DNMT3A is a chromatin-associated DNA cytosine C5 methyltransferase that establishes DNA methylation patterns important for development and cellular identity. It methylates CpG sites and can also methylate non-CpG cytosines. With the noncatalytic activator DNMT3L it forms a heterotetrameric DNA methyltransferase complex in which DNMT3A supplies both active sites, and in germ cells it deposits the methylation that establishes maternal and most paternal genomic imprints. Its ADD domain recognizes the histone H3 amino terminus preferentially when lysine 4 is unmethylated, while its PWWP domain recognizes methylated H3 lysine 36. These reader modules, oligomerization and regulatory partners help target and control DNA methylation, including repression at selected promoters. Nuclear and cytoplasmic pools vary with cell type and developmental stage. Alternative transcripts encode products with different amino termini or extensive truncation. Germline and somatic variants can alter growth and neurodevelopment or contribute to hematological malignancy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:23042785 Control of epigenetic states by WT1 via regulation of de nov... | MODIFY | Summary: Promoter methylation provides a more specific transcriptional-silencing process. Reason: Human WiT49/HEK293 experiments connect DNMT3A promoter occupancy, CpG methylation and repression at selected downstream loci. WT1 increases DNMT3A expression; increased WT1 occupancy at those downstream promoters was not demonstrated. The replacement specifies the methylation-dependent work rather than implying a universal repressive effect of DNMT3A. Proposed replacements: negative regulation of gene expression via chromosomal CpG island methylation Supporting Evidence: |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:19786833 Dnmt3/transcription factor interactions as crucial players i... | MODIFY | Summary: MYC-directed promoter methylation specifies the repressive process. Reason: Human glioma-cell perturbation and promoter assays support MYC-dependent DNMT3A recruitment and repression. CpG-island methylation is the specific supported mechanism, rather than an independent sequence-specific transcription-factor activity. Proposed replacements: negative regulation of gene expression via chromosomal CpG island methylation Supporting Evidence: |
| GO:0000775 chromosome, centromeric region | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Centromeric association is a contextual chromosomal pool. Reason: The ortholog transfer is grounded in mouse localization and Mis18-dependent recruitment, including PMID:22516971. PMID:15456878 separately resolves prominent pericentric major-satellite association; these structures must not be conflated. Retain the curated centromeric pool without asserting a human kinetochore role or exclusive localization. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O88508 SUPPORTS TRANSFER The literal mapping/donor record was traced. The ortholog transfer is grounded in mouse localization and Mis18-dependent recruitment, including PMID:22516971. PMID:15456878 separately resolves prominent pericentric major-satellite association; these structures must not be conflated. Retain the curated centromeric pool without asserting a human kinetochore role or exclusive localization. ensembl:ENSMUSP00000020991 SUPPORTS TRANSFER The literal mapping/donor record was traced. The ortholog transfer is grounded in mouse localization and Mis18-dependent recruitment, including PMID:22516971. PMID:15456878 separately resolves prominent pericentric major-satellite association; these structures must not be conflated. Retain the curated centromeric pool without asserting a human kinetochore role or exclusive localization. |
| GO:0000792 heterochromatin | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Heterochromatin localization is supported in the mouse ortholog. Reason: Mouse experiments document Dnmt3a association with condensed chromatin and major-satellite regions. This positive localization supports the inherited compartment; it does not by itself establish that DNMT3A executes constitutive-heterochromatin formation in every cell type. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O88508 SUPPORTS TRANSFER The literal mapping/donor record was traced. Mouse experiments document Dnmt3a association with condensed chromatin and major-satellite regions. This positive localization supports the inherited compartment; it does not by itself establish that DNMT3A executes constitutive-heterochromatin formation in every cell type. ensembl:ENSMUSP00000020991 SUPPORTS TRANSFER The literal mapping/donor record was traced. Mouse experiments document Dnmt3a association with condensed chromatin and major-satellite regions. This positive localization supports the inherited compartment; it does not by itself establish that DNMT3A executes constitutive-heterochromatin formation in every cell type. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:19786833 Dnmt3/transcription factor interactions as crucial players i... | MODIFY | Summary: The source supports recruited chromatin association, not an autonomous Pol II cis-regulatory recognition activity. Reason: DNMT3A alone has broad DNA-substrate preferences; MYC increases targeting to MYC-containing promoter sequences. Chromatin binding preserves the observed occupancy without assigning MYC sequence recognition to DNMT3A. Proposed replacements: chromatin binding Supporting Evidence: |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:23042785 Control of epigenetic states by WT1 via regulation of de nov... | MODIFY | Summary: Promoter occupancy supports chromatin binding. Reason: The recovered human original measures DNMT3A occupancy by ChIP at methylated downstream promoters and separately shows WT1 regulation of the DNMT3A promoter. Those experiments do not demonstrate autonomous sequence-specific recognition of Pol II cis-regulatory elements by DNMT3A. Chromatin binding preserves the directly observed association. Proposed replacements: chromatin binding Supporting Evidence: |
| GO:0001741 XY body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse meiotic XY-body localization supports a developmental compartment. Reason: PMID:20577743 explicitly reports Dnmt3a on the XY body in wild-type mouse pachytene spermatocytes. Retain this conserved, stage-specific localization without treating it as a constitutive somatic location or asserting an equivalent human imaging experiment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O88508 SUPPORTS TRANSFER The literal mapping/donor record was traced. PMID:20577743 explicitly reports Dnmt3a on the XY body in wild-type mouse pachytene spermatocytes. Retain this conserved, stage-specific localization without treating it as a constitutive somatic location or asserting an equivalent human imaging experiment. ensembl:ENSMUSP00000020991 SUPPORTS TRANSFER The literal mapping/donor record was traced. PMID:20577743 explicitly reports Dnmt3a on the XY body in wild-type mouse pachytene spermatocytes. Retain this conserved, stage-specific localization without treating it as a constitutive somatic location or asserting an equivalent human imaging experiment. Supporting Evidence: |
| GO:0003677 DNA binding | EXP PMID:29414941 Structural basis for DNMT3A-mediated de novo DNA methylation... | MODIFY | Summary: Direct DNA engagement supports the more specific unmethylated CpG-binding term. Reason: Human DNMT3A catalytic-domain structures resolve CpG recognition, and biochemical assays test methylation of ordinary CpG-containing DNA. The covalent crystallographic trap uses zebularine and is distinct from the unmodified DNA used in kinetic assays. Unmethylated CpG binding preserves the interaction claim as a supported descendant of DNA binding. This does not imply exclusive CpG specificity: measurable non-CpG methylation remains represented by the broader catalytic core. Proposed replacements: unmethylated CpG binding Supporting Evidence: |
| GO:0003677 DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: Conserved DNA binding is refined using direct target evidence for unmethylated CpG recognition. Reason: The traced mouse ortholog transfer supports the broad DNA-binding claim. Independent human DNA-bound structures and CpG-substrate assays support the more specific unmethylated CpG-binding term. This is a target-level refinement within the DNA-binding branch; it does not claim that each donor experiment resolved this specificity or that DNMT3A acts exclusively on CpG substrates. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:O88508 SUPPORTS TRANSFER The literal mapping and mouse donor record were traced and support conserved DNA binding. Independent human structural and substrate evidence supplies the narrower unmethylated CpG-binding term; the donor assay is not represented as resolving that specificity. ensembl:ENSMUSP00000020991 SUPPORTS TRANSFER The literal mapping and mouse donor record were traced and support conserved DNA binding. Independent human structural and substrate evidence supplies the narrower unmethylated CpG-binding term; the donor assay is not represented as resolving that specificity. Proposed replacements: unmethylated CpG binding Supporting Evidence: |
