DNMT1 is a regulated DNA methyltransferase that uses S-adenosylmethionine to methylate cytosine in CpG dinucleotides. It preferentially copies methylation onto newly synthesized DNA opposite methylated template strands, helping preserve epigenetic patterns and transcriptional silencing through cell division. Its RFTS regulatory module recognizes paired ubiquitin marks on histone H3, while a CXXC zinc-binding domain and BAH domains coordinate DNA and chromatin engagement with the catalytic domain. DNMT1 acts predominantly in the nucleus and is recruited to replication-associated and heterochromatic sites. Its abundance, activity and recruitment are regulated by protein interactions and post-translational modifications. Alternative transcripts encode three curated protein products with changes in the amino-terminal regulatory region; functional equivalence across these products is not established. Pathogenic DNMT1 variants cause neurological syndromes that can include sensory neuropathy, deafness, dementia or ataxia.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | IBA GO_REF:0000033 | MODIFY | Summary: Conserved CpG DNA methyltransferase activity. Reason: The PAINT IBD at PTN000066774 and the target descendant path are verified; human DNMT1 is a legitimate experimentally grounded descendant, not circular evidence. Human DNMT1 directly methylates cytosine in CpG DNA using S-adenosylmethionine. GO:0051718 specifies the assayed CpG reaction within the broader cytosine-5 methyltransferase activity. The preference for hemimethylated DNA is condition-dependent; neither an invariant twofold preference nor absence of de novo activity is asserted. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000066774 SUPPORTS TRANSFER Verified IBD and target descendant path; target experimental evidence among descendants is legitimate. Specificity refinement does not reject node placement. Proposed replacements: DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates |
| GO:0005634 nucleus | IBA GO_REF:0000033 | MODIFY | Summary: Nuclear localization includes nucleoplasmic and chromatin-associated pools. Reason: The historical PAINT node PTN000066775 and current nucleus IBD node PTN000836042 are both target ancestors in PTHR10629; the historical source assertion is retained. Supported HPA immunofluorescence identifies a nucleoplasmic pool, while independent human DNMT1 chromatin association and substrate/reader experiments establish a chromatin-associated pool. Refine the broad nuclear assertion to both supported locations. Nucleoplasm is not used as a substitute for chromosome-associated DNMT1, and neither replacement asserts exclusive residence or identical localization of all natural products. Chromatin has a typed part_of chromosome relationship rather than a nucleus parent; the biological nuclear location is supported by the experiments, not inferred from a nonexistent ontology edge. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000066775 SUPPORTS TRANSFER Historical node and current PTN000836042 are both target ancestors. The original nucleus assertion is retained; nucleoplasm and chromatin are independent target-level refinements, not a reinterpretation of the ancestral node as chromosome exclusion. Proposed replacements: nucleoplasm chromatin |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IBA GO_REF:0000033 | ACCEPT | Summary: CpG methylation contributes directly to transcriptional silencing. Reason: The verified PTN000066774 IBD carries this conserved epigenetic function. Human DNMT1 performs the DNA-methylation step; promoter occupancy, depletion and methylation measurements support silencing rather than mere expression correlation. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000066774 SUPPORTS TRANSFER Verified IBD and target descendant path; target experimental evidence among descendants is legitimate. Specificity refinement does not reject node placement. Supporting Evidence: PMID:24623306 resulting in DNA hypermethylation and transcriptional silencing |
| GO:0003677 DNA binding | IBA GO_REF:0000033 | MODIFY | Summary: DNA recognition includes unmethylated and methylated CpG substrates. Reason: The verified PAINT node supports inherited DNA binding. Human CXXC-domain and DNMT1 assays demonstrate unmethylated CpG recognition, while catalytic complexes and substrate assays establish binding to hemimethylated CpG DNA. The two replacements describe distinct substrate-recognition states and do not imply sequence-specific transcription-factor activity. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000066774 SUPPORTS TRANSFER Verified IBD and target descendant path; target experimental evidence among descendants is legitimate. Specificity refinement does not reject node placement. Proposed replacements: unmethylated CpG binding methyl-CpG binding |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | MODIFY | Summary: DNA recognition includes unmethylated and methylated CpG substrates. Reason: The combined electronic annotation includes the CXXC-domain mapping; ARBA00029224 explicitly contains a Homo plus IPR002857 condition. Human CXXC-domain and DNMT1 assays demonstrate unmethylated CpG recognition, while catalytic complexes and substrate assays establish binding to hemimethylated CpG DNA. The two replacements describe distinct substrate-recognition states and do not imply sequence-specific transcription-factor activity. Proposed replacements: unmethylated CpG binding methyl-CpG binding |
| GO:0003682 chromatin binding | IEA GO_REF:0000120 | ACCEPT | Summary: DNMT1 binds chromatin through several regulatory interfaces. Reason: IPR001025 maps the BAH domain to chromatin binding. Target chromatin association is independently supported by promoter ChIP and H3Ub2 recognition. These are complementary modes, so the broad chromatin association is retained without assigning every contact to the BAH domain. |
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | IEA GO_REF:0000120 | MODIFY | Summary: Electronic catalytic inference agrees with direct CpG chemistry. Reason: The combined inference includes catalytic-family evidence; the inspected ARBA00088999 rule emits cytosine-5 methyltransferase activity. Human DNMT1 directly methylates cytosine in CpG DNA using S-adenosylmethionine. GO:0051718 specifies the assayed CpG reaction within the broader cytosine-5 methyltransferase activity. The preference for hemimethylated DNA is condition-dependent; neither an invariant twofold preference nor absence of de novo activity is asserted. Proposed replacements: DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates |
| GO:0005634 nucleus | IEA GO_REF:0000120 | MODIFY | Summary: Nuclear localization includes nucleoplasmic and chromatin-associated pools. Reason: The electronic mapping correctly identifies a broad nuclear pool. Supported HPA immunofluorescence identifies a nucleoplasmic pool, while independent human DNMT1 chromatin association and substrate/reader experiments establish a chromatin-associated pool. Refine the broad nuclear assertion to both supported locations. Nucleoplasm is not used as a substitute for chromosome-associated DNMT1, and neither replacement asserts exclusive residence or identical localization of all natural products. Chromatin has a typed part_of chromosome relationship rather than a nucleus parent; the biological nuclear location is supported by the experiments, not inferred from a nonexistent ontology edge. Proposed replacements: nucleoplasm chromatin |
| GO:0006346 DNA methylation-dependent constitutive heterochromatin formation | IEA GO_REF:0000120 | ACCEPT | Summary: DNA methylation contributes to constitutive heterochromatin formation. Reason: The historical combined source includes mouse Dnmt1 and IPR017198; the current ortholog transfer supplies the same biological claim separately. DNMT1 performs the methylation step in this pathway. Snapshot retirement records replacement of the source record, not withdrawal of the conserved function. |
| GO:0008168 methyltransferase activity | IEA GO_REF:0000120 | MODIFY | Summary: The generic methyltransferase term can specify the CpG DNA reaction. Reason: IPR001525 includes several cytosine methyltransferase families and does not alone establish target substrate specificity. Direct human DNMT1 assays resolve the appropriate CpG DNA methyltransferase activity. Proposed replacements: DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates |
