EHMT1, also called GLP, is a nuclear SET-domain protein lysine methyltransferase that cooperates with EHMT2/G9a in histone H3 lysine 9 methylation and epigenetic repression of gene expression. Its ankyrin-repeat region recognizes mono- and dimethylated H3K9 peptides. EHMT1 also methylates nonhistone substrates, including p53 at lysine 373. These chromatin and protein-modification activities contribute to transcriptional programs that vary with cell type and developmental context. Its natural splice products differ substantially in sequence extent and retention of the C-terminal catalytic region.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: EHMT1 contributes to transcriptional repression through chromatin modification. Reason: The target descends from the literal PTN008706806 IBD in PTHR46307. Human GLP recruitment to methylated RelA and repressive chromatin, together with conserved G9a/GLP silencing, supports the inherited negative regulation. The donor list is not a measure of confidence; direct target evidence is complementary to ancestry. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008706806 SUPPORTS TRANSFER The literal IBD node is on the authenticated target ancestry; current donor records and the original source list are kept distinct. Supporting Evidence: GO_REF:0000033 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0000785 chromatin | IBA GO_REF:0000033 | ACCEPT | Summary: Chromatin association is part of EHMT1 function. Reason: The target lies below PTN002505142 and the current IBD explicitly carries chromatin. Human promoter occupancy and histone-directed activity independently support the location; no target-specific loss is evident. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002505142 SUPPORTS TRANSFER The literal IBD node is on the authenticated target ancestry; current donor records and the original source list are kept distinct. Supporting Evidence: GO_REF:0000033 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0000785 chromatin | ISS GO_REF:0000024 | ACCEPT | Summary: The mouse donor supports conserved chromatin association. Reason: Q5DW34 is mouse Ehmt1, matching MGI:1924933. The donor studies identify promoter-bound GLP and chromatin methylation, while human GLP promoter ChIP provides direct corroboration. This is chromatin association, not a claim of sequence-specific DNA recognition. Propagation Review Root cause: NO FAILURE CORE Sources checked: MGI:MGI:1924933 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000024 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0001222 transcription corepressor binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Corepressor binding is supported as a partner-class activity. Reason: The current ARBA00088998 condition set matches both target FunFam identifiers and Primates. Human CDYL and MPP8 associations support binding to independently identified corepressors. This does not establish that EHMT1 itself is a generic noncatalytic corepressor or that every interaction occurs in the same complex. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00088998 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000117 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0001222 transcription corepressor binding | IPI PMID:29628311 A Family of Vertebrate-Specific Polycombs Encoded by the LCO... | KEEP AS NON CORE | Summary: The LCOR-locus interaction concerns the PALI1 complex. Reason: PMID29628311 Figure 2 and FLAG IP methods recover GLP with PALI1, a long LCOR-locus product that associates with PRC2 and the G9a complex. This supports a corepressor-class association, with PALI1/LCOR product distinctions retained; it is not evidence that every short LCOR isoform or an isolated GLP interface was tested. Supporting Evidence: |
| GO:0002039 p53 binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: p53 substrate binding is a supported secondary context. Reason: The current ARBA00087974 target-matching FunFam/Catarrhini condition set and the family mappings are consistent with direct purified GLP methylation of p53 at K373. The functional substrate interaction supports this binding class without making p53 regulation the sole EHMT1 mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: ARBA:ARBA00087974 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. InterPro:IPR038035 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. InterPro:IPR043550 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000117 GO_REF:0000002 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0002039 p53 binding | IPI PMID:20118233 G9a and Glp methylate lysine 373 in the tumor suppressor p53... | KEEP AS NON CORE | Summary: GLP directly engages p53 as a methylation substrate. Reason: The original uses purified human GLP numbered 1β1299 and p53 proteins/peptides, including a K373R substrate control. These assays establish substrate engagement. The historical construct is not an exact current-product sequence proof. The linked correction adds an author and does not alter these results. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16702210 Zinc finger protein Wiz links G9a/GLP histone methyltransfer... | MODIFY | Summary: WIZ binding can be described by its documented scaffold role. Reason: The original shows endogenous human HeLa GLP/WIZ/CtBP coassociation, while the detailed deletion experiments use mouse constructs. WIZ binds GLP/G9a through ZF6 and CtBP through separate motifs, tethering the proteins into a complex. This supports scaffold protein binding without transferring WIZ activity to EHMT1 or treating human host cells as proof of human recombinant inserts. Proposed replacements: scaffold protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19061646 CDYL bridges REST and histone methyltransferases for gene re... | MODIFY | Summary: The CDYL interaction supports transcription corepressor binding. Reason: Human HeLa CDYL purification and purified-protein pull-downs identify GLP association. CDYL is independently characterized as a transcriptional corepressor bridging REST and histone-modifying proteins. The refinement describes the partner class; it does not require an isolated physiological GLPβCDYL interface or assign all CDYL isoforms the same activity. Proposed replacements: transcription corepressor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20871592 Methyl-H3K9-binding protein MPP8 mediates E-cadherin gene si... | MODIFY | Summary: MPP8 is an identified transcriptional corepressor partner. Reason: PMID20871592 Figure 6 reports tagged and endogenous reciprocal GLPβMPP8 coimmunoprecipitation in human 293T cells. MPP8 represses E-cadherin through methylated-chromatin recognition and DNMT3A recruitment. This supports corepressor binding; the data do not require MPP8 to recruit GLP, because GLP promoter occupancy persists after MPP8 depletion. Proposed replacements: transcription corepressor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21131967 Lysine methylation of the NF-ΞΊB subunit RelA by SETD6 couple... | MODIFY | Summary: The human RelA interaction supports DNA-binding transcription factor binding. Reason: The source tests GLP ankyrin recognition of methylated RelA K310, tagged full-length association and endogenous human-cell complexes. Q04206 is the DNA-binding NF-kappa-B subunit RELA. This supports the partner-class refinement while retaining methylation-dependent recognition and avoiding a claim that GLP itself binds the RelA DNA motif. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21131967 Lysine methylation of the NF-ΞΊB subunit RelA by SETD6 couple... | MODIFY | Summary: The mouse RelA partner retains its distinct species scope. Reason: Q04207 is mouse Rela, a DNA-binding transcription factor. The paper includes mouse embryonic fibroblast experiments alongside human-cell and recombinant assays. The imported mouse-partner assertion is retained; the class refinement does not relabel the partner as human or imply that every recombinant construct has a sequence-verified human origin. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: The MPP8 proteomic association supports the same independently verified partner class. Reason: The literal human IntAct record EBI-11059482/IM-24272-454 reports anti-tag coimmunoprecipitation/association in the Hein screen, with supplementary Table S2 as its locator. Independent targeted GLPβMPP8 experiments and MPP8 repression studies establish the corepressor class. The screen is not treated as purified binary binding or proof of MPP8 catalysis. Proposed replacements: transcription corepressor binding Supporting Evidence: file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear localization is conserved and directly supported in human cells. Reason: PTN002505142 is on the target ancestry and carries the literal nuclear IBD. EHMT1 appears among its own evidential descendants legitimately; this is not circularity. Human nuclear-pellet identification and HPA supported nuclear pools corroborate the broad nuclear assertion. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002505142 SUPPORTS TRANSFER The literal IBD node is on the authenticated target ancestry; current donor records and the original source list are kept distinct. Supporting Evidence: GO_REF:0000033 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0005634 nucleus | IC PMID:12004135 A complex with chromatin modifiers that occupies E2F- and My... | ACCEPT | Summary: The broad nuclear location is consistent with the chromatin-modifying activity. Reason: The imported IC relates nuclear localization to chromatin organization. The original 12004135 abstract and curated assertion are retained with its unrecovered full-text limit; independently inspected human nuclear-pellet and chromatin studies make this broad location secure without inventing a finer compartment for that original experiment. |