| GO:0003682 chromatin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Chromatin association supports DNMT3A targeting. Reason: The rat donor has positive promoter ChIP evidence, including the CRH-promoter experiment in PMID:23671328. That study distinguishes Dnmt3a promoter occupancy from the dexamethasone-induced increase and glucocorticoid-receptor interaction of Dnmt3b. Human promoter and nucleosome studies independently establish DNMT3A chromatin association. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q1LZ53 SUPPORTS TRANSFER The literal mapping/donor record was traced. The rat donor has positive promoter ChIP evidence, including the CRH-promoter experiment in PMID:23671328. That study distinguishes Dnmt3a promoter occupancy from the dexamethasone-induced increase and glucocorticoid-receptor interaction of Dnmt3b. Human promoter and nucleosome studies independently establish DNMT3A chromatin association. ensembl:ENSRNOP00000046524 SUPPORTS TRANSFER The literal mapping/donor record was traced. The rat donor has positive promoter ChIP evidence, including the CRH-promoter experiment in PMID:23671328. That study distinguishes Dnmt3a promoter occupancy from the dexamethasone-induced increase and glucocorticoid-receptor interaction of Dnmt3b. Human promoter and nucleosome studies independently establish DNMT3A chromatin association. |
| GO:0003714 transcription corepressor activity | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Transcription-corepressor activity describes a supported partner-directed context. Reason: MYC-dependent recruitment and promoter repression support a coregulator role within selected regulatory complexes. The catalytic methylation mechanism is represented in the core; this broader partner-directed descriptor is retained contextually. The ARBA rule is an automated family-feature association, not an additional direct assay. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00089152 SUPPORTS TRANSFER The literal mapping/donor record was traced. MYC-dependent recruitment and promoter repression support a coregulator role within selected regulatory complexes. The catalytic methylation mechanism is represented in the core; this broader partner-directed descriptor is retained contextually. The ARBA rule is an automated family-feature association, not an additional direct assay. Supporting Evidence: |
| GO:0003714 transcription corepressor activity | TAS PMID:19786833 Dnmt3/transcription factor interactions as crucial players i... | KEEP AS NON CORE | Summary: Transcription-corepressor activity describes a supported partner-directed context. Reason: MYC-dependent recruitment and promoter repression support this coregulator role. Retain the contextual descriptor alongside the more precisely represented catalytic methylation mechanism; no separate transcriptional enzyme is inferred. Supporting Evidence: |
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: DNA cytosine C5 methylation is a central activity. Reason: The exact IBD at PTN000552637 includes the target and mouse evidence, and the human target descends from that node. Target self-evidence is legitimate grounding, not circularity. Human catalytic assays independently agree with this conserved activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000552637 SUPPORTS TRANSFER Exact IBD and target descent verified; self-grounding is legitimate. The exact IBD at PTN000552637 includes the target and mouse evidence, and the human target descends from that node. Target self-evidence is legitimate grounding, not circularity. Human catalytic assays independently agree with this conserved activity. Supporting Evidence: |
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | IDA PMID:12138111 A novel Dnmt3a isoform produced from an alternative promoter... | ACCEPT | Summary: DNA cytosine C5 methylation is a central activity. Reason: The curated human enzyme assertion is consistent with the original abstract describing active human and mouse proteins and with independently recovered human catalytic-domain assays. The historical shortened construct is not equated with the current 723-residue product by its name. |
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | IDA PMID:19786833 Dnmt3/transcription factor interactions as crucial players i... | ACCEPT | Summary: DNA cytosine C5 methylation is a central activity. Reason: The original includes DNMT3A methylation assays and MYC-dependent targeting. Retain the activity without converting targeting preferences into an autonomous transcription-factor function. |
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: DNA cytosine C5 methylation is a central activity. Reason: The EC/Rhea and ortholog mappings identify DNA-cytosine methylation, directly corroborated by human substrate assays. Non-CpG activity remains within this broad enzymatic term. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:O88508 SUPPORTS TRANSFER The literal mapping/donor record was traced. The EC/Rhea and ortholog mappings identify DNA-cytosine methylation, directly corroborated by human substrate assays. Non-CpG activity remains within this broad enzymatic term. ensembl:ENSMUSP00000020991 SUPPORTS TRANSFER The literal mapping/donor record was traced. The EC/Rhea and ortholog mappings identify DNA-cytosine methylation, directly corroborated by human substrate assays. Non-CpG activity remains within this broad enzymatic term. RHEA:13681 SUPPORTS TRANSFER The literal mapping/donor record was traced. The EC/Rhea and ortholog mappings identify DNA-cytosine methylation, directly corroborated by human substrate assays. Non-CpG activity remains within this broad enzymatic term. EC:2.1.1.37 SUPPORTS TRANSFER The literal mapping/donor record was traced. The EC/Rhea and ortholog mappings identify DNA-cytosine methylation, directly corroborated by human substrate assays. Non-CpG activity remains within this broad enzymatic term. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16357870 The Polycomb group protein EZH2 directly controls DNA methyl... | KEEP AS NON CORE | Summary: The EED association is retained with its PRC2 assay scope. Reason: The literal human pair is represented by co-immunoprecipitation and a curated pull-down record. The recovered supplement describes the interaction and nuclear-extract methods. This supports association with a Polycomb component, without establishing a separate EED-reader activity of DNMT3A or assigning EED catalytic activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16357870 The Polycomb group protein EZH2 directly controls DNA methyl... | MODIFY | Summary: The EZH2 pair supports histone methyltransferase binding. Reason: The exact curated pair and human HeLa co-immunoprecipitation support EZH2 association. The recovered supplementary protocol and corrected Figure 2a/S1 document a direct GST/in-vitro-translated domain interaction; S1 uses historical 908-residue DNMT3A numbering, so its species/current-product mapping is not assumed. Together with the established EZH2 histone-methyltransferase class, this supports the bounded partner-class refinement without assigning histone catalysis to DNMT3A. Proposed replacements: histone methyltransferase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16682412 The histone methyltransferase SETDB1 and the DNA methyltrans... | MODIFY | Summary: The SETDB1 pair supports histone methyltransferase binding. Reason: The original abstract explicitly describes direct SETDB1 amino-terminal binding to the DNMT3A PHD region. The exact curated GST pull-down record specifies DNMT3A residues 480β620 and SETDB1 residues 1β527. SETDB1 is a histone methyltransferase, so this bounded partner-class refinement is supported despite unavailable full main text; it does not assign histone methylation to DNMT3A. Proposed replacements: histone methyltransferase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16983096 Recruitment of the de novo DNA methyltransferase Dnmt3a by K... | KEEP AS NON CORE | Summary: Viral LANA binding is a supported recruitment context. Reason: The recovered original shows GST-LANA pull-down of in-vitro-translated DNMT3A, reciprocal tagged co-immunoprecipitation in human cells and promoter recruitment. The viral association is retained without making viral targeting a separate core activity or mapping the historical reagent to every current splice product. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17713477 Structure of Dnmt3a bound to Dnmt3L suggests a model for de ... | KEEP AS NON CORE | Summary: DNMT3L association is supported by an ortholog complex. Reason: The original purified proteins are mouse Dnmt3a and Dnmt3L fragments/full-length constructs, with direct heterotetramer structure and activity effects. Human complex evidence is independently available, but the mouse reagent must remain explicit. DNMT3L is an inactive regulatory partner, so methyltransferase-binding is not inferred from its gene name. |
| GO:0005515 protein binding | IPI PMID:19234465 PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, ... | MODIFY | Summary: The PRMT5 pair supports histone methyltransferase binding. Reason: The human K562 study combines co-immunoprecipitation with GST-PRMT5 binding to in-vitro-translated DNMT3A. PRMT5 catalytic mutants also bind, so the pair supports recognition of a histone methyltransferase partner rather than requiring its catalytic turnover. The separate H4R3 methyl-mark recognition claim is condition-dependent and was not reproduced in PMID:19834512. Proposed replacements: histone methyltransferase binding Supporting Evidence: PMID:19234465 in vitro transcribed and translated DNMT3A to GST-PRMT5 |