| GO:0008270 zinc ion binding | IEA GO_REF:0000120 | ACCEPT | Summary: The CXXC regulatory domain binds structural zinc. Reason: The verified IPR002857 CXXC domain binds two zinc ions, and human structural/biochemical studies establish its DNA-recognition role. This structural metal binding is retained as part of DNMT1 architecture; it is not a separate zinc-dependent catalytic reaction. |
| GO:0006325 chromatin organization | IEA GO_REF:0000043 | MODIFY | Summary: Chromatin organization can be specified as DNA-methylation-dependent heterochromatin formation. Reason: The historical keyword inference is broader than the defined epigenetic work performed by DNMT1. The replacement identifies the pathway that includes methylation of genomic DNA; the source is retired only because it is absent from the current snapshot. Proposed replacements: DNA methylation-dependent constitutive heterochromatin formation |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | MODIFY | Summary: Transferase activity is refined to CpG DNA methyltransferase activity. Reason: Human DNMT1 directly methylates cytosine in CpG DNA using S-adenosylmethionine. GO:0051718 specifies the assayed CpG reaction within the broader cytosine-5 methyltransferase activity. The preference for hemimethylated DNA is condition-dependent; neither an invariant twofold preference nor absence of de novo activity is asserted. Proposed replacements: DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates |
| GO:0032259 methylation | IEA GO_REF:0000043 | MODIFY | Summary: Methylation is refined to chromosomal maintenance methylation. Reason: The broad historical keyword does not identify substrate or biological context. DNMT1 copies CpG methylation after DNA replication; this is the specific supported process, not protein or RNA methylation. Proposed replacements: chromosomal DNA methylation maintenance following DNA replication |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | MODIFY | Summary: Metal binding is refined to structural zinc binding. Reason: The CXXC zinc-coordinating domain provides a defined metal-binding basis. Specify zinc rather than retain an unrestricted metal-ion annotation; this does not imply that zinc is consumed in methyl transfer. Proposed replacements: zinc ion binding |
| GO:0005515 protein binding | IPI PMID:15161933 Comprehensive proteomic analysis of interphase and mitotic 1... | KEEP AS NON CORE | Summary: DNMT1 associates with YWHAZ in a human affinity-proteomics experiment. Reason: The original abstract describes 14-3-3-zeta affinity capture from interphase and mitotic HeLa extracts. The exact MINT DNMT1βYWHAZ pull-down record is positive (MINT-3296749). This supports association; it does not establish purified direct recognition, altered DNMT1 trafficking, or a signaling-scaffold activity. Genericity alone is not grounds for removal. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16357870 The Polycomb group protein EZH2 directly controls DNA methyl... | KEEP AS NON CORE | Summary: DNMT1 associates with EED in Polycomb-related complexes. Reason: The literal source partner is EED/O75530, not EZH2. IntAct records EBI-923799 and EBI-937361 support co-immunoprecipitation/pull-down. The protected cache is abstract-only and the original was not recovered; retain the curated association without assigning a binary interface or an EZH2 catalytic class to EED. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16983096 Recruitment of the de novo DNA methyltransferase Dnmt3a by K... | KEEP AS NON CORE | Summary: DNMT1 itself is a positive LANA interactor. Reason: The recovered original tests DNMT1 with recombinant GST-LANA and in-vitro-translated DNMT1, and by cotransfection co-IP. DNMT3A binds more strongly and has distinct retargeting behavior, but that does not invalidate the DNMT1 pair. Viral-fragment assays are not evidence of a general DNMT1 viral-recruitment function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17934516 The interaction of the SRA domain of ICBP90 with a novel dom... | MODIFY | Summary: DNMT1 binds the ubiquitin ligase UHRF1. Reason: The source reports placental-library two-hybrid, purified-domain pull-down and human cell co-IP. Independent purified human DNMT1/UHRF1 assays in PMID:21745816 map this binary interaction. UHRF1 is an established ubiquitin-protein ligase, so GO:0031625 describes the partner class without assigning ligase catalysis to DNMT1 or claiming that this interaction alone specifies substrate ubiquitination. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:17972916 RIP140 directs histone and DNA methylation to silence Ucp1 e... | MODIFY | Summary: DNMT1 binds the transcriptional corepressor RIP140/NRIP1. Reason: The recovered original demonstrates endogenous human HeLa co-IP and binding of in-vitro-translated DNMT1 to recombinant RIP140 regions. Official NRIP1 function and the checked GO definition support transcription corepressor binding. Mouse adipocyte Ucp1 regulation is a separate context; no DNMT1 sequence-specific DNA-recognition role is inferred. Proposed replacements: transcription corepressor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19282482 Regulation of DNMT1 stability through SET7-mediated lysine m... | MODIFY | Summary: DNMT1 binds the methyltransferase SETD7 as a protein substrate. Reason: Human DNMT1βSET7 association is supported by recombinant pull-down and cellular co-IP in PMID:19282482; PMID:21151116 additionally resolves a short DNMT1 substrate peptide bound to SET7. SETD7 is an established histone methyltransferase, supporting the checked partner-class term. DNMT1 is methylated at K142 in these assays; it does not catalyze histone or protein methylation. Proposed replacements: histone methyltransferase binding |
| GO:0005515 protein binding | IPI PMID:19798101 Np95 interacts with de novo DNA methyltransferases, Dnmt3a a... | MODIFY | Summary: DNMT1 binds the ubiquitin ligase UHRF1. Reason: The source principally tests mouse Np95/Dnmt1 complexes; the human DNMT3B experiment is distinct and the HEK host does not identify every construct as human. Independent purified human DNMT1/UHRF1 assays in PMID:21745816 map this binary interaction. UHRF1 is an established ubiquitin-protein ligase, so GO:0031625 describes the partner class without assigning ligase catalysis to DNMT1 or claiming that this interaction alone specifies substrate ubiquitination. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:21151116 A methylation and phosphorylation switch between an adjacent... | MODIFY | Summary: DNMT1 binds protein kinase B/AKT1. Reason: The recovered original reports endogenous HEK293 nuclear co-IP and GST-fragment mapping between the AKT1 kinase domain and DNMT1 residues 1β446 (Results, Fig. 3 and Supplementary Fig. 5 description), in addition to phosphorylation assays. This supports protein kinase B binding; it does not make DNMT1 a kinase. The supplemental figure itself was not recovered. Proposed replacements: protein kinase B binding Supporting Evidence: PMID:21151116 AKT1 kinase colocalizes and directly interacts with DNMT1 |
| GO:0005515 protein binding | IPI PMID:21653829 Protein interactome reveals converging molecular pathways am... | KEEP AS NON CORE | Summary: The DNMT1βPICK1 pair has positive two-hybrid and co-IP records. Reason: The original human brain interaction-screen Methods were read. Exact MINT records IM-28561-1301 and IM-28561-203 identify DNMT1βPICK1 by two-hybrid and anti-tag co-IP; the two-hybrid record annotates DNMT1 residues 245β446 as a sufficient region. The inaccessible supplementary table is not claimed as read. PICK1 association does not establish a specific DNMT1 physiological or catalytic function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21947282 SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) prote... | KEEP AS NON CORE | Summary: DNMT1 associates with SIRT1. Reason: The recovered original demonstrates reciprocal endogenous/tagged human co-IP, deletion mapping, and SIRT1-dependent deacetylation of immunopurified DNMT1. These positive data support the pair, but immunoprecipitated substrate and native-complex experiments do not independently establish an isolated binary recognition interface. Preserve the association without a specific deacetylase-binding refinement or a new enzymatic function. |
