognition or a requirement that CHD3 itself be a sequence-specific repressor. It does not assign KAP1 E3 activity or its scaffold function to CHD3, and it preserves the SUMO, construct and original-source limits.
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
CHD3 source row 16: exact Q12873–Q13263 pair and PMID:16169070 match 1 positive IntAct records (intact:EBI-731053|imex:IM-16517-882); literal participant, method, publication, taxon, host and feature fields are retained below.
GO:0005515 protein binding
IPI
PMID:19703393
LSD1 is a subunit of the NuRD complex and targets the metast...
KEEP AS NON CORE
Summary: Retain KDM1A association at the measured assay scope.
Reason: Four human co-IP records support association of CHD3 and KDM1A within the NuRD-related preparations. This is complex association, not proof of a binary interface or CHD3 demethylase activity.
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
CHD3 source row 17: exact Q12873–O60341 pair and PMID:19703393 match 4 positive IntAct records (intact:EBI-2461776|imex:IM-12083-4, intact:EBI-2461830|imex:IM-12083-8, intact:EBI-2461848|imex:IM-12083-6, intact:EBI-2461864|imex:IM-12083-3); literal participant, method, publication, taxon, host and feature fields are retained below.
GO:0005515 protein binding
IPI
PMID:20676135
Phosphorylated p68 RNA helicase activates Snail1 transcripti...
UNDECIDED
Summary: Mi-2 associates with DDX5, but the tested Mi-2 paralog is unresolved.
Reason: The full PMID:20676135 reports reciprocal p68/DDX5–Mi-2 complex association in human colon-cancer cells. The inspected antibody description does not resolve CHD3 versus CHD4, so a negative interaction claim would be unjustified. Retain the exact P17844 source object and leave this CHD3-specific assertion undecided pending reagent or peptide identity.
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
PMID:20676135 has positive reciprocal Mi-2/DDX5 complex association; the inspected reagent description does not distinguish CHD3 from CHD4.
GO:0005515 protein binding
IPI
PMID:21642969
KAP-1 phosphorylation regulates CHD3 nucleosome remodeling d...
MODIFY
Summary: Refine verified TRIM28/KAP1 association to transcription corepressor binding.
Reason: The original PMID:21642969 abstract and indexed figure context explicitly describe regulated CHD3 association with SUMOylated KAP1; its complete full experimental series was not archived. Independent full PMID:18082607 directly tests SUMO/SIM-dependent CHD3 binding to KAP1 and describes KAP1 as the scaffold recruiting CHD3, SETDB1 and HP1-associated repression machinery. KAP1 is a KRAB-linked transcription corepressor, making GO:0001222 more informative than the broader scaffold-binding class. The term describes partner binding rather than intrinsic DNA recognition or a requirement that CHD3 itself be a sequence-specific repressor. It does not assign KAP1 E3 activity or its scaffold function to CHD3, and it preserves the SUMO, construct and original-source limits.
Supporting Evidence:
GO:0005515 protein binding
IPI
PMID:21900206
A directed protein interaction network for investigating int...
MODIFY
Summary: Refine the supported SUMO2 association to SUMO binding, retaining its original screen provenance.
Reason: The original PMID:21900206 screen abstract was accessible, but no exact source-specific CHD3–SUMO2 record was recovered from the bounded query. Independent positive same-partner records in PMIDs:15383276 and 16169070, plus SIM-dependent SUMO2 binding in full PMID:18082607, support the capability and its class. Preserve the original citation and mark that provenance gap explicitly; this is neither evidence of conjugation nor a claim that the 2011 target row was inspected.
Proposed replacements: SUMO binding
GO:0005515 protein binding
IPI
PMID:22720776
PHF6 interacts with the nucleosome remodeling and deacetylat...
KEEP AS NON CORE
Summary: Retain the source-specific PHF6-associated CHD3 identification.
Reason: The authentic publisher supplement to PMID:22720776 lists CHD3/Mi-2alpha among human Flag-immunoprecipitated proteins in Table S2. This resolves the target even though the abstract foregrounds CHD4. The assay is complex-level association, not purified binary binding. The supplement antibody/fractionation experiments name CHD4 and are not silently recast as CHD3-specific validation.
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
PMID:22720776 authentic supplemental Table S2 explicitly lists CHD3 (Mi-2alpha), gene CHD3, chromosome 17p13.1 among human Flag-immunoprecipitated proteins; Table S1 antibodies and fractionation panels specifically name CHD4.
GO:0005515 protein binding
IPI
PMID:26816381
Transcription factors LRF and BCL11A independently repress e...
MODIFY
Summary: Refine the positive LRF/ZBTB7A association to DNA-binding transcription factor binding.
Reason: The genuine fresh full PMID:26816381 describes human LRF BTB-domain library screening and CHD3 association validated by immunoprecipitation in the reported Fig. S12B context. The supplementary panel itself was not visually inspected. ZBTB7A is a verified DNA-binding transcription factor, so the measured pair supports this binding class without assigning a CHD3 sequence motif or every endogenous LRF-NuRD mechanism.
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
PMID:26816381 full primary Results identify CHD3 among LRF/ZBTB7A BTB-domain interaction hits and state immunoprecipitation validation; the verified O95365 partner is a DNA-binding transcription factor.