| GO:0005515 protein binding | IPI PMID:19798101 Np95 interacts with de novo DNA methyltransferases, Dnmt3a a... | KEEP AS NON CORE | Summary: UHRF1/Np95 association is supported with ortholog scope. Reason: The recovered study demonstrates mouse Np95βDnmt3a2 association in mouse embryonic stem-cell and fusion-protein experiments. A human host cell does not make the expressed mouse construct human. Retain the curated conserved association; no purified human interface or new ubiquitin-binding activity is inferred. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19834512 Structural basis for recognition of H3K4 methylation status ... | MODIFY | Summary: The H3 interaction is resolved as unmodified-histone reader activity. Reason: Direct human ADD-domain binding and structural experiments establish preferential recognition of the H3 amino terminus when K4 is unmethylated. This source supports a more informative reader activity than generic protein binding. It does not establish universal rejection of every methylated peptide or activity of the short natural product. Proposed replacements: unmodified histone reader activity Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21976679 cAMP-responsive element modulator (CREM)Ξ± protein signaling ... | KEEP AS NON CORE | Summary: CREM-associated recruitment is retained in a T-cell regulatory context. Reason: The recovered original documents CREM-alpha/DNMT3A co-immunoprecipitation and promoter recruitment in the human-cell study. Co-complex and chromatin occupancy evidence do not isolate a binary recognition interface. Keep the positive association without inventing a distinct transcription-factor-binding mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24074865 Dnmt3L antagonizes DNA methylation at bivalent promoters and... | KEEP AS NON CORE | Summary: Human DNMT3AβEZH2 co-complex association is retained. Reason: The recovered original Figure 6D shows endogenous DNMT3AβEZH2 co-immunoprecipitation in human HEK293 cells; inducible murine FLAG-Dnmt3L reduces this association. The separate purified interaction assay tests Ezh2βDnmt3L, not DNMT3A. Retain the contextual DNMT3A association without assigning a directly demonstrated DNMT3AβEZH2 interface from this experiment. |
| GO:0005515 protein binding | IPI PMID:25383530 Structural insight into autoinhibition and histone H3-induce... | KEEP AS NON CORE | Summary: The DNMT3L complex supports catalytic regulation. Reason: The source abstract and accessible original extended-data captions describe human DNMT3AβDNMT3L complexes, recombinant activity and structural contacts. These support the retained pair while the full main text remains unavailable. DNMT3L is an inactive accessory subunit, not an additional methyltransferase enzyme. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: The SP100 binary screen interaction is retained. Reason: Three literal records for PMID:25416956 include pairwise-validated Y2H and discovery assays with negative-interaction flags false. P23497 is SP100, a transcriptional coregulator. These data support a binary screening interaction, but do not establish a particular regulatory mechanism or native chromatin complex. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: The TCL1A screening interaction is retained. Reason: The exact human pair has positive validated Y2H records. TCL1A is a regulatory AKT coactivator, not an AKT kinase. Do not infer kinase binding or a native signaling mechanism from the partner name. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: The TCL1A screening interaction is retained. Reason: The literal pair has WT-versus-variant Y2H records, including a disruptive DNMT3A position-904 variant and separate non-disruptive variants. The WT interaction remains positive; representative orthogonal validation across the study is not pair-specific proof. TCL1A is a regulatory AKT coactivator, not an AKT kinase. Do not infer kinase binding or a native signaling mechanism from the partner name. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32051553 The EGFR-ZNF263 signaling axis silences SIX3 in glioblastoma... | KEEP AS NON CORE | Summary: ZNF263-associated recruitment is retained. Reason: The human U251 study reports AP-MS/co-immunoprecipitation and promoter recruitment. These support a physical association in a complex; they do not establish purified binary binding or prove that ZNF263 class recognition is the contact made by DNMT3A. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: The OTX1 binary pair supports transcription factor binding. Reason: The exact human pair is present in the validated HuRI Y2H records. The official partner is the homeobox transcription factor OTX1. The refinement states only this established partner class; it does not assign OTX1 developmental targets to DNMT3A or establish a native regulatory complex. Proposed replacements: transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The TCL1A screening interaction is retained. Reason: The exact human pair has positive validated Y2H records. TCL1A is a regulatory AKT coactivator, not an AKT kinase. Do not infer kinase binding or a native signaling mechanism from the partner name. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: The historical MEOX2-clone pair supports transcription factor binding. Reason: The literal Q6FHY5 pair has validated Y2H and a separate complementation-assay record. Sequence comparison to reviewed MEOX2 P50222 identifies a single Q81 deletion outside the homeobox; official MEOX2 has demonstrated DNA-dependent transcriptional activity. Preserve the historical accession and clone difference, and infer only the partner class, not shared native promoter regulation. Proposed replacements: transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: The ZNF513 binary pair supports transcription factor binding. Reason: The exact pair is represented by validated HuRI Y2H records. Official ZNF513 is a transcription factor with DNA-dependent transcriptional evidence. This justifies the partner-class term without establishing physiological stoichiometry, shared target genes or an additional catalytic role. Proposed replacements: transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The MDFI binary screen interaction is retained. Reason: Validated HuRI records support the literal pair. MDFI regulates transcription-factor function but the screen alone does not resolve how DNMT3A recognizes it or establish a transcriptional mechanism. Retain the positive interaction without a speculative functional subtype. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: The WFS1 binary screen interaction is retained. Reason: The source pair has positive pooled, array and validated Y2H records. WFS1 is an ER membrane protein; compartment differences do not invalidate a tested binary reagent. No native ER localization of DNMT3A, membrane transport activity or physiological complex is inferred. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32968275 Structure of nucleosome-boundΒ DNA methyltransferases DNMT3A ... | KEEP AS NON CORE | Summary: The purified DNMT3A2βDNMT3B3 complex is retained with tested-product scope. Reason: The original coexpresses human DNMT3A residues 224β912 with full DNMT3B3 and resolves a 3B3β3A2β3A2β3B3 complex. DNMT3B3 is catalytically inactive and anchors the nucleosome acidic patch. Thus this is direct complex evidence, but not binding to an active methyltransferase simply because the partner is DNMT3B. The historical 689-residue DNMT3A2 is not the current 723-residue natural product. Supporting Evidence: PMID:32968275 The structure shows a heterotetrameric 3B3β3A2β3A2β3B3 complex |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: The BioPlex TCL1A association is retained. Reason: Three literal AP-MS records include spoke-expanded complex associations. These support co-purification, not an isolated direct interface. Independent Y2H evidence reinforces the pair, but does not make the AP-MS assay a binary test or assign DNMT3A an AKT-regulatory function. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: The BioPlex DNMT3B association is retained. Reason: The exact non-expanded AP-MS record supports co-purification. It does not resolve the natural DNMT3B splice product or its catalytic competence. Independent purified DNMT3B3 complex evidence supports association but cannot convert this source into a specific active-methyltransferase-binding assay. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | MODIFY | Summary: Nuclear localization is refined to supported chromatin and nucleoplasmic pools. Reason: The target descends from nuclear IBD PTN001497036 with experimental grounding, including the target itself. Human chromatin experiments and HPA nucleoplasmic staining support the narrower, nonexclusive locations at gene level. This refinement does not claim that each original source measured both subcompartments or that nucleoplasm includes chromosomes. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN001497036 SUPPORTS TRANSFER Exact IBD and target descent verified; self-grounding is legitimate. The target descends from nuclear IBD PTN001497036 with experimental grounding, including the target itself. Human chromatin experiments and HPA nucleoplasmic staining support the narrower, nonexclusive locations at gene level. This refinement does not claim that each original source measured both subcompartments or that nucleoplasm includes chromosomes. Proposed replacements: chromatin nucleoplasm |
| GO:0005634 nucleus | IDA PMID:12138111 A novel Dnmt3a isoform produced from an alternative promoter... | MODIFY | Summary: Nuclear localization is refined to supported chromatin and nucleoplasmic pools. Reason: The original human enzyme study supports nuclear localization; its historical shortened product should not be equated with current product 2. Human chromatin experiments and HPA nucleoplasmic staining support the narrower, nonexclusive locations at gene level. This refinement does not claim that each original source measured both subcompartments or that nucleoplasm includes chromosomes. Proposed replacements: chromatin nucleoplasm |
| GO:0005634 nucleus | IDA PMID:25743254 Proteomic analyses reveal that loss of TDP-43 affects RNA pr... | MODIFY | Summary: Nuclear localization is refined to supported chromatin and nucleoplasmic pools. Reason: The original normal cache is abstract-only, so it cannot establish the precise localization protocol. The curated nuclear assertion is nevertheless independently well grounded. Human chromatin experiments and HPA nucleoplasmic staining support the narrower, nonexclusive locations at gene level. This refinement does not claim that each original source measured both subcompartments or that nucleoplasm includes chromosomes. Proposed replacements: chromatin nucleoplasm |