| GO:0005634 nucleus | IDA PMID:19144645 Dynamic Histone H1 Isotype 4 Methylation and Demethylation b... | ACCEPT | Summary: GLP was identified in a human nuclear-pellet purification. Reason: The original Methods and Results identify GLP by mass spectrometry and immunoblot in HeLa nuclear-pellet fractions. Most downstream H1.4K26 functional experiments focus on G9a; nuclear detection of GLP is directly relevant without transferring G9a enzymology. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: The electronic nuclear mapping is biologically supported. Reason: ARBA00026330 contains a matching target FunFam pair/Eukaryota condition set. The imported InterPro and subcellular-location mappings are compatible with direct human nuclear evidence. The broad source location is retained rather than forcing each independent source into a finer HPA pool. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00026330 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. InterPro:IPR007728 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. UniProtKB-SubCell:SL-0191 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000117 GO_REF:0000002 GO_REF:0000044 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Mouse Ehmt1 localization supports the broad nuclear transfer. Reason: The Q5DW34 donor is authentic mouse Ehmt1. PMID15774718 detects endogenous protein in mouse ES-cell and fibroblast nuclei, with exclusion from nucleoli; human evidence independently confirms nuclear localization. The duplicate raw dates collapsed by the fetch workflow do not alter this source assertion. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5DW34 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000024 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: HPA supports nucleoplasmic EHMT1 localization. Reason: The actual EHMT1 HPA page separately labels nucleoplasm as supported, matching the XML target and location. This is antibody-based cell imaging metadata, not a new inspection of image pixels. The distinct supported nuclear-body observation is retained separately. Supporting Evidence: GO_REF:0000052 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md https://www.proteinatlas.org/ENSG00000181090-EHMT1/subcellular |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3788724 | ACCEPT | Summary: The Reactome model places human EHMT1 in the nucleoplasm. Reason: The saved current model has a literal participant/component/referenceEntity path to UniProt Q9H9B1 through EHMT1 entity 1183226, whose compartment is nucleoplasm. This is curated pathway-model localization, not an independent imaging experiment. EHMT1 appearing as a ubiquitination substrate in some events does not imply ubiquitin-transferase activity. Other events model histone/p53 methylation or E2F6-complex assembly. Supporting Evidence: Reactome:R-HSA-3788724 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3788725 | ACCEPT | Summary: The Reactome model places human EHMT1 in the nucleoplasm. Reason: The saved current model has a literal participant/component/referenceEntity path to UniProt Q9H9B1 through EHMT1 entity 1183226, whose compartment is nucleoplasm. This is curated pathway-model localization, not an independent imaging experiment. EHMT1 appearing as a ubiquitination substrate in some events does not imply ubiquitin-transferase activity. Other events model histone/p53 methylation or E2F6-complex assembly. Supporting Evidence: Reactome:R-HSA-3788725 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3788745 | ACCEPT | Summary: The Reactome model places human EHMT1 in the nucleoplasm. Reason: The saved current model has a literal participant/component/referenceEntity path to UniProt Q9H9B1 through EHMT1 entity 1183226, whose compartment is nucleoplasm. This is curated pathway-model localization, not an independent imaging experiment. EHMT1 appearing as a ubiquitination substrate in some events does not imply ubiquitin-transferase activity. Other events model histone/p53 methylation or E2F6-complex assembly. Supporting Evidence: Reactome:R-HSA-3788745 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-3788748 | ACCEPT | Summary: The Reactome model places human EHMT1 in the nucleoplasm. Reason: The saved current model has a literal participant/component/referenceEntity path to UniProt Q9H9B1 through EHMT1 entity 1183226, whose compartment is nucleoplasm. This is curated pathway-model localization, not an independent imaging experiment. EHMT1 appearing as a ubiquitination substrate in some events does not imply ubiquitin-transferase activity. Other events model histone/p53 methylation or E2F6-complex assembly. Supporting Evidence: Reactome:R-HSA-3788748 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5634729 | ACCEPT | Summary: The Reactome model places human EHMT1 in the nucleoplasm. Reason: The saved current model has a literal participant/component/referenceEntity path to UniProt Q9H9B1 through EHMT1 entity 1183226, whose compartment is nucleoplasm. This is curated pathway-model localization, not an independent imaging experiment. EHMT1 appearing as a ubiquitination substrate in some events does not imply ubiquitin-transferase activity. Other events model histone/p53 methylation or E2F6-complex assembly. Supporting Evidence: Reactome:R-HSA-5634729 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5634750 | ACCEPT | Summary: The Reactome model places human EHMT1 in the nucleoplasm. Reason: The saved current model has a literal participant/component/referenceEntity path to UniProt Q9H9B1 through EHMT1 entity 1183226, whose compartment is nucleoplasm. This is curated pathway-model localization, not an independent imaging experiment. EHMT1 appearing as a ubiquitination substrate in some events does not imply ubiquitin-transferase activity. Other events model histone/p53 methylation or E2F6-complex assembly. Supporting Evidence: Reactome:R-HSA-5634750 