GO:0005515 protein binding
IPI
PMID:27068747
Transcription Factor hDREF Is a Novel SUMO E3 Ligase of Mi2Ξ±...
MODIFY
Summary: Refine human hDREF/ZBED1 association to DNA-binding transcription factor binding.
Reason: Human hDREF associates with the CHD3 C terminus and modulates CHD3 SUMOylation, promoter occupancy and repression in PMID:27068747. hDREF is the DNA-binding factor and SUMO E3; the replacement describes CHD3 binding that factor, not those activities being performed by CHD3.
Supporting Evidence:
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
MODIFY
Summary: Retain ZKSCAN8 association with a supported partner-class refinement.
Reason: The human ZKSCAN8–CHD3 pair is a positive affinity/co-IP record. Verified ZKSCAN8 is a DNA-binding transcription factor; the binding-class refinement does not imply that CHD3 performs its DNA recognition or that a native regulatory mechanism was measured.
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
CHD3 source row 24: exact Q12873–Q15776 pair and PMID:33961781 match 1 positive IntAct records (intact:EBI-54496576|imex:IM-29278-619); literal participant, method, publication, taxon, host and feature fields are retained below.
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func...
MODIFY
Summary: Retain the human ZKSCAN8–CHD3 AP-MS association as transcription factor binding.
Reason: The original PMID:40205054 U2OS AP-MS network contains the exact CHD3/ZKSCAN8 edge. Human ORFeome tagged-bait purification measures association, not a purified interface or isoform-specific mechanism. Verified ZKSCAN8 identity justifies the same binding-class treatment as the independent PMID:33961781 pair; it does not establish stronger physiology than other screen hits.
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
Original U2OS AP-MS network edge 629714 connects source node 556856 ZKSCAN8/ENSG00000198315 to target node 548356 CHD3/ENSG00000170004; this is an observed author-network edge, not a multimodal prediction.
GO:0005515 protein binding
IPI
PMID:9804427
Chromatin deacetylation by an ATP-dependent nucleosome remod...
MODIFY
Summary: Refine independently verified pericentrin binding to scaffold protein binding, preserving the original citation gap.
Reason: The recovered original PMID:9804427 concerns CHD3/CHD4-HDAC chromatin complexes, and its exact PCNT link was not located. Independent PMID:17626165 directly tests human CHD3 1566–1966 with mouse pericentrin A 1340–1756, plus endogenous human-cell association; the source P48725 is mouse Pcnt. Pericentrin scaffolds centrosomal complexes, matching GO:0097110. This describes CHD3 binding a scaffold, not CHD3 being a scaffold or a kinase. The original IPI/PMID/partner fields remain unchanged.
Proposed replacements: scaffold protein binding
Supporting Evidence:
file:human/CHD3/CHD3-source-evidence.json
Independent PMID:17626165 tests human CHD3 1566–1966 against murine pericentrin A 1340–1756 and endogenous human-cell association; the original PMID:9804427-to-PCNT citation link remains unresolved.
GO:0005524 ATP binding
IEA
GO_REF:0000002
ACCEPT
Summary: ATP binding supplies the CHD3 remodeling reaction.
Reason: The InterPro-derived assertion agrees with direct human CHD3 ATP hydrolysis and ATP-dependent remodeling. ATP binding is an integral motor property, not evidence for histone deacetylase or SUMO-transferase catalysis.
Supporting Evidence:
GO:0005634 nucleus
EXP
PMID:17626165
Chromatin remodeling proteins interact with pericentrin to r...
ACCEPT
Summary: Retain nucleus as a site of CHD3 chromatin-remodeling activity.
Reason: Endogenous human RPE1 and HeLa experiments show a predominant nuclear pool alongside centrosomal/cytoplasmic staining.
Supporting Evidence:
GO:0005634 nucleus
IBA
GO_REF:0000033
ACCEPT
Summary: Retain nucleus as a site of CHD3 chromatin-remodeling activity.
Reason: The PAINT PTN002473914 inference is independently corroborated; no node reconstruction or donor-count criticism is claimed.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN002473914 UNRESOLVED
The exact PAINT ancestral source is retained; historical node placement was not reconstructed. Independent target evidence supports the function without donor-count or target-self-reference objections.
Supporting Evidence:
GO_REF:0000033
GO:0005634 nucleus
IDA
PMID:22720776
PHF6 interacts with the nucleosome remodeling and deacetylat...
ACCEPT
Summary: Retain nucleus as a site of CHD3 chromatin-remodeling activity.
Reason: The authentic PHF6 supplement names CHD3 in the human IP protein list, but its displayed fractionation antibodies are CHD4-specific; independent CHD3 localization establishes the nuclear assertion without relabeling those panels.
Supporting Evidence:
GO:0005634 nucleus
IDA
PMID:28977666
CHD3 and CHD4 form distinct NuRD complexes with different ye...
ACCEPT
Summary: Retain nucleus as a site of CHD3 chromatin-remodeling activity.
Reason: Human tagged and endogenous CHD3 nuclear distributions were examined in the same study that measures its motor activity.
Supporting Evidence:
GO:0005634 nucleus
IDA
PMID:33283408
Cross-linking mass spectrometry reveals the structural topol...
ACCEPT
Summary: Retain nucleus as a site of CHD3 chromatin-remodeling activity.
Reason: Human HeLa Kyoto nuclear NuRD preparations and cellular assays support this compartment; cross-link mixtures do not prove a single CHD3/CHD4 particle.
Supporting Evidence:
GO:0005634 nucleus
IEA
GO_REF:0000044
ACCEPT
