DNMT3A is a de novo DNA cytosine-5 methyltransferase that establishes and remodels mammalian DNA methylation patterns. Its catalytic domain recognizes cytosines, preferentially in CpG contexts, while PWWP and ADD chromatin-reader domains and interacting proteins guide genomic targeting and activity. Chromatin methylation contributes to transcriptional regulation and cell identity. Alternative N-terminal isoforms differ in chromatin localization.
| 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... | ACCEPT | Summary: DNMT3A can repress transcription through targeted DNA methylation. Reason: Recruitment by transcriptional regulators and promoter hypermethylation provide mechanistic support for negative transcriptional regulation. This does not imply that all DNMT3A-dependent methylation universally represses transcription. Supporting Evidence: PMID:19786833 the invalidation of c-myc reveals that c-myc allows the Dnmt3a recruitment on c-myc box of c-myc-regulated genes. PMID:23042785 DNMT3A recruitment is increased, with hypermethylation being associated with silencing of gene expression. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:19786833 Dnmt3/transcription factor interactions as crucial players i... | ACCEPT | Summary: DNMT3A can repress transcription through targeted DNA methylation. Reason: Recruitment by transcriptional regulators and promoter hypermethylation provide mechanistic support for negative transcriptional regulation. This does not imply that all DNMT3A-dependent methylation universally represses transcription. Supporting Evidence: PMID:19786833 the invalidation of c-myc reveals that c-myc allows the Dnmt3a recruitment on c-myc box of c-myc-regulated genes. PMID:23042785 DNMT3A recruitment is increased, with hypermethylation being associated with silencing of gene expression. |
| GO:0000775 chromosome, centromeric region | IEA GO_REF:0000107 | ACCEPT | Summary: DNMT3A associates with chromatin, including heterochromatic pools. Reason: Isoform localization and chromatin-reader studies establish chromatin association. N-terminal isoforms differ in their distribution, so these gene-level location records should not be read as every isoform occupying identical chromatin. Supporting Evidence: PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. PMID:30478443 Substitutions in the PWWP domain abrogate binding to the histone modifications H3K36me2 and H3K36me3, and alter DNA methylation in patient cells. |
| GO:0000792 heterochromatin | IEA GO_REF:0000107 | ACCEPT | Summary: DNMT3A associates with chromatin, including heterochromatic pools. Reason: Isoform localization and chromatin-reader studies establish chromatin association. N-terminal isoforms differ in their distribution, so these gene-level location records should not be read as every isoform occupying identical chromatin. Supporting Evidence: PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. PMID:30478443 Substitutions in the PWWP domain abrogate binding to the histone modifications H3K36me2 and H3K36me3, and alter DNA methylation in patient cells. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:19786833 Dnmt3/transcription factor interactions as crucial players i... | UNDECIDED | Summary: Promoter occupancy needs distinction from intrinsic transcription-factor-like sequence recognition. Reason: The primary studies establish DNMT3A recruitment to regulatory DNA, including recruitment by MYC or changes downstream of WT1. The available evidence does not clearly resolve whether this specific cis-regulatory sequence-specific binding term describes intrinsic recognition rather than partner-mediated ChIP occupancy. Retain uncertainty rather than removing an experimental annotation from an incomplete assay assessment. Supporting Evidence: PMID:19786833 the invalidation of c-myc reveals that c-myc allows the Dnmt3a recruitment on c-myc box of c-myc-regulated genes. PMID:29414941 Arg836 of the target recognition domain makes crucial contacts with CpG, ensuring DNMT3A enzymatic preference towards CpG sites in cells. |
| 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... | UNDECIDED | Summary: Promoter occupancy needs distinction from intrinsic transcription-factor-like sequence recognition. Reason: The primary studies establish DNMT3A recruitment to regulatory DNA, including recruitment by MYC or changes downstream of WT1. The available evidence does not clearly resolve whether this specific cis-regulatory sequence-specific binding term describes intrinsic recognition rather than partner-mediated ChIP occupancy. Retain uncertainty rather than removing an experimental annotation from an incomplete assay assessment. Supporting Evidence: PMID:19786833 the invalidation of c-myc reveals that c-myc allows the Dnmt3a recruitment on c-myc box of c-myc-regulated genes. PMID:29414941 Arg836 of the target recognition domain makes crucial contacts with CpG, ensuring DNMT3A enzymatic preference towards CpG sites in cells. |
