ELF4

Summary: ELF4 is a chromatin-associated DNA-binding transcription factor.

Reason: The TFClass-derived location is consistent with a nuclear ETS factor that recognizes regulatory DNA and activates target promoters. Human ELF4 sequence-specific promoter binding and transactivation support its chromatin-associated role. This does not imply that ELF4 is a constitutive structural chromatin component or occupies every chromatin region.

Summary: ELF4 recognizes a functional ETS site in the IL8 regulatory region.

Reason: The authentic PMID14625302 abstract explicitly reports specific MEF binding to an ETS sequence required for IL8 promoter responsiveness, with reporter activation and reciprocal overexpression/knockdown effects. This directly fits sequence-specific binding to a polymerase-II cis-regulatory region. Full operative Methods were not recovered; the known human transcription-factor function and the experimentally curated assertion are retained without inventing construct details.

Summary: The PAINT transcription-factor inference is supported by target experiments.

Reason: The human Q99607 leaf PTN002483845 descends from the asserted PTN000218930 node; its 663-residue displayed sequence matches the family MSA. The saved IBD includes a further zebrafish donor absent from this imported list, a preserved snapshot difference rather than evidence of functional loss. Human ELF4 DNA binding and promoter activation independently ground the inherited polymerase-II transcription-factor activity; the target appearing among donors is legitimate.

Summary: The ETS classification agrees with human ELF4 transcription-factor activity.

Reason: TFClass 3.5.2 supplies the imported classification, while target-specific DNA-binding and promoter-reporter evidence establishes the actual activity. ELF4 regulates protein-coding promoters through its ETS DNA-binding domain; no enzymatic transcription-regulator activity is inferred.

Summary: ELF4 directly activates transcription from an IL8 promoter.

Reason: PMID14625302 reports an ELF4-responsive ETS element, promoter activation, increased IL8 output after ELF4 overexpression and reduced output after knockdown. Together these support DNA-binding transcription activator activity rather than merely expression correlation. The correction associated with this paper concerns the second PEA3 PCR primer, not a retraction of the ELF4 result.

Summary: The specific natural killer-cell division claim remains unresolved.

Reason: The literal mouse ELF4 donor Q9Z2U4 has an IDA annotation to this term from PMID12387738. Its authentic abstract supports an important role in NK/NKT development and function, but the available source does not resolve a natural killer-cell proliferation assay or distinguish cell division from altered abundance, survival or differentiation. Bounded original-access attempts did not recover operative Methods/Results. The mouse-to-human transfer and original experimental donor are preserved; this uncertainty is not a rejection based on species or donor count.

Summary: The specific natural killer-cell division claim remains unresolved.

Reason: The literal mouse ELF4 donor Q9Z2U4 has an IDA annotation to this term from PMID12387738. Its authentic abstract supports an important role in NK/NKT development and function, but the available source does not resolve a natural killer-cell proliferation assay or distinguish cell division from altered abundance, survival or differentiation. Bounded original-access attempts did not recover operative Methods/Results. The mouse-to-human transfer and original experimental donor are preserved; this uncertainty is not a rejection based on species or donor count.

Summary: The specific NK T-cell division claim remains unresolved.

Reason: The literal mouse ELF4 donor Q9Z2U4 has an IDA annotation to this term from PMID12387738. Its authentic abstract supports an important role in NK/NKT development and function, but the available source does not resolve a NK T-cell proliferation assay or distinguish cell division from altered abundance, survival or differentiation. Bounded original-access attempts did not recover operative Methods/Results. The mouse-to-human transfer and original experimental donor are preserved; this uncertainty is not a rejection based on species or donor count.

Summary: The specific NK T-cell division claim remains unresolved.

Reason: The literal mouse ELF4 donor Q9Z2U4 has an IDA annotation to this term from PMID12387738. Its authentic abstract supports an important role in NK/NKT development and function, but the available source does not resolve a NK T-cell proliferation assay or distinguish cell division from altered abundance, survival or differentiation. Bounded original-access attempts did not recover operative Methods/Results. The mouse-to-human transfer and original experimental donor are preserved; this uncertainty is not a rejection based on species or donor count.