Summary: Retain nucleus as a site of CHD3 chromatin-remodeling activity.
Reason: The UniProt subcellular-location mapping agrees with direct human localization.
Supporting Evidence:
GO_REF:0000044
GO:0005634 nucleus
NAS
PMID:9688266
Identification of a human 17p-located cDNA encoding a protei...
ACCEPT
Summary: Retain nucleus as a site of CHD3 chromatin-remodeling activity.
Reason: The historical cloning assignment is corroborated by later direct human CHD3 nuclear localization.
Supporting Evidence:
GO:0005654 nucleoplasm
IDA
GO_REF:0000052
ACCEPT
Summary: Retain nucleoplasm as a defining CHD3 nuclear location.
Reason: The original HPA immunofluorescence is independently supported by current HPA staining and CHD3 nuclear/chromatin studies. This location is consistent with the remodeling core; nucleolar signal is assessed separately.
Supporting Evidence:
GO_REF:0000052
file:human/CHD3/CHD3-source-evidence.json
HPA Q12873/ENSG00000170004 antibody HPA076524 cell-expression records include nucleoplasmic and nucleolar staining; the saved U2OS image was visually inspected, without inferring a nucleolar biochemical function.
GO:0005654 nucleoplasm
IEA
GO_REF:0000117
ACCEPT
Summary: Retain nucleoplasm as a defining CHD3 nuclear location.
Reason: The original ARBA inference is independently supported by current HPA staining and CHD3 nuclear/chromatin studies. This location is consistent with the remodeling core; nucleolar signal is assessed separately.
Supporting Evidence:
GO_REF:0000052
file:human/CHD3/CHD3-source-evidence.json
HPA Q12873/ENSG00000170004 antibody HPA076524 cell-expression records include nucleoplasmic and nucleolar staining; the saved U2OS image was visually inspected, without inferring a nucleolar biochemical function.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-3769447
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3.
Supporting Evidence:
Reactome:R-HSA-3769447
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-HSA-3769447 is 'HDAC1:2-containing complex deacetylate histones', with compartment nucleoplasm and species Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6805650
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3.
Supporting Evidence:
Reactome:R-HSA-6805650
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-HSA-6805650 is 'MTA2-NuRD complex deacetylates TP53', with compartment nucleoplasm and species Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8943780
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3.
Supporting Evidence:
Reactome:R-HSA-8943780
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-HSA-8943780 is 'SALL4 recruits NuRD to PTEN gene', with compartment nucleoplasm and species Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8956365
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3.
Supporting Evidence:
Reactome:R-HSA-8956365
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-HSA-8956365 is 'ZBED1 (DREF) SUMOylates CHD3 with SUMO1', with compartment nucleoplasm and species Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9679787
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3.
Supporting Evidence:
Reactome:R-HSA-9679787
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-HSA-9679787 is 'HDAC1:2-containing complex binds HDAC2 Inhibitors', with compartment nucleoplasm and species Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9940468
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3.
Supporting Evidence:
Reactome:R-HSA-9940468
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-HSA-9940468 is 'CHD and CDK2AP subunits are recruited to NuRD', with compartment nucleoplasm and species Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9940948
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3.
Supporting Evidence:
Reactome:R-HSA-9940948
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-HSA-9940948 is 'GATAD2A NuRD binds ZMYND8:ZNF532:ZNF592:ZNF687', with compartment nucleoplasm and species Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9941697
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3.
Supporting Evidence:
Reactome:R-HSA-9941697
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-HSA-9941697 is 'ZNF827 and NR2C2,NR2F2 recruit NuRD to telomeric chromatin', with compartment nucleoplasm and species Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9941704
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3.
Supporting Evidence:
Reactome:R-HSA-9941704
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-HSA-9941704 is 'NuRD deacetylates telomeric nucleosomes', with compartment nucleoplasm and species Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9941744
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3.
Supporting Evidence:
Reactome:R-HSA-9941744
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-HSA-9941744 is 'PHF6 binds NuRD', with compartment nucleoplasm and species Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9944091
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3.
Supporting Evidence:
Reactome:R-HSA-9944091
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-HSA-9944091 is 'NuRD hydrolyzes ATP to affect nucleosome organization', with compartment nucleoplasm and species Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9944092
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3.
Supporting Evidence:
Reactome:R-HSA-9944092
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-HSA-9944092 is 'NuRD deacetylates nucleosomes', with compartment nucleoplasm and species Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9944706