| GO:0001741 XY body | IEA GO_REF:0000107 | UNDECIDED | Summary: The XY-body localization transfer requires germ-cell and isoform-specific evidence. Reason: Broad nuclear/chromatin localization does not establish the specialized meiotic sex-chromosome compartment. The source experiment underlying this ortholog transfer needs tracing. Supporting Evidence: PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. |
| GO:0003677 DNA binding | EXP PMID:29414941 Structural basis for DNMT3A-mediated de novo DNA methylation... | ACCEPT | Summary: DNMT3A binds DNA and catalyzes cytosine methylation. Reason: DNA-bound structures and substrate assays establish catalytic recognition of unmethylated CpG DNA and the de novo methyltransferase reaction. Supporting Evidence: PMID:29414941 the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides PMID:29414941 Arg836 of the target recognition domain makes crucial contacts with CpG, ensuring DNMT3A enzymatic preference towards CpG sites in cells. |
| GO:0003677 DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: DNMT3A binds DNA and catalyzes cytosine methylation. Reason: DNA-bound structures and substrate assays establish catalytic recognition of unmethylated CpG DNA and the de novo methyltransferase reaction. Supporting Evidence: PMID:29414941 the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides PMID:29414941 Arg836 of the target recognition domain makes crucial contacts with CpG, ensuring DNMT3A enzymatic preference towards CpG sites in cells. |
| GO:0003682 chromatin binding | IEA GO_REF:0000107 | ACCEPT | Summary: DNMT3A associates with chromatin, including heterochromatic pools. Reason: Isoform localization and chromatin-reader studies establish chromatin association. N-terminal isoforms differ in their distribution, so these gene-level location records should not be read as every isoform occupying identical chromatin. Supporting Evidence: PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. PMID:30478443 Substitutions in the PWWP domain abrogate binding to the histone modifications H3K36me2 and H3K36me3, and alter DNA methylation in patient cells. |
| GO:0003714 transcription corepressor activity | IEA GO_REF:0000117 | ACCEPT | Summary: DNMT3A regulates gene expression as a recruited epigenetic corepressor. Reason: Interaction with transcriptional regulators targets methylation and can repress promoter activity. Its enzymatic mechanism provides the specificity beyond a generic corepressor label. Supporting Evidence: PMID:19786833 the invalidation of c-myc reveals that c-myc allows the Dnmt3a recruitment on c-myc box of c-myc-regulated genes. PMID:23042785 DNMT3A recruitment is increased, with hypermethylation being associated with silencing of gene expression. |
| GO:0003714 transcription corepressor activity | TAS PMID:19786833 Dnmt3/transcription factor interactions as crucial players i... | ACCEPT | Summary: DNMT3A regulates gene expression as a recruited epigenetic corepressor. Reason: Interaction with transcriptional regulators targets methylation and can repress promoter activity. Its enzymatic mechanism provides the specificity beyond a generic corepressor label. Supporting Evidence: PMID:19786833 the invalidation of c-myc reveals that c-myc allows the Dnmt3a recruitment on c-myc box of c-myc-regulated genes. PMID:23042785 DNMT3A recruitment is increased, with hypermethylation being associated with silencing of gene expression. |
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: DNMT3A binds DNA and catalyzes cytosine methylation. Reason: DNA-bound structures and substrate assays establish catalytic recognition of unmethylated CpG DNA and the de novo methyltransferase reaction. Supporting Evidence: PMID:29414941 the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides PMID:29414941 Arg836 of the target recognition domain makes crucial contacts with CpG, ensuring DNMT3A enzymatic preference towards CpG sites in cells. |
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | IDA PMID:12138111 A novel Dnmt3a isoform produced from an alternative promoter... | ACCEPT | Summary: DNMT3A binds DNA and catalyzes cytosine methylation. Reason: DNA-bound structures and substrate assays establish catalytic recognition of unmethylated CpG DNA and the de novo methyltransferase reaction. Supporting Evidence: PMID:29414941 the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides PMID:29414941 Arg836 of the target recognition domain makes crucial contacts with CpG, ensuring DNMT3A enzymatic preference towards CpG sites in cells. |