| GO:0005634 nucleus | IEA GO_REF:0000120 | MODIFY | Summary: Nuclear localization is refined to supported chromatin and nucleoplasmic pools. Reason: Official ortholog/subcellular-location mappings agree with the observed human nuclear pools. Human chromatin experiments and HPA nucleoplasmic staining support the narrower, nonexclusive locations at gene level. This refinement does not claim that each original source measured both subcompartments or that nucleoplasm includes chromosomes. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: ARBA:ARBA00026330 SUPPORTS TRANSFER The literal mapping/donor record was traced. Official ortholog/subcellular-location mappings agree with the observed human nuclear pools. Human chromatin experiments and HPA nucleoplasmic staining support the narrower, nonexclusive locations at gene level. This refinement does not claim that each original source measured both subcompartments or that nucleoplasm includes chromosomes. UniProtKB:O88508 SUPPORTS TRANSFER The literal mapping/donor record was traced. Official ortholog/subcellular-location mappings agree with the observed human nuclear pools. Human chromatin experiments and HPA nucleoplasmic staining support the narrower, nonexclusive locations at gene level. This refinement does not claim that each original source measured both subcompartments or that nucleoplasm includes chromosomes. ensembl:ENSMUSP00000020991 SUPPORTS TRANSFER The literal mapping/donor record was traced. Official ortholog/subcellular-location mappings agree with the observed human nuclear pools. Human chromatin experiments and HPA nucleoplasmic staining support the narrower, nonexclusive locations at gene level. This refinement does not claim that each original source measured both subcompartments or that nucleoplasm includes chromosomes. UniProtKB:Q1LZ53 SUPPORTS TRANSFER The literal mapping/donor record was traced. Official ortholog/subcellular-location mappings agree with the observed human nuclear pools. Human chromatin experiments and HPA nucleoplasmic staining support the narrower, nonexclusive locations at gene level. This refinement does not claim that each original source measured both subcompartments or that nucleoplasm includes chromosomes. ensembl:ENSRNOP00000046524 SUPPORTS TRANSFER The literal mapping/donor record was traced. Official ortholog/subcellular-location mappings agree with the observed human nuclear pools. Human chromatin experiments and HPA nucleoplasmic staining support the narrower, nonexclusive locations at gene level. This refinement does not claim that each original source measured both subcompartments or that nucleoplasm includes chromosomes. UniProtKB-SubCell:SL-0191 SUPPORTS TRANSFER The literal mapping/donor record was traced. Official ortholog/subcellular-location mappings agree with the observed human nuclear pools. Human chromatin experiments and HPA nucleoplasmic staining support the narrower, nonexclusive locations at gene level. This refinement does not claim that each original source measured both subcompartments or that nucleoplasm includes chromosomes. Proposed replacements: chromatin nucleoplasm |
| GO:0005634 nucleus | NAS PMID:25383530 Structural insight into autoinhibition and histone H3-induce... | MODIFY | Summary: Nuclear localization is refined to supported chromatin and nucleoplasmic pools. Reason: The structural paper supports a nuclear chromatin enzyme, while its accessible extended captions do not independently provide a complete localization assay. Human chromatin experiments and HPA nucleoplasmic staining support the narrower, nonexclusive locations at gene level. This refinement does not claim that each original source measured both subcompartments or that nucleoplasm includes chromosomes. Proposed replacements: chromatin nucleoplasm |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA supports an additional nucleoplasmic pool. Reason: Current HPA ICC/IF records classify nucleoplasmic localization as supported in A-431, U-251MG and U2OS cells, with a further iPSC observation. This positive pool is distinct from chromosome-associated catalytic and reader activity; no absence from other compartments or isoform-specific localization is implied. Image pixels were not independently interpreted. Supporting Evidence: GO_REF:0000052 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-212222 | KEEP AS NON CORE | Summary: The Reactome model supports nucleoplasmic context. Reason: The exact Reactome event connects to the Q9Y6K1 DNMT3A entity in the nucleoplasm through the saved component/set path. This is a modeled compartment, not a soluble-fraction experiment. No additional event-specific catalytic or disease-process annotation is inferred. Supporting Evidence: Reactome:R-HSA-212222 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-212269 | KEEP AS NON CORE | Summary: The Reactome model supports nucleoplasmic context. Reason: The exact Reactome event connects to the Q9Y6K1 DNMT3A entity in the nucleoplasm through the saved component/set path. This is a modeled compartment, not a soluble-fraction experiment. The event combines DNA and histone methylation by different components; it does not assign PRC2 histone catalysis to DNMT3A. Supporting Evidence: Reactome:R-HSA-212269 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5212679 | KEEP AS NON CORE | Summary: The Reactome model supports nucleoplasmic context. Reason: The exact Reactome event connects to the Q9Y6K1 DNMT3A entity in the nucleoplasm through the saved component/set path. This is a modeled compartment, not a soluble-fraction experiment. The associated H4R3me2s-binding mechanism has a condition-specific non-replication in PMID:19834512; that mechanistic disagreement does not negate the independently supported compartment. Supporting Evidence: Reactome:R-HSA-5212679 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9710490 | KEEP AS NON CORE | Summary: The Reactome model supports nucleoplasmic context. Reason: The exact Reactome event connects to the Q9Y6K1 DNMT3A entity in the nucleoplasm through the saved component/set path. This is a modeled compartment, not a soluble-fraction experiment. No additional event-specific catalytic or disease-process annotation is inferred. Supporting Evidence: Reactome:R-HSA-9710490 |
| GO:0005694 chromosome | EXP PMID:12138111 A novel Dnmt3a isoform produced from an alternative promoter... | MODIFY | Summary: Chromatin is a more informative description of the chromosomal pool. Reason: The original chromosome association is consistent with a chromatin-bound DNA methyltransferase and histone-reader protein. Human promoter and nucleosome evidence supports this target-level refinement; it does not imply that the original broad localization source resolved every chromatin substructure. Proposed replacements: chromatin |
| GO:0005694 chromosome | IEA GO_REF:0000044 | MODIFY | Summary: Chromatin is a more informative description of the chromosomal pool. Reason: The original chromosome association is consistent with a chromatin-bound DNA methyltransferase and histone-reader protein. Human promoter and nucleosome evidence supports this target-level refinement; it does not imply that the original broad localization source resolved every chromatin substructure. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB-SubCell:SL-0468 SUPPORTS TRANSFER The literal mapping/donor record was traced. The original chromosome association is consistent with a chromatin-bound DNA methyltransferase and histone-reader protein. Human promoter and nucleosome evidence supports this target-level refinement; it does not imply that the original broad localization source resolved every chromatin substructure. Proposed replacements: chromatin |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: A nonexclusive cytoplasmic pool is retained. Reason: The PAINT IBD at PTN002747444 is an inherited localization judgment supported by descendant evidence, and the target is inside its clade. Mouse germ-cell studies provide positive context for this distribution. Retain it without converting cytoplasmic presence into a cytoplasmic methylation core or interpreting nuclear enrichment as contradictory evidence. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002747444 SUPPORTS TRANSFER Exact IBD and target descent verified; self-grounding is legitimate. The PAINT IBD at PTN002747444 is an inherited localization judgment supported by descendant evidence, and the target is inside its clade. Mouse germ-cell studies provide positive context for this distribution. Retain it without converting cytoplasmic presence into a cytoplasmic methylation core or interpreting nuclear enrichment as contradictory evidence. |