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3.
Supporting Evidence:
Reactome:R-HSA-9944706
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-HSA-9944706 is 'NuRD binds TCF19 at FBP1 gene', with compartment nucleoplasm and species Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9944712
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3.
Supporting Evidence:
Reactome:R-HSA-9944712
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-HSA-9944712 is 'NuRD binds TCF19 at G6PC gene', with compartment nucleoplasm and species Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9944714
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3.
Supporting Evidence:
Reactome:R-HSA-9944714
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-HSA-9944714 is 'NuRD binds TCF19 at PCK1 gene', with compartment nucleoplasm and species Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9944893
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3.
Supporting Evidence:
Reactome:R-HSA-9944893
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-HSA-9944893 is 'NuRD binds Ikaros family member proteins', with compartment nucleoplasm and species Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005654 nucleoplasm
TAS
Reactome:R-NUL-9844000
ACCEPT
Summary: Retain the source-specific nucleoplasmic context.
Reason: The authentic Reactome event supplies NuRD-associated nucleoplasmic context, independently corroborated by human CHD3 nuclear/chromatin evidence. Retain this location consistently with the core, without transferring the event partner or HDAC catalytic activity to CHD3. This is a genuine mixed-species event describing bovine TRIM28 with human CHD3; the R-NUL identifier and species are preserved rather than rewritten as an all-human experiment.
Supporting Evidence:
Reactome:R-NUL-9844000
file:human/CHD3/CHD3-source-evidence.json
Official Reactome:R-NUL-9844000 is 'TRIM28 (KAP1) binds CHD3 (Mi-2alpha)', with compartment nucleoplasm and species Bos taurus, Homo sapiens; this annotation is a location assertion, not assignment of all reaction activities to CHD3.
GO:0005730 nucleolus
IDA
GO_REF:0000052
KEEP AS NON CORE
Summary: Retain observed nucleolar localization outside the defined remodeling core.
Reason: Current HPA XML and the saved U2OS image support nucleolar staining. Localization alone does not establish a nucleolus-specific CHD3 molecular role or ribosome-biogenesis process. Preserve the original IDA assertion.
Supporting Evidence:
GO_REF:0000052
file:human/CHD3/CHD3-source-evidence.json
HPA Q12873/ENSG00000170004 antibody HPA076524 cell-expression records include nucleoplasmic and nucleolar staining; the saved U2OS image was visually inspected, without inferring a nucleolar biochemical function.
GO:0005737 cytoplasm
IDA
PMID:17626165
Chromatin remodeling proteins interact with pericentrin to r...
KEEP AS NON CORE
Summary: Retain the reported cytoplasm pool outside the principal nuclear remodeling core.
Reason: PMID:17626165 detects endogenous human CHD3 outside the nucleus, including centrosomes, and tests local pericentrin retention. This is genuine contextual localization, not a transfer of CHD4 behavior; CHD3 remains centrosomal during mitosis in the inspected experiments.
Supporting Evidence:
GO:0005813 centrosome
IDA
PMID:17626165
Chromatin remodeling proteins interact with pericentrin to r...
KEEP AS NON CORE
Summary: Retain the reported centrosome pool outside the principal nuclear remodeling core.
Reason: PMID:17626165 detects endogenous human CHD3 outside the nucleus, including centrosomes, and tests local pericentrin retention. This is genuine contextual localization, not a transfer of CHD4 behavior; CHD3 remains centrosomal during mitosis in the inspected experiments.
Supporting Evidence:
GO:0005813 centrosome
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Retain the reported centrosome pool outside the principal nuclear remodeling core.
Reason: PMID:17626165 detects endogenous human CHD3 outside the nucleus, including centrosomes, and tests local pericentrin retention. This is genuine contextual localization, not a transfer of CHD4 behavior; CHD3 remains centrosomal during mitosis in the inspected experiments.
Supporting Evidence:
GO:0006338 chromatin remodeling
IBA
GO_REF:0000033
ACCEPT
Summary: Retain chromatin remodeling as CHD3 core biological work.
Reason: Purified human CHD3 itself hydrolyzes ATP and repositions nucleosomes or changes nucleosomal DNA accessibility. This is performed remodeling work rather than a depletion phenotype alone. Preserve the PAINT node PTN002473914; its detailed ancestral history was not reconstructed.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN002473914 UNRESOLVED
The exact PAINT ancestral source is retained; historical node placement was not reconstructed. Independent target evidence supports the function without donor-count or target-self-reference objections.
Supporting Evidence:
GO_REF:0000033
GO:0006338 chromatin remodeling
IDA
PMID:9790534
The dermatomyositis-specific autoantigen Mi2 is a component ...
ACCEPT
Summary: Retain chromatin remodeling as CHD3 core biological work.
Reason: Purified human CHD3 itself hydrolyzes ATP and repositions nucleosomes or changes nucleosomal DNA accessibility. This is performed remodeling work rather than a depletion phenotype alone. The original PMID:9790534 cache is abstract-only and foregrounds Mi2beta; its exact CHD3 assay was not independently resolved. The function is nevertheless directly established for human CHD3 by later studies; no original-curator error is asserted.