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | IDA PMID:19786833 Dnmt3/transcription factor interactions as crucial players i... | ACCEPT | Summary: DNMT3A binds DNA and catalyzes cytosine methylation. Reason: DNA-bound structures and substrate assays establish catalytic recognition of unmethylated CpG DNA and the de novo methyltransferase reaction. Supporting Evidence: PMID:29414941 the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides PMID:29414941 Arg836 of the target recognition domain makes crucial contacts with CpG, ensuring DNMT3A enzymatic preference towards CpG sites in cells. |
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: DNMT3A binds DNA and catalyzes cytosine methylation. Reason: DNA-bound structures and substrate assays establish catalytic recognition of unmethylated CpG DNA and the de novo methyltransferase reaction. Supporting Evidence: PMID:29414941 the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides PMID:29414941 Arg836 of the target recognition domain makes crucial contacts with CpG, ensuring DNMT3A enzymatic preference towards CpG sites in cells. |
| GO:0005515 protein binding | IPI PMID:16357870 The Polycomb group protein EZH2 directly controls DNA methyl... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:16357870 The Polycomb group protein EZH2 directly controls DNA methyl... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:16682412 The histone methyltransferase SETDB1 and the DNA methyltrans... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:16983096 Recruitment of the de novo DNA methyltransferase Dnmt3a by K... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:17713477 Structure of Dnmt3a bound to Dnmt3L suggests a model for de ... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:19234465 PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, ... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:19798101 Np95 interacts with de novo DNA methyltransferases, Dnmt3a a... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:19834512 Structural basis for recognition of H3K4 methylation status ... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:21976679 cAMP-responsive element modulator (CREM)Ξ± protein signaling ... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:24074865 Dnmt3L antagonizes DNA methylation at bivalent promoters and... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:25383530 Structural insight into autoinhibition and histone H3-induce... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | ACCEPT | Summary: DNMT3A participates in a regulated methyltransferase complex. Reason: The DNMT3A-DNMT3L and histone-bound structures establish physical complex formation and catalytic regulation. Generic interaction annotations here are mechanistically grounded by the same structural study. Supporting Evidence: PMID:29414941 the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides PMID:25383530 Histone H3 (but not H3K4me3) disrupts ADD-CD interaction, induces a large movement of the ADD domain, and thus releases the autoinhibition of DNMT3A. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | ACCEPT | Summary: DNMT3A participates in a regulated methyltransferase complex. Reason: The DNMT3A-DNMT3L and histone-bound structures establish physical complex formation and catalytic regulation. Generic interaction annotations here are mechanistically grounded by the same structural study. Supporting Evidence: PMID:29414941 the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides PMID:25383530 Histone H3 (but not H3K4me3) disrupts ADD-CD interaction, induces a large movement of the ADD domain, and thus releases the autoinhibition of DNMT3A. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:32051553 The EGFR-ZNF263 signaling axis silences SIX3 in glioblastoma... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:32968275 Structure of nucleosome-boundΒ DNA methyltransferases DNMT3A ... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | UNDECIDED | Summary: The particular interaction needs partner-level source verification. Reason: DNMT3A has well-characterized regulatory partners, but that does not validate every seeded interaction. The exact gene/partner assay for this row has not been verified in the retrieved publication or supplementary dataset; retain the curated interaction pending that evidence check. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: DNMT3A acts in the nucleus and nucleoplasm. Reason: Direct human tissue imaging and chromatin-localization studies support the nuclear methylation machinery, independently of individual high-throughput location rows. Supporting Evidence: PMID:23042785 co-expression of WT1 and DNMT3A proteins in nuclei of blastemal cells in human fetal kidney and Wilms' tumours. PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. |