| GO:0005515 protein binding | IPI PMID:22094255 Oxidative damage targets complexes containing DNA methyltran... | KEEP AS NON CORE | Summary: DNMT1 associates with EED after oxidative damage. Reason: The recovered human HCT116/NCCIT experiments show EED in DNMT1-associated Polycomb/SIRT1 complexes after hydrogen peroxide treatment. The literal EED pair is retained; native complex capture and sedimentation do not assign direct contact or EZH2 activity to EED or DNMT1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25544563 Global mapping of herpesvirus-host protein complexes reveals... | UNDECIDED | Summary: The exact viral-screen pair remains source-limited. Reason: The original describes Strep-tagged KSHV ORF capture in HEK293T, MiST scoring and partial validation, but the target-specific Q77UV9βDNMT1 table was not recovered: direct supplement requests returned an HTML challenge and the Europe PMC archive endpoint did not return a ZIP. Overall screen quality does not establish this exact record or its validation status. Preserve the imported pair without a false-positive or wrong-virus assertion. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25753001 A Protein Interaction between Ξ²-Catenin and Dnmt1 Regulates ... | KEEP AS NON CORE | Summary: DNMT1 associates with beta-catenin in colorectal cancer cells. Reason: The cache contains abstract/introduction/discussion but not the complete Results/Methods. Exact IntAct records nevertheless verify reciprocal/tagged human DNMT1βCTNNB1 co-IP and colocalization. Retain that association and its cancer-cell context; do not infer an isolated beta-catenin recognition activity or universal Wnt regulation from complex capture. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27728808 Enhancing the Cytotoxic Effects of PARP Inhibitors with DNA ... | KEEP AS NON CORE | Summary: DNMT1 associates with PARP1 in the reported drug/damage context. Reason: The protected cache lacks complete experimental sections. Exact human IntAct co-IP records for PMID:27728808 corroborate the pair, consistent with the accessible discussion of enhanced chromatin recruitment under DNMT/PARP inhibitor treatment. This is not purified direct binding or evidence that DNMT1 has PARP activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29691401 Methylated DNMT1 and E2F1 are targeted for proteolysis by L3... | KEEP AS NON CORE | Summary: DNMT1 associates with DCAF5 through a methyl-reader-dependent degradation pathway. Reason: The original DNMT1 AP-MS and reciprocal IP data identify DCAF5, but loss of L3MBTL3 reduces recruitment of DCAF5 to DNMT1. Thus a specific direct DCAF5-recognition or ubiquitin-ligase-binding activity is not assigned solely from the complex. DNMT1 is the substrate of this pathway. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | KEEP AS NON CORE | Summary: OpenCell reports YWHAZ-bait capture of a DNMT1 protein group. Reason: The exact original CSV line 29629 contains YWHAZ bait and DNMT1 prey, with accession group P26358;P26358-2;P26358-3;K7EP77;K7EMU8;K7EJL0. Preserve the positive endogenous-tag AP-MS association and direction. The group does not identify a natural DNMT1 isoform or prove direct contact or a specific signaling function. Supporting Evidence: |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DNMT1 can repress RNA polymerase II transcription in chromatin complexes. Reason: The historical mouse ortholog transfer is consistent with the independent DNMT1 amino-terminal HDAC2/DMAP1 repression mechanism. This context-dependent repressor-complex activity is retained without equating it to the catalytic maintenance-methylation unit or assigning DNMT1 RNA polymerase activity. Supporting Evidence: |
| GO:0000792 heterochromatin | IEA GO_REF:0000107 | ACCEPT | Summary: DNMT1 associates with heterochromatin. Reason: Mouse Dnmt1 has direct experimental heterochromatin annotations, including PMID:29053958. Human chromatin recognition and maintenance methylation independently support the conserved location. This is a dynamic chromatin-associated pool, not constitutive residence of every natural product. |
| GO:0001674 female germ cell nucleus | IEA GO_REF:0000107 | UNDECIDED | Summary: The historical female germ cell nucleus transfer remains unresolved. Reason: The old GOA maps this location from mouse P13864/ENSMUSP00000004202, but the current complete donor snapshot no longer contains the term and the specific historical experiment was not recovered. General nuclear localization does not establish the germ-cell compartment. Retirement records snapshot absence, not biological exclusion. Propagation Review Root cause: SOURCE STALE OR MISSING Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P13864 SOURCE STALE OR MISSING Historical donor identity verified; complete current donor GOA lacks the specific germ-cell nucleus term and the historical assay was not recovered. No biological absence inferred. Supporting Evidence: GO_REF:0000107 |
| GO:0003723 RNA binding | IEA GO_REF:0000107 | MODIFY | Summary: RNA association can be specified as lncRNA association. Reason: The mouse donor source PMID:20573698 reports Kcnq1ot1βDnmt1 RNA immunoprecipitation, and PMID:25686699 reports Dum association by RIP and RNA pull-down from nuclear extracts. These positive sources support a contextual lncRNA-binding inference; they do not demonstrate purified direct RNA contact, and no DNMT1 ribonuclease or RNA-methyltransferase activity is inferred. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P13864 SUPPORTS TRANSFER Mouse Kcnq1ot1/Dum RIP and nuclear-extract pull-down supply positive lncRNA-association evidence; purified direct contact and a specific human RNA interaction are not asserted. Proposed replacements: lncRNA binding |
| GO:0005657 replication fork | IEA GO_REF:0000107 | ACCEPT | Summary: DNMT1 is recruited to DNA-replication-associated sites. Reason: The mouse donor has a direct replication-fork annotation to PMID:10888872, whose source describes DNMT1/DMAP1 targeting through S phase. Human replication-associated recruitment is also supported by the H3Ub2 maintenance-methylation mechanism. The annotation does not make DNMT1 a DNA polymerase. |
| GO:0005721 pericentric heterochromatin | IEA GO_REF:0000107 | ACCEPT | Summary: Pericentric heterochromatin is a conserved DNMT1-associated pool. Reason: The current mouse donor retains an IDA annotation to PMID:17576694. Human heterochromatin localization and chromatin-coupled methylation independently fit the transferred compartment; no target-specific loss or contradictory localization is established. The donor original was not recovered, so no unseen assay details are supplied. |
| GO:0006351 DNA-templated transcription | IEA GO_REF:0000107 | MODIFY | Summary: Refine the broad transcription context to performed methylation-mediated repression. Reason: The historical broad transcription transfer is less informative than DNMT1's performed regulatory step. Human DNMT1 methylates CpG DNA and participates in silencing complexes, supporting negative regulation of gene expression via chromosomal CpG island methylation. This refinement identifies the supported mechanism without interpreting an upstream regulatory association as RNA-polymerase catalysis. Proposed replacements: negative regulation of gene expression via chromosomal CpG island methylation |
| GO:0008327 methyl-CpG binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DNMT1 recognizes methylated CpG-containing DNA. Reason: GO:0008327 requires binding a methylated CpG dinucleotide and does not require a fully symmetrically methylated duplex or exclude an enzyme substrate. Human DNMT1 complexes and assays directly establish hemimethylated CpG recognition. The mouse PMID:20573698 ChIP evidence is recruitment evidence, not a purified methylation-selectivity assay; the direct human evidence independently supports the capability. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P13864 SUPPORTS TRANSFER Donor PMID:20573698 ChIP is limited as a specificity assay; direct human hemimethylated-DNA recognition independently supports the broad methyl-CpG-binding definition. |