| GO:0005737 cytoplasm | IDA PMID:12138111 A novel Dnmt3a isoform produced from an alternative promoter... | KEEP AS NON CORE | Summary: A nonexclusive cytoplasmic pool is retained. Reason: The curated human localization and ortholog studies support regulated nuclear/cytoplasmic distribution. Mouse germ-cell studies provide positive context for this distribution. Retain it without converting cytoplasmic presence into a cytoplasmic methylation core or interpreting nuclear enrichment as contradictory evidence. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: A nonexclusive cytoplasmic pool is retained. Reason: The curated human localization and ortholog studies support regulated nuclear/cytoplasmic distribution. Mouse germ-cell studies provide positive context for this distribution. Retain it without converting cytoplasmic presence into a cytoplasmic methylation core or interpreting nuclear enrichment as contradictory evidence. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O88508 SUPPORTS TRANSFER The literal mapping/donor record was traced. The curated human localization and ortholog studies support regulated nuclear/cytoplasmic distribution. Mouse germ-cell studies provide positive context for this distribution. Retain it without converting cytoplasmic presence into a cytoplasmic methylation core or interpreting nuclear enrichment as contradictory evidence. ensembl:ENSMUSP00000020991 SUPPORTS TRANSFER The literal mapping/donor record was traced. The curated human localization and ortholog studies support regulated nuclear/cytoplasmic distribution. Mouse germ-cell studies provide positive context for this distribution. Retain it without converting cytoplasmic presence into a cytoplasmic methylation core or interpreting nuclear enrichment as contradictory evidence. UniProtKB-SubCell:SL-0086 SUPPORTS TRANSFER The literal mapping/donor record was traced. The curated human localization and ortholog studies support regulated nuclear/cytoplasmic distribution. Mouse germ-cell studies provide positive context for this distribution. Retain it without converting cytoplasmic presence into a cytoplasmic methylation core or interpreting nuclear enrichment as contradictory evidence. |
| GO:0006346 DNA methylation-dependent constitutive heterochromatin formation | IMP PMID:30478443 Gain-of-function DNMT3A mutations cause microcephalic dwarfi... | KEEP AS NON CORE | Summary: Dnmt3a performs a DNA-methylation step at constitutive pericentric heterochromatin in mouse ES cells. Reason: PMID:15456878 directly reintroduces mouse WT Dnmt3a into Dnmt3a/Dnmt3b-null ES cells and measures restored methylation of pericentric major-satellite DNA. A catalytic mutant fails to restore methylation, while PWWP deletion strongly impairs methylation of these repeats. This supports contextual participation through the performed DNA-methylation step. The measured endpoint is DNA methylation, not de novo chromatin condensation or assembly; structural reinforcement is discussed as a possibility. The original human PMID:30478443 W330R experiments concern Polycomb/H3K27me3-marked developmental valleys and do not independently establish constitutive-heterochromatin formation. Retention uses the complementary mouse evidence without relabeling that human phenotype or changing the original source identity. Supporting Evidence: PMID:15456878 expression of Dnmt3a and Dnmt3b1 in 7aabb cells restored the methylation levels |
| GO:0008168 methyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: The broad InterPro methyltransferase mapping can be specified. Reason: IPR001525 is the C5-cytosine methyltransferase family and maps broadly to methyltransferase activity. Direct human DNA-cytosine assays establish the appropriate target-specific activity, including non-CpG substrates. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR001525 SUPPORTS TRANSFER The literal mapping/donor record was traced. IPR001525 is the C5-cytosine methyltransferase family and maps broadly to methyltransferase activity. Direct human DNA-cytosine assays establish the appropriate target-specific activity, including non-CpG substrates. Proposed replacements: DNA (cytosine-5-)-methyltransferase activity Supporting Evidence: |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Xenobiotic-associated DNMT3A expression changes do not establish response participation. Reason: The only donor evidence is rat RGD annotation by IEP (inferred from expression pattern), projected to human by Ensembl Compara; the cited rat studies report tamoxifen-associated DNMT3A protein decreases and escitalopram-associated transcript changes. A change in DNMT3A abundance identifies DNMT3A as a readout of the exposure, not as a component that performs the response, and no DNMT3A-selective perturbation is reported. The process transfer is therefore over-annotated; the measured expression change itself is not disputed. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q1LZ53 SOURCE WEAK OR INFERRED Rat donor annotation is IEP, an expression-pattern inference; it supports a DNMT3A abundance change, not DNMT3A executing the response. ensembl:ENSRNOP00000046524 SOURCE WEAK OR INFERRED Rat donor annotation is IEP, an expression-pattern inference; it supports a DNMT3A abundance change, not DNMT3A executing the response. |
| GO:0009636 response to toxic substance | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Toxicant-associated DNMT3A transcript changes do not establish response participation. Reason: The only donor evidence is rat RGD annotation by IEP (inferred from expression pattern), projected to human by Ensembl Compara; the cited rat study reports altered testicular DNMT3A transcript abundance after bromopropane exposure. A change in DNMT3A abundance identifies DNMT3A as a readout of the exposure, not as a component that performs the response, and no DNMT3A-selective perturbation is reported. The process transfer is therefore over-annotated; the measured expression change itself is not disputed. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q1LZ53 SOURCE WEAK OR INFERRED Rat donor annotation is IEP, an expression-pattern inference; it supports a DNMT3A abundance change, not DNMT3A executing the response. ensembl:ENSRNOP00000046524 SOURCE WEAK OR INFERRED Rat donor annotation is IEP, an expression-pattern inference; it supports a DNMT3A abundance change, not DNMT3A executing the response. Supporting Evidence: |
| GO:0010212 response to ionizing radiation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Radiation-associated DNMT3A protein changes do not establish response participation. Reason: The only donor evidence is rat RGD annotation by IEP (inferred from expression pattern), projected to human by Ensembl Compara; the cited rat study reports reduced DNMT3A protein in rat mammary tissue after radiation exposure. A change in DNMT3A abundance identifies DNMT3A as a readout of the exposure, not as a component that performs the response, and no DNMT3A-selective perturbation is reported. The process transfer is therefore over-annotated; the measured expression change itself is not disputed. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q1LZ53 SOURCE WEAK OR INFERRED Rat donor annotation is IEP, an expression-pattern inference; it supports a DNMT3A abundance change, not DNMT3A executing the response. ensembl:ENSRNOP00000046524 SOURCE WEAK OR INFERRED Rat donor annotation is IEP, an expression-pattern inference; it supports a DNMT3A abundance change, not DNMT3A executing the response. Supporting Evidence: |
| GO:0010288 response to lead ion | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Lead-associated expression is established, but functional response participation is not resolved. Reason: The full rat study measures nuclear DNMT3A protein by immunoblot after developmental lead exposure, with sex-, dose- and exposure-window-dependent effects. These are positive response-associated observations. They do not identify DNMT3A as an executing component of lead response; the human process transfer is over-annotated rather than contradicted. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q1LZ53 SOURCE WEAK OR INFERRED The literal mapping/donor record was traced. The full rat study measures nuclear DNMT3A protein by immunoblot after developmental lead exposure, with sex-, dose- and exposure-window-dependent effects. These are positive response-associated observations. They do not identify DNMT3A as an executing component of lead response; the human process transfer is over-annotated rather than contradicted. ensembl:ENSRNOP00000046524 SOURCE WEAK OR INFERRED The literal mapping/donor record was traced. The full rat study measures nuclear DNMT3A protein by immunoblot after developmental lead exposure, with sex-, dose- and exposure-window-dependent effects. These are positive response-associated observations. They do not identify DNMT3A as an executing component of lead response; the human process transfer is over-annotated rather than contradicted. Supporting Evidence: |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000002 | MODIFY | Summary: The broad gene-expression mapping can be specified to methylation-dependent silencing. Reason: IPR044108 is the DNMT3A ADD domain and supplies a broad regulation-of-gene-expression mapping. Human locus-targeting and methylation experiments establish CpG-island-mediated repression as a more informative target-level process, without implying that every instance of DNMT3A activity silences a gene. Germline imprint establishment (genomic imprinting, from mouse ortholog conditional knockout) is a second supported descendant and is listed as well. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR044108 SUPPORTS TRANSFER The literal mapping/donor record was traced. IPR044108 is the DNMT3A ADD domain and supplies a broad regulation-of-gene-expression mapping. Human locus-targeting and methylation experiments establish CpG-island-mediated repression as a more informative target-level process, without implying that every instance of DNMT3A activity silences a gene. Proposed replacements: negative regulation of gene expression via chromosomal CpG island methylation genomic imprinting Supporting Evidence: PMID:15215868 both Dnmt3a and Dnmt3L are required for methylation of most imprinted loci in germ cells |
| GO:0016363 nuclear matrix | IDA PMID:12138111 A novel Dnmt3a isoform produced from an alternative promoter... | UNDECIDED | Summary: The specific nuclear-matrix assertion cannot yet be resolved. Reason: PMID:12138111 remains abstract-only after attempted original recovery, and the abstract does not resolve the extraction controls underlying this specific compartment. Other studies document operational nuclear-matrix fractionation in a viral-recruitment context, but that is not a substitute for the cited experiment or proof of a constitutive matrix pool. Retain uncertainty without denying nuclear localization. |