| GO:0005634 nucleus | IDA PMID:12138111 A novel Dnmt3a isoform produced from an alternative promoter... | ACCEPT | Summary: DNMT3A acts in the nucleus and nucleoplasm. Reason: Direct human tissue imaging and chromatin-localization studies support the nuclear methylation machinery, independently of individual high-throughput location rows. Supporting Evidence: PMID:23042785 co-expression of WT1 and DNMT3A proteins in nuclei of blastemal cells in human fetal kidney and Wilms' tumours. PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. |
| GO:0005634 nucleus | IDA PMID:25743254 Proteomic analyses reveal that loss of TDP-43 affects RNA pr... | ACCEPT | Summary: DNMT3A acts in the nucleus and nucleoplasm. Reason: Direct human tissue imaging and chromatin-localization studies support the nuclear methylation machinery, independently of individual high-throughput location rows. Supporting Evidence: PMID:23042785 co-expression of WT1 and DNMT3A proteins in nuclei of blastemal cells in human fetal kidney and Wilms' tumours. PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: DNMT3A acts in the nucleus and nucleoplasm. Reason: Direct human tissue imaging and chromatin-localization studies support the nuclear methylation machinery, independently of individual high-throughput location rows. Supporting Evidence: PMID:23042785 co-expression of WT1 and DNMT3A proteins in nuclei of blastemal cells in human fetal kidney and Wilms' tumours. PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. |
| GO:0005634 nucleus | NAS PMID:25383530 Structural insight into autoinhibition and histone H3-induce... | ACCEPT | Summary: DNMT3A acts in the nucleus and nucleoplasm. Reason: Direct human tissue imaging and chromatin-localization studies support the nuclear methylation machinery, independently of individual high-throughput location rows. Supporting Evidence: PMID:23042785 co-expression of WT1 and DNMT3A proteins in nuclei of blastemal cells in human fetal kidney and Wilms' tumours. PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: DNMT3A acts in the nucleus and nucleoplasm. Reason: Direct human tissue imaging and chromatin-localization studies support the nuclear methylation machinery, independently of individual high-throughput location rows. Supporting Evidence: PMID:23042785 co-expression of WT1 and DNMT3A proteins in nuclei of blastemal cells in human fetal kidney and Wilms' tumours. PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-212222 | ACCEPT | Summary: DNMT3A acts in the nucleus and nucleoplasm. Reason: Direct human tissue imaging and chromatin-localization studies support the nuclear methylation machinery, independently of individual high-throughput location rows. Supporting Evidence: PMID:23042785 co-expression of WT1 and DNMT3A proteins in nuclei of blastemal cells in human fetal kidney and Wilms' tumours. PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-212269 | ACCEPT | Summary: DNMT3A acts in the nucleus and nucleoplasm. Reason: Direct human tissue imaging and chromatin-localization studies support the nuclear methylation machinery, independently of individual high-throughput location rows. Supporting Evidence: PMID:23042785 co-expression of WT1 and DNMT3A proteins in nuclei of blastemal cells in human fetal kidney and Wilms' tumours. PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5212679 | ACCEPT | Summary: DNMT3A acts in the nucleus and nucleoplasm. Reason: Direct human tissue imaging and chromatin-localization studies support the nuclear methylation machinery, independently of individual high-throughput location rows. Supporting Evidence: PMID:23042785 co-expression of WT1 and DNMT3A proteins in nuclei of blastemal cells in human fetal kidney and Wilms' tumours. PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9710490 | ACCEPT | Summary: DNMT3A acts in the nucleus and nucleoplasm. Reason: Direct human tissue imaging and chromatin-localization studies support the nuclear methylation machinery, independently of individual high-throughput location rows. Supporting Evidence: PMID:23042785 co-expression of WT1 and DNMT3A proteins in nuclei of blastemal cells in human fetal kidney and Wilms' tumours. PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. |
