EGR2 (Krox20) is a C2H2 zinc-finger transcription factor that binds regulatory DNA and activates RNA polymerase II transcription in the nucleus. Its transcriptional programs promote Schwann-cell differentiation and peripheral myelination and contribute to hindbrain development. Context-dependent targets include the proapoptotic genes BNIP3L and BAK in colon cancer cells. EGR2 interacts with transcriptional coregulators, including HCF-1 and NAB proteins. A conserved SUMO E3 ligase activity toward NAB coregulators links their sumoylation to feedback on transcriptional output. Human EGR2 variants cause inherited peripheral myelinopathies. The two natural human products differ at the N terminus.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved binding of RNA polymerase II regulatory DNA. Reason: The literal PAINT IBD for this term is on PTN004619861, an ancestor of the verified human P11161 leaf in PTHR23235. The ungapped target MSA sequence matches the official 476-residue sequence. Human EGR2 promoter-motif and nuclear-extract binding experiments in PMID:12687019 independently support regulatory DNA binding. The target appearing among descendant evidence is legitimate grounding, not circular propagation. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN004619861 SUPPORTS TRANSFER Literal IBD and target path are retained in the raw-derived PAINT proof. Target self-evidence is legitimate experimental grounding. Supporting Evidence: PMID:9537424 Egr2, (also known as Krox20) ... encoding a protein that binds DNA in a sequence-specific manner and acts as a transcription factor PMID:14532282 Krox20, a zinc finger transcription factor required for Schwann cell differentiation file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: Conserved RNA polymerase II transcription-factor activity. Reason: The current target descends from the literal PTN004619861 IBD for this activity. Human promoter activation and sequence-specific nuclear-extract binding in PMID:12687019 agree with that placement. The broad family includes other zinc-finger transcription factors, but the target sequence and ancestral path are resolved; neither a short donor list nor inclusion of EGR2 among descendant sources undermines the inference. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN004619861 SUPPORTS TRANSFER Literal IBD and target path are retained in the raw-derived PAINT proof. Target self-evidence is legitimate experimental grounding. Supporting Evidence: PMID:17717711 Mutations in the EGR2 gene cause a spectrum of Charcot-Marie-Tooth disease and related inherited peripheral neuropathies PMID:14532282 Krox20, a zinc finger transcription factor required for Schwann cell differentiation, ... showed a strong requirement for functional HCF-1 to activate transcription file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear localization supports the conserved transcriptional role. Reason: The nucleus IBD is at PTN009066117 and lies on the resolved EGR2 path. Human EGR2 nuclear-extract DNA-binding experiments and the explicit human EGR2 nucleoplasmic entity in Reactome corroborate this location. These are positive localization/function data, while the condition-dependent cytoplasmic pool is retained separately. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN009066117 SUPPORTS TRANSFER Literal IBD and target path are retained in the raw-derived PAINT proof. Target self-evidence is legitimate experimental grounding. Supporting Evidence: PMID:14532282 Krox20, a zinc finger transcription factor required for Schwann cell differentiation file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of RNA polymerase II transcription is conserved. Reason: The PTN004619861 IBD reaches the verified EGR2 leaf without an identified loss branch. Human EGR2 activates BNIP3L and BAK promoter reporters with motif-dependent binding in PMID:12687019; mouse Krox20 coactivation and other target-promoter studies agree. The IBA is a phylogenetic assertion, not a pairwise transfer or a count of independent human experiments. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN004619861 SUPPORTS TRANSFER Literal IBD and target path are retained in the raw-derived PAINT proof. Target self-evidence is legitimate experimental grounding. Supporting Evidence: PMID:12687019 EGR2 could induce apoptosis in a large proportion of these lines ... EGR2 directly transactivates expression of BNIP3L and BAK file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | MODIFY | Summary: Refine to the demonstrated molecular specificity. Reason: The historical combined electronic source is retained, with its existing retired lifecycle flag. Human EGR2 promoter-motif and nuclear-extract experiments in PMID:12687019 establish sequence-specific binding to RNA polymerase II cis-regulatory DNA. Refine the generic DNA-binding term to GO:0000978, an is_a descendant already present in the review. This specificity correction does not delete the historical source or infer biological loss from its disappearance. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: GO_REF:0000120 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:9537424 encoding a protein that binds DNA in a sequence-specific manner file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: The electronic nuclear location agrees with direct transcriptional evidence. Reason: The current combined mapping includes mouse Egr2 and the UniProt nucleus location. Human EGR2 acts on nuclear regulatory DNA, and the Reactome target entity is explicitly nucleoplasmic. Different source contexts for the same correct location are preserved rather than treated as redundant biological errors. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005654 nucleoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: Nucleoplasm is a supported location. Reason: The historical ARBA assertion agrees with the independently resolved human Reactome entity R-HSA-977385, whose own compartment is GO:0005654 and whose reference identifier is P11161. This is target-level compartment evidence, not merely an event-compartment inference. The old ARBA source key remains preserved despite its absence from the current GOA snapshot. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO_REF:0000117 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0008270 zinc ion binding | IEA GO_REF:0000043 | ACCEPT | Summary: The zinc-finger DNA-binding region supports zinc binding. Reason: The official human EGR2 product has three C2H2 zinc-finger regions, consistent with the keyword-derived zinc-binding assertion and its transcriptional DNA-binding mechanism. No new residue-specific affinity or metal-stoichiometry measurement is inferred. The historical source identity is retained independently of whether this keyword mapping is still emitted. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO_REF:0000043 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | MODIFY | Summary: Refine to the demonstrated molecular specificity. Reason: The defined reaction in PMID:21836637 demonstrates mouse Krox20 promotion of NAB2 sumoylation with E1, UBC9, human SUMO1 and ATP. Refine the uninformative transferase term to its supported is_a descendant GO:0061665, SUMO ligase activity, already represented in the review and core functions. The conserved human assignment remains an ortholog inference; EGR2 is not assigned the E2 reaction or an experimentally demonstrated human purified-protein assay. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: GO_REF:0000043 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Proposed replacements: SUMO ligase activity Supporting Evidence: PMID:21836637 we show that Krox20 functions as a SUMO ligase for its coregulators--the Nab proteins file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | MODIFY | Summary: Refine to the demonstrated molecular specificity. Reason: The official human EGR2 product contains three C2H2 zinc-finger regions supporting its DNA-binding mechanism. Refine generic metal ion binding to the is_a descendant GO:0008270, zinc ion binding, already present in the review. This identifies the supported metal without implying binding to other metal species or inventing affinity measurements. The historical source and retired lifecycle flag remain preserved. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: GO_REF:0000043 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Proposed replacements: zinc ion binding Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000107 | MODIFY | Summary: Refine to the demonstrated molecular specificity. Reason: The current Ensembl transfer identifies mouse Egr2/P08152. PMID:17938205 supplies promoter ChIP and DNA-binding evidence, and human EGR2 promoter-motif and nuclear-extract experiments in PMID:12687019 independently establish sequence-specific regulatory-DNA recognition. Refine cis-regulatory region binding to GO:0000978, its supported RNA polymerase II sequence-specific is_a descendant. This is a specificity correction, not deletion of a duplicate source. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: RNA polymerase II regulatory DNA binding transfers coherently. Reason: The literal mouse ortholog source carries experimentally grounded regulatory DNA-binding annotations. Independent human EGR2 motif-mutagenesis and nuclear-extract binding in PMID:12687019 support the same activity. The transfer is retained without claiming that every mouse donor paper or natural human isoform was tested in that human study. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: DNA-binding transcription-factor activity is conserved. Reason: Mouse Egr2 has experimental transcription-factor annotations, including promoter studies, and the verified human EGR2 experiments in PMID:12687019 establish the same function. The Ensembl source and the separate experimental/phylogenetic contexts are all retained. Ordinary source qualifiers do not change this biological assessment. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0003682 chromatin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Chromatin binding has direct ortholog grounding. Reason: Mouse Egr2 is annotated by IDA to chromatin binding from PMID:17938205. That study reports association of mouse EGR2/CITED1 with the ErbB2 promoter by chromatin immunoprecipitation, in addition to reporter and DNA-binding assays. This is stronger grounding than assuming that any nuclear transcription factor must bind chromatin; the human transfer remains appropriate. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000107 | ACCEPT | Summary: The broad DNA-binding transcription-factor term is correct. Reason: The mapped mouse Egr2 record contains experimental DNA-binding transcription-factor evidence. Human EGR2 promoter activation with sequence-dependent binding in PMID:12687019 independently supports the broad activity. More specific accepted transcription-factor terms do not invalidate this separate imported source context. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cytoplasmic EGR2 is a positive, regulated localization context. Reason: The mouse donor IDA points to PMID:17938205. In TM15 mammary tumor cells, increased 14-3-3sigma/SFN was associated with EGR2 redistribution from nucleus to cytoplasm; the related zeta isoform did not reproduce this result. Retain the positive cytoplasmic pool as non-core, without describing it as unmeasured transit or dismissing it because the main transcriptional function is nuclear. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0006611 protein export from nucleus | IEA GO_REF:0000107 | REMOVE | Summary: The export assertion conflates transported EGR2 with export machinery. Reason: The exact mouse donor carries GO:0006611 IDA from PMID:17938205, so the transfer chain is real. The operative Results and Figure 5 describe 14-3-3sigma-dependent redistribution/sequestration of EGR2 itself from nucleus to cytoplasm. GO:0006611 describes directed protein movement out of the nucleus; these experiments establish EGR2 as the relocated cargo, not an exporter, transport cofactor or structural participant carrying out that movement. Remove this inferred process assertion on that source-role mismatch, while retaining the positive cytoplasmic annotations. This is not a wrong-gene allegation or an argument from an unavailable human assay. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P08152 SOURCE BAD The literal current GO:0006611 IDA from PMID:17938205 exists. The objection is its assignment of an export-process role to relocated EGR2 cargo, not source absence, paralog confusion or lack of human data. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0014040 positive regulation of Schwann cell differentiation | IEA GO_REF:0000107 | ACCEPT | Summary: EGR2 promotes Schwann-cell differentiation. Reason: The mouse ortholog has IMP support for positive regulation of Schwann-cell differentiation, including PMID:10068633, whose abstract describes arrest before myelination in Krox20 mutants. Human hereditary myelinopathy findings in PMID:9537424 support the conserved peripheral-glial role. This is a major physiological context of EGR2 transcriptional regulation, not an assertion that the human disease study itself was a mouse knockout experiment. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: PMID:9537424 Stable expression of Egr2 is specifically associated with the onset of myelination in the peripheral nervous system (PNS). Egr2(-/-) mice display disrupted hindbrain segmentation and development, and a block of Schwann-cell differentiation at an early stage file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0016925 protein sumoylation | IEA GO_REF:0000120 | ACCEPT | Summary: Conserved SUMO E3 activity directly participates in sumoylation. Reason: The current combined source includes mouse Egr2 and the sumoylation pathway. PMID:21836637 reconstituted modification of mouse NAB2 with purified mouse Krox20, mouse E1/E2, human SUMO1 and ATP, and connected NAB modification to transcriptional feedback. EGR2 does some of the enzymatic work rather than merely being a SUMO substrate. This supports the human ortholog annotation without claiming a purified human EGR2 assay. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: PMID:21836637 Krox20 functions as a SUMO ligase for its coregulators--the Nab proteins--and that Nab sumoylation negatively modulates Krox20 transcriptional activity in vivo file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0021612 facial nerve structural organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Facial-nerve organization is a conserved developmental context. Reason: The mouse donor has experimental facial-nerve structural-organization annotations, including the Hoxa1/Krox20 genetic study PMID:9806922. The source context concerns hindbrain patterning and cranial motor projections. Retain it as a developmental, non-core consequence of the transcriptional program; the human neuropathy abstract alone is not treated as a direct facial-nerve patterning assay. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: PMID:17717711 respiratory compromise and cranial nerve dysfunction are commonly associated with EGR2 mutations file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0021659 rhombomere 3 structural organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Rhombomere 3 organization is supported by mouse developmental evidence. Reason: The term concerns structural organization of rhombomere 3. The mouse donor has direct Egr2-dependent Hox enhancer evidence in PMID:8093858, and Krox20-null hindbrain abnormalities in PMID:7903221 provide developmental context. Retain this positive, context-specific process as non-core rather than denying participation merely because transcription is the molecular mechanism. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0021665 rhombomere 5 structural organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Rhombomere 5 organization is a supported developmental role. Reason: The current mouse donor carries rhombomere 5 organization evidence, including the Hox regulatory work in PMID:8093858. The PMID:7903221 abstract reports marked reduction of the corresponding odd rhombomeres in Krox20-null mice, with initial delimitation distinguished from later organization. Retain the conserved developmental role as non-core without inferring a direct human embryonic assay. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0031643 positive regulation of myelination | IEA GO_REF:0000107 | ACCEPT | Summary: EGR2 positively regulates peripheral myelination. Reason: The transferred mouse annotation is experimentally grounded, including PMID:7935840, whose abstract reports failure of peripheral myelin formation in Krox20 mutants. Human EGR2-associated hypomyelinating neuropathies independently support the conserved role. This is a principal physiological transcriptional program, while details of individual mouse experiments are not relabeled as human data. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: PMID:9537424 Stable expression of Egr2 is specifically associated with the onset of myelination in the peripheral nervous system file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0035904 aorta development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Aortic-valve development is a positive contextual role. Reason: The mouse source is IMP from PMID:25344368. Its abstract reports Krox20-mutant aortic-valve hyperplasia/regurgitation and regulation of fibrillar collagen genes; human valve expression is a separate observation. This supports a bounded cardiovascular developmental context rather than generic growth-factor induction. Retain the imported aorta-development term as non-core, without generalizing to all aortic tissues. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Sequence-specific DNA binding is well established. Reason: The current transfer points to mouse Egr2 with experimentally grounded sequence-specific DNA binding. Independent human EGR2 promoter-motif and nuclear-extract experiments in PMID:12687019 support the same chemistry. The broad term is correct even though more specific regulatory-DNA annotations are also present. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0045444 fat cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Adipocyte differentiation is a supported non-core context. Reason: The mouse donor has IMP annotations from PMID:16054051 and PMID:18396140. The latter reports Krox20 cooperation with KLF4 in a 3T3-L1 differentiation program and partial bypass of KLF4 knockdown, rather than expression alone. Retain the contextual differentiation role; this does not establish a dominant human adipose function or replace the principal neural transcriptional program. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000107 | ACCEPT | Summary: Positive transcriptional regulation is conserved. Reason: Mouse Egr2 has direct positive-transcription evidence, including ErbB2 promoter regulation in PMID:17938205. Human EGR2 direct activation in PMID:12687019 independently corroborates the regulatory sign. Coregulator-dependent repression in other contexts does not negate this positive activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IEA GO_REF:0000107 | ACCEPT | Summary: Binding to the DNA-binding transcription factor KLF4 is supported. Reason: The current mouse donor annotation is IPI from PMID:18396140 with KLF4/Q60793. That source reports Krox20-KLF4 co-immunoprecipitation and GST-KLF4 pull-down of translated Krox20, with controls. KLF4 is independently established as a sequence-specific RNA polymerase II transcription factor. This supports GO:0061629; HCFC1 and NAB coregulators are not the basis for this partner-class assignment. Exact assayed Krox20 natural-product identity was not independently established. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0061665 SUMO ligase activity | IEA GO_REF:0000107 | ACCEPT | Summary: Mouse ortholog assays support conserved SUMO E3 ligase activity. Reason: PMID:21836637 and its supplement identify mouse Krox20, UBC9, E1 and NAB2 with human SUMO1 in the reconstituted reaction. Substrate modification and the substoichiometric Krox20 experiment support catalytic E3 participation, not only association or necessity. Retain the human ortholog transfer; do not call EGR2 an E2 or claim purified human protein was assayed. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: PMID:21836637 Krox20 functions as a SUMO ligase for its coregulators--the Nab proteins file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ... | ACCEPT | Summary: Sequence-specific double-stranded DNA binding is accepted with dataset limits. Reason: The source is a curator-assigned IDA from the human transcription-factor SELEX study. Its original cohort Methods were inspected, but the exact EGR2 supplement row, construct and methylation-preference class were not recovered. Independent human EGR2 promoter-motif and nuclear-extract binding in PMID:12687019 makes the annotated function clearly correct. Retain the curator assertion without inventing an EGR2-specific SELEX result or methylation class. Supporting Evidence: PMID:28473536 By analysis of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment), we found that there are also many TFs that prefer CpG-methylated sequences file:human/EGR2/EGR2-source-guide.md |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Summary: The manual ortholog transfer agrees with human transcriptional activation. Reason: Mouse Egr2 experimentally activates regulatory reporters, and human EGR2 directly activates BNIP3L and BAK reporters in PMID:12687019. The current mouse donor and original ISS source are preserved. This is positive regulation of RNA polymerase II transcription, without assuming all EGR2-regulated genes or cellular contexts have the same sign. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0014037 Schwann cell differentiation | ISS GO_REF:0000024 | ACCEPT | Summary: Schwann-cell differentiation is a major conserved EGR2 role. Reason: The mouse donor record includes IMP evidence from Krox20 loss and Schwann-cell developmental studies. The PMID:7935840 abstract reports failure at an early myelination stage, and PMID:9537424 links human EGR2 variants to inherited myelinopathies. Retain the conserved differentiation role while distinguishing animal perturbations from human genetic evidence. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: PMID:9537424 Egr2(-/-) mice display disrupted hindbrain segmentation and development, and a block of Schwann-cell differentiation at an early stage file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0014040 positive regulation of Schwann cell differentiation | ISS GO_REF:0000024 | ACCEPT | Summary: Positive regulation of Schwann-cell differentiation is retained. Reason: The manually transferred mouse annotation is supported by PMID:10068633, which reports differentiation arrest in Krox20 mutants, and by the conserved human peripheral-neuropathy phenotype. This is a positive regulatory role in a principal EGR2 transcriptional program, not a new mechanistic claim inferred only from the disease name. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0021612 facial nerve structural organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Facial-nerve organization remains a developmental context. Reason: The exact mouse donor has experimental annotations for this term, including the Hoxa1/Krox20 genetic interaction source PMID:9806922. Retain the nerve-patterning contribution as non-core. Human cranial-nerve symptoms provide context but are not substituted for the donor developmental experiments. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: PMID:17717711 respiratory compromise and cranial nerve dysfunction are commonly associated with EGR2 mutations file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0021659 rhombomere 3 structural organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Rhombomere 3 organization is retained as a contextual process. Reason: The mouse ortholog source is experimentally grounded in hindbrain/Hox regulation, including PMID:8093858, and the Krox20-null phenotype is described in PMID:7903221. This is structural organization of rhombomere 3, not an assertion of a distinct enzyme activity. The positive developmental annotation is preserved as non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0021665 rhombomere 5 structural organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Rhombomere 5 organization is retained as a contextual process. Reason: Mouse Egr2 has direct Hox regulatory and mutant-developmental evidence for the rhombomere 5 context. The accessed PMID:7903221 abstract distinguishes later rhombomere reduction from initial delimitation. Retain the imported manual transfer as non-core without claiming direct experimentation on human embryonic tissue. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0031643 positive regulation of myelination | ISS GO_REF:0000024 | ACCEPT | Summary: Positive regulation of myelination is a central physiological role. Reason: The mouse Egr2 donor carries IMP evidence from PMID:7935840, consistent with loss of peripheral myelin in the abstract. Human EGR2 genetic neuropathies independently support conservation. Preserve this manual transfer separately from electronic and human genetic source contexts. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0035914 skeletal muscle cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Skeletal-muscle differentiation is retained with source-resolution limits. Reason: The mouse donor carries IMP annotations from PMID:22147266 and PMID:11509834. The former abstract describes a C2C12 transcription-regulator screen but does not resolve the Egr2 target row; the latter concerns jaw-opener musculature with motor-neuron/innervation context. Retain the curated positive transfer as a non-core developmental role, without converting the jaw phenotype into proof of an autonomous myogenic mechanism or claiming the target screen table was read. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:17717711 Functional, histopathologic and natural history study of neu... | ACCEPT | Summary: Transcription-factor activity is clearly correct despite incomplete source access. Reason: The authentic PMID:17717711 abstract and publisher preview were read, but the operative functional-assay body was not recovered. The IDA assertion is retained under curator deference because independent human EGR2 promoter and DNA-binding experiments in PMID:12687019 establish this function. Specific R359W/E412K assay results from the unavailable body are not asserted. Supporting Evidence: PMID:17717711 Mutations in the EGR2 gene cause a spectrum of Charcot-Marie-Tooth disease and related inherited peripheral neuropathies file:human/EGR2/EGR2-source-guide.md |