| GO:0030182 neuron differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Neuronal differentiation is retained as a contextual developmental role, grounded in mouse ortholog perturbation rather than the rat expression donor. Reason: The rat donor annotation is IEP (PMID:19660178 follows Dnmt3a expression during dorsal-root-ganglion neural-stem-cell differentiation with only a nonselective methylation inhibitor), which alone would not establish participation. Independent ortholog evidence does. Mouse Dnmt3a (O88508, the same PANTHER subfamily PTHR23068:SF10 as human DNMT3A) is required cell-autonomously for neuronal differentiation of postnatal neural stem cells; acute deletion impairs it, and the defect is rescued by wild-type but not catalytically inactive Dnmt3a. Dnmt3a methylates nonpromoter regions of neurogenic genes, antagonising Polycomb repression of them (PMID:20651149). DNMT3A therefore does work in this process through its methylation activity. It is a developmental context of the core activity, not a separate function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q1LZ53 SOURCE WEAK OR INFERRED The rat donor annotation is an expression-pattern (IEP) inference. The process term holds for the target on independent mouse ortholog perturbation and rescue evidence (PMID:20651149), not on this donor. ensembl:ENSRNOP00000046524 SOURCE WEAK OR INFERRED Same rat IEP donor as above; the transfer outcome is correct for reasons the donor does not itself establish. Supporting Evidence: PMID:20651149 Thus, specific and cell-autonomous functions of Dnmt3a are required for neurogenesis from postnatal NSCs. PMID:20651149 the neurogenesis deficit in Dnmt3a -null cultures was rescued by re-expressing physiological levels of WT Dnmt3a, but not catalytically inactive mutant Dnmt3a |
| GO:0031048 regulatory ncRNA-mediated heterochromatin formation | IGI PMID:23435381 A pseudogene long-noncoding-RNA network regulates PTEN trans... | KEEP AS NON CORE | Summary: The ncRNA-directed silencing context is retained. Reason: Human PTENpg1 antisense-alpha experiments show RNA-associated DNMT3A and promoter recruitment, with depletion affecting chromatin silencing marks and gene expression. The evidence supports participation in this locus-specific ncRNA-mediated silencing machinery; it does not make DNMT3A a histone methyltransferase or a universal RNA-directed heterochromatin factor. Supporting Evidence: |
| GO:0031667 response to nutrient levels | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Nutrient-associated expression does not isolate a DNMT3A response function. Reason: The full rat folate/methyl-deficient diet study measures increased Dnmt3a RNA while its protein level is not detectably changed, alongside multiple epigenetic regulators. The observed expression response is real; a target-specific executing role in nutrient response is not established by those measurements. The broad human process transfer is therefore over-annotated. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q1LZ53 SOURCE WEAK OR INFERRED The literal mapping/donor record was traced. The full rat folate/methyl-deficient diet study measures increased Dnmt3a RNA while its protein level is not detectably changed, alongside multiple epigenetic regulators. The observed expression response is real; a target-specific executing role in nutrient response is not established by those measurements. The broad human process transfer is therefore over-annotated. ensembl:ENSRNOP00000046524 SOURCE WEAK OR INFERRED The literal mapping/donor record was traced. The full rat folate/methyl-deficient diet study measures increased Dnmt3a RNA while its protein level is not detectably changed, alongside multiple epigenetic regulators. The observed expression response is real; a target-specific executing role in nutrient response is not established by those measurements. The broad human process transfer is therefore over-annotated. Supporting Evidence: |
| GO:0032355 response to estradiol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Estradiol-associated DNMT3A expression changes do not establish response participation. Reason: The only donor evidence is rat RGD annotation by IEP (inferred from expression pattern), projected to human by Ensembl Compara; the cited rat study reports miR-29-associated changes in DNMT3A expression after estradiol exposure. A change in DNMT3A abundance identifies DNMT3A as a readout of the exposure, not as a component that performs the response, and no DNMT3A-selective perturbation is reported. The process transfer is therefore over-annotated; the measured expression change itself is not disputed. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q1LZ53 SOURCE WEAK OR INFERRED Rat donor annotation is IEP, an expression-pattern inference; it supports a DNMT3A abundance change, not DNMT3A executing the response. ensembl:ENSRNOP00000046524 SOURCE WEAK OR INFERRED Rat donor annotation is IEP, an expression-pattern inference; it supports a DNMT3A abundance change, not DNMT3A executing the response. Supporting Evidence: |
| GO:0033189 response to vitamin A | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Vitamin A-associated DNMT3A expression differences do not establish response participation. Reason: The only donor evidence is rat RGD annotation by IEP (inferred from expression pattern), projected to human by Ensembl Compara; the cited rat study reports DNMT3A expression differences in embryonic heart under vitamin A deficiency. A change in DNMT3A abundance identifies DNMT3A as a readout of the exposure, not as a component that performs the response, and no DNMT3A-selective perturbation is reported. The process transfer is therefore over-annotated; the measured expression change itself is not disputed. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q1LZ53 SOURCE WEAK OR INFERRED Rat donor annotation is IEP, an expression-pattern inference; it supports a DNMT3A abundance change, not DNMT3A executing the response. ensembl:ENSRNOP00000046524 SOURCE WEAK OR INFERRED Rat donor annotation is IEP, an expression-pattern inference; it supports a DNMT3A abundance change, not DNMT3A executing the response. Supporting Evidence: |
| GO:0042220 response to cocaine | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Cocaine-associated DNMT expression changes do not establish a DNMT3A response role. Reason: The only donor evidence is rat RGD annotation by IEP (inferred from expression pattern), projected to human by Ensembl Compara; the cited rat study reports DNMT expression and promoter-methylation changes after cocaine exposure, with only a nonselective DNMT inhibitor as perturbation. A change in DNMT3A abundance identifies DNMT3A as a readout of the exposure, not as a component that performs the response, and no DNMT3A-selective perturbation is reported. The process transfer is therefore over-annotated; the measured expression change itself is not disputed. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q1LZ53 SOURCE WEAK OR INFERRED Rat donor annotation is IEP, an expression-pattern inference; it supports a DNMT3A abundance change, not DNMT3A executing the response. ensembl:ENSRNOP00000046524 SOURCE WEAK OR INFERRED Rat donor annotation is IEP, an expression-pattern inference; it supports a DNMT3A abundance change, not DNMT3A executing the response. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:24656771 The R882H DNMT3A mutation associated with AML dominantly inh... | KEEP AS NON CORE | Summary: Self-association is an experimentally established assembly property. Reason: Human WT DNMT3A purification, coexpression and gel-filtration experiments support tetrameric/higher assemblies and effects of R882H on those assemblies. Mixing separately purified proteins is not equivalent to coexpression. Retain the positive self-binding property as part of the catalytic architecture without creating a separate generic oligomerization core. |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IDA PMID:12138111 A novel Dnmt3a isoform produced from an alternative promoter... | ACCEPT | Summary: CpG-island methylation-dependent repression is supported. Reason: The historical human enzyme study is curator-backed and consistent with independently recovered human promoter methylation/repression experiments. Its abstract-only access is explicit; no unobserved assay detail is supplied. |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IDA PMID:19786833 Dnmt3/transcription factor interactions as crucial players i... | ACCEPT | Summary: CpG-island methylation-dependent repression is supported. Reason: MYC-dependent DNMT3A recruitment and promoter methylation/repression support this process; the targeting factor and methylating enzyme retain distinct roles. Supporting Evidence: |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IDA PMID:23042785 Control of epigenetic states by WT1 via regulation of de nov... | ACCEPT | Summary: CpG-island methylation-dependent repression is supported. Reason: Human WT1 perturbation, DNMT3A ChIP, promoter methylation and expression results connect the enzyme to repression at selected loci. DNMT3A supplies the methylation activity; WT1 regulation is not evidence that DNMT3A itself recognizes WT1 DNA motifs. Supporting Evidence: |