| GO:0005694 chromosome | EXP PMID:12138111 A novel Dnmt3a isoform produced from an alternative promoter... | ACCEPT | Summary: DNMT3A associates with chromatin, including heterochromatic pools. Reason: Isoform localization and chromatin-reader studies establish chromatin association. N-terminal isoforms differ in their distribution, so these gene-level location records should not be read as every isoform occupying identical chromatin. Supporting Evidence: PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. PMID:30478443 Substitutions in the PWWP domain abrogate binding to the histone modifications H3K36me2 and H3K36me3, and alter DNA methylation in patient cells. |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: DNMT3A associates with chromatin, including heterochromatic pools. Reason: Isoform localization and chromatin-reader studies establish chromatin association. N-terminal isoforms differ in their distribution, so these gene-level location records should not be read as every isoform occupying identical chromatin. Supporting Evidence: PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. PMID:30478443 Substitutions in the PWWP domain abrogate binding to the histone modifications H3K36me2 and H3K36me3, and alter DNA methylation in patient cells. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: DNMT3A can occupy a cytoplasmic pool. Reason: Retain the experimentally curated additional localization; its principal catalytic and chromatin-targeting role is nuclear. The source study also examines distinct isoforms, so the annotation does not mean all DNMT3A isoforms act primarily in the cytoplasm. Supporting Evidence: PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. |
| GO:0005737 cytoplasm | IDA PMID:12138111 A novel Dnmt3a isoform produced from an alternative promoter... | KEEP AS NON CORE | Summary: DNMT3A can occupy a cytoplasmic pool. Reason: Retain the experimentally curated additional localization; its principal catalytic and chromatin-targeting role is nuclear. The source study also examines distinct isoforms, so the annotation does not mean all DNMT3A isoforms act primarily in the cytoplasm. Supporting Evidence: PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: DNMT3A can occupy a cytoplasmic pool. Reason: Retain the experimentally curated additional localization; its principal catalytic and chromatin-targeting role is nuclear. The source study also examines distinct isoforms, so the annotation does not mean all DNMT3A isoforms act primarily in the cytoplasm. Supporting Evidence: PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. |
| GO:0006346 DNA methylation-dependent constitutive heterochromatin formation | IMP PMID:30478443 Gain-of-function DNMT3A mutations cause microcephalic dwarfi... | ACCEPT | Summary: DNMT3A-dependent methylation changes chromatin silencing states. Reason: The PWWP mutant study directly measures aberrant methylation of normally protected Polycomb-associated domains during differentiation, establishing a role in methylation-dependent chromatin organization. Supporting Evidence: PMID:30478443 Substitutions in the PWWP domain abrogate binding to the histone modifications H3K36me2 and H3K36me3, and alter DNA methylation in patient cells. |
| GO:0008168 methyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: DNA cytosine-5 methyltransferase activity is the informative catalytic term. Reason: Structures and assays resolve the methyl acceptor as DNA cytosine; replace the generic methyltransferase ancestor. Proposed replacements: DNA (cytosine-5-)-methyltransferase activity Supporting Evidence: PMID:29414941 the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000107 | UNDECIDED | Summary: This context-specific transfer needs its underlying experimental evidence. Reason: The general role in epigenetic gene regulation does not independently establish this particular exposure response, developmental context or germline pathway. Trace the source ortholog experiment and distinguish causal participation from altered DNMT3A expression or methylation as a readout. |
| GO:0009636 response to toxic substance | IEA GO_REF:0000107 | UNDECIDED | Summary: This context-specific transfer needs its underlying experimental evidence. Reason: The general role in epigenetic gene regulation does not independently establish this particular exposure response, developmental context or germline pathway. Trace the source ortholog experiment and distinguish causal participation from altered DNMT3A expression or methylation as a readout. |
| GO:0010212 response to ionizing radiation | IEA GO_REF:0000107 | UNDECIDED | Summary: This context-specific transfer needs its underlying experimental evidence. Reason: The general role in epigenetic gene regulation does not independently establish this particular exposure response, developmental context or germline pathway. Trace the source ortholog experiment and distinguish causal participation from altered DNMT3A expression or methylation as a readout. |