| GO:0043565 sequence-specific DNA binding | IDA PMID:17717711 Functional, histopathologic and natural history study of neu... | ACCEPT | Summary: Sequence-specific DNA binding is retained without invented variant details. Reason: PMID:17717711 remains the original curator source. Its abstract is authentic, while full functional Methods and Results were unavailable. Human EGR2 motif-dependent binding in PMID:12687019 independently supports the activity, so the positive IDA is retained rather than overruled on incomplete access. No exact disease-variant binding result is claimed from an unread figure. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:17717711 Functional, histopathologic and natural history study of neu... | ACCEPT | Summary: Positive RNA polymerase II transcriptional regulation is established. Reason: The original PMID:17717711 IDA is preserved despite incomplete access to its functional experiments. Independent human EGR2 activation of BNIP3L and BAK in PMID:12687019 supports the same activity. The decision does not depend on unverified claims about particular mutant constructs in the neuropathy paper. |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: Chromatin localization is consistent with the TFClass assertion. Reason: The imported TFClass assignment identifies the EGR zinc-finger transcription-factor class. Mouse Egr2 promoter ChIP in PMID:17938205 and human regulatory-DNA activity support the chromatin context. This ISA classification is not represented as an independent imaging or biochemical assay. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO_REF:0000113 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: TFClass transcription-factor classification agrees with direct evidence. Reason: The TFClass 2.3.1 source classification is consistent with the official EGR2 zinc-finger sequence and independent human EGR2 activation/binding experiments. Retain its classification-based assertion without conflating it with a separate IDA study. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO_REF:0000113 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0016925 protein sumoylation | ISS GO_REF:0000024 | ACCEPT | Summary: Protein sumoylation is supported by direct mouse E3 participation. Reason: The ISS source is mouse Egr2. PMID:21836637 and its supplement establish a defined mouse Krox20/E1/UBC9/NAB2 reaction with human SUMO1 and ATP. This is positive catalytic participation in NAB2 modification and supports the conserved human role. The previous description of independent human EGR2 experimental evidence is not warranted by these reagents. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: PMID:21836637 Krox20 functions as a SUMO ligase for its coregulators--the Nab proteins file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0061665 SUMO ligase activity | ISS GO_REF:0000024 | ACCEPT | Summary: SUMO ligase activity is retained with the correct organismal scope. Reason: The actual purified E3 in PMID:21836637 is mouse Krox20, not human EGR2. Its promotion of NAB2 modification in a defined E1/E2/SUMO1/ATP system and the substoichiometric experiment support SUMO E3 activity. Retain the manual ortholog transfer while avoiding human-construct equivalence, E2 activity, ubiquitin-ligase activity or a measured kinetic rate. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: PMID:21836637 we show that Krox20 functions as a SUMO ligase for its coregulators--the Nab proteins--and that Nab sumoylation negatively modulates Krox20 transcriptional activity in vivo file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:12687019 EGR2 induces apoptosis in various cancer cell lines by direc... | ACCEPT | Summary: Human EGR2 binds promoter cis-regulatory DNA. Reason: Selected original Methods, Results and the Figure 5 caption in PMID:12687019 support human EGR2 promoter reporters, wild-type/mutant binding motifs, nuclear-extract EMSA, competition and anti-Egr2 supershift. These establish regulatory-DNA binding; the experiment is not a purified-protein assay. The precise natural isoform of the historical 1.4-kb construct remains unresolved. Supporting Evidence: PMID:12687019 EGR2 directly transactivates expression of BNIP3L and BAK file:human/EGR2/EGR2-source-guide.md |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:12687019 EGR2 induces apoptosis in various cancer cell lines by direc... | ACCEPT | Summary: Human EGR2 directly activates RNA polymerase II target promoters. Reason: PMID:12687019 combines promoter activation with motif dependence and nuclear-extract DNA-binding evidence for BNIP3L and BAK. This supports the specific DNA-binding activator function. The nonverbatim inherited ellipsis excerpt is retired while its primary reference is retained; no new quotation or exact natural-product assignment is introduced. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:12687019 EGR2 induces apoptosis in various cancer cell lines by direc... | ACCEPT | Summary: Direct positive transcriptional regulation is supported in human cells. Reason: Human SW480 adenoviral EGR2 and promoter assays in PMID:12687019 support positive regulation of BNIP3L and BAK transcription. Binding and motif-mutagenesis evidence connect EGR2 to the promoter step. This is a cellular assay context, without claiming universal activation or resolving the historical construct to both natural human products. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9612073 | ACCEPT | Summary: The Reactome model explicitly places human EGR2 in nucleoplasm. Reason: The saved Reactome chain resolves 9612073 output 9612066; 9612066 hasMember 977385 to human EGR2 entity 977385, reference P11161, residues 1–476. The protein entity itself is explicitly in GO:0005654 nucleoplasm. Here EGR2 is an expression output; that role supports the modeled protein location, not a claim that EGR2 catalyzes its own induction. Retain the localization as core-relevant. These curated models are not twelve independent human localization experiments and do not establish equivalence of the Short product. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9612483 | ACCEPT | Summary: The Reactome model explicitly places human EGR2 in nucleoplasm. Reason: The saved Reactome chain resolves 9612483 input 9612485; 9612485 hasMember 977385 to human EGR2 entity 977385, reference P11161, residues 1–476. The protein entity itself is explicitly in GO:0005654 nucleoplasm. The event is EGR1,2,3 bind the NAB2 promoter. This is a target-resolved regulatory participant or complex/set member, not an inference from the event compartment alone. Retain the localization as core-relevant. These curated models are not twelve independent human localization experiments and do not establish equivalence of the Short product. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9613210 | ACCEPT | Summary: The Reactome model explicitly places human EGR2 in nucleoplasm. Reason: The saved Reactome chain resolves 9613210 input 9613165; 9613165 hasMember 977385 to human EGR2 entity 977385, reference P11161, residues 1–476. The protein entity itself is explicitly in GO:0005654 nucleoplasm. The event is EGR1, EGR2 bind the RRAD promoter. This is a target-resolved regulatory participant or complex/set member, not an inference from the event compartment alone. Retain the localization as core-relevant. These curated models are not twelve independent human localization experiments and do not establish equivalence of the Short product. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9613213 | ACCEPT | Summary: The Reactome model explicitly places human EGR2 in nucleoplasm. Reason: The saved Reactome chain resolves 9613213 input 9613167; 9613167 hasComponent 977385 to human EGR2 entity 977385, reference P11161, residues 1–476. The protein entity itself is explicitly in GO:0005654 nucleoplasm. The event is NAB2 and CHD4 bind and repress EGR-mediated RRAD gene expression. This is a target-resolved regulatory participant or complex/set member, not an inference from the event compartment alone. Retain the localization as core-relevant. These curated models are not twelve independent human localization experiments and do not establish equivalence of the Short product. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9613476 | ACCEPT | Summary: The Reactome model explicitly places human EGR2 in nucleoplasm. Reason: The saved Reactome chain resolves 9613476 input 977385 to human EGR2 entity 977385, reference P11161, residues 1–476. The protein entity itself is explicitly in GO:0005654 nucleoplasm. The event is EGR2:NAB2 and CHD4 bind the ID2 and ID4 promoter regions. This is a target-resolved regulatory participant or complex/set member, not an inference from the event compartment alone. Retain the localization as core-relevant. These curated models are not twelve independent human localization experiments and do not establish equivalence of the Short product. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9613760 | ACCEPT | Summary: The Reactome model explicitly places human EGR2 in nucleoplasm. Reason: The saved Reactome chain resolves 9613760 output 977385 to human EGR2 entity 977385, reference P11161, residues 1–476. The protein entity itself is explicitly in GO:0005654 nucleoplasm. Here EGR2 is an expression output; that role supports the modeled protein location, not a claim that EGR2 catalyzes its own induction. Retain the localization as core-relevant. These curated models are not twelve independent human localization experiments and do not establish equivalence of the Short product. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9616116 | ACCEPT | Summary: The Reactome model explicitly places human EGR2 in nucleoplasm. Reason: The saved Reactome chain resolves 9616116 input 977385 to human EGR2 entity 977385, reference P11161, residues 1–476. The protein entity itself is explicitly in GO:0005654 nucleoplasm. The event is EGR2 and SOX10 bind the MAG gene. This is a target-resolved regulatory participant or complex/set member, not an inference from the event compartment alone. Retain the localization as core-relevant. These curated models are not twelve independent human localization experiments and do not establish equivalence of the Short product. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9618559 | ACCEPT | Summary: The Reactome model explicitly places human EGR2 in nucleoplasm. Reason: The saved Reactome chain resolves 9618559 input 977385 to human EGR2 entity 977385, reference P11161, residues 1–476. The protein entity itself is explicitly in GO:0005654 nucleoplasm. The event is EGR2, SOX10 and TEAD1 bind enhancers in the PMP22 gene. This is a target-resolved regulatory participant or complex/set member, not an inference from the event compartment alone. Retain the localization as core-relevant. These curated models are not twelve independent human localization experiments and do not establish equivalence of the Short product. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9618725 | ACCEPT | Summary: The Reactome model explicitly places human EGR2 in nucleoplasm. Reason: The saved Reactome chain resolves 9618725 input 977385 to human EGR2 entity 977385, reference P11161, residues 1–476. The protein entity itself is explicitly in GO:0005654 nucleoplasm. The event is SOX10, EGR2 and NAB proteins bind the GJB1 promoter. This is a target-resolved regulatory participant or complex/set member, not an inference from the event compartment alone. Retain the localization as core-relevant. These curated models are not twelve independent human localization experiments and do not establish equivalence of the Short product. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9621400 | ACCEPT | Summary: The Reactome model explicitly places human EGR2 in nucleoplasm. Reason: The saved Reactome chain resolves 9621400 input 977385 to human EGR2 entity 977385, reference P11161, residues 1–476. The protein entity itself is explicitly in GO:0005654 nucleoplasm. The event is EGR2 and SREBF2 dimer bind SCD5 gene. This is a target-resolved regulatory participant or complex/set member, not an inference from the event compartment alone. Retain the localization as core-relevant. These curated models are not twelve independent human localization experiments and do not establish equivalence of the Short product. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9621406 | ACCEPT | Summary: The Reactome model explicitly places human EGR2 in nucleoplasm. Reason: The saved Reactome chain resolves 9621406 input 977385 to human EGR2 entity 977385, reference P11161, residues 1–476. The protein entity itself is explicitly in GO:0005654 nucleoplasm. The event is EGR2 and SREBF2 dimer bind CYP51A1 gene. This is a target-resolved regulatory participant or complex/set member, not an inference from the event compartment alone. Retain the localization as core-relevant. These curated models are not twelve independent human localization experiments and do not establish equivalence of the Short product. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9621411 | ACCEPT | Summary: The Reactome model explicitly places human EGR2 in nucleoplasm. Reason: The saved Reactome chain resolves 9621411 input 977385 to human EGR2 entity 977385, reference P11161, residues 1–476. The protein entity itself is explicitly in GO:0005654 nucleoplasm. The event is EGR2 and SREBF2(1-484) dimer bind HMGCR gene. This is a target-resolved regulatory participant or complex/set member, not an inference from the event compartment alone. Retain the localization as core-relevant. These curated models are not twelve independent human localization experiments and do not establish equivalence of the Short product. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0000976 transcription cis-regulatory region binding | ISS GO_REF:0000024 | MODIFY | Summary: Refine to the demonstrated molecular specificity. Reason: The mouse donor has IDA evidence from PMID:17938205, whose promoter ChIP and DNA-binding experiments were inspected. Human regulatory-DNA experiments in PMID:12687019 corroborate sequence-specific binding at RNA polymerase II promoters. Refine this ISS assertion to the supported is_a descendant GO:0000978 while preserving its independent source identity and the mouse-to-human evidence boundary. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0003682 chromatin binding | ISS GO_REF:0000024 | ACCEPT | Summary: Chromatin binding is supported by the literal mouse donor experiment. Reason: Mouse Egr2 has IDA chromatin-binding evidence from PMID:17938205, including promoter chromatin immunoprecipitation with mouse EGR2/CITED1. This is target-resolved donor evidence, not an inference from a nuclear localization label alone. Retain the conserved human manual transfer. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: The manually transferred nuclear location is correct. Reason: The donor has positive nuclear localization and nuclear transcriptional evidence, including PMID:17938205; human EGR2 nuclear-extract assays independently agree. Two current raw GOA contexts differing only by date normalize to this existing source key; they are preserved in the raw reconciliation rather than counted as separate functional experiments. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: A regulated cytoplasmic EGR2 pool is positively supported. Reason: PMID:17938205 reports 14-3-3sigma-dependent nuclear-to-cytoplasmic redistribution of EGR2 in mouse TM15 cells with a zeta-isoform control. Preserve this positive donor localization as a non-core cellular context. It is not dismissed as speculative transit, and the result is not relabeled as a direct human localization experiment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0006611 protein export from nucleus | ISS GO_REF:0000024 | REMOVE | Summary: The inferred export role confuses cargo localization with transport participation. Reason: The current mouse IDA source for GO:0006611 is explicitly present and derives from PMID:17938205. The inspected experiment measures EGR2 itself being redistributed/sequestered by 14-3-3sigma. It supports cytoplasmic localization, but not EGR2 acting as the exporter, cofactor or structural transport machinery responsible for directed protein export. Remove this source-role overextension in the human ISS assertion; do not erase the donor record or the independently retained cytoplasmic pool. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:P08152 SOURCE BAD The literal current GO:0006611 IDA from PMID:17938205 exists. The objection is its assignment of an export-process role to relocated EGR2 cargo, not source absence, paralog confusion or lack of human data. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0045893 positive regulation of DNA-templated transcription | ISS GO_REF:0000024 | ACCEPT | Summary: Positive DNA-templated transcriptional regulation is retained. Reason: Mouse Egr2 directly regulates promoter output in PMID:17938205, and human EGR2 directly activates BNIP3L and BAK in PMID:12687019. These support the positive sign of the manual transfer. Context-dependent corepressor feedback does not contradict a demonstrated activator capability. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005634 nucleus | IC PMID:14532282 HCF-1 functions as a coactivator for the zinc finger protein... | ACCEPT | Summary: Nuclear location is a sound inference from the transcriptional assays. Reason: The original IC is based on DNA-binding transcription-factor activity. PMID:14532282 used mouse Krox20 in heterologous cellular reporter/coactivation experiments, not an independently mapped human isoform. Human EGR2 nuclear-extract binding in PMID:12687019 provides additional target-specific support for the nuclear location. Supporting Evidence: PMID:14532282 Krox20, a zinc finger transcription factor required for Schwann cell differentiation, ... showed a strong requirement for functional HCF-1 to activate transcription file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0045444 fat cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Adipocyte differentiation is retained as a positive contextual process. Reason: Mouse Egr2 has IMP evidence from PMID:16054051 and PMID:18396140. The latter includes differentiation perturbation/rescue context and Krox20-KLF4 cooperation in 3T3-L1 cells. This supports the manual transfer as non-core; it is more than an expression association but does not establish a primary physiological role in human adipose tissue. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | ISS GO_REF:0000024 | ACCEPT | Summary: The DNA-binding transcription-factor partner is KLF4. Reason: The exact mouse source for GO:0061629 is PMID:18396140 with KLF4/Q60793, whose DNA-binding transcription-factor class is independently established. The original reports Krox20-KLF4 co-immunoprecipitation and GST pull-down with controls. Retain the conserved binding-class assertion; the previous use of HCFC1 or NAB association as evidence for a DNA-binding partner class was inappropriate. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:19651900 The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-i... | KEEP AS NON CORE | Summary: WWP2 binding is positive but belongs to regulation of EGR2 turnover. Reason: PMID:19651900 reports a human Jurkat cDNA-library screen, cellular co-immunoprecipitation and a purified GST-WWP2-WW-region/His-EGR2 pull-down with GST and PPXY-motif controls. WWP2 is independently an E3 ubiquitin ligase, so the partner-class term is supported. The assayed interaction promotes ubiquitination and proteasomal turnover of EGR2; retain it as non-core regulatory context rather than transferring WWP2 catalytic activity to EGR2. The selected Methods do not resolve every recombinant EGR2 insert to a natural human product. Supporting Evidence: PMID:19651900 AIP2 interacts with and promotes ubiquitin-mediated degradation of EGR2, a zinc finger transcription factor that has been found to regulate Fas ligand (FasL) expression during activation-induced T-cell death file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0005515 protein binding | IPI PMID:14532282 HCF-1 functions as a coactivator for the zinc finger protein... | MODIFY | Summary: HCFC1 is a transcription coactivator, supporting a specific binding class. Reason: PMID:14532282 explicitly used full-length murine Krox20 and N-terminal fragments. Its cellular transcriptional-complementation/recruitment assay, binding-motif mutations and HCF-1 controls support association with HCFC1; the authors did not detect a stable purified complex in their attempted gel-shift or in-vitro co-immunoprecipitation assays. HCFC1 is independently a transcription coactivator and does not itself supply the sequence-specific DNA-binding activity. Replace generic protein binding with GO:0001223 transcription coactivator binding, not GO:0061629. The human reference ROGIDs in IntAct identify database parent sequences, not proof that the assayed Krox20 construct was human. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:14532282 HCF-1 functions as a coactivator for the zinc finger protein Krox20 ... In Krox20, the HCF-binding motif lies within the N-terminal activation domain and mutation of this sequence diminishes both transactivation and association with the HCF-1 beta-propeller file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:14532282 HCF-1 functions as a coactivator for the zinc finger protein... | ACCEPT | Summary: The cellular Krox20 study supports conserved transcription-factor activity. Reason: PMID:14532282 used mouse Krox20 constructs in heterologous reporter assays and demonstrated HCF-1-dependent activation with motif controls. Preserve the curator-assigned human IDA and make that source scope explicit; independent human EGR2 binding/activation in PMID:12687019 establishes that the function is correct for the target. The source does not establish equivalence of both natural human products. Supporting Evidence: PMID:14532282 Krox20, a zinc finger transcription factor required for Schwann cell differentiation, ... showed a strong requirement for functional HCF-1 to activate transcription file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0007420 brain development | TAS PMID:9537424 Mutations in the early growth response 2 (EGR2) gene are ass... | KEEP AS NON CORE | Summary: Brain development is retained as a broad developmental context. Reason: The authentic PMID:9537424 abstract distinguishes human hereditary myelinopathy variants from mouse hindbrain segmentation/development and Schwann-cell background. The broad brain-development statement is biologically consistent with EGR2 hindbrain patterning but is retained as non-core rather than generalized to all brain-development programs. Supporting Evidence: PMID:9537424 Egr2(-/-) mice display disrupted hindbrain segmentation and development file:human/EGR2/EGR2-source-guide.md |
| GO:0007422 peripheral nervous system development | TAS PMID:9537424 Mutations in the early growth response 2 (EGR2) gene are ass... | ACCEPT | Summary: Peripheral nervous-system development is a central physiological context. Reason: PMID:9537424 reports human EGR2 variants in inherited myelinopathies and explicitly discusses the mouse Schwann-cell differentiation/myelination phenotype. Together these support the conserved peripheral nervous-system role. Preserve the human genetics versus mouse developmental-evidence distinction; the abstract does not itself provide a new human mechanistic rescue assay. Supporting Evidence: PMID:9537424 Stable expression of Egr2 is specifically associated with the onset of myelination in the peripheral nervous system ... we have identified one recessive and two dominant missense mutations in EGR2 ... in patients with congenital hypomyelinating neuropathy (CHN) and a family with Charcot-Marie-Tooth type 1 (CMT1) file:human/EGR2/EGR2-source-guide.md |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: The newly fetched source context supports transcriptional activator activity. Reason: This row is a genuine normal Ensembl transfer from mouse Egr2, not an authored NEW assertion. The donor carries IDA activator evidence from PMID:18396140, and human EGR2 binding plus activation in PMID:12687019 independently corroborates the activity. Retain the exact fetched source object and distinguish this additional source context from a newly proposed biological function. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
| GO:0003677 DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: Refine to the demonstrated molecular specificity. Reason: This genuine normal Ensembl source points to mouse Egr2, with DNA-binding evidence including PMID:8093858. Human promoter-motif and nuclear-extract experiments in PMID:12687019 establish the more informative RNA polymerase II cis-regulatory region sequence-specific binding activity. Refine generic DNA binding to the is_a descendant GO:0000978; retain the fetched source object and its separate historical counterpart rather than relabeling it as NEW. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:P08152 SUPPORTS TRANSFER Source-specific scope and limitations are stated in the review reason; no missing publication is treated as evidence of wrong-gene curation. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: file:human/EGR2/EGR2-source-guide.md file:human/EGR2/EGR2-bioinformatics/RESULTS.md |
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