GO:0006338 chromatin remodeling
IEA
GO_REF:0000120
ACCEPT
Summary: Retain chromatin remodeling as CHD3 core biological work.
Reason: Purified human CHD3 itself hydrolyzes ATP and repositions nucleosomes or changes nucleosomal DNA accessibility. This is performed remodeling work rather than a depletion phenotype alone.
Supporting Evidence:
GO_REF:0000120
GO:0006338 chromatin remodeling
IMP
PMID:30397230
CHD3 helicase domain mutations cause a neurodevelopmental sy...
ACCEPT
Summary: Retain chromatin remodeling as CHD3 core biological work.
Reason: Purified human CHD3 itself hydrolyzes ATP and repositions nucleosomes or changes nucleosomal DNA accessibility. This is performed remodeling work rather than a depletion phenotype alone. The original source directly compares WT and patient-associated mutants; hydrolysis and remodeling defects can be separable.
Supporting Evidence:
GO:0006355 regulation of DNA-templated transcription
NAS
PMID:9688266
Identification of a human 17p-located cDNA encoding a protei...
ACCEPT
Summary: Retain context-dependent transcription regulation by CHD3.
Reason: The historical NAS source is supported by direct human CHD3 promoter, expression and chromatin-remodeling studies. Depending on target and cell context, CHD3-containing assemblies support repression or activation; this is not an intrinsic sequence-specific transcription-factor assignment.
GO:0007051 spindle organization
IDA
PMID:17626165
Chromatin remodeling proteins interact with pericentrin to r...
KEEP AS NON CORE
Summary: Retain the experimentally supported spindle-organization contribution.
Reason: Human CHD3 depletion and a competing C-terminal construct disturb pericentrin/gamma-tubulin retention, microtubule regrowth and spindle organization in PMID:17626165. Pair/domain, localization and rapid-displacement evidence supports a local contribution beyond generic necessity, but the paper does not resolve all transcriptional alternatives or establish CHD3 as a microtubule motor/polymerase.
Supporting Evidence:
GO:0007098 centrosome cycle
IDA
PMID:17626165
Chromatin remodeling proteins interact with pericentrin to r...
MODIFY
Summary: Refine centrosome-cycle attribution to demonstrated protein localization and retention at the centrosome.
Reason: GO:0007098 concerns centrosome duplication and separation, neither of which is established by the inspected experiments. GO:0071539 includes maintenance at the centrosome. Human CHD3–pericentrin interaction/domain evidence, rapid pericentrin displacement and endogenous localization/RNAi effects support this more precise performed contribution. Centrin-positive structures persist; the exact anchoring mechanism and possible transcriptional contribution remain unresolved.
Supporting Evidence:
PMID:17626165
centrosomal anchoring of pericentrin
GO:0008270 zinc ion binding
NAS
PMID:9688266
Identification of a human 17p-located cDNA encoding a protei...
KEEP AS NON CORE
Summary: Retain structural zinc binding by CHD3 zinc-finger domains.
Reason: The early sequence/antigen studies identify zinc-finger regions; independent isolated human CHD3 PHD structures and histone-binding assays support this structural metal-binding property. It is not a separate catalytic core or evidence of a zinc-dependent hydrolase.
Supporting Evidence:
GO:0008270 zinc ion binding
TAS
PMID:7560064
Molecular analysis of a major antigenic region of the 240-kD...
KEEP AS NON CORE
Summary: Retain structural zinc binding by CHD3 zinc-finger domains.
Reason: The early sequence/antigen studies identify zinc-finger regions; independent isolated human CHD3 PHD structures and histone-binding assays support this structural metal-binding property. It is not a separate catalytic core or evidence of a zinc-dependent hydrolase.
Supporting Evidence:
GO:0016581 NuRD complex
IBA
GO_REF:0000033
ACCEPT
Summary: Retain CHD3 membership in NuRD.
Reason: Human CHD3-containing NuRD assemblies are independently established. CHD3 supplies ATP-dependent remodeling; HDAC subunits supply deacetylation. Mixed cross-link preparations do not prove CHD3 and CHD4 occupy the same individual particle. The PAINT PTN000085004 node history was not reconstructed; target self-evidence is legitimate.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000085004 UNRESOLVED
The exact PAINT ancestral source is retained; historical node placement was not reconstructed. Independent target evidence supports the function without donor-count or target-self-reference objections.
Supporting Evidence:
GO_REF:0000033
GO:0016581 NuRD complex
IDA
PMID:17827154
Differential distribution of unmodified and phosphorylated h...
ACCEPT
Summary: Retain CHD3 membership in NuRD.
Reason: Human CHD3-containing NuRD assemblies are independently established. CHD3 supplies ATP-dependent remodeling; HDAC subunits supply deacetylation. Mixed cross-link preparations do not prove CHD3 and CHD4 occupy the same individual particle. The original PMID:17827154 abstract was inspected, not its full CHD3-specific assay; retain the experimental annotation with direct independent complex corroboration.
GO:0016581 NuRD complex
IDA
PMID:33283408
Cross-linking mass spectrometry reveals the structural topol...
ACCEPT
Summary: Retain CHD3 membership in NuRD.
Reason: Human CHD3-containing NuRD assemblies are independently established. CHD3 supplies ATP-dependent remodeling; HDAC subunits supply deacetylation. Mixed cross-link preparations do not prove CHD3 and CHD4 occupy the same individual particle.