| GO:0009008 DNA-methyltransferase activity | IEA GO_REF:0000107 | MODIFY | Summary: DNA methyltransferase activity is refined to the CpG reaction. Reason: Human DNMT1 directly methylates cytosine in CpG DNA using S-adenosylmethionine. GO:0051718 specifies the assayed CpG reaction within the broader cytosine-5 methyltransferase activity. The preference for hemimethylated DNA is condition-dependent; neither an invariant twofold preference nor absence of de novo activity is asserted. Proposed replacements: DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000107 | MODIFY | Summary: The broad expression-regulation inference can identify CpG-mediated silencing. Reason: The historical electronic term is broader than the established DNA-methylation step. Human DNMT1 promoter occupancy, depletion and CpG methylation measurements support negative regulation of gene expression via chromosomal CpG island methylation. This replacement does not assert that every DNMT1-dependent expression change uses that mechanism. Proposed replacements: negative regulation of gene expression via chromosomal CpG island methylation |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | MODIFY | Summary: The broad expression-regulation inference can identify CpG-mediated silencing. Reason: The historical electronic term is broader than the established DNA-methylation step. Human DNMT1 promoter occupancy, depletion and CpG methylation measurements support negative regulation of gene expression via chromosomal CpG island methylation. This replacement does not assert that every DNMT1-dependent expression change uses that mechanism. Proposed replacements: negative regulation of gene expression via chromosomal CpG island methylation |
| GO:0042127 regulation of cell population proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DNMT1 affects cell proliferation in defined cellular contexts. Reason: The current mouse donor includes experimental genetic-interaction evidence for proliferation regulation (PMID:10919675). Human DNMT1 depletion and rescue studies also show cell-cycle/proliferation consequences. Retain this contextual role without making proliferation control a separate catalytic core or specifying a universal regulatory sign. |
| GO:0043045 epigenetic programming of gene expression | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: DNMT1 contributes to developmental epigenetic programming. Reason: The current mouse donor retains independent IMP/IGI evidence, including PMID:1606615, PMID:27841881 and PMID:29117290. DNMT1 performs the maintenance-methylation step, but the term specifically concerns embryonic programming and later expression potential. Retain the developmental role separately from the general maintenance-methylation core; retirement is source lifecycle only. The donor originals were not individually recovered. |
| GO:0043073 germ cell nucleus | IEA GO_REF:0000107 | UNDECIDED | Summary: The historical germ cell nucleus transfer remains unresolved. Reason: The old GOA maps this location from mouse P13864/ENSMUSP00000004202, but the current complete donor snapshot no longer contains the term and the specific historical experiment was not recovered. General nuclear localization does not establish the germ-cell compartment. Retirement records snapshot absence, not biological exclusion. Propagation Review Root cause: SOURCE STALE OR MISSING Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P13864 SOURCE STALE OR MISSING Historical donor identity verified; complete current donor GOA lacks the specific germ-cell nucleus term and the historical assay was not recovered. No biological absence inferred. Supporting Evidence: GO_REF:0000107 |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic silencing annotation matches the direct DNMT1 role. Reason: CpG methylation is work performed by DNMT1 itself, and human promoter methylation and expression studies corroborate this conserved silencing function. It is not inferred merely because DNMT1 expression changes in a tumor. |
| GO:0045892 negative regulation of DNA-templated transcription | IEA GO_REF:0000107 | MODIFY | Summary: The broad expression-regulation inference can identify CpG-mediated silencing. Reason: The historical electronic term is broader than the established DNA-methylation step. Human DNMT1 promoter occupancy, depletion and CpG methylation measurements support negative regulation of gene expression via chromosomal CpG island methylation. This replacement does not assert that every DNMT1-dependent expression change uses that mechanism. Proposed replacements: negative regulation of gene expression via chromosomal CpG island methylation |
| GO:0071230 cellular response to amino acid stimulus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: The amino-acid response transfer does not establish DNMT1 as an executing response factor. Reason: The traced mouse source PMID:20548288 uses a diet simultaneously low in methionine and lacking choline/folate and measures liver proteins, miRNAs and pathology. The selected original Results emphasize altered DNMT3A/3B levels; the Methods include Dnmt1 measurement but do not establish a Dnmt1-dependent amino-acid response. Transferring this diet-associated measurement as a human DNMT1 response function conflates an observed molecular readout with demonstrated participation. This is an electronic inference assessment, not a claim that the mouse experiment or expression measurement is false. The observed expression response is real, and the term definition encompasses gene-expression changes. This is therefore treated as over-annotation of an executing role, not a contradicted biological assertion. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P13864 SUPPORTS SOURCE BUT NOT TARGET Actual mouse source PMID:20548288 measures a diet/exposure-associated molecular readout; it does not establish execution of the corresponding response by human DNMT1. Supporting Evidence: |
| GO:0106222 lncRNA binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Conserved lncRNA association is retained with native-complex limits. Reason: The mouse donor's Dum source shows specific Dnmt1 RIP and biotin-RNA pull-down from C2C12 nuclear extracts and association in regenerating muscle. These positive results support the contextual lncRNA inference; absence of a purified binary assay does not justify the old blanket removal. No specific human Dum interaction, RNA catalysis, or independent core reader unit is asserted. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P13864 SUPPORTS TRANSFER Mouse Kcnq1ot1/Dum RIP and nuclear-extract pull-down supply positive lncRNA-association evidence; purified direct contact and a specific human RNA interaction are not asserted. |
| GO:0141119 chromosomal DNA methylation maintenance following DNA replication | IEA GO_REF:0000107 | ACCEPT | Summary: DNMT1 directly performs maintenance methylation after replication. Reason: The historical mouse transfer is consistent with direct human substrate/structural evidence and the independently added human IDA source. Preserve the scientific verdict while recording that this old electronic identity is absent from the current GOA. |
| GO:1903926 cellular response to bisphenol A | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: BPA-associated Dnmt1 expression is not a demonstrated human response function. Reason: The traced mouse original measures embryonic-brain mRNA after maternal dietary BPA exposure. It reports a sex-by-diet trend for Dnmt1 and a lower level in exposed females, but does not perturb Dnmt1 to establish its execution of a BPA response. The inherited electronic assertion overextends this expression readout to a human gene-product function; the measured association itself is not disputed. The observed expression response is real, and the term definition encompasses gene-expression changes. This is therefore treated as over-annotation of an executing role, not a contradicted biological assertion. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION CONTEXT OR TISSUE MISMATCH Sources checked: UniProtKB:P13864 SUPPORTS SOURCE BUT NOT TARGET Actual mouse source PMID:21980460 measures a diet/exposure-associated molecular readout; it does not establish execution of the corresponding response by human DNMT1. Supporting Evidence: |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | KEEP AS NON CORE | Summary: MitoCoP supports contextual mitochondrial-associated DNMT1 detection. Reason: The exact original workbook group 4315 contains P26358/P26358-3 and additional accessions and is selected in MitoCoP pool 3 with importomics class 1: log2 TOMM40-depletion/mock is -1.18000978898823 across four ratios. Spatial and subtractive datasets have different or missing resolution, and a separate P26358-2-containing group is not selected. Preserve the positive protein-group evidence; do not infer isoform-specific localization, mitochondrial DNA methylation, or contamination from the predominant nuclear function. Supporting Evidence: |