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6805755 | ACCEPT | Summary: The Reactome model places human EHMT1 in the nucleoplasm. Reason: The saved current model has a literal participant/component/referenceEntity path to UniProt Q9H9B1 through EHMT1 entity 1183226, whose compartment is nucleoplasm. This is curated pathway-model localization, not an independent imaging experiment. EHMT1 appearing as a ubiquitination substrate in some events does not imply ubiquitin-transferase activity. Other events model histone/p53 methylation or E2F6-complex assembly. Supporting Evidence: Reactome:R-HSA-6805755 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8953418 | ACCEPT | Summary: The Reactome model places human EHMT1 in the nucleoplasm. Reason: The saved current model has a literal participant/component/referenceEntity path to UniProt Q9H9B1 through EHMT1 entity 1183226, whose compartment is nucleoplasm. This is curated pathway-model localization, not an independent imaging experiment. EHMT1 appearing as a ubiquitination substrate in some events does not imply ubiquitin-transferase activity. Other events model histone/p53 methylation or E2F6-complex assembly. Supporting Evidence: Reactome:R-HSA-8953418 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8953452 | ACCEPT | Summary: The Reactome model places human EHMT1 in the nucleoplasm. Reason: The saved current model has a literal participant/component/referenceEntity path to UniProt Q9H9B1 through EHMT1 entity 1183226, whose compartment is nucleoplasm. This is curated pathway-model localization, not an independent imaging experiment. EHMT1 appearing as a ubiquitination substrate in some events does not imply ubiquitin-transferase activity. Other events model histone/p53 methylation or E2F6-complex assembly. Supporting Evidence: Reactome:R-HSA-8953452 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9007283 | ACCEPT | Summary: The Reactome model places human EHMT1 in the nucleoplasm. Reason: The saved current model has a literal participant/component/referenceEntity path to UniProt Q9H9B1 through EHMT1 entity 1183226, whose compartment is nucleoplasm. This is curated pathway-model localization, not an independent imaging experiment. EHMT1 appearing as a ubiquitination substrate in some events does not imply ubiquitin-transferase activity. Other events model histone/p53 methylation or E2F6-complex assembly. Supporting Evidence: Reactome:R-HSA-9007283 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0005694 chromosome | IEA GO_REF:0000044 | MODIFY | Summary: Chromatin is the informative supported chromosome-associated pool. Reason: The imported subcellular chromosome mapping is consistent with a chromatin-modifying enzyme. Human promoter ChIP and the conserved histone-directed mechanism resolve the relevant association to chromatin; this does not claim attachment to every chromosomal structure or mitotic chromosome region. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB-SubCell:SL-0468 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Proposed replacements: chromatin Supporting Evidence: GO_REF:0000044 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0005694 chromosome | ISS GO_REF:0000024 | MODIFY | Summary: The mouse chromosome transfer can be resolved to chromatin. Reason: Q5DW34 mouse Ehmt1 participates in promoter chromatin and nuclear histone methylation. Human GLP chromatin occupancy independently supports this more informative location. The donor and its species remain explicit rather than treating the ISS record as direct human imaging. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q5DW34 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Proposed replacements: chromatin Supporting Evidence: GO_REF:0000024 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0006325 chromatin organization | IDA PMID:12004135 A complex with chromatin modifiers that occupies E2F- and My... | ACCEPT | Summary: Chromatin organization is central to EHMT1 biology. Reason: The source abstract describes an E2F6 complex containing an H3K9 methyltransferase at target promoters. Its full operative text remains unavailable, but the curated assertion is consistent with independently established GLP histone methylation and promoter-associated chromatin regulation. No inaccessible methyl-state-specific assay is claimed. |
| GO:0006346 DNA methylation-dependent constitutive heterochromatin formation | ISS GO_REF:0000024 | MODIFY | Summary: The donor supports epigenetic silencing rather than a specific constitutive-heterochromatin compartment. Reason: The current mouse donor points to PMID18818694. Its mutant/rescue, promoter ChIP and bisulfite assays establish cooperative H3K9/DNA methylation-associated silencing at Mage-a2 and Wfdc15a, including a methyltransferase-independent contribution. These experiments do not establish formation of constitutive heterochromatin. GO0045814 preserves the demonstrated epigenetic repression mechanism without assigning GLP DNA methyltransferase chemistry. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q5DW34 SUPPORTS SOURCE BUT NOT TARGET The donor supports the reported epigenetic mechanism, but its assays do not resolve the narrower imported process; see the source-specific reason. Proposed replacements: negative regulation of gene expression, epigenetic Supporting Evidence: GO_REF:0000024 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0008168 methyltransferase activity | IDA PMID:12004135 A complex with chromatin modifiers that occupies E2F- and My... | MODIFY | Summary: H3K9 methyltransferase activity is more informative than generic methyltransferase activity. Reason: The source abstract specifically identifies histone H3 lysine 9 methylation, and the independently inspected human GLP SET-domain study supports this substrate specificity. Full-text access to the earlier source remains limited; no precise methyl-state or historical insert-sequence claim is inferred from its abstract. Proposed replacements: histone H3K9 methyltransferase activity |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Zinc binding supports the structural integrity of the catalytic region. Reason: The current target has the imported pre-SET/cysteine-rich domain matches and multiple curated Zn coordination sites supported by PMID20434463. This is a structural cofactor-binding context, not a separate zinc-signaling or zinc-transport function; the feature annotation is distinguished from independent figure inspection. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: InterPro:IPR007728 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. InterPro:IPR047762 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000002 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0016279 protein-lysine N-methyltransferase activity | IDA PMID:20118233 G9a and Glp methylate lysine 373 in the tumor suppressor p53... | ACCEPT | Summary: EHMT1 has protein-lysine methyltransferase activity, including a demonstrated nonhistone substrate. Reason: Purified human GLP methylates p53 K373, with loss on K373R and methyl-state substrate assays favoring the dimethyl product. This directly supports the broad enzyme class. The p53 context is distinct from the principal histone H3K9 mechanism, and its physiological consequences are not generalized to all cells or products. Supporting Evidence: |
| GO:0016279 protein-lysine N-methyltransferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: The family mapping correctly identifies protein-lysine methyltransferase activity. Reason: Both target InterPro assignments describe the EHMT catalytic family/domain. Direct human H3K9 and p53 assays support the enzyme class; no unsupported universal substrate or methyl-state specificity is introduced by accepting this broader class. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR038035 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. InterPro:IPR043550 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000002 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0016604 nuclear body | IDA GO_REF:0000052 | ACCEPT | Summary: HPA separately supports a nuclear-body pool. Reason: The actual target page labels nuclear bodies as supported, independently of its overall gene-level reliability and supported nucleoplasm label. The imported IDA location is retained. The metadata do not identify a particular nuclear-body subtype or establish a distinct biochemical mechanism there. Supporting Evidence: GO_REF:0000052 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md https://www.proteinatlas.org/ENSG00000181090-EHMT1/subcellular |
| GO:0018026 peptidyl-lysine monomethylation | ISS GO_REF:0000024 | ACCEPT | Summary: Lysine monomethylation is part of the conserved EHMT1 writer mechanism. Reason: Q5DW34 mouse Ehmt1 is the correct donor. Its biochemical and knockout/rescue studies support H3K9 mono/di methylation, and human GLP is an established H3K9 methyltransferase. This broad process does not imply that every protein lysine or every natural product is a substrate/catalyst. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5DW34 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000024 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0018027 peptidyl-lysine dimethylation | IDA PMID:20118233 G9a and Glp methylate lysine 373 in the tumor suppressor p53... | ACCEPT | Summary: GLP can produce dimethylated protein lysine. Reason: The original human GLP assays compare unmethylated, mono- and dimethylated p53K373 peptides and test cellular K373me2. They support lysine dimethylation with this substrate scope; the weak signal on pre-dimethylated p53 is not extrapolated to histone H3K9 trimethylation. Supporting Evidence: |
| GO:0040029 epigenetic regulation of gene expression | IBA GO_REF:0000033 | ACCEPT | Summary: Epigenetic gene-expression regulation is an inherited central role. Reason: The literal PTN008706806 IBD is on the target ancestry. Mouse G9a/GLP promoter experiments and human GLP recruitment support chromatin-mediated regulation. The current IBD also lists a zebrafish source absent from the frozen row; that version difference is recorded without changing the imported donors or relying on donor count. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008706806 SUPPORTS TRANSFER The literal IBD node is on the authenticated target ancestry; current donor records and the original source list are kept distinct. Supporting Evidence: GO_REF:0000033 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0042054 histone methyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: The histone methyltransferase mapping can be refined to H3K9. Reason: The imported pre-SET/EHMT family annotations are authentic and the target human enzyme has directly established H3K9 activity. The refinement identifies its principal demonstrated histone residue without importing the G9a trimethylation mutant or asserting physiological H3K27 methylation from a weak donor assay. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR007728 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. InterPro:IPR043550 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Proposed replacements: histone H3K9 methyltransferase activity Supporting Evidence: GO_REF:0000002 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0045892 negative regulation of DNA-templated transcription | ISS GO_REF:0000024 | ACCEPT | Summary: Negative transcriptional regulation is conserved in the Ehmt1 donor. Reason: Mouse GLP loss and complementation affect silencing of defined target genes, with promoter chromatin and DNA methylation analyses supporting an active regulatory contribution. Human GLP chromatin recruitment and repression provide independent corroboration. This is not inferred from expression correlation alone. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5DW34 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000024 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0045995 regulation of embryonic development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Embryonic-development regulation is a supported organismal context. Reason: Mouse Ehmt1-null embryos show growth retardation and lethality together with reduced H3K9 dimethylation. The conserved chromatin regulator plausibly underlies this existing ISS annotation, but the donor phenotype does not define a single autonomous embryonic-patterning activity or an exact human developmental assay. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q5DW34 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000024 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0046974 histone H3K9 methyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The H3K9 writer activity is supported by ancestry and direct human biochemistry. Reason: PTN008706806 is the literal ancestral node and the target lies within its descendant clade. Current alignment and donor identities are compatible with the EHMT catalytic family, while human GLP SET-domain assays directly support H3K9 methylation. Target self-donation is legitimate experimental grounding, not circular evidence. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008706806 SUPPORTS TRANSFER The literal IBD node is on the authenticated target ancestry; current donor records and the original source list are kept distinct. Supporting Evidence: GO_REF:0000033 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0046974 histone H3K9 methyltransferase activity | IDA PMID:12004135 A complex with chromatin modifiers that occupies E2F- and My... | ACCEPT | Summary: The original H3K9 assignment agrees with independently established human GLP activity. Reason: The original abstract explicitly describes a histone H3 lysine 9 methyltransferase in the E2F6 complex. Full operative text was not recovered, so detailed assay conditions are not reconstructed. Independent human GLP structural/enzymatic evidence makes the broad H3K9 activity secure. |
| GO:0046974 histone H3K9 methyltransferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: The EHMT1 SET-domain mapping supports H3K9 methyltransferase activity. Reason: The target contains IPR038035 and the experimentally established human GLP catalytic region. This mapping is consistent with direct H3K9 writer assays; it is not evidence that all natural truncated products retain an intact SET domain. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR038035 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000002 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0046974 histone H3K9 methyltransferase activity | ISS GO_REF:0000024 | ACCEPT | Summary: The mouse Ehmt1 transfer supports the conserved H3K9 activity. Reason: The donor Q5DW34 is correctly mapped to mouse Ehmt1. Purified mouse SET1002β1296 methylates H3K9, and cellular mono/di methylation depends on the G9a/GLP complex. Direct human GLP assays independently support transfer of the broad residue-specific activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5DW34 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000024 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0046976 histone H3K27 methyltransferase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Weak in-vitro H3K27 activity is retained as a secondary biochemical context. Reason: PMID15774718 directly tests purified mouse GLP SET1002β1296 against GST-H3-tail lysine variants and reports weak K27 methylation relative to K9. The authentic donor supports this existing ISS claim, but the assay does not establish EHMT1 as the physiological PRC2-like H3K27 writer or show activity in every human product. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q5DW34 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000024 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0050873 brown fat cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Brown-fat differentiation is a supported tissue-specific regulatory role. Reason: The mouse Ehmt1 donor is involved in PRDM16-dependent repression of competing muscle programs, with conditional loss impairing brown-fat development. The source includes a chromatin/protein-stability contribution rather than only generic necessity. It remains a specialized organismal context rather than a separate universal molecular activity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: MGI:MGI:1924933 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000024 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0060992 response to fungicide | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Rat expression changes alone do not establish EHMT1 participation in the fungicide response. Reason: A0A8I6AB09/ENSRNOP00000090039 is rat Ehmt1 and the current expression donor cites PMID:22496781. The reanalysis reports modest statistically significant Ehmt1 down-regulation after vinclozolin exposure, below the stated 1.5-fold cutoff in each generation. That positive expression observation is retained. Although GO:0060992 encompasses changes in gene expression, measuring the Ehmt1 transcript and coexpression does not establish that the EHMT1 protein performs a step in the response. The involved_in role is therefore overextended; this is not evidence of absent exposure responsiveness, a wrong ortholog, or a demonstrated human mechanism. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION SOURCE EVIDENCE WEAK Sources checked: UniProtKB:A0A8I6AB09 SOURCE WEAK OR INFERRED The authentic rat source supports the exposure-associated expression observation, but expression/coexpression alone is insufficient evidence that the gene product performs a response step. Weakness here concerns the claimed functional role, not the donor identity or statistical result. ensembl:ENSRNOP00000090039 SOURCE WEAK OR INFERRED The authentic rat source supports the exposure-associated expression observation, but expression/coexpression alone is insufficient evidence that the gene product performs a response step. Weakness here concerns the claimed functional role, not the donor identity or statistical result. Supporting Evidence: GO_REF:0000107 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0120162 positive regulation of cold-induced thermogenesis | ISS PMID:24196706 EHMT1 controls brown adipose cell fate and thermogenesis thr... | KEEP AS NON CORE | Summary: Positive cold-induced thermogenesis is supported in the mouse adipose context. Reason: Conditional mouse Ehmt1 loss compromises brown-fat thermogenesis and cold tolerance in the cited study, with PRDM16-complex mechanisms providing biological context. This supports the existing orthology-based process annotation while keeping the human transfer and tissue dependence explicit. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q5DW34 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. |
| GO:0140947 histone H3K9me2 methyltransferase activity | IEA GO_REF:0000116 | UNDECIDED | Summary: The specific conversion of H3K9me2 to H3K9me3 remains unresolved. Reason: GO0140947 means methylating an already dimethylated H3K9 input, not producing dimethyl H3K9. The Rhea mapping therefore requires direct final-step chemistry. Inspected human GLP evidence supports H3K9 methylation but does not resolve that step; the trimethylation-enabling mutant in PMID20084102 is G9a. Retain the electronic source assertion pending adequate target-specific reaction evidence. Propagation Review Root cause: UNRESOLVED Sources checked: RHEA:60288 UNRESOLVED The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000116 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0140947 histone H3K9me2 methyltransferase activity | ISS GO_REF:0000024 | UNDECIDED | Summary: The mouse donor does not independently resolve the final H3K9 methylation step. Reason: The current Q5DW34 record links this reaction-specific term to PMID24196706. That study measures promoter H3K9me2/me3 and methylation by an immunopurified complex; loss of a cellular me3 mark does not isolate GLP catalysis on a me2 substrate. The positive chromatin phenotype is preserved, while direct human final-step activity remains unresolved. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q5DW34 UNRESOLVED Current mouse donor maps to PMID24196706; me3 ChIP and complex bulk methylation do not isolate the specified catalytic reaction. Supporting Evidence: GO_REF:0000024 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0140948 histone H3K9 monomethyltransferase activity | EXP PMID:12004135 A complex with chromatin modifiers that occupies E2F- and My... | ACCEPT | Summary: H3K9 monomethyltransferase activity is supported by the curated human reaction and corroborating GLP biochemistry. Reason: UniProt Q9H9B1 assigns RHEA:60280, addition of the first methyl group to H3K9, to ECO:0000269/PMID:12004135 (EHMT1-uniprot.txt, catalytic activity lines 379β385). This is also the reaction source behind the accepted electronic assertion, not independent experimental replication. Together with corroborating human GLP H3K9 writer and conserved mono/di evidence, it supports retaining the original curatorβs EXP assignment. The normal cache remains abstract-only and its operative assays were not recovered; no source-specific construct, kinetics or methyl-state assay is newly reconstructed. |