GO:0016581 NuRD complex
IEA
GO_REF:0000107
ACCEPT
Summary: Retain CHD3 membership in NuRD.
Reason: Human CHD3-containing NuRD assemblies are independently established. CHD3 supplies ATP-dependent remodeling; HDAC subunits supply deacetylation. Mixed cross-link preparations do not prove CHD3 and CHD4 occupy the same individual particle. Current mouse B1AR17/Chd3 carries experimental NuRD evidence, but the historical Ensembl mapping was not reconstructed.
Supporting Evidence:
GO_REF:0000107
GO:0016581 NuRD complex
IPI
PMID:27068747
Transcription Factor hDREF Is a Novel SUMO E3 Ligase of Mi2Ξ±...
ACCEPT
Summary: Retain CHD3 membership in NuRD.
Reason: Human CHD3-containing NuRD assemblies are independently established. CHD3 supplies ATP-dependent remodeling; HDAC subunits supply deacetylation. Mixed cross-link preparations do not prove CHD3 and CHD4 occupy the same individual particle. The human hDREF/SUMO experiments retain CHD3 association with the assayed NuRD subunits.
GO:0016581 NuRD complex
NAS
PMID:16428440
MBD2/NuRD and MBD3/NuRD, two distinct complexes with differe...
ACCEPT
Summary: Retain CHD3 membership in NuRD.
Reason: Human CHD3-containing NuRD assemblies are independently established. CHD3 supplies ATP-dependent remodeling; HDAC subunits supply deacetylation. Mixed cross-link preparations do not prove CHD3 and CHD4 occupy the same individual particle.
GO:0016605 PML body
IDA
PMID:27068747
Transcription Factor hDREF Is a Novel SUMO E3 Ligase of Mi2Ξ±...
KEEP AS NON CORE
Summary: Retain context-dependent PML-body localization.
Reason: PMID:27068747 reports CHD3/Mi2alpha redistribution in the hDREF/SUMO1 overexpression setting. The source supports this localization without establishing constitutive PML residence of every endogenous CHD3 product or a separate PML-body core function.
Supporting Evidence:
GO:0016605 PML body
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Retain context-dependent PML-body localization.
Reason: PMID:27068747 reports CHD3/Mi2alpha redistribution in the hDREF/SUMO1 overexpression setting. The source supports this localization without establishing constitutive PML residence of every endogenous CHD3 product or a separate PML-body core function.
Supporting Evidence:
GO:0016887 ATP hydrolysis activity
EXP
PMID:30397230
CHD3 helicase domain mutations cause a neurodevelopmental sy...
ACCEPT
Summary: Retain direct CHD3 ATP hydrolysis.
Reason: Purified human CHD3 ATP hydrolysis is directly measured, and some mutants uncouple hydrolysis from nucleosome remodeling. Current GO:0016887 explicitly supports annotating hydrolysis alongside the overall ATP-dependent activity. Retain this real catalytic property while representing the defining combined activity with one remodeler core.
Supporting Evidence:
GO:0016887 ATP hydrolysis activity
IBA
GO_REF:0000033
ACCEPT
Summary: Retain direct CHD3 ATP hydrolysis.
Reason: Purified human CHD3 ATP hydrolysis is directly measured, and some mutants uncouple hydrolysis from nucleosome remodeling. Current GO:0016887 explicitly supports annotating hydrolysis alongside the overall ATP-dependent activity. Retain this real catalytic property while representing the defining combined activity with one remodeler core. The PTN002473914 ancestral placement was not reconstructed, with no target-specific loss inferred.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN002473914 UNRESOLVED
The exact PAINT ancestral source is retained; historical node placement was not reconstructed. Independent target evidence supports the function without donor-count or target-self-reference objections.
Supporting Evidence:
GO_REF:0000033
GO:0016887 ATP hydrolysis activity
IDA
PMID:28977666
CHD3 and CHD4 form distinct NuRD complexes with different ye...
ACCEPT
Summary: Retain direct CHD3 ATP hydrolysis.
Reason: Purified human CHD3 ATP hydrolysis is directly measured, and some mutants uncouple hydrolysis from nucleosome remodeling. Current GO:0016887 explicitly supports annotating hydrolysis alongside the overall ATP-dependent activity. Retain this real catalytic property while representing the defining combined activity with one remodeler core.
Supporting Evidence:
GO:0016887 ATP hydrolysis activity
IEA
GO_REF:0000116
ACCEPT
Summary: Retain direct CHD3 ATP hydrolysis.
Reason: Purified human CHD3 ATP hydrolysis is directly measured, and some mutants uncouple hydrolysis from nucleosome remodeling. Current GO:0016887 explicitly supports annotating hydrolysis alongside the overall ATP-dependent activity. Retain this real catalytic property while representing the defining combined activity with one remodeler core.
Supporting Evidence:
GO_REF:0000116
GO:0016887 ATP hydrolysis activity
TAS
Reactome:R-HSA-9944091
ACCEPT
Summary: Retain direct CHD3 ATP hydrolysis.
Reason: Purified human CHD3 ATP hydrolysis is directly measured, and some mutants uncouple hydrolysis from nucleosome remodeling. Current GO:0016887 explicitly supports annotating hydrolysis alongside the overall ATP-dependent activity. Retain this real catalytic property while representing the defining combined activity with one remodeler core. Reactome explicitly assigns the ATPase step to CHD components, not to the deacetylases.
Supporting Evidence:
Reactome:R-HSA-9944091
GO:0042393 histone binding
IBA
GO_REF:0000033
ACCEPT
Summary: Retain histone recognition as an integral CHD3 chromatin interaction.