| GO:0045322 unmethylated CpG binding | EXP PMID:29414941 Structural basis for DNMT3A-mediated de novo DNA methylation... | ACCEPT | Summary: Unmethylated CpG engagement is directly supported. Reason: The human catalytic-domain DNA complexes and methylation assays establish binding to unmethylated CpG substrates. The term describes a supported substrate interaction, not exclusive recognition of CpG or denial of the separately measured CpA/CpT activity. Supporting Evidence: |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ethanol-associated expression and total enzyme measurements are broader than a DNMT3A-specific response mechanism. Reason: The full adolescent-rat study measures DNMT3A RNA increases in BNST after repeated ethanol, unchanged amygdala RNA, and total DNMT activity. These source-specific effects are genuine but the total activity assay is not DNMT3A-selective. Mark the human response transfer over-annotated without denying the measurements. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q1LZ53 SOURCE WEAK OR INFERRED The literal mapping/donor record was traced. The full adolescent-rat study measures DNMT3A RNA increases in BNST after repeated ethanol, unchanged amygdala RNA, and total DNMT activity. These source-specific effects are genuine but the total activity assay is not DNMT3A-selective. Mark the human response transfer over-annotated without denying the measurements. ensembl:ENSRNOP00000046524 SOURCE WEAK OR INFERRED The literal mapping/donor record was traced. The full adolescent-rat study measures DNMT3A RNA increases in BNST after repeated ethanol, unchanged amygdala RNA, and total DNMT activity. These source-specific effects are genuine but the total activity assay is not DNMT3A-selective. Mark the human response transfer over-annotated without denying the measurements. Supporting Evidence: |
| GO:0045892 negative regulation of DNA-templated transcription | IBA GO_REF:0000033 | MODIFY | Summary: The conserved repressive process can be specified to CpG-island-mediated silencing. Reason: The target descends from IBD PTN002747444 and its own experimental evidence legitimately grounds the node. Human promoter methylation and repression support a more informative process; the refinement is based on mechanism, not a challenge to donor count or alleged self-circularity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002747444 SUPPORTS TRANSFER Exact IBD and target descent verified; self-grounding is legitimate. The target descends from IBD PTN002747444 and its own experimental evidence legitimately grounds the node. Human promoter methylation and repression support a more informative process; the refinement is based on mechanism, not a challenge to donor count or alleged self-circularity. Proposed replacements: negative regulation of gene expression via chromosomal CpG island methylation Supporting Evidence: |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:19786833 Dnmt3/transcription factor interactions as crucial players i... | KEEP AS NON CORE | Summary: MYC-associated recruitment supports a contextual transcription-factor interaction. Reason: The original combines human MYC/DNMT3A co-immunoprecipitation, proximity and promoter-targeting experiments. Retain this curated interaction in its regulatory context, without equating protein association with DNMT3A recognition of MYC DNA motifs or creating an independent catalytic core. Supporting Evidence: |
| GO:0071361 cellular response to ethanol | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: The cellular ethanol response is measured chiefly through DNMT3A abundance. Reason: The recovered rat astrocyte study measures DNMT3A protein changes, total methyltransferase activity and downstream promoter effects after ethanol. The inhibitor is not isoform-selective. This establishes response-associated biology but does not isolate DNMT3A as the executing cellular-response component; retain the observations while marking the propagated process over-annotated. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q1LZ53 SOURCE WEAK OR INFERRED The literal mapping/donor record was traced. The recovered rat astrocyte study measures DNMT3A protein changes, total methyltransferase activity and downstream promoter effects after ethanol. The inhibitor is not isoform-selective. This establishes response-associated biology but does not isolate DNMT3A as the executing cellular-response component; retain the observations while marking the propagated process over-annotated. ensembl:ENSRNOP00000046524 SOURCE WEAK OR INFERRED The literal mapping/donor record was traced. The recovered rat astrocyte study measures DNMT3A protein changes, total methyltransferase activity and downstream promoter effects after ethanol. The inhibitor is not isoform-selective. This establishes response-associated biology but does not isolate DNMT3A as the executing cellular-response component; retain the observations while marking the propagated process over-annotated. Supporting Evidence: |
| GO:0071456 cellular response to hypoxia | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: A hypoxia-associated cellular role is supported contextually. Reason: Rat bladder-cell experiments show hypoxia-dependent DNMT3A abundance and nuclear redistribution. Independent rat neuronal oxygen-glucose-deprivation experiments selectively reduce Dnmt3a and alter injury outcomes, supporting a contextual cellular role beyond expression alone. The perturbation evidence does not establish direct oxygen sensing or a universal hypoxia program. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q1LZ53 SUPPORTS TRANSFER The literal mapping/donor record was traced. Rat bladder-cell experiments show hypoxia-dependent DNMT3A abundance and nuclear redistribution. Independent rat neuronal oxygen-glucose-deprivation experiments selectively reduce Dnmt3a and alter injury outcomes, supporting a contextual cellular role beyond expression alone. The perturbation evidence does not establish direct oxygen sensing or a universal hypoxia program. ensembl:ENSRNOP00000046524 SUPPORTS TRANSFER The literal mapping/donor record was traced. Rat bladder-cell experiments show hypoxia-dependent DNMT3A abundance and nuclear redistribution. Independent rat neuronal oxygen-glucose-deprivation experiments selectively reduce Dnmt3a and alter injury outcomes, supporting a contextual cellular role beyond expression alone. The perturbation evidence does not establish direct oxygen sensing or a universal hypoxia program. |
| GO:0097284 hepatocyte apoptotic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Declining DNMT3A abundance during hepatocyte death does not establish participation in apoptosis. Reason: The only donor evidence is rat RGD annotation by IEP (inferred from expression pattern), projected to human by Ensembl Compara; the cited rat study reports decreasing DNMT3A transcript and protein abundance during hepatocyte apoptosis. A change in DNMT3A abundance identifies DNMT3A as a readout of the exposure, not as a component that performs the response, and no DNMT3A-selective perturbation is reported. The process transfer is therefore over-annotated; the measured expression change itself is not disputed. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q1LZ53 SOURCE WEAK OR INFERRED Rat donor annotation is IEP, an expression-pattern inference; it supports a DNMT3A abundance change, not DNMT3A executing the response. ensembl:ENSRNOP00000046524 SOURCE WEAK OR INFERRED Rat donor annotation is IEP, an expression-pattern inference; it supports a DNMT3A abundance change, not DNMT3A executing the response. Supporting Evidence: |
| GO:0106222 lncRNA binding | IDA PMID:23435381 A pseudogene long-noncoding-RNA network regulates PTEN trans... | KEEP AS NON CORE | Summary: Association with a regulatory lncRNA is supported in a specific chromatin context. Reason: Human native RNA immunoprecipitation and depletion/recruitment experiments support DNMT3A association with PTENpg1 antisense-alpha RNA. They do not isolate a purified binary RNA-contact surface or establish a general RNA catalytic activity. Retain the positive RNA-binding context without promoting it to a separate molecular core. Supporting Evidence: PMID:23435381 DNMT3a and PTENpg1 asRNA Ξ± to co-IP and thus interact within the same protein:RNA complex |
| GO:0106222 lncRNA binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse Dum-lncRNA association supports a conserved contextual RNA interaction. Reason: Mouse myoblast formaldehyde-RIP and nuclear-extract RNA pull-down experiments identify Dnmt3a with Dum and Dppa2 regulatory chromatin. These positive data support the ortholog transfer, but retain the native-complex and mouse context rather than claiming purified human direct binding. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O88508 SUPPORTS TRANSFER The literal mapping/donor record was traced. Mouse myoblast formaldehyde-RIP and nuclear-extract RNA pull-down experiments identify Dnmt3a with Dum and Dppa2 regulatory chromatin. These positive data support the ortholog transfer, but retain the native-complex and mouse context rather than claiming purified human direct binding. ensembl:ENSMUSP00000020991 SUPPORTS TRANSFER The literal mapping/donor record was traced. Mouse myoblast formaldehyde-RIP and nuclear-extract RNA pull-down experiments identify Dnmt3a with Dum and Dppa2 regulatory chromatin. These positive data support the ortholog transfer, but retain the native-complex and mouse context rather than claiming purified human direct binding. Supporting Evidence: |