| GO:0010288 response to lead ion | IEA GO_REF:0000107 | UNDECIDED | Summary: This context-specific transfer needs its underlying experimental evidence. Reason: The general role in epigenetic gene regulation does not independently establish this particular exposure response, developmental context or germline pathway. Trace the source ortholog experiment and distinguish causal participation from altered DNMT3A expression or methylation as a readout. |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000002 | ACCEPT | Summary: DNMT3A regulates gene expression as a recruited epigenetic corepressor. Reason: Interaction with transcriptional regulators targets methylation and can repress promoter activity. Its enzymatic mechanism provides the specificity beyond a generic corepressor label. Supporting Evidence: PMID:19786833 the invalidation of c-myc reveals that c-myc allows the Dnmt3a recruitment on c-myc box of c-myc-regulated genes. PMID:23042785 DNMT3A recruitment is increased, with hypermethylation being associated with silencing of gene expression. |
| GO:0016363 nuclear matrix | IDA PMID:12138111 A novel Dnmt3a isoform produced from an alternative promoter... | UNDECIDED | Summary: Nuclear-matrix association needs the original fractionation/localization details. Reason: The source study establishes chromatin and isoform-dependent localization; the accessible abstract does not resolve the separate nuclear-matrix fraction. Nuclear residence alone is insufficient. Supporting Evidence: PMID:12138111 Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. |
| GO:0030182 neuron differentiation | IEA GO_REF:0000107 | UNDECIDED | Summary: This context-specific transfer needs its underlying experimental evidence. Reason: The general role in epigenetic gene regulation does not independently establish this particular exposure response, developmental context or germline pathway. Trace the source ortholog experiment and distinguish causal participation from altered DNMT3A expression or methylation as a readout. |
| GO:0031048 regulatory ncRNA-mediated heterochromatin formation | IGI PMID:23435381 A pseudogene long-noncoding-RNA network regulates PTEN trans... | ACCEPT | Summary: DNMT3A associates with an antisense lncRNA in a repressive chromatin pathway. Reason: The primary human study uses RNA immunoprecipitation and perturbation to connect DNMT3A with PTENpg1 antisense RNA and PTEN repression. Co-immunoprecipitation establishes complex association rather than purified direct RNA affinity. Supporting Evidence: PMID:23435381 RNA immunoprecipitation (IP) of DNMT3a showed DNMT3a and PTENpg1 asRNA Ξ± to co-IP and thus interact within the same protein:RNA complex |
| GO:0031667 response to nutrient levels | IEA GO_REF:0000107 | UNDECIDED | Summary: This context-specific transfer needs its underlying experimental evidence. Reason: The general role in epigenetic gene regulation does not independently establish this particular exposure response, developmental context or germline pathway. Trace the source ortholog experiment and distinguish causal participation from altered DNMT3A expression or methylation as a readout. |
| GO:0032355 response to estradiol | IEA GO_REF:0000107 | UNDECIDED | Summary: This context-specific transfer needs its underlying experimental evidence. Reason: The general role in epigenetic gene regulation does not independently establish this particular exposure response, developmental context or germline pathway. Trace the source ortholog experiment and distinguish causal participation from altered DNMT3A expression or methylation as a readout. |
| GO:0033189 response to vitamin A | IEA GO_REF:0000107 | UNDECIDED | Summary: This context-specific transfer needs its underlying experimental evidence. Reason: The general role in epigenetic gene regulation does not independently establish this particular exposure response, developmental context or germline pathway. Trace the source ortholog experiment and distinguish causal participation from altered DNMT3A expression or methylation as a readout. |
| GO:0042220 response to cocaine | IEA GO_REF:0000107 | UNDECIDED | Summary: This context-specific transfer needs its underlying experimental evidence. Reason: The general role in epigenetic gene regulation does not independently establish this particular exposure response, developmental context or germline pathway. Trace the source ortholog experiment and distinguish causal participation from altered DNMT3A expression or methylation as a readout. |
| GO:0042802 identical protein binding | IPI PMID:24656771 The R882H DNMT3A mutation associated with AML dominantly inh... | ACCEPT | Summary: DNMT3A self-association is integral to catalysis. Reason: Mutant/WT coexpression perturbs homotetramerization and methylation, while DNA-bound structures show the homodimeric DNA-recognition interface. Supporting Evidence: PMID:24656771 coexpression of the two proteins in cells profoundly inhibits the WT enzyme by disrupting its ability to homotetramerize. PMID:29414941 the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides |
| 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: DNMT3A can repress transcription through targeted DNA methylation. Reason: Recruitment by transcriptional regulators and promoter hypermethylation provide mechanistic support for negative transcriptional regulation. This does not imply that all DNMT3A-dependent methylation universally represses transcription. Supporting Evidence: PMID:19786833 the invalidation of c-myc reveals that c-myc allows the Dnmt3a recruitment on c-myc box of c-myc-regulated genes. PMID:23042785 DNMT3A recruitment is increased, with hypermethylation being associated with silencing of gene expression. |
| 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: DNMT3A can repress transcription through targeted DNA methylation. Reason: Recruitment by transcriptional regulators and promoter hypermethylation provide mechanistic support for negative transcriptional regulation. This does not imply that all DNMT3A-dependent methylation universally represses transcription. Supporting Evidence: PMID:19786833 the invalidation of c-myc reveals that c-myc allows the Dnmt3a recruitment on c-myc box of c-myc-regulated genes. PMID:23042785 DNMT3A recruitment is increased, with hypermethylation being associated with silencing of gene expression. |
| 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: DNMT3A can repress transcription through targeted DNA methylation. Reason: Recruitment by transcriptional regulators and promoter hypermethylation provide mechanistic support for negative transcriptional regulation. This does not imply that all DNMT3A-dependent methylation universally represses transcription. Supporting Evidence: PMID:19786833 the invalidation of c-myc reveals that c-myc allows the Dnmt3a recruitment on c-myc box of c-myc-regulated genes. PMID:23042785 DNMT3A recruitment is increased, with hypermethylation being associated with silencing of gene expression. |
| GO:0045322 unmethylated CpG binding | EXP PMID:29414941 Structural basis for DNMT3A-mediated de novo DNA methylation... | ACCEPT | Summary: DNMT3A binds DNA and catalyzes cytosine methylation. Reason: DNA-bound structures and substrate assays establish catalytic recognition of unmethylated CpG DNA and the de novo methyltransferase reaction. Supporting Evidence: PMID:29414941 the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides PMID:29414941 Arg836 of the target recognition domain makes crucial contacts with CpG, ensuring DNMT3A enzymatic preference towards CpG sites in cells. |
| GO:0045471 response to ethanol | IEA GO_REF:0000107 | UNDECIDED | Summary: This context-specific transfer needs its underlying experimental evidence. Reason: The general role in epigenetic gene regulation does not independently establish this particular exposure response, developmental context or germline pathway. Trace the source ortholog experiment and distinguish causal participation from altered DNMT3A expression or methylation as a readout. |
| GO:0045892 negative regulation of DNA-templated transcription | IBA GO_REF:0000033 | ACCEPT | Summary: DNMT3A can repress transcription through targeted DNA methylation. Reason: Recruitment by transcriptional regulators and promoter hypermethylation provide mechanistic support for negative transcriptional regulation. This does not imply that all DNMT3A-dependent methylation universally represses transcription. Supporting Evidence: PMID:19786833 the invalidation of c-myc reveals that c-myc allows the Dnmt3a recruitment on c-myc box of c-myc-regulated genes. PMID:23042785 DNMT3A recruitment is increased, with hypermethylation being associated with silencing of gene expression. |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:19786833 Dnmt3/transcription factor interactions as crucial players i... | ACCEPT | Summary: Transcription-factor binding helps target DNMT3A. Reason: The MYC recruitment and interaction study directly connects transcription-factor contacts to site-selective promoter methylation. Supporting Evidence: PMID:19786833 the invalidation of c-myc reveals that c-myc allows the Dnmt3a recruitment on c-myc box of c-myc-regulated genes. |
| GO:0071361 cellular response to ethanol | IEA GO_REF:0000107 | UNDECIDED | Summary: This context-specific transfer needs its underlying experimental evidence. Reason: The general role in epigenetic gene regulation does not independently establish this particular exposure response, developmental context or germline pathway. Trace the source ortholog experiment and distinguish causal participation from altered DNMT3A expression or methylation as a readout. |
| GO:0071456 cellular response to hypoxia | IEA GO_REF:0000107 | UNDECIDED | Summary: This context-specific transfer needs its underlying experimental evidence. Reason: The general role in epigenetic gene regulation does not independently establish this particular exposure response, developmental context or germline pathway. Trace the source ortholog experiment and distinguish causal participation from altered DNMT3A expression or methylation as a readout. |