Summary: Refine the broad ETS transcription-factor term to polymerase-II-specific activity.

Reason: IPR000418 and IPR046328 genuinely map to DNA-binding transcription-factor activity. Human ELF4 experiments identify sequence-specific binding and activation of protein-coding promoters, supporting the polymerase-II-specific descendant rather than the broader all-polymerase term. The refinement rests on target experiments, not domain identity alone.

Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific

Summary: ELF4 binds the DNA-binding transcription factor RUNX1.

Reason: PMID10207087 contains reciprocal GST/in-vitro-translated-protein association assays, GST controls, ethidium-bromide resistance, interaction-region mapping and cellular co-immunoprecipitation. Human MEF and AML1B also cooperate on an IL3 promoter reporter in COS7 host cells. This establishes a mechanistic transcription-factor interaction beyond a generic screen-pair classification and supports GO0140297. It does not make the monkey reporter host a human cell assay.

Proposed replacements: DNA-binding transcription factor binding

Summary: The RUNX1 interaction supports transcription-factor binding with partner-product limits.

Reason: The source retains Q01196-8 as the partner. Current UniProt names that product AML-1G, whereas PMID10207087 uses historical AML1/AML1B nomenclature and a 479-residue AML1B construct. Exact insert equivalence to the current partner isoform was not established. Nevertheless, the directly assayed RUNX1 proteins retain their DNA-binding transcription-factor role, and reciprocal interaction mapping plus IL3 reporter cooperation supports GO0140297 at that bounded functional level. No isoform-specific affinity or functional equivalence is asserted.

Proposed replacements: DNA-binding transcription factor binding

Summary: ELF4–AML1 association fits the independently established transcription-factor interaction.

Reason: PMID14970218 actually includes FLAG-MEF/Myc-AML1 co-immunoprecipitation in transfected human 293T cells, with other ETS proteins as controls. Its BLK reporter and deletion experiments concern NERF2, so those are not assigned to ELF4. The more specific binding function is supported by the independent reciprocal and domain-mapping ELF4–RUNX1 assays and IL3 reporter cooperation in PMID10207087, not by the partner label alone.

Proposed replacements: DNA-binding transcription factor binding

Summary: The AML1B-associated source supports a bounded transcription-factor-binding refinement.

Reason: The imported partner Q01196-1 is the current displayed AML-1B product. PMID14970218 assays tagged MEF–AML1 association in human 293T cells; exact identity of the expressed insert with the present reference sequence is not proven. Independent ELF4–RUNX1 binding and functional cooperation in PMID10207087 support GO0140297. The NERF2-specific BLK reporter results and deletion phenotypes are not transferred to ELF4, and no new ELF4 isoform is inferred.

Proposed replacements: DNA-binding transcription factor binding

Summary: Refine ELF4–PML binding to transcription coactivator binding in the demonstrated lysozyme-transactivation context.

Reason: PMID14976184 combines reciprocal tagged co-immunoprecipitation in HeLa cells, endogenous association in HEK293 cells and mammalian two-hybrid mapping with PML enhancement of MEF-dependent lysozyme-promoter activation and endogenous lysozyme RNA. MEF protein abundance was unchanged by PML coexpression. Thus PML has a positive transcriptional cofactor role for ELF4 in the same experimental system, supporting GO:0001223 transcription coactivator binding beyond a partner-identity-only inference. The directly assayed interaction fragment spans MEF residues 477–663; the importance of residues 477–517 was inferred from overlapping truncations rather than an isolated 41-residue binding assay. The downstream recruitment or modification mechanism remains unresolved; no direct contact with basal transcription machinery, purified-pair affinity, autonomous ELF4 coactivator/scaffold activity or natural-isoform equivalence is asserted.

Proposed replacements: transcription coactivator binding

Summary: Nuclear activity is supported by both the PAINT lineage and human experiments.