| GO:0106363 protein-cysteine methyltransferase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Cysteine automethylation is retained as a conditional side activity. Reason: The cited mouse enzyme study reports slow irreversible cysteine automethylation in the AdoMet-bound binary complex, enhanced by Dnmt3L, whereas CpG DNA is the preferred substrate and suppresses the detected side reaction. The current GO definition explicitly includes this chemistry and cites the source. Retain the conserved biochemical capability without asserting a demonstrated human physiological protein-methylation function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O88508 SUPPORTS TRANSFER The literal mapping/donor record was traced. The cited mouse enzyme study reports slow irreversible cysteine automethylation in the AdoMet-bound binary complex, enhanced by Dnmt3L, whereas CpG DNA is the preferred substrate and suppresses the detected side reaction. The current GO definition explicitly includes this chemistry and cites the source. Retain the conserved biochemical capability without asserting a demonstrated human physiological protein-methylation function. ensembl:ENSMUSP00000020991 SUPPORTS TRANSFER The literal mapping/donor record was traced. The cited mouse enzyme study reports slow irreversible cysteine automethylation in the AdoMet-bound binary complex, enhanced by Dnmt3L, whereas CpG DNA is the preferred substrate and suppresses the detected side reaction. The current GO definition explicitly includes this chemistry and cites the source. Retain the conserved biochemical capability without asserting a demonstrated human physiological protein-methylation function. RHEA:66544 SUPPORTS TRANSFER The literal mapping/donor record was traced. The cited mouse enzyme study reports slow irreversible cysteine automethylation in the AdoMet-bound binary complex, enhanced by Dnmt3L, whereas CpG DNA is the preferred substrate and suppresses the detected side reaction. The current GO definition explicitly includes this chemistry and cites the source. Retain the conserved biochemical capability without asserting a demonstrated human physiological protein-methylation function. Supporting Evidence: |
| GO:0106363 protein-cysteine methyltransferase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cysteine automethylation is retained as a conditional side activity. Reason: The cited mouse enzyme study reports slow irreversible cysteine automethylation in the AdoMet-bound binary complex, enhanced by Dnmt3L, whereas CpG DNA is the preferred substrate and suppresses the detected side reaction. The current GO definition explicitly includes this chemistry and cites the source. Retain the conserved biochemical capability without asserting a demonstrated human physiological protein-methylation function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O88508 SUPPORTS TRANSFER The literal mapping/donor record was traced. The cited mouse enzyme study reports slow irreversible cysteine automethylation in the AdoMet-bound binary complex, enhanced by Dnmt3L, whereas CpG DNA is the preferred substrate and suppresses the detected side reaction. The current GO definition explicitly includes this chemistry and cites the source. Retain the conserved biochemical capability without asserting a demonstrated human physiological protein-methylation function. Supporting Evidence: |
| GO:0141196 transposable element silencing by piRNA-mediated DNA methylation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: piRNA-directed transposon methylation is a developmental context for DNMT3A. Reason: The mouse gonocyte study places Dnmt3a in a SPOCD1-associated methylation complex downstream of piRNA recognition. DNMT3A performs DNA methylation in that machinery rather than serving merely as a substrate. Preserve the inherited germline process with organism/stage limits; the experiment does not identify direct DNMT3AβpiRNA binding. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:O88508 SUPPORTS TRANSFER The literal mapping/donor record was traced. The mouse gonocyte study places Dnmt3a in a SPOCD1-associated methylation complex downstream of piRNA recognition. DNMT3A performs DNA methylation in that machinery rather than serving merely as a substrate. Preserve the inherited germline process with organism/stage limits; the experiment does not identify direct DNMT3AβpiRNA binding. ensembl:ENSMUSP00000020991 SUPPORTS TRANSFER The literal mapping/donor record was traced. The mouse gonocyte study places Dnmt3a in a SPOCD1-associated methylation complex downstream of piRNA recognition. DNMT3A performs DNA methylation in that machinery rather than serving merely as a substrate. Preserve the inherited germline process with organism/stage limits; the experiment does not identify direct DNMT3AβpiRNA binding. Supporting Evidence: |
| GO:1900039 positive regulation of cellular response to hypoxia | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: A positive contribution to hypoxic-injury responses is supported in the rat donor. Reason: The full oxygen-glucose-deprivation and cerebral-ischemia study uses Dnmt3a-targeted RNA interference and measures reduced cell death/infarct outcomes. That is more than an expression-only response, but does not establish direct oxygen sensing or the same physiological outcome across human tissues. Retain the contextual regulatory role. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q1LZ53 SUPPORTS TRANSFER The literal mapping/donor record was traced. The full oxygen-glucose-deprivation and cerebral-ischemia study uses Dnmt3a-targeted RNA interference and measures reduced cell death/infarct outcomes. That is more than an expression-only response, but does not establish direct oxygen sensing or the same physiological outcome across human tissues. Retain the contextual regulatory role. ensembl:ENSRNOP00000046524 SUPPORTS TRANSFER The literal mapping/donor record was traced. The full oxygen-glucose-deprivation and cerebral-ischemia study uses Dnmt3a-targeted RNA interference and measures reduced cell death/infarct outcomes. That is more than an expression-only response, but does not establish direct oxygen sensing or the same physiological outcome across human tissues. Retain the contextual regulatory role. Supporting Evidence: |
| GO:1902494 catalytic complex | IPI PMID:25383530 Structural insight into autoinhibition and histone H3-induce... | MODIFY | Summary: The DNMT3A-DNMT3L heterotetramer is a DNA methyltransferase complex, a more specific descendant of catalytic complex. Reason: The cited human study characterises DNMT3A-DNMT3L complexes with regulated DNA methylation activity, and the human DNMT3A-DNMT3L-DNA crystal structure shows the heterotetramer methylating DNA through its two DNMT3A active sites. GO:0140020 DNA methyltransferase complex ("a protein complex that possesses DNA methyltransferase activity") is an is_a descendant of GO:1902494 catalytic complex and states what this complex does. Correcting the earlier assessment, which retained the generic parent on the assumption that no named GO complex existed. DNMT3A supplies the catalytic sites; DNMT3L is the noncatalytic activating subunit. Proposed replacements: DNA methyltransferase complex Supporting Evidence: PMID:29414941 DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides |
| GO:0140003 histone H3K36me3 reader activity | IDA PMID:30478443 Gain-of-function DNMT3A mutations cause microcephalic dwarfi... | NEW | Summary: The human PWWP domain directly recognizes histone H3K36me3. Reason: Purified human WT GST-PWWP binds H3K36me3 peptide but not the corresponding unmodified peptide; histone-tail arrays additionally show H3K36me2 recognition. W330R loses the measured interaction. These direct WT recognition assays support the reader activity already represented in the core, without inferring it solely from mutant methylation phenotypes or assigning the fragment assay to every natural product. No imported annotation or proposed replacement is an ancestor or descendant of this reader term; the ADD unmodified-histone reader is complementary. The annotation does not imply exclusive recognition of H3K36me3 or an independently demonstrated constitutive-heterochromatin process. Supporting Evidence: PMID:30478443 interacted with an H3K36me3 modified histone-tail peptide but not the corresponding unmodified peptide |
| GO:0071514 genomic imprinting | ISO PMID:15215868 Essential role for de novo DNA methyltransferase Dnmt3a in p... | NEW | Summary: DNMT3A performs the de novo methylation that establishes maternal and most paternal germline imprints, shown for the mouse ortholog in the same PANTHER subfamily. Reason: Germ-cell-specific deletion of mouse Dnmt3a (O88508, PANTHER PTHR23068:SF10 like human DNMT3A) abolishes methylation and allele-specific expression at all maternally imprinted loci examined and at two of three paternally imprinted loci, whereas germline Dnmt3b deletion has no phenotype (PMID:15215868). This is participation rather than necessity alone, because the imprint is the methylation mark itself and DNMT3A is the catalytic subunit that deposits it; DNMT3L, its noncatalytic activator, is required for the same loci. In a comparator check, mouse Dnmt3a carries this term by IMP from this paper, mouse and human DNMT3L carry it, yet human DNMT3A does not, so the catalytic partner is missing a term its activator has. No imported or proposed term is an ancestor or descendant of GO:0071514; GO:0044027 (CpG-island methylation-dependent silencing) is a sibling under epigenetic regulation of gene expression. Human-specific germline evidence is not available; the transfer rests on subfamily orthology. Supporting Evidence: PMID:15215868 Offspring from Dnmt3a conditional mutant females die in utero and lack methylation and allele-specific expression at all maternally imprinted loci examined. PMID:15215868 both Dnmt3a and Dnmt3L are required for methylation of most imprinted loci in germ cells |
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Download this section (compressed HTML)Q: Which cell types express the 723- and 166-residue natural products, and what molecular activities do they retain independently of the historically named 689-residue DNMT3A2 reagent?
Q: Under which cellular and biochemical conditions does DNMT3A recognize H4R3me2s, given the positive PRMT5-linked report and the condition-specific non-replication in the independent ADD study?
Q: Which exposure-associated expression changes reflect DNMT3A executing a response, rather than DNMT3A abundance being a downstream readout?
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