| GO:0097284 hepatocyte apoptotic process | IEA GO_REF:0000107 | UNDECIDED | Summary: This context-specific transfer needs its underlying experimental evidence. Reason: The general role in epigenetic gene regulation does not independently establish this particular exposure response, developmental context or germline pathway. Trace the source ortholog experiment and distinguish causal participation from altered DNMT3A expression or methylation as a readout. |
| GO:0106222 lncRNA binding | IDA PMID:23435381 A pseudogene long-noncoding-RNA network regulates PTEN trans... | ACCEPT | Summary: DNMT3A associates with an antisense lncRNA in a repressive chromatin pathway. Reason: The primary human study uses RNA immunoprecipitation and perturbation to connect DNMT3A with PTENpg1 antisense RNA and PTEN repression. Co-immunoprecipitation establishes complex association rather than purified direct RNA affinity. Supporting Evidence: PMID:23435381 RNA immunoprecipitation (IP) of DNMT3a showed 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 | ACCEPT | Summary: DNMT3A associates with an antisense lncRNA in a repressive chromatin pathway. Reason: The primary human study uses RNA immunoprecipitation and perturbation to connect DNMT3A with PTENpg1 antisense RNA and PTEN repression. Co-immunoprecipitation establishes complex association rather than purified direct RNA affinity. Supporting Evidence: PMID:23435381 RNA immunoprecipitation (IP) of DNMT3a showed DNMT3a and PTENpg1 asRNA Ξ± to co-IP and thus interact within the same protein:RNA complex |
| GO:0106363 protein-cysteine methyltransferase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Cysteine automethylation is an observed biochemical side reaction. Reason: The mouse catalytic-domain study demonstrates slow automethylation in the absence of DNA; natural CpG DNA suppresses this reaction. It does not establish an evolved protein-methylation function in vivo. Retain as non-core biochemical capacity, not a second central catalytic role. Supporting Evidence: PMID:21481189 In the presence of CpG containing dsDNA, which is the natural substrate for Dnmt3a, the transfer of the methyl group from AdoMet to the flipped target base was preferred and auto-methylation was not detected. |
| GO:0106363 protein-cysteine methyltransferase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cysteine automethylation is an observed biochemical side reaction. Reason: The mouse catalytic-domain study demonstrates slow automethylation in the absence of DNA; natural CpG DNA suppresses this reaction. It does not establish an evolved protein-methylation function in vivo. Retain as non-core biochemical capacity, not a second central catalytic role. Supporting Evidence: PMID:21481189 In the presence of CpG containing dsDNA, which is the natural substrate for Dnmt3a, the transfer of the methyl group from AdoMet to the flipped target base was preferred and auto-methylation was not detected. |
| GO:0141196 transposable element silencing by piRNA-mediated DNA methylation | IEA GO_REF:0000107 | UNDECIDED | Summary: This context-specific transfer needs its underlying experimental evidence. Reason: The general role in epigenetic gene regulation does not independently establish this particular exposure response, developmental context or germline pathway. Trace the source ortholog experiment and distinguish causal participation from altered DNMT3A expression or methylation as a readout. |
| GO:1900039 positive regulation of cellular response to hypoxia | IEA GO_REF:0000107 | UNDECIDED | Summary: This context-specific transfer needs its underlying experimental evidence. Reason: The general role in epigenetic gene regulation does not independently establish this particular exposure response, developmental context or germline pathway. Trace the source ortholog experiment and distinguish causal participation from altered DNMT3A expression or methylation as a readout. |
| GO:1902494 catalytic complex | IPI PMID:25383530 Structural insight into autoinhibition and histone H3-induce... | ACCEPT | Summary: DNMT3A participates in a regulated methyltransferase complex. Reason: The DNMT3A-DNMT3L and histone-bound structures establish physical complex formation and catalytic regulation. Generic interaction annotations here are mechanistically grounded by the same structural study. Supporting Evidence: PMID:29414941 the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides PMID:25383530 Histone H3 (but not H3K4me3) disrupts ADD-CD interaction, induces a large movement of the ADD domain, and thus releases the autoinhibition of DNMT3A. |
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)