Reason: The nucleus IBD lies on the ELF4 lineage at PTN000218930 and its donor set matches the imported list. Human promoter-regulatory activity, endogenous nuclear localization and supported HPA nuclear-body/nucleoplasmic staining corroborate the location. The imported is_active_in qualifier is preserved, without claiming exclusive nuclear residence or treating nuclear-body localization as the entirety of nuclear activity.

Summary: Refine transcription regulation to the polymerase-II process.

Reason: The ETS-domain InterPro mapping genuinely supports transcription regulation. ELF4 binds and regulates mammalian protein-coding promoters, which establishes the polymerase-II-specific process GO0006357. This refinement preserves the broad mapping premise while using target evidence to define the transcription system.

Proposed replacements: regulation of transcription by RNA polymerase II

Summary: Polymerase-II transcription regulation is a conserved and experimentally supported ELF4 role.

Reason: The GO0006357 IBD at PTN000218930 is ancestral to the human ELF4 leaf and has the exact imported donor set. Human MEF DNA binding, promoter activation and RUNX1-dependent cooperation establish the corresponding target activity. There is no observed negative path annotation or target-specific functional loss in the saved evidence.

Summary: The combined rule/domain prediction agrees with ELF4 polymerase-II regulation.

Reason: The official ARBA00028137 condition set 33 requires IPR000418, IPR022084 and IPR046328, all present in the official target record; the rule outputs GO0006357. The ETS-family InterPro mapping also outputs this process. Human promoter experiments independently establish the function, so the decision does not depend only on a rule description.

Summary: Human ELF4 is detected in nuclear bodies.

Reason: The current HPA record reports supported nuclear-body staining using antibody HPA060277 in A-431 and U-251MG cells, with additional nucleoplasmic localization in A-431. This directly fits the generic nuclear-body term. The HPA observation is not itself PML-marker evidence, and the separate PML-body study is not used to relabel every HPA focus.

Summary: PML-body localization is supported, with a reference assignment requiring clarification.

Reason: PMID14976184 reports MEF/PML colocalization and endogenous MEF redistribution with PML after heat shock in human HEK293 cells, supporting this location. The imported PMID14970218 is preserved, but its inspected operative experiments concern MEF–AML1 association and NERF2 promoter activity, not PML bodies. The biological annotation is retained while the reference assignment is raised as a conditional curator query. No exclusive or universal PML-body residence is asserted.

Summary: The UniProt PML-body location mapping is consistent with human localization evidence.

Reason: SL-0465 explicitly maps to GO0016605. Human-cell localization and endogenous heat-shock redistribution with PML in PMID14976184 support the mapped location. This is a documented subnuclear distribution under the inspected conditions, not evidence that all ELF4 molecules or all nuclear bodies are PML bodies.

Summary: Retain the inherited cell-differentiation process as contextual.

Reason: The cell-differentiation IBD is placed at PTN000218930 on the human ELF4 lineage. The saved IBD and imported assertion differ in three zebrafish donor identifiers; both versions remain intact, and the cause is not guessed. This broad developmental process is compatible with conserved ETS transcriptional regulation and the positive ELF4 immune-development literature, but is less informative than ELF4’s direct DNA-binding and transcriptional mechanism. There is no demonstrated target loss warranting rejection of the curated ancestral inference.

Summary: Retain the mouse-to-human IL1-beta regulatory inference as contextual.

Reason: The exact mouse ELF4 donor carries an IMP assertion from PMID34326534. Mouse Elf4-deficient/mutant macrophages show elevated inflammatory cytokines after receptor stimulation; the same paper independently reports increased IL1-beta in human patient PBMCs and ELF4-disrupted human macrophages. These data support a transcriptional restraint on cytokine production rather than cytokine processing by ELF4 itself. The immune-stimulation context is retained as non-core.

Summary: Human perturbation evidence supports restraint of IL1-beta production.

Reason: PMID34326534 reports increased IL1-beta after stimulation of patient PBMCs and ELF4-disrupted human macrophages, with separate mouse knockout/W250S experiments. Human W251S and mouse W250S numbering are not interchanged. The process is supported as an immune-context output of ELF4-dependent transcriptional regulation, without assigning ELF4 a cytokine-cleaving or secreting activity.