| GO:0140948 histone H3K9 monomethyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The initial H3K9 methylation step is biologically consistent with the EHMT1 writer mechanism. Reason: The imported Rhea/EC reaction describes transfer to unmethylated H3K9. Human GLP writer evidence and conserved mono/di H3K9 biochemistry support this electronic assertion. ARBA00098062 is currently unavailable (genuine 404), so its historical predicates are not reconstructed; the retained biology does not depend on pretending that rule was inspected. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00098062 SOURCE STALE OR MISSING Official rule endpoint returned 404; no historical predicate reconstruction. Other biological and reaction sources support the retained first-methylation claim. RHEA:60280 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. EC:2.1.1.367 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000117 GO_REF:0000116 GO_REF:0000003 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0140949 histone H3K9 trimethyltransferase activity | ISS GO_REF:0000024 | UNDECIDED | Summary: Direct H3K9 trimethyltransferase activity is not resolved by the donor chromatin phenotype. Reason: GO0140949 requires all three methyl additions to unmethylated H3K9. The mouse donor PMID24196706 reports me3 ChIP changes and bulk complex activity, not a purified GLP three-step reaction. Earlier mouse GLP loss leaves global me3 unchanged in ES cells, which is context-specific rather than universal absence. Retain the imported ISS assertion as unresolved without manufacturing a negative catalytic claim. Propagation Review Root cause: UNRESOLVED Sources checked: MGI:MGI:1924933 UNRESOLVED Current mouse donor maps to PMID24196706; me3 ChIP and complex bulk methylation do not isolate the specified catalytic reaction. Supporting Evidence: GO_REF:0000024 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0160274 beige fat cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Beige-fat differentiation is a supported PRDM16-associated context. Reason: The mouse donor PMID35978186 shows EHMT1 competes with APPBP2 for PRDM16 association and reduces PRDM16 polyubiquitination, within a beige-adipocyte study. EHMT1 construct species is not established merely by HEK293T expression. The existing tissue-specific transfer is retained without assigning ubiquitin-ligase activity or treating every paper phenotype as an Ehmt1-specific perturbation. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q5DW34 SUPPORTS TRANSFER The literal source identity is preserved; target-specific biological support and access limitations are stated in the reason. Supporting Evidence: GO_REF:0000024 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
| GO:0160275 negative regulation of white fat cell differentiation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Repression of white-fat marker genes in brown adipocytes is narrower than inhibition of white-fat differentiation. Reason: The current donor PMID24703692 studies Prdm16-dependent EHMT1 occupancy at Retn/Agt and an inhibitor-associated increase in white-fat gene expression within brown adipocytes. These results support a repressive chromatin mechanism, but do not directly establish reduced differentiation into white adipocytes. Preserve the positive donor finding while marking the specific differentiation process as overextended, not absent. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:Q5DW34 SUPPORTS SOURCE BUT NOT TARGET The donor supports the reported epigenetic mechanism, but its assays do not resolve the narrower imported process; see the source-specific reason. Supporting Evidence: GO_REF:0000024 file:human/EHMT1/EHMT1-bioinformatics/evidence/RESULTS.md |
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Download this section (compressed HTML)Q: Can purified human EHMT1 catalyze conversion of H3K9me2 to H3K9me3 under defined conditions, distinct from complex-mediated changes in mark abundance?
Q: Which natural EHMT1 splice products are expressed as stable proteins, and which retain catalytic or methyl-histone-recognition activity?
Q: What is the contribution of endogenous EHMT1-dependent p53 K373 methylation relative to EHMT2 and other p53 modifications in defined cell states?
Experiment: Compare sequence-confirmed purified human EHMT1 and EHMT1/EHMT2 complexes on defined H3K9me0, me1 and me2 substrates, measuring products by mass spectrometry with catalytic controls.
Hypothesis: Direct final-step H3K9 methylation can be distinguished from complex and cellular effects.
Type: Defined-substrate enzymology
Experiment: Confirm endogenous product-specific transcripts and peptides, then test sequence-verified proteins for H3K9 methyl transfer and mono/di-H3K9 binding without assigning activity solely from sequence length.
Hypothesis: Natural splice products differ in stability and retained biochemical activities.
Type: Product-resolved expression and biochemical assays
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