Reason: The PAINT PTN002473914 assertion is independently supported by purified human CHD3 PHD domains binding histone H3 tails and nucleosomes. H3K9 modification alters affinity and H3K4 methylation can inhibit binding; this is not histone-modifying catalysis. Isolated-domain behavior is not assumed to define every full-length NuRD configuration.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN002473914 UNRESOLVED
The exact PAINT ancestral source is retained; historical node placement was not reconstructed. Independent target evidence supports the function without donor-count or target-self-reference objections.
Supporting Evidence:
GO:0042659 regulation of cell fate specification
NAS
PMID:22560079
NuRD suppresses pluripotency gene expression to promote tran...
KEEP AS NON CORE
Summary: Retain regulation of cell fate specification at source-qualified developmental scope.
Reason: The original PMID:22560079 mainly assays mouse Mbd3/NuRD and Mi2beta, so it is not described as a human CHD3-specific perturbation. Independent PMID:40835974 directly examines isogenic human CHD3-deficient iPSCs during cranial neural crest specification, with altered chromatin accessibility and lineage expression. KO cells retain initial pluripotency but fail normal neural-crest differentiation; this supports the broad existing assertion without manufacturing a BMP-signaling function or claiming Wnt inhibition restores neural crest identity.
Supporting Evidence:
GO:0045892 negative regulation of DNA-templated transcription
NAS
PMID:22560079
NuRD suppresses pluripotency gene expression to promote tran...
ACCEPT
Summary: Retain transcriptional repression as one outcome of CHD3 remodeling.
Reason: The original NuRD-family source mainly tests mouse Mbd3/Mi2beta and is kept at that scope. Independent human CHD3 promoter and expression assays in PMID:27068747 establish repression, while other contexts permit activation. HDAC-mediated deacetylation is not assigned to CHD3 itself.
Supporting Evidence:
GO:0045893 positive regulation of DNA-templated transcription
NAS
PMID:19927129
NuRD mediates activating and repressive functions of GATA-1 ...
ACCEPT
Summary: Retain positive transcriptional regulation at the independently supported CHD3 scope.
Reason: Full PMID:19927129 mainly tests mouse FOG1/NuRD with Mi2beta, while explicitly discussing prior Mi2alpha/MYB activation; its own FOG1 assays are not recast as CHD3-specific. Independent human CHD3 studies show activated as well as repressed targets and CHD3-dependent regulatory accessibility during neural crest specification. This supports the original broad positive-regulation assertion without assigning an autonomous sequence-specific TF or deacetylase function.
GO:0140658 ATP-dependent chromatin remodeler activity
IBA
GO_REF:0000033
ACCEPT
Summary: Retain ATP-dependent chromatin remodeler activity as the defining CHD3 function.
Reason: Direct human CHD3 ATPase and nucleosome repositioning/accessibility assays establish this activity. The tested recombinant/tagged constructs are not silently mapped to every current alternative product. CHD3 and CHD4 are distinct paralogs, and NuRD-associated deacetylation remains HDAC-subunit work.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN002473914 UNRESOLVED
The exact PAINT ancestral source is retained; historical node placement was not reconstructed. Independent target evidence supports the function without donor-count or target-self-reference objections.
Supporting Evidence:
GO:0140658 ATP-dependent chromatin remodeler activity
IDA
PMID:28977666
CHD3 and CHD4 form distinct NuRD complexes with different ye...
ACCEPT
Summary: Retain ATP-dependent chromatin remodeler activity as the defining CHD3 function.
Reason: Direct human CHD3 ATPase and nucleosome repositioning/accessibility assays establish this activity. The tested recombinant/tagged constructs are not silently mapped to every current alternative product. CHD3 and CHD4 are distinct paralogs, and NuRD-associated deacetylation remains HDAC-subunit work.
Supporting Evidence:
GO:0140658 ATP-dependent chromatin remodeler activity
IDA
PMID:30397230
CHD3 helicase domain mutations cause a neurodevelopmental sy...
ACCEPT
Summary: Retain ATP-dependent chromatin remodeler activity as the defining CHD3 function.
Reason: Direct human CHD3 ATPase and nucleosome repositioning/accessibility assays establish this activity. The tested recombinant/tagged constructs are not silently mapped to every current alternative product. CHD3 and CHD4 are distinct paralogs, and NuRD-associated deacetylation remains HDAC-subunit work.
Supporting Evidence:
PMID:30397230
restriction enzyme accessibility to nucleosomal DNA
GO:2000736 regulation of stem cell differentiation
NAS
PMID:22560079
NuRD suppresses pluripotency gene expression to promote tran...
KEEP AS NON CORE
Summary: Retain regulation of stem cell differentiation at source-qualified developmental scope.
Reason: The original PMID:22560079 mainly assays mouse Mbd3/NuRD and Mi2beta, so it is not described as a human CHD3-specific perturbation. Independent PMID:40835974 directly examines isogenic human CHD3-deficient iPSCs during cranial neural crest specification, with altered chromatin accessibility and lineage expression. KO cells retain initial pluripotency but fail normal neural-crest differentiation; this supports the broad existing assertion without manufacturing a BMP-signaling function or claiming Wnt inhibition restores neural crest identity.
Supporting Evidence:

Core Functions

CHD3 uses ATP hydrolysis to reposition nucleosomes and alter chromatin accessibility. This motor activity supports context-dependent transcription regulation in CHD3-containing NuRD assemblies; deacetylation is performed by the HDAC subunits. Human purified-protein assays establish the remodeling step directly, while histone recognition and nuclear chromatin localization provide substrate and cellular context.

Supporting Evidence:

References

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Suggested Questions for Experts

Q: Which current CHD3 alternative products were used in each purified motor assay, and do their C-terminal differences alter remodeling or partner selection?

Q: Does the Mi-2 reagent in the DDX5 study distinguish CHD3 from CHD4, and what original record links PMID:9804427 to mouse pericentrin?

Q: What molecular step retains pericentrin at centrosomes, and how much of the CHD3 depletion phenotype is independent of transcriptional changes?

Q: Which RNAs and CHD3 regions underlie the positive UV-crosslink interactome capture, and does that binding regulate remodeling in a defined cellular context?

Q: Which CHD3 activities during human neural crest specification require NuRD, and which operate in other assemblies?

Suggested Experiments

Experiment: Map the exact recombinant sequences to current products and compare ATPase and nucleosome-accessibility assays under matched conditions.

Experiment: Use paralog-specific endogenous tagging or unique peptides to resolve the DDX5-associated Mi-2 protein.

Experiment: Separate acute centrosomal CHD3 perturbation from longer transcriptional changes while measuring pericentrin exchange and retention.

πŸ“š Additional Documentation

Notes

(CHD3-notes.md)

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