| GO:0141119 chromosomal DNA methylation maintenance following DNA replication | TAS PMID:20820192 BRCA1 affects global DNA methylation through regulation of D... | ACCEPT | Summary: Maintenance methylation is the established DNMT1 process. Reason: PMID:20820192 principally studies BRCA1-dependent regulation of DNMT1 expression and explicitly describes DNMT1 maintenance methylation. Direct human DNMT1 enzyme/structural studies independently establish the performed step. BRCA1 loss in that source lowers DNMT1, contrary to the old reference summary. |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | TAS PMID:20820192 BRCA1 affects global DNA methylation through regulation of D... | ACCEPT | Summary: DNMT1 contributes to CpG-mediated silencing. Reason: The cited BRCA1 paper discusses DNMT1-dependent methylation and imprinting, while its direct perturbation concerns BRCA1. Independent human DNMT1 promoter/depletion studies supply direct silencing support; this TAS entry is not represented as a purified assay from PMID:20820192. |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IMP PMID:24623306 A KRAS-directed transcriptional silencing pathway that media... | ACCEPT | Summary: Human DNMT1 is an active component of a promoter-silencing system. Reason: In human DLD-1 colorectal cells, DNMT1 knockdown derepresses INK4-ARF genes and reduces p14ARF promoter hypermethylation; ChIP places DNMT1 at the affected promoters in a ZNF304-dependent complex. The performed methylation step supports this process, without transferring ZNF304 sequence specificity to DNMT1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24492612 Methyllysine reader plant homeodomain (PHD) finger protein 2... | KEEP AS NON CORE | Summary: PHF20L1 recognizes methylated DNMT1. Reason: Purified DNMT1/peptide and reader-domain assays plus cellular co-IP support the association. PHF20L1 is the methyl-lysine reader and DNMT1 is its modified ligand. This does not make DNMT1 a PHF20L1-like reader or an inhibitor activity solely because degradation is reduced. Supporting Evidence: |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-4655431 | ACCEPT | Summary: Reactome places SUMO-modified DNMT1 in nucleoplasm. Reason: The event connects DNMT1 EWAS 212181 to monoSUMO1-K-DNMT1 4655353; both resolve to human P26358 residues 1β1616 and nucleoplasm. DNMT1 is the SUMO substrate, not the SUMO-transfer catalyst. The location assertion remains valid. Supporting Evidence: Reactome:R-HSA-4655431 |
| GO:0005515 protein binding | IPI PMID:32051553 The EGFR-ZNF263 signaling axis silences SIX3 in glioblastoma... | KEEP AS NON CORE | Summary: ZNF263-associated human complexes contain DNMT1. Reason: The U251 study identifies DNMT1 by ZNF263 affinity purification and validates association by co-IP. These data support complex association, not an isolated binary interface or a transcription-factor-binding refinement solely from the partner's class. DNMT1 is not assigned ZNF263 DNA recognition. Supporting Evidence: |
| GO:0010629 negative regulation of gene expression | IMP PMID:27021683 MiR-140-5p regulates hypoxia-mediated human pulmonary artery... | MODIFY | Summary: The SOD2 expression effect is consistent with CpG-mediated repression. Reason: The source abstract describes human pulmonary artery smooth-muscle DNMT1-dependent SOD2 repression through promoter CpG hypermethylation. Specify that epigenetic mechanism rather than generic negative gene regulation, supported independently by direct human DNMT1 silencing studies. Full source Methods were not recovered, so exact constructs, methylation assays and effect sizes are not invented. Proposed replacements: negative regulation of gene expression via chromosomal CpG island methylation |
| GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation | IMP PMID:27021683 MiR-140-5p regulates hypoxia-mediated human pulmonary artery... | KEEP AS NON CORE | Summary: DNMT1 promotes proliferation in the reported hypoxic smooth-muscle context. Reason: The verified source abstract explicitly describes human pulmonary artery smooth-muscle proliferation, apoptosis and differentiation under hypoxia and opposing effects of miR-140-5p and DNMT1 through SOD2 regulation. Preserve the curator-backed contextual phenotype without claiming an independently reconstituted mechanism or making it a universal DNMT1 core. Full Methods were inaccessible. For the historical GO:1905931 record, retirement preserves its identity while the current source uses GO:1900240 and GO:1905064; no source ID is silently rewritten. Supporting Evidence: |
| GO:1905460 negative regulation of vascular associated smooth muscle cell apoptotic process | IMP PMID:27021683 MiR-140-5p regulates hypoxia-mediated human pulmonary artery... | KEEP AS NON CORE | Summary: DNMT1 opposes apoptosis in the reported hypoxic smooth-muscle context. Reason: The verified source abstract explicitly describes human pulmonary artery smooth-muscle proliferation, apoptosis and differentiation under hypoxia and opposing effects of miR-140-5p and DNMT1 through SOD2 regulation. Preserve the curator-backed contextual phenotype without claiming an independently reconstituted mechanism or making it a universal DNMT1 core. Full Methods were inaccessible. For the historical GO:1905931 record, retirement preserves its identity while the current source uses GO:1900240 and GO:1905064; no source ID is silently rewritten. Supporting Evidence: |
| GO:1905931 obsolete negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching | IMP PMID:27021683 MiR-140-5p regulates hypoxia-mediated human pulmonary artery... | KEEP AS NON CORE | Summary: The historical phenotypic-switching assertion records a contextual vascular role. Reason: The verified source abstract explicitly describes human pulmonary artery smooth-muscle proliferation, apoptosis and differentiation under hypoxia and opposing effects of miR-140-5p and DNMT1 through SOD2 regulation. Preserve the curator-backed contextual phenotype without claiming an independently reconstituted mechanism or making it a universal DNMT1 core. Full Methods were inaccessible. For the historical GO:1905931 record, retirement preserves its identity while the current source uses GO:1900240 and GO:1905064; no source ID is silently rewritten. Supporting Evidence: |
| GO:1990841 promoter-specific chromatin binding | IDA PMID:24623306 A KRAS-directed transcriptional silencing pathway that media... | ACCEPT | Summary: DNMT1 occupies promoter-associated chromatin. Reason: Human DLD-1/HCT116/HCT15 ChIP identifies DNMT1 at INK4-ARF and CIMP promoters, with IgG and irrelevant-region controls. GO:1990841 describes promoter-associated chromatin binding, not sequence-specific transcription-factor binding or proof of direct naked-DNA contact. Supporting Evidence: |
| GO:0005634 nucleus | HDA PMID:16791210 Dynamic proteomics in individual human cells uncovers widesp... | MODIFY | Summary: Nuclear localization includes nucleoplasmic and chromatin-associated pools. Reason: The endogenous-tagging screen supports the curated nuclear observation, but its DNMT1-specific full table was not independently recovered. The finer locations below are supplied by independent target evidence, not by an unseen screen result. Supported HPA immunofluorescence identifies a nucleoplasmic pool, while independent human DNMT1 chromatin association and substrate/reader experiments establish a chromatin-associated pool. Refine the broad nuclear assertion to both supported locations. Nucleoplasm is not used as a substitute for chromosome-associated DNMT1, and neither replacement asserts exclusive residence or identical localization of all natural products. Chromatin has a typed part_of chromosome relationship rather than a nucleus parent; the biological nuclear location is supported by the experiments, not inferred from a nonexistent ontology edge. Proposed replacements: nucleoplasm chromatin |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-212222 | ACCEPT | Summary: Reactome explicitly locates the DNMT1 protein pool in nucleoplasm. Reason: The PRC2 recruitment event uses defined set 212315, which explicitly includes DNMT1 212181. EWAS 212181 resolves to human UniProt P26358 residues 1β1616 and nucleoplasm. Partner histone-modifying or regulatory activities are not transferred to DNMT1. Supporting Evidence: Reactome:R-HSA-212222 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-212269 | ACCEPT | Summary: Reactome explicitly locates the DNMT1 protein pool in nucleoplasm. Reason: Catalyst