Summary: Retain the contextual IL6 regulatory transfer with human corroboration.

Reason: The mouse donor Q9Z2U4 has an experimental GO0032715 assertion from PMID34326534. Its stimulated macrophage phenotypes agree with increased IL6 in the human patient-cell comparison in that paper. This supports negative regulation of IL6 production in the tested immune setting; it is not a claim that ELF4 directly acts on IL6 protein or regulates every cytokine in every cell.

Summary: ELF4 loss of function increases stimulated IL6 output in the reported context.

Reason: The inspected PMID34326534 human patient-cell results and separate mouse experiments support restraint of IL6 production. The finding is a downstream consequence of an ELF4 transcriptional regulatory program, including altered anti-inflammatory-gene expression, rather than direct catalytic control of IL6. Retain it as a context-dependent process.

Summary: The mouse TNF-regulation transfer is supported in a virus-stimulation context.

Reason: The literal mouse donor assertion cites PMID35266071. The published Figure5 and its publisher caption show increased Tnf-alpha transcripts and TNF-alpha protein in mutant mouse macrophage comparisons after VSV or HSV1-GFP exposure, with human patient PBMC transcript/protein comparisons in the same figure. These positive source data support contextual negative regulation of TNF production. Full article Methods and supplement were not recovered; no broader assay details are inferred from the earlier preprint.

Summary: Published patient-cell data support restraint of TNF-alpha production.

Reason: PMID35266071 Figure5E/F reports human healthy-control versus ELF4-W231R patient PBMC qPCR and ELISA after 12-hour viral stimulation; Figure5G/H separately presents mouse macrophage experiments. The published figure and complete caption were inspected directly, supporting the TNF-alpha polarity without treating all TNF-superfamily proteins as equivalent. The cellular context is non-core, and unavailable full Methods are not claimed read.

Summary: Refine sequence-specific DNA binding to double-stranded DNA binding.

Reason: ARBA00026779 condition set 0 requires IPR000418, IPR036388 and Primates, all matched by target metadata, and outputs the broad sequence-specific DNA-binding term. ELF4’s promoter-binding activity and the double-stranded DNA substrates used in the cited HT-SELEX study support the more precise GO1990837. The individual ELF4 supplement construct was not recovered, so no particular assayed truncation or full-length insert is asserted.

Proposed replacements: sequence-specific double-stranded DNA binding

Summary: Use the polymerase-II-specific positive transcription process.

Reason: The ELF4-responsive IL8 promoter, ETS-site dependence and activation reported in PMID14625302 concern a polymerase-II-transcribed gene. GO0045944 is the verified descendant that preserves the positive regulatory mechanism while making the transcription system explicit. The associated primer correction does not invalidate that ELF4 claim.

Proposed replacements: positive regulation of transcription by RNA polymerase II

Summary: Refine the original MEF transactivation result to polymerase-II regulation.

Reason: The authentic PMID8895518 abstract explicitly describes human MEF DNA binding and transactivation of GM-CSF and IL3 promoters. Those protein-coding promoters support GO0045944, a verified direct child of GO0045893. Original full Methods/figures were not recovered, so this preserves the positive abstract and curator-supported activity without asserting an exact experimental insert, a natural isoform or a universal physiological effect.

Proposed replacements: positive regulation of transcription by RNA polymerase II

Summary: Refine established ELF4 positive transcription regulation to the polymerase-II process.

Reason: The imported PMID9524226 identifies human ELFR/ELF4 but its accessible abstract does not resolve the annotated transactivation assay; that source-specific access limit remains explicit. Independent human MEF promoter-transactivation evidence in PMID8895518 and operative IL3 reporter experiments in PMID10207087 establish the same gene product’s positive polymerase-II regulatory function. The broad annotation is refined on that combined evidence, without claiming that the unread PMID9524226 Methods were verified or that the source is about the wrong gene.