activity 212303 resolves through complex 212288 and set 212315 to DNMT1 212181. EWAS 212181 resolves to human UniProt P26358 residues 1β1616 and nucleoplasm. Partner histone-modifying or regulatory activities are not transferred to DNMT1. Supporting Evidence: Reactome:R-HSA-212269 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9710490 | ACCEPT | Summary: Reactome explicitly locates the DNMT1 protein pool in nucleoplasm. Reason: The promoter-methylation catalyst resolves through activity 212303 and complex 212288/set 212315 to DNMT1 212181. EWAS 212181 resolves to human UniProt P26358 residues 1β1616 and nucleoplasm. Partner histone-modifying or regulatory activities are not transferred to DNMT1. Supporting Evidence: Reactome:R-HSA-9710490 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9851058 | ACCEPT | Summary: Reactome explicitly locates the DNMT1 protein pool in nucleoplasm. Reason: The event forms complex 9850883, containing DNMT1 212181 with modified STAT3 and IL2RG DNA. EWAS 212181 resolves to human UniProt P26358 residues 1β1616 and nucleoplasm. Partner histone-modifying or regulatory activities are not transferred to DNMT1. Supporting Evidence: Reactome:R-HSA-9851058 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9851071 | ACCEPT | Summary: Reactome explicitly locates the DNMT1 protein pool in nucleoplasm. Reason: Complex 9850942 contains DNMT1 212181 with STAT3, HDAC1 and PTPN6 DNA. EWAS 212181 resolves to human UniProt P26358 residues 1β1616 and nucleoplasm. Partner histone-modifying or regulatory activities are not transferred to DNMT1. Supporting Evidence: Reactome:R-HSA-9851071 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9851145 | ACCEPT | Summary: Reactome explicitly locates the DNMT1 protein pool in nucleoplasm. Reason: The translation-regulation event has DNMT1 mRNA as input and protein 212181 as output; the annotation is to the protein's compartment, not an assignment of translational regulation to DNMT1. EWAS 212181 resolves to human UniProt P26358 residues 1β1616 and nucleoplasm. Partner histone-modifying or regulatory activities are not transferred to DNMT1. Supporting Evidence: Reactome:R-HSA-9851145 |
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | IDA PMID:21745816 The USP7/Dnmt1 complex stimulates the DNA methylation activi... | MODIFY | Summary: Direct human enzyme assays support CpG-specific methyltransferase activity. Reason: Purified full-length human DNMT1 assays compare unmethylated and hemimethylated duplexes with radiolabeled methyl donor. Human DNMT1 directly methylates cytosine in CpG DNA using S-adenosylmethionine. GO:0051718 specifies the assayed CpG reaction within the broader cytosine-5 methyltransferase activity. The preference for hemimethylated DNA is condition-dependent; neither an invariant twofold preference nor absence of de novo activity is asserted. Proposed replacements: DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates |
| GO:0005515 protein binding | IPI PMID:17673620 UHRF1 plays a role in maintaining DNA methylation in mammali... | MODIFY | Summary: DNMT1 binds the ubiquitin ligase UHRF1. Reason: The protected source abstract reports direct UHRF1βDNMT1 association and recruitment; the full original was not recovered. Independent purified human DNMT1/UHRF1 assays in PMID:21745816 map this binary interaction. UHRF1 is an established ubiquitin-protein ligase, so GO:0031625 describes the partner class without assigning ligase catalysis to DNMT1 or claiming that this interaction alone specifies substrate ubiquitination. Proposed replacements: ubiquitin protein ligase binding |
| GO:0005515 protein binding | IPI PMID:21745816 The USP7/Dnmt1 complex stimulates the DNA methylation activi... | MODIFY | Summary: DNMT1 directly binds ubiquitin-specific protease USP7. Reason: Purified human proteins and mapped DNMT1 TS/USP7 U3 fragments support a binary association in PMID:21745816. Official USP7 function and GO:1990381 identify the partner class. This is protease binding by DNMT1, not DNMT1 deubiquitinase activity. Proposed replacements: ubiquitin-specific protease binding Supporting Evidence: |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IDA PMID:21745816 The USP7/Dnmt1 complex stimulates the DNA methylation activi... | ACCEPT | Summary: DNMT1 participates in human promoter CpG silencing. Reason: The source combines purified human methylation assays with occupancy/silencing studies of methylated promoters in human cells. DNMT1 supplies DNA methylation; USP7 and UHRF1 recruitment/regulation are distinguished from its catalytic step. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19450230 SUMOylation enhances DNA methyltransferase 1 activity. | UNDECIDED | Summary: The literal UBE2I binding evidence remains incompletely accessible. Reason: The protected abstract establishes DNMT1 SUMOylation and altered methyltransferase activity, but does not specify the imported UBE2I pair assay. The relevant full original was not recovered. Preserve the curated interaction without inferring that substrate modification alone proves a binary UBE2I interface or that the pair is false. Supporting Evidence: |
| GO:0003677 DNA binding | IDA PMID:18754681 CXXC domain of human DNMT1 is essential for enzymatic activi... | MODIFY | Summary: The assayed CXXC-dependent DNA binding recognizes unmethylated CpG. Reason: The original indexed Results describe human CXXC constructs, wild-type and cysteine mutants, and gel-shift comparison of unmethylated, hemimethylated and methylated duplexes. Specify the measured unmethylated CpG binding. This regulatory recognition is distinct from the enzyme's preference for hemimethylated substrate during catalysis. Proposed replacements: unmethylated CpG binding Supporting Evidence: PMID:18754681 bound specifically to unmethylated CpG dinucleotides |
| GO:0009008 DNA-methyltransferase activity | IDA PMID:18754681 CXXC domain of human DNMT1 is essential for enzymatic activi... | MODIFY | Summary: Direct DNMT1 enzyme assays specify the CpG methylation reaction. Reason: The original indexed Results assay purified human full-length and CXXC-mutant/truncated proteins on CpG substrates. Mutations markedly reduce activity; the old absolute claim of zero activity is not retained. Human DNMT1 directly methylates cytosine in CpG DNA using S-adenosylmethionine. GO:0051718 specifies the assayed CpG reaction within the broader cytosine-5 methyltransferase activity. The preference for hemimethylated DNA is condition-dependent; neither an invariant twofold preference nor absence of de novo activity is asserted. Proposed replacements: DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates |
| GO:0010628 positive regulation of gene expression | IMP PMID:18413740 DNA methyltransferase 1 and 3B activate BAG-1 expression via... | KEEP AS NON CORE | Summary: DNMT1 can promote BAG1 expression in a defined cellular setting. Reason: The recovered original shows human DNMT1 overexpression/depletion effects on BAG1 expression. BAG1 promoter DNA methylation was not changed; altered histone marks and BORIS/CTCF occupancy provide a different context. Preserve the positive regulatory phenotype without claiming that DNMT1 is itself a sequence-specific transcriptional activator or directly methylates histones. Supporting Evidence: |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IDA PMID:18754681 CXXC domain of human DNMT1 is essential for enzymatic activi... | ACCEPT | Summary: DNMT1-dependent CpG methylation contributes to gene silencing. Reason: The source tests human DNMT1 DNA binding/catalysis and CXXC-mutant cellular methylation effects. The broader silencing claim is independently corroborated by direct human promoter methylation/depletion studies. This does not assert that every CXXC deletion completely eliminates enzymatic function. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | TAS PMID:10888872 DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a c... | KEEP AS NON CORE | Summary: DNMT1 can support methylation-independent transcriptional repression. Reason: The source abstract identifies an amino-terminal DNMT1/HDAC2/DMAP1 repressive complex at replication foci. Retain this established contextual repression role without equating all effects with CpG catalysis or inventing detailed full-text assays that were not recovered. Supporting Evidence: |
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | TAS PMID:8940105 New 5' regions of the murine and human genes for DNA (cytosi... | MODIFY | Summary: The historical active human enzyme is consistent with the CpG-specific reaction. Reason: The verified source abstract reports active full-ORF methyltransferase expression and a second-start product; it does not authenticate every present UniProt alternative product. Direct human substrate studies establish the narrower CpG reaction. Proposed replacements: DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates |
| GO:0005634 nucleus | TAS PMID:8940105 New 5' regions of the murine and human genes for DNA (cytosi... | MODIFY | Summary: Nuclear localization includes nucleoplasmic and chromatin-associated pools. Reason: The historical TAS nuclear assertion is retained; its inaccessible original Methods are not claimed to resolve a finer compartment. Supported HPA immunofluorescence identifies a nucleoplasmic pool, while independent human DNMT1 chromatin association and substrate/reader experiments establish a chromatin-associated pool. Refine the broad nuclear assertion to both supported locations. Nucleoplasm is not used as a substitute for chromosome-associated DNMT1, and neither replacement asserts exclusive residence or identical localization of all natural products. Chromatin has a typed part_of chromosome relationship rather than a nucleus parent; the biological nuclear location is supported by the experiments, not inferred from a nonexistent ontology edge. Proposed replacements: nucleoplasm chromatin |
| GO:0005515 protein binding | IPI PMID:16357870 The Polycomb group protein EZH2 directly controls DNA methyl... | KEEP AS NON CORE | Summary: DNMT1 associates with EZH2 in the source Polycomb system. Reason: This genuine split source row names EZH2/Q15910 separately from EED. Exact IntAct pull-down/co-IP records support the association, but the full original was inaccessible and the abstract emphasizes PRC2/3 complexes. Preserve the pair without asserting an isolated histone-methyltransferase-binding interface from an uninspected pull-down design. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21151116 A methylation and phosphorylation switch between an adjacent... | MODIFY | Summary: DNMT1 binds the methyltransferase SETD7 as a protein substrate. Reason: Human DNMT1βSET7 association is supported by recombinant pull-down and cellular co-IP in PMID:19282482; PMID:21151116 additionally resolves a short DNMT1 substrate peptide bound to SET7. SETD7 is an established histone methyltransferase, supporting the checked partner-class term. DNMT1 is methylated at K142 in these assays; it does not catalyze histone or protein methylation. Proposed replacements: histone methyltransferase binding |
| GO:0005515 protein binding | IPI PMID:22094255 Oxidative damage targets complexes containing DNA methyltran... | KEEP AS NON CORE | Summary: DNMT1 associates with EZH2 in oxidative-damage complexes. Reason: The recovered human cell study places EZH2 in DNMT1-associated Polycomb/SIRT1 complexes. It does not establish purified direct recognition by DNMT1; the known catalytic class of EZH2 alone does not justify a specific binding MF. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22094255 Oxidative damage targets complexes containing DNA methyltran... | KEEP AS NON CORE | Summary: DNMT1 associates with SIRT1. Reason: The recovered oxidative-damage study demonstrates DNMT1/SIRT1 association within large nuclear complexes. These positive data support the pair, but immunoprecipitated substrate and native-complex experiments do not independently establish an isolated binary recognition interface. Preserve the association without a specific deacetylase-binding refinement or a new enzymatic function. |
| GO:0005515 protein binding | IPI PMID:29691401 Methylated DNMT1 and E2F1 are targeted for proteolysis by L3... | KEEP AS NON CORE | Summary: L3MBTL3 recognizes methylated DNMT1 during regulated degradation. Reason: The source supplies endogenous interaction and purified reader-domain/methylated-DNMT1-peptide assays. L3MBTL3 is the reader, while DNMT1 supplies the modified substrate. Retain that positive pair without reversing the molecular roles or inventing an independent DNMT1 reader function. Supporting Evidence: |
| GO:0000792 heterochromatin | IDA PMID:29053958 Structure of the Dnmt1 Reader Module Complexed with a Unique... | ACCEPT | Summary: DNMT1 is associated with heterochromatin. Reason: The imported experimental assertion is consistent with ubiquitinated-H3 recruitment and direct human chromatin-associated maintenance-methylation evidence. PMID:29053958 remains abstract-only locally; independent PMID:36414620 supports the mechanistic context without claiming the unavailable 2017 localization figure was read. |
| GO:0003886 DNA (cytosine-5-)-methyltransferase activity | IDA PMID:26070743 Crystal Structure of Human DNA Methyltransferase 1. | MODIFY | Summary: Human structural and enzyme experiments establish CpG DNA methyltransferase activity. Reason: The source uses engineered human DNMT1 residues 351β1600, with a short cloning-derived C-terminal extension, and independent LC-MS methylation assays on hemimethylated DNA. Those constructs are not natural isoform 3. The observed CpG reaction supports the specific replacement. Proposed replacements: DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates Supporting Evidence: |
| GO:0005634 nucleus | EXP PMID:12145218 Co-operation and communication between the human maintenance... | MODIFY | Summary: Nuclear localization includes nucleoplasmic and chromatin-associated pools. Reason: The original detects endogenous DNMT1 in human nuclear extracts and images human DNMT1 residues 1β446 in transfected COS-7 cells. The fragment experiment is not assigned to every natural product. Supported HPA immunofluorescence identifies a nucleoplasmic pool, while independent human DNMT1 chromatin association and substrate/reader experiments establish a chromatin-associated pool. Refine the broad nuclear assertion to both supported locations. Nucleoplasm is not used as a substitute for chromosome-associated DNMT1, and neither replacement asserts exclusive residence or identical localization of all natural products. Chromatin has a typed part_of chromosome relationship rather than a nucleus parent; the biological nuclear location is supported by the experiments, not inferred from a nonexistent ontology edge. Proposed replacements: nucleoplasm chromatin |
| GO:0005634 nucleus | EXP PMID:24492612 Methyllysine reader plant homeodomain (PHD) finger protein 2... | MODIFY | Summary: Nuclear localization includes nucleoplasmic and pericentric heterochromatin pools. Reason: The original reports perinucleolar DNMT1/PHF20L1 colocalization and explicitly identifies endogenous DNMT1, PHF20L1 and 5-methylcytosine in pericentric heterochromatin in HeLa cells (Figure 4B). Preserve that source-specific pericentric heterochromatin location alongside the independently supported HPA nucleoplasmic pool. Nucleoplasm is not used as a substitute for chromosome-associated DNMT1, and neither replacement asserts exclusive residence or identical localization of all natural products. Chromatin has a typed part_of chromosome relationship rather than a nucleus parent; the biological nuclear location is supported by the experiments, not inferred from a nonexistent ontology edge. Proposed replacements: nucleoplasm pericentric heterochromatin |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: HPA directly supports nucleoplasmic localization. Reason: The saved official HPA XML for ENSG00000130816 classifies nucleoplasm as the main ICC/IF location with supported reliability. Antibody-based localization is gene-level evidence, not a natural-isoform-specific assay or evidence excluding all other pools. Image pixels were not independently interpreted. Supporting Evidence: GO_REF:0000052 |
| GO:0005694 chromosome | EXP PMID:29053958 Structure of the Dnmt1 Reader Module Complexed with a Unique... | MODIFY | Summary: Chromosome association is refined to chromatin association. Reason: The imported experimental source concerns H3Ub-dependent DNMT1 chromatin recruitment; its full original remains inaccessible, while independent human structural and cellular work corroborates chromatin engagement. GO:0005694 chromosome is a live term. GO:0000785 chromatin is its supported part, linked by part_of; this is a specificity refinement, not an obsolete-term or synonym replacement. Preserve the original source identity. Proposed replacements: chromatin |