Proposed replacements: positive regulation of transcription by RNA polymerase II

Summary: Refine the supported positive transcription output to polymerase-II regulation.

Reason: The combined source includes mouse ELF4 and ARBA00029082. The mouse record cites PMID12387738; its full operative assay was not recovered. The current ARBA ETS condition set requires IPR006715, absent from the saved target InterPro list, so that particular branch is not claimed to match and other alternative branches remain untested. Independent human MEF promoter experiments establish the positive polymerase-II process and justify GO0045944 without rewriting the original rule/donor assertion.

Proposed replacements: positive regulation of transcription by RNA polymerase II

Summary: ELF4 positively regulates IL8 promoter transcription.

Reason: The source reports a functional ELF4-binding ETS site, promoter activation and complementary perturbation of IL8 output. This supports positive regulation of transcription by RNA polymerase II. The normalized row collapses two otherwise identical raw assertions from different assigned-by/date contexts; both raw records remain preserved and are not counted as independent experiments.

Summary: Positive polymerase-II transcription regulation is established, while the cited source assignment is queried.

Reason: The function is directly supported by ELF4–RUNX1 IL3 reporter cooperation in PMID10207087 and ELF4-dependent lysozyme promoter activation in PMID14976184. PMID14970218 genuinely assays MEF–AML1 association, but its inspected BLK transactivation experiments concern NERF2/ELF2. Retain the biological claim and imported reference, with a conditional source-reference query rather than misassigning NERF2 reporter results to ELF4.

Summary: The original human MEF report supports positive polymerase-II transcription regulation.

Reason: PMID8895518 explicitly reports human MEF binding and transactivation of GM-CSF and IL3 promoters. This directly supports the process at the level reported in the authentic abstract and agrees with later target experiments. Full original Methods and figures were not available, so neither exact insert identity nor a broad physiological program is claimed from this source alone.

Summary: Retain the established ELF4 polymerase-II activation function with a source-specific access boundary.

Reason: The authentic PMID9524226 abstract establishes human ELFR identity and expression but does not describe the curated reporter assay. Its full paper was not recovered. Human MEF transactivation in PMID8895518 and operative IL3 reporter assays in PMID10207087 independently establish the annotated function, allowing the clearly correct biological claim to be retained while the particular PMID9524226 assay remains unverified.

Summary: The inferred positive polymerase-II regulatory function has direct human support.

Reason: The mouse Q9Z2U4 donor carries experimental GO0045944 from PMID12387738, whose operative assay remains inaccessible. This does not leave the human function unresolved: human MEF promoter transactivation in PMID8895518 and the source-resolved IL3 reporter experiments in PMID10207087 independently support the same process. The imported donor and qualifier remain unchanged; no mouse-only construct is presented as the current human product.

Summary: Retain the contextual anti-inflammatory process inferred from mouse ELF4.

Reason: The current mouse donor cites PMID34326534. Its experimentally increased inflammatory responses after Elf4 loss agree with human patient and macrophage perturbation evidence in the same study. The source supports restraint of inflammatory responses through an ELF4-dependent transcriptional program, not a separate anti-inflammatory enzyme activity. Species, stimulation and cellular context remain explicit.

Summary: ELF4 restrains inflammatory responses in the studied human and mouse contexts.

Reason: PMID34326534 combines human disease/immune-cell evidence with mouse knockout and missense-model experiments. Increased stimulated inflammatory outputs, altered anti-inflammatory gene expression and exacerbated mouse inflammatory phenotypes support this process. These contextual consequences are retained separately from ELF4’s direct DNA-binding/transcription mechanism, without treating disease association alone as participation evidence.

Summary: Retain experimentally curated sequence-specific double-stranded DNA binding.

Reason: PMID28473536 uses recombinant transcription factors and repeated selection of double-stranded DNA libraries to measure sequence preferences. The inspected Methods establish that assay class, while the ELF4-specific supplementary construct/table was not recovered from genuine workbook routes. The target’s independent promoter-site binding supports the same molecular function, so the experimental assertion is retained without inventing a table hit, full-length construct or quantitative affinity.