| GO:0005694 chromosome | IEA GO_REF:0000044 | MODIFY | Summary: Chromosome association is refined to chromatin association. Reason: The genuine UniProt subcellular-location mapping is broader than the established protein-DNA chromatin association. GO:0005694 chromosome is a live term. GO:0000785 chromatin is its supported part, linked by part_of; this is a specificity refinement, not an obsolete-term or synonym replacement. Preserve the original source identity. Proposed replacements: chromatin |
| GO:0006346 DNA methylation-dependent constitutive heterochromatin formation | IEA GO_REF:0000107 | ACCEPT | Summary: Conserved DNA methylation supports constitutive heterochromatin formation. Reason: The current mouse donor has experimental support for this process, and human DNMT1 performs its DNA methylation step. This current electronic source complements the retired historical combined source without adding a fabricated annotation. |
| GO:0140254 histone H3K18ub reader activity | IDA PMID:29053958 Structure of the Dnmt1 Reader Module Complexed with a Unique... | ACCEPT | Summary: DNMT1 reads the H3K18 ubiquitin mark within a cooperative module. Reason: The 2017 source abstract describes simultaneous H3K18ub/H3K23ub engagement. The recovered 2022 human structural/biochemical original independently tests the paired marks, hemimethylated DNA and DNMT1 activation. Retain the specific reader capability, while distinguishing the structural isopeptide reagent from disulfide-linked kinetic substrate and not asserting that either isolated mark alone fully activates DNMT1. |
| GO:0140254 histone H3K18ub reader activity | IEA GO_REF:0000107 | ACCEPT | Summary: DNMT1 reads the H3K18 ubiquitin mark within a cooperative module. Reason: The 2017 source abstract describes simultaneous H3K18ub/H3K23ub engagement. The recovered 2022 human structural/biochemical original independently tests the paired marks, hemimethylated DNA and DNMT1 activation. Retain the specific reader capability, while distinguishing the structural isopeptide reagent from disulfide-linked kinetic substrate and not asserting that either isolated mark alone fully activates DNMT1. |
| GO:0140257 histone H3K23ub reader activity | IDA PMID:29053958 Structure of the Dnmt1 Reader Module Complexed with a Unique... | ACCEPT | Summary: DNMT1 reads the H3K23 ubiquitin mark within a cooperative module. Reason: The 2017 source abstract describes simultaneous H3K18ub/H3K23ub engagement. The recovered 2022 human structural/biochemical original independently tests the paired marks, hemimethylated DNA and DNMT1 activation. Retain the specific reader capability, while distinguishing the structural isopeptide reagent from disulfide-linked kinetic substrate and not asserting that either isolated mark alone fully activates DNMT1. |
| GO:0140257 histone H3K23ub reader activity | IEA GO_REF:0000107 | ACCEPT | Summary: DNMT1 reads the H3K23 ubiquitin mark within a cooperative module. Reason: The 2017 source abstract describes simultaneous H3K18ub/H3K23ub engagement. The recovered 2022 human structural/biochemical original independently tests the paired marks, hemimethylated DNA and DNMT1 activation. Retain the specific reader capability, while distinguishing the structural isopeptide reagent from disulfide-linked kinetic substrate and not asserting that either isolated mark alone fully activates DNMT1. |
| GO:0140258 histone H3K14ub reader activity | IDA PMID:29053958 Structure of the Dnmt1 Reader Module Complexed with a Unique... | UNDECIDED | Summary: The specific H3K14ub reader claim remains unresolved. Reason: The source identity and curated annotation are preserved. The protected 2017 abstract explicitly describes K18/K23, and full original recovery failed; the independently recovered 2022 study resolves K18/K23 rather than K14. This access gap is not evidence that K14 recognition is false, nor a reason to infer it from the other lysines. The electronic mouse transfer traces back to the same 2017 experimental source and provides no independently inspected K14 assay. |
| GO:0140258 histone H3K14ub reader activity | IEA GO_REF:0000107 | UNDECIDED | Summary: The specific H3K14ub reader claim remains unresolved. Reason: The source identity and curated annotation are preserved. The protected 2017 abstract explicitly describes K18/K23, and full original recovery failed; the independently recovered 2022 study resolves K18/K23 rather than K14. This access gap is not evidence that K14 recognition is false, nor a reason to infer it from the other lysines. The electronic mouse transfer traces back to the same 2017 experimental source and provides no independently inspected K14 assay. Propagation Review Root cause: UNRESOLVED Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:P13864 UNRESOLVED Current donor has IDA PMID:29053958 as well as propagated rows. This is not automatically circular; the unresolved point is access to the original K14-specific assay. |
| GO:0141119 chromosomal DNA methylation maintenance following DNA replication | IDA PMID:26070743 Crystal Structure of Human DNA Methyltransferase 1. | ACCEPT | Summary: DNMT1 catalyzes replication-coupled maintenance methylation. Reason: The human enzyme/structural source directly supports methylation of hemimethylated DNA; recruitment and activation studies connect that chemistry to copying chromosomal CpG methylation after replication. The engineered study fragment is not a natural alternative product. |
| GO:1900240 negative regulation of phenotypic switching | IDA PMID:27021683 MiR-140-5p regulates hypoxia-mediated human pulmonary artery... | KEEP AS NON CORE | Summary: DNMT1 influences phenotypic switching in hypoxic human smooth-muscle cells. Reason: The verified source abstract explicitly describes human pulmonary artery smooth-muscle proliferation, apoptosis and differentiation under hypoxia and opposing effects of miR-140-5p and DNMT1 through SOD2 regulation. Preserve the curator-backed contextual phenotype without claiming an independently reconstituted mechanism or making it a universal DNMT1 core. Full Methods were inaccessible. For the historical GO:1905931 record, retirement preserves its identity while the current source uses GO:1900240 and GO:1905064; no source ID is silently rewritten. Supporting Evidence: |
| GO:1905064 negative regulation of vascular associated smooth muscle cell differentiation | IMP PMID:27021683 MiR-140-5p regulates hypoxia-mediated human pulmonary artery... | KEEP AS NON CORE | Summary: DNMT1 negatively influences vascular smooth-muscle differentiation in the reported context. Reason: The verified source abstract explicitly describes human pulmonary artery smooth-muscle proliferation, apoptosis and differentiation under hypoxia and opposing effects of miR-140-5p and DNMT1 through SOD2 regulation. Preserve the curator-backed contextual phenotype without claiming an independently reconstituted mechanism or making it a universal DNMT1 core. Full Methods were inaccessible. For the historical GO:1905931 record, retirement preserves its identity while the current source uses GO:1900240 and GO:1905064; no source ID is silently rewritten. Supporting Evidence: |
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Download this section (compressed HTML)Q: How do the three natural DNMT1 products differ in recruitment, regulation and CpG methylation under matched expression conditions?
Q: What is the direct binding and activation contribution of H3K14 ubiquitination, compared with the structurally resolved cooperative K18/K23 module?
Q: Does the MitoCoP DNMT1 protein-group signal reflect a reproducible mitochondrial pool, and which natural product and intramitochondrial compartment account for it?
Experiment: Compare accession-matched DNMT1 products using matched expression, compartment-resolved localization and methylation assays on defined unmethylated and hemimethylated CpG substrates.
Experiment: Test purified human DNMT1 against separately defined H3K14ub, H3K18ub, H3K23ub and paired-mark reagents, separating binding from catalytic activation and preserving linkage chemistry controls.
Experiment: Validate the mitochondrial-associated DNMT1 signal with endogenous isoform-resolving peptides, fraction-purity and protease-protection controls, without presupposing mitochondrial DNA methylation activity.
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Download this section (compressed HTML)π View Pathway Visualization Interactive pathway diagram with detailed annotations